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Sample records for acute immune-mediated thrombocytopenia

  1. Treatment of presumptive primary immune-mediated thrombocytopenia with mycophenolate mofetil versus cyclosporine in dogs.

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    Cummings, F O; Rizzo, S A

    2017-02-01

    The objective of this study was to compare hospitalisation duration, survival times, adverse events and cost of therapy in dogs with presumptive primary immune-mediated thrombocytopenia undergoing therapy with mycophenolate mofetil and corticosteroids versus cyclosporine and corticosteroids. A retrospective study of medical case records of dogs with presumed primary immune-mediated thrombocytopenia was conducted. Data collected included signalment, presenting complaints, haematologic and biochemical profiles, vector-borne disease testing, thoracic and abdominal radiographs, abdominal ultrasound, medications administered, duration of hospitalisation, 30- and 60-day survival, adverse events and cost of therapy. Variables were compared between dogs treated solely with mycophenolate mofetil and corticosteroids or cyclosporine and corticosteroids. A total of 55 dogs with primary immune-mediated thrombocytopenia were identified. Eighteen were excluded because multiple immunosuppressive medications were used during treatment. Hospitalisation times, 30-day survival and 60-day survival times were similar between both groups. Dogs in the mycophenolate mofetil/corticosteroid group experienced fewer adverse events than the cyclosporine/corticosteroid group. Therapy with mycophenolate mofetil was less expensive than that with cyclosporine. These results suggest that using the combination of mycophenolate mofetil and corticosteroids appears to be as effective as cyclosporine and corticosteroids in the treatment of presumed primary immune-mediated thrombocytopenia in dogs. Adverse events were less common and cost of therapy was lower in the mycophenolate mofetil group. Additional larger prospective, controlled, double-masked, outcome-based, multi-institutional studies are required to substantiate these preliminary findings. © 2017 British Small Animal Veterinary Association.

  2. Systemic neosporosis in a dog treated for immune-mediated thrombocytopenia and hemolytic anemia.

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    Magaña, Angie; Sánchez, Félix; Villa, Karina; Rivera, Liliana; Morales, Elizabeth

    2015-12-01

    A 4-year-old male Toy Poodle was presented to the Small Animal Veterinary Hospital of the Faculty of Veterinary Medicine of the Autonomous University of Mexico (FMVZ, UNAM) because of depression, lethargy, and hemorrhages involving several areas of the skin and around the eyes. Hematology data and a bone marrow analysis suggested hemolytic anemia and immune-mediated thrombocytopenia. The dog was treated with prednisone, and after one month the hematology variables improved. However, the dog's clinical condition inexplicably worsened and it was euthanized. On necropsy, there were no relevant findings. However, in histology, multifocal lymphoplasmacytic and histiocytic meningoencephalitis and necrosis, and a protozoan cyst in the cerebellum were identified. In addition, moderate multifocal lymphoplasmacytic and necrotizing pancreatitis, hepatitis, myocarditis, and diffuse lymphoplasmacytic enteritis were observed. Immunohistochemistry of the cerebellum, liver, pancreas, and intestine with a specific antibody against Neospora caninum confirmed the diagnosis of systemic neosporosis. The systemic neosporosis in this dog was most likely caused by reactivation of latent parasites due to prednisone administration during the one month of treatment. It should be kept in mind that in dogs being treated with immunosuppressants for immune-mediated conditions, opportunistic parasites, such as Toxoplasma gondii and N caninum, can be reactivated from a latent state, as it probably happened in the present case. © 2015 American Society for Veterinary Clinical Pathology.

  3. Anemia and thrombocytopenia in acute and chronic renal failure.

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    Dorgalaleh, Akbar; Mahmudi, Mohammad; Tabibian, Shadi; Khatib, Zahra Kashani; Tamaddon, Gholam Hossein; Moghaddam, Esmaeil Sanei; Bamedi, Taregh; Alizadeh, Shaban; Moradi, Eshagh

    2013-01-01

    Acute renal failure describes as a syndrome by rapid decline in the ability of the kidney to eliminate waste products, regulate acid-base balance, and manage water homeostasis. When this impairment is prolonged and entered chronic phase, erythropoietin secretion by this organ is decreasing and toxic metabolic accumulates and causes hematological changes include decrease of HCT, MCV and RBC and platelet counts. This study evaluates present of anemia and thrombocytopenia in patients with acute and chronic renal failure. This study conducted on 132 patients with renal impairment and also 179 healthy individuals as two separated control groups. Initially patients with renal problem were tested and after confirmation of impairment, patients were divided in two groups, acute with less than 3 months and chronic with more than 3 months renal failure, based on duration of the disease. Then complete blood count performed for each patient and finally obtained data were analyzed by SPSS software. Comparison between 96 patients with acute and 36 patients with chronic renal failure revealed that severity of anemia (HCT, Hb and MCV) between these two groups were statistically high in comparison with control groups (P > 0.05) but thrombocytopenia in patients with chronic renal failure was statistically different from control and the acute ones (P renal failure, to prevent the risk of bleeding, platelet count should be checked periodically.

  4. Immune mediated liver failure.

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    Wang, Xiaojing; Ning, Qin

    2014-01-01

    Liver failure is a clinical syndrome of various etiologies, manifesting as jaundice, encephalopathy, coagulopathy and circulatory dysfunction, which result in subsequent multiorgan failure. Clinically, liver failure is classified into four categories: acute, subacute, acute-on-chronic and chronic liver failure. Massive hepatocyte death is considered to be the core event in the development of liver failure, which occurs when the extent of hepatocyte death is beyond the liver regenerative capacity. Direct damage and immune-mediated liver injury are two major factors involved in this process. Increasing evidence has suggested the essential role of immune-mediated liver injury in the pathogenesis of liver failure. Here, we review the evolved concepts concerning the mechanisms of immune-mediated liver injury in liver failure from human and animal studies. Both innate and adaptive immunity, especially the interaction of various immune cells and molecules as well as death receptor signaling system are discussed. In addition, we highlight the concept of "immune coagulation", which has been shown to be related to the disease progression and liver injury exacerbation in HBV related acute-on-chronic liver failure.

  5. Oral exposure to Phytomonas serpens attenuates thrombocytopenia and leukopenia during acute infection with Trypanosoma cruzi.

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    da Silva, Rosiane V; Malvezi, Aparecida D; Augusto, Leonardo da Silva; Kian, Danielle; Tatakihara, Vera Lúcia H; Yamauchi, Lucy M; Yamada-Ogatta, Sueli F; Rizzo, Luiz V; Schenkman, Sergio; Pinge-Filho, Phileno

    2013-01-01

    Mice infected with Trypanosoma cruzi, the agent of Chagas disease, rapidly develop anemia and thrombocytopenia. These effects are partially promoted by the parasite trans-sialidase (TS), which is shed in the blood and depletes sialic acid from the platelets, inducing accelerated platelet clearance and causing thrombocytopenia during the acute phase of disease. Here, we demonstrate that oral immunization of C57BL/6 mice with Phytomonas serpens, a phytoflagellate parasite that shares common antigens with T. cruzi but has no TS activity, reduces parasite burden and prevents thrombocytopenia and leukopenia. Immunization also reduces platelet loss after intraperitoneal injection of TS. In addition, passive transfer of immune sera raised in mice against P. serpens prevented platelet clearance. Thus, oral exposure to P. serpens attenuates the progression of thrombocytopenia induced by TS from T. cruzi. These findings are not only important for the understanding of the pathogenesis of T. cruzi infection but also for developing novel approaches of intervention in Chagas disease.

  6. Acute ST Elevation Myocardial Infarction in Patients With Immune Thrombocytopenia Purpura: A Case Report.

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    Dhillon, Sandeep K; Lee, Edwin; Fox, John; Rachko, Maurice

    2011-02-01

    Acute myocardial infarction (AMI) in patients with immune thrombocytopenic purpura (ITP) is rare. We describe a case of AMI in patient with ITP. An 81-year-old woman presented with acute inferoposterior MI with low platelet count on admission (34,000/µl). Coronary angiography revealed significant mid right coronary artery (RCA) stenosis with thrombus, subsequently underwent successful percutaneous coronary intervention (PCI). In some patients with immune thrombocytopenia purpura and acute myocardial infarction, percutaneous coronary intervention is a therapeutic option.

  7. Effect of high dose of steroid on plateletcount in acute stage of dengue Fever with thrombocytopenia.

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    Shashidhara, K C; Murthy, K A Sudharshan; Gowdappa, H Basavana; Bhograj, Abhijith

    2013-07-01

    Dengue infection is the most rapidly spreading mosquito-borne viral disease in the world and an estimated 50 million dengue infections reported annually. The pathogenesis of Thrombocytopenia in dengue fever (DF) is not clearly understood. Increased peripheral destruction of antibody coated platelets and acute bone marrow suppression were strongly suspected as the possible mechanism. This often leads to life threatening dengue hemorrhagic fever (DHF) and Dengue shock syndrome (DSS). Steroids are used in the treatment of Idiopathic thrombocytopenic purpura to increase the platelet count which is mediated by auto antibodies .This hypothesis would support the use of steroids in dengue fever. The objective of this study was to test whether an intravenous high dose dexamethasone was efficacious in increasing the platelet count in acute stage of dengue fever with thrombocytopenia. During the study period between June 2010 - 2011 in JSS Hospital Mysore, 127 patients were screened for dengue fever with thrombocytopenia (dengue fever.

  8. Acute Severe Thrombocytopenia Following Non-Ionic Low-Osmolarity Intravenous Contrast Medium Injection

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    Bata Pal; Domonkos, Adam; Tamoki, David Laszio; Horvath, Evelin; Berczi, Viktor; Szalay, Ferenc [Semmelweis University, Budapest (Hungary)

    2012-07-15

    Intravenous contrast medium (ICM) rarely induces anaphylactic reactions, including urticaria, hypotension and respiratory failure. Even the most modern ICM may cause such adverse events. Thrombocytopenia has been reported as an extreme rare consequence of ICM. Here we report on a case of a 72-year-old male patient with a self-limiting severe acute thrombocytopenia following administration of intravenous non-ionic low-osmolarity contrast medium. No such low platelet count has ever been reported. We also present a review of the literature.

  9. Human Herpesvirus 6 Infection Presenting as an Acute Febrile Illness Associated with Thrombocytopenia and Leukopenia

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    Maja Arnež

    2016-01-01

    Full Text Available We present an infant with acute fever, thrombocytopenia, and leukopenia, coming from an endemic region for tick-borne encephalitis, human granulocytic anaplasmosis, and hantavirus infection. The primary human herpesvirus 6 infection was diagnosed by seroconversion of specific IgM and IgG and by identification of viral DNA in the acute patient’s serum. The patient did not show skin rash suggestive of exanthema subitum during the course of illness.

  10. Bone Marrow-Derived Mesenchymal Stem Cells Attenuate Immune-Mediated Liver Injury and Compromise Virus Control During Acute Hepatitis B Virus Infection in Mice.

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    Qu, Mengmeng; Yuan, Xu; Liu, Dan; Ma, Yuhong; Zhu, Jun; Cui, Jun; Yu, Mengxue; Li, Changyong; Guo, Deyin

    2017-06-01

    Mesenchymal stem cells (MSCs) have been used as therapeutic tools not only for their ability to differentiate toward different cells, but also for their unique immunomodulatory properties. However, it is still unknown how MSCs may affect immunity during hepatitis B virus (HBV) infection. This study was designed to explore the effect of bone marrow-derived MSCs (BM-MSCs) on hepatic natural killer (NK) cells in a mouse model of acute HBV infection. Mice were injected with 1 × 10 6 BM-MSCs, which stained with chloromethyl derivatives of fluorescein diacetate fluorescent probe, 24 h before hydrodynamic injection of viral DNA (pHBV1.3) through the tail vein. In vivo imaging system revealed that BM-MSCs were accumulated in the injured liver, and they attenuated immune-mediated liver injury during HBV infection, as shown by lower alanine aminotransferase levels, reduced proinflammatory cytokine production, and decreased inflammatory cell infiltration in the liver. Importantly, administration of BM-MSCs restrained the increased expression of natural-killer group 2, member D (NKG2D), an important receptor required for NK cell activation in the liver from HBV-infected mice. BM-MSCs also reduced NKG2D expression on NK cells and suppressed the cytotoxicity of NK cells in vitro. Furthermore, BM-MSC-derived transforming growth factor-β1 suppressed NKG2D expression on NK cells. As a consequence, BM-MSC treatment enhanced HBV gene expression and replication in vivo. These results demonstrate that adoptive transfer of BM-MSCs influences innate immunity and limits immune-mediated liver injury during acute HBV infection by suppressing NK cell activity. Meanwhile, the effect of BM-MSCs on prolonging virus clearance needs to be considered in the future.

  11. Successful management of acute thromboembolic disease complicated with heparin induced thrombocytopenia type II (HIT II: a case series

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    Trellopoulos George

    2008-07-01

    Full Text Available Abstract Heparin-induced thrombocytopenia type II (HIT II is a rare immune-mediated complication of heparin. The diagnosis of HIT is considered in patients exposed to heparin, presenting with thrombocytopenia and thrombosis. We present two cases with massive pulmonary embolism and HIT, successfully treated with the administration of fondaparinux, an alternative anticoagulant, combined with the insertion of an inferior vena cava filter for the prevention of new thromboembolic events. The two cases supplement the available data of the use of fondaparinux in patients with HIT and pulmonary embolism, before further large studies establish its efficacy and safety in this group of patients. Moreover, the management of these patients reveals the need for future evaluation of the combined therapy of alternative anticoagulant agents with the placement of vena cava filters.

  12. Oral exposure to Phytomonas serpens attenuates thrombocytopenia and leukopenia during acute infection with Trypanosoma cruzi.

    Directory of Open Access Journals (Sweden)

    Rosiane V da Silva

    Full Text Available Mice infected with Trypanosoma cruzi, the agent of Chagas disease, rapidly develop anemia and thrombocytopenia. These effects are partially promoted by the parasite trans-sialidase (TS, which is shed in the blood and depletes sialic acid from the platelets, inducing accelerated platelet clearance and causing thrombocytopenia during the acute phase of disease. Here, we demonstrate that oral immunization of C57BL/6 mice with Phytomonas serpens, a phytoflagellate parasite that shares common antigens with T. cruzi but has no TS activity, reduces parasite burden and prevents thrombocytopenia and leukopenia. Immunization also reduces platelet loss after intraperitoneal injection of TS. In addition, passive transfer of immune sera raised in mice against P. serpens prevented platelet clearance. Thus, oral exposure to P. serpens attenuates the progression of thrombocytopenia induced by TS from T. cruzi. These findings are not only important for the understanding of the pathogenesis of T. cruzi infection but also for developing novel approaches of intervention in Chagas disease.

  13. Immune-mediated epilepsies in children

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    E. D. Belousova

    2015-01-01

    Full Text Available The paper reviews the current literature on immune-mediated pediatric epilepsies. It describes the clinical picture, laboratory diagnosis, and treatment of autoimmune encephalitides (limbic encephalitis and anti-NMDA-receptor antibody encephalitis, Hashimoto's encephalopathy, opsoclonus-myoclonus-syndrome, and Rasmussen's syndrome, as well as groups of acute encephalopathies with immune-mediated status epilepticus (FIRES-, DESK-, HHE- syndrome. A clinical case of Hashimoto's encephalopathy is described. Emphasis is laid on a close relationship between epilepsy and inflammation, including the development of an autoimmune process due to recurrent epileptic seizures.

  14. Prevention of Non-immune Mediated Transfusion-related Acute Lung Injury; from Blood Bank to Patient

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    van Bruggen, Robin; de Korte, Dirk

    2012-01-01

    Transfusion-related acute lung injury (TRALI) is a severe form of pulmonary insufficiency induced by transfusion. TRALI is the leading cause of transfusion-related death, and is caused by the infusion of either anti-leukocyte antibodies in plasma containing blood products or neutrophil priming

  15. Parvovirus B19-triggered acute hemolytic anemia and thrombocytopenia in a child with Evans syndrome

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    ELPIS MANTADAKIS

    2018-03-01

    Full Text Available Background: Human parvovirus B19 (HPV-B19 is the etiologic agent of erythema infectiosum, of transient aplastic crises in individuals with underlying chronic hemolytic disorders, and of chronic pure red cell aplasia in immunocompromised individuals. Case report. We describe a 14-year-old girl with long-standing Evans syndrome, who presented with severe anemia, reticulocytopenia and thromocytopenia. A bone marrow aspirate revealed severe erythroid hypoplasia along with presence of giant pronormoblasts, while serological studies and real-time PCR of whole blood were positive for acute parvovirus B19 infection. The patient was initially managed with corticosteroids, but both cytopenias resolved only after administration of intravenous gamma globulin 0.8g/kg. Conclusion: Acute parvovirus B19 infection should be suspected in patients with immunologic diseases, who present with reticulocytopenic hemolytic anemia and thrombocytopenia. In this setting, intravenous gamma globulin is effective for both cytopenias.

  16. Initial Management of Childhood Acute Immune Thrombocytopenia: Single-Center Experience of 32 Years.

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    Yildiz, Inci; Ozdemir, Nihal; Celkan, Tiraje; Soylu, Selen; Karaman, Serap; Canbolat, Aylin; Dogru, Omer; Erginoz, Ethem; Apak, Hilmi

    2015-01-01

    Immune thrombocytopenia (ITP) is an acute self-limited disease of childhood, mostly resolving within 6 months irrespective of whether therapy is given or not. Treatment options when indicated include corticosteroids, intravenous immune globulin (IVIG), and anti-RhD immunoglobulin. We reviewed our 32 years' experience for first-line therapy of acute ITP. Five hundred forty-one children (mean age: 5.3 years) diagnosed and treated for ITP were evaluated retrospectively. Among 491 acute ITP patients, IVIG was used in 27%, high-dose steroids in 27%, low-dose steroids in 20%, anti-D immunoglobulin G (IgG) in 2%, and no therapy in 22%. When the initial response (platelets >50 × 10(9)/L) to first-line treatment modalities were compared, 89%, 84%, and 78% patients treated by low-dose steroids, high-dose steroids, and IVIG responded to treatment, respectively (P > .05). Mean time to recovery of platelets was 16.8, 3.8, and 3.0 days in patients treated with low-dose steroids, high-dose steroids, and IVIG, respectively (P < .0001). Thrombocytopenia recurred in 23% of low-dose steroid, 39% of high-dose steroid, and in 36% of IVIG (P < .0001) treatment groups. Of 108 patients who were observed alone, 4 (3%) had a recurrence on follow-up and only 2 of these required treatment subsequently. Recurrence was significantly less in no therapy group compared with children treated with 1 of the 3 options of pharmacotherapy (P < .0001). Response rates were similar between patients treated by IVIG and low- and high-dose steroids; however, time to response was slower in patients treated with low-dose steroids compared with IVIG and high-dose steroids.

  17. Rethinking platelet function: thrombocytopenia induced immunodeficiency in critical illness

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    Ostrowski, Sisse R; Johansson, Per Ingemar

    2011-01-01

    traditional innate immune cells, platelets are recruited immediately into injured and inflamed tissue, they release immune mediators, express and shed immunologically active membrane receptors, they interact with other immune cells and they recognize and clear pathogens. We hypothesize that thrombocytopenia...

  18. Immune mediated liver failure

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    Wang, Xiaojing; Ning, Qin

    2014-01-01

    Liver failure is a clinical syndrome of various etiologies, manifesting as jaundice, encephalopathy, coagulopathy and circulatory dysfunction, which result in subsequent multiorgan failure. Clinically, liver failure is classified into four categories: acute, subacute, acute-on-chronic and chronic liver failure. Massive hepatocyte death is considered to be the core event in the development of liver failure, which occurs when the extent of hepatocyte death is beyond the liver regenerative capac...

  19. Two patients with acute thrombocytopenia following gold administration and five-year follow-up

    NARCIS (Netherlands)

    M.-D. Levin (Mark-David); M.B. van 't Veer (Mars); J.C. de Veld; H.M. Markusse

    2003-01-01

    textabstractThrombocytopenia is a well-known side effect following intramuscular gold therapy in patients with rheumatoid arthritis. Thrombocytopenia may occur at any time and it can be irreversible and sometimes fatal despite cytotoxic or immunosuppressive therapy. We describe two

  20. Acute renal failure, thrombocytopenia, and elevated liver enzymes after concurrent abuse of alcohol and cocaine

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    Alireza Hosseinnezhad

    2011-05-01

    Full Text Available Cocaine has been associated with known adverse effects on cardiac, cerebrovascular and pulmonary systems. However, the effect of cocaine on other organs has not been extensively reported. A middle age man presented with abdominal pain and nausea after inhalation of crack cocaine. On admission, he was found to be hypertensive and tachycardic. Physical examination revealed mild abdominal tenderness without rebound. Laboratory investigations were significant for acute kidney failure with elevated serum creatinine (3.72 mg/dL, thrombocytopenia (platelet count 74,000/UL, elevated alanine and aspartate transaminases (ALT 331 U/L; AST 462 U/L and elevated creatine phosphokinase (CPK 5885 U/L. Urine toxicology screening solely revealed cocaine. A clinical diagnosis of cocaine toxicity was made and patient was admitted to the intensive care unit because of multi organ failure. Despite downward trending of liver enzymes during the hospital course, he continued to have residual renal insufficiency and a low platelet count at the time of discharge. In a patient with history of recent cocaine use presenting with these manifestations, cocaine itself should be considered as a likely cause.

  1. THROMBOCYTOPENIA AND ALBUMINURIA- EARLY PREDICTORS OF ACUTE KIDNEY INJURY IN VENOMOUS SNAKEBITE- A COMPARATIVE STUDY

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    Ramasamy S

    2016-11-01

    Full Text Available BACKGROUND Snakebites and accidents caused by venomous arthropods are important public health problem. Envenomation by snakebite, independently of the species responsible for the bite, enforces medical emergencies since different organs and tissues can be affected at the same time. The hypothesis for pathogenesis of venom-induced AKI includes both a direct cytotoxic action of the venom on different renal structures and a secondary response of the whole organism resulting from systemic envenomation. The aim of the study is to assess the early predictors for acute kidney injury due to snakebite by comparing it with the patients who had not developed acute kidney injury after the snakebite. MATERIALS AND METHODS A prospective comparative study was undertaken at the Government Medical College Hospital, Salem, during the period of April 2015-March 2016. A total of 115 patients were included in the study in which 42 patients were having AKI due to snakebite and 73 patients were without AKI after snakebite. Haematological and biochemical investigations were performed in all patients, including haemoglobin, complete and differential leukocyte counts, platelet count, peripheral blood smear, bleeding and clotting times, Prothrombin Time (PT and Activated Partial Thromboplastin Time (APTT, blood urea, serum creatinine, serum electrolytes, liver function tests and urine examination. RESULTS Thrombocytopenia and albuminuria, which is to be considered as the major early marker for acute kidney injury among snakebite patients was found to be present in 85.7% and 100% in our patients with AKI whereas it was only 1.3% and 4.1% respectively among the patients without AKI and the difference was found to be statistically significant (p<.05. The survival rate was higher among the patients without AKI when compared to the patients with AKI and the difference is statistically significant (p<.05. CONCLUSION Early detection of AKI due to snakebite should be assessed by

  2. How to approach thrombocytopenia.

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    Stasi, Roberto

    2012-01-01

    Thrombocytopenia is a common hematologic finding with variable clinical expression. A low platelet count may be the initial manifestation of infections such as HIV and hepatitis C virus or it may reflect the activity of life-threatening disorders such as the thrombotic microangiopathies. A correct identification of the causes of thrombocytopenia is crucial for the appropriate management of these patients. In this review, we present a systematic evaluation of adults with thrombocytopenia. The approach is clearly different between outpatients, who are frequently asymptomatic and in whom we can sometimes indulge in sophisticated and relatively lengthy investigations, and the dramatic presentation of acute thrombocytopenia in the emergency department or in the intensive care unit, which requires immediate intervention and for which only a few diagnostic tests are available. A brief discussion of the most common etiologies seen in both settings is provided.

  3. Acute brucellosis as unusual cause of immune thrombocytopenia: a case report and review of the literature

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    Tajeldin Mohammedien Abdallah

    2014-09-01

    Full Text Available A 25 year-old male patient was admitted to the causality with complaints of fever, joints pain, epistaxis and gingival bleeding, for the last week, the complete blood count revealed pancytopenia. Serological test for brucella was reported positive as 1/320, but the patient failed to respond to brucella treatment for 4 d. On day 5th the diagnosis of immune thrombocytopenia was confirmed after bone marrow aspiration. Steroid was initiated on 6th day after admission and on the 3rd day of steroid therapy thrombocytes count was raised to 55×109/L and came up to 180×109/L on 12th day after admission. Brucella-induced immune thrombocytopenia should be considered in patient presenting with bleeding and febrile illness especially in endemic region.

  4. Therapeutic Challenges in the Management of Acute Pulmonary Embolism in a Cancer Patient with Chemotherapy-induced Thrombocytopenia

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    Abuajela Sreh

    2017-11-01

    Full Text Available This case demonstrates the therapeutic challenges encountered when managing an acute pulmonary embolism in a cancer patient with thrombocytopenia. A 64-year-old man with a history of lung cancer receiving chemotherapy was admitted to Walsall Manor Hospital with haemodynamic instability consistent with a pulmonary embolism, proven on computed tomographic pulmonary angiogram. His platelet count was noted to be 35×109/l (chemotherapy-induced thrombocytopenia. After discussions, he was deemed not suitable for thrombolysis based on risk versus benefits. The patient was initially transfused one adult dose of platelets and treated with half the therapeutic dose of low molecular weight heparin (LMWH. The same management plan was followed until the platelet count exceeded 50×10sup>9/l, after which the patient was established on the full therapeutic dose of LMWH. Clinically, the patient improved and was discharged. Three months after discharge, follow-up revealed sustained clinical improvement while the patient continued to be on the full therapeutic dose of LMWH with a stable platelet count.

  5. Immune Thrombocytopenia

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    ... information about platelet transfusions, go to the Health Topics Blood Transfusion article. Treating Infections Some infections can briefly lower ... experiences with clinical research. More Information Related Health Topics Blood ... Tests Thrombocytopenia Thrombotic Thrombocytopenic Purpura Other ...

  6. Acute Kidney Injury, Recurrent Seizures, and Thrombocytopenia in a Young Patient with Lupus Nephritis: A Diagnostic Dilemma

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    Hector Alvarado Verduzco

    2016-01-01

    Full Text Available Introduction. Posterior reversible encephalopathy syndrome (PRES is a constellation of clinical and radiologic findings. Fluctuations in blood pressure, seizures, and reversible brain MRI findings mainly in posterior cerebral white matter are the main manifestations. PRES has been associated with multiple conditions such as autoimmune disorders, pregnancy, organ transplant, and thrombotic microangiopathy (TMA. Case Presentation. A 22-year-old woman with history of Systemic Lupus Erythematous complicated with chronic kidney disease secondary to lupus nephritis class IV presented with recurrent seizures and uncontrolled hypertension. She was found to have acute kidney injury and thrombocytopenia. Repeat kidney biopsy showed diffuse endocapillary and extracapillary proliferative and membranous lupus nephritis (ISN-RPS class IV-G+V and endothelial swelling secondary to severe hypertension but no evidence of TMA. Brain MRI showed reversible left frontal and parietal lesions that resolved after controlling the blood pressure, making PRES the diagnosis. Conclusion. PRES is an important entity that must be recognized and treated early due to the potential reversibility in the early stages. Physicians must have high suspicion for these unusual presentations. We present a case where performing kidney biopsy clinched the diagnosis in our patient with multiple confounding factors.

  7. Thrombocytopenia Is Associated With Multi-organ System Failure in Patients With Acute Liver Failure

    NARCIS (Netherlands)

    Stravitz, R. Todd; Ellerbe, Caitlyn; Durkalski, Valerie; Reuben, Adrian; Lisman, Ton; Lee, William M.

    BACKGROUND & AIMS: Acute liver failure (ALF) is a syndrome characterized by an intense systemic inflammatory response (SIRS) and multi-organ system failure (MOSF). Platelet-derived microparticles increase in proportion to the severity of the SIRS and MOSF, and are associated with poor outcome. We

  8. Malaria-induced immune thrombocytopenia

    DEFF Research Database (Denmark)

    Sørensen, P G; Mickley, H; Schmidt, K G

    1984-01-01

    On return from Liberia, a previously healthy 36-year-old man showed signs of malaria accompanied by severe haemolysis and slight thrombocytopenia. We found evidence of a platelet-associated IgG being responsible for the thrombocytopenia, inasmuch as the direct platelet suspension immunofluorescence...... test was strongly positive, the indirect immunofluorescence test and tests for drug-dependent antibodies at the same time being negative. We suggest that autoimmunity may be a contributing mechanism for platelet destruction in acute malaria....

  9. A Case of Thrombocytopenia due to Odontogenic Infection.

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    Kumar Verma, Dinesh; Rajan, Ritesh

    2011-01-01

    Thrombocytopenia in surgical patients is a potentially serious condition,faced by surgeons. A close relationship between sepsis and thrombocytopenia has been suggested. Thrombocytopenia has even been suggested to be indicative of an acute infection. Platelet count in a septicemic patient may also serve as a prognostic tool. There are many reports of thrombocy-topenia due to septicemia in the literature but the occurrence of thrombocytopenia in maxillofacial infections is rare. Thrombocytopenia in a patient with odontogenic infection presents unique diagnostic and management challenges. A case report of an adult male patient with odontogenic infection, who developed life-threatening thrombocytopenia, is presented.

  10. A Case of Thrombocytopenia due to Odontogenic Infection

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    Dinesh Kumar Verma

    2011-12-01

    Full Text Available Thrombocytopenia in surgical patients is a potentially serious condition, faced by surgeons. A close relationship between sepsis and thrombocytopenia has been suggested. Thrombocytopenia has even been suggested to be indicative of an acute infection. Platelet count in a septicemic patient may also serve as a prognostic tool. There are many reports of thrombocytopenia due to septicemia in the literature but the occurrence of thrombocytopenia in maxillofacial infections is rare. Thrombocytopenia in a patient with odontogenic infection presents unique diagnostic and management challenges. A case report of an adult male patient with odontogenic infection, who developed life-threatening thrombocytopenia, is presented.

  11. Microangiopathic Hemolytic Anemia and Thrombocytopenia in Patients With Cancer.

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    Morton, Jordan M; George, James N

    2016-06-01

    The unexpected occurrence of thrombotic microangiopathy (TMA), characterized by microangiopathic hemolytic anemia and thrombocytopenia, in a patient with cancer requires urgent diagnosis and appropriate management. TMA is a term used to describe multiple syndromes caused by microvascular thrombosis, including thrombotic thrombocytopenic purpura (TTP), Shiga toxin-mediated hemolytic uremic syndrome, and complement-mediated TMA. In patients with cancer, systemic microvascular metastases and bone marrow involvement can cause microangiopathic hemolytic anemia and thrombocytopenia. This occurs most often in patients with known metastatic cancer, but microangiopathic hemolytic anemia and thrombocytopenia may occur unexpectedly in patients without known metastatic disease or be the presenting features of undiagnosed cancer. TMA may also be caused by commonly used chemotherapy agents, either through dose-dependent toxicity or an acute immune-mediated reaction. These causes of TMA must be distinguished from TTP, which results from a severe deficiency of ADAMTS13 and is the most common cause of TMA among adults without cancer. The importance of this distinction is to avoid inappropriate use of plasma exchange, which is associated with major complications. Plasma exchange is the essential treatment for TTP, but it has no known benefit for patients with cancer-induced or drug-induced TMA. We will describe cancer-induced and drug-induced TMA using the experience of the Oklahoma TTP-Hemolytic Uremic Syndrome Registry and data from a systematic review of all published reports of drug-induced TMA. We will illustrate the principles of evaluation and management of these disorders with patients' stories. Copyright © 2016 by American Society of Clinical Oncology.

  12. Immune thrombocytopenia in two unrelated Fanconi anemia patients – a mere coincidence?

    Directory of Open Access Journals (Sweden)

    Anna eKarastaneva

    2015-06-01

    Full Text Available Thrombocytopenia and pancytopenia, occurring in patients with Fanconi anemia (FA, are interpreted either as progression to bone marrow failure or as developing myelodysplasia. On the other hand, immune thrombocytopenia (ITP represents an acquired and often self-limiting benign hematologic disorder, associated with peripheral, immune-mediated, platelet destruction requiring different management modalities than those used in congenital bone marrow failure syndromes, including FA. Here we describe the clinical course of two independent FA patients with atypical - namely immune - thrombocytopenia. While in one patient belonging to complementation group FA-A, the ITP started at 17 months of age and showed a chronically persisting course with severe purpura, responding well to intravenous immunoglobulins (IVIG and later also danazol, a synthetic androgen, the other patient (of complementation group FA-D2 had a self-limiting course that resolved after one administration of IVIG. No cytogenetic aberrations or bone marrow abnormalities other than FA-typical mild dysplasia were detected. Our data show that acute and chronic ITP may occur in FA patients and impose individual diagnostic and therapeutic challenges in this rare congenital bone marrow failure / tumor predisposition syndrome. The management and a potential context of immune pathogenesis with the underlying marrow disorder are discussed.

  13. Anti-thymocyte serum as part of an immunosuppressive regimen in treating haematological immune-mediated diseases in dogs.

    Science.gov (United States)

    Cuq, B; Blois, S L; Mathews, K A

    2017-06-01

    To report the outcomes associated with the use of rabbit anti-dog thymocyte serum in dogs with haematological immune-mediated diseases. Medical records from 2000 to 2016 of patients diagnosed with immune-mediated haemolytic anaemia, immune-mediated thrombocytopenia, pancytopenia and myelofibrosis were reviewed. All dogs had a severe or refractory disease and received rabbit anti-dog thymocyte serum. Lymphocyte counts were used to monitor the immediate anti-thymocyte effect of therapy; long-term patient outcome was recorded. A total of 10 dogs were included. All dogs except one had a notable decrease in their lymphocyte count after rabbit anti-dog thymocyte serum; four of nine had a decrease to less than 10% of the initial lymphocyte count and one dog reached 10·8%. All dogs were discharged from the hospital following their treatment. The dog with no alteration of lymphocyte count following therapy with rabbit anti-dog thymocyte serum had refractory immune mediated haemolytic anemia and was euthanised within two weeks. All other cases achieved clinical remission with immunosuppressive therapy eventually being tapered (3 of 10) or discontinued (6 of 10). Rabbit anti-dog thymocyte serum therapy might be of interest as an adjunctive therapy in refractory immune-mediated diseases and suppressed lymphocyte counts in most dogs. © 2017 British Small Animal Veterinary Association.

  14. Immune-Mediated Therapies for Liver Cancer

    Directory of Open Access Journals (Sweden)

    Rajagopal N. Aravalli

    2017-02-01

    Full Text Available In recent years, immunotherapy has gained renewed interest as an alternative therapeutic approach for solid tumors. Its premise is based on harnessing the power of the host immune system to destroy tumor cells. Development of immune-mediated therapies, such as vaccines, adoptive transfer of autologous immune cells, and stimulation of host immunity by targeting tumor-evasive mechanisms have advanced cancer immunotherapy. In addition, studies on innate immunity and mechanisms of immune evasion have enhanced our understanding on the immunology of liver cancer. Preclinical and clinical studies with immune-mediated therapies have shown potential benefits in patients with liver cancer. In this review, we summarize current knowledge and recent developments in tumor immunology by focusing on two main primary liver cancers: hepatocellular carcinoma and cholangiocarcinoma.

  15. Pathobiology of secondary immune thrombocytopenia

    Science.gov (United States)

    Cines, Douglas B.; Liebman, Howard; Stasi, Roberto

    2009-01-01

    Primary immune thrombocytopenic purpura (ITP) remains a diagnosis of exclusion both from nonimmune causes of thrombocytopenia and immune thrombocytopenia that develops in the context of other disorders (secondary immune thrombocytopenia). The pathobiology, natural history, and response to therapy of the diverse causes of secondary ITP differ from each other and from primary ITP, so accurate diagnosis is essential. Immune thrombocytopenia can be secondary to medications or to a concurrent disease, such as an autoimmune condition (eg, systemic lupus erythematosus [SLE], antiphospholipid antibody syndrome [APS], immune thyroid disease, or Evans syndrome), a lymphoproliferative disease (eg, chronic lymphocytic leukemia or large granular T-lymphocyte lymphocytic leukemia), or chronic infection, eg, with Helicobacter pylori, human immunodeficiency virus (HIV), or hepatitis C virus (HCV). Response to infection may generate antibodies that cross-react with platelet antigens (HIV, H pylori) or immune complexes that bind to platelet Fcγ receptors (HCV) and platelet production may be impaired by infection of megakaryocyte bone marrow-dependent progenitor cells (HCV and HIV), decreased production of thrombopoietin (TPO), and splenic sequestration of platelets secondary to portal hypertension (HCV). Sudden and severe onset of thrombocytopenia has been observed in children after vaccination for measles, mumps, and rubella or natural viral infections, including Epstein-Barr virus, cytomegalovirus, and varicella zoster virus. This thrombocytopenia may be caused by cross-reacting antibodies and closely mimics acute ITP of childhood. Proper diagnosis and treatment of the underlying disorder, where necessary, play an important role in patient management. PMID:19245930

  16. Thrombocytopenia in Pregnancy

    Directory of Open Access Journals (Sweden)

    Mehmet Ozsurmeli

    2016-09-01

    Full Text Available Thrombocytopenia, which is encountered in 7-10% of pregnancies is characterized with decreased number of thrombocytes. The most frequent cause of thrombocytopenia during pregnancy is gestational thrombocytopenia. These patients usually do not have symptoms due to mild thrombocytopenia. The diagnosis is usually established by excluding connective tissue disorders, drug effects and obstetric causes. The etiology of thrombocytopenia during early pregnancy is most frequently due to autoimmune causes. Thrombocytopenia secondary to obstetric causes like preeclampsia, HELLP syndrome should always be kept in mind. Under these circumstances the thrombocytopenia will not resolve unless pregnancy is terminated. The clinician should be able to distinguish between thrombocytopenia that does not require treatment and the causes that require emergent and serious medical interventions. [Archives Medical Review Journal 2016; 25(3.000: 420-432

  17. Thrombocytopenia in HIV

    African Journals Online (AJOL)

    2007-06-15

    experienced patients, thrombocytopenia was found to be one of 8 factors ... treatment of. HIV-induced thrombocytopenia and there is a paucity of forthcoming trials on this topic since antiretrovirals have become commonly used.

  18. Prevalencia de trombocitopenia en niños con HIV/sida Prevalence of thrombocytopenia in HIV infected children

    Directory of Open Access Journals (Sweden)

    Graciela Barboni

    2010-10-01

    Full Text Available La trombocitopenia es una de las múltiples alteraciones hematológicas presentes en pacientes infectados con el virus de la inmunodeficiencia humana (HIV. Puede ser de curso crónico, en la cual la destrucción inmune, el secuestro esplénico o el daño en la producción son los mecanismos primariamente involucrados, o aguda, acompañando a otra intercurrencia. En este trabajo se evaluó la prevalencia de trombocitopenia en un lapso de 14 años, en una población pediátrica con HIV/sida, analizando las características clínicas y la relación con el estado inmuno-virológico. La prevalencia de trombocitopenia fue de 8.5%, (29 de los 339 niños en seguimiento. En 22 fue de curso crónico y en 7 aguda. Los pacientes evaluados presentaron niveles porcentuales de TCD4+ variables y la presencia de trombocitopenia no estuvo en relación con el compromiso inmunitario. Los pacientes trombocitopénicos tuvieron niveles de carga viral significativamente mayores que los que no la presentaron. En 10 de los 29 niños con recuentos plaquetarios disminuidos, la trombocitopenia fue la manifestación inicial de la infección por HIV. Las manifestaciones hemorrágicas de las trombocitopenias crónicas fueron leves, presentes en el 23% de los niños y no se asociaron al deterioro inmunológico, mientras que en las agudas fueron más graves y condicionadas a la evolución de la enfermedad coexistente. El desarrollo de trombocitopenias se ve favorecido por la continua actividad viral y la falla en la implementación del tratamiento antirretroviral adecuado.Thrombocytopenia is a common hematologic finding in patients infected with the human immunodeficiency virus. Multiple mechanisms may contribute to the development of chronic thrombocytopenia as immune-mediated platelet destruction, enhanced platelet splenic sequestration and impaired platelet production. Acute thrombocytopenia is frequently associated with coexisting disorders. In this study, the prevalence of

  19. Immune-mediated diseases and microbial exposure in early life

    DEFF Research Database (Denmark)

    Bisgaard, H; Bønnelykke, K; Stokholm, Jacob

    2014-01-01

    The non-communicable disease pandemic includes immune-mediated diseases such as asthma and allergy, which are likely originating in early life where the immature immune system is prone to alterations caused by the exposome. The timing of exposure seems critical for the developing immune system......-gene interaction is a fascinating paradigm that fosters exiting research and promises a breakthrough in the understanding of the mechanisms driving asthma, allergy and eczema, and potentially also other immune-mediated non-communicable diseases....

  20. Advances in alloimmune thrombocytopenia: perspectives on current concepts of human platelet antigens, antibody detection strategies, and genotyping.

    Science.gov (United States)

    Hayashi, Tomoya; Hirayama, Fumiya

    2015-07-01

    Alloimmunisation to platelets leads to the production of antibodies against platelet antigens and consequently to thrombocytopenia. Numerous molecules located on the platelet surface are antigenic and induce immune-mediated platelet destruction with symptoms that can be serious. Human platelet antigens (HPA) cause thrombocytopenias, such as neonatal alloimmune thrombocytopenia, post-transfusion purpura, and platelet transfusion refractoriness. Thirty-four HPA are classified into 28 systems. Assays to identify HPA and anti-HPA antibodies are critically important for preventing and treating thrombocytopenia caused by anti-HPA antibodies. Significant progress in furthering our understanding of HPA has been made in the last decade: new HPA have been discovered, antibody-detection methods have improved, and new genotyping methods have been developed. We review these advances and discuss issues that remain to be resolved as well as future prospects for preventing and treating immune thrombocytopenia.

  1. Drug-induced thrombocytopenia

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, U; Andersen, M; Hansen, P B

    1997-01-01

    induced by non-cytotoxic drugs is characterised by heterogeneous clinical picture and recovery is generally rapid. Although corticosteroids seem inefficient, we still recommend that severe symptomatic cases of drug-induced thrombocytopenia are treated as idiopathic thrombocytopenic purpura due...

  2. How Is Thrombocytopenia Diagnosed?

    Science.gov (United States)

    ... information about this procedure, go to the Health Topics Blood Transfusion article. Splenectomy A splenectomy is surgery to remove ... experiences with clinical research. More Information Related Health Topics Aplastic ... Thrombocytopenia Thrombotic Thrombocytopenic Purpura ...

  3. How Is Thrombocytopenia Treated?

    Science.gov (United States)

    ... information about this procedure, go to the Health Topics Blood Transfusion article. Splenectomy A splenectomy is surgery to remove ... experiences with clinical research. More Information Related Health Topics Aplastic ... Thrombocytopenia Thrombotic Thrombocytopenic Purpura ...

  4. Living with Thrombocytopenia

    Science.gov (United States)

    ... information about this procedure, go to the Health Topics Blood Transfusion article. Splenectomy A splenectomy is surgery to remove ... experiences with clinical research. More Information Related Health Topics Aplastic ... Thrombocytopenia Thrombotic Thrombocytopenic Purpura ...

  5. What Causes Thrombocytopenia?

    Science.gov (United States)

    ... information about this procedure, go to the Health Topics Blood Transfusion article. Splenectomy A splenectomy is surgery to remove ... experiences with clinical research. More Information Related Health Topics Aplastic ... Thrombocytopenia Thrombotic Thrombocytopenic Purpura ...

  6. Living with Immune Thrombocytopenia

    Science.gov (United States)

    ... information about platelet transfusions, go to the Health Topics Blood Transfusion article. Treating Infections Some infections can briefly lower ... experiences with clinical research. More Information Related Health Topics Blood ... Tests Thrombocytopenia Thrombotic Thrombocytopenic Purpura Other ...

  7. Mechanisms of conduction block in immune-mediated polyneuropathies

    NARCIS (Netherlands)

    Straver, D.C.G.

    2013-01-01

    Multifocal motor neuropathy (MMN) and chronic inflammatory demyelinating polyneuropathy (CIDP) are immune-mediated neuropathies. Despite treatment being available, patients suffer from disabling weakness of arm and leg muscles and fatigue. Pathogenesis of MMN and CIDP is unclear, but the development

  8. Eltrombopag for the Treatment of Immune Thrombocytopenia: The Aegean Region of Turkey Experience

    Directory of Open Access Journals (Sweden)

    Füsun Özdemirkıran

    2015-12-01

    Full Text Available INTRODUCTION: OBJECTIVE: Immune thrombocytopenia (ITP is an immune mediated disease characterized by transient or persistent decrease of the platelet count to less than 100 × 109/l. Although it is included in a benign disease group, bleeding complications may be mortal. With a better understanding of the pathophysiology of the disease, thrombopoietin receptor agonists which came into use in recent years, seem to be an effective option in the treatment of resistant patients. METHODS: In this study, retrospective data of 40 patients who were treated with Eltrombopag due to the diagnosis of refractory ITP in the Aegean region were examined and evaluated. RESULTS: In the study total rate of response was 87%, and in the cases with response the median period that number of platelets reached over 50. × 109/l was determined as 19.5 (5-60 days. DISCUSSION AND CONCLUSION: CONCLUSION: In one patient venous sinus thrombosis was observed and showed no other additional risk factor due to/ related to thrombosis. The other patient with complete response and irregular follow-up for 12 months was lost due to sudden death as the result of propable acute myocardial infarction.

  9. Thalidomide-associated thrombocytopenia

    NARCIS (Netherlands)

    Duyvendak, M; Naunton, M.; Kingma, B.J; Brouwers, J.R.B.J.

    2005-01-01

    OBJECTIVE: To report thrombocytopenia in a patient prescribed thalidomide for multiple myeloma (MM). CASE SUMMARY: A 70-year-old woman was diagnosed in 2003 with MM. At diagnosis, melphalan 0.25 mg/kg/day and prednisolone 2 mg/kg/day were started; however, the patient became refractory to therapy.

  10. THROMBOCYTOPENIA IN DENGUE HAEMORRHAGIC FEVER

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    I Wayan Putu Sutirta-Yasa

    2013-04-01

    Full Text Available The incidence and geographical distribution of dengue has gradually increased during the past decade. Today, dengue is considered one of the most important arthropod-borne viral diseasases in humans in term of morbidity and mortality. Dengue infection   a potential life-threatening dengue hemorrhagic fever (DHF / dengue shock syndrome(DSS, characterized by thrombocytopenia and increased vascular permiability. Thrombocytopenia causes bleeding, but in   DHF patients with thrombocytopenia do not always develop bleeding manifestation. The pathogenesis of thrombocytopenia are not cleared. Multiple factors  may be involved in the machanisms leading to thrombocytopenia in DHF/DSS patients.

  11. Immune-mediated rippling muscle disease and myasthenia gravis.

    Science.gov (United States)

    Bettini, Mariela; Gonorazky, Hernan; Chaves, Marcelo; Fulgenzi, Ernesto; Figueredo, Alejandra; Christiansen, Silvia; Cristiano, Edgardo; Bertini, Enrico S; Rugiero, Marcelo

    2016-10-15

    Cases of acquired rippling muscle disease in association with myasthenia gravis have been reported. We present three patients with iRMD (immune-mediated rippling muscle disease) and AChR-antibody positive myasthenia gravis. None of them had thymus pathology. They presented exercise-induced muscle rippling combined with generalized myasthenia gravis. One of them had muscle biopsy showing a myopathic pattern and a patchy immunostaining with caveolin antibodies. They were successfully treated steroids and azathioprine. The immune nature of this association is supported by the response to immunotherapies and the positivity of AChR-antibodies. Copyright © 2016 Elsevier B.V. All rights reserved.

  12. [Immune-mediated encephalomyelitis following varicella-zoster virus infection after allogeneic stem cell transplantation].

    Science.gov (United States)

    Tachibana, Takayoshi; Takasaki, Hirotaka; Tanaka, Masatsugu; Numata, Ayumi; Yamazaki, Etsuko; Segawa, Fuminori; Fujisawa, Shin; Maruta, Atsuo; Ishigatsubo, Yoshiaki; Kanamori, Heiwa

    2012-04-01

    A 40-year-old Japanese man with acute myeloid leukemia received allogeneic bone marrow transplantation. On day 101, varicella-zoster virus (VZV) infection occurred, but was improved by administration of acyclovir and immunoglobulin. On day 119, he complained of numbness and double vision, and he was admitted due to exacerbation of the symptoms. The findings of cerebrospinal fluid and magnetic resonance image examination were consistent with the diagnosis of immune-mediated encephalomyelitis (IMEM). Intravenous immunoglobulin therapy was effective and his neurological findings dramatically improved without recurrence. IMEM is a rare non-infectious inflammatory demyelinating disease that can occur after transplantation. We herein describe a case report with a review of the associated literature.

  13. The Gut Microbiota in Immune-Mediated Inflammatory Diseases

    Directory of Open Access Journals (Sweden)

    Jessica D Forbes

    2016-07-01

    Full Text Available The collection of microbes and their genes that exist within and on the human body, collectively known as the microbiome has emerged as a principal factor in human health and disease. Humans and microbes have established a symbiotic association over time, and perturbations in this association have been linked to several immune-mediated inflammatory diseases (IMID including inflammatory bowel disease, rheumatoid arthritis and multiple sclerosis. IMID is a term used to describe a group of chronic, highly disabling diseases that affect different organ systems. Though a cornerstone commonality between IMID is the idiopathic nature of disease, a considerable portion of their pathobiology overlaps including epidemiological co-occurrence, genetic susceptibility loci and environmental risk factors. At present, it is clear that persons with an IMID are at an increased risk for developing comorbidities, including additional IMID. Advancements in sequencing technologies and a parallel explosion of 16S rDNA and metagenomics community profiling studies have allowed for the characterization of microbiomes throughout the human body including the gut, in a myriad of human diseases and in health. The main challenge now is to determine if alterations of gut flora are common between IMID or, if particular changes in the gut community are in fact specific to a single disease. Herein, we review and discuss the relationships between the gut microbiota and IMIDKeywords: gut microbiome, systems microbiology gut metagenome, chronic immune mediated inflammatory diseases

  14. Inflammatory Bowel Disease: Autoimmune or Immune-mediated Pathogenesis?

    Directory of Open Access Journals (Sweden)

    Zhonghui Wen

    2004-01-01

    Full Text Available The pathogenesis of Crohn's disease (CD and ulcerative colitis (UC, the two main forms of inflammatory bowel disease (IBD, is still unclear, but both autoimmune and immune-mediated phenomena are involved. Autoimmune phenomena include the presence of serum and mucosal autoantibodies against intestinal epithelial cells in either form of IBD, and against human tropomyosin fraction five selectively in UC. In addition, perinuclear antineutrophil cytoplasmic antibodies (pANCA are common in UC, whereas antibodies against Saccharomyces cerevisiae (ASCA are frequently found in CD. Immune-mediate phenomena include a variety of abnormalities of humoral and cell-mediated immunity, and a generalized enhanced reactivity against intestinal bacterial antigens in both CD and UC. It is currently believed that loss of tolerance against the indigenous enteric flora is the central event in IBD pathogenesis. Various complementary factors probably contribute to the loss of tolerance to commensal bacteria in IBD. They include defects in regulatory T-cell function, excessive stimulation of mucosal dendritic cells, infections or variants of proteins critically involved in bacterial antigen recognition, such as the products of CD-associated NOD2/CARD15 mutations.

  15. Life-Threatening Thrombocytopenia Following Intravenous Contrast Media Infusion.

    Science.gov (United States)

    Park, Mihwa; Kim, Minjeong; Park, Jisun; Cho, Jinhyun

    2018-01-01

    Radiocontrast media-induced acute severe thrombocytopenia is a very rare complication and potentially life-threatening. Here, we report the case of a 63-year-old male patient with severe acute thrombocytopenia following first exposure to intravenous non-ionic contrast media without immediate allergic reactions. His platelet count dropped from 107000/μL to 2000/μL after six hours of radiocontrast infusion. After administration of corticosteroid and transfusion of platelet concentrates, the platelet count returned gradually to normal within 5 days. To the best of our knowledge, non-ionic contrast media-induced isolated acute severe thrombocytopenia following no signs or symptoms of immediate allergic reaction has never been described. © Copyright: Yonsei University College of Medicine 2018.

  16. Protective Effect of Akkermansia muciniphila against Immune-Mediated Liver Injury in a Mouse Model

    Directory of Open Access Journals (Sweden)

    Wenrui Wu

    2017-09-01

    Full Text Available Accumulating evidence indicates that gut microbiota participates in the pathogenesis and progression of liver diseases. The severity of immune-mediated liver injury is associated with different microbial communities. Akkermansia muciniphila can regulate immunologic and metabolic functions. However, little is known about its effects on gut microbiota structure and function. This study investigated the effect of A. muciniphila on immune-mediated liver injury and potential underlying mechanisms. Twenty-two C57BL/6 mice were assigned to three groups (N = 7–8 per group and continuously administrated A. muciniphila MucT or PBS by oral gavage for 14 days. Mouse feces were collected for gut microbiota analysis on the 15th day, and acute liver injury was induced by Concanavalin A (Con A, 15 mg/kg injection through the tail vein. Samples (blood, liver, ileum, colon were assessed for liver injury, systemic inflammation, and intestinal barrier function. We found that oral administration of A. muciniphila decreased serum ALT and AST and alleviated liver histopathological damage induced by Con A. Serum levels of pro-inflammatory cytokines and chemokines (IL-2, IFN-γ, IL-12p40, MCP-1, MIP-1a, MIP-1b were substantially attenuated. A. muciniphila significantly decreased hepatocellular apoptosis; Bcl-2 expression increased, but Fas and DR5 decreased. Further investigation showed that A. muciniphila enhanced expression of Occludin and Tjp-1 and inhibited CB1 receptor, which strengthened intestinal barriers and reduced systemic LPS level. Fecal 16S rRNA sequence analysis indicated that A. muciniphila increased microbial richness and diversity. The community structure of the Akk group clustered distinctly from that of mice pretreated with PBS. Relative abundance of Firmicutes increased, and Bacteroidetes abundance decreased. Correlation analysis showed that injury-related factors (IL-12p40, IFN-γ, DR5 were negatively associated with specific genera

  17. Bevacizumab-Induced Reversible Thrombocytopenia in a Patient with Adenocarcinoma of Colon: Rare Adverse Effect of Bevacizumab

    Directory of Open Access Journals (Sweden)

    Jeevan Kumar

    2012-01-01

    Full Text Available We report a case of bevacizumab- (BEV- induced thrombocytopenia in a 59-year-old man with adenocarcinoma of colon. After colectomy, the patient was treated with twelve cycles of FOLFOX-4 (folinic acid, 5-fluorouracil, and oxaliplatin regimen. On relapse, he was treated with FOLFIRI (folinic acid, 5-fluorouracil, and irinotecan regimen along with BEV 10 mg/kg for 6 cycles. After that, BEV was continued for maintenance as a single agent at an interval of three weeks. After the13th cycle of BEV, the patient developed melena with epistaxis and thrombocytopenia, from which he recovered on withdrawal of BEV. On rechallenge with half the initial dose, there was once again a reversible drop in platelet count. The proposed mechanism of thrombocytopenia may be immune-mediated peripheral destruction of platelets.

  18. Acute Compressive Ulnar Neuropathy in a Patient of Dengue Fever: An Unusual Presentation

    Directory of Open Access Journals (Sweden)

    Anil K Mehtani

    2013-04-01

    Full Text Available Introduction: Dengue haemorrhagic fever is known for its haemorrhagic and neurologic complications. Neurologic complications are caused by three mechanism namely neurotropism, systemic complications causing encephalopathy and postinfectious immune-mediated mechanisms. However acute compressive neuropathy due to haemorrhage is not frequent and we could find no literature describing this Case Report: We report a case of acute compressive ulnar neuropathy due to peri neural hematoma, following an attempt at intravenous cannulation in the cubital fossa in a patient of dengue haemorrhagic fever with thrombocytopenia. Immediate fasciotomy and removal of haematoma was performed to relieve the symptoms. Conclusion: Compression neuropathies can be seen in dengue hemorrhagic fever and removal of compressing hematoma relieves symptoms. Keywords: Dengue haemmorrhagic fever; coagulopathy; peri neural haematoma.

  19. Recurrent Acute Myocardial Infarction in Patients with Immune Thrombocytopenic Purpura

    Directory of Open Access Journals (Sweden)

    Fengyi Shen

    2014-01-01

    Full Text Available Immune thrombocytopenic purpura (ITP, also known as idiopathic thrombocytopenic purpura, is an acquired immune-mediated disease of adults and children characterized by a transient or persistent decrease of platelets and, depending upon the degree of thrombocytopenia, an increased risk of bleeding. The use of standard treatments for acute myocardial infarction (AMI, such as antiplatelet agents and anticoagulants, pose serious problems in patients with ITP due to the potential higher risk of bleeding complications. There are no current guidelines available for management of ITP patients with AMI. In this brief review of the limited available literature, we discuss the proposed pathophysiological link between ITP and arterial thrombosis and the challenging medical and interventional treatment of these patients.

  20. Epileptic encephalopathy in children possibly related to immune-mediated pathogenesis.

    Science.gov (United States)

    Specchio, Nicola; Fusco, Lucia; Claps, Dianela; Vigevano, Federico

    2010-01-01

    Severe epilepsy in the paediatric population negatively influences neurological and cognitive development. Different etiological factors could be responsible of these severe epilepsies, and an early diagnosis could change, in some cases, the neurological and cognitive development. Immune mechanisms have been reported in epilepsy. Epilepsy has been associated with systemic lupus erythematosus, with the presence of anti-phospholipid antibodies (aPL), anti-cardiolipin antibodies, anti-nuclear antibodies, Beta2-glycoprotein antibodies, and anti-glutamic acid decarboxylase (anti-GAD) antibodies. CNS inflammation and markers of adaptive immunity have been, also, associated with some epileptic syndromes, such as West syndrome, temporal lobe epilepsy, febrile seizures, tonic-clonic seizures, and tuberous sclerosis. Inflammation and blood-brain barrier (BBB) disruption could be one of the mechanisms responsible for seizure recurrence. Recently clinical entities, characterized by severe epilepsy with a febrile, acute or sub-acute onset, sometimes associated with status epilepticus, followed by drug-resistant, partial epilepsy have been described. Some of these publications also suggested acronyms for the condition described: Acute Encephalitis with Refractory, Repetitive Partial Seizures (AERRPS) reported by Japanese authors, Devastating Epileptic Encephalopathy in School-aged Children (DESC) reported by French authors. Among children with acquired symptomatic severe epilepsy, we identified a group of previously normal children who had developed severe partial epilepsy after an acute/sub-acute illness resembling encephalitis. The etiological factors for those patients seems to remain unknown, and a possible immune-mediating or inflammatory process as pathogenesis of the disease could be hypothesized. More studies need to be addressed to finally define this peculiar epileptic entity. Copyright 2009 Elsevier B.V. All rights reserved.

  1. Romiplostim as a treatment for immune thrombocytopenia: a review

    Directory of Open Access Journals (Sweden)

    Chalmers S

    2015-01-01

    Full Text Available Sarah Chalmers,1,2 Michael D Tarantino1–31University of Illinois College of Medicine – Peoria, 2The Children's Hospital of Illinois, 3The Bleeding and Clotting Disorders Institute, Peoria, Illinois, USAAbstract: “Immune thrombocytopenia” (ITP is an autoimmune disorder that leads to peripheral destruction, as well as a decreased production of platelets. ITP most commonly presents as mild mucocutaneous bleeding. Though it is rare, the leading cause of mortality in persons with ITP is intracranial hemorrhage and those that do not respond to therapy are at increased risk. Our understanding of the pathophysiology of ITP has evolved immensely, especially over the last 60 years. The discovery of the platelet-production stimulator, thrombopoietin (TPO, lent clarity to an earlier hypothesis that inhibition of platelet production at the level of the megakaryocyte, at least in part, accounts for thrombocytopenia in adults with ITP. This facilitated the development of TPO-based therapies to treat ITP. Thrombopoietin receptor agonists are one of the most recent treatments to enter the landscape. Original production of a recombinant human TPO was halted after clinical trials revealed the untoward effect of autoantibodies to the recombinant human TPO with cross-reactivity to endogenous TPO. Next-step development focused on stimulation of the TPO receptor with fewer immunogenic agents. Currently, two such thrombopoietin receptor agonists, romiplostim and eltrombopag, are licensed in the USA to treat thrombocytopenia in adults with persistent or chronic ITP. Ongoing research will assess their efficacy in other immune-mediated and nonimmune-mediated primary and secondary thrombocytopenias.Keywords: thrombopoietin, thrombopoietin receptor agonist, megakaryocyte, peptibody

  2. How Is Immune Thrombocytopenia Treated?

    Science.gov (United States)

    ... information about platelet transfusions, go to the Health Topics Blood Transfusion article. Treating Infections Some infections can briefly lower ... experiences with clinical research. More Information Related Health Topics Blood ... Tests Thrombocytopenia Thrombotic Thrombocytopenic Purpura Other ...

  3. How Is Immune Thrombocytopenia Diagnosed?

    Science.gov (United States)

    ... information about platelet transfusions, go to the Health Topics Blood Transfusion article. Treating Infections Some infections can briefly lower ... experiences with clinical research. More Information Related Health Topics Blood ... Tests Thrombocytopenia Thrombotic Thrombocytopenic Purpura Other ...

  4. Management of refractory bleeding post-cardiopulmonary bypass in an acute heparin-induced thrombocytopenia type II renal failure patient who underwent urgent cardiac surgery with bivalirudin (Angiox®) anticoagulation.

    Science.gov (United States)

    Hassen, Kimberly; Maccaroni, Maria R; Sabry, Haytham; Mukherjee, Smitangshu; Serumadar, Shankari; Birdi, Inderpaul

    2018-04-01

    Acute heparin-induced thrombocytopenia (HIT) patients present a myriad of anticoagulation management challenges, in clinical settings where unfractionated heparin (UFH) is the traditional drug of choice. UFH use in cardiac surgery is a known entity that has been subject to rigorous research. Research has, thus, led to its unparalleled use and the development of well-established protocols for cardiac surgery. In comparison to UFH, bivalirudin use for acute HIT patients requiring urgent cardiac surgery with cardiopulmonary bypass (CPB) is still in its infancy. We describe the tailored post-CPB management of refractory bleeding in a 65-year-old infective endocarditis, acute HIT patient with renal failure who underwent urgent aortic valve replacement and mitral valve repair with bivalirudin anticoagulation. A management approach that entailed a combination of continuous venovenous haemofiltration (CVVH), 4-Factor prothrombin complex concentrate (PCC) (Beriplex), recombinant factor VIIa (rFactor VIIa) and desmopressin (DDAVP) were consecutively used post-operatively in theatre. Based on this case study experience, two modifications to institutional protocols are recommended. The first is the use of CVVH in theatre to eliminate bivalirudin in renal failure patients or in patients where bivalirudin elimination is prolonged. Secondly, a 'rescue therapy/intervention' algorithm for the swift identification of refractory bleeding post-CPB is also recommended. Rescue therapy agents, such as a 4-Factor PCCs and rFactor VIIa, should be incorporated into the protocol after a robust evidence-based search and agreement with the haematologist. The aim of these recommendations is to reduce the risk of bleeding associated with bivalirudin use for inexperienced institutions and experienced institutions alike, until larger randomized, controlled studies provide more in-depth knowledge to expand our clinical practice.

  5. Adiponectin in inflammatory and immune-mediated diseases.

    Science.gov (United States)

    Fantuzzi, Giamila

    2013-10-01

    Circulating levels of adiponectin (APN) are reduced in obesity and associated comorbidities, with inflammation playing an important role in downregulating APN production. In contrast to obesity and metabolic disease, elevated systemic and local levels of APN are present in patients with inflammatory and immune-mediated diseases, including autoimmune and pulmonary conditions, heart and kidney failure, viral hepatitis, organ transplantation and perhaps critical illness. A positive association between inflammation and APN is usually reported in inflammatory/immune pathologies, in contrast with the negative correlation typical of metabolic disease. This review discusses the role of APN in modulation of inflammation and immunity and the potential mechanisms leading to increased levels of APN in inflammatory/immune diseases, including modification of adipose tissue physiology; relative contribution of different tissues and adipose depots; hormonal, pharmacological, nutritional and life style factors; the potential contribution of the microbiota as well as the role of altered APN clearance and release from T-cadherin-associated tissue reservoirs. Potential reasons for some of the apparently contradictory findings on the role of APN as a modulator of immunity and inflammation are also discussed, including a comparison of types of recombinant APN used for in vitro studies and strain-dependent differences in the phenotype of APN KO mice. Copyright © 2013 Elsevier Ltd. All rights reserved.

  6. Immune-Mediated Inner Ear Disease: Diagnostic and therapeutic approaches.

    Science.gov (United States)

    Penêda, José Ferreira; Lima, Nuno Barros; Monteiro, Francisco; Silva, Joana Vilela; Gama, Rita; Condé, Artur

    2018-03-07

    Immune Mediated Inner Ear Disease (IMIED) is a rare form of sensorineural bilateral hearing loss, usually progressing in weeks to months and responsive to immunosuppressive treatment. Despite recent advances, there is no consensus on diagnosis and optimal treatment. A review of articles on IMIED from the last 10 years was conducted using PubMed ® database. IMIED is a rare disease, mostly affecting middle aged women. It may be a primary ear disease or secondary to autoimmune systemic disease. A dual immune response (both cellular and humoral) seems to be involved. Cochlin may be the inner ear protein targeted in this disease. Distinction from other (core common) forms of neurosensory hearing loss is a challenge. Physical examination is mandatory for exclusion of other causes of hearing loss; audiometry identifies characteristic hearing curves. Laboratory and imaging studies are controversial since no diagnostic marker is available. Despite recent research, IMIED diagnosis remains exclusive. Steroids are the mainstay treatment; other therapies need further investigation. For refractory cases, cochlear implantation is an option and with good relative outcome. Copyright © 2018 Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. Publicado por Elsevier España, S.L.U. All rights reserved.

  7. Aggravating Impact of Nanoparticles on Immune-Mediated Pulmonary Inflammation

    Directory of Open Access Journals (Sweden)

    Ken-Ichiro Inoue

    2011-01-01

    Full Text Available Although the adverse health effects of nanoparticles have been proposed and are being clarified, their aggravating effects on pre-existing pathological conditions have not been fully investigated. In this review, we provide insights into the immunotoxicity of both airborne and engineered nanoparticles as an exacerbating factor on hypersusceptible subjects, especially those with immune-mediated pulmonary inflammation, using our in vivo experimental model. First, we exhibit the effects of nanoparticles on pulmonary inflammation induced by bacterial endotoxin (lipopolysaccharide: LPS as a disease model in innate immunity, and demonstrate that nanoparticles instilled through both an intratracheal tube and an inhalation system can exacerbate the lung inflammation. Second, we introduce the effects of nanoparticles on allergic pulmonary inflammation as a disease model in adaptive immunity, and show that repetitive pulmonary exposure to nanoparticles has aggravating effects on allergic inflammation, including adjuvant effects on Th2-milieu. Third, we show that very small nanoparticle exposure exacerbates emphysematous pulmonary inflammation, which is concomitant with enhanced lung expression of proinflammatory molecules (including those that are innate immunity related. Taken together, nanoparticle exposure may synergistically facilitate pathological pulmonary inflammation via both innate and adaptive immunological impairment.

  8. Type 1 immune-mediated polyarthritis in dogs and lack of a temporal relationship to vaccination.

    Science.gov (United States)

    Idowu, O A; Heading, K L

    2018-03-01

    To investigate whether there is a temporal relationship between vaccination and the onset of type 1 immune-mediated polyarthritis in dogs. Retrospective case-control study: 39 dogs from a referral hospital with a diagnosis of type 1 immune-mediated polyarthritis were age-matched with 78 control dogs with other diagnoses. A temporal association between vaccination and polyarthritis was considered positive if recent vaccination had been performed within 28 days of the onset of clinical signs of immune-mediated polyarthritis. The odds ratio association of recent vaccination with immune-mediated polyarthritis was calculated using matched case-control methods. Of the 39 dogs in the type 1 immune-mediated polyarthritis group, four had been vaccinated within 28 days before onset of clinical signs compared to six dogs in the control group. The odds ratio for a dog developing type 1 immune-mediated polyarthritis if vaccinated within the last 28 days was estimated to be 1·44 (95% confidence interval 0·25 to 8·24, P = 0·88). There was no evidence of a temporal relationship between vaccination and type 1 immune-mediated polyarthritis, although the large confidence interval on the odds ratio suggests a need for larger studies to confirm this finding. © 2017 British Small Animal Veterinary Association.

  9. Ceftazidime-induced thrombocytopenia.

    Science.gov (United States)

    Domingo-Chiva, E; Díaz-Rangel, M; Monsalve-Naharro, J Á; Cuesta-Montero, P; Catalá-Ripoll, J V; García-Martínez, E M

    2017-12-01

    Ceftazidime is an antibiotic belonging to the group of third generation cephalosporins, frequently used in clinical practice for its broad antibacterial spectrum. A case report is presented on a 78-year-old man who entered the intensive care unit due to respiratory failure secondary to nosocomial pneumonia in the postoperative period of a laparoscopic hepatic bisegmentectomy for a hepatocarcinoma. It required invasive mechanical ventilation and was treated with ceftazidime, developing a progressive decrease in platelet count after the onset of this drug and after re-exposure to it, not coinciding with the introduction of other drugs. The adverse reaction was reported to the Spanish pharmacosurveillance system and according to the Naranjo algorithm the causal relationship was probable. Since no case of ceftazidime-induced thrombocytopenia was found in the literature, we consider knowledge of it relevant as an adverse effect to be taken into account given its potential severity, especially when it cannot be explained by other causes. Copyright © 2017 Sociedad Española de Anestesiología, Reanimación y Terapéutica del Dolor. Publicado por Elsevier España, S.L.U. All rights reserved.

  10. C-reactive protein enhances IgG-mediated phagocyte responses and thrombocytopenia

    NARCIS (Netherlands)

    Kapur, Rick; Heitink-Polle, Katja M. J.; Porcelijn, Leendert; Bentlage, Arthur E. H.; Bruin, MCA; Visser, Remco; Roos, Dirk; Schasfoort, Richard B. M.; de Haas, Masja; van der Schoot, C. Ellen; Vidarsson, Gestur

    2015-01-01

    Immune-mediated platelet destruction is most frequently caused by allo-or autoantibodies via Fc gamma receptor-dependent phagocytosis. Disease severity can be predicted neither by antibody isotype nor by titer, indicating that other factors play a role. Here we show that the acute phase protein

  11. The Role of Histone Demethylase Jmjd3 in Immune-Mediated Aplastic Anemia

    Science.gov (United States)

    2017-03-01

    AWARD NUMBER: W81XWH-16-1-0055 TITLE: The Role of Histone Demethylase Jmjd3 in Immune-Mediated Aplastic Anemia PRINCIPAL INVESTIGATOR: Yi...Immune-Mediated Aplastic Anemia 5a. CONTRACT NUMBER 5b. GRANT NUMBER W81XWH-16-1-0055 5c. PROGRAM ELEMENT NUMBER 6. AUTHOR(S) Yi Zhang 5d... anemia (AA) is a condition of bone marrow failure (BMF) characterized by blood pancytopenia and BM hypoplasia. In most cases, AA is an immune-mediated

  12. Significance of anti-cyclic citrullinated peptide autoantibodies in immune-mediated inflammatory skin disorders with and without arthritis

    Directory of Open Access Journals (Sweden)

    Chander Grover

    2016-01-01

    Full Text Available Background: Anti-cyclic citrullinated peptides (CCPs are autoantibodies directed against citrullinated peptides. Rheumatoid factor (RF, an antibody against the Fc portion of IgG, is known to form immune complexes and contribute to the etiopathogenesis of various skin disorders. C-reactive protein (CRP, an acute-phase protein, increases following secretion of interleukin-6 from macrophages and T cells. Anti-CCP, RF, and CRP are well-established immune-markers, their diagnostic potential in immune-mediated skin disorders remains less widely studied. Aims and Objectives: To determine the correlation between anti-CCP, RF, and CRP in immune-mediated inflammatory skin diseases. Materials and Methods: About 61 clinically diagnosed cases of various immune-mediated skin diseases (psoriasis [n = 38], connective tissue diseases such as systemic lupus erythematosus and systemic sclerosis [n = 14], and immunobullous disorders including pemphigus vulgaris and pemphigus foliaceus [n = 9] were included in the study. These patients were subclassified on the basis of presence or absence of arthritis. Arthritis was present in nine cases of psoriasis and seven connective tissue disorder patients. Detection of serum anti-CCP was done using enzyme-linked immunosorbent assay, whereas CRP and RF levels were detected using latex agglutination technique. Results: Of the 61 specimens, 14.75% had elevated serum anti-CCP levels. RF and CRP levels were elevated in 18.03% and 39.34% specimens, respectively. RF was elevated in 13.16% of inflammatory and 42.88% of connective tissue disorders, whereas anti-CCP was raised in 10.53% of inflammatory and 35.71% of connective tissue disorders. CRP positivity was highest in connective tissue disorders (50%, followed by 39.47% in inflammatory and 22.22% in immunobullous conditions. In none of the immunobullous patients, anti-CCP or RF levels were found to be elevated. Association of the presence of arthritis with elevated anti-CCP was

  13. Cardiovascular disease in immune-mediated inflammatory diseases

    Science.gov (United States)

    Fernández-Gutiérrez, Benjamín; Perrotti, Pedro P.; Gisbert, Javier P.; Domènech, Eugeni; Fernández-Nebro, Antonio; Cañete, Juan D.; Ferrándiz, Carlos; Tornero, Jesús; García-Sánchez, Valle; Panés, Julián; Fonseca, Eduardo; Blanco, Francisco; Rodríguez-Moreno, Jesús; Carreira, Patricia; Julià, Antonio; Marsal, Sara; Rodriguez-Rodriguez, Luis

    2017-01-01

    Abstract To analyze in several immune-mediated inflammatory diseases (IMIDs) the influence of demographic and clinical-related variables on the prevalence of cardiovascular disease (CVD), and compare their standardized prevalences. Cross-sectional study, including consecutive patients diagnosed with rheumatoid arthritis, psoriatic arthritis, psoriasis, systemic lupus erythematosus, Crohn disease, or ulcerative colitis, from rheumatology, gastroenterology, and dermatology tertiary care outpatient clinics located throughout Spain, between 2007 and 2010. Our main outcome was defined as previous diagnosis of angina, myocardial infarction, peripheral vascular disease, and/or stroke. Bivariate and multivariate logistic and mixed-effects logistic regression models were performed for each condition and the overall cohort, respectively. Standardized prevalences (in subjects per 100 patients, with 95% confidence intervals) were calculated using marginal analysis. We included 9951 patients. For each IMID, traditional cardiovascular risk factors had a different contribution to CVD. Overall, older age, longer disease duration, presence of traditional cardiovascular risk factors, and male sex were independently associated with a higher CVD prevalence. After adjusting for demographic and traditional cardiovascular risk factors, systemic lupus erythematosus exhibited the highest CVD standardized prevalence, followed by rheumatoid arthritis, psoriasis, Crohn disease, psoriatic arthritis, and ulcerative colitis (4.5 [95% confidence interval (CI): 2.2, 6.8], 1.3 [95% CI: 0.8, 1.8], 0.9 [95% CI: 0.5, 1.2], 0.8 [95% CI: 0.2, 1.3], 0.6 [95% CI: 0.2, 1.0], and 0.5 [95% CI: 0.1, 0.8], respectively). Systemic lupus erythematosus, rheumatoid arthritis, and psoriasis are associated with higher prevalence of CVD compared with other IMIDs. Specific prevention programs should be established in subjects affected with these conditions to prevent CVD. PMID:28658137

  14. Immune-Mediated Mechanisms of Action of Probiotics and Synbiotics in Treating Pediatric Intestinal Diseases

    Science.gov (United States)

    Gil-Campos, Mercedes

    2018-01-01

    The pediatric population is continually at risk of developing infectious and inflammatory diseases. The treatment for infections, particularly gastrointestinal conditions, focuses on oral or intravenous rehydration, nutritional support and, in certain case, antibiotics. Over the past decade, the probiotics and synbiotics administration for the prevention and treatment of different acute and chronic infectious diseases has dramatically increased. Probiotic microorganisms are primarily used as treatments because they can stimulate changes in the intestinal microbial ecosystem and improve the immunological status of the host. The beneficial impact of probiotics is mediated by different mechanisms. These mechanisms include the probiotics’ capacity to increase the intestinal barrier function, to prevent bacterial transferation and to modulate inflammation through immune receptor cascade signaling, as well as their ability to regulate the expression of selected host intestinal genes. Nevertheless, with respect to pediatric intestinal diseases, information pertaining to these key mechanisms of action is scarce, particularly for immune-mediated mechanisms of action. In the present work, we review the biochemical and molecular mechanisms of action of probiotics and synbiotics that affect the immune system. PMID:29303974

  15. Abundant genetic overlap between blood lipids and immune-mediated diseases indicates shared molecular genetic mechanisms.

    Directory of Open Access Journals (Sweden)

    Ole A Andreassen

    Full Text Available Epidemiological studies suggest a relationship between blood lipids and immune-mediated diseases, but the nature of these associations is not well understood. We used genome-wide association studies (GWAS to investigate shared single nucleotide polymorphisms (SNPs between blood lipids and immune-mediated diseases. We analyzed data from GWAS (n~200,000 individuals, applying new False Discovery Rate (FDR methods, to investigate genetic overlap between blood lipid levels [triglycerides (TG, low density lipoproteins (LDL, high density lipoproteins (HDL] and a selection of archetypal immune-mediated diseases (Crohn's disease, ulcerative colitis, rheumatoid arthritis, type 1 diabetes, celiac disease, psoriasis and sarcoidosis. We found significant polygenic pleiotropy between the blood lipids and all the investigated immune-mediated diseases. We discovered several shared risk loci between the immune-mediated diseases and TG (n = 88, LDL (n = 87 and HDL (n = 52. Three-way analyses differentiated the pattern of pleiotropy among the immune-mediated diseases. The new pleiotropic loci increased the number of functional gene network nodes representing blood lipid loci by 40%. Pathway analyses implicated several novel shared mechanisms for immune pathogenesis and lipid biology, including glycosphingolipid synthesis (e.g. FUT2 and intestinal host-microbe interactions (e.g. ATG16L1. We demonstrate a shared genetic basis for blood lipids and immune-mediated diseases independent of environmental factors. Our findings provide novel mechanistic insights into dyslipidemia and immune-mediated diseases and may have implications for therapeutic trials involving lipid-lowering and anti-inflammatory agents.

  16. Thrombocytopenia with Tedizolid and Linezolid.

    Science.gov (United States)

    Lee, Erica Yookyung; Caffrey, Aisling R

    2018-01-01

    Several studies have suggested the risk of thrombocytopenia with tedizolid, a second-in-class oxazolidinone antibiotic (approved June 2014), is less than that observed with linezolid (first-in-class oxazolidinone). Using data from the Food and Drug Administration adverse event reporting system (July 2014 through December 2016), we observed significantly increased risks of thrombocytopenia of similar magnitudes with both antibiotics: linezolid reporting odds ratio [ROR], 37.9 (95% confidence interval [CI], 20.78 to 69.17); tedizolid ROR, 34.0 (95% CI, 4.67 to 247.30). Copyright © 2017 American Society for Microbiology.

  17. Immune thrombocytopenia in the newborn

    Directory of Open Access Journals (Sweden)

    Murat Yurdakök

    2017-02-01

    Full Text Available The leading cause of moderate or severe thrombocytopenia in otherwise healthy appearing neonates is immune thrombocytopenia. Immune thrombocytopenia in the fetus or newborn may result from platelet alloantibodies against paternal antigens inherited by the fetus (alloimmune thrombocytopenia or platelet autoantibodies in the mother with immune thrombocytopenic purpura (ITP. Only 10% of human platelet antigen (HPA-1a negative mothers who are exposed to HPA-1a positive fetal platelets during pregnancy develop HPA-1a alloantibodies, and 30% of fetuses/neonates will develop thrombocytopenia and 20% of these cases being severe. The most serious complication of severe fetal and neonatal alloimmune thrombocytopenia (FNAIT is intracranial hemorrhage (ICH, which is detected in 10-20% of affected fetuses/neonates, with most cases occurring antenatally. ICH leads to neurological sequelae in 20%, and deaths in 5-10% cases. There is no evidence-based optimal treatment strategy. Platelet antibody titration in maternal plasma is not helpful for decision-making. The best indicator for current pregnancy is the outcome of the previous pregnancy. The risk of recurrence among subsequent HPA-positive sibling is close to 100% where the previous sibling was affected with antenatal intracranial ICH. The risk of ICH becomes higher with more severe and earlier onset in each subsequent pregnancy. Serial platelet counts should be obtained for the first 5-7 days of delivery to keep the platelet counts higher than 30,000/µL without active bleeding and higher that 50,000-100,000/µL with active bleeding. Intravenous immunoglobulin (IVIG is not alternative to platelet transfusions, since platelet counts don’t rise before 24-48 h. In platelet- transfused patients, IVIG can be given to potentially prolong the survival of the incompatible platelets. ITP during pregnancy is not considered a serious risk of perinatal bleeding, but may cause a moderate thrombocytopenia in neonate

  18. Management of Platelet Transfusion Therapy in Patients With Blood Cancer or Treatment-Induced Thrombocytopenia

    Science.gov (United States)

    2018-02-15

    Acute Biphenotypic Leukemia; Acute Lymphoblastic Leukemia; Acute Myeloid Leukemia; B-Cell Non-Hodgkin Lymphoma; Chronic Lymphocytic Leukemia; Chronic Myelogenous Leukemia, BCR-ABL1 Positive; Hematologic and Lymphocytic Disorder; Hematopoietic Cell Transplantation Recipient; Myelodysplastic Syndrome; Primary Myelofibrosis; Secondary Myelofibrosis; T-Cell Non-Hodgkin Lymphoma; Thrombocytopenia; Venous Thromboembolism

  19. CLINICAL STUDY OF FEVER WITH THROMBOCYTOPENIA

    OpenAIRE

    Rekha; Sumangala; Ishwarya

    2014-01-01

    BACKGROUND: In recent days fever with Thrombocytopenia is a common clinical presentation in the medical wards. This study has been undertaken to know the modes of clinical presentations and possible causes of fever with Thrombocytopenia. OBJECTIVE: 1. To determine possible infective etiology for fever with Thrombocytopenia. 2. To correlate clinical features, laboratory studies and infective etiology. METHODS: Case record analysis of fever with Thrombocytopenia admitted to ...

  20. The prevalence of thrombocytopenia in plasmodium falciparum ...

    African Journals Online (AJOL)

    Their platelet counts were evaluated using the auto-analyser Sysmex KX-21N. Results: The overall prevalence of thrombocytopenia was 5.0%, but it was higher in children with severe malaria. None of the children in the control group had thrombocytopenia. Conclusion: The prevalence of thrombocytopenia in falciparum ...

  1. Preoperative predictors of thrombocytopenia in Caesarean delivery ...

    African Journals Online (AJOL)

    Preoperative predictors of thrombocytopenia in Caesarean delivery: is routine platelet count testing necessary? ... moderate thrombocytopenia. All asymptomatic patients, including those who were HIV positive, had platelet counts > 70 000/μl. Keywords: Caesarean delivery, HIV, obstetrics, pregnancy, thrombocytopenia ...

  2. Thrombocytopenia and leptospirosis Trombocitopenia e leptospirose

    Directory of Open Access Journals (Sweden)

    Antonio Carlos Nicodemo

    1990-08-01

    Full Text Available The present study has intended to contribute to the elucidation of the pathogenic mechanisms, involved in the thrombocytopenia and in the bleeding diathesis seen in the course of Leptospirosis. The group of cases included in the present prospective study consisted of 30 patients with Leptospirosis, admitted to the Infectious and Parasitic Diseases Ward, Hospital das Clínicas, Faculty of Medicine, University of São Paulo. The following possible mechanisms of thrombocytopenia have been considered and therefore investigated: platelet consumption, due to disseminated intravascular coagulation; immune-mediated platelet destruction, due to platelet-associated antibodies and an inhibited platelet production in the bone marrow. Thrombocytopenia occurred in 86.6% of 30 patients and did not seem to be immune-mediated by platelet-associated antibodies. Furthermore it did not seem to be due to a disseminated intravascular coagulation consumption. Although there was a statistically-significant correlation between bone marrow platelet production and platelet counts we think that the static microscopic examination of a bone marrow aspirate cannot accurately depict the dynamic mechanisms of platelet production when these cells are being consumed in peripheral blood. Vasculitis should be considered as the most important factor for the pathogenesis of the bleeding disturbances in Leptospirosis. However, we believe that thrombocytopenia, uremia and coagulation disorders, individually or as a group, should be included among the contributing factors that lead to and worsen bleeding episodes, which represent the leading cause of death in this disease.O propósito do presente trabalho é colaborar para o estudo da patogenia da plaquetopenia que ocorre na Leptospirose. A pesquisa foi feita de maneira prospectiva e o grupo de casos foi constituído por 30 pacientes internados com hipótese diagnostica de Leptospirose na Clínica de Doenças Infecciosas e Parasit

  3. Assessment of Equine Autoimmune Thrombocytopenia (EAT by flow cytometry

    Directory of Open Access Journals (Sweden)

    Schwarzwald Colin

    2001-04-01

    Full Text Available Abstract Rationale Thrombocytopenia is a platelet associated process that occurs in human and animals as result of i decreased production; ii increased utilization; iii increased destruction coupled to the presence of antibodies, within a process know as immune-mediated thrombocytopenia (IMT; or iv platelet sequestration. Thus, the differentiation of the origin of IMT and the development of reliable diagnostic approaches and methodologies are important in the clarification of IMT pathogenesis. Therefore, there is a growing need in the field for easy to perform assays for assessing platelet morphological characteristics paired with detection of platelet-bound IgG. Objectives This study is aimed to develop and characterize a single color flow cytometric assay for detection of platelet-bound IgG in horses, in combination with flow cytometric assessment of platelet morphological characteristics. Findings The FSC and SSC evaluation of the platelets obtained from the thrombocytopenic animals shows several distinctive features in comparison to the flow cytometric profile of platelets from healthy animals. The thrombocytopenic animals displayed i increased number of platelets with high FSC and high SSC, ii a significant number of those gigantic platelets had strong fluorescent signal (IgG bound, iii very small platelets or platelet derived microparticles were found significantly enhanced in one of the thrombocytopenic horses, iv significant numbers of these microplatelet/microparticles/platelet-fragments still carry very high fluorescence. Conclusions This study describes the development and characterization of an easy to perform, inexpensive, and noninvasive single color flow cytometric assay for detection of platelet-bound IgG, in combination with flow cytometric assessment of platelet morphological characteristics in horses.

  4. Management of symptomatic thrombocytopenia associated with dengue haemorrhagic fever

    International Nuclear Information System (INIS)

    Jameel, T.; Saleem, I.U.; Mehmood, K.; Tanvir, I.; Saadia, A.

    2010-01-01

    Introduction: Immune - mediated destruction of platelets is thought to be the mechanism of thrombocytopenia seen after the viraemic phase of dengue haemorrhagic fever (DHF). Immuno - suppressants such as steroids, immune globulin and Anti D immune globulin are effective in the treatment of this type of immune thrombocytopenic purpura. Objective: To evaluate the efficacy of oral Prednisolone in the rate of resolution of thrombocytopenia and monitoring of complications in patients recovering from Dengue haemorrhagic fever. Method: A controlled study was carried out on diagnosed cases Dengue haemorrhagic patients presenting with sever thrombocytopenia and symptoms like confluent ecchymosis, epistaxis and purpuric rashes. In study was conducted in Ittefaq hospital (trust) Lahore, during the period of October to December 2008. Treatment group received steroids in two forms i.e. first line therapy prednisolone (1 mg / kg) orally or as second line therapy of initial I/V high dose (prednisolone) in pulse doses i.e. 40 mg / bd for four days and later oral prednisolone as in first line therapy with omeprazole 20 mg / bd in addition to standard treatment. Control group received standard supportive care only. Results: A total of 341 suspected patients were admitted in hospital. Serological diagnosis was confirmed in 166 patients. CBC revealed platelet count . 100 x 109 / l in 106 patients. A group of symptomatic febrile patients have platelet count < 20 x 109 / l was selected for therapeutic intervention. first line therapy (oral prednisolone was stated in 43 patients. In Fourteen patients second line therapy (high dose dexamethasone pulse) therapy was instituted. Seven of them attained complete response whereas two patients achieved partial response. Four patients were shifted to Anti D therapy. Three deaths occurred during our study. Rest of all the patients improved and were discharged in due course of time. Conclusion: This small scale preliminary study shows promising

  5. Is Thrombocytopenia an Early Prognostic Marker in Septic Shock?

    Science.gov (United States)

    Thiery-Antier, Nadiejda; Binquet, Christine; Vinault, Sandrine; Meziani, Ferhat; Boisramé-Helms, Julie; Quenot, Jean-Pierre

    2016-04-01

    To assess whether early thrombocytopenia during septic shock is associated with an increased risk of death at day 28 and to identify risk factors associated with a low platelet count. Prospective, multicenter, observational cohort study. Fourteen ICUs from 10 French university teaching and nonacademic hospitals. Consecutive adult patients with septic shock admitted between November 2009 and September 2011 were eligible. None. Of the 1,495 eligible patients, 1,486 (99.4%) were included. Simplified Acute Physiology Score II score of greater than or equal to 56, immunosuppression, age of more than 65 years, cirrhosis, bacteremia (p ≤ 0.001 for each), and urinary sepsis (p = 0.005) were globally associated with an increased risk of thrombocytopenia within the first 24 hours following the onset of septic shock. Survival at day 28 estimated by the Kaplan-Meier method was lower in patients with thrombocytopenia and decreased with thrombocytopenia severity. By multivariate Cox regression, a platelet count of less than or equal to 100,000/mm3 was independently associated with a significantly increased risk of death within the 28 days following septic shock onset. The risk of death increased with the severity of thrombocytopenia (hazard ratio, 1.65; 95% CI, 1.31-2.08 for a platelet count below 50,000/mm3 vs > 150,000/mm3; p septic shock onset as a prognostic marker of survival at day 28 in a large cohort of ICU patients. Measuring platelet count is inexpensive and easily feasible for the physician in routine practice, and thus, it could represent an easy "alert system" among patients in septic shock.

  6. Cytomegalovirus-associated encephalomyelitis in an immunocompetent adult: a two-stage attack of direct viral and delayed immune-mediated invasions. case report.

    Science.gov (United States)

    Daida, Kensuke; Ishiguro, Yuta; Eguchi, Hiroto; Machida, Yutaka; Hattori, Nobutaka; Miwa, Hideto

    2016-11-17

    It is clinically rare to find cytomegalovirus (CMV)-associated encephalomyelitis in immunocompetent adults. Here, we present the case of an adult patient who developed acute transverse myelitis that was followed by immune-mediated disseminated encephalomyelitis. A 38-year-old man developed acute paraplegia with paresthesia below the level of the T7-8 dermatome. Both brain and spinal cord MRIs performed at admission appeared normal. Corticosteroid therapy was initiated, with the later addition of high-dose intravenous immunoglobulins. After polymerase chain reaction analysis indicated the presence of CMV DNA in his cerebrospinal fluid (CSF), anti-viral therapy was added. Forty days after symptom onset, despite an initial positive response to this therapy, he developed dysarthria and truncal ataxia. Repeated magnetic resonance imaging scans demonstrated progressively expanding lesions involving not only the spinal cord but also the cerebral white matter, suggestive of extensive immune-mediated demyelination involving the central nervous system (CNS), as is observed in acute disseminated encephalomyelitis (ADEM). This case report underscores the importance of careful patient observation following the initial diagnosis of a CMV-associated CNS infection, such as transverse myelitis, on the possibility that post-infectious ADEM may appear.

  7. Thrombocytopenia associated with environmental exposure to polyurethane

    Energy Technology Data Exchange (ETDEWEB)

    Michelson, A.D. (Department of Pediatrics, University of Massachusetts Medical School, Worcester (United States))

    1991-10-01

    Few chemicals in the environment have been implicated as causes of isolated thrombocytopenia, and the evidence is usually less than convincing because the patients were not rechallenged with the chemical in vivo. In the present paper, a child is reported with the onset of thrombocytopenia in temporal association with environmental exposure to polyurethane. Five years after the initial thrombocytopenia had resolved, an inadvertent in vivo rechallenge with environmental polyurethane resulted in recurrence of the thrombocytopenia. This recurrence, together with the fact that only 1-4% of cases of idiopathic thrombocytopenic purpura in children recur, provided strong evidence for a causal role for the polyurethane exposure in this patient's thrombocytopenia. In summary, environmental exposure to polyurethane should be considered in the differential diagnosis of acquired thrombocytopenia in childhood.

  8. Houttuynia cordata modulates oral innate immune mediators: potential role of herbal plant on oral health.

    Science.gov (United States)

    Satthakarn, S; Chung, W O; Promsong, A; Nittayananta, W

    2015-05-01

    Epithelial cells play an active role in oral innate immunity by producing various immune mediators. Houttuynia cordata Thunb (H. cordata), a herbal plant found in Asia, possesses many activities. However, its impacts on oral innate immunity have never been reported. The aim of this study was to determine the effects of H. cordata extract on the expression of innate immune mediators produced by oral epithelial cells. Primary gingival epithelial cells (GECs) were treated with various concentrations of the extract for 18 h. The gene expression of hBD2, SLPI, cytokines, and chemokines was measured using quantitative real-time RT-PCR. The secreted proteins in the culture supernatants were detected by ELISA or Luminex assay. Cytotoxicity of the extract was assessed using CellTiter-Blue Assay. H. cordata significantly induced the expression of hBD2, SLPI, IL-8, and CCL20 in a dose-dependent manner without cytotoxicity. The secreted hBD2 and SLPI proteins were modulated, and the levels of IL-2, IL-6, IL-8, and IFN-γ were significantly induced by the extract. Our data indicated that H. cordata can modulate oral innate immune mediators. These findings may lead to the development of new topical agents from H. cordata for the prevention and treatment of immune-mediated oral diseases. © 2015 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  9. Review: Immune-mediated necrotizing myopathies - a heterogeneous group of diseases with specific myopathological features

    NARCIS (Netherlands)

    Stenzel, W.; Goebel, H.-H.; Aronica, E.

    2012-01-01

    Immune-mediated necrotizing myopathies (IMNMs) are now well recognized among the so-called idiopathic inflammatory myopathies (IIMs), which also comprise dermatomyositis (DM), polymyositis (PM), sporadic inclusion body myositis (sIBM) and non-specific myositis. All of these conditions are defined on

  10. High intravascular tissue factor expression in dogs with idiopathic immune-mediated haemolytic anaemia

    NARCIS (Netherlands)

    Piek, C.J.; Brinkhof, B.; Teske, E.; Rothuizen, J.; Dekker, A.; Penning, L.C.

    2011-01-01

    A high mortality occurs in dogs with idiopathic immune-mediated haemolytic anaemia (IMHA) during the first 2 weeks after the diagnosis. The aim of this study was to investigate the inflammatory response and coagulation abnormalities in dogs with IMHA in relation to the prognosis and to establish the

  11. Genetics of immune-mediated disorders : from genome-wide association to molecular mechanism

    NARCIS (Netherlands)

    Kumar, Vinod; Wijmenga, Cisca; Xavier, Ramnik J.

    2014-01-01

    Genetic association studies have identified not only hundreds of susceptibility loci to immune-mediated diseases but also pinpointed causal amino-acid variants of HLA genes that contribute to many autoimmune reactions. Majority of non-HLA genetic variants are located within non-coding regulatory

  12. Shared genetics in coeliac disease and other immune-mediated diseases

    NARCIS (Netherlands)

    Gutierrez-Achury, J.; Coutinho de Almeida, R.; Wijmenga, C.

    Gutierrez-Achury J, Coutinho de Almeida R, Wijmenga C (University Medical Centre Groningen and University of Groningen, Groningen, the Netherlands; University of Brasilia School of Health Sciences, Brasilia, DF, Brazil). Shared genetics in coeliac disease and other immune-mediated diseases

  13. A case of non-regenerative immune-mediated anemia treated by ...

    African Journals Online (AJOL)

    A 12-year-old female Shih Tzu dog was referred with diarrhea. Hematological examination indicated severe nonregenerative anemia. Bone marrow aspiration smears and core biopsy specimens revealed normal bone marrow. Based on those results, non-regenerative immune mediated anemia was diagnosed. The dog ...

  14. Hypocholesterolemia and nonregenerative, suspected immune-mediated, anemia: Report of 3 canine cases.

    Science.gov (United States)

    Robbins, Rachel; Viviano, Katrina R

    2017-10-01

    This report describes hypocholesterolemia in 3 dogs with nonregenerative, suspected immune-mediated anemias. Common causes of hypocholesterolemia were ruled out, raising suspicion for a mechanistic link between anemia and hypocholesterolemia in dogs. As observed in humans with concurrent anemia and hypocholesterolemia, cholesterol concentrations increased to within the reference interval once the dogs' anemia resolved.

  15. The study of thrombocytopenia in sick neonates

    International Nuclear Information System (INIS)

    Aman, I.; Hassan, K.A.; Ahmad, T.M.

    2004-01-01

    Objective: To determine the number of cases and manifestations of thrombocytopenia in sick neonates. Subjects and Methods: A total of 365 neonates from 0-28 days of age admitted with different clinical problems irrespective of birth weight and gestational age were evaluated for thrombocytopenia. These neonates were categorized into five different groups (A-E), which were of neonatal infections, asphyxia neonatorum, preterm and smallness for gestational age, jaundice and miscellaneous respectively. Results: Out of 365 cases, 88 were found to have thrombocytopenia (platelet counts < 150,000 per mm/sup 3/) which was 24.1% of the total. In group A (neonatal infections), out of 152 neonates, 62 had low platelet counts (40.78%). In group B (neonatal asphyxia), out of 90 only 11 had thrombocytopenia (12.2%). In group C (preterm and small for gestational age), out of 60 cases only 9 had thrombocytopenia. In group D (jaundice), all 33 cases had normal platelet counts. In group E (miscellaneous), out of 30 cases only 6 had thrombocytopenia. The common manifestations in thrombocytopenic babies were petechiae and bruises followed by gastrointestinal hemorrhages. The percentage of manifest thrombocytopenia cases was 56.8% and of occult thrombocytopenia 43.1 %. Conclusion: The leading causes of thrombocytopenia in sick neonates are infections, asphyxia, complicated pre- maturity and smallness for gestational age. Apart from the platelet counts the bleeding mainfestations also depend upon the underlying ailments. (author)

  16. Thrombocytopenia

    Science.gov (United States)

    ... your platelets. You may need vaccines for mumps, measles, rubella, and chickenpox. You may want to have your child vaccinated for these viruses as well. Talk with your child's doctor about these vaccines. Signs, Symptoms, and Complications Mild to serious bleeding causes the main signs ...

  17. Management of thrombocytopenia in cancer.

    Science.gov (United States)

    Castaman, Giancarlo; Pieri, Lisa

    2018-04-01

    Thrombocytopenia is a common finding in cancer patients and can have different and/or multifactorial pathogenesis. While in solid tumors it occurs often as a consequence of chemotherapy treatment, it is frequently observed at diagnosis in patients with hematological malignancies being aggravated to a potentially life-threatening level during chemotherapy. Other associated conditions (infections, drugs, consumption coagulopathy etc.) can add to influence the degree of thrombocytopenia and the inherent risk of bleeding and they should be recognized and corrected to improve platelet count. Platelet transfusion remains the cornerstone of treatment, but its use should always be weighted taking into consideration the actual risk of bleeding to avoid inappropriate use and wasting of resources. While in hematological malignancies a threshold level of 10,000 platelets/μL is widely accepted as the minimal level prompting prophylactic platelet transfusion, this limit is less frequently observed in patients with solid tumors and platelet transfusions are usually administered for a few days, possibly at a higher platelet level. Alternative treatments for the latter patients including thrombopoietin-mimetic agents are increasingly used and found to be promising. Copyright © 2018 Elsevier Ltd. All rights reserved.

  18. Thrombocytopenia and disseminated histoplasmosis in immunocompetent adults

    OpenAIRE

    Kutkut, Issa; Vater, Laura; Goldman, Mitchell; Czader, Magdalena; Swenberg, Jessica; Fulkerson, Zachary; Mehta, Rakesh

    2017-01-01

    Key Clinical Message Disseminated histoplasmosis among immunocompetent patients is rare, but may be associated with clinically significant refractory thrombocytopenia. Platelet counts often return to normal levels following antifungal therapy. Therefore, the most important management of this refractory thrombocytopenia is the recognition and treatment of histoplasmosis infection.

  19. Integrated genomics identifies convergence of ankylosing spondylitis with global immune mediated disease pathways.

    Science.gov (United States)

    Uddin, Mohammed; Codner, Dianne; Hasan, S M Mahmud; Scherer, Stephen W; O'Rielly, Darren D; Rahman, Proton

    2015-05-18

    Ankylosing spondylitis(AS), a highly heritable complex inflammatory arthritis. Although, a handful of non-HLA risk loci have been identified, capturing the unexplained genetic contribution to AS pathogenesis remains a challenge attributed to additive, pleiotropic and epistatic-interactions at the molecular level. Here, we developed multiple integrated genomic approaches to quantify molecular convergence of non-HLA loci with global immune mediated diseases. We show that non-HLA genes are significantly sensitive to deleterious mutation accumulation in the general population compared with tolerant genes. Human developmental proteomics (prenatal to adult) analysis revealed that proteins encoded by non-HLA AS risk loci are 2-fold more expressed in adult hematopoietic cells.Enrichment analysis revealed AS risk genes overlap with a significant number of immune related pathways (p pathways with other immune mediated diseases. This information will be pivotal to fully explain AS pathogenesis and identify new therapeutic targets.

  20. Psoriasis and cardiovascular risk: Immune-mediated crosstalk between metabolic, vascular and autoimmune inflammation

    Directory of Open Access Journals (Sweden)

    R.A. Kölliker Frers

    2015-03-01

    Results and conclusions: Psoriasis and psoriatic arthritis diseases illustrate that immune-mediated activated crossroads of inflammation beyond enhanced cardiovascular risk factors are the result of an interplay between different proatherogenic mediators derived from metabolic, vascular and autoimmune joint and skin inflamed target tissue. Consistent with this point of view, psoriasis and psoriatic arthritis diseases offer an invaluable opportunity to reinforce our knowledge about atherosclerotic cardiovascular disease.

  1. Metastases in immune-mediated dormancy: a new opportunity for targeting cancer.

    Science.gov (United States)

    Romero, Irene; Garrido, Federico; Garcia-Lora, Angel M

    2014-12-01

    The aim of any anticancer treatment is to avoid, control, or eliminate disseminated tumor cells. Clinical and experimental evidence has revealed that metastases can remain in a latency state, that is, metastasis dormancy. Three mechanisms are thought to be involved in cancer dormancy: cellular dormancy, angiogenic dormancy, and immune-mediated dormancy. Here, we review the mechanisms and cells involved in immune-mediated cancer dormancy and discuss current and future immunotherapeutic strategies. Recent results indicate that the immune system can restrain disseminated cancer cells, promoting their permanent dormancy. CD8(+) T lymphocytes play a relevant role in maintaining immune equilibrium with metastatic dormant cells, and MHC class I surface expression on tumor cells may also be involved. Natural killer (NK) cells have an activator function that triggers a cytotoxic T lymphocyte (CTL) response. Furthermore, immune dormancy promotes cancer cell growth arrest and angiogenic control. Immunotherapeutic interventions in metastatic dormancy may help to control or eradicate cancer disease. Treatments that activate or increase the CTL immune response or reverse cancer cell-induced CTL immunosuppression might be useful to restrain or destroy metastatic cells. These objectives may be achieved by recovering or increasing MHC class I surface expression on cancer cells or even by activating NK cells. Immune-mediated metastasis dormancy provides an opportunity for targeting cancer in novel immune treatments. ©2014 American Association for Cancer Research.

  2. Vesicular trafficking of immune mediators in human eosinophils revealed by immunoelectron microscopy

    International Nuclear Information System (INIS)

    Melo, Rossana C.N.; Weller, Peter F.

    2016-01-01

    Electron microscopy (EM)-based techniques are mostly responsible for our current view of cell morphology at the subcellular level and continue to play an essential role in biological research. In cells from the immune system, such as eosinophils, EM has helped to understand how cells package and release mediators involved in immune responses. Ultrastructural investigations of human eosinophils enabled visualization of secretory processes in detail and identification of a robust, vesicular trafficking essential for the secretion of immune mediators via a non-classical secretory pathway associated with secretory (specific) granules. This vesicular system is mainly organized as large tubular-vesicular carriers (Eosinophil Sombrero Vesicles – EoSVs) actively formed in response to cell activation and provides a sophisticated structural mechanism for delivery of granule-stored mediators. In this review, we highlight the application of EM techniques to recognize pools of immune mediators at vesicular compartments and to understand the complex secretory pathway within human eosinophils involved in inflammatory and allergic responses. - Highlights: • Application of EM to understand the complex secretory pathway in human eosinophils. • EM techniques reveal an active vesicular system associated with secretory granules. • Tubular vesicles are involved in the transport of granule-derived immune mediators.

  3. Vesicular trafficking of immune mediators in human eosinophils revealed by immunoelectron microscopy

    Energy Technology Data Exchange (ETDEWEB)

    Melo, Rossana C.N., E-mail: rossana.melo@ufjf.edu.br [Laboratory of Cellular Biology, Department of Biology, ICB, Federal University of Juiz de Fora, UFJF, Rua José Lourenço Kelmer, Juiz de Fora, MG 36036-900 (Brazil); Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, CLS 943, Boston, MA 02215 (United States); Weller, Peter F. [Department of Medicine, Beth Israel Deaconess Medical Center, Harvard Medical School, 330 Brookline Avenue, CLS 943, Boston, MA 02215 (United States)

    2016-10-01

    Electron microscopy (EM)-based techniques are mostly responsible for our current view of cell morphology at the subcellular level and continue to play an essential role in biological research. In cells from the immune system, such as eosinophils, EM has helped to understand how cells package and release mediators involved in immune responses. Ultrastructural investigations of human eosinophils enabled visualization of secretory processes in detail and identification of a robust, vesicular trafficking essential for the secretion of immune mediators via a non-classical secretory pathway associated with secretory (specific) granules. This vesicular system is mainly organized as large tubular-vesicular carriers (Eosinophil Sombrero Vesicles – EoSVs) actively formed in response to cell activation and provides a sophisticated structural mechanism for delivery of granule-stored mediators. In this review, we highlight the application of EM techniques to recognize pools of immune mediators at vesicular compartments and to understand the complex secretory pathway within human eosinophils involved in inflammatory and allergic responses. - Highlights: • Application of EM to understand the complex secretory pathway in human eosinophils. • EM techniques reveal an active vesicular system associated with secretory granules. • Tubular vesicles are involved in the transport of granule-derived immune mediators.

  4. Systemic Lupus Erythematosus Presenting as Thrombotic Thrombocytopenia Purpura: How Close Is Close Enough?

    Directory of Open Access Journals (Sweden)

    Cesar A. Perez

    2011-01-01

    Full Text Available Thrombotic thrombocytopenic purpura (TTP is an uncommon life-threatening disease characterized by microangiopathic hemolytic anemia and thrombocytopenia, commonly associated with infections, malignancy, drugs, and autoimmune diseases. We report a case of 19-year-old previously healthy female that presents with anemia and thrombocytopenia diagnosed with thrombotic thrombocytopenic purpura that was treated successfully with plasmapheresis and corticosteroids. Laboratory findings also revealed antinuclear antibodies and antibodies to double-stranded DNA. Two weeks after presentation developed inflammatory arthritis, fulfilling diagnostic criteria for systemic lupus erythematosus (SLE. Prompt diagnosis and treatment with plasma exchange and corticosteroids should be instituted as soon as the diagnosis of TTP is suspected, even if other diagnoses, including lupus, are possible. When present, the coexistence of these two etiologies can have a higher mortality than either disease alone. An underlying diagnosis of SLE should be considered in all patients presenting TTP and the study of this association may provide a better understanding of their immune-mediated pathophysiology.

  5. Application of the 2012 revised diagnostic definitions for paediatric multiple sclerosis and immune-mediated central nervous system demyelination disorders

    NARCIS (Netherlands)

    van Pelt, E. Danielle; Neuteboom, Rinze F.; Ketelslegers, Immy A.; Boon, Maartje; Catsman-Berrevoets, Coriene E.; Hintzen, Rogier Q.

    Background Recently, the International Paediatric Multiple Sclerosis Study Group (IPMSSG) definitions for the diagnosis of immune-mediated acquired demyelinating syndromes (ADS) of the central nervous system, including paediatric multiple sclerosis (MS), have been revised. Objective To evaluate the

  6. [Immune-mediated neuromyotonia (Isaacs' syndrome)--clinical aspects and pathomechanism].

    Science.gov (United States)

    Arimura, Kimiyoshi; Watanabe, Osamu

    2010-04-01

    Neuromyotonia occurs due to several causes such as hereditary, immune-mediated and degenerative neurological disorders. Isaacs' syndrome (immune-mediated neuromyotonia) is an antibody-mediated potassium channel disorder (channelopathy). Clinical symptoms of Isaacs' syndrome are characterized by muscle cramp, slow relaxation following muscle contraction (pseudomyotonia), and hyperhidrosis; these symptoms are due to hyperexcitability of the peripheral nerve, including autonomic nerve. These symptoms are relieved by the administration of Na channel blocker and immunotherapy. Recent studies show that this disease is not infrequently associated with neoplasm, especially thymoma. The target channel proteins of the antigens are voltage-gated potassium channels (VGKCs), specifically dendrotoxin-sensitive fast potassium channels. The suppression of voltage-gated outward K+ current by antibodies induces the hyper- excitability of the peripheral nerve. The findings of patch clamp studies show that antibodies may not directly block the kinetics of VGKCs, but may decrease channel density. From the electrophysiologic, pharmacologic and immunologic view points, the site of origin of spontaneous discharges is located principally in the distal portion of the motor nerve and/or within the terminal arborization. Anti-VGKC antibodies were also found to be positive in patients with Morvan's syndrome, limbic encephalitis and temporal epilepsy. Thus, an increasing number of immune-mediated neurological disorders with anti-VGKC antibodies are being identified. However, except in Morvan's syndrome, it is rare to find symptoms pertaining to involvement of both the peripheral and central nervous system in the same patient with anti-VGKC antibodies. The differences in the pathomechanism of Isaacs' syndrome and limbic encephalitis are still unclear.

  7. Equine immune-mediated hemolytic anemia associated with Clostridium perfringens infection.

    Science.gov (United States)

    Weiss, Douglas J; Moritz, Andreas

    2003-01-01

    Previous studies have suggested an association between equine immune-mediated hemolytic anemia and clostridial infections or neck abscesses. The purpose of this report was to describe and characterize the hematologic abnormalities in a horse with Clostridium-associated immune-mediated hemolytic anemia. We also retrospectively evaluated hematologic abnormalities in 8 horses with clostridial myositis or subcutaneous emphysema. A 7-year-old Foreign Warm-Blood gelding was evaluated for anemia and a cervical abscess. CBCs and reticulocyte counts were obtained using an Advia 120 analyzer and evaluation of Wright's-stained smears. All cases of equine Clostridium spp.myositis or subcutaneous emphysema over a 7-year period were identified in a retrospective search of the University of Minnesota Veterinary Teaching Hospital database. Clinical, hematologic, and microbiological findings were recorded. Clostridium perfringens genotype A was isolated from the neck wound of the gelding. The CBC was characterized by severe regenerative anemia, intravascular hemolysis, and RBC agglutination. A direct Coombs' test was positive. Moderate numbers of spheroechinocytes were observed. The total automated reticulocyte count was 4.5% (56,700/microliter), with most reticulocytes having low absorbance (mature reticulocytes). The anemia responded to penicillin and steroidal and nonsteroidal immunosuppressive drugs. Of 8 horses with myositis, all of which involved the cervical region, 5 were anemic, 1 had a positive direct Coombs' test, and 2 had increased numbers of type III echinocytes and spheroechinocytes. The presence of type III echinocytes or spheroechinocytes may be helpful in diagnosing immune-mediated hemolytic anemia associated with clostridial infections in horses. Automated reticulocyte counts may detect very low levels of reticulocytosis in hemolytic anemia in horses.

  8. Changing the concepts of immune-mediated glomerular diseases through proteomics.

    Science.gov (United States)

    Caster, Dawn J; Hobeika, Liliane; Klein, Jon B; Powell, David W; McLeish, Kenneth R

    2015-12-01

    Standard classification of glomerular diseases is based on histopathologic abnormalities. The recent application of proteomic technologies has resulted in paradigm changes in the understanding and classification of idiopathic membranous nephropathy and membranoproliferative glomerulonephritis. Those examples provide evidence that proteomics will lead to advances in understanding of the molecular basis of other glomerular diseases, such as lupus nephritis. Proof of principle experiments show that proteomics can be applied to patient renal biopsy specimens. This viewpoint summarizes the advances in immune-mediated glomerular diseases that have relied on proteomics, and potential future applications are discussed. © 2015 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

  9. Activation and Regulation of Hemostasis in Acute Liver Failure and Acute Pancreatitis

    NARCIS (Netherlands)

    Lisman, Ton; Porte, Robert J.

    Acute liver failure and acute pancreatitis are accompanied by substantial changes in the hemostatic system. In acute liver failure, defective synthesis of coagulation factors and intravascular activation of coagulation results in thrombocytopenia and reduced levels of proteins involved in

  10. Investigation of corneal autoantibodies in horses with immune mediated keratitis (IMMK).

    Science.gov (United States)

    Braus, B K; Miller, I; Kummer, S; Kleinwort, K J H; Hirmer, S; Hauck, S M; McMullen, R J; Kerschbaumer, M; Deeg, C A

    2017-05-01

    Immune mediated keratitis (IMMK) is primarily a non-ulcerative keratitis in horses causing intermittent ocular pain, eventually resulting in visual impairment. Affected horses typically respond to immunomodulatory treatment. However, the underlying cause of the disease remains enigmatic. The current study was undertaken to investigate the presence of autoantibodies in horses with immune mediated keratitis. Using 28 horses with IMMK and 27 healthy controls screening for serum autoantibodies against the corneal proteome using indirect immunofluorescence, one-dimensional (1DE) and two-dimensional electrophoresis (2DE) with subsequent western blot analysis was performed followed by mass spectrometric identification of bands or spots of interest. Indirect immunofluorescence did not reveal a difference in immune response towards corneal proteins between healthy horses and those with IMMK. Using western blot analysis some horses affected by IMMK (4/28) showed a single band (1D) or a single spot (2DE) (5/28) not detected in healthy controls. The corresponding spot was identified as maspin (SERPINB5), a protein responsible for the inhibition of corneal vascularisation, cell migration and cell adhesion to the extracellular matrix. Tests with a recombinant human protein commercially available did not verify blot findings, but the human protein may not be fully cross-reactive. Still, maspin might play a role in some cases of equine IMMK. Further research is needed to clarify the etiology of this disease. Copyright © 2017. Published by Elsevier B.V.

  11. Stiff person syndrome and other immune-mediated movement disorders - new insights.

    Science.gov (United States)

    Balint, Bettina; Bhatia, Kailash P

    2016-08-01

    This review highlights the recent developments in immune-mediated movement disorders and how they reflect on clinical practice and our understanding of the underlying pathophysiological mechanisms. The antibody spectrum associated with stiff person syndrome and related disorders (SPSD) has broadened and, apart from the classic glutamic acid decarboxylase (GAD)- and amphiphysin-antibodies, includes now also antibodies against dipeptidyl-peptidase-like protein-6 (DPPX), gamma-aminobutyric acid type A receptor (GABAAR), glycine receptor (GlyR) and glycine transporter 2 (GlyT2). The field of movement disorders with neuronal antibodies keeps expanding with the discovery for example of antibodies against leucine rich glioma inactivated protein 1 (LGI1) and contactin associated protein 2 (Caspr2) in chorea, or antibodies targeting ARHGAP26- or Na/K ATPase alpha 3 subunit (ATP1A3) in cerebellar ataxia. Moreover, neuronal antibodies may partly account for movement disorders attributed for example to Sydenham's chorea, coeliac disease, or steroid responsive encephalopathy with thyroid antibodies. Lastly, there is an interface of immunology, genetics and neurodegeneration, e.g. in Aicardi-Goutières syndrome or the tauopathy with IgLON5-antibodies. Clinicians should be aware of new antibodies such as dipeptidyl-peptidase-like protein-6, gamma-aminobutyric acid type A receptor and glycine transporter 2 in stiff person syndrome and related disorders, as well as of the expanding spectrum of immune-mediated movement disorders.

  12. Statin-associated immune-mediated myopathy: biology and clinical implications.

    Science.gov (United States)

    Christopher-Stine, Lisa; Basharat, Pari

    2017-04-01

    In the last 6 years, our understanding of statin-associated myopathy expanded to include not only a toxic myopathy with limited and reversible side-effects but also an autoimmune variety in which statins likely induce an autoimmune myopathy that is both associated with a specific autoantibody and responsive to immunosuppression and immune modulation. This review widens the reader's understanding of statin myopathy to include an autoimmune process. Statin-associated immune-mediated myopathy provides an example of an environmental trigger (statins) directly implicated in an autoimmune disease associated with a genetic predisposition as well as potential risk factors including concomitant diseases and specific statins. Given a median exposure to statins of 38 months, providers should be aware that anti-3-hydroxy-3-methyl-glutaryl-coenzyme A reductase (HMGCR) myopathy may occur even after several years of statin exposure. It is important for the reader to understand the clinical presentation of statin-associated immune-mediated myopathy and the difference in its clinical presentation to that of statins as direct myotoxins. Prompt recognition of such an entity allows the clinician to immediately stop the offending agent if it has not already been discontinued as well as to recognize that statin rechallenge is not a likely option, and that prompt treatment with immunosuppression and/or immunomodulation is usually of enormous benefit to the patient in restoring muscle strength and physical function. VIDEO ABSTRACT.

  13. Golimumab as Rescue Therapy for Refractory Immune-Mediated Uveitis: A Three-Center Experience

    Directory of Open Access Journals (Sweden)

    Miguel Cordero-Coma

    2014-01-01

    Full Text Available Objective. To evaluate, in three Spanish tertiary referral centres, the short-term safety and efficacy of golimumab (GLM for treatment of immune-mediated uveitis resistant to previous immunosuppressive therapy. Methods. Nonrandomized retrospective interventional case series. Thirteen patients with different types of uveitis that were resistant to treatment with at least 2 previous immunosuppressors were included in this study. All included patients were treated with GLM (50 mg every four weeks during at least 6 months. Clinical evaluation and treatment-related side effects were assessed at least four times in all included patients. Results. Eight men and 5 women (22 affected eyes with a median age of 30 years (range 20–38 and active immune-mediated uveitides were studied. GLM was used in combination with conventional immunosuppressors in 7 patients (53.8%. GLM therapy achieved complete control of inflammation in 12/13 patients (92.3% after six months of treatment. There was a statistically significant improvement in mean BCVA (0.60 versus 0.68, P=0.009 and mean 1 mm central retinal thickness (317 versus 261.2 μ, P=0.05 at the six-month endpoint when compared to basal values. No major systemic adverse effects associated with GLM therapy were observed. Conclusions. GLM is a new and promising therapeutic option for patients with severe and refractory uveitis.

  14. Immunohistochemistry and electrophysiological findings in swine abattoir workers with immune-mediated polyradiculoneuropathy.

    Science.gov (United States)

    Muley, Suraj A; Holzbauer, Stacy; Clark, Brent; Sejvar, James; Lynfield, Ruth; Parry, Gareth; DeVries, Aaron S

    2018-02-15

    Workers exposed to aerosolized brain in a swine-processing plant developed immune-mediated polyradiculoneuropathy (IP) possibly triggered by an immune response. Immunohistochemistry results were correlated with electrophysiological variables to examine the immunopathogenesis of this disorder. Laboratory studies used normal nerve tissue that was exposed to sera from 12 IP patients; 10 exposed controls; and 10 unexposed controls. Clinical and electrophysiological data from IP patients were obtained from medical record reviews. Analysis included electromyography results of IP patients and nerve conduction studies examining CMAP amplitude, distal motor latency, motor conduction velocity, F-wave latency, sensory nerve action potential amplitude, and sensory nerve conduction velocity. Case and control results were compared relative to distance from exposure. Electrodiagnostic findings revealed prolongation of the distal and f-wave latencies suggestive of demyelination at the level of the nerve root and distal nerve terminals. Immunohistochemical results identified an antibody to the peripheral nerve, with staining at the level of the axolemma. Thus, IP may be a primary axonopathy with secondary paranodal demyelination causing the conduction changes. Staining of the distal and proximal portions of the nerve appears consistent with easier access through the blood-nerve barrier. IP is an immune-mediated neuropathy related to antibodies to an axon-based antigen on peripheral nerves. Secondary paranodal demyelination is likely. Further studies to identify the primary axonal antigenic target would be useful. Copyright © 2017. Published by Elsevier B.V.

  15. Imaging the microanatomy of astrocyte-T-cell interactions in immune-mediated inflammation

    Directory of Open Access Journals (Sweden)

    Carlos eBarcia

    2013-04-01

    Full Text Available The role of astrocytes in the immune-mediated inflammatory response in the brain is more prominent than previously thought. Astrocytes become reactive in response to neuro-inflammatory stimuli through multiple pathways, contributing significantly to the machinery that modifies the parenchymal environment. In particular, astrocytic signaling induces the establishment of critical relationships with infiltrating blood cells, such as lymphocytes, which is a fundamental process for an effective immune response. The interaction between astrocytes and T-cells involves complex modifications to both cell types, which undergo micro-anatomical changes and the redistribution of their binding and secretory domains. These modifications are critical for different immunological responses, such as for the effectiveness of the T-cell response, for the specific infiltration of these cells and their homing in the brain parenchyma, and for their correct apposition with antigen-presenting cells to form immunological synapses. In this article, we review the current knowledge of the interactions between T-cells and astrocytes in the context of immune-mediated inflammation in the brain, based on the micro-anatomical imaging of these appositions by high-resolution confocal microscopy and three-dimensional rendering. The study of these dynamic interactions using detailed technical approaches contributes to understanding the function of astrocytes in inflammatory responses and paves the way for new therapeutic strategies.

  16. [Foetal/neonatal alloimmune thrombocytopenia. A review and case report].

    Science.gov (United States)

    Rodríguez Wilhelmi, P; Aranguren, A; Muñiz, E; Aranburu, E; Ezpeleta, I; Ardanaz, M F; Ayape, M L

    2008-01-01

    Foetal/neonatal alloimmune thrombocytopenia is the most common cause of severe thrombocytopenia in the newborn. It is an acute disorder which implies that foetal platelets are destroyed during the pregnancy due to a maternal alloimmune IgG antibody. More than 80% of Caucasians are HPA-1a specific. Intracranial haemorrhage, which occurs in 30% of cases, is the most serious complication, with a 10% mortality rate or a 20% rate of irreversible neurological sequels. The high risk of a recurrence of serious bleeding in future pregnancies led us to consider prophylaxis or prenatal treatment. An early diagnosis of this process allows an effective therapy to be carried out based on the infusion of compatible phenotype HPA platelets or endovenous immunoglobulins. We present the case of a 27 year old pregnant woman, who in the 35th week of a second pregnancy was diagnosed using echography with a bilateral foetal hydrocephaly. After caesarean delivery in the 36th week, the newborn presented haematomas in the left shoulder and gluteus, macrocephalia with tension of the fontanellas and hemorrhagic cerebrospinal fluid after insertion of an external ventricular derivation catheter. The haemogram revealed a severe trombocytopenia (9 x 109/L). In the light of clinical suspicion of foetal/neonatal alloimmune thrombocytopenia, infusion was made of platelets from a non-phenotyped donor for the HPA-1a system, and an endovenous immunoglobulin treatment was followed, with a recovery of platelet counts, but with neurological sequels that are probably irreversible. The immunohaematologal study confirmed the negative HPA-1a maternal phenotype, the neonatal HPA-1a positive phenotype and the presence of anti-HPA-1a alloantibodies in the maternal serum. Nowadays, the prophylaxis and treatment continue to be a controversial issue that is open to discussion, as is the possibility of implementing antenatal screening.

  17. Hepatitis and thrombocytopenia: markers of dengue mortality.

    Science.gov (United States)

    Krishnamoorthy, Smitha; Bhatt, Arun N; Mathew, Celine Thalappillil; Ittyachen, Abraham M

    2017-04-01

    Dengue fever is of great concern to public health in India as it contributes significantly to the burden of healthcare. The aim of our study was to measure mortality in dengue and its association with hepatitis and thrombocytopenia. Our study was performed in a tertiary care setting in the state of Kerala in southern India. Adult patients admitted in the year 2013 were included. Among 1308 confirmed dengue patients, the mortality rate was 1.76%. Hepatitis and thrombocytopenia were present in over 80% of all patients, but severe hepatitis was seen in 11.4% and severe thrombocytopenia in 9.3%. These were markers of fatal outcome. Other factors significantly associated with mortality were age >60 years, male sex, diabetes and the presence of any co-morbidity.

  18. Idiopathic Thrombocytopenia with Iron Deficiency Anemia

    Directory of Open Access Journals (Sweden)

    Ramy Ibrahim

    2013-01-01

    Full Text Available We report a rare case of anemia and thrombocytopenia as a result of uterine fibroid and adenomyosis, complicated by immune thrombocytopenic purpura (ITP. Symptoms were presented as menorrhagia and metrorrhagia in a 34-year-old African American woman, who was later treated with blood and platelet transfusion and iron therapy with steroids. Uterine fibroids are commonly found to cause hematologic disturbances such as anemia and reactive thrombocytosis and, less commonly, thrombocytopenia. Moreover, such hematologic disturbances are secondary to heavy and irregular uterine bleeding, which is typically presented. A previous uterine fibroid diagnosis was made and reconfirmed by pelvic and transvaginal ultrasound to exclude other locoregional pathologies. ITP was suggested by Coombs test and several other serologies, leading to confirmation via bone marrow biopsy. In a previous case study, we reported positive responses in hemotecrit and platelet count after the introduction of iron therapy to an iron-depleted middle-aged female presenting severe anemia and thrombocytopenia. 1

  19. Anemia hemolítica imunomediada não regenerativa em um cão Nonregenerative immune-mediated hemolytic anemia in a dog

    Directory of Open Access Journals (Sweden)

    Leonardo Pinto Brandão

    2004-04-01

    Full Text Available Quadros hemolíticos não eritrorregenerativos são descritos em cães e podem ser decorrentes de doença medular primária, bem como, da destruição dos precursores eritróides medulares por imunoglobulinas. Um cão macho, de três anos de idade, sem raça definida, foi atendido no Hospital Veterinário da Faculdade de Medicina Veterinária e Zootecnia da Universidade de São Paulo apresentando sinais de anemia hemolítica aguda arregenerativa. Após a instituição de terapia imunossupressora (prednisona, houve remissão da hemólise sem, no entanto, sinais de eritrorregeneração. No décimo dia de tratamento, o mielograma demonstrou discreta hipoplasia e displasia eritróide, descartando a possibilidade de aplasia medular. Associou-se ciclofosfamida e azatioprina ao tratamento, tendo havido resposta eritrorregenerativa e recuperação dos valores hematológicos. A ocorrência deste caso de anemia hemolítica não eritrorregenerativa deve servir como alerta para a ocorrência desta condição mórbida, como também, da importância da utilização do mielograma como método auxiliar no diagnóstico de anemias arregenerativas.Nonregenerative forms of immune-mediated hemolytic anemia has been describe in dogs and are attributed to bone marrow diseases or immune-mediated destruction of erythroid progenitors. A 3-year-old, male mongrel dog was received at the Veterinary Hospital of the Faculdade of Medicina Veterinária e Zootecnia da Universidade de São Paulo (USP, Brazil showing signs of acute hemolytic anemia without erythroregeneration. After immunosuppressive therapy (prednisone the hemolysis was suppressed but the dog didn’t show hematologic signs of erythroid response. On the 10th day after treatment a bone marrow aspiration was performed and signs of hypoplasia and mild erythroid cell dysplasia were the main features observed, which could exclude the suspicious of marrow aplasia. After the addiction of cyclophosphamide and

  20. Coexistence of Cushing syndrome from functional adrenal adenoma and Addison disease from immune-mediated adrenalitis.

    Science.gov (United States)

    Colucci, Randall; Jimenez, Rafael E; Farrar, William; Malgor, Ramiro; Kohn, Leonard; Schwartz, Frank L

    2012-06-01

    A 56-year-old woman presented with an incidental adrenal adenoma and physical examination findings that included moderate obesity, a slight cervicothoracic fat pad ("buffalo hump"), increased supraclavicular fat pads, and white abdominal striae. Biochemical workup revealed elevated levels of 24-hour urinary free cortisol but normal serum morning cortisol and suppressed levels of corticotropin, suggestive of adrenal-dependent Cushing syndrome. The resected adrenal gland revealed macronodular cortical hyperplasia with a dominant nodule. Other findings included an absent cortisol response to corticotropin stimulation, presence of serum anti-21-hydroxylase antibodies, and mononuclear cell infiltration--consistent with adrenalitis. The findings represent, to the authors' knowledge, the first known case of a patient with coexistent functional cortisol-secreting macronodular adrenal tumor resulting in Cushing syndrome and immune-mediated adrenalitis resulting in Addison disease.

  1. Clinical development of reovirus for cancer therapy: An oncolytic virus with immune-mediated antitumor activity.

    Science.gov (United States)

    Gong, Jun; Sachdev, Esha; Mita, Alain C; Mita, Monica M

    2016-03-26

    Reovirus is a double-stranded RNA virus with demonstrated oncolysis or preferential replication in cancer cells. The oncolytic properties of reovirus appear to be dependent, in part, on activated Ras signaling. In addition, Ras-transformation promotes reovirus oncolysis by affecting several steps of the viral life cycle. Reovirus-mediated immune responses can present barriers to tumor targeting, serve protective functions against reovirus systemic toxicity, and contribute to therapeutic efficacy through antitumor immune-mediated effects via innate and adaptive responses. Preclinical studies have demonstrated the broad anticancer activity of wild-type, unmodified type 3 Dearing strain reovirus (Reolysin(®)) across a spectrum of malignancies. The development of reovirus as an anticancer agent and available clinical data reported from 22 clinical trials will be reviewed.

  2. Gestational thrombocytopenia among pregnant Ghanaian women ...

    African Journals Online (AJOL)

    The platelet counts were performed using Sysmex KX-21N automated hematology analyzer. The study design was cross sectional. Proportions were analyzed for statistical significance with the Chi square, Odds ratio was also calculated Results: The prevalence of thrombocytopenia in pregnant women in this study was ...

  3. Venous Thromboembolism in Patients With Thrombocytopenia

    DEFF Research Database (Denmark)

    Bælum, Jens Kristian; Ellingsen Moe, Espen; Nybo, Mads

    2017-01-01

    BACKGROUND: Venous thromboembolism (VTE) is a frequent and potentially lethal condition. Venous thrombi are mainly constituted of fibrin and red blood cells, but platelets also play an important role in VTE formation. Information about VTE in patients with thrombocytopenia is, however, missing. O...

  4. Heparin and heparin-induced thrombocytopenia

    African Journals Online (AJOL)

    2007-06-15

    Jun 15, 2007 ... therapy, namely heparin-induced thrombocytopenia (HIT). Pharmacology. Unfractionated heparin (UFH) ... UFH, because inpatient therapy with careful monitoring of aPTT is not required. Thus LMWH have allowed ... in 1909,7 and is derived from the medicinal leech. Lepirudin is recombinant hirudin, and ...

  5. Thrombocytopenia in Children Infected with the Human ...

    African Journals Online (AJOL)

    Thrombocytopenia in Children Infected with the Human Immunodeficiency Virus: Prevalence among Nigerian Igbo Children. ... The CDC Immunological classification showed that 32(13.3%) had no suppression, 71(39.5%) had moderate suppression and 130(56.2%) were severely suppressed. One hundred and sixty-eight ...

  6. REFRACTORY THROMBOCYTOPENIA AND NEUTROPENIA: A DIAGNOSTIC CHALLENGE

    Directory of Open Access Journals (Sweden)

    Emmanuel Gyan

    2015-02-01

    Full Text Available Background. The 2008 WHO classification identified refractory cytopenia with unilineage dysplasia (RCUD as a composite entity encompassing refractory anemia, refractory thrombocytopenia (RT, and refractory neutropenia (RN, characterized by 10% or more dysplastic cells in the bone marrow respective lineage. The diagnosis of RT and RN is complicated by several factors.  Diagnosing RT first requires exclusion of familial thrombocytopenia, chronic auto-immune thrombocytopenia, concomitant medications, viral infections, or hypersplenism. Diagnosis of RN should also be made after ruling out differential diagnoses such as ethnic or familial neutropenia, as well as acquired, drug-induced, infection-related or malignancy-related neutropenia. An accurate quantification of dysplasia should be performed in order to distinguish RT or RN from the provisional entity named idiopathic cytopenia of unknown significance (ICUS. Cytogenetic analysis, and possibly in the future somatic mutation analysis (of genes most frequently mutated in MDS, and flow cytometry analysis aberrant antigen expression on myeloid cells may help in this differential diagnosis. Importantly, we and others found that, while isolated neutropenia and thrombocytopenia are not rare in MDS, those patients can generally be classified (according to WHO 2008 classification as refractory cytopenia with multilineage dysplasia or refractory anemia with excess blasts, while RT and RN (according to WHO 2008 are quite rare.These results suggest in particular that identification of RT and RN as distinct entities could be reconsidered in future WHO classification updates.

  7. Infections and Thrombocytopenia in Chronic Idiopathic ...

    African Journals Online (AJOL)

    This is a case report to study the association between episodes of thrombocytopenia and bacterial infections in a patient with chronic idiopathic thrombocytopenic purpura (ITP).The case was a 31 year old female patient, with a history of chronic ecchymosis, melaena stool and menorrhagia, who presented at the female ...

  8. Splenic irradiation in HIV-related thrombocytopenia

    International Nuclear Information System (INIS)

    Leung, J.T.; Kuan, R.

    1996-01-01

    Splenic irradiation has been used in patients with HIV-related thrombocytopenia. This retrospective review deals with four patients treated with low dose splenic irradiation. All patients had an increase in platelet count and tolerated the treatment without side effects. However, the treatment response lasted for several months only. 9 refs., 1 tab

  9. Urothelial Cancer With Occult Bone Marrow Metastases and Isolated Thrombocytopenia

    Directory of Open Access Journals (Sweden)

    Ajjai Alva

    2015-07-01

    Full Text Available Bladder cancer rarely presents clinically with a myelophthisic picture from diffuse bone marrow infiltration especially in the absence of detectable skeletal metastases. A 75-year old man presented with newly diagnosed urothelial cell carcinoma of the bladder. Pathology from transurethral resection of bladder tumor demonstrated muscle-invasive disease. Pre-therapy imaging including CT abdomen/pelvis, CXR and bone scan demonstrated liver lesions concerning for metastatic disease but no skeletal metastases. Labs were notable for isolated thrombocytopenia, hypercalcemia and acute kidney injury prompting hospitalization. Hematologic work-up including bone marrow aspiration and biopsy revealed diffuse infiltration of the bone marrow by urothelial cancer. The case illustrates the importance of fully investigating otherwise unexplained clinical findings in patients with clinically localized urothelial cancer prior to curative intent surgery.

  10. Use of thrombopoietin receptor agonists in childhood immune thrombocytopenia

    Directory of Open Access Journals (Sweden)

    Angelica Maria Garzon

    2015-08-01

    Full Text Available Most children with immune thrombocytopenia (ITP will have spontaneous remission regardless of therapy, while about 20% will go on to have chronic ITP. In those children with chronic ITP who need treatment, standard therapies for acute ITP may have adverse effects that complicate their long term use. Thus, alternative treatment options are needed for children with chronic ITP. Thrombopoietin receptor agonists (TPO-RA have been shown to be safe and efficacious in adults with ITP, and represent a new treatment option for children with chronic ITP. One TPO-RA, eltrombopag, is now approved for children. Clinical trials in children are ongoing and data is emerging on safety and efficacy. This review will focus on the physiology of TPO-RA, their clinical use in children, as well as the long term safety issues that need to be considered when using these agents

  11. Good agreement of conventional and gel-based direct agglutination test in immune-mediated haemolytic anaemia

    NARCIS (Netherlands)

    Piek, C.J.; Teske, E.; van Leeuwen, M.W.; Day, M.J.

    2012-01-01

    Abstract Background The aim of this study was to compare a gel-based test with the traditional direct agglutination test (DAT) for the diagnosis of immune-mediated haemolytic anaemia (IMHA). Methods Canine (n = 247) and feline (n = 74) blood samples were submitted for DAT testing to two

  12. Lack of evidence of a beneficial effect of azathioprine immune-mediated hemolytic anemia: a retrospective cohort study

    NARCIS (Netherlands)

    Piek, C.J.; Spil, Van W.E.; Junius, G.; Dekker, A.

    2011-01-01

    Background Azathioprine is used as an immunosuppressant in canine immune-mediated hemolytic anemia (IMHA), but this potentially toxic and carcinogenic drug has not been proven to be beneficial. The aim of this study was to determine the difference in outcome and survival of dogs with idiopathic IMHA

  13. Noninvasive Sampling of Mucosal Lining Fluid for the Quantification of In Vivo Upper Airway Immune-mediator Levels

    DEFF Research Database (Denmark)

    Wolsk, Helene Mygind; Chawes, Bo L.; Thorsen, Jonathan

    2017-01-01

    This protocol describes noninvasive sampling of undisturbed upper airway mucosal lining fluid. It also details the extraction procedure used prior to the analysis of immune mediators in fluid eluates for the study of the airway topical immune signature, without the need for stimulation procedures...

  14. A coculture model mimicking the intestinal mucosa reveals a regulatory role for myofibroblasts in immune-mediated barrier disruption

    NARCIS (Netherlands)

    Willemsen, L. E. M.; Schreurs, C. C. H. M.; Kroes, H.; Spillenaar Bilgen, E. J.; van Deventer, S. J. H.; van Tol, E. A. F.

    2002-01-01

    The pathogenesis of Crohn's disease involves a mucosal inflammatory response affecting the barrier function of the gut. Myofibroblasts directly underlining the intestinal epithelium may have a regulatory role in immune-mediated barrier disruption. A coculture system of T84 epithelial and CCD-18Co

  15. Pathobiology and Treatment of Hepatitis Virus-Related Thrombocytopenia

    Science.gov (United States)

    Stasi, Roberto; Chia, Lian Wea; Kalkur, Pallavi; Lowe, Robert; Shannon, Muriel S.

    2009-01-01

    Thrombocytopenia is a well recognized complication of infections, including those from hepatotropic viruses. Thrombocytopenia may actually be the only manifestation of vital hepatitis, which should therefore be considered in the differential diagnosis of primary immune thrombocytopenia (ITP). The mechanisms of thrombocytopenia associated with viral hepatitis vary widely depending on the specific infectious agent and the severity of liver disease. Most of the studies have described thrombocytopenia in association with chronic hepatitis C virus (HCV) infection, the most common cause of chronic infection worldwide. Studies have shown that treatment of HCV infection often results in substantial improvement or complete recovery of the thrombocytopenia. In patients with thrombocytopenia associated with HCV-related chronic liver disease, the use of eltrombopag, a thrombopoietin receptor agonist, normalizes platelet levels thereby permitting the initiation of antiviral therapy. PMID:21415958

  16. PATHOBIOLOGY AND TREATMENT OF HEPATITIS VIRUS-RELATED THROMBOCYTOPENIA

    Directory of Open Access Journals (Sweden)

    Roberto Stasi

    2009-11-01

    Full Text Available Thrombocytopenia is a well recognized complication of infections, including those from hepatotropic viruses. Thrombocytopenia may actually be the only manifestation of vital hepatitis, which should therefore be considered in the differential diagnosis of primary immune thrombocytopenia (ITP. The mechanisms of thrombocytopenia associated with viral hepatitis vary widely depending on the specific infectious agent and the severity of liver disease. Most of the studies have described thrombocytopenia in association with chronic hepatitis C virus (HCV infection, the most common cause of chronic infection worldwide. Studies have shown that treatment of HCV infection often results in substantial improvement or complete recovery of the thrombocytopenia. In patients with thrombocytopenia associated with HCV-related chronic liver disease, the use of eltrombopag, a thrombopoietin receptor agonist, normalizes platelet levels thereby permitting the initiation of antiviral therapy.

  17. Clinical and laboratory characteristics of severe fever with thrombocytopenia syndrome in Chinese patients.

    Science.gov (United States)

    Weng, Yali; Chen, Nian; Han, Yaping; Xing, Yiping; Li, Jun

    2014-01-01

    Severe fever with thrombocytopenia syndrome (SFTS) associated with severe fever with thrombocytopenia syndrome virus (SFTSV) is an emerging infectious disease. 12 patients with severe fever with thrombocytopenia syndrome in our study were presented mainly with fever and severe malaise. The clinical manifestations typically became worse on the 6th or 7th day. The average fever time is 9.11 ± 1.54 days. Most of them had multiorgan dysfunction, and part of them had hemophagocytic lymphohistiocytosis histiocytosis (HLH). The characteristic laboratory findings in the early stage were the drop of white blood cells (WBC), platelets (PLT) and serum Ca++, while increase of aspartate amino transferase (AST), creatine kinase (CK), and lactate dehydrogenase (LDH). CD3+CD4+ were significantly decreased, while CD3-CD56+ were significantly increased, whereas CD3+CD8+ were constantly elevated throughout the disease course. Ten to 14 days after illness onset, symptoms were improved, accompanied by resolution of laboratory abnormalities. These results indicate that severe fever with thrombocytopenia syndrome has an acute onset and self-limited course. It is a systemic infection. The host immune response caused tissues and organs injury. The improvement of symptoms and laboratory tests is consistent with the elimination of the virus and recover of immune response. Further investigation should be done in order to better understand this disease and guide the clinical treatment. Copyright © 2013 Elsevier Editora Ltda. All rights reserved.

  18. Thrombocytopenia in Dengue: Interrelationship between Virus and the Imbalance between Coagulation and Fibrinolysis and Inflammatory Mediators

    Directory of Open Access Journals (Sweden)

    Elzinandes Leal de Azeredo

    2015-01-01

    Full Text Available Dengue is an infectious disease caused by dengue virus (DENV. In general, dengue is a self-limiting acute febrile illness followed by a phase of critical defervescence, in which patients may improve or progress to a severe form. Severe illness is characterized by hemodynamic disturbances, increased vascular permeability, hypovolemia, hypotension, and shock. Thrombocytopenia and platelet dysfunction are common in both cases and are related to the clinical outcome. Different mechanisms have been hypothesized to explain DENV-associated thrombocytopenia, including the suppression of bone marrow and the peripheral destruction of platelets. Studies have shown DENV-infected hematopoietic progenitors or bone marrow stromal cells. Moreover, anti-platelet antibodies would be involved in peripheral platelet destruction as platelets interact with endothelial cells, immune cells, and/or DENV. It is not yet clear whether platelets play a role in the viral spread. Here, we focus on the mechanisms of thrombocytopenia and platelet dysfunction in DENV infection. Because platelets participate in the inflammatory and immune response by promoting cytokine, chemokine, and inflammatory mediator secretion, their relevance as “immune-like effector cells” will be discussed. Finally, an implication for platelets in plasma leakage will be also regarded, as thrombocytopenia is associated with clinical outcome and higher mortality.

  19. Epidemiologic investigation of immune-mediated polyradiculoneuropathy among abattoir workers exposed to porcine brain.

    Directory of Open Access Journals (Sweden)

    Stacy M Holzbauer

    2010-03-01

    associated with removing porcine brains with compressed air. An autoimmune mechanism is supported by higher levels of IFNgamma in cases than in controls consistent with other immune mediated illnesses occurring in association with neural tissue exposure. Abattoirs should not use compressed air to remove brains and should avoid procedures that aerosolize CNS tissue. This outbreak highlights the potential for respiratory or mucosal exposure to cause an immune-mediated illness in an occupational setting.

  20. STAT3 activity is necessary and sufficient for the development of immune-mediated myocarditis in mice and promotes progression to dilated cardiomyopathy

    Science.gov (United States)

    Camporeale, Annalisa; Marino, Francesca; Papageorgiou, Anna; Carai, Paolo; Fornero, Sara; Fletcher, Steven; Page, Brent D G; Gunning, Patrick; Forni, Marco; Chiarle, Roberto; Morello, Mara; Jensen, Ole; Levi, Renzo; Heymans, Stephane; Poli, Valeria

    2013-01-01

    Myocarditis, often triggered by viral infection, may lead to heart auto-immunity and dilated cardiomyopathy. What determines the switch between disease resolution and progression is however incompletely understood. We show that pharmacological inhibition of STAT3, the main mediator of IL-6 signalling and of Th17-cell differentiation, protects mice from the development of Experimental Auto-immune Myocarditis reducing liver production of the complement component C3, and can act therapeutically when administered at disease peak. Further, we demonstrate that STAT3 is sufficient when constitutively active for triggering the onset of immune-mediated myocarditis, involving enhanced complement C3 production and IL-6 signalling amplification in the liver. Disease development can be prevented by C3 depletion and IL-6 receptor neutralization. This appears to be relevant to disease pathogenesis in humans, since acute myocarditis patients display significantly elevated circulating IL-6 and C3 levels and activated heart STAT3. Thus, aberrant IL-6/STAT3-mediated induction of liver acute phase response genes including C3, which occurs as a consequence of pre-existing inflammatory conditions, might represent an important factor determining the degree of myocarditis and its clinical outcome. PMID:23460527

  1. Steroid sparing regimens for management of oral immune-mediated diseases

    Directory of Open Access Journals (Sweden)

    Arti Agrawal

    2014-01-01

    Full Text Available Immune-mediated mucocutaneous disease may present oral symptoms as a first sign of the disease. The primary etiology could be the cellular and/or humoral immune responses directed against epithelial or connective tissue, in a chronic and recurrent pattern. Lichen planus, pemphigus vulgaris and bullous pemphigoid are the most frequent immunologically mediated mucocutaneous diseases. More often than not, patients present with complaints of blisters, oral ulcers, pain, burning sensation, and bleeding from the various oral sites. Steroids, whether topical or systemic, are the treatment of choice as they have both anti-inflammatory and immune-suppressant properties; however, challenges in the treatment of autoimmune diseases are the complexity of symptoms, the need to manage long-term medications for preserving organ function, and the long-term adverse effects of steroids. In such situations steroid sparing agents, such as, tacrolimus, dapsone, azathioprine, cyclosporine, and so on, may be helpful. Here an attempt is made to review various treatment regimens that could be used as alternatives to steroids for management of such diseases.

  2. Month of birth, vitamin D and risk of immune-mediated disease: a case control study

    Directory of Open Access Journals (Sweden)

    Disanto Giulio

    2012-07-01

    Full Text Available Abstract Background A season of birth effect in immune-mediated diseases (ID such as multiple sclerosis and type 1 diabetes has been consistently reported. We aimed to investigate whether season of birth influences the risk of rheumatoid arthritis, Crohn's disease, ulcerative colitis and systemic lupus erythematosus in addition to multiple sclerosis, and to explore the correlation between the risk of ID and predicted ultraviolet B (UVB light exposure and vitamin D status during gestation. Methods The monthly distribution of births of patients with ID from the UK (n = 115,172 was compared to that of the general population using the Cosinor test. Predicted UVB radiation and vitamin D status in different time windows during pregnancy were calculated for each month of birth and correlated with risk of ID using the Spearman's correlation coefficient. Results The distributions of ID births significantly differed from that of the general population (P = 5e-12 with a peak in April (odds ratio = 1.045, 95% confidence interval = 1.024, 1.067, P P P = 0.00005 and third trimester vitamin D status (Spearman's rho = -0.44, P = 0.0003. Conclusions The risk of different ID in the UK is significantly influenced by the season of birth, suggesting the presence of a shared seasonal risk factor or factors predisposing to ID. Gestational UVB and vitamin D exposure may be implicated in the aetiology of ID.

  3. Monocyte scintigraphy in rheumatoid arthritis: the dynamics of monocyte migration in immune-mediated inflammatory disease.

    Directory of Open Access Journals (Sweden)

    Rogier M Thurlings

    2009-11-01

    Full Text Available Macrophages are principal drivers of synovial inflammation in rheumatoid arthritis (RA, a prototype immune-mediated inflammatory disease. Conceivably, synovial macrophages are continuously replaced by circulating monocytes in RA. Animal studies from the 1960s suggested that macrophage replacement by monocytes is a slow process in chronic inflammatory lesions. Translation of these data into the human condition has been hampered by the lack of available techniques to analyze monocyte migration in man.We developed a technique that enabled us to analyze the migration of labelled autologous monocytes in RA patients using single photon emission computer tomography (SPECT. We isolated CD14+ monocytes by CliniMACS in 8 patients and labeled these with technetium-99m (99mTc-HMPAO. Monocytes were re-infused into the same patient. Using SPECT we calculated that a very small but specific fraction of 3.4 x 10(-3 (0.95-5.1 x 10(-3 % of re-infused monocytes migrated to the inflamed joints, being detectable within one hour after re-infusion.The results indicate monocytes migrate continuously into the inflamed synovial tissue of RA patients, but at a slow macrophage-replacement rate. This suggests that the rapid decrease in synovial macrophages that occurs after antirheumatic treatment might rather be explained by an alteration in macrophage retention than in monocyte influx and that RA might be particularly sensitive to treatments targeting inflammatory cell retention.

  4. Physical comorbidities increase the risk of psychiatric comorbidity in immune-mediated inflammatory disease.

    Science.gov (United States)

    Marrie, Ruth Ann; Walld, Randy; Bolton, James M; Sareen, Jitender; Walker, John R; Patten, Scott B; Singer, Alexander; Lix, Lisa M; Hitchon, Carol A; El-Gabalawy, Renée; Katz, Alan; Fisk, John D; Bernstein, Charles N

    2018-01-11

    We tested the association between physical comorbidity and incident depression, anxiety disorder and bipolar disorder in three immune-mediated inflammatory diseases (IMID): inflammatory bowel disease (IBD), multiple sclerosis (MS) and rheumatoid arthritis (RA) versus age-, sex- and geographically-matched controls. Using population-based administrative data we identified 6119 persons with IBD, 3514 persons with MS, 10,206 persons with RA and 97,727 matched controls. We identified incident cases of depression, anxiety disorder and bipolar disorder in these populations. We evaluated the association of physical comorbidities with incident psychiatric comorbidity using Cox regression, adjusting for sociodemographic factors and index year. The risk of incident depression, anxiety disorders and bipolar disorder was higher in each IMID cohort versus their matched cohorts. The risk of incident psychiatric comorbidity increased with an increasing number of physical comorbidities for each psychiatric comorbidity evaluated, across all IMID. Adjustment for physical comorbidity did not attenuate the increased risk of psychiatric comorbidity in the IMID cohorts versus their matched cohorts. The increased incidence of psychiatric comorbidity in IMID versus matched general population cohorts is not accounted for by their increased prevalence of physical comorbidities. However, within IMID cohorts, physical comorbidity increases the risk of psychiatric comorbidity. Copyright © 2018. Published by Elsevier Inc.

  5. The Protective Effects of Extra Virgin Olive Oil on Immune-mediated Inflammatory Responses.

    Science.gov (United States)

    Casas, Rosa; Estruch, Ramon; Sacanella, Emilio

    2018-01-01

    The increasing interest in the Mediterranean diet (MeDiet) hinges on the relevant role it plays in inflammatory diseases. Several clinical, epidemiological and experimental evidences suggest that consumption of the MeDiet reduces the incidence of certain pathologies related to oxidative stress, chronic inflammation and immune system diseases such as cancer, atherosclerosis and cardiovascular disease (CVD). These reductions can be partially attributed to extra virgin olive oil (EVOO) consumption which has been described as a key bioactive food because of its high nutritional quality and its particular composition of fatty acids, vitamins and polyphenols. Indeed, the beneficial effects of EVOO have been linked to its fatty acid composition, which is very rich in monounsaturated fatty acids (MUFA), and has moderate saturated and polyunsaturated fatty acids (PUFA). The current knowledge available on the beneficial effects of EVOO and its phenolic compounds, specifically its biological properties and antioxidant capacity against immune-mediated inflammatory responses (atherosclerosis, rheumatoid arthritis, diabetes, obesity, cancer, inflammatory bowel disease or neurodegenerative disease, among others) in addition to its potential clinical applications. The increasing body of studies carried out provides compelling evidence that olive polyphenols are potential candidates to combat chronic inflammatory states. Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.org.

  6. Lack of collagen XVIII/endostatin exacerbates immune-mediated glomerulonephritis.

    Science.gov (United States)

    Hamano, Yuki; Okude, Takashi; Shirai, Ryota; Sato, Ikumi; Kimura, Ryota; Ogawa, Makoto; Ueda, Yoshihiko; Yokosuka, Osamu; Kalluri, Raghu; Ueda, Shiro

    2010-09-01

    Collagen XVIII is a component of the highly specialized extracellular matrix associated with basement membranes of epithelia and endothelia. In the normal kidney, collagen XVIII is distributed throughout glomerular and tubular basement membranes, mesangial matrix, and Bowman's capsule. Proteolytic cleavage within its C-terminal domain releases the fragment endostatin, which has antiangiogenic properties. Because damage to the glomerular basement membrane (GBM) accompanies immune-mediated renal injury, we investigated the role of collagen XVIII/endostatin in this disorder. We induced anti-GBM glomerulonephritis in collagen XVIII alpha1-null and wild-type mice and compared the resulting matrix accumulation, inflammation, and capillary rarefaction. Anti-GBM disease upregulated collagen XVIII/endostatin expression within the GBM and Bowman's capsule of wild-type mice. Collagen XVIII/endostatin-deficient mice developed more severe glomerular and tubulointerstitial injury than wild-type mice. Collagen XVIII/endostatin deficiency altered matrix remodeling, enhanced the inflammatory response, and promoted capillary rarefaction and vascular endothelial cell damage, but did not affect endothelial proliferation. Supplementing collagen XVIII-deficient mice with exogenous endostatin did not affect the progression of anti-GBM disease. Taken together, these results suggest that collagen XVIII/endostatin preserves the integrity of the extracellular matrix and capillaries in the kidney, protecting against progressive glomerulonephritis.

  7. Gene Expression by PBMC in Primary Sclerosing Cholangitis: Evidence for Dysregulation of Immune Mediated Genes

    Directory of Open Access Journals (Sweden)

    Christopher A. Aoki

    2006-01-01

    Full Text Available Primary sclerosing cholangitis (PSC is a chronic disease of the bile ducts characterized by an inflammatory infiltrate and obliterative fibrosis. The precise role of the immune system in the pathogenesis of PSC remains unknown. We used RNA microarray analysis to identify immune-related genes and pathways that are differentially expressed in PSC. Messenger RNA (mRNA from peripheral blood mononuclear cells (PBMC was isolated from both patients with PSC and age and sex matched healthy controls. Samples from 5 PSC patients and 5 controls were analyzed by microarray and based upon rigorous statistical analysis of the data, relevant genes were chosen for confirmation by RT-PCR in 10 PSC patients and 10 controls. Using unsupervised hierarchical clustering, gene expression in PSC was statistically different from our control population. Interestingly, genes within the IL-2 receptor beta, IL-6 and MAP Kinase pathways were found to be differently expressed in patients with PSC compared to controls. Further, individual genes, TNF-α induced protein 6 (TNFaip6 and membrane-spanning 4-domains, subfamily A (ms4a were found to be upregulated in PSC while similar to Mothers against decapentaplegic homolog 5 (SMAD 5 was downregulated. In conclusion, several immune-related pathways and genes were differentially expressed in PSC compared to control patients, giving further evidence that this disease is systemic and immune-mediated.

  8. Thrombocytopenia and Cornelia de Lange syndrome: Still an enigma?

    Science.gov (United States)

    Cavalleri, Valeria; Bettini, Laura R; Barboni, Chiara; Cereda, Anna; Mariani, Milena; Spinelli, Marco; Gervasini, Cristina; Russo, Silvia; Biondi, Andrea; Jankovic, Momcilo; Selicorni, Angelo

    2016-01-01

    Cornelia de Lange Syndrome (CdLS) is a rare genetic disorder caused by mutations in the cohesion complex and its regulators. The syndrome is characterized by multiple organ system abnormalities, pre- and post-natal growth retardation and typical facial features. Thrombocytopenia is a reduction in platelet count to <150 × 10(9)  L. It can be caused by congenital or acquired decreased production, increased destruction, or sequestration of platelets. In recent years, several papers reported thrombocytopenia and immune thrombocytopenia in patients affected by CdLS. In 2011, Lambert et al. estimated the risk of idiopathic thrombocytopenia purpura in CdLS patients to be 31-633 times greater than in the general population. We describe the incidence of thrombocytopenia in 127 Italian CdLS patients, identifying patients with transient or persistent thrombocytopenia, but a lower incidence of true idiopathic thrombocytopenic purpura (ITP). © 2015 Wiley Periodicals, Inc.

  9. Thrombocytopenia during Pregnancy and Its Outcome – A Prospective Study

    Directory of Open Access Journals (Sweden)

    Pallavi Satish Vishwekar

    2017-01-01

    Full Text Available Background: Thrombocytopenia is second to anemia as the most common hematological abnormality during pregnancy. Accurate etiological diagnosis is essential for optimal therapeutic management and thus can prevent maternal and fetal morbidity and mortality. Aims and Objectives: To determine various etiologies of maternal thrombocytopenia, their complications and fetomaternal outcome compared with normal pregnancy. Material and Methods: A prospective study was carried out in tertiary hospital, 1460 pregnant women who attended the Antenatal clinic regularly were enrolled. All were screened for thrombocytopenia in third trimester (after 28 weeks, women with normal platelet (n=1350 were taken in control group and those with low counts less than 150 x109/L (n=130 were included in study group. Etiology and fetomaternal outcome of thrombocytopenia in third trimester of pregnancy were evaluated and compared. Results: Gestational thrombocytopenia was the commonest etiology (68.46%. Incidence of thrombocytopenia due to severe preeclampsia and Hemolysis, Elevated Liver enzymes, Low Platelet (HELLP syndrome in study group was 18.46% and 7.69% of them had medical cause like malarial or dengue fever. Major causes were Gestational Thrombocytopenia (GT, Idiopathic Thrombocytopenic Purpura (ITP, preeclampsia, HELLP syndrome, malaria, and dengue. Maternal complications due to bleeding tendencies like placental abruption, postpartum hemorrhage were evident in the study population. Fetal complications were significantly higher in study group. Early neonatal thrombocytopenia depended on etiology rather than severity of maternal thrombocytopenia. Conclusions: Outcome of pregnancy with moderate to severe thrombocytopenia depends mainly on the etiology of thrombocytopenia. Adverse outcomes are especially seen with pregnancy complicated by preeclampsia and HELLP syndrome. Fetomaternal outcome is favorable in gestational thrombocytopenia. Thus accurate etiological

  10. Major Histocompatibility Complex I and II Expression and Lymphocytic Subtypes in Muscle of Horses with Immune?Mediated Myositis

    OpenAIRE

    Durward?Akhurst, S.A.; Finno, C.J.; Barnes, N.; Shivers, J.; Guo, L.T.; Shelton, G.D.; Valberg, S.J.

    2016-01-01

    Background Major histocompatibility complex (MHC) I and II expression is not normally detected on sarcolemma, but is detected with lymphocytic infiltrates in immune?mediated myositis (IMM) of humans and dogs and in dysferlin?deficient muscular dystrophy. Hypothesis/Objectives To determine if sarcolemmal MHC is expressed in active IMM in horses, if MHC expression is associated with lymphocytic subtype, and if dysferlin is expressed in IMM. Animals Twenty?one IMM horses of Quarter Horse?related...

  11. Risk of venous thromboembolism in people admitted to hospital with selected immune-mediated diseases: record-linkage study

    Directory of Open Access Journals (Sweden)

    Handel Adam E

    2011-01-01

    Full Text Available Abstract Background Venous thromboembolism (VTE is a common complication during and after a hospital admission. Although it is mainly considered a complication of surgery, it often occurs in people who have not undergone surgery, with recent evidence suggesting that immune-mediated diseases may play a role in VTE risk. We, therefore, decided to study the risk of deep vein thrombosis (DVT and pulmonary embolism (PE in people admitted to hospital with a range of immune-mediated diseases. Methods We analysed databases of linked statistical records of hospital admissions and death certificates for the Oxford Record Linkage Study area (ORLS1:1968 to 1998 and ORLS2:1999 to 2008 and the whole of England (1999 to 2008. Rate ratios for VTE were determined, comparing immune-mediated disease cohorts with comparison cohorts. Results Significantly elevated risks of VTE were found, in all three populations studied, in people with a hospital record of admission for autoimmune haemolytic anaemia, chronic active hepatitis, dermatomyositis/polymyositis, type 1 diabetes mellitus, multiple sclerosis, myasthenia gravis, myxoedema, pemphigus/pemphigoid, polyarteritis nodosa, psoriasis, rheumatoid arthritis, Sjogren's syndrome, and systemic lupus erythematosus. Rate ratios were considerably higher for some of these diseases than others: for example, for systemic lupus erythematosus the rate ratios were 3.61 (2.36 to 5.31 in the ORLS1 population, 4.60 (3.19 to 6.43 in ORLS2 and 3.71 (3.43 to 4.02 in the England dataset. Conclusions People admitted to hospital with immune-mediated diseases may be at an increased risk of subsequent VTE. Our findings need independent confirmation or refutation; but, if confirmed, there may be a role for thromboprophylaxis in some patients with these diseases.

  12. [21-year-old patient with myocardial infarct, transient cerebral ischemia and thrombocytopenia].

    Science.gov (United States)

    Rank, A; Lindner, L; Hiller, E

    2003-03-01

    We report on a case of a young female soccer player who first experienced a transient ischemic attack at the age of 21 and then suffered an acute myocardial infarction accompanied by thrombocytopenia 6 months later. The underlying cause was antiphospholipid syndrome. This clinical picture is caused by a very heterogeneous group of antiphospholipid antibodies, which interfere with plasmatic coagulation at various sites and are able to activate thrombocytes, endothelial cells, and monocytes. This leads to a thrombophilic condition with clinical manifestation of recurrent venous thromboses, arterial embolisms, or premature birth or miscarriage. The main therapeutic options are thus anticoagulation, heparins, and aspirin. Steroids are recommended for cases of pronounced thrombocytopenias; if treatment fails, immunosuppressants are also advisable. The antiphospholipid syndrome should be kept in mind especially in cases of young patients with thromboembolic events since the presence of antiphospholipid antibodies can be detected in 10-20% of this patient group and effective therapy after diagnosis lowers the rate of recurrence.

  13. Treatment with Quinoline-3-carboxamide does not successfully prevent immune-mediated glomerulonephritis in mice.

    Science.gov (United States)

    Draibe, Juliana; Pepper, Ruth J; Salama, Alan D

    Quinoline-3-carboximide compounds, such as paquinimod, which targets the protein S100A9, have demonstrated efficacy in treating autoimmune diseases. S100A9, in association with S100A8, forms the heterodimer S100A8/S100A9, known as calprotectin; that has been shown to be upregulated in numerous inflammatory disorders. We had previously demonstrated protection from glomerular disease in S100A9-deficient mice. The aim of this study was to assess the efficacy of paquinimod in the prevention and treatment of experimental glomerulonephritis. Nephrotoxic nephritis (NTN) was induced in C57BL/6 mice according to our standard protocol. Mice were treated with different doses of paquinimod either at disease induction (prevention group) or two days following induction (therapeutic group) and sacrificed 8 days following induction. Disease was assessed histologically (number of glomerular crescents, degree of glomerular thrombosis, number of infiltrating leucocytes and calprotectin expression) and biochemically (serum creatinine and urea levels, and urinary levels of protein). Neither treatment with low (0.5mg/kg) or high (25mg/kg) doses of paquinimod, given preventatively or therapeutically, led to disease attenuation, as assessed by biochemical or histological parameters. Additionally, we found trends for an increase in renal glomerular calprotectin expression in the high dose groups, suggesting a possible feedback regulation of calprotectin expression. Our results show that paquinimod does not successfully prevent or treat mice with NTN. Other models of immune-mediated glomerulonephritis need to be tested to investigate the therapeutic potential of this compound in renal disease. Copyright © 2016 Sociedad Española de Nefrología. Published by Elsevier España, S.L.U. All rights reserved.

  14. Increased incidence of psychiatric disorders in immune-mediated inflammatory disease.

    Science.gov (United States)

    Marrie, Ruth Ann; Walld, Randy; Bolton, James M; Sareen, Jitender; Walker, John R; Patten, Scott B; Singer, Alexander; Lix, Lisa M; Hitchon, Carol A; El-Gabalawy, Renée; Katz, Alan; Fisk, John D; Bernstein, Charles N

    2017-10-01

    Although psychiatric comorbidity is known to be more prevalent in immune-mediated inflammatory diseases (IMID) than in the general population, the incidence of psychiatric comorbidity in IMID is less understood, yet incidence is more relevant for understanding etiology. Using population-based administrative (health) data, we conducted a retrospective cohort study over the period 1989-2012 in Manitoba, Canada. We identified 19,572 incident cases of IMID including 6119 persons with inflammatory bowel disease (IBD), 3514 persons with multiple sclerosis (MS), 10,206 persons with rheumatoid arthritis (RA), and 97,727 age-, sex- and geographically-matched controls. After applying validated case definitions, we estimated the incidence of depression, anxiety disorder, bipolar disorder and schizophrenia in each of the study cohorts. Using negative binomial regression models, we tested whether the incidence rate of psychiatric comorbidity was elevated in the individual and combined IMID cohorts versus the matched cohorts, adjusting for sex, age, region of residence, socioeconomic status and year. The relative incidence of depression (incidence rate ratio [IRR] 1.71; 95%CI: 1.64-1.79), anxiety (IRR 1.34; 95%CI: 1.29-1.40), bipolar disorder (IRR 1.68; 95%CI: 1.52-1.85) and schizophrenia (IRR 1.32; 95%CI: 1.03-1.69) were elevated in the IMID cohort. Depression and anxiety affected the MS population more often than the IBD and RA populations. Individuals with IMID, including IBD, MS and RA are at increased risk of psychiatric comorbidity. This increased risk appears non-specific as it is seen for all three IMIDs and for all psychiatric disorders studied, implying a common underlying biology for psychiatric comorbidity in those with IMID. Copyright © 2017 The Authors. Published by Elsevier Inc. All rights reserved.

  15. Rising incidence of psychiatric disorders before diagnosis of immune-mediated inflammatory disease.

    Science.gov (United States)

    Marrie, R A; Walld, R; Bolton, J M; Sareen, J; Walker, J R; Patten, S B; Singer, A; Lix, L M; Hitchon, C A; El-Gabalawy, R; Katz, A; Fisk, J D; Bernstein, C N

    2017-11-03

    After the diagnosis of immune-mediated inflammatory diseases (IMID) such as inflammatory bowel disease (IBD), multiple sclerosis (MS) and rheumatoid arthritis (RA), the incidence of psychiatric comorbidity is increased relative to the general population. We aimed to determine whether the incidence of psychiatric disorders is increased in the 5 years before the diagnosis of IMID as compared with the general population. Using population-based administrative health data from the Canadian province of Manitoba, we identified all persons with incident IBD, MS and RA between 1989 and 2012, and cohorts from the general population matched 5 : 1 on year of birth, sex and region to each disease cohort. We identified members of these groups with at least 5 years of residency before and after the IMID diagnosis date. We applied validated algorithms for depression, anxiety disorders, bipolar disorder, schizophrenia, and any psychiatric disorder to determine the annual incidence of these conditions in the 5-year periods before and after the diagnosis year. We identified 12 141 incident cases of IMID (3766 IBD, 2190 MS, 6350 RA) and 65 424 matched individuals. As early as 5 years before diagnosis, the incidence of depression [incidence rate ratio (IRR) 1.54; 95% CI 1.30-1.84) and anxiety disorders (IRR 1.30; 95% CI 1.12-1.51) were elevated in the IMID cohort as compared with the matched cohort. Similar results were obtained for each of the IBD, MS and RA cohorts. The incidence of bipolar disorder was elevated beginning 3 years before IMID diagnosis (IRR 1.63; 95% CI 1.10-2.40). The incidence of psychiatric comorbidity is elevated in the IMID population as compared with a matched population as early as 5 years before diagnosis. Future studies should elucidate whether this reflects shared risk factors for psychiatric disorders and IMID, a shared final common inflammatory pathway or other aetiology.

  16. Tandem plasmapheresis and haemodialysis as a safe procedure in 82 patients with immune-mediated disease.

    Science.gov (United States)

    Dechmann-Sültemeyer, Thomas; Linkeschova, Renata; Lenzen, Karl; Kuril, Zdravko; Grabensee, Bernd; Voiculescu, Adina

    2009-01-01

    A number of medical, mostly immune-mediated conditions call for a combination therapy consisting of plasmapheresis and haemodialysis. While the two treatments are most commonly applied separately, we describe here the technical details of providing a combined 'tandem' treatment. Method. The components of a dialyzer (polysulfon membrane) and plasma filter are serially connected by a continuous arteriovenous haemofiltration (CAVH) system. In an extracorporeal circulation, using a blood pump the patient's blood is led first to the plasma filter and then into the dialyzer. The substituate connection is located behind the plasma filter and before the dialyzer. At the beginning it is obligatory to carry out an inspection of tubing system leakages. Afterwards, the system is flushed with a heparinized (5000 IE) sodium chloride solution that is removed thereafter. During the treatment, a blood flow of 150-200 ml/min is possible. In each case, the plasmafiltration and the ultrafiltration should not exceed 25% of the blood flow. The whole time, an intermittent check of blood pressure and heart rate is necessary. The total procedure does not take longer than a routine haemodialysis (3-4 h). In 82 patients we performed 483 tandem treatments during the last 16 years. None of the patients had volume disturbances caused by plasma shifts and derangements of electrolytes and acid-base balance were immediately equalized. There were no episodes of hypotension or bleeding. Back-filtration did not occur. Providing both haemodialysis and plasmapheresis at the same time reduces treatment time and thus, overall cost of the treatment. This retrospective analysis shows the tandem treatment to be safe and effective.

  17. Targeted disruption of Nrf2 causes regenerative immune-mediated hemolytic anemia

    Science.gov (United States)

    Lee, Jong-Min; Chan, Kaimin; Kan, Yuet Wai; Johnson, Jeffrey A.

    2004-01-01

    A basic leucine zipper transcription factor, NF-E2-related factor 2 (Nrf2), plays a critical role in the cellular defense mechanism by mediating a coordinate up-regulation of antioxidant responsive element-driven detoxification and antioxidant genes. Here, we report that targeted disruption of Nrf2 causes regenerative immune-mediated hemolytic anemia due to increased sequestration of damaged erythrocytes. Splenomegaly and spleen toxicity in Nrf2-/- mice raised a possibility of hemolytic anemia and splenic extramedullary hematopoiesis in Nrf2-/- mice. In support of this, hematology analysis revealed that Nrf2-/- mice suffer from anemia with abnormal red cell morphologies (i.e., Howell-Jolly bodies, acantocytes, and schistocytes). In addition, Nrf2-/- erythrocytes were more sensitive to H2O2-induced hemolysis, and erythrocyte-bound IgG levels were markedly increased in Nrf2-/- mice compared with Nrf2+/+ mice. Because IgG bound to erythrocytes in the presence of oxidative damage in erythrocytes (regardless of Nrf2 genotype), these data support that Nrf2-/- erythrocytes have higher levels of damage compared with Nrf2+/+ cells. Finally, Nrf2-/- mice showed increased levels of erythrocyte-bound IgG compared with Nrf2+/+ mice after H2O2 injection in vivo, suggesting that the decreased glutathione and increased H2O2 render the Nrf2-/- mice more susceptible to toxicity. Taken together, these observations indicate that a chronic increase in oxidative stress due to decreased antioxidant capacity sensitizes erythrocytes and causes hemolytic anemia in Nrf2-/- mice, suggesting a pivotal role of Nrf2-antioxidant responsive element pathway in the cellular antioxidant defense system. PMID:15210949

  18. Cardiovascular disease in immune-mediated inflammatory diseases: A cross-sectional analysis of 6 cohorts.

    Science.gov (United States)

    Fernández-Gutiérrez, Benjamín; Perrotti, Pedro P; Gisbert, Javier P; Domènech, Eugeni; Fernández-Nebro, Antonio; Cañete, Juan D; Ferrándiz, Carlos; Tornero, Jesús; García-Sánchez, Valle; Panés, Julián; Fonseca, Eduardo; Blanco, Francisco; Rodríguez-Moreno, Jesús; Carreira, Patricia; Julià, Antonio; Marsal, Sara; Rodriguez-Rodriguez, Luis

    2017-06-01

    To analyze in several immune-mediated inflammatory diseases (IMIDs) the influence of demographic and clinical-related variables on the prevalence of cardiovascular disease (CVD), and compare their standardized prevalences.Cross-sectional study, including consecutive patients diagnosed with rheumatoid arthritis, psoriatic arthritis, psoriasis, systemic lupus erythematosus, Crohn disease, or ulcerative colitis, from rheumatology, gastroenterology, and dermatology tertiary care outpatient clinics located throughout Spain, between 2007 and 2010. Our main outcome was defined as previous diagnosis of angina, myocardial infarction, peripheral vascular disease, and/or stroke. Bivariate and multivariate logistic and mixed-effects logistic regression models were performed for each condition and the overall cohort, respectively. Standardized prevalences (in subjects per 100 patients, with 95% confidence intervals) were calculated using marginal analysis.We included 9951 patients. For each IMID, traditional cardiovascular risk factors had a different contribution to CVD. Overall, older age, longer disease duration, presence of traditional cardiovascular risk factors, and male sex were independently associated with a higher CVD prevalence. After adjusting for demographic and traditional cardiovascular risk factors, systemic lupus erythematosus exhibited the highest CVD standardized prevalence, followed by rheumatoid arthritis, psoriasis, Crohn disease, psoriatic arthritis, and ulcerative colitis (4.5 [95% confidence interval (CI): 2.2, 6.8], 1.3 [95% CI: 0.8, 1.8], 0.9 [95% CI: 0.5, 1.2], 0.8 [95% CI: 0.2, 1.3], 0.6 [95% CI: 0.2, 1.0], and 0.5 [95% CI: 0.1, 0.8], respectively).Systemic lupus erythematosus, rheumatoid arthritis, and psoriasis are associated with higher prevalence of CVD compared with other IMIDs. Specific prevention programs should be established in subjects affected with these conditions to prevent CVD.

  19. Thrombocytopenia responding to red blood cell transfusion

    International Nuclear Information System (INIS)

    Mubarak, Ahmad A.; Awidi, Abdalla; Rasul, Kakil I.; Al-Homsi, Ussama

    2004-01-01

    Three patients with severe symptomatic iron defficiency anemia and thrombocytopenia had a significant rise in the platelet count a few days following packed red blood cell transfusion. Pretransfusion platelet count of of patient one was 17x10/L. 22x10/Lin patient two and 29x10/L in patient three. On the 6th day of post tranfusion, the platelet count rose to 166x10/Lin patient one, 830x10/L in patient two and 136x10/L in patient three. The possible mechcnism behind such an unreported observation are discussed. (author)

  20. Thrombocytopenia in leptospirosis and role of platelet transfusion

    Directory of Open Access Journals (Sweden)

    Sharma Jayashree

    2007-01-01

    Full Text Available Aim : The study was designed to find out the incidence of thrombocytopenia in leptospirosis and to correlate thrombocytopenia with other parameters like renal failure, hepatic failure and bleeding manifestation like adult respiratory distress syndrome and to assess the role of platelet transfusion. Materials and Methods : 50 cases of leptospirosis during the month of July and August 2005 were retrospectively analyzed. Criteria for selection were Lepto Tek Dri - dot test positive cases of the clinically suspected cases of Leptospirosis. Degree of thrombocytopenia was categorized as severe, moderate and mild. Presence of thrombocytopenia was clinically correlated with parameters like renal dysfunction, hepatic dysfunction and hemorrhagic manifestations (mainly ARDS. Role of platelet transfusion was assessed with reference to presence and degree of thrombcytopenia and hemorrhagic manifestations. Results : Out of total 50 patients 26 were male and 24 were females. Major bleeding manifestation in the form of ARDS was seen in 15 (30% of patients. 28 (56% patients had thrombocytopenia and 22 (44% patients had normal platelet counts. Total number of patients with renal dysfunction was 24 (48%. Only four (18.18% patients with normal platelet counts had renal dysfunction while 20 (71.42% patients with thrombocytopenia had renal dysfunction. Only two (9.09% patients with normal platelet counts and 48 (46.42% patients with thrombocytopenia had hepatorenal dysfunction. Total number of patients with ARDS was 15 (30%. Of these two (13.33% had normal platelet count while 13 (86.6% patients were thrombocytopenic. Total 47 units of platelets were transfused to 12 patients in our study. Of these seven patients with severe thrombocytopenia required total 28 units, two patients with moderate thrombocytopenia required total seven units and patients with mild thrombocytopenia were transfused total 12 units of platelets. Conclusion : It is important to anticipate and

  1. CD40 dependent exacerbation of immune mediated hepatitis by hepatic CD11b+ Gr-1+ myeloid derived suppressor cells in tumor bearing mice

    Science.gov (United States)

    Kapanadze, Tamar; Medina-Echeverz, José; Gamrekelashvili, Jaba; Weiss, Jonathan M.; Wiltrout, Robert H.; Kapoor, Veena; Hawk, Nga; Terabe, Masaki; Berzofsky, Jay A.; Manns, Michael P.; Wang, Ena; Marincola, Francesco M.; Korangy, Firouzeh; Greten, Tim F.

    2015-01-01

    Immunosuppressive CD11b+Gr-1+ myeloid-derived suppressor cells (MDSC) accumulate in the livers of tumor-bearing mice. We studied hepatic MDSC in two murine models of immune mediated hepatitis. Unexpectedly, treatment of tumor bearing mice with Concanavalin A or α-Galactosylceramide resulted in increased ALT and AST serum levels in comparison to tumor free mice. Adoptive transfer of hepatic MDSC into naïve mice exacerbated Concanavalin A induced liver damage. Hepatic CD11b+Gr-1+ cells revealed a polarized pro-inflammatory gene signature after Concanavalin A treatment. An interferon gamma- dependent up-regulation of CD40 on hepatic CD11b+Gr-1+ cells along with an up-regulation of CD80, CD86, and CD1d after Concanavalin A treatment was observed. Concanavalin A treatment resulted in a loss of suppressor function by tumor-induced CD11b+Gr-1+ MDSC as well as enhanced reactive oxygen species-mediated hepatotoxicity. CD40 knockdown in hepatic MDSC led to increased arginase activity upon Concanavalin A treatment and lower ALT/AST serum levels. Finally, blockade of arginase activity in Cd40−/− tumor-induced myeloid cells resulted in exacerbation of hepatitis and increased reactive oxygen species production in vivo. Our findings indicate that in a setting of acute hepatitis, tumor-induced hepatic MDSC act as pro-inflammatory immune effector cells capable of killing hepatocytes in a CD40-dependent manner. PMID:25616156

  2. The patterns of Osmotic Fragility and Thrombocytopenia in Nigerian ...

    African Journals Online (AJOL)

    Thrombocytopenia in severe malaria was significantly higher than that in uncomplicated malaria (X2 = 6.4 – 13.7; P < 0.05). At day 3 to 4 of treatment with quinine, parasitaemia became zero in all the malaria subjects but resolution of thrombocytopenia and osmotic fragility (except in uncomplicated malaria) to normalcy was ...

  3. Thrombocytopenia induced by noncytotoxic drugs in Denmark 1968-91

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, U; Andersen, M; Hansen, P B

    1996-01-01

    numerously reported. The still-growing list of thrombocytopenia-inducing agents contained 110 different drugs. At present, 20% of reported cases concern drugs not previously registered as causing thrombocytopenia in Denmark. Twenty-five per cent of all cases were caused by drugs which appeared only...

  4. Thrombocytopenia-absent radius syndrome: a clinical genetic study.

    NARCIS (Netherlands)

    Greenhalgh, K.L.; Howell, R.; Bottani, A.; Ancliff, P.J.; Brunner, H.G.; Verschuuren-Bemelmans, C.C.; Vernon, E.; Brown, K.W.; Newbury-Ecob, R.

    2002-01-01

    The thrombocytopenia-absent radius (TAR) syndrome is a congenital malformation syndrome characterised by bilateral absence of the radii and a thrombocytopenia. The lower limbs, gastrointestinal, cardiovascular, and other systems may also be involved. Shaw and Oliver in 1959 were the first to

  5. Thrombocytopenia-absent radius syndrome : a clinical genetic study

    NARCIS (Netherlands)

    Greenhalgh, KL; Howell, RT; Bottani, A; Ancliff, PJ; Brunner, HG; Verschuuren-Bemelmans, CC; Vernon, E; Brown, KW; Newbury-Ecob, RA

    2002-01-01

    The thrombocytopenia-absent radius (TAR) syndrome is a congenital malformation syndrome characterised by bilateral absence of the radii and a thrombocytopenia. The lower limbs, gastrointestinal, cardiovascular, and other systems may also be involved. Shaw and Oliver in 1959 were the first to

  6. Thrombocytopenia in neonatal sepsis: Incidence, severity and risk factors

    NARCIS (Netherlands)

    Ree, Isabelle M. C.; Fustolo-Gunnink, Suzanne F.; Bekker, Vincent; Fijnvandraat, Karin J.; Steggerda, Sylke J.; Lopriore, Enrico

    2017-01-01

    Thrombocytopenia is a frequent problem in neonatal sepsis and is among the most predictive, independent risk factors for sepsis-associated mortality. This study aims to clarify the occurrence, severity and duration of thrombocytopenia in neonatal sepsis. A cohort study was carried out among all

  7. Thrombocytopenia in Haart naive HIV infected patients attending the ...

    African Journals Online (AJOL)

    Background: Haematological abnormalities are common in HIV infected patients. Thrombocytopenia has been associated with progression of disease. The presence of thrombocytopenia is significantly associated with decreased survival and is a predictor of mortality. Objective: To determine the prevalence of ...

  8. Incidence and risk factors of neonatal thrombocytopenia: a pr

    Directory of Open Access Journals (Sweden)

    Nila Kusumasari

    2010-03-01

    Conclusions The incidence of neonatal thrombocytopenia was 12.2%. Significant risk factor of mother that caused thrombocytopenia was pre-eclampsia, while risk factors of neonates were asphyxia, sepsis and necrotizing enterocolitis.[Paediatr Indones. 2010;50:31-7].

  9. How do we approach thrombocytopenia in critically ill patients?

    Science.gov (United States)

    Thachil, Jecko; Warkentin, Theodore E

    2017-04-01

    A low platelet count is a frequently encountered haematological abnormality in patients treated in intensive treatment units (ITUs). Although severe thrombocytopenia (platelet count classical view for thrombocytopenia in this setting is consumption associated with thrombin-mediated platelet activation, but other concepts, including platelet adhesion to endothelial cells and leucocytes, platelet aggregation by increased von Willebrand factor release, red cell damage and histone release, and platelet destruction by the complement system, have recently been described. The management of severe thrombocytopenia is platelet transfusion in the presence of active bleeding or invasive procedure, but the risk-benefit of prophylactic platelet transfusions in this setting is uncertain. In this review, the incidence and mechanisms of thrombocytopenia in patients with ITU, its prognostic significance and the impact on organ function is discussed. A practical approach based on the authors' experience is described to guide management of a critically ill patient who develops thrombocytopenia. © 2016 John Wiley & Sons Ltd.

  10. Dogs cast NETs too: Canine neutrophil extracellular traps in health and immune-mediated hemolytic anemia.

    Science.gov (United States)

    Jeffery, Unity; Kimura, Kayoko; Gray, Robert; Lueth, Paul; Bellaire, Bryan; LeVine, Dana

    2015-12-15

    Neutrophil extracellular traps (NETs) are webs of DNA and protein with both anti-microbial and pro-thrombotic properties which have not been previously reported in dogs. To confirm dog neutrophils can form NETs, neutrophils were isolated from healthy dogs, and stimulated in vitro with 2μM, 8μM, 31μM, and 125μM platelet activating factor (PAF) or 0.03μM, 0.1μM, 0.4μM, 1.6μM and 6.4μM phorbol-12-myristate-13-acetate (PMA). Extracellular DNA was measured using the cell impermeable dye Sytox Green every hour for 4h. At 4h, extracellular DNA was significantly greater than non-stimulated cells at concentrations ≥31μM and ≥0.1μM for PAF and PMA, respectively. Cells stimulated with 31.25μM PAF reached maximal fluorescence by 1h, whereas maximal fluorescence was not achieved until 2h for cells stimulated with 0.1μM PMA. Immunofluorescent imaging using DAPI and anti-elastase antibody confirmed that extracellular DNA is released as NETs. As NETs have been implicated in thrombosis, nucleosomes, a marker correlated with NET formation, were measured in the serum of dogs with the thrombotic disorder primary immune-mediated hemolytic anemia (IMHA) (n=7) and healthy controls (n=20) using a commercially available ELISA. NETs were significantly higher in IMHA cases than controls (median 0.12 and 0.90, respectively, p=0.01), but there were large positive interferences associated with hemolysis and icterus. In summary, the study is the first to describe NET generation by canine neutrophils and provides preliminary evidence that a marker associated with NETs is elevated in IMHA. However, this apparent elevation must be interpreted with caution due to the effect of interference, emphasizing the need for a more specific and robust assay for NETs in clinical samples. Copyright © 2015 Elsevier B.V. All rights reserved.

  11. Imbalanced immune homeostasis in immune thrombocytopenia.

    Science.gov (United States)

    Yazdanbakhsh, Karina

    2016-04-01

    Immune thrombocytopenia (ITP) is an autoimmune bleeding disorder resulting from low platelet counts caused by inadequate production as well as increased destruction by autoimmune mechanisms. As with other autoimmune disorders, chronic ITP is characterized by perturbations of immune homeostasis with hyperactivated effector cells as well as defective regulatory arm of the adaptive immune system, which will be reviewed here. Interestingly, some ITP treatments are associated with restoring the regulatory imbalance, although it remains unclear whether the immune system is redirected to a state of tolerance once treatment is discontinued. Understanding the mechanisms that result in breakdown of immune homeostasis in ITP will help to identify novel pathways for restoring tolerance and inhibiting effector cell responses. This information can then be translated into developing therapies for averting autoimmunity not only in ITP but also many autoimmune disorders. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. Ultrastructural changes of endothelium associated with thrombocytopenia

    Energy Technology Data Exchange (ETDEWEB)

    Kitchens, C.S.; Weiss, L.

    1975-10-01

    In a study of the relationship between thrombocytopenia and increased vascular fragility, changes in the endothelium of capillaries and postcapillary venules of the tongue were examined by electron microscopy. Adult male albino rabbits (4 kg) were maintained thrombocytopenic (platelets <20,000/cu mm) up to 24 hr by one to three injections of guinea pig antirabbit platelet serum. Within 6 hr the normal projections and folds of the lumenal surface of the endothelial surface were largely effaced. In addition, the endothelium became thinner. In places, pores and membranous diaphragms were observed. Endothelial junctions appeared normal. Identical findings were observed if rabbits were made thrombocytopenic by administration of intraperitoneal busulfan. Intravenously administered Thorotrast was observed in endothelial cells and in the extravascular spaces within 3 min after injection into thrombocytopenic animals, while it was seen only intravascularly in control rabbits. With the spontaneous restoration of circulating platelets, the endothelium reverted to normal.

  13. Intramuscular anti-D in chronic immune thrombocytopenia children with severe thrombocytopenia.

    Science.gov (United States)

    Sirachainan, Nongnuch; Anurathapan, Usanarat; Chuansumrit, Ampaiwan; Songdej, Duantida; Wongwerawattanakoon, Pakawan; Hutspardol, Sakara; Kitpoka, Pimpun

    2013-12-01

    Nine patients with chronic immune thrombocytopenia and platelet counts anti-D. Phase 1 was anti-D daily for 5 days, followed by phase 2, anti-D weekly for 12 weeks and withheld when platelet counts ≥ 20 × 10(9) /L, and then phase 3 was anti-D once every 2 weeks for 24 weeks. According to the International Working Group criteria, in phase 1, 66.7% of patients responded to the treatment. In phases 2 and 3, 11.1% (0-41.7%) and 7.7% (0-33.3%) of total episodes of follow up, respectively, responded to the treatment. Therefore, intramuscular anti-D given at a dose of 10 mcg/kg for 5 days is an alternative method to raise platelet counts in chronic immune thrombocytopenia children with severe thrombocytopenia where the intravenous form of anti-D is not available. © 2013 The Authors. Pediatrics International © 2013 Japan Pediatric Society.

  14. Thrombocytopenia in pregnancy – pathogenesis and diagnostic approach

    Directory of Open Access Journals (Sweden)

    Anna Jodkowska

    2015-11-01

    Full Text Available Thrombocytopenia (TP affects 7-10% of pregnant women. It occurs 4 times more frequently in pregnancy than in the non-pregnant women population. Women with thrombocytopenia in pregnancy are a heterogeneous and poorly known group.There are several possible causes of thrombocytopenia in pregnancy. The most common are: gestational thrombocytopenia (GE (60-75%, preeclampsia (PE and HELLP (hemolysis, elevated liver enzymes, low platelets syndrome associated TP (21%, and idiopathic immune thrombocytopenia (ITP (3-10%. Although thrombocytopenia diagnosed in pregnancy in most cases has a mild course, it has also been reported to be associated with a higher rate of preterm birth and premature detachment of the placenta. Some cases of severe thrombocytopenia with systemic involvement are associated with high risk of serious perinatal complications and require early diagnosis, careful clinical monitoring and medical treatment.The differential diagnosis and proper assessment of clinical risk of TP during pregnancy may be of great concern. The article discusses these issues, focusing on pathophysiology of TP in pregnancy.

  15. Refractory Immunological Thrombocytopenia Purpura and Splenectomy in Pregnancy

    Directory of Open Access Journals (Sweden)

    Santiago Bernal-Macías

    2015-01-01

    Full Text Available Thrombocytopenia is defined as a platelet count of less than 100,000 platelets per microlitre (mcL. Thrombocytopenia develops in approximately 6-7% of women during pregnancy and at least 3% of these cases are caused by immunological platelet destruction. Herein, we present a pregnant woman who develops at the first trimester autoimmune thrombocytopenia purpura associated with positive antiphospholipid antibodies. The disease was refractory to pharmacological treatments but had a favourable response to splenectomy. The patient carried the pregnancy to term without complication and gave birth to a healthy baby girl.

  16. Correlation study between platelet count, leukocyte count, nonhemorrhagic complications, and duration of hospital stay in dengue fever with thrombocytopenia

    Science.gov (United States)

    Jayanthi, Hari Kishan; Tulasi, Sai Krishna

    2016-01-01

    Introduction: Dengue is one of the common diseases presenting as fever with thrombocytopenia, also causing significant morbidity and complications. Objectives: Though the correlation between platelet count, bleeding manifestations and hemorrhagic complications has been extensively studied, less is known about the correlation between platelet count and non hemorrhagic complications. This study was done to see the correlation between platelet count and non hemorrhagic complications, duration of hospital stay and additive effect of leucopenia with thrombocytopenia on complications. Methods: Our study is prospective observational study done on 99 patients who had dengue fever with thrombocytopenia. Correlations were obtained using scatter plot and SPSS software trail version. Results: Transaminitis (12.12%) was the most common complication followed by acute renal injury (2%). In our study we found that, as the platelet count decreased the complication rate increased (P = 0.0006). In our study duration of hospital increased (P is 0.00597) with decreasing platelet count when compared to other study where there was no correlation between the two. There was no correlation between thrombocytopenia with leucopenia and complications (P is 0.292), similar to other study. Conclusion: Platelet count can be used to predict the complication and duration of hospital stay and hence better use of resources. PMID:27453855

  17. Correlation study between platelet count, leukocyte count, nonhemorrhagic complications, and duration of hospital stay in dengue fever with thrombocytopenia

    Directory of Open Access Journals (Sweden)

    Hari Kishan Jayanthi

    2016-01-01

    Full Text Available Introduction: Dengue is one of the common diseases presenting as fever with thrombocytopenia, also causing significant morbidity and complications. Objectives: Though the correlation between platelet count, bleeding manifestations and hemorrhagic complications has been extensively studied, less is known about the correlation between platelet count and non hemorrhagic complications. This study was done to see the correlation between platelet count and non hemorrhagic complications, duration of hospital stay and additive effect of leucopenia with thrombocytopenia on complications. Methods: Our study is prospective observational study done on 99 patients who had dengue fever with thrombocytopenia. Correlations were obtained using scatter plot and SPSS software trail version. Results: Transaminitis (12.12% was the most common complication followed by acute renal injury (2%. In our study we found that, as the platelet count decreased the complication rate increased (P = 0.0006. In our study duration of hospital increased (P is 0.00597 with decreasing platelet count when compared to other study where there was no correlation between the two. There was no correlation between thrombocytopenia with leucopenia and complications (P is 0.292, similar to other study. Conclusion: Platelet count can be used to predict the complication and duration of hospital stay and hence better use of resources.

  18. Effects of Food Additives on Immune Cells As Contributors to Body Weight Gain and Immune-Mediated Metabolic Dysregulation

    Science.gov (United States)

    Paula Neto, Heitor A.; Ausina, Priscila; Gomez, Lilian S.; Leandro, João G. B.; Zancan, Patricia; Sola-Penna, Mauro

    2017-01-01

    Food additives are compounds used in order to improve food palatability, texture, and shelf life. Despite a significant effort to assure safety of use, toxicological analysis of these substances, generally, rely on their direct toxicity to target organs (liver and kidney) or their genotoxic effects. Much less attention is paid to the effects of these compounds on cells of the immune system. This is of relevance given that metabolic dysregulation and obesity have a strong immune-mediated component. Obese individuals present a state of chronic low-grade inflammation that contributes to the establishment of insulin resistance and other metabolic abnormalities known as the metabolic syndrome. Obesity and metabolic syndrome are currently recognized as worldwide epidemics that pose a profound socioeconomic impact and represent a concern to public health. Cells of the immune system contribute to both the maintenance of “lean homeostasis” and the metabolic dysregulation observed in obese individuals. Although much attention has been drawn in the past decades to obesity and metabolic syndrome as a result of ingesting highly processed food containing large amounts of fat and simple sugars, mounting evidence suggest that food additives may also be important contributors to metabolic derangement. Herein, we review pieces of evidence from the literature showing that food additives have relevant effects on cells of the immune system that could contribute to immune-mediated metabolic dysregulation. Considering their potential to predispose individuals to develop obesity and metabolic syndrome, their use should be taken with caution or maybe revisited. PMID:29163542

  19. Effects of Food Additives on Immune Cells As Contributors to Body Weight Gain and Immune-Mediated Metabolic Dysregulation

    Directory of Open Access Journals (Sweden)

    Heitor A. Paula Neto

    2017-11-01

    Full Text Available Food additives are compounds used in order to improve food palatability, texture, and shelf life. Despite a significant effort to assure safety of use, toxicological analysis of these substances, generally, rely on their direct toxicity to target organs (liver and kidney or their genotoxic effects. Much less attention is paid to the effects of these compounds on cells of the immune system. This is of relevance given that metabolic dysregulation and obesity have a strong immune-mediated component. Obese individuals present a state of chronic low-grade inflammation that contributes to the establishment of insulin resistance and other metabolic abnormalities known as the metabolic syndrome. Obesity and metabolic syndrome are currently recognized as worldwide epidemics that pose a profound socioeconomic impact and represent a concern to public health. Cells of the immune system contribute to both the maintenance of “lean homeostasis” and the metabolic dysregulation observed in obese individuals. Although much attention has been drawn in the past decades to obesity and metabolic syndrome as a result of ingesting highly processed food containing large amounts of fat and simple sugars, mounting evidence suggest that food additives may also be important contributors to metabolic derangement. Herein, we review pieces of evidence from the literature showing that food additives have relevant effects on cells of the immune system that could contribute to immune-mediated metabolic dysregulation. Considering their potential to predispose individuals to develop obesity and metabolic syndrome, their use should be taken with caution or maybe revisited.

  20. Immune mediators of sea-cucumber Holothuria tubulosa (Echinodermata) as source of novel antimicrobial and anti-staphylococcal biofilm agents

    Science.gov (United States)

    2013-01-01

    The present study aims to investigate coelomocytes, immune mediators cells in the echinoderm Holothuria tubulosa, as an unusual source of antimicrobial and antibiofilm agents. The activity of the 5kDa peptide fraction of the cytosol from H. tubulosa coelomocytes (5-HCC) was tested against a reference group of Gram-negative and Gram-positive human pathogens. Minimal inhibitory concentrations (MICs) ranging from 125 to 500 mg/ml were determined against tested strains. The observed biological activity of 5-HCC could be due to two novel peptides, identified by capillary RP-HPLC/nESI-MS/MS, which present the common chemical-physical characteristics of antimicrobial peptides. Such peptides were chemically synthesized and their antimicrobial activity was tested. The synthetic peptides showed broad-spectrum activity at 12.5 mg/ml against the majority of the tested Gram-positive and Gram-negative strains, and they were also able to inhibit biofilm formation in a significant percentage at a concentration of 3.1 mg/ml against staphylococcal and Pseudomonas aeruginosa strains. The immune mediators in H. tubulosa are a source of novel antimicrobial peptides for the development of new agents against biofilm bacterial communities that are often intrinsically resistant to conventional antibiotics. PMID:23800329

  1. Effects of Food Additives on Immune Cells As Contributors to Body Weight Gain and Immune-Mediated Metabolic Dysregulation.

    Science.gov (United States)

    Paula Neto, Heitor A; Ausina, Priscila; Gomez, Lilian S; Leandro, João G B; Zancan, Patricia; Sola-Penna, Mauro

    2017-01-01

    Food additives are compounds used in order to improve food palatability, texture, and shelf life. Despite a significant effort to assure safety of use, toxicological analysis of these substances, generally, rely on their direct toxicity to target organs (liver and kidney) or their genotoxic effects. Much less attention is paid to the effects of these compounds on cells of the immune system. This is of relevance given that metabolic dysregulation and obesity have a strong immune-mediated component. Obese individuals present a state of chronic low-grade inflammation that contributes to the establishment of insulin resistance and other metabolic abnormalities known as the metabolic syndrome. Obesity and metabolic syndrome are currently recognized as worldwide epidemics that pose a profound socioeconomic impact and represent a concern to public health. Cells of the immune system contribute to both the maintenance of "lean homeostasis" and the metabolic dysregulation observed in obese individuals. Although much attention has been drawn in the past decades to obesity and metabolic syndrome as a result of ingesting highly processed food containing large amounts of fat and simple sugars, mounting evidence suggest that food additives may also be important contributors to metabolic derangement. Herein, we review pieces of evidence from the literature showing that food additives have relevant effects on cells of the immune system that could contribute to immune-mediated metabolic dysregulation. Considering their potential to predispose individuals to develop obesity and metabolic syndrome, their use should be taken with caution or maybe revisited.

  2. Linezolid-induced thrombocytopenia in two patients with renal dysfunction

    Directory of Open Access Journals (Sweden)

    Engin Melek

    2016-12-01

    Full Text Available Linezolid is an oxazolidinone antibiotic, active against gram positive bacteria that are resistant to other antibiotics including glycopeptides. Thrombocytopenia is an adverse effect of linezolid. Although various risk factors have been suggested, the mechanisms behind this side effect are largely unknown. Here, we report two adolescents with the diagnosis of chronic kidney disease who developed thrombocytopenia following treatment with linezolid. Our purpose in highlighting these cases is to increase the clinical awareness concerning this side effect of linezolid. While it is well known that thrombocytopenia may develop during linezolid treatment, it is relatively unknown that patients with renal dysfunction have an increased risk for the development of thrombocytopenia compared to patients without renal dysfunction. [Cukurova Med J 2016; 41(4.000: 808-810

  3. Fetal and neonatal thrombopoietin levels in alloimmune thrombocytopenia

    NARCIS (Netherlands)

    Porcelijn, L.; Folman, C. C.; de Haas, M.; Kanhai, H. H. H.; Murphy, M. F.; von dem Borne, A. E. G. Kr; Bussel, J. B.

    2002-01-01

    Thrombopoietin (Tpo) is the main hematopoietic growth factor for platelet production. Plasma Tpo levels in autoimmune thrombocytopenic patients are normal or slightly elevated. Although thrombocytopenia exists, Tpo levels are not increased because the produced megakaryocytes and platelets can bind

  4. Reversible Thrombocytopenia after Gabapentin in an HIV-Positive Patient

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    Mohammed Basith

    2018-01-01

    Full Text Available Gabapentin has become increasingly used in psychiatric practice specifically for anxiety disorders. Even though gabapentin is not approved by the US Food and Drug Administration to treat anxiety, physicians sometimes use it as an alternative to benzodiazepines in patients with a history of substance abuse. Gabapentin is also prescribed when individuals are at risk of thrombocytopenia which is not considered a side effect. Among patients at risk of thrombocytopenia are those positive for human immunodeficiency virus (HIV. Here we present a case of an HIV-positive man who presented for inpatient psychiatric care with severe anxiety and a history of alcohol and benzodiazepine abuse. In this patient, gabapentin worsened thrombocytopenia after repeated exposure to this medication. We suggest caution when considering gabapentin for patients with preexisting low platelet counts, as there seems to be a risk for worsening thrombocytopenia with this antiepileptic in the presence of HIV infection.

  5. What Are the Signs and Symptoms of Thrombocytopenia?

    Science.gov (United States)

    ... information about this procedure, go to the Health Topics Blood Transfusion article. Splenectomy A splenectomy is surgery to remove ... experiences with clinical research. More Information Related Health Topics Aplastic ... Thrombocytopenia Thrombotic Thrombocytopenic Purpura ...

  6. Anterior Chamber-Associated Immune Deviation (ACAID: An Acute Response to Ocular Insult Protects from Future Immune-Mediated Damage?

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    Robert E. Cone

    2009-01-01

    Full Text Available The “immune privilege” that inhibits immune defense mechanisms that could lead to damage to sensitive ocular tissue is based on the expression of immunosuppressive factors on ocular tissue and in ocular fluids. In addition to this environmental protection, the injection of antigen into the anterior chamber or infection in the anterior chamber induces a systemic suppression of potentially damaging cell-mediated and humoral responses to the antigen. Here we discuss evidence that suggests that Anterior Chamber-Associated Immune Deviation (ACAID a is initiated by an ocular response to moderate inflammation that leads to a systemic immunoregulatory response. Injection into the anterior chamber induces a rise in TNF-α and MCP-1 in aqueous humor and an infiltration of circulating F4/80 + monocytes that home to the iris. The induction of ACAID is dependent on this infiltration of circulating monocytes that eventually emigrate to the thymus and spleen where they induce regulatory T cells that inhibit the inductive or effector phases of a cell-mediated immune response. ACAID therefore protects the eye from the collateral damage of an immune response to infection by suppressing a future potentially damaging response to infection.

  7. Risk factors for ganciclovir-induced thrombocytopenia and leukopenia.

    Science.gov (United States)

    Matsumoto, Kazuaki; Shigemi, Akari; Ikawa, Kazuro; Kanazawa, Naoko; Fujisaki, Yuko; Morikawa, Norifumi; Takeda, Yasuo

    2015-01-01

    Ganciclovir is a nucleoside guanosine analogue that exhibits therapeutic activity against human cytomegalovirus infection, and is primarily excreted via glomerular filtration and active tubular secretion. The adverse effects induced by ganciclovir therapy are generally of a hematological nature and include thrombocytopenia and leukopenia. Low marrow cellularity and elevated serum creatinine have been identified as risk factors for ganciclovir-induced neutropenia. However, the risk factors for thrombocytopenia have yet to be determined. Therefore, this study investigated patients administered ganciclovir to determine the risk factors for thrombocytopenia and leukopenia. Thrombocytopenia occurred in 41 of these patients (30.6%). Multivariate logistic regression analysis identified three independent risk factors for thrombocytopenia: cancer chemotherapy (odds ratio (OR)=3.1), creatinine clearance (Leukopenia occurred in 36 patients (28.6%), and white blood cell count (leukopenia, and suggest that special attention should be paid to patients receiving cancer chemotherapy with a low creatinine clearance (<20 mL/min) and high dose (≥12 mg/kg/d) in order to avoid ganciclovir-induced thrombocytopenia.

  8. Efalizumab-induced severe thrombocytopenia can be resolved

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    Francesca Prignano

    2008-11-01

    Full Text Available Francesca Prignano, F Zanieri, S Mokhtarzadeh, T LottiUniversity Unit of Dermatology and Physiotherapy, School of Medicine, University of Florence, Florence, ItalyAbstract: Efalizumab is a monoclonal a humanized recombinant IgG1 monoclonal antibody which targets the CD11a, the alpha-subunit of LFA-1 (lymphocyte function-associated antigen-1. It acts by blocking the T-lymphocyte pathogenetic mechanisms of psoriasis. Thrombocytopenia is an adverse event that occurs during therapy. Thrombocytopenia can be mild and can occur quite early during treatment, together with leukocytosis. Both adverse events tend to normalize with ongoing therapy, or, in cases worsening, with therapy suspension. There have been multiple reports of thrombocytopenia associated with efalizumab therapy for the treatment of psoriasis. The general recommendation is to check platelet counts monthly for the first 3 months of efalizumab therapy, then every 3 months for the duration of therapy. According to our experience on a wide range of patients, it is useful to check platelets every month for the first 6 months of therapy. We report a case of efalizumab-associated thrombocytopenia that occurred after 16 weeks of therapy together with clinical worsening of skin lesions. The peculiarity of our case is the absence of signs and symptoms linked to thrombocytopenia and the quick return to normal platelet count without corticosteroid therapy.Keywords: efalizumab, thrombocytopenia, psoriasis

  9. Chicken pox associated thrombocytopenia in adults.

    Science.gov (United States)

    Ali, Nadir; Anwar, Masood; Majeed, Irfan; Tariq, Waheed Uz Zaman

    2006-04-01

    To determine the frequency and magnitude of thrombocytopenia associated with chicken pox in adults. Observational descriptive study. Combined Military Hospital, Attock, from July 2003 to June 2004. All patients of age 15 years and above with history of fever, followed by appearance of the typical vesicular chicken pox rash, were inducted after informed consent. Two milliliters of whole blood was collected on day 1 of admission, and blood counts were performed. Patients were admitted and given 800 mg oral acyclovir, 5 times/day, for 7 days, in addition to symptomatic treatment. Patients were followed till 8 weeks. A total of 410 patients of chicken pox were received, out of which 270 were included. Age of patients ranged between 15 and 40 years with median age of 21 years. Platelet count on the day of admission ranged between 29 x 10(9)/L to 513 x 10(9)/L, mean platelet count 178 x 10(9)/L. Platelet count chicken pox is a common entity. Platelet count remains above 25 x 10(9) /L, which is usually not associated with bleeding manifestations. None of the patients in this series developed purpura. No specific pattern of total leukocyte counts was predictive of the progression or regression in platelet count.

  10. Immune thrombocytopenia: pathophysiologic and clinical update.

    Science.gov (United States)

    Stasi, Roberto

    2012-07-01

    Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by both reduced platelet survival and suppression of megakaryocyte and platelet development. It can either be primary or secondary to other autoimmune disorders, infections, vaccines, lymphoproliferative disorders, and drugs. Antibodies reacting against platelet glycoproteins are typical of ITP; these antibodies can mediate destruction of platelets by the monocyte-macrophage system as well as suppress megakaryocyte proliferation and maturation. Abnormalities of cell-mediated immunity are known to contribute to the pathologic process. Like many other autoimmune diseases, ITP has a T helper cell type 1 bias and a reduced activity of T-regulatory cells. Cytotoxic T cells may directly lyse platelets and possibly suppress megakaryopoiesis. Recent studies suggest that mesenchymal stem cells are dysfunctional in ITP and may contribute to an aberrant amplification of the autoimmune response. Significant advances in the treatment of chronic ITP have been witnessed in the past decade, first with the introduction of rituximab and more recently with the thrombopoietin-receptor agonists. While splenectomy is still considered the gold standard in this setting, effective medical therapy is now available for patients in whom surgery is not an option. Thieme Medical Publishers 333 Seventh Avenue, New York, NY 10001, USA.

  11. 2,3,7,8-TCDD enhances the sensitivity of mice to concanavalin A immune-mediated liver injury

    Energy Technology Data Exchange (ETDEWEB)

    Fullerton, Aaron M., E-mail: fuller22@msu.edu [Department of Pharmacology and Toxicology, Center for Integrative Toxicology, Michigan State University, 1129 Farm Lane, Room 215, East Lansing, MI 48824 (United States); Roth, Robert A., E-mail: rothr@msu.edu [Department of Pharmacology and Toxicology, Center for Integrative Toxicology, Michigan State University, Food Safety and Toxicology Building, 1129 Farm Lane, Room 221, East Lansing, MI 48824 (United States); Ganey, Patricia E., E-mail: ganey@msu.edu [Department of Pharmacology and Toxicology, Center for Integrative Toxicology, Michigan State University, Food Safety and Toxicology Building, 1129 Farm Lane, Room 214, East Lansing, MI 48824 (United States)

    2013-01-15

    Inflammation plays a major role in immune-mediated liver injury, and exposure to environmental pollutants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been reported to alter the inflammatory response as well as affect immune cell activity. In this study, we tested the hypothesis that TCDD pretreatment exacerbates hepatotoxicity in a murine model of immune-mediated liver injury induced by concanavalin A (Con A) administration. Mice were pretreated with 30 μg/kg TCDD or vehicle control on day zero and then given either Con A or saline intravenously on day four. Mice treated with TCDD did not develop liver injury; however, TCDD pretreatment increased liver injury resulting from moderate doses of Con A (4–10 mg/kg). TCDD-pretreated mice had altered plasma concentrations of inflammatory cytokines, including interferon gamma (IFNγ), and TCDD/Con A-induced hepatotoxicity was attenuated in IFNγ knockout mice. At various times after treatment, intrahepatic immune cells were isolated, and expression of cell activation markers as well as cytolytic proteins was determined. TCDD pretreatment increased the proportion of activated natural killer T (NKT) cells and the percent of cells expressing Fas ligand (FasL) after Con A administration. In addition FasL knockout mice and mice treated with CD18 antiserum were both protected from TCDD/Con A-induced hepatotoxicity, suggesting a requirement for direct cell–cell interaction between effector immune cells and parenchymal cell targets in the development of liver injury from TCDD/Con A treatment. In summary, exposure to TCDD increased NKT cell activation and exacerbated immune-mediated liver injury induced by Con A through a mechanism involving IFNγ and FasL expression. -- Highlights: ► TCDD pretreatment sensitizes mice to Con A-induced hepatotoxicity. ► TCDD pretreatment increased concentration of IFNγ in plasma after Con A. ► Con A-induced activation of NKT cells was increased by TCDD pretreatment. ► Fas

  12. 2,3,7,8-TCDD enhances the sensitivity of mice to concanavalin A immune-mediated liver injury

    International Nuclear Information System (INIS)

    Fullerton, Aaron M.; Roth, Robert A.; Ganey, Patricia E.

    2013-01-01

    Inflammation plays a major role in immune-mediated liver injury, and exposure to environmental pollutants such as 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) has been reported to alter the inflammatory response as well as affect immune cell activity. In this study, we tested the hypothesis that TCDD pretreatment exacerbates hepatotoxicity in a murine model of immune-mediated liver injury induced by concanavalin A (Con A) administration. Mice were pretreated with 30 μg/kg TCDD or vehicle control on day zero and then given either Con A or saline intravenously on day four. Mice treated with TCDD did not develop liver injury; however, TCDD pretreatment increased liver injury resulting from moderate doses of Con A (4–10 mg/kg). TCDD-pretreated mice had altered plasma concentrations of inflammatory cytokines, including interferon gamma (IFNγ), and TCDD/Con A-induced hepatotoxicity was attenuated in IFNγ knockout mice. At various times after treatment, intrahepatic immune cells were isolated, and expression of cell activation markers as well as cytolytic proteins was determined. TCDD pretreatment increased the proportion of activated natural killer T (NKT) cells and the percent of cells expressing Fas ligand (FasL) after Con A administration. In addition FasL knockout mice and mice treated with CD18 antiserum were both protected from TCDD/Con A-induced hepatotoxicity, suggesting a requirement for direct cell–cell interaction between effector immune cells and parenchymal cell targets in the development of liver injury from TCDD/Con A treatment. In summary, exposure to TCDD increased NKT cell activation and exacerbated immune-mediated liver injury induced by Con A through a mechanism involving IFNγ and FasL expression. -- Highlights: ► TCDD pretreatment sensitizes mice to Con A-induced hepatotoxicity. ► TCDD pretreatment increased concentration of IFNγ in plasma after Con A. ► Con A-induced activation of NKT cells was increased by TCDD pretreatment. ► Fas

  13. Pattern and prevalence of neonatal thrombocytopenia in Port Harcourt, Nigeria

    Directory of Open Access Journals (Sweden)

    Zaccheaus A Jeremiah

    2010-04-01

    Full Text Available Zaccheaus A Jeremiah1, Justina E Oburu21Hematology and Blood Transfusion Science Unit, Department of Medical Laboratory Sciences, College of Health Sciences, Niger Delta University, Wilberforce Island, Bayelsa State, Nigeria; 2Department of Hematology and Blood Transfusion University of Port Harcourt Teaching Hospital, Port Harcourt, NigeriaBackground: In Port Harcourt, evidence-based guidelines for platelet transfusion therapy in neonatal patients are yet to be defined and the prevalence and pattern of neonatal thrombocytopenia has not yet been reported.Methods: Platelet counts of 132 neonatal patients admitted into the special care baby unit (SCBU at the University of Port Harcourt Teaching Hospital in Nigeria were assessed using the International Committee on Standards in Hematology (ICSH approved manual procedures for hemocytometry.6Study design: This is a cross sectional study carried out on neonates to determine the prevalence and pattern of neonatal thrombocytopenia.Results: The median platelet count of the neonates was 97.0 × 109/L (interquartile range [IQR] 50–152 while the mean age was 61.7 hours (range 1–336 hours. The overall prevalence of neonatal thrombocytopenia was 53.0%. Mild thrombocytopenia (platelet count 51–100 × 109/L was found in 39.4% of the neonates, 12.1% had moderate thrombocytopenia (platelet count 30–50 × 109/L, while severe thrombocytopenia (platelet count <30 × 109/L was detected in 1.5% of the neonates. Of these, 84.84% of the cases occurred within 72 hours (early onset. The most common clinical diagnosis among the neonates was severe birth asphyxia (33.3%, followed by neonatal jaundice (19.7%, neonatal sepsis (16.7%, low birth weight (13.6%, anemia and bleeding (6.1%, and other clinical conditions (10.6%. There was no association between clinical diagnosis and thrombocytopenia (Fisher’s exact test = 10.643; P = 0.923.Conclusion: There is a high prevalence of early onset neonatal thrombocytopenia

  14. Good agreement of conventional and gel-based direct agglutination test in immune-mediated haemolytic anaemia

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    Piek Christine J

    2012-02-01

    Full Text Available Abstract Background The aim of this study was to compare a gel-based test with the traditional direct agglutination test (DAT for the diagnosis of immune-mediated haemolytic anaemia (IMHA. Methods Canine (n = 247 and feline (n = 74 blood samples were submitted for DAT testing to two laboratories. A subset of canine samples was categorized as having idiopathic IMHA, secondary IMHA, or no IMHA. Results The kappa values for agreement between the tests were in one laboratory 0.86 for canine and 0.58 for feline samples, and in the other 0.48 for canine samples. The lower agreement in the second laboratory was caused by a high number of positive canine DATs for which the gel test was negative. This group included significantly more dogs with secondary IMHA. Conclusions The gel test might be used as a screening test for idiopathic IMHA and is less often positive in secondary IMHA than the DAT.

  15. Tanshinone IIA protects against immune-mediated liver injury through activation of T-cell subsets and regulation of cytokines.

    Science.gov (United States)

    Qin, Xiao-Yan; Li, Tang; Yan, Li; Liu, Qing-Shan; Tian, Yu

    2010-03-01

    Tanshione IIA (TSN) is the major active component of Salvia miltiorrhiza, a traditional Chinese Medicine. TSN protects against antioxidant-induced liver injury, although the exact mechanism is not well understood. In this study, the protective effects of TSN was examined by enzyme-linked immunosorbent assay (ELISA) and histochemistry of several cytokines. TSN is found to significantly reduce plasma alanin aminotransferase and aspartate amino transferase levels in mice with concanavalin A-induced immune-mediated liver injury. TSN increases T lymphocyte subset CD3+, CD4+ and CD8+ ratios.Also, TSN significantly reduces inflammatory cytokines, including interleukin-2, interleukin-4, interferon-gamma and tumor necrosis factor alpha, while elevates anti-inflammatory cytokine, interleukin-10. TSN may provide a potential drug candidate for liver injury therapeutics.

  16. Adherence to systemic therapies for immune-mediated inflammatory diseases in Lebanon: a physicians' survey from three medical specialties.

    Science.gov (United States)

    Ammoury, Alfred; Okais, Jad; Hobeika, Mireille; Sayegh, Raymond B; Shayto, Rani H; Sharara, Ala I

    2017-01-01

    Immune-mediated inflammatory diseases (IMIDs) are chronic conditions that may cause tissue damage and disability, reduced quality of life and increased mortality. Various treatments have been developed for IMIDs, including immune modulators and targeted biologic agents. However, adherence remains suboptimal. An adherence survey was used to evaluate physicians' beliefs about adherence to medication in IMID and to evaluate if and how they manage adherence. The survey was distributed to 100 randomly selected physicians from three different specialties. Results were analyzed by four academic experts commissioned to develop an action plan to address practical and perceptual barriers to adherence, integrating it into treatment goals to maximize outcomes in IMID, thereby elevating local standards of care. Eighty-two physicians participated in this study and completed the questionnaire. Most defined adherence as compliance with prescribed treatment. Although the majority of surveyed physicians (74%) did not systematically measure adherence in their practice, 54% identified adherence as a treatment goal of equal or greater importance to therapeutic endpoints. Lack of time and specialized nursing support was reported as an important barrier to measuring adherence. The expert panel identified four key areas for action: 360° education (patient-nurse-physician), patient-physician communication, patient perception and concerns, and market access/cost. An action plan was developed centered on education and awareness, enhanced benefit-risk communication, development of adherence assessment tools and promotion of patient support programs. Nonadherence to medication is a commonly underestimated problem with important consequences. A customized target-based strategy to address the root causes of non-adherence is essential in the management of chronic immune-mediated diseases.

  17. Major Histocompatibility Complex I and II Expression and Lymphocytic Subtypes in Muscle of Horses with Immune-Mediated Myositis.

    Science.gov (United States)

    Durward-Akhurst, S A; Finno, C J; Barnes, N; Shivers, J; Guo, L T; Shelton, G D; Valberg, S J

    2016-07-01

    Major histocompatibility complex (MHC) I and II expression is not normally detected on sarcolemma, but is detected with lymphocytic infiltrates in immune-mediated myositis (IMM) of humans and dogs and in dysferlin-deficient muscular dystrophy. To determine if sarcolemmal MHC is expressed in active IMM in horses, if MHC expression is associated with lymphocytic subtype, and if dysferlin is expressed in IMM. Twenty-one IMM horses of Quarter Horse-related breeds, 3 healthy and 6 disease controls (3 pasture myopathy, 3 amylase-resistant polysaccharide storage myopathy [PSSM]). Immunohistochemical staining for MHC I, II, and CD4+, CD8+, CD20+ lymphocytes was performed on archived muscle of IMM and control horses. Scores were given for MHC I, II, and lymphocytic subtypes. Immunofluorescent staining for dysferlin, dystrophin, and a-sarcoglycan was performed. Sarcolemmal MHC I and II expression was detected in 17/21 and 15/21 of IMM horses, respectively, and in specific fibers of PSSM horses, but not healthy or pasture myopathy controls. The CD4+, CD8+, and CD20+ cells were present in 20/21 IMM muscles with CD4+ predominance in 10/21 and CD8+ predominance in 6/21 of IMM horses. Dysferlin, dystrophin, and a-sarcoglycan staining were similar in IMM and control muscles. Deficiencies of dysferlin, dystrophin, and a-sarcoglycan are not associated with IMM. Sarcolemmal MHC I and II expression in a proportion of myofibers of IMM horses in conjunction with lymphocytic infiltration supports an immune-mediated etiology for IMM. The MHC expression also occured in specific myofibers in PSSM horses in the absence of lymphocytic infiltrates. Copyright © 2016 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  18. Thrombocytopenia induced by a taurine-containing energy drink: an adverse reaction to herbal medicine

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    Federico Pasin

    2014-02-01

    Full Text Available Thrombocytopenia is a well-recognized adverse effect of many drugs. The association of thrombocytopenia with herbal remedies, nutritional supplements, foods and beverages, complementary or alternative medicines, has been rarely described. There are reports of thrombocytopenia caused by quinine-containing beverages, cow�s milk, cranberry juice, Jui, a Chinese herbal tea, Lupinus termis bean and tahini. A definite evidence of a causal association with thrombocytopenia is warranted; nevertheless not always there is provided probable or possible evidence in the association with thrombocytopenia. We report the first case, to our knowledge, of thrombocytopenia induced by taurine, present in an energy drink prescribed to our patient as tonic treatment.

  19. THROMBOCYTOPENIA IN PATIENTS WITH CHRONIC HEPATITIS C VIRUS INFECTION

    Directory of Open Access Journals (Sweden)

    Sumit Dahal

    2017-03-01

    Full Text Available Thrombocytopenia in patients with chronic hepatitis C virus (HCV infection is a major problem. The pathophysiology is multifactorial, with auto-immunogenicity, direct bone marrow suppression, hypersplenism, decreased production of thrombopoietin and therapeutic adverse effect all contributing to thrombocytopenia in different measures. The greatest challenge in the care of chronic HCV patients with thrombocytopenia is the difficulty in initiating or maintaining IFN containing anti-viral therapy. Although at present, it is possible to avoid this challenge with the use of the sole Direct Antiviral Agents ( DAAs as the primary treatment modality, thrombocytopenia remains of particular interest, especially in cases of advanced liver disease. The increased risk of bleeding with thrombocytopenia may also impede the initiation and maintenance of different invasive diagnostic and therapeutic procedures. While eradication of HCV infection itself is the most practical strategy for the remission of thrombocytopenia, various pharmacological and non-pharmacological therapeutic options, which vary in their effectiveness and adverse effect profiles, are available. Sustained increase in platelet count is seen with splenectomy and splenic artery embolization, in contrast to only transient rise with platelet transfusion. However, their routine use is limited by complications. Different thrombopoietin analogues have been tried. The use of synthetic thrombopoietins, such as recombinant human TPO and pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMDGF, has been hampered by the development of neutralizing antibodies. Thrombopoietin-mimetic agents, in particular, eltrombopag and romiplostim, have been shown to be safe and effective for HCV-related thrombocytopenia in various studies, and they increase platelet count without eliciting any immunogenicity Other treatment modalities including newer TPO analogues- AMG-51, PEG-TPOmp and AKR

  20. Thrombocytopenia: diagnosis with flow cytometry and antiplatelet antibodies.

    Science.gov (United States)

    Guerra, João Carlos de Campos; Kanayama, Ruth Hissae; Nozawa, Sonia Tsukasa; Ioshida, Márcia Regina; Takiri, Irina Yoko; Lazaro, Robson José; Hamerschlak, Nelson; Rosenfeld, Luiz Gastão Mange; Guerra, Celso Carlos de Campos; Bacal, Nydia Strachman

    2011-06-01

    To identify antiplatelet antibodies by flow cytometry (direct method) in patients with thrombocytopenia. Between January 1997 and March 2004 a total of 15100 patients were referred to the Centro de Hematologia de São Paulo for hematological investigation of several diagnoses (anemia, leukopenia, thrombocytopenia, coagulation abnormalities, adenomegaly, leukemia and others). Of those, 1057 were referred because of thrombocytopenia and were divided into two groups: Group Idiopathic thrombocytopenic purpura, with no identifiable cause; and Group Other thrombocytopenia, which included low normal platelet counts cause to be established, hepatitis C and HIV infection, hypersplenism, EDTA-induced artifacts, laboratory error, and other causes. Flow cytometry immunophenotyping was done in 115 cases to identify platelet autoantibodies (direct method). Of the total number of patients, 1057 (7%) presented low platelet counts, 670 were females (63.4%) and age range of one to 75 years. Of the 115 cases (9.7%) submitted to immunophenotyping, the results were positive in 40% and the test was inconclusive in 5%. Idiopathic thrombocytopenic purpura was found in 52% of patients, more often in women. Hepatitis C virus infection was found in 7% and HIV infection in 1%. Low normal platelet counts were found in 17%, laboratory errors in 6%, and laboratory artifacts in 1% of cases. Platelet autoantibodies were found in 76.9% of all idiopathic thrombocytopenic purpura cases. It was negative in 83.3% of the low normal counts. antiplatelet autoantibodies when present help to diagnose idiopathic thrombocytopenic purpura. When absent, suggest other causes of thrombocytopenia.

  1. Clinical and Laboratory Findings in Various Reasons of Thrombocytopenia

    Directory of Open Access Journals (Sweden)

    Serkan Akin

    2017-12-01

    Full Text Available Background: Thrombocytopenia is an important cause of bleeding. Different clinical conditions associated with thrombocytopenia and their reflections to the hemostatic table will be examined in this study. Methods: A total of 100 patients with thrombocytopenia who were treated in Hacettepe University between 1993 and 2013, 29 with thrombotic thrombocytopenic purpura (TTP, 36 with immune thrombocytopenic purpura (ITP, and 35 with aplastic anemia (AA, were included in the study. Clinical features and laboratory values were reviewed. Results: Thrombosis, fever, and sepsis were more frequently seen in TTP. The most common bleeding type was subcutaneous bleeding in all patient groups. Among patients with TTP, twenty-five patients (86, 2% had fever, 26 patients (89, 7% had a neurologic disorder, and 16 patients (55, 1% had renal dysfunction. Regarding the diagnostic criteria of TTP, 13 patients (44, 8% met five, 12 (41, 4% patients met four and 4 (13, 8% patients met three criteria. The median session of plasmapheresis was 17 (range; 2-127. There was no relation between session count and remission (p=0.28. Conclusion: The severity of clinical presentation and underlying disorders are the most important points with which to approach patients with thrombocytopenia. Clinical reflections may help to identify the cause of thrombocytopenia but not sufficiently demonstrative for diagnosis. [J Contemp Med 2017; 7(4.000: 316-322

  2. Cutaneous Alternaria infectoria infection in a dog in association with therapeutic immunosuppression for the management of immune-mediated haemolytic anaemia

    NARCIS (Netherlands)

    Dedola, C.; Stuart, A.P.G.; Ridyard, A.E.; Else, R.W.; Van den Broek, T.; Choi, J.S.; de Hoog, G.S.; Thoday, K.L.

    2010-01-01

    A 4-year-old, ovariohysterectomized, English springer spaniel on immunosuppressive therapy was re-examined for the review of its immune-mediated haemolytic anaemia and the recent development of skin lesions. For the 3 months since hospital discharge, the dog had been receiving 1.3 mg/kg prednisolone

  3. Influence of Human Leukocyte Antigen (HLA) Alleles and Killer Cell Immunoglobulin-Like Receptors (KIR) Types on Heparin-Induced Thrombocytopenia (HIT).

    Science.gov (United States)

    Karnes, Jason H; Shaffer, Christian M; Cronin, Robert; Bastarache, Lisa; Gaudieri, Silvana; James, Ian; Pavlos, Rebecca; Steiner, Heidi E; Mosley, Jonathan D; Mallal, Simon; Denny, Joshua C; Phillips, Elizabeth J; Roden, Dan M

    2017-09-01

    Heparin-induced thrombocytopenia (HIT) is an unpredictable, life-threatening, immune-mediated reaction to heparin. Variation in human leukocyte antigen (HLA) genes is now used to prevent immune-mediated adverse drug reactions. Combinations of HLA alleles and killer cell immunoglobulin-like receptors (KIR) are associated with multiple autoimmune diseases and infections. The objective of this study is to evaluate the association of HLA alleles and KIR types, alone or in the presence of different HLA ligands, with HIT. HIT cases and heparin-exposed controls were identified in BioVU, an electronic health record coupled to a DNA biobank. HLA sequencing and KIR type imputation using Illumina OMNI-Quad data were performed. Odds ratios for HLA alleles and KIR types and HLA*KIR interactions using conditional logistic regressions were determined in the overall population and by race/ethnicity. Analysis was restricted to KIR types and HLA alleles with a frequency greater than 0.01. The p values for HLA and KIR association were corrected by using a false discovery rate qtypes were associated with HIT, although a significant interaction was observed between KIR2DS5 and the HLA-C1 KIR binding group (p=0.03). The HLA-DRB3*01:01 allele was identified as a potential risk factor for HIT. This class II HLA gene and allele represent biologically plausible candidates for influencing HIT pathogenesis. We found limited evidence of the role of KIR types in HIT pathogenesis. Replication and further study of the HLA-DRB3*01:01 association is necessary. © 2017 Pharmacotherapy Publications, Inc.

  4. Immune thrombocytopenia (ITP): a rare association of lymph node tuberculosis.

    Science.gov (United States)

    Surana, Anuj P; Shelgikar, Kishor M; Melinkeri, Sameer; Phadke, Arvind

    2014-01-01

    Although various haematologic abnormalities are known to occur with tuberculosis, association of immune thrombocytopenia with tuberculosis is uncommon. We report a case of retroperitoneal lymph node tuberculosis who presented with ITP. A 76 year old female was admitted to our hospital with oral mucosal bleed and petechial lesions over extremities and abdomen. A diagnosis of immune thrombocytopenia (ITP) was established. Intravenous Anti-D immunoglobulin and Dexamethasone therapy was started, but failed to elicit any sustained platelet response. CT abdomen revealed multiple retroperitoneal lymph nodes with central necrosis. Histopathology (HPE) of these revealed caseating lymphadenitis suggestive of tuberculosis. After 2 months of anti-tuberculous therapy, the platelet counts returned to normal and patient was off all therapy for ITP thereby suggesting likely association between tuberculosis and immune thrombocytopenia.

  5. Pathophysiology of acute small bowel disease with CT correlation

    Energy Technology Data Exchange (ETDEWEB)

    Sarwani, N., E-mail: nsarwani@hmc.psu.ed [Department of Radiology, Section of Abdominal Imaging, Penn State Milton Hershey Medical Center, Hershey, PA (United States); Tappouni, R.; Tice, J. [Department of Radiology, Section of Abdominal Imaging, Penn State Milton Hershey Medical Center, Hershey, PA (United States)

    2011-01-15

    The objective of this article is to review the pathophysiology of acute small bowel diseases, and to correlate the mechanisms of disease with computed tomography (CT) findings. Disease entities will be classified into the following: immune mediated and infectious causes, vascular causes, mechanical causes, trauma, and others. Having an understanding of acute small bowel pathophysiology is a useful teaching tool, and can lead to imaging clues to the most likely diagnosis of acute small bowel disorders.

  6. [Two-year incidence of new immune-mediated inflammatory diseases in patients with inflammatory bowel disease: A study in the AQUILES cohort].

    Science.gov (United States)

    Marín-Jiménez, Ignacio; Gisbert, Javier P; Pérez-Calle, José L; García-Sánchez, Valle; Tabernero, Susana; García-Vicuña, Rosario; Romero, Cristina; Juliá, Berta; Vanaclocha, Francisco; Cea-Calvo, Luis

    2015-12-01

    To describe the 2-year incidence of new immune-mediated inflammatory diseases (spondylarthritis, uveitis, psoriasis) in the cohort of patients with inflammatory bowel disease (IBD) included in the AQUILES study. Over a 2-year period, 341 patients with IBD (53% women, mean age 40 years) diagnosed with Crohn's disease (60.5%), ulcerative colitis (38.1%) and indeterminate colitis (1.4%) were followed up. New diagnoses made during follow-up were based on reports of the corresponding specialists (rheumatologists, ophthalmologists, and dermatologists). A total of 22 new diagnoses of immune-mediated inflammatory diseases were established in 21 patients (cumulative incidence of 6.5%, 95% confidence interval [CI] 3.7-9.2, incidence rate of 26 cases per 10,000 patient-years). Most diagnoses were new cases of spondylarthritis (n=15). The cumulative incidence of new diagnoses of immune-mediated inflammatory diseases was similar in patients with Crohn's disease (5.8%, 95% CI 3.4-9.9) and in patients with ulcerative colitis (7.7%, 95% CI 4.2-13.6). On multivariate analysis, the incidence of new immune-mediated inflammatory diseases was significantly associated with a family history of IBD (odds ratio=3.6, 95% CI 1.4-9.4) and the presence of extraintestinal manifestations of IBD (odds ratio=1.8, 95% CI .7-5.2). In patients with IBD, the incidence of new immune-mediated inflammatory diseases at 2 years of follow-up was 6.5%. These diseases were more frequent in patients with extraintestinal manifestations of IBD and a family history of IBD. Copyright © 2015 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

  7. Massive hemorrhage due to hemodialysis-associated thrombocytopenia.

    Science.gov (United States)

    Vicks, S L; Gross, M L; Schmitt, G W

    1983-01-01

    Marked declines in platelet numbers were noted in association with hemodialysis. This resulted in gastrointestinal bleeding and the need for packed RBC and platelet transfusions. This hemodialysis-associated thrombocytopenia was ameliorated by changing the dialyzer in use. The gastrointestinal bleeding stopped and the need for platelet transfusions was obviated. The degree of platelet loss during hemodialysis is probably affected by the composition of the dialyzer membrane used as well as other factors. Hemodialysis-associated thrombocytopenia may be a contributing factor in the increased bleeding tendency noted in hemodialysis patients.

  8. Simultaneous occurrence of foetal and neonatal alloimmune thrombocytopenia and neonatal neutropenia due to maternal neutrophilic autoantibodies

    DEFF Research Database (Denmark)

    Morling Taaning, Ellen Birkerod; Jensen, Lise; Varming, Kim

    2012-01-01

    Foetal and neonatal alloimmune thrombocytopenia (FNAIT) and neonatal neutropenia caused by maternal autoantibodies against neutrophils are rare disorders. We describe a newborn with severe thrombocytopenia and intracerebral bleeding caused by maternal anti-HPA-3a alloantibodies and mild neutropenia...

  9. High level increase in liver enzymes and severe thrombocytopenia in a male case of anorexia nervosa

    Directory of Open Access Journals (Sweden)

    Mojgan Karahmadi

    2011-01-01

    Conclusions: Improvement of initial clinical symptoms and recovery of liver enzymes and thrombocytopenia after the treatment suggested that liver dysfunction and thrombocytopenia may be observed in AN patients and should be taken care of by physicians.

  10. Eltrombopag for management of chronic immune thrombocytopenia (RAISE): a 6-month, randomised, phase 3 study

    DEFF Research Database (Denmark)

    Cheng, Gregory; Saleh, Mansoor N; Marcher, Claus

    2011-01-01

    Eltrombopag is an oral thrombopoietin receptor agonist for the treatment of thrombocytopenia. We aimed to compare the response to once daily eltrombopag versus placebo in patients with chronic immune thrombocytopenia during a 6-month period....

  11. Acute thrombocytopenic crisis following burns complicated by staphylococcal septicaemia.

    Science.gov (United States)

    George, A; Bang, R L; Lari, A R; Gang, R K

    2001-02-01

    The pathophysiological changes in a burn patient can at times manifest as severe complications, the management of which can be extremely challenging to the burn surgeon. A case report of an adult male with burns (18% total body surface area) who developed an acute unexpected thrombocytopenia crisis (2x10(9) l(-1)) on day 3 followed by disseminated intravascular coagulation is presented. The various etiological factors and possible mechanisms leading to thrombocytopenia in burns are discussed. Minor burns may present acute major complications in the presence of other thrombocytopenic factors like trauma and sepsis and thrombocytopenia by it self can be a good indicator of sub-clinical infection.

  12. Labor analgesia in a patient with paroxysmal nocturnal hemoglobinuria with thrombocytopenia.

    Science.gov (United States)

    Stocche, R M; Garcia, L V; Klamt, J G

    2001-01-01

    Paroxysmal nocturnal hemoglobinuria (PNH) is a form of acquired hemolytic anemia in which a defect of glycophosphatidylinositol anchor proteins in the cell membrane of bone marrow stem cells leads to activation of the complement system and consequent destruction of defective cells. The characteristics of this disease are an increased frequency of thrombotic events, anemia, and thrombocytopenia. We report a case of a pregnant patient with PNH with thrombocytopenia who delivered vaginally after receiving epidural labor analgesia. Prophylaxis of thromboembolism was performed with heparin 1 hour after the removal of the epidural catheter, and repeated at 12-hour intervals. Sensory changes or motor changes and pain were monitored every 10 minutes for 8 hours after delivery. During analgesia, the patient reported complete pain relief. Delivery and the immediate postpartum period were without any untoward events. Four major factors influenced the anesthetic conduct used for the present patient: (1) the risk of an acute hemolytic crisis, (2) the need to perform prophylaxis for thromboembolism, (3) the need to reduce labor stress, and (4) minimizing the risk of missing an epidural hematoma. We also present a survey of the literature about PNH and discuss the anesthetic conduct in this patient.

  13. Adherence to systemic therapies for immune-mediated inflammatory diseases in Lebanon: a physicians’ survey from three medical specialties

    Directory of Open Access Journals (Sweden)

    Ammoury A

    2017-05-01

    Full Text Available Alfred Ammoury,1 Jad Okais,2 Mireille Hobeika,3 Raymond B Sayegh,4 Rani H Shayto,5 Ala I Sharara5 1Division of Dermatology, St George Hospital University Medical Center, 2Division of Rheumatology, St Joseph University, 3AbbVie Levant, 4Division of Gastroenterology, St Joseph University, 5Department of Internal Medicine, Division of Gastroenterology, American University of Beirut Medical Center, Beirut, Lebanon Background: Immune-mediated inflammatory diseases (IMIDs are chronic conditions that may cause tissue damage and disability, reduced quality of life and increased mortality. Various treatments have been developed for IMIDs, including immune modulators and targeted biologic agents. However, adherence remains suboptimal. Methods: An adherence survey was used to evaluate physicians’ beliefs about adherence to medication in IMID and to evaluate if and how they manage adherence. The survey was distributed to 100 randomly selected physicians from three different specialties. Results were analyzed by four academic experts commissioned to develop an action plan to address practical and perceptual barriers to adherence, integrating it into treatment goals to maximize outcomes in IMID, thereby elevating local standards of care. Results: Eighty-two physicians participated in this study and completed the questionnaire. Most defined adherence as compliance with prescribed treatment. Although the majority of surveyed physicians (74% did not systematically measure adherence in their practice, 54% identified adherence as a treatment goal of equal or greater importance to therapeutic endpoints. Lack of time and specialized nursing support was reported as an important barrier to measuring adherence. The expert panel identified four key areas for action: 360° education (patient–nurse–physician, patient–physician communication, patient perception and concerns, and market access/cost. An action plan was developed centered on education and awareness

  14. Thrombocytopenia during pregnancy in women with HIV infection ...

    African Journals Online (AJOL)

    Background. Thrombocytopenia (TCP) complicates 5 - 8% of pregnancies. Most cases of TCP are gestational, and the condition is usually mild and occurs in the latter part of pregnancy. Apart from pregnancy-associated medical complications such as pre-eclampsia, HIV infection is a recognised cause of TCP, and a ...

  15. Refractory primary immune thrombocytopenia with subsequent del(5q) MDS

    DEFF Research Database (Denmark)

    Bech Mortensen, Thomas; Frederiksen, Henrik; Marcher, Claus Werenberg

    2017-01-01

    A patient with refractory primary immune thrombocytopenia (ITP) characterised by severe skin and mucosal bleedings was treated with several ITP-directed therapies including cyclophosphamide. He later developed therapy-related del(5q) myelodysplastic syndrome with no dysplastic morphological featu...

  16. Petechial Hemorrhage: A clinical diagnosis of neonatal Thrombocytopenia and sepsis

    Directory of Open Access Journals (Sweden)

    Deepak Kumar sharma

    2015-02-01

    Full Text Available A preterm female baby with birth weight of 1.5kg was referred to our hospital on day 6 for difficulty in breathing. Baby was admitted at birth for respiratory distress and feed intolerance to other hospital and in view of clinical deterioration baby was referred. Baby had thrombocytopenia with platelets counts of 11000/ mm3 and high CRP titer. Baby had petechial haemorrhagic spots all over the body with hepatosplenomegaly and sclerema (figure 1,2,3. Baby further platelets counts were 3000, 43000, 67000 and then normal. Baby was managed with antibiotics and platelets transfusion. Gradually baby counts improved and petechial spots disappeared. Discussion Neonatal Sepsis is a common complication in the neonatal intensive care unit. It is most common in the smallest and most premature infants in whom the clinical presentation can be subtle and nonspecific. Thrombocytopenia is the common manifestation of neonatal sepsis in sick babies(1. The manifestation can be seen in newborn as petechial spots over the body with predominance over chest and abdomen(2.Thrombocytopenia is seen in 18% to 35% of NICU patients, and in 73% of extremely low birth weight (ELBW infants(3. Bacterial,fungal and viral infection causes thrombocytopenia. Infection causes damage to vascular endothelium which increases the destruction of platelets and there removal by reticuloendothelial system(4

  17. The diagnostic value of thrombopoietin level measurements in thrombocytopenia

    NARCIS (Netherlands)

    Porcelijn, L.; Folman, C. C.; Bossers, B.; Huiskes, E.; Overbeeke, M. A.; van der Schoot, C. E.; de Haas, M.; von dem Borne, A. E.

    1998-01-01

    It has been reported that blood trombopoietin (TPO) levels can discriminate between thrombocytopenia due to increased platelet destruction and decreased platelet production. With our TPO ELISA and a glycocalicin ELISA we analysed a large group of patients in detail and could confirm and amplify the

  18. Severe fever with thrombocytopenia syndrome virus, South Korea, 2013.

    Science.gov (United States)

    Park, Sun-Whan; Han, Myung-Guk; Yun, Seok-Min; Park, Chan; Lee, Won-Ja; Ryou, Jungsang

    2014-11-01

    During 2013, severe fever with thrombocytopenia syndrome was diagnosed in 35 persons in South Korea. Environmental temperature probably affected the monthly and regional distribution of case-patients within the country. Phylogenetic analysis indicated that the isolates from Korea were closely related to isolates from China and Japan.

  19. Early Endometriosis in Females Is Directed by Immune-Mediated Estrogen Receptor α and IL-6 Cross-Talk.

    Science.gov (United States)

    Burns, Katherine A; Thomas, Seddon Y; Hamilton, Katherine J; Young, Steven L; Cook, Donald N; Korach, Kenneth S

    2018-01-01

    Endometriosis is a gynecological disease that negatively affects the health of 1 in 10 women. Although more information is known about late stage disease, the early initiation of endometriosis and lesion development is poorly understood. Herein, we use a uterine tissue transfer mouse model of endometriosis to examine early disease development and its dependence on estradiol (E2) and estrogen receptor (ER) α within 72 hours of disease initiation. Using wild-type and ERα knockout mice as hosts or donors, we find substantial infiltration of neutrophils and macrophages into the peritoneal cavity. Examining cell infiltration, lesion gene expression, and peritoneal fluid, we find that E2/ERα plays a minor role in early lesion development. Immune-mediated signaling predominates E2-mediated signaling, but 48 hours after the initiation of disease, a blunted interleukin (IL)-6-mediated response is found in developing lesions lacking ERα. Our data provide evidence that the early initiation of endometriosis is predominantly dependent on the immune system, whereas E2/ERα/IL-6-mediated cross-talk plays a partial role. These findings suggest there are two phases of endometriosis-an immune-dependent phase and a hormone-dependent phase, and that targeting the innate immune system could prevent lesion attachment in this susceptible population of women.

  20. Intact but not denatured ovine serum immunoglobulins positively modulate mucosal immune mediators in the growing rat challenged with Salmonella enteritidis.

    Science.gov (United States)

    Balan, Prabhu; Moughan, Paul J

    2013-09-28

    Immunoglobulins are major glycoproteins that modulate the immune response of gut-associated lymphoid tissue. In the present study, we sought to determine whether orally administered ovine serum immunoglobulins modulate selected indices of mucosal immune function and immune mediators in the growing rat challenged with Salmonella enteritidis. Rats were fed a casein-based basal control diet (BD; unchallenged). Three groups of rats were challenged orally with 1 x 10(7) viable S. enteritidis on day 15 of the study and were fed the BD, the BD containing freeze-dried ovine immunoglobulins (FDOI), or the BD containing autoclaved ovine immunoglobulins (AOI; negative control diet). The rats were randomly allocated to one of the four groups (n 15) and consumed their diet for 18 d. In all of the intestinal segments, the challenged rats fed either the BD or AOI diet produced higher (Pimmunoglobulin fraction positively modulated some selected indices of mucosal immune function and its mediators in growing rats challenged with S. enteritidis.

  1. Anasarca, Fever, Thrombocytopenia, Organomegaly, and Multiorgan Failure in a 24-Year-Old Pregnant Woman

    Directory of Open Access Journals (Sweden)

    Guillaume Morel

    2017-01-01

    Full Text Available TAFRO syndrome is a distinct idiopathic multicentric Castleman disease characterized by the association of thrombocytopenia, anasarca, fever, reticulin fibrosis, and organomegaly. We report the first case occurring in a Caucasian pregnant woman. At 34 weeks of gestation, our patient presented with all clinical and biological symptoms compatible with a TAFRO syndrome. Tough quick cesarean section was performed as symptoms got worse with onset of multiorgan failure requiring mechanical ventilation for acute respiratory distress, continuous renal replacement, and vasopressors. Nine days after ICU admission, steroid boluses were started and allowed spectacular clinical and biological improvement. As systemic inflammatory manifestations are important, TAFRO syndrome can be mistaken with severe autoimmune diseases, systemic infections, hematological malignancies, or hemophagocytic lymphohistiocytosis.

  2. Shared Genetic Basis for Type 1 Diabetes, Islet Autoantibodies, and Autoantibodies Associated With Other Immune-Mediated Diseases in Families With Type 1 Diabetes

    DEFF Research Database (Denmark)

    Brorsson, Caroline Anna; Pociot, Flemming

    2015-01-01

    Type 1 diabetes (T1D) is a polygenic autoimmune disease that is often present with autoantibodies directed against pancreatic islet proteins. Many genetic susceptibility loci are shared with other autoimmune or immune-mediated diseases that also cosegregate in families with T1D. The aim of this s......Type 1 diabetes (T1D) is a polygenic autoimmune disease that is often present with autoantibodies directed against pancreatic islet proteins. Many genetic susceptibility loci are shared with other autoimmune or immune-mediated diseases that also cosegregate in families with T1D. The aim...... of this study was to investigate whether susceptibility loci identified in genome-wide association studies (GWAS) of T1D were also associated with autoantibody positivity in individuals with diabetes. Fifty single nucleotide polymorphisms (SNPs) were genotyped in 6,556 multiethnic cases collected by the Type 1...

  3. The role of basic leucine zipper transcription factor E4BP4 in the immune system and immune-mediated diseases.

    Science.gov (United States)

    Yin, Jinghua; Zhang, Jian; Lu, Qianjin

    2017-07-01

    Basic leucine zipper transcription factor E4BP4 (also known as NFIL3) has been implicated in the molecular and cellular mechanisms of functions and activities in mammals. The interactions between E4BP4 and major regulators of cellular processes have triggered significant interest in the roles of E4BP4 in the pathogenesis of certain chronic diseases. Indeed, novel discoveries have been emerging to illustrate the involvement of E4BP4 in multiple disorders. It is recognized that E4BP4 is extensively involved in some immune-mediated diseases, but the mechanisms of E4BP4 involvement in these complex diseases remain poorly defined. Here we review the regulatory mechanisms of E4BP4 engaging in not only the biological function but also the development of immune-mediated diseases, paving the way for future therapies. Copyright © 2017. Published by Elsevier Inc.

  4. Severe thrombocytopenia induced by iodinated contrast after coronary angiography: The use of gadolinium contrast and intravascular ultrasound as an alternative to guide percutaneous coronary intervention.

    Science.gov (United States)

    Cubero-Gómez, José María; Guerrero Márquez, Francisco J; Diaz-de la-Llera, Luis; Fernández-Quero, Mónica; Guisado-Rasco, Agustín; Villa-Gil-Ortega, Manuel

    2017-01-01

    Acute contrast-induced thrombocytopenia is a rare event with the use of modern low osmolarity iodinated contrast media. The pathophysiological mechanism that causes platelet counts to drop has not been identified, but an immunological mechanism is suspected due to cytotoxicity after previous exposure to contrast. We report the case of a 47-year-old male patient with acute severe thrombocytopenia due to iodinated contrast media exposure. His platelet count after the procedure with the highest amount of contrast was zero, which is the lowest reported platelet count to date. Percutaneous coronary revascularization under both intravascular ultrasound and gadolinium contrast guidance was performed without complications. The most feared complication after the use of gadolinium is nephrogenic systemic fibrosis, especially in patients on hemodialysis. Copyright © 2016 Sociedade Portuguesa de Cardiologia. Publicado por Elsevier España, S.L.U. All rights reserved.

  5. Acute disseminated encephalomyelitis in dengue viral infection.

    Science.gov (United States)

    Wan Sulaiman, Wan Aliaa; Inche Mat, Liyana Najwa; Hashim, Hasnur Zaman; Hoo, Fan Kee; Ching, Siew Mooi; Vasudevan, Ramachandran; Mohamed, Mohd Hazmi; Basri, Hamidon

    2017-09-01

    Dengue is the most common arboviral disease affecting many countries worldwide. An RNA virus from the flaviviridae family, dengue has four antigenically distinct serotypes (DEN-1-DEN-4). Neurological involvement in dengue can be classified into dengue encephalopathy immune-mediated syndromes, encephalitis, neuromuscular or dengue muscle dysfunction and neuro-ophthalmic involvement. Acute disseminated encephalomyelitis (ADEM) is an immune mediated acute demyelinating disorder of the central nervous system following recent infection or vaccination. This monophasic illness is characterised by multifocal white matter involvement. Many dengue studies and case reports have linked ADEM with dengue virus infection but the association is still not clear. Therefore, this article is to review and discuss concerning ADEM in dengue as an immune-medicated neurological complication; and the management strategy required based on recent literature. Copyright © 2017 Elsevier Ltd. All rights reserved.

  6. Extensive Intracardiac and Deep Venous Thromboses in a Young Woman with Heparin-Induced Thrombocytopenia and May-Thurner Syndrome

    Directory of Open Access Journals (Sweden)

    Yekaterina Kim

    2017-01-01

    Full Text Available A 38-year-old woman with a history of recurrent deep venous thromboses (DVTs on chronic anticoagulation presented with acute left leg swelling. The patient was diagnosed with an acute left lower extremity (LLE DVT in the setting of May-Thurner syndrome for which treatment with unfractionated heparin was started. Her hospital course was complicated by a new diagnosis of heparin-induced thrombocytopenia (HIT, with an incidental discovery of a large tricuspid valve mobile mass on a transthoracic echocardiogram (TTE. Subsequent imaging confirmed multiple right atrial thrombi along with LLE venous stent thrombosis and a new right LE acute DVT. Anticoagulation with argatroban for HIT thrombosis was started. She underwent a right atrial percutaneous thrombectomy and bilateral lower extremity thrombectomy with directed angioplasty and stent placement. This presentation is a rare manifestation of HIT with extensive intracardiac and deep venous thrombi, with successful staged interventions.

  7. [Immune-mediated inflammatory diseases in patients with inflammatory bowel disease. Baseline data from the Aquiles study].

    Science.gov (United States)

    Marín-Jiménez, Ignacio; García Sánchez, Valle; Gisbert, Javier P; Lázaro Pérez Calle, José; Luján, Marisol; Gordillo Ábalos, Jordi; Tabernero, Susana; Juliá, Berta; Romero, Cristina; Cea-Calvo, Luis; García-Vicuña, Rosario; Vanaclocha, Francisco

    2014-11-01

    To determine the prevalence of immune-mediated inflammatory diseases (IMID) in a cohort of patients with inflammatory bowel disease (IBD) enrolled in hospital gastroenterology outpatients units for the AQUILES study, a prospective 2-year follow-up study. We included patients ≥18 years old with a prior or new diagnosis of IBD (Crohn disease [CD], ulcerative colitis [UC] or indeterminate colitis). Diagnoses were collected in a cross-sectional manner from the clinical records at enrollment of a new patient in the study. We included 526 patients (mean age 40.2 years; 47.3% men, 52.7% women), 300 with CD (57.0%), 218 with UC (41.4%) and 8 with indeterminate colitis. Other types of IMID were present in 71 patients (prevalence: 13.5%, 95% CI: 10.8-16.7): 47 were spondyloarthropathies (prevalence: 8.9%); 18 psoriasis (3.4%); 5 pyoderma gangrenosum (1.0%), and 11 uveitis (2.1%). The prevalence of IMID was higher in patients with CD than in those with UC (17.0% [95% CI: 13.2-21.7] vs 9.2% [95% CI: 6.0-13.8], p=0.011). In the multivariate analysis, the variables associated with the presence of IMID were diagnosis of CD (OR=1.8 [95% CI: 1.1-3.2]) and duration of IBD ≥4 years (OR=2.1 [95% CI: 1.1-4.1] in those with disease duration 4-8 years, and OR=2.1 [95% CI: 1.2-3.9] in those with ≥8 years vs. 4 years since disease onset. Copyright © 2013 Elsevier España, S.L.U. and AEEH y AEG. All rights reserved.

  8. A live attenuated combination vaccine evokes effective immune-mediated protection against Edwardsiella tarda and Vibrio anguillarum.

    Science.gov (United States)

    Gao, Yuan; Wu, Haizhen; Wang, Qiyao; Qu, Jiangbo; Liu, Qin; Xiao, Jingfan; Zhang, Yuanxing

    2014-10-14

    Edwardsiella tarda and Vibrio anguillarum are the two main pathogenic bacteria that cause edwardsiellosis and vibriosis in various species of fish raised in aquaculture. In our previous study, the live attenuated vaccines E. tarda WED and V. anguillarum MVAV6203 showed robust relative protection when vaccinated zebrafish or turbot were challenged with virulent E. tarda or V. anguillarum, respectively. Additionally, vaccinated fish processed the two vaccines through different pathways of antigen processing and presentation. Here, the immune protection of a combination vaccination consisting of E. tarda WED and V. anguillarum MVAV6203 was initially evaluated in zebrafish. After challenge with E. tarda and V. anguillarum at 1 month post-vaccination, the vaccinated zebrafish exhibited the relative protective survival of 70% and 90%, respectively. The expression of genes related to antigen recognition, processing and presentation were measured in the liver and spleen of vaccinated zebrafish. Gene expression profiling showed that more than one Toll-like receptor signaling pathway was activated and that both MHC I and II pathways of antigen processing and presentation were evoked. Later, the immune protection of the combination vaccine was evaluated in turbot and it showed similarly effective immune-mediated protection. By ELISA analysis, we found that the specific antibody levels in vaccinated turbot increased compared to those of fish vaccinated by a single vaccine during 2 months post-vaccination. Meanwhile, the expression levels of MHC I and II in the liver, spleen and kidney of vaccinated turbot were both up-regulated, suggesting that the MHC I and II pathways of antigen processing and presentation are activated in vaccinated turbot, similar to vaccinated zebrafish. In summary, a combination vaccine of live attenuated E. tarda WED and V. anguillarum MVAV6203 is effective and could be used widely in the future. Copyright © 2014 Elsevier Ltd. All rights reserved.

  9. Predicting Outcome in dogs with Primary Immune-Mediated Hemolytic Anemia: Results of a Multicenter Case Registry.

    Science.gov (United States)

    Goggs, R; Dennis, S G; Di Bella, A; Humm, K R; McLauchlan, G; Mooney, C; Ridyard, A; Tappin, S; Walker, D; Warman, S; Whitley, N T; Brodbelt, D C; Chan, D L

    2015-01-01

    Outcome prediction in dogs with immune-mediated hemolytic anemia (IMHA) is challenging and few prognostic indicators have been consistently identified. An online case registry was initiated to: prospectively survey canine IMHA presentation and management in the British Isles; evaluate 2 previously reported illness severity scores, Canine Hemolytic Anemia Score (CHAOS) and Tokyo and to identify independent prognostic markers. Data from 276 dogs with primary IMHA across 10 referral centers were collected between 2008 and 2012. Outcome prediction by previously reported illness-severity scores was tested using univariate logistic regression. Independent predictors of death in hospital or by 30-days after admission were identified using multivariable logistic regression. Purebreds represented 89.1% dogs (n = 246). Immunosuppressive medications were administered to 88.4% dogs (n = 244), 76.1% (n = 210) received antithrombotics and 74.3% (n = 205) received packed red blood cells. Seventy-four per cent of dogs (n = 205) were discharged from hospital and 67.7% (n = 187) were alive 30-days after admission. Two dogs were lost to follow-up at 30-days. In univariate analyses CHAOS was associated with death in hospital and death within 30-days. Tokyo score was not associated with either outcome measure. A model containing SIRS-classification, ASA classification, ALT, bilirubin, urea and creatinine predicting outcome at discharge was accurate in 82% of cases. ASA classification, bilirubin, urea and creatinine were independently associated with death in hospital or by 30-days. Markers of kidney function, bilirubin concentration and ASA classification are independently associated with outcome in dogs with IMHA. Validation of this score in an unrelated population is now warranted. Copyright © 2015 The Authors. Journal of Veterinary Internal Medicine published by Wiley Periodicals, Inc. on behalf of the American College of Veterinary Internal Medicine.

  10. CD8 T cells primed in the gut-associated lymphoid tissue induce immune-mediated cholangitis in mice.

    Science.gov (United States)

    Seidel, Daniel; Eickmeier, Ira; Kühl, Anja A; Hamann, Alf; Loddenkemper, Christoph; Schott, Eckart

    2014-02-01

    The pathogenesis of primary sclerosing cholangitis (PSC) remains poorly understood. Since PSC predominantly occurs in patients with inflammatory bowel disease, autoimmunity triggered by activated T cells migrating from the gut to the liver is a possible mechanism. We hypothesized that T cells primed in the gut-associated lymphoid tissue (GALT) by a specific antigen migrate to the liver and cause cholangitis when they recognize the same antigen on cholangiocytes. We induced ovalbumin-dependent colitis in mice that express ovalbumin in biliary epithelia (ASBT-OVA mice) and crossed ASBT-OVA mice with mice that express ovalbumin in enterocytes (iFABP-OVA mice). We analyzed T-cell activation in the GALT and crossreactivity to the same antigen in the liver as well as the effects of colitis per se on antigen-presentation and T-cell activation in the liver. Intrarectal application of ovalbumin followed by transfer of CD8 OT-I T cells led to antigen-dependent colitis. CD8 T cells primed in the GALT acquired effector function and the capability to migrate to the liver, where they caused cholangitis in a strictly antigen-dependent manner. Likewise, cholangitis developed in mice expressing ovalbumin simultaneously in biliary epithelia and enterocytes after transfer of OT-I T cells. Dextran sodium sulfate colitis led to increased levels of inflammatory cytokines in the portal venous blood, induced activation of resident liver dendritic cells, and promoted the induction of T-cell-dependent cholangitis. Our data strengthen the notion that immune-mediated cholangitis is caused by T cells primed in the GALT and provide the first link between colitis and cholangitis in an antigen-dependent mouse model. © 2013 by the American Association for the Study of Liver Diseases.

  11. Analysis of audiometric relapse-free survival in patients with immune-mediated hearing loss exclusively treated with corticosteroids.

    Science.gov (United States)

    Mata-Castro, Nieves; García-Chilleron, Raimon; Gavilanes-Plasencia, Javier; Ramírez-Camacho, Rafael; García-Fernández, Alfredo; García-Berrocal, José Ramón

    2017-10-12

    To describe the results in terms of audiometric relapse-free survival and relapse rate in immunomediated hearing loss patients treated exclusively with corticosteroids. Retrospective study of patients with audiometric relapses, monitored from 1995 to 2014, in two centres of the Community of Madrid. We evaluated 31 patients with a mean age of 48.52 years (14.67 SD), of which 61.3% were women. Most hearing loss was fluctuating (48.4%). Only 16.1% of patients had systemic autoimmune disease. There is a moderate positive correlation between the sex variable and the systemic involvement variable (Spearman's correlation coefficient=0.356): specifically, between being female and systemic disease. The relative incidence rate of relapse in the first year was 2.01 relapses/year with a 95% CI (1.32 to 2.92). The mean survival time of the event (audiometric relapse) was 5.25 months (SD 0.756). With multivariate analysis, the only variable that achieved statistical significance was age, with a hazard ratio of 1.032 (95% CI; 1.001-1.063, P=.043). Immune-mediated disease of the inner ear is a chronic disease with relapses. Half of the patients with immunomediated hearing loss treated exclusively with corticosteroids relapse before 6 months of follow-up. In addition, if a patient has not relapsed, they are more likely to relapse as each year passes. Analysis of the of audiometric relapse- free survival will enable the effect of future treatments to be compared and their capacity to reduce the rhythm of relapses. Copyright © 2017 Elsevier España, S.L.U. and Sociedad Española de Otorrinolaringología y Cirugía de Cabeza y Cuello. All rights reserved.

  12. Kinetic profiles and management of hepatitis B virus reactivation in patients with immune-mediated inflammatory diseases.

    Science.gov (United States)

    Droz, Nina; Gilardin, Laurent; Cacoub, Patrice; Berenbaum, Francis; Wendling, Daniel; Godeau, Bertrand; Piette, Anne-Marie; Dernis, Emmanuelle; Ebbo, Mikael; Fautrel, Bruno; Le Guenno, Guillaume; Mekinian, Arsène; Bernard-Chabert, Brigitte; Costedoat-Chalumeau, Nathalie; Descloux, Elodie; Michot, Jean-Marie; Radenne, Sylvie; Rigolet, Aude; Rivière, Sophie; Yvin, Jean-Luc; Thibault, Vincent; Thabut, Dominique; Pol, Stanislas; Guillevin, Loïc; Mouthon, Luc; Terrier, Benjamin

    2013-09-01

    Immunosuppressive therapy may trigger hepatitis B virus (HBV) reactivation for increased morbidity and mortality. We aimed to describe HBV reactivation in patients receiving treatment for immune-mediated inflammatory diseases (IMIDs) and to evaluate a predefined algorithm for its prevention. Physicians submitted data for patients receiving treatment for IMIDs and exhibiting HBV reactivation, defined as an increase of >1 log10 IU/ml of HBV DNA levels or DNA reappearance. We systematically reviewed cases in the literature. The 35 physician-collected patients had rheumatoid arthritis (n = 14), connective tissue disease (n = 7), vasculitis (n = 5), and other diseases (n = 9). At baseline, 65.7% of patients were positive for hepatitis B surface antigen (HBsAg), 31.4% had a history of HBV infection, and 2.9% had occult HBV infection. Reactivation occurred a median of 35 weeks (range 2-397 weeks) after the start of corticosteroid and/or immunosuppressive therapy. In all, 88.6% of patients were clinically asymptomatic, but 25.7% had severe hepatitis; none had fulminant hepatitis. Management was antiviral therapy for 91.4%, with discontinuation or decrease of immunosuppressive therapy for 45.7%. In pooling these 35 cases and 103 patients from the literature, 73.9% of patients were clinically asymptomatic, 33.3% had severe hepatitis, and 12.3% died and/or had fulminant hepatitis. Reactivation occurred early with rituximab or cyclophosphamide therapy and in HBsAg-positive/HBV DNA-positive patients. Using the predefined algorithm, 78% of patients with reactivation would have received preemptive antiviral therapy. We provide new insights into HBV reactivation in patients receiving treatment for IMIDs. A predefined algorithm may be effective in reducing the risk of HBV reactivation in this population. Copyright © 2013 by the American College of Rheumatology.

  13. Acute folate deficiency in a critically ill patient

    NARCIS (Netherlands)

    Geerlings, S. E.; Rommes, J. H.; van Toorn, D. W.; Bakker, J.

    1997-01-01

    A 19-year-old male patient developed thrombocytopenia and leukopenia due to acute folate deficiency while recovering from a multiple organ failure syndrome. Risk factors for acute folate deficiency are extensive tissue damage due to sepsis, trauma or surgery and acute renal failure requiring renal

  14. Thrombocytopenia induced by noncytotoxic drugs in Denmark 1968-91

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, U; Andersen, M; Hansen, P B

    1996-01-01

    OBJECTIVES: To analyse the distribution of noncytotoxic drugs reported as cause of thrombocytopenia during a 24-year period, and to draw attention to the most commonly involved drugs in modern clinical practice. DESIGN/SETTING: Retrospective study of spontaneous case reports from the Danish...... reporting system on adverse drug reactions. SUBJECTS: A total of 309 critically reviewed cases of drug-induced thrombocytopenia reported during the period from 1968 to the end of 1991. RESULTS: Sodiumaurothiomalate and the combination sulfamethoxazole with trimethoprim were the most commonly reported single...... drugs, and nonsteroid anti-inflammatory drugs were the most frequently reported category of drugs. A pronounced shift in the spectrum of causal drugs was observed due to the introduction of new drugs and alterations in drug consumption. At present, valproic acid and measlesmumps-rubella vaccine are most...

  15. Immune Thrombocytopenia in a Child with T Cell Lymphoblastic Lymphoma

    Directory of Open Access Journals (Sweden)

    Kayo Tokeji

    2016-01-01

    Full Text Available We describe the case of a 13-year-old boy who presented with persistent thrombocytopenia during maintenance chemotherapy with mercaptopurine and methotrexate for T cell lymphoblastic lymphoma. He was diagnosed with immune thrombocytopenia (ITP after thorough investigations for the relapse of lymphoma and was successfully treated with immunoglobulin and steroids. ITP is known to be associated with chronic lymphocytic leukemia, Hodgkin lymphoma, and various types of non-Hodgkin lymphoma but rarely with T cell non-Hodgkin lymphoma or in children. Diagnosis of ITP with lymphoma is challenging due to the many factors affecting platelet counts, and ITP often complicates the diagnosis or treatment course of lymphoma. The underlying mechanism of ITP with NHL is still unclear. Drug-induced immunomodulation with a reduction of regulatory T cells might have contributed to the development of ITP in our case.

  16. Tyrosine kinase inhibitors induced immune thrombocytopenia in chronic myeloid leukemia?

    Directory of Open Access Journals (Sweden)

    Avital F. Barak

    2011-12-01

    Full Text Available The outcome and quality of life of chronic myeloid leukemia (CML patients has remarkably changed with the treatment of tyrosine kinase inhibitors (TKIs. Currently, hematopoietic stem cell transplantation (HSCT is considered mainly as a third line salvage therapy in cases of TKIs resistance or intolerance. Here we describe a patient with chronic phase CML who developed both resistance and late occurrence of s severe thrombocytopenia on first and second generation TKIs and eventually underwent HSCT. Although the mechanism of the myelosuppression is not fully understood, we showed for the first time the development of dose dependent platelet antibodies in the presence of TKIs, suggesting the possibility of TKIs induced thrombocytopenia. Our case emphasizes that late development of severe myelosuppression during imatinib treatment is probably an important indication for consideration of early HSCT.

  17. Thrombocytopenia in late preterm and term neonates after perinatal asphyxia.

    Science.gov (United States)

    Christensen, Robert D; Baer, Vickie L; Yaish, Hassan M

    2015-01-01

    A recent NHLBI conference concluded that platelet (PLT) transfusions of neonates must become more evidence based. One neonatal disorder for which transfusions are given is a poorly defined entity, the "thrombocytopenia of perinatal asphyxia." To expand the evidence base for this entity, we performed a multicentered, retrospective analysis of neonates with perinatal asphyxia. We analyzed records of term and late preterm neonates with perinatal asphyxia defined by a cord blood pH of not more than 6.99 and/or base deficit of at least 16 mmol/L. From these we identified neonates with at least two PLT counts of fewer than 150 × 10(9) /L in the first week of life and described the severity, nadir, and duration of the thrombocytopenia. Thrombocytopenia occurred in 31% (117/375) of neonates with asphyxia versus 5% of matched nonasphyxiated controls admitted to a neonatal intensive care unit (p neonates were excluded from the remaining analysis due to disseminated intravascular coagulation or extracorporeal membrane oxygenation. Nadir PLT counts of the remaining 96 were on Day 3 (75 × 10(9) /L; 90% confidence interval, 35.7 × 10(9) -128.6 × 10(9) /L) and normalized by Days 19 to 21. PLT counts after asphyxia roughly correlated inversely with elevated nucleated red blood cell count (NRBC) counts at birth. Thirty of the 96 received at least one PLT transfusion, all given prophylactically, none for bleeding. We maintain that the thrombocytopenia of perinatal asphyxia is an authentic entity. Its association with elevated NRBC counts suggests that hypoxia is involved in the pathogenesis. Because PLT counts are only moderately low, the condition is transient, and bleeding problems seem rare, we speculate that PLT transfusions should not be needed for most neonates with this condition. © 2014 AABB.

  18. [Retrospective analysis of patients with thrombocytopenia after patent ductus arteriosus interventional occlusion].

    Science.gov (United States)

    Liao, Qi-wei; Zhang, Wei-hua; Guang, Xue-feng; Lu, Yi-bing

    2013-03-01

    To explore the risk factors of patent ductus arteriosus (PDA) patients with thrombocytopenia after PDA interventional occlusion. Thrombocytopenia occurred in 14 out of 350 patients underwent PDA occlusion. Age, gender, body weight, PDA size, occluder size, mean pulmonary arterial pressure, the dose of heparin, the manufacturer of occluder, residual shunt after operation were analyzed. The recovery time of different grades of thrombocytopenia was observed. Multivariate logistic regression showed that the PDA size (OR = 2.238, P < 0.05), the dose of heparin (OR = 3.247, P < 0.05), residual shunt after operation (OR = 1.912, P < 0.01) were the independent risk factors of thrombocytopenia after PDA occlusion. The recovery time of mild thrombocytopenia was (7 ± 2) days without treatment. The recovery time of moderate thrombocytopenia was (12 ± 4) days with glucocorticoids treatment. The recovery time of severe thrombocytopenia was (21 ± 7) days with platelet transfusion. The occluder size, dose of heparin, residual shunt are the independent risk factors of thrombocytopenia after PDA interventional occlusion. Recover time of thrombocytopenia after PDA interventional occlusion is closely related to the severity of thrombocytopenia.

  19. VALPROIC ACID-INDUCED THROMBOCYTOPENIA: A LONGITUDINAL STUDY

    Directory of Open Access Journals (Sweden)

    Manoj Kumar Sahu

    2016-08-01

    Full Text Available BACKGROUND Valproate shows the most promising efficiency in treating mood as well as anxiety disorders; however, thrombocytopenia is one of the most common side effects associated with it. The perceived novelty and under recognition of the platelet lowering effects of valproate is illustrated by various case reports of thrombocytopenia associated with valproate in psychiatric populations. AIMS Present study aims is to investigate the relationship between platelet count & VPA therapy, age, and duration of medication. SETTINGS AND DESIGN It was a longitudinal observational study conducted at Department of Psychiatry, Pt. JNM Medical College, Raipur. METHODS AND MATERIAL The sample consisted of patients of either sex, aged between 18 to 65 years who were prescribed valproate therapy by the treating doctor. Patients were evaluated at baseline, at every month up to three months and at six months. The platelet counts were determined using an automatic haematology analyser. STATISTICAL ANALYSIS Correlation statistics were used to analyse the collected data. CONCLUSION Most of the time thrombocytopenia is mild and transient which resolves spontaneously. Regular monitoring of platelet level is required in the high risk groups.

  20. Immune thrombocytopenia after bee venom therapy: a case report.

    Science.gov (United States)

    Abdulsalam, Mohammad Adel; Ebrahim, Bader Esmael; Abdulsalam, Ahmad Jasem

    2016-03-25

    Immune thrombocytopenia (ITP) is a hematological disorder with an isolated decrease in number of circulating platelets. Bee venom therapy (BVT) is a form of alternative medicine. It is still being practiced in the Middle East and other parts of Asia. In BVT, acupuncture points are used to inject diluted bee venom into the body. The pharmacological basis behind BVT is not fully understood. However, it has been used to treat various medical conditions such as arthritis and low back pain. On the other hand there have been a number of reported complications of BVT use such as ITP. We present a case report on ITP after BVT. A 61 year old lady presented with gum bleeding and ecchymosis and found to have isolated thrombocytopenia (platelet count of 9 × 10(9)/L) after receiving four direct bee sting sessions. There was no evidence of any other risk factors of ITP. Bee venom components and toxicity may be associated with thrombocytopenia as a complication. Further research is needed to postulate guidelines and protocol for BVT. In the meantime, monitoring of the practice of BVT should be made, with an emphasis on patient education regarding the safety profile and associated risks compared to the gained benefits.

  1. Clinical spectrum of thrombocytopenia in adult population of karachi

    International Nuclear Information System (INIS)

    Rehman, Z.; Alam, M.; Mubarik, A.; Ahmed, M.

    2001-01-01

    Objective: To determine the etiology and clinical features of patients presenting with bleeding due to thrombocytopenia. Design: A cross sectional study. Place and duration of study:.Th study was carries out at PNS Shifa Hospital, Karachi during the period form 1994-1996. Subjects and Methods: A total of 500 consecutive patients of 15 years or more age with a platelet count of less than 150 x 10/sup 9/L were included in the study. Complete blood count including platelets count was carried out by using electronic counter model T-890 for each patient. Very low platelet count was also confirmed by manual method. Results: among 500 patients of thrombocytopenia the commonest cause was malaria consisting of 216 (43.2%) cases. Megaloblastic anemia was the leading hematological cause, comprising of 31 (6.2%) patients. Other miscellaneous causes like dengue hemorrhagic fever, idiopathic thrombocytopenic purpura aplastic anemia and leukemias were responsible for the rest of cases of thrombocytopenia. Epistaxis followed by gum bleeding was the leading clinical manifestation. Conclusion: We conclude that malaria and viral infections are common causes of transient ghtombocytopenia. Epistaxis and gum bleeding are the leading clinical manifestations in various disease processes in adult population. (author)

  2. Building an immune-mediated coagulopathy consensus: early recognition and evaluation to enhance post-surgical patient safety

    Directory of Open Access Journals (Sweden)

    Voils Stacy A

    2009-05-01

    Full Text Available Abstract Topical hemostats, fibrin sealants, and surgical adhesives are regularly used in a variety of surgical procedures involving multiple disciplines. Generally, these adjuncts to surgical hemostasis are valuable means for improving wound visualization, reducing blood loss or adding tissue adherence; however, some of these agents are responsible for under-recognized adverse reactions and outcomes. Bovine thrombin, for example, is a topical hemostat with a long history of clinical application that is widely used alone or in combination with other hemostatic agents. Hematologists and coagulation experts are aware that these agents can lead to development of an immune-mediated coagulopathy (IMC. A paucity of data on the incidence of IMC contributes to under-recognition and leaves many surgeons unaware that this clinical entity, originating from normal immune responses to foreign antigen exposure, requires enhanced post-operative vigilance and judicious clinical judgment to achieve best outcomes. Postoperative bleeding may result from issues such as loosened ties or clips or the occurrence of a coagulopathy due to hemodilution, vitamin K deficiency, disseminated intravascular coagulation (DIC or post-transfusion, post-shock coagulopathic states. Other causes, such as liver disease, may be ruled out by a careful patient history and common pre-operative liver function tests. Less common are coagulopathies secondary to pathologic immune responses. Such coagulopathies include those that may result from inherent patient problems such as patients with an immune dysfunction related to systemic lupus erythrematosus (SLE or lymphoma that can invoke antibodies against native coagulation factors. Medical interventions may also provoke antibody formation in the form of self-directed anti-coagulation factor antibodies, that result in problematic bleeding; it is these iatrogenic post-operative coagulopathies, including those associated with bovine thrombin

  3. RIG-I/MAVS and STING signaling promote gut integrity during irradiation- and immune-mediated tissue injury

    NARCIS (Netherlands)

    Fischer, Julius C.; Bscheider, Michael; Eisenkolb, Gabriel; Lin, Chia Ching; Wintges, Alexander; Otten, Vera; Lindemans, Caroline A.; Heidegger, Simon; Rudelius, Martina; Monette, Sébastien; Rodriguez, Kori A.Porosnicu; Calafiore, Marco; Liebermann, Sophie; Liu, Chen; Lienenklaus, Stefan; Weiss, Siegfried; Kalinke, Ulrich; Ruland, Jürgen; Peschel, Christian; Shono, Yusuke; Docampo, Melissa; Velardi, Enrico; Jenq, Robert R; Hanash, Alan M; Dudakov, Jarrod A; Haas, Tobias; van den Brink, Marcel R M; Poeck, Hendrik

    2017-01-01

    The molecular pathways that regulate the tissue repair function of type I interferon (IFN-I) during acute tissue damage are poorly understood. We describe a protective role for IFN-I and the RIG-I/MAVS signaling pathway during acute tissue damage in mice. Mice lacking mitochondrial

  4. Heparin-Related Thrombocytopenia Triggered by Severe Status of Systemic Lupus Erythematosus and Bacterial Infection

    Directory of Open Access Journals (Sweden)

    Satoshi Suzuki

    2016-01-01

    Full Text Available A patient with severe lupus nephritis developed thrombocytopenia during treatment with high-dose steroids. In addition to viral- or disease-induced cytopenia, the pathology was believed to arise from diverse contributing factors, such as thrombotic microangiopathy and heparin-related thrombocytopenia (HIT. By combining plasma exchange therapy and intravenous cyclophosphamide, we successfully controlled the SLE activity and improved the thrombocytopenia. An antecedent bacterial infection or SLE activity is believed to have contributed to the concurrent HIT.

  5. Lower segment cesarean section in a patient with severe thrombocytopenia and pregnancy induced hypertension

    Directory of Open Access Journals (Sweden)

    Minal Harde

    2013-01-01

    Full Text Available Thrombocytopenia in pregnancy carries a major risk of feto-maternal morbidity and mortality. We present a case of hypocellular bone marrow with severe thrombocytopenia with pregnancy induced hypertension (PIH for emergency lower segment cesarean section (LSCS. This disease is characterized by pancytopenia and hypocellular bone marrow with impaired morphology and maturation. Causes of death due to this disease include hemorrhage and infection secondary to thrombocytopenia and neutropenia especially following surgery. We report successful management of emergency LSCS with severe thrombocytopenia with severe PIH.

  6. Thrombocytopenia Associated with Localized Scleroderma: Report of Four Pediatric Cases and Review of the Literature.

    Science.gov (United States)

    Jindal, Ankur Kumar; Gupta, Anju; Dogra, Sunil; Rawat, Amit; Suri, Deepti; Ahluwalia, Jasmina; Singh, Surjit

    2017-07-01

    We report on four children with localized scleroderma (morphea) and thrombocytopenia. All four had the en coup de sabre subtype of morphea and had varying degrees of thrombocytopenia (8 × 10 9 /L to 120 × 10 9 /L). None of them had major bleeding manifestations, and thrombocytopenia resolved with treatment of morphea. (One patient was also given an injection of anti-D immunoglobulin.) We propose that thrombocytopenia associated with localized scleroderma is usually benign and requires no specific therapy. © 2017 Wiley Periodicals, Inc.

  7. Is the thrombopoietin assay useful for differential diagnosis of thrombocytopenia? Analysis of a cohort of 160 patients with thrombocytopenia and defined platelet life span.

    Science.gov (United States)

    Gouin-Thibault, I; Cassinat, B; Chomienne, C; Rain, J D; Najean, Y; Schlageter, M H

    2001-09-01

    Thrombopoietin (TPO), the major hormone controlling platelet production, has been measured in thrombocytopenias with discordant results. The aim of our work was to assess the value of the TPO assay for differential diagnosis of thrombocytopenias in a large cohort of patients classified according to the results of their platelet isotopic study. We measured TPO (R&D Systems) in serum of 160 thrombocytopenic patients referred to our department for platelet life span isotopic studies. We classified patients as follows: (a) idiopathic or autoimmune thrombocytopenia group (ITP; patients with increased platelet destruction and shortened platelet life span; n = 67); (b) pure genetic thrombocytopenia group (patients with decreased platelet production, normal platelet life span, and without bone marrow aplasia; n = 55); (c) bone marrow aplasia group (BM; patients with decreased platelet production, normal platelet life span, and bone marrow aplasia; n = 13). In patients with pure genetic thrombocytopenia, TPO (median, 55 ng/L) was not different from TPO in patients with ITP (median, 58 ng/L) or controls (n = 54; median, 51 ng/L). Only in patients with bone marrow aplasia was TPO significantly higher (median, 155 ng/L) and negatively correlated to the platelet count (r(2) = 0.5014). Although the median serum TPO is increased in thrombocytopenia with decreased platelet production from bone marrow aplasia, it does not differentiate patients with pure genetic thrombocytopenia from those with ITP.

  8. A Case of Alloimmune Thrombocytopenia, Hemorrhagic Anemia-Induced Fetal Hydrops, Maternal Mirror Syndrome, and Human Chorionic Gonadotropin–Induced Thyrotoxicosis

    Directory of Open Access Journals (Sweden)

    Venu Jain

    2013-05-01

    Full Text Available Fetal/neonatal alloimmune thrombocytopenia (FNAIT can be a cause of severe fetal thrombocytopenia, with the common presentation being intracranial hemorrhage in the fetus, usually in the third trimester. A very unusual case of fetal anemia progressed to hydrops. This was further complicated by maternal Mirror syndrome and human chorionic gonadotropin–induced thyrotoxicosis. Without knowledge of etiology, and possibly due to associated cardiac dysfunction, fetal transfusion resulted in fetal demise. Subsequent testing revealed FNAIT as the cause of severe hemorrhagic anemia. In cases with fetal anemia without presence of red blood cell antibodies, FNAIT must be ruled out as a cause prior to performing fetal transfusion. Fetal heart may adapt differently to acute hemorrhagic anemia compared with a more subacute hemolytic anemia.

  9. Immune Mediators of protective and pathogenic immune responses in patients with mild and fatal human monocytotropic ehrlichiosis

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    Ismail Nahed

    2012-05-01

    Full Text Available Abstract Background Ehrlichia chaffeensis is a bacterial pathogen that causes fatal human monocytic ehrlichiosis (HME that mimic toxic shock-like syndrome. Murine studies indicate that over activation of cellular immunity followed by immune suppression plays a central role in mediating tissue injury and organ failure during fatal HME. However, there are no human studies that examine the correlates of resistance or susceptibility to severe and fatal HME. Results In this study, we compared the immune responses in two patients with mild/non fatal and severe/fatal HME who had marked lymphopenia, thrombocytopenia and elevated liver enzymes. The levels of different immunological factors in the blood of those patients were examined and compared to healthy controls. Our data showed that fatal HME is associated with defective production of Th1 cytokines such as ( IFNγ and IL-2, increased anti-inflammatory (IL-10 and IL-13 and pro-inflammatory (TNF-α, IL-1α, IL-1β, and IL-6 cytokines, increased levels of macrophages, T cells, and NK cells chemokines such as MCP-1, MIP-1α, MIP-1β, but not RANTES and IP-10, increased levels of neutrophils chemokine and growth factor (IL-8 and G-CSF, and elevated expression of tumor necrosis factor receptor (TNFR, and toll like receptors 2 and 4 compared to patients with non fatal HME and healthy controls. Conclusions Fatal Ehrlichia-induced toxic shock is associated with defective Th1 responses, possible immune suppression mediated by IL-10. In addition, marked leukopenia observed in patients with fatal disease could be attributed to enhanced apoptosis of leukocytes and/or elevated chemokine production that could promote migration of immune cells to sites of infection causing tissue injury.

  10. Frequency of FOXP3+ Regulatory T-cells in the Blood of Chronic Hepatitis C Patients with Immune Mediated Skin Manifestations; Relationship to Hepatic Condition and Viral Load.

    Science.gov (United States)

    Farid, Carmen; Sheikh, Wafaa El; Swelem, Rania; El-Ghitany, Engy

    2016-12-01

    Chronic hepatitis C (CHC) infection causes a wide range of immune mediated hepatic and extrahepatic manifestations. Cutaneous manifestations constitute a major portion of the latter group. Host immune response to the virus - particularly regulatory T lymphocytes - is important in determining the outcome of the infection and the possibility of extrahepatic manifestations. The present study aims to investigate the relationship between immune-mediated cutaneous manifestations of CHC infection and the frequency of CD4+CD25 high FOXP3+ T regulatory lymphocytes. We also investigated the relationships to viral load and hepatic conditions. A total of 58 CHC patients (30 had cutaneous manifestations and 28 did not) and 30 healthy HCV free subjects were enrolled in this study. The frequency of CD4+CD25 high FOXP3+ Treg cells was measured in the peripheral blood of all participants. Additionally, serum ALT, RNA viral load, and hepatic ultrasonographic studies were performed for all patients. Skin manifestations were dominated by small vessel vasculitis and to a lesser extent lichen planus. Treg cell frequency was significantly lower in CHC patients with skin manifestations compared to those without. Chronic hepatic insult was significantly more common among patients with skin manifestations, although serum ALT levels were significantly lower in this group. Treg frequencies did not correlate to either ALT level or viral load. HCV-associated skin lesions are associated with low frequency of Treg cells. They are not related to liver enzymes or viral load; however, they are associated with a more advanced gross liver insult.

  11. Parvalbumin overexpression alters immune-mediated increases in intracellular calcium, and delays disease onset in a transgenic model of familial amyotrophic lateral sclerosis

    Science.gov (United States)

    Beers, D. R.; Ho, B. K.; Siklos, L.; Alexianu, M. E.; Mosier, D. R.; Mohamed, A. H.; Otsuka, Y.; Kozovska, M. E.; McAlhany, R. E.; Smith, R. G.; hide

    2001-01-01

    Intracellular calcium is increased in vulnerable spinal motoneurons in immune-mediated as well as transgenic models of amyotrophic lateral sclerosis (ALS). To determine whether intracellular calcium levels are influenced by the calcium-binding protein parvalbumin, we developed transgenic mice overexpressing parvalbumin in spinal motoneurons. ALS immunoglobulins increased intracellular calcium and spontaneous transmitter release at motoneuron terminals in control animals, but not in parvalbumin overexpressing transgenic mice. Parvalbumin transgenic mice interbred with mutant SOD1 (mSOD1) transgenic mice, an animal model of familial ALS, had significantly reduced motoneuron loss, and had delayed disease onset (17%) and prolonged survival (11%) when compared with mice with only the mSOD1 transgene. These results affirm the importance of the calcium binding protein parvalbumin in altering calcium homeostasis in motoneurons. The increased motoneuron parvalbumin can significantly attenuate the immune-mediated increases in calcium and to a lesser extent compensate for the mSOD1-mediated 'toxic-gain-of-function' in transgenic mice.

  12. Histones induce rapid and profound thrombocytopenia in mice

    Science.gov (United States)

    Bhandari, Ashish A.

    2011-01-01

    Histones are released from dying cells and contribute to antimicrobial defense during infection. However, extracellular histones are a double-edged sword because they also damage host tissue and may cause death. We studied the interactions of histones with platelets. Histones bound to platelets, induced calcium influx, and recruited plasma adhesion proteins such as fibrinogen to induce platelet aggregation. Hereby fibrinogen cross-linked histone-bearing platelets and triggered microaggregation. Fibrinogen interactions with αIIbβ3 integrins were not required for this process but were necessary for the formation of large platelet aggregates. Infused histones associated with platelets in vivo and caused a profound thrombocytopenia within minutes after administration. Mice lacking platelets or αIIbβ3 integrins were protected from histone-induced death but not from histone-induced tissue damage. Heparin, at high concentrations, prevented histone interactions with platelets and protected mice from histone-induced thrombocytopenia, tissue damage, and death. Heparin and histones are evolutionary maintained. Histones may combine microbicidal with prothrombotic properties to fight invading microbes and maintain hemostasis after injury. Heparin may provide an innate counter mechanism to neutralize histones and diminish collateral tissue damage. PMID:21700775

  13. Coexistence of Antiphospholipid Syndrome and Heparin-Induced Thrombocytopenia in a Patient with Recurrent Venous Thromboembolism

    Directory of Open Access Journals (Sweden)

    Samuel Adediran

    2017-01-01

    Full Text Available Heparin-induced thrombocytopenia (HIT is a prothrombotic adverse drug reaction in which heparin forms complexes with platelet factor 4 forming neoantigens that are recognized by autoantibodies. Antiphospholipid syndrome (APS is similar to HIT in that it is mediated by autoantibodies that are also prothrombotic. We present a case of rare coexistence of antiphospholipid antibody syndrome and heparin-induced thrombocytopenia.

  14. Heparin-induced thrombocytopenia among patients of a comprehensive cancer center

    Directory of Open Access Journals (Sweden)

    Weixin Wu

    2014-07-01

    Full Text Available Most clinical studies of heparin-induced thrombocytopenia have not included cancer patients who have high risk of thromboembolism, frequent exposure to heparin, and many potential causes of thrombocytopenia other than heparin-induced thrombocytopenia. To estimate the incidence and prevalence of heparin-induced thrombocytopenia in cancer patients, we identified cases based on diagnostic codes, anti-heparin antibody testing, and clinical characteristics (4T score at a comprehensive cancer center between 1 October 2008 and 31 December 2011. We estimated that the prevalence of heparin-induced thrombocytopenia to be 0.02% among all cancer patients and 0.24% among cancer patients exposed to heparin. The annual incidence of heparin-induced thrombocytopenia was 0.57 cases per 1000 cancer patients exposed to heparin. Of the 40 cancer patients with the International Classification of Diseases (Ninth Revision; ICD-9 code for heparin-induced thrombocytopenia, positive anti-heparin antibody, and 4T score ≥4, 5 (12.5% died of related thromboembolic or hemorrhagic complications. In a multivariate logistic regression model, male gender was a significant (p = 0.035 factor, and non-hematological malignancy was a significant (p = 0.017 factor associated with anti-heparin antibody positivity. Future studies may further examine the risk factors associated with heparin-induced thrombocytopenia in larger cohorts.

  15. Isolated anti-Ro/SSA thrombocytopenia: a rare feature of neonatal ...

    African Journals Online (AJOL)

    We report a rare case of isolated thrombocytopenia related to anti-Ro/SSA antibodies. The mother was followed for unlabeled familial thrombocytopenia. The mother had positive anti-Ro/SSA antibodies. She was asymptomatic without skin lesions or other criteria neither of systemic lupus erythematosus nor other connective ...

  16. Drug-specific characteristics of thrombocytopenia caused by non-cytotoxic drugs

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, U; Andersen, M; Hansen, P B

    1999-01-01

    registered. Severe thrombocytopenia with haemorrhagic manifestations was reported following exposure to gold salts, non-steroid anti-inflammatory drugs, sulfonamide antibiotics, cinchona alkaloids and vaccines. Valproic acid-induced thrombocytopenia was dose-dependent. The differences were primarily......OBJECTIVE: To analyse drug-specific clinical characteristics and to investigate the possible influence of epidemiological and other factors on thrombocytopenia induced by selected non-cytotoxic drugs. METHODS: A retrospective analysis of drug-induced thrombocytopenia reported to the Danish...... Committee on Adverse Drug Reactions. One-hundred and ninety-two cases induced by the most frequently reported drugs were included and analysed from data extracted from report forms and discharge summaries. RESULTS: Pronounced drug-specific differences in the clinical appearance of thrombocytopenia were...

  17. Thrombocytopenia as a thrombotic risk factor in patients with antiphospholipid antibodies without disease criteria.

    Science.gov (United States)

    Demetrio Pablo, Rosalia; Muñoz, Pedro; López-Hoyos, Marcos; Calvo, Vanesa; Riancho, Leyre; Martínez-Taboada, Victor Manuel

    2017-05-10

    The antiphospholipid syndrome (APS) is an acquired immune disorder defined by the presence of thrombosis (arterial and/or venous) and/or pregnancy morbidity along with the presence of positive antiphospholipid antibodies (aPL). There is a clear relationship between aPL and some events not included in the clinical criteria, including haematologic. a) to study the probability of developing clinical APS in patients with positive aPL and thrombopenia; b) to identify potential risk factors for thrombosis, and c) to study the association between thrombocytopenia and aPL. A retrospective study of 138 patients with positive aPL without fulfilling clinical criteria for APS. Thrombocytopenia was defined as a platelet count≤100,000/μl. Patients with other causes of thrombocytopenia were excluded. Seventeen of the 138 (12%) patients in the study had thrombocytopenia. The mean platelet count was 60,000/μl. The risk of developing thrombocytopenia was higher in smokers (OR 2.8; P=.044), in those with lupus anticoagulant (OR 13.5; P<.001) and those with higher burden of aPL (OR 50.8; P<.001). After a mean follow-up of 146±60.3 months, 5 patients with thrombocytopenia (29.4%) developed thrombosis. In our series, the incidence of thrombocytopenia is 12%. aPL-positive patients who develop thrombocytopenia have a potential risk of developing thrombosis. Tobacco could be a risk factor for thrombocytopenia. Autoantibodies load is a risk factor for the development of thrombocytopenia. Copyright © 2016 Elsevier España, S.L.U. All rights reserved.

  18. CD44 antibodies and immune thrombocytopenia in the amelioration of murine inflammatory arthritis.

    Directory of Open Access Journals (Sweden)

    Patrick J Mott

    Full Text Available Antibodies to CD44 have been used to successfully ameliorate murine models of autoimmune disease. The most often studied disease model has been murine inflammatory arthritis, where a clear mechanism for the efficacy of CD44 antibodies has not been established. We have recently shown in a murine passive-model of the autoimmune disease immune thrombocytopenia (ITP that some CD44 antibodies themselves can induce thrombocytopenia in mice, and the CD44 antibody causing the most severe thrombocytopenia (IM7, also is known to be highly effective in ameliorating murine models of arthritis. Recent work in the K/BxN serum-induced model of arthritis demonstrated that antibody-induced thrombocytopenia reduced arthritis, causing us to question whether CD44 antibodies might primarily ameliorate arthritis through their thrombocytopenic effect. We evaluated IM7, IRAWB14.4, 5035-41.1D, KM201, KM114, and KM81, and found that while all could induce thrombocytopenia, the degree of protection against serum-induced arthritis was not closely related to the length or severity of the thrombocytopenia. CD44 antibody treatment was also able to reverse established inflammation, while thrombocytopenia induced by an anti-platelet antibody targeting the GPIIbIIIa platelet antigen, could not mediate this effect. While CD44 antibody-induced thrombocytopenia may contribute to some of its therapeutic effect against the initiation of arthritis, for established disease there are likely other mechanisms contributing to its efficacy. Humans are not known to express CD44 on platelets, and are therefore unlikely to develop thrombocytopenia after CD44 antibody treatment. An understanding of the relationship between arthritis, thrombocytopenia, and CD44 antibody treatment remains critical for continued development of CD44 antibody therapeutics.

  19. Atorvastatin induced thrombocytopenia: A case report and review of literature

    Directory of Open Access Journals (Sweden)

    Saibal Moitra

    2016-01-01

    Full Text Available A 65-year-old hypertensive male, with co-existing benign prostatic hyperplasia for last 5 years was on tab telmisartan 40 mg and tab tamsulosin 0.4 mg, both once daily. He was found dyslipidemic on a routine investigation and was put on tab atorvastatin 10 mg once daily. The patient developed a petechial rash and bleeding from gums within a week of starting atorvastatin, and his platelet count dropped to 15,000/cmm. Atorvastatin was suspected to be the offender as no other causes of thrombocytopenia could be implicated. Atorvastatin was discontinued and intravenous steroid and platelet transfusion given. Platelet count improved gradually and became normal after 10 days. Causality assessment as per the Naranjo algorithm revealed a "probable association" with atorvastatin therapy.

  20. Predicting risk severity and response of fetal neonatal alloimmune thrombocytopenia.

    Science.gov (United States)

    Salomon, Ophira; Rosenberg, Nurit

    2013-08-01

    Fetal neonatal alloimmune thrombocytopenia (FNAIT) is a devastating bleeding disorder in the fetus or neonate caused by transplacental transport of maternal alloantibodies to paternal-derived antigen on fetal platelets. In Caucasians, up to 80% of FNAIT cases result from maternal immunization to human platelet antigen (HPA)-1a. New methods have developed facilitating detection of common and private antibodies against HPAs triggering FNAIT. Understanding the pathogenesis of FNAIT made it possible to develop a novel strategy to treat this disorder. To date, recombinant monoclonal antibodies directed against the β3 integrin and Fc receptors have been tested in a mouse model of FNAIT, and seem to be promising. Whether those novel treatments will eventually replace the conventional high dose immunoglobulin G in women with FNAIT is yet unknown. © 2013 John Wiley & Sons Ltd.

  1. Cost-effectiveness of antenatal screening for neonatal alloimmune thrombocytopenia

    DEFF Research Database (Denmark)

    Killie, M K; Kjeldsen-Kragh, J; Husebekk, A

    2007-01-01

    OBJECTIVES: To estimate the costs and health consequences of three different screening strategies for neonatal alloimmune thrombocytopenia (NAIT). DESIGN: Cost-utility analysis on the basis of a decision tree that incorporates the relevant strategies and outcomes. SETTING: Three health regions...... in Norway encompassing a 2.78 million population. POPULATION: Pregnant women (n = 100,448) screened for human platelet antigen (HPA) 1a and anti-HPA 1a antibodies, and their babies. METHOD: Decision tree analysis. In three branches of the decision tree, pregnant women entered a programme while in one...... additional QALYs among 100,000 pregnant women, and at the same time, reduce health care costs by approximately 1.7 million euros. The sensitivity analyses indicate that screening is cost effective or even cost saving within a wide range of probabilities and costs. CONCLUSION: Our calculations indicate...

  2. Romiplostim as early treatment of immune thrombocytopenia with severe immunodeficiency

    Directory of Open Access Journals (Sweden)

    Francesca Palandri

    2012-06-01

    Full Text Available Immunosuppressive agents are the standard therapeutic approach for immune thrombocytopenia (ITP. Their prolonged use may increase the risk of infectious complications, particularly when the patient is already at higher infectious risk. In this setting, the use of drugs with a mechanism of action alternative to immunosuppression, like thrombopoietin receptor agonists (TRAs, may find particular indication. We report the unique case of a patient with severe immunodeficiency and ITP, who experienced a serious infectious complication while on steroids treatment, and who was successfully treated with Romiplostim second- line. The present experience supports the effectiveness and safety of TRAs as early treatment of ITP patients with drug-induced immunodeficiency or with active infections.

  3. [Head drop syndrome in a patient with immune-mediated necrotizing myopathy with anti-signal recognition particle antibody: a case report].

    Science.gov (United States)

    Kushimura, Yukie; Shiga, Kensuke; Mukai, Mao; Yoshida, Masakatu; Mizuno, Toshiki; Nakagawa, Masanori

    2013-01-01

    We report an 87-year-old female patient who presented a dropped head and progressive weakness in proximal muscles over five months. The value of serum creatine kinase was 2,708 IU/l and the antibody against signal recognition particle (SRP) was detected by means of immunoprecipitation. The computed tomography of skeletal muscles revealed atrophy and fatty degeneration preferentially in the neck extensors and paraspinal muscles. The biopsied specimen of the deltoid muscle showed necrotic fibers scattered in fascicles with marked myophagia. The mononuclear cells in necrotic fibers were positive against CD68, leading to the diagnosis of immune-mediated necrotizing myopathy. We hypothesize that a group of patients with necrotizing myopathy can present a preferential involvement in neck extensors resulting in dropped head syndrome.

  4. Combination of recombinant factor VIIa and fibrinogen corrects clot formation in primary immune thrombocytopenia at very low platelet counts

    DEFF Research Database (Denmark)

    Larsen, Ole H; Stentoft, Jesper; Radia, Deepti

    2013-01-01

    Haemostatic treatment modalities alternative to platelet transfusion are desirable to control serious acute bleeds in primary immune thrombocytopenia (ITP). This study challenged the hypothesis that recombinant activated factor VII (rFVIIa) combined with fibrinogen concentrate may correct whole...... blood (WB) clot formation in ITP. Blood from ITP patients (n = 12) was drawn into tubes containing 3·2% citrate and corn trypsin inhibitor 18·3 μg/ml. WB [mean platelet count 22 × 10(9) /l (range 0-42)] was spiked in vitro with buffer, donor platelets (+40 × 10(9) /l), rFVIIa (1 or 4 μg/ml), fibrinogen...... low platelet counts. These data suggest that rFVIIa combined with fibrinogen corrects the coagulopathy of ITP even at very low platelet counts, and may represent an alternative to platelet transfusion....

  5. In Vitro Infection of Human Nervous Cells by Two Strains of Toxoplasma gondii: A Kinetic Analysis of Immune Mediators and Parasite Multiplication

    Science.gov (United States)

    Mammari, Nour; Vignoles, Philippe; Halabi, Mohamad Adnan; Darde, Marie Laure; Courtioux, Bertrand

    2014-01-01

    The severity of toxoplasmic infection depends mainly on the immune status of the host, but also on the Toxoplasma gondii strains, which differ by their virulence profile. The relationship between the human host and T. gondii has not yet been elucidated because few studies have been conducted on human models. The immune mechanisms involved in the persistence of T. gondii in the brains of immunocompetent subjects and during the reactivation of latent infections are still unclear. In this study, we analyzed the kinetics of immune mediators in human nervous cells in vitro, infected with two strains of T. gondii. Human neuroblast cell line (SH SY5Y), microglial (CMH5) and endothelial cells (Hbmec) were infected separately by RH (type I) or PRU (type II) strains for 8 h, 14 h, 24 h and 48 h (ratio 1 cell: 2 tachyzoites). Pro-inflammatory protein expression was different between the two strains and among different human nervous cells. The cytokines IL-6, IL-8 and the chemokines MCP-1 and GROα, and SERPIN E1 were significantly increased in CMH5 and SH SY5Y at 24 h pi. At this point of infection, the parasite burden declined in microglial cells and neurons, but remained high in endothelial cells. This differential effect on the early parasite multiplication may be correlated with a higher production of immune mediators by neurons and microglial cells compared to endothelial cells. Regarding strain differences, PRU strain, but not RH strain, stimulates all cells to produce pro-inflammatory growth factors, G-CSF and GM-CSF. These proteins could increase the inflammatory effect of this type II strain. These results suggest that the different protein expression profiles depend on the parasitic strain and on the human nervous cell type, and that this could be at the origin of diverse brain lesions caused by T. gondii. PMID:24886982

  6. Thrombocytopenia as an adverse effect of complementary and alternative medicines, herbal remedies, nutritional supplements, foods, and beverages.

    Science.gov (United States)

    Royer, Derek J; George, James N; Terrell, Deirdra R

    2010-05-01

    Thrombocytopenia is a well-recognized adverse effect of many drugs. However, the association of thrombocytopenia with complementary/alternative medicines, herbal remedies, nutritional supplements, foods, and beverages has been rarely described, except for reports of thrombocytopenia caused by quinine-containing beverages. To systematically identify all published reports of thrombocytopenia associated with these substances and to assess the evidence supporting their causal association with thrombocytopenia. Eleven databases were searched to identify relevant published reports. A priori criteria were defined for article selection and assessment. Each selected article was independently assessed by the three authors to document the presence of the criteria and determine the level of evidence for a causal association of the reported substance with thrombocytopenia. Twenty-seven articles were identified that reported the occurrence of thrombocytopenia with 25 substances (other than quinine). However, only six articles describing five substances (cow's milk, cranberry juice, Jui [Chinese herbal tea], Lupinus termis bean, and tahini [pulped sesame seeds]) reported clinical data supporting definite evidence of a causal association with thrombocytopenia. Four articles provided probable evidence for four additional substances, and five articles provided possible evidence for five additional substances. In the remaining articles, the association with thrombocytopenia was unlikely or the articles were excluded from review. Reports of thrombocytopenia describing definite or probable evidence for an association of a complementary/alternative medicines, herbal remedies, nutritional supplements, foods, and beverages are rare. Whether the occurrence of thrombocytopenia with these substances is uncommon or unrecognized is unknown.

  7. Drug-specific characteristics of thrombocytopenia caused by non-cytotoxic drugs

    DEFF Research Database (Denmark)

    Pedersen-Bjergaard, U; Andersen, M; Hansen, P B

    1999-01-01

    Committee on Adverse Drug Reactions. One-hundred and ninety-two cases induced by the most frequently reported drugs were included and analysed from data extracted from report forms and discharge summaries. RESULTS: Pronounced drug-specific differences in the clinical appearance of thrombocytopenia were...... registered. Severe thrombocytopenia with haemorrhagic manifestations was reported following exposure to gold salts, non-steroid anti-inflammatory drugs, sulfonamide antibiotics, cinchona alkaloids and vaccines. Valproic acid-induced thrombocytopenia was dose-dependent. The differences were primarily...

  8. A successful method for severe gestational thrombocytopenia: A rare case study

    Directory of Open Access Journals (Sweden)

    Adnan İncebıyık

    2013-01-01

    Full Text Available In a normally progressing pregnancy, especially in thethird trimester thrombocyte numbers reduce by about10%. The reason for this reduction is thought to be thehemodilution and increased consumption in pregnancy.Generally, it is recognized by chance during routine bloodcount and it is the second most common hematologicanomaly during pregnancy. Once thrombocytopenia isdiagnosed in pregnancy, research must be done to determinewhether it is a life-threatening risk factor in terms ofthe mother-fetus-infant. The majority of thrombocytopeniaseen in pregnancy is gestational thrombocytopenia. Thispaper examines an active labor, normal birthing case witha thrombocyte count of 7916/mm3.Key words: Gestational thrombocytopenia, idiopathicthrombocytopenic purpura, normal birth

  9. [Clinical effect of anti-D immunoglobulin in treatment of childhood immune thrombocytopenia: a Meta analysis].

    Science.gov (United States)

    Qin, Wei; Huang, Shao-Ling; Li, Ting-Ting

    2017-10-01

    To investigate the clinical effect and safety of anti-D immunoglobulin (anti-D) in the treatment of children with newly diagnosed acute immune thrombocytopenia (ITP) through a Meta analysis. PubMed, EMBASE, Cohrane Library, Ovid, CNKI, and Wanfang Data were searched for randomized controlled trials (RCTs) published up to April 2017. Review Manager 5.3 was used for the Meta analysis. Seven RCTs were included. The Meta analysis showed that after 72 hours and 7 days of treatment, the intravenous immunoglobulin (IVIG) group had a significantly higher percentage of children who achieved platelet count >20×10 9 /L than the anti-D group (Panti-D (50 μg/kg) group and the IVIG group (P>0.05), and there were also no significant differences in platelet count after 24 hours and 7 days of treatment between the 50 μg/kg and 75 μg/kg anti-D groups (P>0.05). The anti-D group had a significantly greater reduction in the hemoglobin level than the IVIG group after treatment, but did not need transfusion. No children in the anti-D group or the IVIG group experienced serious adverse reactions. Intravenous injection of anti-D may have a similar effect as IVIG in improving platelet count in children with acute ITP, but it may be slightly inferior to IVIG in the rate of platelet increase after treatment. The anti-D dose of 50 μg/kg may have a similar effect as 75 μg/kg. The recommended dose of anti-D for treatment of ITP is safe.

  10. The first reported case of concurrent trimethoprim-sulfamethoxazole-induced immune hemolytic anemia and thrombocytopenia.

    Science.gov (United States)

    Linnik, Yevgeniy A; Tsui, Edison W; Martin, Isabella W; Szczepiorkowski, Zbigniew M; Denomme, Gregory A; Gottschall, Jerome L; Hill, John M; Dunbar, Nancy M

    2017-12-01

    Drug-induced immune hemolytic anemia (DIIHA) and drug-induced immune thrombocytopenia (DIIT) are rare but dangerous complications of pharmacotherapy that may be underrecognized in hematopoietic stem cell transplant (HSCT) patients due to overlap of signs and symptoms with those of more common disease processes. A 61-year-old woman with NK-cell deficiency and GATA-2-associated myelodysplastic syndrome, status post-recent allogeneic HSCT (Day +58), presented with 3 days of acute-onset severe back pain, muscle cramps, and increasingly dark urine. She was found to be anemic, thrombocytopenic, and in acute renal failure. On admission, the direct antiglobulin test was positive for complement (C3) only. After careful review of her medication list, the possibility of DIIHA was raised. She had started taking trimethoprim-sulfamethoxazole (TMP-SMX) for Pneumocystis jiroveci pneumonia prophylaxis 24 days prior on a weekend dose schedule. Serologic tests on peripheral blood samples were performed using standard methods. Drug studies were performed at an immunohematology reference laboratory. The patient's serum showed hemolysis of donor red blood cells in the presence of TMP-SMX and also TMP-SMX-induced platelet antibodies. The patient was treated with transfusions, hemodialysis, and immunosuppressive agents. Her clinical condition improved and she was discharged after 8 days in stable condition. This case describes the first reported concurrent DIIHA and DIIT due to TMP-SMX-induced antibodies in an HSCT patient. DIIHA and DIIT can present a diagnostic challenge in the setting of intermittent medication dosing. © 2017 AABB.

  11. Acute hematologic emergencies in oncology

    International Nuclear Information System (INIS)

    Kristof, L.

    2012-01-01

    Malignant disease and its treatment are often being complicated by development of serious and at times life-threatening emergencies. Early recognition and treatment of these acute events are important to reduce morbidity and mortality in cancer patients. The following article provides an overview of several hematologic emergencies, which occur due abnormal hemopoiesis (e.g. hyperleukocytosis, anemia, thrombocytopenia), abnormal hemo stasis (e.g. hemorrhage, pulmonary embolism, disseminated intravascular coagulation), or are related to blood products transfusions (transfuse reactions). (author)

  12. Perinatal outcome in normal pregnant women with incidental thrombocytopenia at delivery

    Directory of Open Access Journals (Sweden)

    Ying-Hsuan Lin

    2013-09-01

    Conclusions: The results indicate that women who suffered from incidental thrombocytopenia at delivery but did not have other diseases during pregnancy were not at increased risk for adverse pregnancy outcomes.

  13. Fetal/neonatal allo-immune thrombocytopenia (FNAIT): past, present, and future.

    NARCIS (Netherlands)

    Serrarens-Janssen, V.M.; Semmekrot, B.A.; Novotny, V.M.J.; Porcelijn, L.; Lotgering, F.K.; Delemarre, F.M.C.; Steegers, E.A.P.

    2008-01-01

    We reviewed the English, American, and German literature for articles describing the prevalence, clinical presentation, outcome, therapeutic options, and screening possibilities for fetal/neonatal allo-immune thrombocytopenia (FNAIT), published between January 1950 and March 2007. The reported

  14. Screening in pregnancy for fetal or neonatal alloimmune thrombocytopenia: systematic review

    NARCIS (Netherlands)

    Kamphuis, M. M.; Paridaans, N.; Porcelijn, L.; de Haas, M.; van der Schoot, C. E.; Brand, A.; Bonsel, G. J.; Oepkes, D.

    2010-01-01

    Background Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a potentially devastating disease, which may lead to intracranial haemorrhage (ICH), with neurological damage as a consequence. In the absence of screening, FNAIT is only diagnosed after bleeding symptoms, with preventive options

  15. International consensus report on the investigation and management of primary immune thrombocytopenia

    NARCIS (Netherlands)

    Provan, Drew; Stasi, Roberto; Newland, Adrian C.; Blanchette, Victor S.; Bolton-Maggs, Paula; Bussel, James B.; Chong, Beng H.; Cines, Douglas B.; Gernsheimer, Terry B.; Godeau, Bertrand; Grainger, John; Greer, Ian; Hunt, Beverley J.; Imbach, Paul A.; Lyons, Gordon; McMillan, Robert; Rodeghiero, Francesco; Sanz, Miguel A.; Tarantino, Michael; Watson, Shirley; Young, Joan; Kuter, David J.

    2010-01-01

    Previously published guidelines for the diagnosis and management of primary immune thrombocytopenia (ITP) require updating largely due to the introduction of new classes of therapeutic agents, and a greater understanding of the disease pathophysiology. However, treatment-related decisions still

  16. Triad of Iron Deficiency Anemia, Severe Thrombocytopenia and Menorrhagia—A Case Report and Literature Review

    OpenAIRE

    Ibrahim, Ramy; Khan, Areej; Raza, Shahzad; Kafeel, Muhammad; Dabas, Ridhima; Haynes, Elizabeth; Gandhi, Anjula; Majumder, Omran L.; Zaman, Mohammad

    2012-01-01

    Introduction Thrombocytosis is a common disorder in patients diagnosed with iron deficiency anemia. The decreased platelet counts commonly found iron deficiency anemia is rarely reported in clinical practice. The exact mechanism of the occurrence of thrombocytopenia in iron deficiency anemia remains unclear. In this case report we discuss a triad of symptoms seen in the African American population: Iron deficiency anemia, menorrhagia and thrombocytopenia. Case presentation A 40 year old multi...

  17. Evolutionary and molecular analysis of the emergent severe fever with thrombocytopenia syndrome virus

    OpenAIRE

    Lam, Tommy Tsan-Yuk; Liu, Wei; Bowden, Thomas A.; Cui, Ning; Zhuang, Lu; Liu, Kun; Zhang, Yao-Yun; Cao, Wu-Chun; Pybus, Oliver G.

    2013-01-01

    In 2009, a novel Bunyavirus, called severe fever with thrombocytopenia syndrome virus (SFTSV) was identified in the vicinity of Huaiyangshan, China. Clinical symptoms of this zoonotic virus included severe fever, thrombocytopenia, and leukocytopenia, with a mortality rate of ?10%. By the end of 2011 the disease associated with this pathogen had been reported from eleven Chinese provinces and human-to-human transmission suspected. However, current understanding of the evolution and molecular e...

  18. Prevalence and etiological classification of thrombocytopenia among a group of pregnant women in Erbil City, Iraq

    Directory of Open Access Journals (Sweden)

    Rawand Pouls Shamoon

    2009-09-01

    Full Text Available Objective: To determine the prevalence and define the causes of pregnancy-associated thrombocytopenia. Materials and Methods: A total of 850 pregnant women at different ages of gestation were screened for thrombocytopenia. A control group of 150 age-matched non-pregnant women were tested for platelet count. Newborns of thrombocytopenic women were tested within 24 hours of delivery and reassessment of the women's platelets was done within 7-10 days post-delivery. Results: The mean platelet count in pregnant women was significantly lower than in non-pregnant women (221±59.9/mm3 vs. 273±66.9/mm3. Thrombocytopenia affected 8% of cases, with peak incidence during the third trimester. Gestational thrombocytopenia was found to be the principal cause (73.8%; hypertensive disorders caused thrombocytopenia in 23% of cases and two cases (4% were due to immune thrombocytopenic purpura. No maternal or fetal complications were noted. The mean platelet count of 51 newborns of thrombocytopenic women was 240±7.1. Two newborns (4% had low platelet counts. Conclusion: The majority of thrombocytopenias were mild gestational and occurred in late pregnancy. No maternal or neonatal bleeding complications were observed.

  19. The use of indium-111 oxine platelet scintigraphy and survival studies in pediatric patients with thrombocytopenia

    International Nuclear Information System (INIS)

    Castle, V.P.; Shulkin, B.L.; Coates, G.; Andrew, M.

    1989-01-01

    We have utilized 111 In-labeled heterologous platelets to investigate the mechanism of thrombocytopenia in ten children. From the scintigraphic findings, platelet survival times, and clinical information, thrombocytopenia was ascribed to decreased production or to increased destruction. Two patients were found to have bone marrow production defects. Two patients with hemangiomas were studied. In one, the hemangioma was shown not to be the cause of thrombocytopenia. In the second, the hemangioma was proven the source of platelet destruction, but was much more extensive than clinically evident. In both, surgical manipulation of the hemangioma was avoided. Six additional patients had thrombocytopenia due to accelerated destruction. In four, the spleen was shown responsible. In two, however, the spleen was shown not to be responsible for the low platelet counts, and splenectomy was avoided. Thus, 111 In-platelet scintigraphy and survival studies are valuable in the classification and management of childhood thrombocytopenia. We believe that this study should be performed, when possible, in any child with thrombocytopenia where the mechanism is unclear or the therapeutic intervention involves splenectomy or resection of a hemangioma

  20. Patient-reported treatment burden of chronic immune thrombocytopenia therapies

    Directory of Open Access Journals (Sweden)

    Brown T

    2012-03-01

    Full Text Available Abstract Background Chronic immune thrombocytopenia (ITP is a debilitating autoimmune disorder that causes a reduction in blood platelets and increased risk of bleeding. ITP is currently managed with various pharmacologic therapies and splenectomy. This study was conducted to assess patient perceived and reported treatment side effects, as well as the perceived burden or bother, and need to reduce or stop treatment, associated with these side effects among adult patients with chronic ITP. Methods A Web-enabled survey was administered to members of a US-based ITP patient support group. Patients reported demographic and clinical characteristics, ITP treatments' side effects for treatments received since diagnosed, level of bother (or distress, and need to reduce or stop treatment, associated with side effects. Current and past exposure was assessed for five specific treatment types: corticosteroids (CS, intravenous immunoglobulin (IVIg, anti-D immunoglobulin (anti-D, rituximab (RT, and splenectomy (SPL, as well as for other patient-referenced therapies (captured as "other". Results The survey was completed by 589 patients; 78% female, 89% white, mean age 48 years (SD = 14.71, and 68% reported a typical low platelet count of P P P P Conclusions Current ITP treatments, particularly corticosteroids, are associated with multiple bothersome side effects that may lead to patients stopping or reducing therapy. Open, informed and complete communication between clinician and patient regarding both the benefits and the side effects of ITP treatment may better prepare patients for their prescribed regimens.

  1. State of the art - how I manage immune thrombocytopenia.

    Science.gov (United States)

    Cooper, Nichola

    2017-04-01

    The management of patients with immune thrombocytopenia (ITP) is rapidly evolving. Over the last 15 years, a number of novel treatments have improved practice, with many steroid-sparing agents and a reduction in the progression to splenectomy. Although this has improved clinical care, many therapeutic challenges remain. There is no diagnostic test, no biomarkers to direct treatment and few comparative studies to help management decisions. Development of up to date guidelines is difficult with little high-grade evidence. First line treatment continues to be steroids and intravenous immunoglobulins (IVIG) although both are often poorly tolerated and not curative. Common second line treatments include rituximab, immunosuppressive agents, such as azathioprine and mycophenolate mofetil, and the thrombopoietin receptor agonists romiplostim and eltrombopag. There are no comparative studies to decide between these agents and treatment is generally individualized, depending on comorbidity. Use of splenectomy has declined and is generally reserved for patients with chronic disease, although the exact position of splenectomy is subject to debate. Further understanding of the cause of disease in individual patients may help guide treatment. Randomized controlled studies of common treatments and novel treatments for refractory patients are urgently needed. © 2017 John Wiley & Sons Ltd.

  2. Fetal/Neonatal Alloimmune Thrombocytopenia: Pathogenesis, Diagnostics and Prevention.

    Science.gov (United States)

    Brojer, Ewa; Husebekk, Anne; Dębska, Marzena; Uhrynowska, Małgorzata; Guz, Katarzyna; Orzińska, Agnieszka; Dębski, Romuald; Maślanka, Krystyna

    2016-08-01

    Fetal/neonatal alloimmune thrombocytopenia (FNAIT) is a relatively rare condition (1/1000-1/2000) that was granted orphan status by the European Medicines Agency in 2011. Clinical consequences of FNAIT, however, may be severe. A thrombocytopenic fetus or new-born is at risk of intracranial hemorrhage that may result in lifelong disability or death. Preventing such bleeding is thus vital and requires a solution. Anti-HPA1a antibodies are the most frequent cause of FNAIT in Caucasians. Its pathogenesis is similar to hemolytic disease of the newborn (HDN) due to anti-RhD antibodies, but is characterized by platelet destruction and is more often observed in the first pregnancy. In 75 % of these women, alloimmunization by HPA-1a antigens, however, occurs at delivery, which enables development of antibody-mediated immune suppression to prevent maternal immunization. As for HDN, the recurrence rate of FNAIT is high. For advancing diagnostic efforts and treatment, it is thereby crucial to understand the pathogenesis of FNAIT, including cellular immunity involvement. This review presents the current knowledge on FNAIT. Also described is a program for HPA-1a screening in identifying HPA-1a negative pregnant women at risk of immunization. This program is now performed at the Institute of Hematology and Transfusion Medicine in cooperation with the Department of Obstetrics and Gynecology of the Medical Centre of Postgraduate Education in Warsaw as well as the UiT The Arctic University of Norway.

  3. Long-term complications of splenectomy in adult immune thrombocytopenia.

    Science.gov (United States)

    Thai, Lan-Huong; Mahévas, Matthieu; Roudot-Thoraval, Françoise; Limal, Nicolas; Languille, Laetitia; Dumas, Guillaume; Khellaf, Mehdi; Bierling, Philippe; Michel, Marc; Godeau, Bertrand

    2016-11-01

    The recent large decrease in splenectomy use for chronic immune thrombocytopenia (ITP) is partly due to still-unsolved questions about long-term safety. We performed the first single-center exposed/unexposed cohort study evaluating the long-term incidence of splenectomy complications in patients with primary ITP. Overall, 83 patients who underwent splenectomy more than 10 years ago (exposed) were matched with 83 nonsplenectomized patients (unexposed) on the date of ITP diagnosis ±5 years, age and gender. After a median follow-up of 192 months (range 0.5-528), 43 patients (52%) achieved overall response after splenectomy. Splenectomized patients experienced more venous thromboembolism (VTE) than controls (n = 13 vs n = 2, P = 0.005). On multivariate analysis, splenectomy was an independent risk factor of VTE (hazard ratio = 4.006, P = 0.032 [95% confidence interval: 1.13-14.21]). Splenectomized patients presented more severe infections on long-term follow-up: all required hospitalization, and 5/26 (19%) infections led to severe sepsis or septic shock and to death for 3 cases (none in controls). However, the incidence of malignancy was similar in both groups, as was cardiovascular risk, which appeared to be related more to ITP than splenectomy. Finally, splenectomy did not significantly decrease overall survival. Despite the risk of thrombosis and severe sepsis, splenectomy remains an effective and curative treatment for ITP.

  4. Drug utilization of biological drugs in the treatment of chronic Immune-Mediated Inflammatory Diseases (IMIDs: an observational study on Italian patients

    Directory of Open Access Journals (Sweden)

    Paolo Faccendini

    2017-09-01

    Full Text Available Drug utilization of biological drugs in the treatment of chronic Immune-Mediated Inflammatory Diseases (IMIDs: an observational study on Italian patientsObjectives:The aim of this analysis was to provide an estimate of drug utilization indicators (dose escalation and dose tapering related to biologic drugs in the chronic treatment of adult patients with Immune-Mediated Inflammatory Diseases (IMIDs.Methods:We conducted an observational retrospective cohort analysis using the Policlinico di Tor Vergata (PTV database. We considered all biologic drugs dispensed by the PTV hospital pharmacy between January 2010 and December 2015:abatacept, adalimumab, certolizumab, etanercept, golimumab, infliximab (originator and biosimilar, tocilizumab, and ustekinumab were included. Drug dose escalation and dose tapering were calculated and compared with their Defined Daily Dose (DDD.Results:A total of 1803 patients with IMID and biologic drug prescription were analyzed (male: 51.2%. The majority of patients were in the class 36-50 years (n = 612. The median follow-up was 33.8 months (IQR 14.43-56.20. Dermatology was the ward with the largest number of patients (n = 882; 48.9%, followed by rheumatology (n = 619; 34.3% and gastroenterology (n = 302; 16.8%. Dose escalation was observed in 406 patients (22.5%. Infliximab biosimilar (n = 51 was the biological drug with the highest dose escalation rate (86.3%, followed by infliximab originator (n = 28; 60.3% and ustekinumab (37.8%. Etanercept was the biological drug with the lowest dose escalation rate (7.4%, followed by golimumab (12.2% and adalimumab (13.8%. In 677 patients (37.5% a dose tapering was observed. Etanercept showed the highest rate of patients with dose tapering (41.6%, followed by adalimumab (33.6%.Conclusions:The results of this analysis show that dose modification is quite common in PTV clinical practice. Considering the strong focus on the pharmaceutical expenditure and the need of cost containment

  5. Sex bias in experimental immune-mediated, drug-induced liver injury in BALB/c mice: suggested roles for Tregs, estrogen, and IL-6.

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    Joonhee Cho

    Full Text Available Immune-mediated, drug-induced liver injury (DILI triggered by drug haptens is more prevalent in women than in men. However, mechanisms responsible for this sex bias are not clear. Immune regulation by CD4+CD25+FoxP3+ regulatory T-cells (Tregs and 17β-estradiol is crucial in the pathogenesis of sex bias in cancer and autoimmunity. Therefore, we investigated their role in a mouse model of immune-mediated DILI.To model DILI, we immunized BALB/c, BALB/cBy, IL-6-deficient, and castrated BALB/c mice with trifluoroacetyl chloride-haptenated liver proteins. We then measured degree of hepatitis, cytokines, antibodies, and Treg and splenocyte function.BALB/c females developed more severe hepatitis (p<0.01 and produced more pro-inflammatory hepatic cytokines and antibodies (p<0.05 than did males. Castrated males developed more severe hepatitis than did intact males (p<0.001 and females (p<0.05. Splenocytes cultured from female mice exhibited fewer Tregs (p<0.01 and higher IL-1β (p<0.01 and IL-6 (p<0.05 than did those from males. However, Treg function did not differ by sex, as evidenced by absence of sex bias in programmed death receptor-1 and responses to IL-6, anti-IL-10, anti-CD3, and anti-CD28. Diminished hepatitis in IL-6-deficient, anti-IL-6 receptor α-treated, ovariectomized, or male mice; undetectable IL-6 levels in splenocyte supernatants from ovariectomized and male mice; elevated splenic IL-6 and serum estrogen levels in castrated male mice, and IL-6 induction by 17β-estradiol in splenocytes from naïve female mice (p<0.05 suggested that 17β-estradiol may enhance sex bias through IL-6 induction, which subsequently discourages Treg survival. Treg transfer from naïve female mice to those with DILI reduced hepatitis severity and hepatic IL-6.17β-estradiol and IL-6 may act synergistically to promote sex bias in experimental DILI by reducing Tregs. Modulating Treg numbers may provide a therapeutic approach to DILI.

  6. PROSPECTIVE STUDY OF THROMBOCYTOPENIA IN PREGNANCY AND ITS EFFECT ON MATERNAL AND FOETAL OUTCOME

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    Usha Suresh

    2016-11-01

    Full Text Available BACKGROUND Thrombocytopenia is the second most common haematological finding in pregnancy after anaemia. The aim of the study is to study the various aetiological factors associated with thrombocytopenia and its management in pregnancy. MATERIALS AND METHODS It is a prospective study carried out in 160 cases, which were identified to have moderate-to-severe thrombocytopenia during over a period of 2 years. History taken regarding preeclampsia, ITP, drug usage, viral infection, thrombocytopenia in previous pregnancy. General, systemic and obstetric examination were done. RESULTS The highest incidence of thrombocytopenia was found in the age group of 21-25 years, i.e. 83 cases (51.8%. Out of total 160 cases, 90 (56.25% cases are multigravida while 61 (38.1% are primigravida. Out of total 160 cases, 128 i.e. 80% are unbooked while 32 i.e. 20% are booked. Of 68 cases delivered by LSCS, spinal anaesthesia was given in 45 cases, i.e. 66.1% general anaesthesia in 22 cases (32.3%, epidural was given in 1 case (1.47%. Gestational thrombocytopenia has highest aetiology of 21.25%, i.e. 34 cases. Severe preeclampsia were 30 cases (18.75%. Dengue, SLE and chronic liver disease are least with incidence of 1.25%, i.e. 2 cases each. Partial HELLP are 25 cases (15.6% and HELLP are 24 cases (15%. Severe preeclampsia with abruption 21 cases (13.1%. DIC are 9 (5.6%. Pancytopenia are 4 (2.5%. Platelet transfusions were required in 69 patients out of 160, i.e. in 43.1% of cases. All the cases of IUGR belonged to preeclampsia and associated disorders group. 26 out of 109 cases of preeclampsia were associated with IUGR. In preeclampsia and associated disorders group, 49 out of 109 cases were IUD, stillborn, nonviable. Chi-square test, p value is 0.0001, which is highly statistically significant, implying there is an association between IUD, stillborn and thrombocytopenia due to severe preeclampsia group when compared to other group including ITP, gestational

  7. Vancomycin-induced Immune Thrombocytopenia Proven by the Detection of Vancomycin-dependent Anti-platelet Antibody with Flow Cytometry

    OpenAIRE

    Yamanouchi, Jun; Hato, Takaaki; Shiraishi, Sanshiro; Takeuchi, Kazuto; Yakushijin, Yoshihiro; Yasukawa, Masaki

    2016-01-01

    Vancomycin-induced thrombocytopenia is a rare adverse reaction that may be overlooked because no specific diagnostic test is currently available. We herein report a patient with vancomycin-induced immune thrombocytopenia who was diagnosed by the detection of vancomycin-dependent anti-platelet antibody with flow cytometry. An IgG antibody in the patient's serum reacted with platelets only in the presence of vancomycin. Severe thrombocytopenia gave rise to life-threatening gastrointestinal blee...

  8. Extrapolation in the development of paediatric medicines: examples from approvals for biological treatments for paediatric chronic immune-mediated inflammatory diseases.

    Science.gov (United States)

    Stefanska, Anna M; Distlerová, Dorota; Musaus, Joachim; Olski, Thorsten M; Dunder, Kristina; Salmonson, Tomas; Mentzer, Dirk; Müller-Berghaus, Jan; Hemmings, Robert; Veselý, Richard

    2017-10-01

    The European Union (EU) Paediatric Regulation requires that all new medicinal products applying for a marketing authorisation (MA) in the EU provide a paediatric investigation plan (PIP) covering a clinical and non-clinical trial programme relating to the use in the paediatric population, unless a waiver applies. Conducting trials in children is challenging on many levels, including ethical and practical issues, which may affect the availability of the clinical evidence. In scientifically justified cases, extrapolation of data from other populations can be an option to gather evidence supporting the benefit-risk assessment of the medicinal product for paediatric use. The European Medicines Agency (EMA) is working on providing a framework for extrapolation that is scientifically valid, reliable and adequate to support MA of medicines for children. It is expected that the extrapolation framework together with therapeutic area guidelines and individual case studies will support future PIPs. Extrapolation has already been employed in several paediatric development programmes including biological treatment for immune-mediated diseases. This article reviews extrapolation strategies from MA applications for products for the treatment of juvenile idiopathic arthritis, paediatric psoriasis and paediatric inflammatory bowel disease. It also provides a summary of extrapolation advice expressed in relevant EMA guidelines and initiatives supporting the use of alternative approaches in paediatric medicine development. © Article author(s) (or their employer(s) unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  9. Insight into Genotype-Phenotype Associations through eQTL Mapping in Multiple Cell Types in Health and Immune-Mediated Disease.

    Directory of Open Access Journals (Sweden)

    James E Peters

    2016-03-01

    Full Text Available Genome-wide association studies (GWAS have transformed our understanding of the genetics of complex traits such as autoimmune diseases, but how risk variants contribute to pathogenesis remains largely unknown. Identifying genetic variants that affect gene expression (expression quantitative trait loci, or eQTLs is crucial to addressing this. eQTLs vary between tissues and following in vitro cellular activation, but have not been examined in the context of human inflammatory diseases. We performed eQTL mapping in five primary immune cell types from patients with active inflammatory bowel disease (n = 91, anti-neutrophil cytoplasmic antibody-associated vasculitis (n = 46 and healthy controls (n = 43, revealing eQTLs present only in the context of active inflammatory disease. Moreover, we show that following treatment a proportion of these eQTLs disappear. Through joint analysis of expression data from multiple cell types, we reveal that previous estimates of eQTL immune cell-type specificity are likely to have been exaggerated. Finally, by analysing gene expression data from multiple cell types, we find eQTLs not previously identified by database mining at 34 inflammatory bowel disease-associated loci. In summary, this parallel eQTL analysis in multiple leucocyte subsets from patients with active disease provides new insights into the genetic basis of immune-mediated diseases.

  10. Chinese Herbal Formula, Modified Danggui Buxue Tang, Attenuates Apoptosis of Hematopoietic Stem Cells in Immune-Mediated Aplastic Anemia Mouse Model

    Directory of Open Access Journals (Sweden)

    Jingwei Zhou

    2017-01-01

    Full Text Available A derivative formula, DGBX, which is composed of three herbs (Radix astragali, Radix Angelicae sinensis, and Coptis chinensis Franch, is derived from a famous Chinese herbal formula, Danggui Buxue Tang (DBT (Radix astragali and Radix Angelicae sinensis. We aimed to investigate the effects of DGBX on the regulation of the balance between proliferation and apoptosis of hematopoietic stem cells (HSCs due to the aberrant immune response in a mouse model of aplastic anemia (AA. Cyclosporine (CsA, an immunosuppressor, was used as the positive control. Our results indicated that DGBX could downregulate the production of IFNγ in bone marrow cells by interfering with the binding between SLAM and SAP and the expressions of Fyn and T-bet. This herbal formula can also inhibit the activation of Fas-mediated apoptosis, interferon regulatory factor-1-induced JAK/Stat, and eukaryotic initiation factor 2 signaling pathways and thereby induce proliferation and attenuate apoptosis of HSCs. In conclusion, DGBX can relieve the immune-mediated destruction of HSCs, repair hematopoietic failure, and recover the hematopoietic function of HSCs in hematogenesis. Therefore, DGBX can be used in traditional medicine against AA as a complementary and alternative immunosuppressive therapeutic formula.

  11. [Screening of Serum Markers in Primary Immune Thrombocytopenia].

    Science.gov (United States)

    Zhang, Yang; Bai, Ju; Zhang, Wang-Gang; He, Ai-Li

    2016-06-01

    To analyze the serum protein fingerprints of immune thrombocytopenia (ITP) patients and healthy controls by using weak cation exchange nanometer magnetic beads and MALDI-TOF-MAS technology, to identify the proteins with different expression, to establish the diagnostic model for ITP and to explore the pathogenesis of ITP. A total of 40 patients with ITP and 40 healthy controls were selected, the serum protein components were captured by using weak cation exchange nanaometer magnetic beads, the protein spectra of all specimens were detected by Autoflex II matrix assisted laser desorption/ionization time of flight mass spectrometry (MALDI- TOF-MS) and then the data were analyzed by CliprotoolsTM2.2 software, by which the distinct protein molecules were screened to set up ITP diagnostic model. To identify the established model, the sera of 20 ITP patients and 20 healthy controls were selected to make category and cross validations. The detection of Clinprot system and the analysis of CliprotoolsTM2.2 software showed that about 55 protein peaks were detected with the range of 700 Da to 10 000 Da of molecular weight in the protein spectrum of serum speciments from 40 ITP patients and 40 healthy controls. Compared with healthy controls, 19 protein expression peaks with statistically significant difference were found in ITP patients (P Neural Network Algorithm (SNN) was established through 10 MS peaks with strongest capability in ITP group and control group automatically distinguished by software, and it is expected that the sensitivity of model group reached to 100%, and the specificity to 100%. The category validation showed that this diagnostic model correctly identificed all 20 ITP patients and 20 healthy controls, and in cross validation, the model sensitivity was 100% and the specificity was 100%. The ITP SNN model ertablished by using ChinProt System with high flax and good repetition is composed of 10 protein peaks with significant difference, this model can

  12. Platelet reactive alloantibodies responsible for immune thrombocytopenia in Malay population

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    Mohd I. Armawai

    2014-10-01

    Full Text Available Background: Alloantibodies against human platelet alloantigens (HPAs are responsible for the development of platelet transfusion refractoriness (PTR in patients receiving random platelets and bleeding disorder in babies with fetal neonatal alloimmune thrombocytopenia (FNAIT. Recently, our results based on the analysis of the allelic distribution of HPAs indicated that immunization may occur among Malay. In this study, we sought to analyze the frequencies of platelet reactive alloantibodies responsible for FNAIT and PTR in Malaysia.Methods: Sera from suspected FNAIT (n = 295 and PTR (n = 74 were collected in five years period (2008-2013 and tested for the presence of platelet reactive antibodies by the use of antigen capture assay.Results: In 5/74 (5.41% platelet specific antibodies against HPA-2b (n = 1, HPA-5a (n = 1, HPA-5b (n = 1, HPA-15b (n = 2 could be identified in our PTR cohort. In FNAIT cohort, platelet specific alloantibodies could be detected in 18 sera (6.10% consisting anti-HPA-1a (n = 1, anti-HPA-3a (n = 3, anti-HPA-5a (n = 6, anti-HPA-5b (n = 6, anti-HPA-15a (n = 1, and anti-HPA-15b (n = 1.Conclusion: Our study indicates that anti-HPA-3, -HPA-5 and -HPA-15 antibodies seems to be the most platelet specific antibodies involved in FNAIT and PTR cases in Malaysian population. Since similar HPA allelic distribution among Malaysian and Indonesian populations have been observed, immunization against these three HPA systems are expected to be the most potential risk of alloimmune mediated platelet disorders in Indonesia.

  13. Fetal and neonatal alloimmune thrombocytopenia: predictive factors of intracranial hemorrhage.

    Science.gov (United States)

    Delbos, Florent; Bertrand, Gérald; Croisille, Laure; Ansart-Pirenne, Hélène; Bierling, Philippe; Kaplan, Cécile

    2016-01-01

    In Caucasians, fetal/neonatal alloimmune thrombocytopenia (FNAIT) is most frequently caused by maternal alloimmunization against the human platelet antigen HPA-1a. The most serious complication of severe FNAIT is intracranial hemorrhage (ICH). ICH mainly occurs in utero; therefore, there is a need to identify noninvasive predictive factors of ICH to facilitate early identification of this condition and to determine response to maternal therapy. We studied gynecologic and immunogenetic variables of severe cases of anti-HPA-1a FNAIT within three groups: Group I, FNAIT without ICH; Group II, FNAIT with ICH; and Group III, suspected FNAIT cases without detectable maternal anti-HPA-1a alloantibodies. ICH was associated with a poor outcome because it led to death in 59% of cases. Multigravida (two or more pregnancies) was overrepresented in Group II, consistent with the high concentrations of maternal HPA-1a alloantibody and the frequent detection of a strong newborn-specific HLA class I antibody response at delivery. The proportion of HLA-DRB4*01:01P (*01:01 or *01:03) women was similar in Groups I and II, but this allele was overrepresented in Group III, in which FNAIT was less severe than in the other two groups. Finally, antenatal intravenous immunoglobulin therapy tended to be more effective in HLA-DRB3*01:01(+)/HLA-DRB4*01:01P(+) women than for HLA-DRB3*01:01(+)/HLA-DRB4*01:01P(-) women. The number of gestations is a predictive factor of ICH in anti-HPA-1a-alloimmunized women. Maternal immunogenetic variables should be investigated in the context of maternal immunization and may predict response to maternal therapy in subsequent pregnancies. © 2015 AABB.

  14. Stent thrombosis caused by metal allergy complicated by protein S deficiency and heparin-induced thrombocytopenia: a case report and review of the literature.

    Science.gov (United States)

    Konishi, Takao; Yamamoto, Tadashi; Funayama, Naohiro; Yamaguchi, Beni; Sakurai, Seiichiro; Nishihara, Hiroshi; Yamazaki, Koko; Kashiwagi, Yusuke; Sasa, Yasuki; Gima, Mitsuru; Tanaka, Hideichi; Hotta, Daisuke; Kikuchi, Kenjiro

    2015-01-01

    A 43-year-old woman recipient of a bare metal coronary stent during an acute anterior myocardial infarction was repeatedly hospitalized with recurrent stent thrombosis (ST) over the following 3 years. Emergent coronary angiography showed a thrombus in the in-stent segment of the proximal left anterior descending artery. We repeatedly aspirated the thrombus, which immediately reformed multiple times. The discontinuation of heparin and administration of thrombolytics and argatroban, followed by repeated balloon dilatations, ended the formation of new thrombi. The patient was found to be allergic to nickel, protein S deficient and carrier of heparin-induced thrombocytopenia antibody. We discuss this case in the context of a) literature pertaining to acute coronary syndromes in the young, and b) the detailed investigations needed to identify thrombotic risk factors. Steroids may be effective to prevent recurrent ST caused by stent allergy.

  15. Congenital thrombocytopenia with nephritis: The first case of MYH9 related disorder in Serbia

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    Kuzmanović Miloš

    2014-01-01

    Full Text Available Introduction. The group of autosomal dominant disorders - Epstein syndrome, Sebastian syndrome, Fechthner syndrome and May-Hegglin anomaly - are characterised by thrombocytopenia with giant platelets, inclusion bodies in granulocytes and variable levels of deafness, disturbances of vision and renal function impairment. A common genetic background of these disorders are mutations in MYH9 gene, coding for the nonmuscle myosin heavy chain IIA. Differential diagnosis is important for the adequate treatment strategy. The aim of this case report was to present a patient with MYH9 disorder in Serbia. Case report. A 16-year-old boy was referred to our hospital with the diagnosis of resistant immune thrombocytopenia for splenectomy. Thrombocytopenia was incidentally discovered at the age of five. The treatment with corticosteroids on several occasions was unsuccessful. Although the platelet count was below 10 × 109/L, there were no bleeding symptoms. Besides thrombocytopenia with giant platelets, on admission the patient also suffered sensorineuronal hearing loss and proteinuria. The diagnosis was confirmed with immunofluorescence and genetic analyses. Conclusion. Early recognition of MYH9-related diseases is essential to avoid unnecessary and potentially harmful treatments for misdiagnosed immune thrombocytopenia, and also for timely and proper therapy in attempt to delay end-stage renal failure and improve quality of life. [Projekat Ministartsva nauke Republike Srbije, br. 175056 i br. 15079

  16. Hepatitis C virus-associated thrombocytopenia in pregnancy: impact upon multidisciplinary care provision.

    LENUS (Irish Health Repository)

    Monteith, Cathy

    2014-01-01

    Abstract Objective: Recent studies have implicated hepatitis C virus (HCV) in the pathogenesis of immune thrombocytopenia. In pregnancy-associated immune thrombocytopenia, multidisciplinary management is required due to a potential for bleeding complications. We performed a retrospective review of HCV-infected pregnant women and age-matched controls who were not infected with HCV. Methods: One hundred and six women with a HCV viral load were identified from 2009 to 2011. Results: Thrombocytopenia was identified in 10.3% of HCV-infected pregnant women and 1.6% of age-matched controls (P<0.001). Mean platelet count during pregnancy was 120±23×109\\/L in HCV-infected women and at delivery was significantly lower in HCV-infected women than in controls (P=0.01). Despite the significant difference in platelet counts, there was no significant difference in estimated blood loss (EBL) at delivery. Regional anaesthesia was performed in 73% of thrombocytopenic HCV-infected women and no complications were recorded. There were no fetal bleeding complications. Conclusion: In the first study to date to investigate the impact of HCV on maternal platelet count we demonstrated a significantly higher frequency of thrombocytopenia and a significantly lower platelet count in HCV-infected pregnant women compared with controls. Interestingly, thrombocytopenia had no detectable impact on EBL at delivery.

  17. The role of eltrombopag in the management of hepatitis C virus-related thrombocytopenia

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    Danish FA

    2013-03-01

    Full Text Available Fazal-i-Akbar Danish,1 Saeeda Yasmin21James Paget University Hospital, Great Yarmouth, Norfolk, United Kingdom; 2Shifa International Hospital, Islamabad, PakistanAbstract: Eltrombopag is a 2nd generation thrombopoietin-receptor agonist. It binds with the thrombopoietin-receptors found on the surfaces of the megakaryocytes & increases platelet production. Many recent studies have suggested a potential role for this novel agent in the treatment of thrombocytopenia associated with hepatitis-C infection. Studies have shown that adjunct treatment with Eltrombopag can help avoid dose reductions/withdrawals of pegylated interferon secondary to thrombocytopenia. It may also have a role in priming up platelet levels to help initiate antiviral therapy. Similarly, chronic liver disease patients with thrombocytopenia who need to undergo an invasive procedure may be potential candidates for short two-week courses of eltrombopag in the periprocedural period to help reduce the risk of bleeding. Besides the price (deemed very expensive and probably not cost-effective, there are some legitimate concerns about the safety profile of this novel agent (most importantly, portal vein thrombosis, bone marrow fibrosis and hepatotoxicity. In this article, the potential role of eltrombopag in the context of hepatitis C virus (HCV-related thrombocytopenia is reviewed. To write this article, a MEDLINE search was conducted (1990 to November 2012 using the search terms “eltrombopag,” “HCV,” and “thrombocytopenia.”Keywords: liver disease, chronic immune thrombocytopenic purpura, thrombopoietin-receptor agonist, romiplostim

  18. Antiphospholipid Syndrome in a Pregnant Female Presenting with Severe Thrombocytopenia and Bleeding

    Directory of Open Access Journals (Sweden)

    Kunal Mahajan

    2015-01-01

    Full Text Available The antiphospholipid antibody syndrome (APS is defined by the persistent presence of antiphospholipid antibodies in patients with recurrent venous or arterial thromboembolism or pregnancy morbidity. Antithrombotic therapy is the mainstay of treatment given the high risk of recurrent thromboembolism that characterizes this condition. Despite the prothrombotic nature of APS, thrombocytopenia is present in a proportion of patients, which can complicate management and limit the use of antithrombotic therapy. The mechanism of APS-associated thrombocytopenia is multifactorial and its relation to thrombotic risk is poorly characterized. The presence of thrombocytopenia does not appear to reduce thrombotic risk in patients with APS, who can develop thromboembolic complications necessitating antithrombotic treatment. In these cases, treatment of the thrombocytopenia may be necessary to facilitate administration of antithrombotic agents. We present such a pregnant lady with history of recurrent pregnancy losses who presented with severe thrombocytopenia and bleeding manifestations, who was subsequently diagnosed to have antiphospholipid antibody syndrome. She was initially managed with steroids and when her platelet counts improved, antithrombotic therapy was started. She delivered an uneventful and successful pregnancy outcome without any complications during follow-up.

  19. Mechanisms and etiologies of thrombocytopenia in the intensive care unit: impact of extensive investigations.

    Science.gov (United States)

    Antier, Nadiejda; Quenot, Jean-Pierre; Doise, Jean-Marc; Noel, Robin; Demaistre, Emmanuel; Devilliers, Hervé

    2014-01-01

    Thrombocytopenia is common in the intensive care unit. Potential mechanisms and etiologies behind this phenomenon are multiple and often entangled. We assessed the effect of a systematic approach, using routinely available tests, on the proportion of patients in whom the mechanism (primary objective) and etiology (secondary objective) of thrombocytopenia in a mixed intensive care unit (ICU) could be identified. Before-and-after study of all patients with thrombocytopenia was used. 'Before' group had no intervention. New standard operating procedures for thrombocytopenia management were introduced. In the 'After' group, bone marrow aspiration; determination of fibrinogen dosage, prothrombin time, factor V, D-dimers; assay of fibrin monomers, ferritin, triglycerides, lactic acid dehydrogenase, aspartate transaminase, alanine aminotransferase, vitamin B12, folates, reticulocytes, haptoglobin, and bilirubin were performed. In the Before group (n = 20), the mechanism (central, peripheral, or mixed) was identified in 10 % versus 83% in After group (n = 23) (p < 0.001) (48% peripheral, 35% mixed). Before intervention, ≥1 etiology was identified in 15% versus 95.7% in the After group (p < 0.001). Systematic and extensive investigation using routine tests highlights the mechanisms and etiology of thrombocytopenia in most cases.

  20. Thrombotic microangiopathies and acute kidney injury induced by ...

    African Journals Online (AJOL)

    Thrombotic microangiopathy (TMA) is a rare, but potentially lethal condition requiring rapid recognition, diagnosis and initiation of therapy. Here, we present two cases of women with hemolytic anemia, thrombocytopenia and acute kidney injury shortly after surgical termination of pregnancy. Histological examination of their ...

  1. Are patients with erythema migrans who have leukopenia and/or thrombocytopenia coinfected with Anaplasma phagocytophilum or tick-borne encephalitis virus?

    Directory of Open Access Journals (Sweden)

    Franc Strle

    Full Text Available Lyme borreliosis (LB, tick-borne encephalitis (TBE and human granulocytic anaplasmosis (HGA are endemic in central part of Slovenia. We tested the hypothesis that patients with erythema migrans (EM from this region, who have leukopenia and/or thrombocytopenia (typical findings in HGA and in the initial phase of TBE but not in patients with LB are coinfected with Anaplasma phagocytophilum and/or with TBE virus, i.e. that cytopenia is a result of concomitant HGA or the initial phase of TBE. Comparison of clinical and laboratory findings for 67 patients with EM who disclosed leukopenia/thrombocytopenia with the corresponding results in sex- and age-matched patients with EM and normal blood cell counts revealed no differences. In addition, patients with typical EM and leukopenia and/or thrombocytopenia tested negative for the presence of IgM and IgG antibodies to TBE virus by ELISA as well as for the presence of specific IgG antibodies to A. phagocytophilum antigens by IFA in acute and convalescent serum samples. Thus, none of 67 patients (95% CI: 0 to 5.3% with typical EM (the presence of this skin lesion attests for early Lyme borreliosis and is the evidence for a recent tick bite was found to be coinfected with A. phagocytophilum or had a recent primary infection with TBE virus. The findings in the present study indicate that in Slovenia, and probably in other European countries endemic for LB, TBE and HGA, patients with early LB are rarely coinfected with the other tick-transmitted agents.

  2. Are patients with erythema migrans who have leukopenia and/or thrombocytopenia coinfected with Anaplasma phagocytophilum or tick-borne encephalitis virus?

    Science.gov (United States)

    Strle, Franc; Bogovič, Petra; Cimperman, Jože; Maraspin, Vera; Ogrinc, Katarina; Rojko, Tereza; Stupica, Daša; Lusa, Lara; Avšič-Županc, Tatjana; Smrdel, Katja Strašek; Jelovšek, Mateja; Lotrič-Furlan, Stanka

    2014-01-01

    Lyme borreliosis (LB), tick-borne encephalitis (TBE) and human granulocytic anaplasmosis (HGA) are endemic in central part of Slovenia. We tested the hypothesis that patients with erythema migrans (EM) from this region, who have leukopenia and/or thrombocytopenia (typical findings in HGA and in the initial phase of TBE but not in patients with LB) are coinfected with Anaplasma phagocytophilum and/or with TBE virus, i.e. that cytopenia is a result of concomitant HGA or the initial phase of TBE. Comparison of clinical and laboratory findings for 67 patients with EM who disclosed leukopenia/thrombocytopenia with the corresponding results in sex- and age-matched patients with EM and normal blood cell counts revealed no differences. In addition, patients with typical EM and leukopenia and/or thrombocytopenia tested negative for the presence of IgM and IgG antibodies to TBE virus by ELISA as well as for the presence of specific IgG antibodies to A. phagocytophilum antigens by IFA in acute and convalescent serum samples. Thus, none of 67 patients (95% CI: 0 to 5.3%) with typical EM (the presence of this skin lesion attests for early Lyme borreliosis and is the evidence for a recent tick bite) was found to be coinfected with A. phagocytophilum or had a recent primary infection with TBE virus. The findings in the present study indicate that in Slovenia, and probably in other European countries endemic for LB, TBE and HGA, patients with early LB are rarely coinfected with the other tick-transmitted agents.

  3. Steroid-induced femoral head osteonecrosis in immune thrombocytopenia treatment with osteochondral autograft transplantation.

    Science.gov (United States)

    Fotopoulos, Vasileios Ch; Mouzopoulos, George; Floros, Themistoklis; Tzurbakis, Matthaios

    2015-09-01

    Osteonecrosis of the femoral head is a devastating complication of steroid administration and has rarely been observed in the treatment of immune thrombocytopenia. The treatment of osteochondral defects in advanced stages of avascular necrosis (AVN), characterized by collapse of the subchondral bone, remains an unsolved burden in orthopedic surgery. In this report, we present a case of a 19-year-old female that was admitted in the Emergency Department with walking disability and painful hip joint movement due to steroid-induced femoral head osteonecrosis. Two years before she was diagnosed with immune thrombocytopenia, for which she received pulse steroid therapy with high dose of dexamethasone and underwent a splenectomy. This case report is the first to describe the use of osteochondral autograft transplantation as a treatment of steroid-induced AVN of the femoral head due to immune thrombocytopenia at the age of 19 years with very good clinical and radiological results 3 years postoperatively.

  4. Acute pancreatitis : a newly recognised potential complication of canine babesiosis

    Directory of Open Access Journals (Sweden)

    A.J. Möhr

    2000-07-01

    Full Text Available This retrospective study describes 4 cases of canine babesiosis with histologically confirmed acute pancreatitis. In addition, 16 dogs with babesiosis are reported with serum amylase (>3500 U/l and/or lipase (>650 U/l activity elevations of a magnitude that would support a diagnosis of probable acute pancreatitis, although extra-pancreatic sources of the enzymes could not be excluded in these cases. Median time of pancreatitis diagnosis was 2.5 days post-admission, with primarily young (median age 3 years, sexually intact dogs affected. The development of pancreatitis was unrelated to the degree of anaemia at time of admission. In addition to pancreatitis, 80 % of cases suffered from other babesial complications, namely icterus (13, acute respiratory distress syndrome (6, immune-mediated haemolytic anaemia (6, renal failure (3, haemoconcentration (2 and cerebral syndrome (2. Acute respiratory distress syndrome, renal failure and cerebral syndrome were associated with a poor prognosis, with 4 of the 5 dogs included in the overall 26 % mortality rate having at least 1 of these complications. Haemolytic anaemia with ischaemia-reperfusion injury to the pancreas is proposed as a possible primary pathophysiological mechanism in babesial pancreatitis. Hypotensive shock, immune-mediated haemolytic anaemia, haemoconcentration and possibly altered lipid metabolism in babesiosis may also be involved. The previously postulated pro-inflammatory cytokine milieu of complicated babesiosis may underlie the progression, if not the primary initiation, of pancreatic pathology. Acute pancreatitis may represent the previously reported 'gut' form of babesiosis.

  5. Role of the mitochondria in immune-mediated apoptotic death of the human pancreatic β cell line βLox5.

    Directory of Open Access Journals (Sweden)

    Yaíma L Lightfoot

    Full Text Available Mitochondria are indispensable in the life and death of many types of eukaryotic cells. In pancreatic beta cells, mitochondria play an essential role in the secretion of insulin, a hormone that regulates blood glucose levels. Unregulated blood glucose is a hallmark symptom of diabetes. The onset of Type 1 diabetes is preceded by autoimmune-mediated destruction of beta cells. However, the exact role of mitochondria has not been assessed in beta cell death. In this study, we examine the role of mitochondria in both Fas- and proinflammatory cytokine-mediated destruction of the human beta cell line, βLox5. IFNγ primed βLox5 cells for apoptosis by elevating cell surface Fas. Consequently, βLox5 cells were killed by caspase-dependent apoptosis by agonistic activation of Fas, but only after priming with IFNγ. This beta cell line undergoes both apoptotic and necrotic cell death after incubation with the combination of the proinflammatory cytokines IFNγ and TNFα. Additionally, both caspase-dependent and -independent mechanisms that require proper mitochondrial function are involved. Mitochondrial contributions to βLox5 cell death were analyzed using mitochondrial DNA (mtDNA depleted βLox5 cells, or βLox5 ρ(0 cells. βLox5 ρ(0 cells are not sensitive to IFNγ and TNFα killing, indicating a direct role for the mitochondria in cytokine-induced cell death of the parental cell line. However, βLox5 ρ(0 cells are susceptible to Fas killing, implicating caspase-dependent extrinsic apoptotic death is the mechanism by which these human beta cells die after Fas ligation. These data support the hypothesis that immune mediators kill βLox5 cells by both mitochondrial-dependent intrinsic and caspase-dependent extrinsic pathways.

  6. Ponesimod, a selective S1P1 receptor modulator: a potential treatment for multiple sclerosis and other immune-mediated diseases

    Science.gov (United States)

    D’Ambrosio, Daniele; Freedman, Mark S.; Prinz, Joerg

    2016-01-01

    The first oral treatment for relapsing multiple sclerosis, the nonselective sphingosine-1-phosphate receptor (S1PR) modulator fingolimod, led to identification of a pivotal role of sphingosine-1-phosphate and one of its five known receptors, S1P1R, in regulation of lymphocyte trafficking in multiple sclerosis. Modulation of S1P3R, initially thought to cause some of fingolimod’s side effects, prompted the search for novel compounds with high selectivity for S1P1R. Ponesimod is an orally active, selective S1P1R modulator that causes dose-dependent sequestration of lymphocytes in lymphoid organs. In contrast to the long half-life/slow elimination of fingolimod, ponesimod is eliminated within 1 week of discontinuation and its pharmacological effects are rapidly reversible. Clinical data in multiple sclerosis have shown a dose-dependent therapeutic effect of ponesimod and defined 20 mg as a daily dose with desired efficacy, and acceptable safety and tolerability. Phase II clinical data have also shown therapeutic efficacy of ponesimod in psoriasis. These findings have increased our understanding of psoriasis pathogenesis and suggest clinical utility of S1P1R modulation for treatment of various immune-mediated disorders. A gradual dose titration regimen was found to minimize the cardiac effects associated with initiation of ponesimod treatment. Selectivity for S1P1R, rapid onset and reversibility of pharmacological effects, and an optimized titration regimen differentiate ponesimod from fingolimod, and may lead to better safety and tolerability. Ponesimod is currently in phase III clinical development to assess efficacy and safety in relapsing multiple sclerosis. A phase II study is also ongoing to investigate the potential utility of ponesimod in chronic graft versus host disease. PMID:26770667

  7. Differential profiles of immune mediators and in vitro HIV infectivity between endocervical and vaginal secretions from women with Chlamydia trachomatis infection: a pilot study.

    Science.gov (United States)

    Sperling, Rhoda; Kraus, Thomas A; Ding, Jian; Veretennikova, Alina; Lorde-Rollins, Elizabeth; Singh, Tricia; Lo, Yungtai; Quayle, Alison J; Chang, Theresa L

    2013-09-01

    Chlamydia trachomatis infection is one of the most prevalent bacterial STIs in the USA and worldwide, and women with C. trachomatis infection are at increased risk of acquiring HIV. Because immune activation at the genital mucosa facilitates HIV/SIV infection, C. trachomatis-mediated cytokine induction may contribute to increased HIV transmission in asymptomatic women. To begin to elucidate the mechanisms, we longitudinally analyzed profiles of innate immune factors and HIV infectivity in genital secretions from anatomically specific sites in asymptomatic women during C. trachomatis infection and post-antibiotic treatment. We found higher levels of cytokines and chemokines in endocervical secretions than vaginal secretions. Compared with the convalescent state, G-CSF, IL-1α, and RANTES were elevated in endocervical secretions, IFN-γ and TNF-α were elevated in vaginal secretions, and IFNγ, IL-1β, and MIP1-α were elevated in cervicolavage fluid (CVL), before adjustment of multiple comparisons. Elevated endocervical levels of IP-10 and MCP-1 were associated with the use of hormonal contraception in infected women after successful treatment, suggesting the role of hormonal contraception in inflammation independent of STIs. Importantly, soluble factors found in endocervical secretions during infection enhanced HIV infectivity while no difference in HIV infectivity was found with vaginal secretions or CVL during infection or at convalescence. Taken together, the profiles of immune mediators and in vitro HIV infectivity indicate that the endocervical and vaginal mucosa are immunologically distinct. Our results underscore the importance of considering anatomical site and local sampling methodology when measuring mucosal responses, particularly in the presence of C. trachomatis infection. Copyright © 2013 The Authors. Published by Elsevier Ireland Ltd.. All rights reserved.

  8. Spontaneous, Immune-Mediated Gastric Inflammation in SAMP1/YitFc Mice, a Model of Crohn’s-Like Gastritis

    Science.gov (United States)

    Reuter, Brian K.; Pastorelli, Luca; Brogi, Marco; Garg, Rekha R.; McBride, James A.; Rowlett, Robert M.; Arrieta, Marie C.; Wang, Xiao-Ming; Keller, Erik J.; Feldman, Sanford H.; Mize, James R.; Cominelli, Fabio; Meddings, Jonathan B.; Pizarro, Theresa T.

    2011-01-01

    Background & Aims Crohn’s disease (CD) can develop in any region of the gastrointestinal tract, including the stomach. The etiology and pathogenesis of Crohn’s gastritis are poorly understood, treatment approaches are limited, and there are not many suitable animal models for study. We characterized the features and mechanisms of chronic gastritis in SAMP1/YitFc (SAMP) mice, a spontaneous model of CD-like ileitis, along with possible therapeutic approaches. Methods Stomachs from specific pathogen-free and germ-free SAMP and AKR mice (controls) were evaluated histologically; the presence of Helicobacter spp. was tested in fecal pellets by PCR analysis. In vivo gastric permeability was quantified by fractional excretion of sucrose and epithelial tight junction protein expression was measured by quantitative reverse transcription PCR analysis. The effects of a proton pump inhibitor (PPI) or corticosteroids were measured and the ability of pathogenic immune cells to mediate gastritis was assessed in adoptive transfer experiments. Results SAMP mice developed Helicobacter-negative gastritis, characterized by aggregates of mononuclear cells, diffuse accumulation of neutrophils, and disruption of epithelial architecture; SAMP mice also had increased in gastric permeability compared with controls, without alterations in expression of tight junction proteins. The gastritis and associated permeability defect observed in SAMP mice were independent of bacterial colonization and reduced by administration of corticosteroids but not a PPI. CD4+ T cells isolated from draining mesenteric lymph nodes of SAMP mice were sufficient to induce gastritis in recipient SCID mice. Conclusions In SAMP mice, gastritis develops spontaneously and has many features of CD-like ileitis. These mice are a useful model to study Helicobacter-negative, immune-mediated Crohn’s gastritis. PMID:21704001

  9. Gluten-free diet does not influence the occurrence and the Th1/Th17-Th2 nature of immune-mediated diseases in patients with coeliac disease.

    Science.gov (United States)

    Imperatore, Nicola; Rispo, Antonio; Capone, Pietro; Donetto, Sara; De Palma, Giovanni Domenico; Gerbino, Nicolò; Rea, Matilde; Caporaso, Nicola; Tortora, Raffaella

    2016-07-01

    Coeliac disease (CD) is the most common Th1-mediated enteropathy, frequently associated with other immune-mediated disorders (IMD). To evaluate: (1) the prevalence of IMD at the time of and after CD diagnosis; (2) a possible change in immune response to gluten free diet (GFD); (3) the potential role of GFD in reducing and/or preventing IMD in CD. Prospective study including all consecutive adult CD patients who underwent investigations for Th1-Th17/Th2-IMD at the time of CD diagnosis and after a 5-year follow-up period. 1255 CD were enrolled. Of these, 257 patients (20.5%) showed IMD at the time of CD diagnosis, with 58.4% presenting a Th1/Th17-IMD. After a 5-year follow-up period, 682 patients (54.3%) showed new IMD despite GFD. Of these, 57.3% presented a Th1/Th17-IMD and 42.7% a Th2-IMD (p=0.8). When compared the prevalence of each type of IMD before and after CD diagnosis, we did not identify any significant "switch" from Th1/Th17- to Th2-IMD or vice versa. The number of patients with Th1/Th17- and/or Th2-IMD increased during the GFD period (20.5% vs 54.3%; p<0.01; OR 1.9). The prevalence of IMD at the time of CD diagnosis is high and it seems to increase in the follow-up period despite GFD. Copyright © 2016 Editrice Gastroenterologica Italiana S.r.l. Published by Elsevier Ltd. All rights reserved.

  10. The WxxxE effector EspT triggers expression of immune mediators in an Erk/JNK and NF-κB-dependent manner.

    Science.gov (United States)

    Raymond, Benoit; Crepin, Valerie F; Collins, James W; Frankel, Gad

    2011-12-01

    Enteropathogenic Escherichia coli (EPEC), enterohaemorrhagic E. coli (EHEC) and Citrobacter rodentium colonize their respective hosts while forming attaching and effacing lesions. Their infection strategy relies on translocation of a battery of type III secretion system effectors, including Map, EspM and EspT, which belong to the WxxxE/SopE family of guanine nucleotide exchange factors. Using the C. rodentium mouse model we found that EspT triggers expression of KC and TNFα in vivo. Indeed, a growing body of evidence suggests that, in addition to subversion of actin dynamics, the SopE and the WxxxE effectors activate signalling pathways involved in immune responses. In this study we found that EspT induces expression of the pro-inflammatory mediators cyclooxygenase-2 (COX-2) an enzyme involved in production of prostaglandin E(2) (PGE2), interleukin (Il)-8 and Il-1β in U937 human macrophages by activating the nuclear factor kappa-B (NF-κB), the extracellular signal-regulated kinases 1 and 2 (Erk1/2) and c-Jun N-terminal kinase (JNK) pathways. Since EspT modulates the activation of Cdc42 and Rac1, which mediates bacterial invasion into epithelial cells, we investigated the involvement of these Rho GTPases and bacterial invasion on pro-inflammatory responses and found that (i) Rac1, but not Cdc42, is involved in EspT-induced Il-8 and Il-1β secretion and (ii) cytochalasin D inhibits EspT-induced EPEC invasion into U937 but not Il-8 or Il-1β secretion. These results suggest that while EPEC translocates a number of effectors (i.e. NleC, NleD, NleE, NleH) that inhibit inflammation, a subset of strains, which encode EspT, employ an infection strategy that also involves upregulation of immune mediators. © 2011 Blackwell Publishing Ltd.

  11. An Evaluation of Twenty Years of EU Framework Programme-funded Immune-mediated Inflammatory Translational Research in Non-human Primates

    Directory of Open Access Journals (Sweden)

    Krista Geraldine Haanstra

    2016-11-01

    Full Text Available Ageing western societies are facing an increasing prevalence of chronic inflammatory and degenerative diseases for which often no effective treatments exist, resulting in increasing health care expenditure. Despite high investments in drug development, the number of promising new drug candidates decreases. We propose that preclinical research in non-human primate can help to bridge the gap between drug discovery and drug prescription.Translational research covers various stages of drug development of which pre-clinical efficacy tests in valid animal models is usually the last stage. Pre-clinical research in non-human primates may be essential in the evaluation of new drugs or therapies when a relevant rodent model is not available. Non-human primate models for life-threatening or severely debilitating diseases in humans are available at the Biomedical Primate Research Centre (BPRC. These have been instrumental in translational research for several decades.In order to stimulate European health research and innovation from bench to bedside, the European Commission (EC has invested heavily in access to non-human primate research for more than 20 years. BPRC has hosted European users in a series of transnational access programs covering a wide range of research areas with the common theme being immune-mediated inflammatory disorders. We present an overview of the results and give an account of the studies performed as part of European Union Framework Programme (EU FP-funded translational non-human primate research performed at the BPRC. The data illustrate value of translational non-human primate research for the development of new therapies and emphasize the importance of EU FP funding

  12. Biosimilars in immune-mediated inflammatory diseases: initial lessons from the first approved biosimilar anti-tumour necrosis factor monoclonal antibody.

    Science.gov (United States)

    Isaacs, J D; Cutolo, M; Keystone, E C; Park, W; Braun, J

    2016-01-01

    The introduction of targeted biological therapies has revolutionised the management of immune-mediated inflammatory diseases (IMIDs) such as rheumatoid arthritis, ankylosing spondylitis, psoriasis and inflammatory bowel disease. Following treatment with these therapies, many patients experience significant improvements in different aspects of their disease, including symptoms, work productivity and other outcomes relevant for individuals and society. However, due to the complexity of biological drug development and manufacturing processes, the costs of these therapies are relatively high. Indeed, the financial burden on healthcare systems due to biological therapies is considerable and lack of patient access to effective treatment remains a concern in many parts of the world. As many reference biological therapies have now reached or are near to patent expiry, a number of 'biosimilar' drugs have been developed for use in various clinical settings, and some of these drugs are already in use in several countries. While the potential pharmacoeconomic benefits of cost-effective biosimilars seem clear, several issues have been raised regarding, for example, the definition of biosimilarity and the validity of indication extrapolation, as well as the 'switchability' and relative immunogenicity of biosimilars and their reference drugs. In this review, these issues will be discussed with reference to CT-P13, a biosimilar of the anti-tumour necrosis factor monoclonal antibody infliximab, which is approved in Europe and elsewhere for the treatment of various IMIDs. Other important issues, including those related to data collection during nonclinical and clinical development of biosimilars, are also discussed. © 2015 The Association for the Publication of the Journal of Internal Medicine.

  13. [A case of immune-mediated encephalopathy showing refractory epilepsy and extensive brain MRI lesions associated with anti-glutamic acid decarboxylase antibody].

    Science.gov (United States)

    Kobayakawa, Yuko; Tateishi, Takahisa; Kawamura, Nobutoshi; Doi, Hikaru; Ohyagi, Yasumasa; Kira, Jun-ichi

    2010-02-01

    We reported a patient with immune-mediated encephalopathy showing refractory epilepsy and multiple brain lesions on MRI. The patient had high titers of anti-glutamic acid decarboxylase (GAD) antibody in sera and cerebrospinal fluid (CSF). A 36-year-old previously healthy woman was admitted to our hospital with onset of sudden generalized seizure that then persisted for one month. She had repeated epileptic attacks accompanied with loss of consciousness, and was refractory to valproic acid, zonisamide (200 mg/day) and phenobarbital (200 mg/day). Brain MRI showed multiple hyperintense lesions in predominantly bilateral frontal lobes, parietal lobes, occipital lobes and cingulate cortices. EEG showed epileptic activities (frequent sharp waves) in bilateral frontal regions. After admission, attacks disappeared through the administration of clonazepam (1.5 mg/day), though the patient remained slightly disoriented. As titers of anti-GAD antibody in sera and CSF were extremely high, we implemented plasma exchanges. After treatment, titers of anti-GAD antibody in sera and CSF decreased. The patient completely recovered to an alert state and the abnormal MRI lesions almost disappeared. Since GAD catalyzes production of gamma-aminobutyric acid (GABA), it is proposed that anti-GAD antibodies reduce synthesis of GABA or interferes with exocytosis of GABA in the nervous system. Anti-GAD antibodies are detected in some rare neurological disorders such as stiff-person syndrome. Recently, anti-GAD antibodies have been reported as implicated in cerebellar ataxia, palatal myoclonus, refractory epilepsy and limbic encephalitis. Epilepsy associated with the anti-GAD antibody is mostly pharmacoresistant temporal lobe epilepsy; with brain MRI showing no abnormality or only hippocampal sclerosis. It is very rare that brain MRI shows extensive abnormal lesions except in the hippocampus. This case suggests that anti-GAD antibodies could contribute to unexplained encephalopathy with

  14. Thrombotic thrombocytopenic purpura and myoglobinuric acute renal failure following radiation therapy in a patient with polymyositis and cervical cancer

    International Nuclear Information System (INIS)

    Makino, Hirofumi; Nagake, Yoshio; Moriwaki, Kazuhiko; Hirakawa, Shuzo; Katayama, Takaaki; Yanai, Hiroyuki; Takahashi, Kiyoshi; Akagi, Tadaatsu; Ota, Zensuke

    1995-01-01

    A 73-year-old woman was admitted to receive radiation treatment for uterine cervical cancer, however a complex series of events ensued, leading to death. She developed an acute exacerbation of polymyositis complicated by thrombocytopenic purpura, rhabdomyolysis and acute renal failure. Radiation therapy may have produced an immune disturbance leading to the acute exacerbation of polymyositis. Auto-immune-mediated endothelial damage might have triggered a series of events leading to thrombotic thrombocytopenic purpura. Rhabdomyolysis seemed to be the main cause of acute renal failure. (author)

  15. Thrombotic thrombocytopenic purpura and myoglobinuric acute renal failure following radiation therapy in a patient with polymyositis and cervical cancer

    Energy Technology Data Exchange (ETDEWEB)

    Makino, Hirofumi; Nagake, Yoshio; Moriwaki, Kazuhiko; Hirakawa, Shuzo; Katayama, Takaaki; Yanai, Hiroyuki; Takahashi, Kiyoshi; Akagi, Tadaatsu; Ota, Zensuke [Okayama Univ. (Japan). School of Medicine

    1995-01-01

    A 73-year-old woman was admitted to receive radiation treatment for uterine cervical cancer, however a complex series of events ensued, leading to death. She developed an acute exacerbation of polymyositis complicated by thrombocytopenic purpura, rhabdomyolysis and acute renal failure. Radiation therapy may have produced an immune disturbance leading to the acute exacerbation of polymyositis. Auto-immune-mediated endothelial damage might have triggered a series of events leading to thrombotic thrombocytopenic purpura. Rhabdomyolysis seemed to be the main cause of acute renal failure. (author).

  16. Vancomycin-induced thrombocytopenia in a 60-year-old man: a case report

    Directory of Open Access Journals (Sweden)

    Shah Ravish A

    2009-06-01

    Full Text Available Abstract Introduction Vancomycin, a glycopeptide antibiotic, is used to treat resistant gram-positive infections. There has been a 10- to 20-fold increase in its use over the past 25 years. Although ototoxicity and nephrotoxicity are well known side effects of vancomycin, it can also induce platelet reactive antibodies leading to life-threatening thrombocytopenia. Vancomycin is often clinically overlooked as a cause of thrombocytopenia, especially in a scenario of sepsis or when there is use of heparin. We report a proven case of vancomycin-induced thrombocytopenia and its reversal after discontinuation of vancomycin. Case presentation A 60-year-old man with a history of hypertension, congestive heart failure and dyslipidemia was admitted for a right shoulder rotator cuff tear. He underwent right-shoulder arthroscopy and rotator cuff repair. About three weeks later, he developed pain, swelling and purulent drainage from his right shoulder. Arthroscopic irrigation and drainage was then performed. Intraoperative fluid revealed the presence of Methicillin susceptible Staphylococcus aureus, vancomycin-sensitive Enterococcus spp. and Serratia marcescens. The patient had no known allergies. After reviewing his antimicrobial susceptibility, he was started on vancomycin 1500 mgs intravenously every 12 hours (to treat both Staphylococcus aureus and Enterococcus spp and ciprofloxacin 750 mgs by oral induction every 12 hours. The patient's condition improved following antibiotic treatment. He was discharged and allowed to go home on IV vancomycin and oral ciprofloxacin. The patient's platelet count on the day of starting vancomycin therapy was 253 × 103/mm3. At weeks one, two and three, the counts were 231 × 103/mm3, 272 × 103/mm and 6 × 103/mm3, respectively. The patient was admitted for further work-up of the thrombocytopenia. He was later shown to have vancomycin-induced platelet-reactive antibodies, causing significant thrombocytopenia, and then

  17. Dapsone for primary immune thrombocytopenia in adults and children: an evidence-based review.

    Science.gov (United States)

    Rodrigo, C; Gooneratne, L

    2013-11-01

    Primary immune thrombocytopenia is a potentially life-threatening condition. Approximately two-thirds of adult patients do not have a sustained response to steroids (first-line therapy). For these patients, a number of other treatment options exist, such as rituximab, splenectomy, immunosuppressants, and thrombopoietin receptor agonists, but they are costly and have side effects. Dapsone is an inexpensive drug with a well-established safety profile. Unfortunately, this treatment option has not been explored adequately. This review is aimed at analyzing the currently available evidence for the use of dapsone as second-line or third-line therapy in primary immune thrombocytopenia. © 2013 International Society on Thrombosis and Haemostasis.

  18. Drug-Induced Thrombocytopenia following a Transvaginal Oocyte Retrieval for In Vitro Fertilization

    Directory of Open Access Journals (Sweden)

    Ioanna A. Comstock

    2015-01-01

    Full Text Available Drug-induced immune thrombocytopenia has been associated with hundreds of medications and can lead to devastating consequences for the patient. We present a case of a healthy 33-year-old female undergoing in vitro fertilization who developed a severe drug-induced thrombocytopenia, petechiae, and a large hemoperitoneum after receiving Cefazolin antibiotic prophylaxis for a transvaginal oocyte retrieval. The patient was admitted to the intensive care unit for resuscitation with blood products. The presence of drug-dependent platelet antibodies to Cefazolin was confirmed serologically.

  19. Prevalence of thrombocytopenia in HIV-infected and non-HIV infected drug users and homosexual men

    NARCIS (Netherlands)

    Mientjes, G. H.; van Ameijden, E. J.; Mulder, J. W.; van den Hoek, J. A.; Coutinho, R. A.; von dem Borne, A. E.

    1992-01-01

    We studied the prevalence and risk factors for thrombocytopenia among 299 drug users and 461 homosexual men. The prevalence of thrombocytopenia was 3.3% in HIV-negative homosexual men, 8.7% in HIV-negative drug users, 16.4% in HIV-positive homosexual men, and 36.9% in HIV-positive drug users. With

  20. Immune-mediated statin myopathy.

    Science.gov (United States)

    Loganathan, Priyadarshini; Oddis, Chester V; Aggarwal, Rohit

    2016-01-01

    Statin-induced necrotizing autoimmune myopathy (SINAM) is associated with a unique clinical 5 phenotype of severe proximal muscle weakness during or after exposure to statins in patients with high creatine kinase (CK) levels. Electromyography (EMG) and muscle biopsy reveal features of a necrotizing myopathy and the anti-HMGCR autoantibody is frequently detected. Treatment requires a combination of statin discontinuation as well as immunomodulatory or immunosuppressive therapy. HLA typing (HLADRB1*1101) is strongly associated with anti-10 HMGCR autoantibody positivity in statin-exposed patients. It is well documented that statin triggers autoimmune disease in those with a genetic susceptibility. With the commercial availability of an accurate ELISA test, the natural history of the disease and its phenotypic features are becoming increasingly understood.

  1. Idiopathic Atypical Haemolytic Uraemic Syndrome presenting with acute dystonia

    LENUS (Irish Health Repository)

    Maduemem, Rizwan K E

    2017-09-01

    Hemolytic Uremic Syndrome (HUS), a triad of microangiopathic hemolytic anemia, thrombocytopenia and acute kidney injury. The atypical HUS (aHUS) results from over activation of complement system with formation of micro thrombi and damage to endothelial cells resulting in renal impairment in 50 % and death in 25 %, commonly in untreated patients. We report an intriguing case of aHUS presenting with acute onset of movement disorder and fluctuating delirium.

  2. Spontaneous acute subdural hematoma in a patient with multiple myeloma

    Directory of Open Access Journals (Sweden)

    Abrar Ahad Wani

    2012-01-01

    Full Text Available Acute spontaneous subdural hematoma in a patient of multiple myeloma receiving chemotherapy is an unknown event, needing an urgent neurosurgical management. We report this patient who presented with progressive neurological deterioration and a low platelet count. She was successfully managed by craniotomy and evacuation of subdural hematoma with intraoperative transfusion of platelets. The acute spontaneous subdural hematoma in her was probably related to the bleeding diathesis due to thrombocytopenia associated with chemotherapy.

  3. [Effect of environmental humidity on the epistaxis of patients with acute thrombocytopenia].

    Science.gov (United States)

    Tersea Sedas, M; Dorantes, S

    1975-01-01

    The effect of humidification of the environment was studied on the frequency and severeness of spistaxes in a group of 16 children. A control group was composed of 18 children with the idea that they were similar, but the hematologic conditions of the latter group were more unfavorable. A decrease of epistaxis was not found; there was a minimal prolongation of the days between one and the next nosebleeding picture. A definite decrease in the severeness of bleeding was found in the second group as judged by a lesser necessity of transfusions.

  4. Use of intravenous immunoglobulin in neonates with haemolytic disease and immune thrombocytopenia

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    Marković-Sovtić Gordana

    2013-01-01

    Full Text Available Background/Aim. Intravenous immunoglobulin is a blood product made of human polyclonal immunoglobulin G. The mode of action of intravenous immunoglobulin is very complex. It is indicated in treatment of neonatal immune thrombocytopenia and haemolytic disease of the newborn. The aim of the study was to present our experience in the use of intravenous immunoglobulin in a group of term neonates. Methods. We analysed all relevant clinical and laboratory data of 23 neonates who recieved intravenous immunoglobulin during their hospitalization in Neonatal Intensive Care Unit of Mother and Child Health Care Institute over a five year period, from 2006. to 2010. Results. There were 11 patients with haemolytic disease of the newborn and 12 neonates with immune thrombocytopenia. All of them recieved 1-2 g/kg intravenous immunoglobulin in the course of their treatment. There was no adverse effects of intravenous immunoglobulin use. The use of intravenous immunoglobulin led to an increase in platelet number in thrombocytopenic patients, whereas in those with haemolytic disease serum bilirubin level decreased significantly, so that some patients whose bilirubin level was very close to the exchange transfusion criterion, avoided this procedure. Conclusion. The use of intravenous immunoglobulin was shown to be an effective treatment in reducing the need for exchange transfusion, duration of phototherapy and the length of hospital stay in neonates with haemolytic disease. When used in treatment of neonatal immune thrombocytopenia, it leads to an increase in the platelet number, thus decreasing the risk of serious complications of thrombocytopenia.

  5. Immune Thrombocytopenia and JAK2V617F Positive Essential Thrombocythemia: Literature Review and Case Report.

    Science.gov (United States)

    Sobas, M A; Wróbel, T; Zduniak, K; Podolak-Dawidziak, M; Rybka, J; Biedroń, M; Sawicki, M; Dybko, J; Kuliczkowski, K

    2017-01-01

    We present the case where immune thrombocytopenia (ITP) and essential thrombocythemia (ET) sequentially appeared in the space of twenty-one years of follow-up. Impaired platelet production is present in both diseases, but clinical presentation and treatment are different. On the basis of this case history a possible role of autoimmunity as a predisposing factor to myeloproliferation has been discussed.

  6. Twenty-year mortality of adult patients with primary immune thrombocytopenia

    DEFF Research Database (Denmark)

    Frederiksen, Henrik; Maegbaek, Merete Lund; Nørgaard, Mette

    2014-01-01

    Studies have reported a 1·3- to 2·2-fold higher mortality rate among patients with primary immune thrombocytopenia (ITP) compared to the general population. However, long-term mortality estimates as well as cause-specific mortality data are sparse. In our population-based cohort of adult patients...

  7. Anaesthetic dilemma: spinal anaesthesia in an eclamptic patient with mild thrombocytopenia and an "impossible" airway.

    Science.gov (United States)

    Nafiu, O O; Salam, R A; Elegbe, E O

    2004-04-01

    We present our anaesthetic management of a 27-year-old woman with antepartum eclampsia, mild thrombocytopenia, difficult airway and clinical evidence of impending upper airway obstruction. She required urgent delivery by caesarean section, which was conducted uneventfully under spinal anaesthesia. We discuss the management conundrums presented by this case and why we chose spinal anaesthesia over other anaesthetic options.

  8. Thrombocytopenia impairs host defense in gram-negative pneumonia-derived sepsis in mice

    NARCIS (Netherlands)

    de Stoppelaar, Sacha F.; van 't Veer, Cornelis; Claushuis, Theodora A. M.; Albersen, Bregje J. A.; Roelofs, Joris J. T. H.; van der Poll, Tom

    2014-01-01

    Thrombocytopenia is a common finding in sepsis and associated with a worse outcome. We used a mouse model of pneumonia-derived sepsis caused by the human pathogen Klebsiella pneumoniae to study the role of platelets in host response to sepsis. Platelet counts (PCs) were reduced to less than a median

  9. Danazol improves thrombocytopenia in HCV patients treated with peginterferon and ribavirin.

    Science.gov (United States)

    Alvarez, Guillermo Cabrera; Gómez-Galicia, Diana; Rodríguez-Fragoso, Lourdes; Marina, Vicente Madrid; Dorantes, Luis Cañedo; Sánchez-Alemán, Miguel; Méndez-Sánchez, Nahum; Esparza, Jorge Reyes

    2011-01-01

    Thrombocytopenia is a common hematologic disorder observed in patients with chronic hepatitis C virus (HCV) infection. Combined peginterferon (PEG-INF) and ribavirin treatment may exacerbate thrombocytopenia in patients with HCV. The aim of this pilot clinical trial was to assess the efficacy, tolerability and safety of Danazol in thrombocytopenia associated with PEG-INF and ribavirin treatment in patients with HCV. We included patients whose platelets were 100,000 platelets/mm³, and 71% of patients maintained their initial platelet levels. Sustained viral response (SVR) was achieved in 63% of patients. SVR rates were high in patients with genotype non 1 (78.7%) and decreased in patients with genotype 1 (60.1%). The increase in platelet levels was associated to an increase in fibrinogen levels and a decrease in the activity of ALT. By contrast, patients without SVR presented a delayed response to increased platelet levels and showed no significant improvement in liver function when they received Danazol. Danazol can be used along with PEG-INF and ribavirin to treat thrombocytopenia in patients with HCV.

  10. Idiopathic pulmonary embolism in a case of severe family ANKRD26 thrombocytopenia

    Directory of Open Access Journals (Sweden)

    Jérôme Guison

    2017-06-01

    Full Text Available Venous thrombosis affecting thrombocytopenic patients is challenging. We report the case of a thrombocytopenic woman affected by deep vein thrombosis and pulmonary embolism leading to the discovery of a heterozygous mutation in the gene encoding ankyrin repeat domain 26 (ANKRD26 associated with a heterozygous factor V (FV Leiden mutation. This woman was diagnosed with left lower-limb deep vein thrombosis complicated by pulmonary embolism. Severe thrombocytopenia was observed. The genetic study evidenced a heterozygous FV Leiden mutation. Molecular study sequencing was performed after learning that her family had a history of thrombocytopenia. Previously described heterozygous mutation c-127C>A in the 5′ untranslated region (5′UTR of the ANKRD26 gene was detected in the patient, her aunt, and her grandmother. ANKRD26-related thrombocytopenia and thrombosis are rare. This is, to our knowledge, the first case reported in the medical literature. This mutation should be screened in patients with a family history of thrombocytopenia.

  11. Idiopathic Pulmonary Embolism in a case of Severe Family ANKRD26 Thrombocytopenia

    Science.gov (United States)

    Guison, Jerome; Blaison, Gilles; Stoica, Oana; Hurstel, Remy; Favier, Marie; Favier, Remy

    2017-01-01

    Venous thrombosis affecting thrombocytopenic patients is challenging. We report the case of a woman affected by deep vein thrombosis and pulmonary embolism in a thrombocytopenic context leading to the discovery of a heterozygous mutation in the gene encoding ankyrin repeat domain 26 (ANKRD26) associated with a heterozygous factor V (FV) Leiden mutation. This woman was diagnosed with lower-limb deep vein thrombosis complicated by pulmonary embolism. Severe thrombocytopenia was observed. The genetic study evidenced a heterozygous FV Leiden mutation. Molecular study sequencing was performed after learning that her family had a history of thrombocytopenia. Previously described heterozygous mutation c-127C>A in the 5′untranslated region (5′UTR) of the ANKRD26 gene was detected in the patient, her aunt, and her grandmother. ANKRD26-related thrombocytopenia and thrombosis are rare. This is, to our knowledge, the first case reported in the medical literature. This mutation should be screened in patients with a family history of thrombocytopenia. PMID:28698781

  12. Chronic Subdural Hematoma Associated with Thrombocytopenia in a Patient with Human Immunodeficiency Virus Infection in Cameroon

    Directory of Open Access Journals (Sweden)

    Clovis Nkoke

    2017-01-01

    Full Text Available Hematological abnormalities including thrombocytopenia are common in patients living with HIV infection. Patients with HIV infection related thrombocytopenia present generally with only minor bleeding problems. But cases of subdural hematoma are very rare. A 61-year-old female with a history of HIV infection of 9 years’ duration presented with a 3-month history of generalized headache associated with visual blurring and anterograde amnesia. There was no history of trauma or fever. She was treated empirically for cerebral toxoplasmosis for 6 weeks without any improvement of the symptoms. One week prior to admission, she developed weakness of the left side of the body. Clinical examination revealed left-sided hemiparesis. Computed tomography scan of the brain showed a 25 mm chronic right frontoparietotemporal subdural hematoma compressing the lateral ventricle with midline shift. There was no appreciable cerebral atrophy. A complete blood count showed leucopenia and thrombocytopenia at 92,000 cells/mm3. Her CD4-positive cell count was 48 cells/mm3 despite receiving combination antiretroviral therapy for 9 years. A complete blood count analysis suggestive of thrombocytopenia should raise suspicion of possibilities of noninfectious focal brain lesions like subdural hematoma amongst HIV infected patients presenting with nonspecific neurological symptoms. This will enable prompt diagnosis and allow early appropriate intervention.

  13. Thrombocytopenia associated with olanzapine: A case report and review of literature

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    Swapnajeet Sahoo

    2016-01-01

    Full Text Available There is limited literature on olanzapine-associated thrombocytopenia. In this report, we present a case of a 32-year-old female, suffering from persistent delusional disorder who had thrombocytopenia (46,000/mm3 with the use of olanzapine 25 mg/day, 6 weeks after starting medication. Blood film did not reveal any evidence of any dysplastic cells, disturbance in the count of other cell lines, and autoimmune workup including antinuclear antibodies and anti-neutrophil cytoplasmic antibodies were found to be negative. Given no other etiology, olanzapine was gradually tapered, and platelet counts were monitored. Reduction in the dose of olanzapine led to an improvement in platelet counts which reached the normal range after complete stoppage of olanzapine. In view of continued psychotic symptoms, she was started on clozapine and which was gradually increased to 200 mg/day with biweekly monitoring of total platelet counts before each increment in the dose of clozapine. Thrombocytopenia did not recur with use of clozapine. With clozapine, her psychosis improved by nearly 60%. A review of literature revealed only eight case reports supporting the association of olanzapine and thrombocytopenia.

  14. Fibroproliferative activity in patients with immune thrombocytopenia (ITP) treated with thrombopoietic agents

    DEFF Research Database (Denmark)

    Ghanima, W.; Bussel, J.B.; Junker, P.

    2011-01-01

    This study assessed the grade of bone marrow (BM) fibrosis and its association with a seromarker for collagen-III formation and fibrosis-related cytokines in 25 immune thrombocytopenia (ITP) patients treated with thrombopoietin receptor agonists (Tpo-RA) who had at least one BM biopsy. Assessment...

  15. Splenic arteriovenous malformation manifested by thrombocytopenia in hereditary hemorrhagic telangiectasia: a case report

    Energy Technology Data Exchange (ETDEWEB)

    Kwon, Hee Jin; Choi, Jong Cheol; Oh, Jong Yeong; Cho, Jin Han; Kang, Myong Jin; Lee, Jin Hwa; Yoon, Seong Kuk; Nam, Kyeong Jin [College of Medicine, Dong-A University, Busan (Korea, Republic of)

    2008-09-15

    Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant inherited disease characterized by epistaxis, telangiectases and visceral arteriovenous malformations (AVMs). The involvement of the gastrointestinal tract, liver, lung and cerebrum for HHT has been described, whereas little is known about AVMs of the spleen. We report here the radiological findings of a case of a splenic AVM manifested by thrombocytopenia in HHT.

  16. Splenic arteriovenous malformation manifested by thrombocytopenia in hereditary hemorrhagic telangiectasia: a case report

    International Nuclear Information System (INIS)

    Kwon, Hee Jin; Choi, Jong Cheol; Oh, Jong Yeong; Cho, Jin Han; Kang, Myong Jin; Lee, Jin Hwa; Yoon, Seong Kuk; Nam, Kyeong Jin

    2008-01-01

    Hereditary hemorrhagic telangiectasia (HHT) is an autosomal dominant inherited disease characterized by epistaxis, telangiectases and visceral arteriovenous malformations (AVMs). The involvement of the gastrointestinal tract, liver, lung and cerebrum for HHT has been described, whereas little is known about AVMs of the spleen. We report here the radiological findings of a case of a splenic AVM manifested by thrombocytopenia in HHT

  17. Prevalence of HIV-related thrombocytopenia among clients at Mbarara Regional Referral Hospital, Mbarara, southwestern Uganda

    Directory of Open Access Journals (Sweden)

    Taremwa IM

    2015-04-01

    Full Text Available Ivan M Taremwa,1 Winnie R Muyindike,2 Enoch Muwanguzi,1 Yap Boum II,1,3 Bernard Natukunda1 1Department of Medical Laboratory Sciences, Faculty of Medicine, Mbarara University of Science and Technology, 2Immune Suppression Syndrome Clinic, Mbarara Regional Referral Hospital, 3Epicentre Mbarara Research Centre, Mbarara, Uganda Aims/objectives: We aimed to determine the prevalence and correlates of thrombocytopenia among people living with human immunodeficiency virus (HIV/acquired immune deficiency syndrome (AIDS and to assess occurrence of antiplatelet antibodies, among thrombocytopenic HIV clients at Mbarara Regional Referral Hospital, southwestern Uganda.Materials and methods: This was a retrospective review of hematologic results at enrollment to HIV care from 2005 to 2013. The prevalence and correlates of thrombocytopenia were estimated based on the Immune Suppressed Syndrome (ISS Clinic electronic database. A cross-sectional study determined the occurrence of antiplatelet antibodies, using the monoclonal antibody-specific immobilization of platelet antigens (MAIPA technique.Results: We reviewed 15,030 client records. The median age was 35.0 (range 18–78; interquartile range [IQR] 28–42 years, and there were 63.2% (n=9,500 females. The overall prevalence of thrombocytopenia was 17.4% (95% confidence interval [CI]: 16.8%–18.0%. The prevalence of thrombocytopenia was 17.8% (95% CI: 17.1%–18.4% among antiretroviral therapy (ART-naïve clients (n=2,675 and was 13.0% (95% CI: 0.3%–21.9% for clients who were on ART (n=6. The study found a significant association between thrombocytopenia and other cytopenias, CD4 counts, ART, and deteriorating HIV stage (P<0.05. Two of the 40 participants (5.0% had antiplatelet antibodies.Conclusion: This study has showed a high prevalence of HIV-related thrombocytopenia. Antiplatelet antibodies were found in 5.0% of HIV-infected thrombocytopenic participants. Our study shows a significant association of

  18. Persistence with golimumab in immune-mediated rheumatic diseases: a systematic review of real-world evidence in rheumatoid arthritis, axial spondyloarthritis, and psoriatic arthritis

    Directory of Open Access Journals (Sweden)

    Svedbom A

    2017-04-01

    Full Text Available Axel Svedbom,1 Chiara Storck,2 Sumesh Kachroo,3 Marinella Govoni,4 Ahmed Khalifa5 1Real World Strategy and Analytics, Mapi Group, Stockholm, Sweden; 2Real World Strategy and Analytics, Mapi Group, Munich, Germany; 3Center for Observational and Real-World Evidence (CORE, Merck & Co, Kenilworth, NJ, USA; 4MSD Italy, Rome, Italy; 5Medical Affairs Immunology, MSD Switzerland, Luzern, Switzerland Purpose: In immune-mediated rheumatic diseases (IMRDs, persistence to treatment may be used as a surrogate marker for long-term treatment success. In previous comparisons of persistence to tumor necrosis factor α inhibitors (TNFis, a paucity of data for subcutaneous (SC golimumab was identified. The aim of this study was to conduct a systematic review of persistence to SC golimumab in clinical practice and contextualize these data with five-year persistence estimates from long-term open-label extension (OLE trials of SC TNFis in IMRDs.Patients and methods: PubMed, Embase, MEDLINE, and conference proceedings from European League Against Rheumatism (EULAR, American College of Rheumatology (ACR, and International Society for Pharmacoeconomics and Outcomes Research (ISPOR were searched. All studies on patients treated with SC golimumab for IMRD were included if they reported data on the persistence to golimumab.Results: Of 376 available references identified through the searches, 12 studies with a total of 4,910 patients met the inclusion criteria. Furthermore, nine OLE trials were available. Among the included studies from clinical practice, at six months, one year, two years, and three years, the proportion of patients persistent to treatment ranged from 63% to 91%, 47% to 80%, 40% to 77%, and 32% to 67%, respectively. In the four studies that included comparisons to other biologics, golimumab was either statistically noninferior or statistically superior to other treatments, an observation that was supported by indirect comparisons of unadjusted point

  19. Risk of subsequent coronary heart disease in patients hospitalized for immune-mediated diseases: a nationwide follow-up study from Sweden.

    Directory of Open Access Journals (Sweden)

    Bengt Zöller

    Full Text Available BACKGROUND: Certain immune-mediated diseases (IMDs, such as rheumatoid arthritis and systemic lupus erythematosus, have been linked to cardiovascular disorders. We examined whether there is an association between 32 different IMDs and risk of subsequent hospitalization for coronary heart disease (CHD related to coronary atherosclerosis in a nationwide follow up study in Sweden. METHODS AND FINDINGS: All individuals in Sweden hospitalized with a main diagnosis of an IMD (n = 336,479 without previous or coexisting CHD, between January 1, 1964 and December 31 2008, were followed for first hospitalization for CHD. The reference population was the total population of Sweden. Standardized incidence ratios (SIRs for CHD were calculated. Overall risk of CHD during the first year after hospitalization for an IMD was 2.92 (95% CI 2.84-2.99. Twenty-seven of the 32 IMDs studied were associated with an increased risk of CHD during the first year after hospitalization. The overall risk of CHD decreased over time, from 1.75 after 1-5 years (95% CI 1.73-1.78, to 1.43 after 5-10 years (95% CI 1.41-1.46 and 1.28 after 10+ years (95% CI 1.26-1.30. Females generally had higher SIRs than males. The IMDs for which the SIRs of CDH were highest during the first year after hospitalization included chorea minor 6.98 (95% CI 1.32-20.65, systemic lupus erythematosus 4.94 (95% CI 4.15-5.83, rheumatic fever 4.65 (95% CI 3.53-6.01, Hashimoto's thyroiditis 4.30 (95% CI 3.87-4.75, polymyositis/dermatomyositis 3.81 (95% CI 2.62-5.35, polyarteritis nodosa 3.81 (95% CI 2.72-5.19, rheumatoid arthritis 3.72 (95% CI 3.56-3.88, systemic sclerosis 3.44 (95% CI 2.86-4.09, primary biliary cirrhosis 3.32 (95% CI 2.34-4.58, and autoimmune hemolytic anemia 3.17 (95% CI 2.16-4.47. CONCLUSIONS: Most IMDs are associated with increased risk of CHD in the first year after hospital admission. Our findings suggest that many hospitalized IMDs are tightly linked to coronary atherosclerosis.

  20. Phylogenetic and Geographic Relationships of Severe Fever With Thrombocytopenia Syndrome Virus in China, South Korea, and Japan.

    Science.gov (United States)

    Yoshikawa, Tomoki; Shimojima, Masayuki; Fukushi, Shuetsu; Tani, Hideki; Fukuma, Aiko; Taniguchi, Satoshi; Singh, Harpal; Suda, Yuto; Shirabe, Komei; Toda, Shoichi; Shimazu, Yukie; Nomachi, Taro; Gokuden, Mutsuyo; Morimitsu, Toshiharu; Ando, Katsuyuki; Yoshikawa, Akira; Kan, Miki; Uramoto, Marina; Osako, Hideo; Kida, Kouji; Takimoto, Hirokazu; Kitamoto, Hiroaki; Terasoma, Fumio; Honda, Akiko; Maeda, Ken; Takahashi, Toru; Yamagishi, Takuya; Oishi, Kazunori; Morikawa, Shigeru; Saijo, Masayuki

    2015-09-15

    Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne acute infectious disease caused by the SFTS virus (SFTSV). SFTS has been reported in China, South Korea, and Japan as a novel Bunyavirus. Although several molecular epidemiology and phylogenetic studies have been performed, the information obtained was limited, because the analyses included no or only a small number of SFTSV strains from Japan. The nucleotide sequences of 75 SFTSV samples in Japan were newly determined directly from the patients' serum samples. In addition, the sequences of 7 strains isolated in vitro were determined and compared with those in the patients' serum samples. More than 90 strains that were identified in China, 1 strain in South Korea, and 50 strains in Japan were phylogenetically analyzed. The viruses were clustered into 2 clades, which were consistent with the geographic distribution. Three strains identified in Japan were clustered in the Chinese clade, and 4 strains identified in China and 26 in South Korea were clustered in the Japanese clade. Two clades of SFTSV may have evolved separately over time. On rare occasions, the viruses were transmitted overseas to the region in which viruses of the other clade were prevalent. © The Author 2015. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals.permissions@oup.com.

  1. Impact of antiepileptic drugs on thrombocytopenia in glioblastoma patients treated with standard chemoradiotherapy.

    Science.gov (United States)

    Simó, Marta; Velasco, Roser; Graus, Francesc; Verger, Eugenia; Gil, Miguel; Pineda, Estela; Blasco, Jaume; Bruna, Jordi

    2012-07-01

    Epilepsy in glioblastoma multiforme (GBM) patients is common. Hematological toxicity is a potential side effect of antiepileptic drugs (AEDs) and a frequent limiting-dose effect of temozolomide (TMZ). The aim of the study was to investigate the impact of AEDs on thrombocytopenia in GBM patients treated with radiotherapy and TMZ. A cohort of 101 newly diagnosed GBM patients treated with radiotherapy and TMZ was reviewed. Clinical data, presence of seizures, AEDs use, platelet count, and accumulated TMZ dose were analyzed at each cycle. Thrombocytopenia was operationalized as a continuous platelet count and a dichotomic variable (cut-off <100.000/mm(3)). This cut-off represents the threshold beyond which TMZ treatment is modified. A linear and a probit pooled cross-sectional regression analysis were used to study the impact of age, gender, AEDs, and accumulated TMZ on thrombocytopenia. Impact of AEDs on survival was also analyzed. Thirty-five patients (35%) presented seizures at onset and 18 (27%) during follow-up. Seven (13%) needed two or more AEDs for seizure control. Grade 3-4 thrombocytopenia was found in 8%. Decrease in platelet count was related to accumulated TMZ (p < 0.001), age (p < 0.001), and valproate (p = 0.004). Platelet count <100.000/mm(3) was only associated with accumulated TMZ (p = 0.001). Recursive Partitioning Analysis prognostic class was the only variable with significant impact on survival. Valproate and age had an independent negative effect on total platelet count, although neither had an effect on critical thrombocytopenia (<100.000/mm(3)). Therefore, the systematic withhold of valproate in GBM patients might not be justified. Nevertheless, this negative effect may be taken into account especially in elderly patients.

  2. Association of severe thrombocytopenia and poor prognosis in pregnancies with aplastic anemia.

    Directory of Open Access Journals (Sweden)

    Jae Eun Shin

    Full Text Available PURPOSE: We sought to estimate the risks of adverse obstetric outcomes and disease outcomes associated with severe thrombocytopenia in pregnant women with aplastic anemia (AA. METHODS: In a retrospective study, we compared demographics, clinical characteristics, laboratory results, and outcomes between severe thrombocytopenia (ST and non-severe thrombocytopenia (non-ST groups comprising pregnant women with AA. RESULTS: Of 61 AA patients, 43 (70% were diagnosed as AA before pregnancy and 18 (30% were AA during pregnancy. The ST group exhibited lower gestational age at nadir of platelet count (26.0 versus 37.0 weeks, p<0.001 and at delivery (37.3 versus 39.1 weeks, p = 0.008, and a higher rate of bleeding gums (33.8 versus 7.7%, p = 0.015 than the non-ST group. In addition, the ST group exhibited more transfusions during pregnancy (72.7 versus 15.4%, p<0.001 and postpartum period (45.0 versus 2.7%, p<0.001, and more bone marrow transplant after delivery (25.0 versus 0.0%, p<0.001 than the non-ST group. The ST group had a higher odds ratio of composite disease complications (OR, 9.63; 95% CI, 2.82-32.9; p<0.001 and composite obstetric complications (OR, 6.78; 95% CI, 2.11-21.8; p = 0.001 than the non-ST group. CONCLUSIONS: Severe thrombocytopenia is more associated with obstetric and disease complications than is non-severe thrombocytopenia in pregnant women with AA.

  3. Risk of subsequent ischemic and hemorrhagic stroke in patients hospitalized for immune-mediated diseases: a nationwide follow-up study from Sweden

    Directory of Open Access Journals (Sweden)

    Zöller Bengt

    2012-06-01

    Full Text Available Abstract Background Certain immune-mediated diseases (IMDs have been associated with increased risk for cardiovascular disorders. The aim of the present study was to examine whether there is an association between 32 different IMDs and first hospitalization for ischemic or hemorrhagic stroke. Methods All individuals in Sweden hospitalized with a main diagnosis of IMD (without previous or coexisting stroke, between January 1, 1987 and December 31, 2008 (n = 216,291, were followed for first hospitalization for ischemic or hemorrhagic stroke. The reference population was the total population of Sweden. Adjusted standardized incidence ratios (SIRs for ischemic and hemorrhagic stroke were calculated. Results Totally 20 and 15 of the 32 IMDs studied, respectively, were associated with an increased risk of ischemic and hemorrhagic stroke during the follow-up. The overall risks of ischemic and hemorrhagic stroke during the first year after hospitalization for IMD were 2.02 (95% CI 1.90–2.14 and 2.65 (95% CI 2.27–3.08, respectively. The overall risk of ischemic or hemorrhagic stroke decreased over time, to 1.50 (95% CI 1.46–1.55 and 1.83 (95% CI 1.69–1.98, respectively, after 1–5 years, and 1.29 (95% CI 1.23–1.35 and 1.47 (95% CI 1.31–1.65, respectively, after 10+ years. The risk of hemorrhagic stroke was ≥2 during the first year after hospitalization for seven IMDs: ankylosing spondylitis (SIR = 8.11, immune thrombocytopenic purpura (SIR = 8.60, polymyalgia rheumatica (SIR = 2.06, psoriasis (SIR = 2.88, rheumatoid arthritis (SIR = 3.27, systemic lupus erythematosus (SIR = 8.65, and Wegener´s granulomatosis (SIR = 5.83. The risk of ischemic stroke was ≥2 during the first year after hospitalization for twelve IMDs: Addison’s disease (SIR = 2.71, Crohn´s disease (SIR = 2.15, Grave´s disease (SIR = 2.15, Hashimoto´s thyroiditis (SIR = 2.99, immune thrombocytopenic purpura (SIR = 2

  4. Vancomycin-induced thrombocytopenia: a rare adverse effect in a patient -submitted to bone graft in the jaw.

    Science.gov (United States)

    Danieletto, Carolina Ferrairo; Ferreira, Gustavo Zanna; Farah, Gustavo Jacobucci; Cuman, Roberto Kenji Nakamura

    2017-01-01

    Thrombocytopenia is the reduction in the number of blood -platelets, which may be caused by -several different conditions such as sepsis, disseminated intravascular -clotting, and large blood losses. Additionally, in rare situations, thrombocytopenia may also be induced by the use of medicaments. One of these drugs is the vancomycin, a glycopeptide presently used against -serious infections involving Gram-positive bacteria such as the methicillin-resistant Staphylococcus aureus and penicillin-resistant Streptococcus. The objective of this study is to report on a case of serious vancomycin-induced thrombocytopenia in a patient infected with methicillin-resistant S. aureus after mandibular reconstruction with autogenous bone graft, and to draw attention to the importance of this clinically rare adverse effect. Vancomycin-induced thrombocytopenia is a rare condition, which is also a significant disorder that demands attention and the rapid identification and replacement of the antimicrobial agent. © 2016 Special Care Dentistry Association and Wiley Periodicals, Inc.

  5. Prevalence of thrombocytopenia among pregnant women attending antenatal care service at Gondar University Teaching Hospital in 2014, northwest Ethiopia

    Directory of Open Access Journals (Sweden)

    Asrie F

    2017-06-01

    Full Text Available Fikir Asrie, Bamlaku Enawgaw, Zegeye Getaneh Department of Hematology and Immunohematology, School of Biomedical and Laboratory Sciences, College of Medicine and Health Sciences, University of Gondar, Gondar, Ethiopia Introduction: Thrombocytopenia is a common hematologic abnormality during pregnancy. Pregnant women with thrombocytopenia have a higher risk of bleeding excessively during or after childbirth, particularly if they need to have a cesarean section or other surgical intervention during pregnancy, labor or in the puerperium. The main aim of this study was to determine the prevalence of thrombocytopenia among pregnant women attending antenatal care service at Gondar University Hospital, northwest Ethiopia.Materials and methods: A cross-sectional study was used to assess the prevalence of thrombocytopenia among pregnant women attending antenatal care service at Gondar University Hospital from January to April 2015. A total of 217 pregnant women were included in the study and a structured pretested questionnaire was used to obtain sociodemographic information, nutritional factors, obstetrics and gynecological factors, history and clinical condition. Blood samples were collected for platelet count and other platelet parameters, which were determined by using SysmexKX 21 automation. The data were entered to Epi info version 6 software and analyzed using SPSS version 20 software. Bivariable and multivariable statistical analyses were used to evaluate the effect of independent variable over the dependent variable. A p-value of <0.05 was considered as statistically significant.Result: A total of 217 women receiving antenatal care service at Gondar University Hospital participated in the study. Thrombocytopenia among 19 pregnant women showed a prevalence of 8.8%. The mean ± standard deviation platelet count was 238.85×109/L (±74.57. Thrombocytopenia was significantly associated with patients who lived rurally (crude odds ratio =4.3, 95

  6. Platelet cold agglutinins and thrombocytopenia: A diagnostic dilemma in the intensive care unit

    Directory of Open Access Journals (Sweden)

    TV Bharath Kumar

    2014-01-01

    Full Text Available We report a case of pseudo-thrombocytopenia due to cold agglutinins against platelets. These cold agglutinins were the cause for diagnostic confusion and resulted in extensive workup and unnecessary therapeutic precautions. A thirty two year old female with Guillain-Barre syndrome was admitted in the ICU and serial work-up showed markedly low levels of platelets. The patient had no symptoms of bleeding and patient was investigated extensively for deciphering the etiology of low platelet count. In-vitro clumping of platelets was suspected and in-vitro studies showed marked clumping of platelets with ethylene-diamine-tetra-acetic acid, citrate and heparinized samples. The manual platelet count was found to be within normal limits. Thrombocytopenia as a result of platelet cold agglutinins is a rare cause of in-vitro low platelet counts. No clinical problems have been reported due to the same.

  7. The immune thrombocytopenia syndrome: a disorder of diverse pathogenesis and clinical presentation.

    Science.gov (United States)

    Cines, Douglas B; Liebman, Howard A

    2009-12-01

    This article presents a brief history of immune thrombocytopenia (ITP) from the first clinical description written in 1735, through years of controversy about the nature and causes of what was first known as idiopathic thrombocytopenia purpura, then immune thrombocytopenic purpura, and, finally, ITP. Current understanding of ITP's primary and secondary forms and the effect of diverse defects in immune self tolerance that result in the development of antiplatelet antibodies is described. This overview is followed by a narrative list of other articles in this issue on topics ranging from a comprehensive review of the role of antiplatelet antibodies in platelet destruction and production to a review of classic treatment modalities and newer approaches to initial treatment.

  8. Contemporary management of neonatal alloimmune thrombocytopenia: good outcomes in the intravenous immunoglobulin era: results from the Australian neonatal alloimmune thrombocytopenia registry.

    Science.gov (United States)

    Crighton, Gemma L; Scarborough, Ri; McQuilten, Zoe K; Phillips, Louise E; Savoia, Helen F; Williams, Bronwyn; Holdsworth, Rhonda; Henry, Amanda; Wood, Erica M; Cole, Stephen A

    2017-10-01

    To describe the natural history, antenatal and postnatal therapy, and clinical outcomes of Australian patients with fetomaternal/neonatal alloimmune thrombocytopenia (NAIT) recorded in the Australian NAIT registry. Analysis of registry data of Australian mothers treated antenatally for NAIT and any fetus/newborn with thrombocytopenia (TCP) and maternal human platelet antigen (HPA) antibodies. Ninety four potential cases (91 pregnancies; three twin pregnancies) were registered between December 2004 and September 2015 with 76 confirmed or treated as NAIT. NAIT was frequently unanticipated (44 cases, 58%), whilst 32 cases (42%) were anticipated due to personal or family history. In 70/76 cases, the diagnosis of NAIT was made based on HPA antibody results; anti-HPA-1a was most commonly detected (58/70, 82%), followed by anti-HPA-5b (5/70, 7%). Intracranial haemorrhage (ICH) was detected in seven cases (9%). Maternal antenatal therapy resulted in improved clinical outcomes. For antenatally treated cases, whilst 10/29 (34%) neonates had severe TCP, only one ICH was detected. This study provides data on contemporary "real world" management of Australian mothers and babies with NAIT. Antenatal IVIG therapy was associated with better neonatal outcomes. Maternal side-effects and treatment costs were substantial.

  9. ANA Negative Systemic Lupus Erythematosus Leading to CTEPH, TTP-Like Thrombocytopenia, and Skin Ulcers

    OpenAIRE

    Changal, Khalid Hamid; Sofi, Fayaz; Altaf, Sheikh Shoaib; Raina, Adnan; Raina, Ab. Hameed

    2016-01-01

    SLE affects almost every organ system, with differing degrees of severity. During its clinical course periods of flares may alternate with periods of remission culminating in disease and therapy related damage. We describe a case of ANA negative SLE with severe thrombocytopenia, cutaneous vasculitis, antiphospholipid antibody syndrome, and pulmonary artery hypertension. As there is no definitive cure for SLE the treatment lies in caring for the individual organ systems involved and simultaneo...

  10. ANA Negative Systemic Lupus Erythematosus Leading to CTEPH, TTP-Like Thrombocytopenia, and Skin Ulcers

    Directory of Open Access Journals (Sweden)

    Khalid Hamid Changal

    2016-01-01

    Full Text Available SLE affects almost every organ system, with differing degrees of severity. During its clinical course periods of flares may alternate with periods of remission culminating in disease and therapy related damage. We describe a case of ANA negative SLE with severe thrombocytopenia, cutaneous vasculitis, antiphospholipid antibody syndrome, and pulmonary artery hypertension. As there is no definitive cure for SLE the treatment lies in caring for the individual organ systems involved and simultaneously taking care of the patient as a whole.

  11. Immune Thrombocytopenia and JAK2V617F Positive Essential Thrombocythemia: Literature Review and Case Report

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    M. A. Sobas

    2017-01-01

    Full Text Available We present the case where immune thrombocytopenia (ITP and essential thrombocythemia (ET sequentially appeared in the space of twenty-one years of follow-up. Impaired platelet production is present in both diseases, but clinical presentation and treatment are different. On the basis of this case history a possible role of autoimmunity as a predisposing factor to myeloproliferation has been discussed.

  12. Prognostic Factors for Immune Thrombocytopenia Outcome in Greek Children: A Retrospective Single-Centered Analysis

    OpenAIRE

    Makis, Alexandros; Gkoutsias, Athanasios; Palianopoulos, Theodoros; Pappa, Eleni; Papapetrou, Evangelia; Tsaousi, Christina; Hatzimichael, Eleftheria; Chaliasos, Nikolaos

    2017-01-01

    Immune thrombocytopenia (ITP) in children has a varied course and according to duration is distinguished as newly diagnosed (12) types. Several studies have evaluated the prognostic factors for the progression of the disease, but similar works have yet to be performed in Greece. We aimed to identify prognostic markers for the three forms of the disease in 57 Greek children during a 13-year period. Information regarding age, gender, preceding infection, bleeding type, duration of symptoms and ...

  13. Persistent intestinal bleeding due to severe CMV-related thrombocytopenia in a preterm newborn.

    Science.gov (United States)

    Berardi, Alberto; Spaggiari, Eugenio; Cattelani, Chiara; Roversi, Maria Federica; Pecorari, Monica; Lazzarotto, Tiziana; Ferrari, Fabrizio

    2018-05-01

    The optimal threshold for neonatal platelet transfusions in sick newborns is still uncertain. We report a congenital cytomegalovirus (CMV) infection in a premature neonate with severe thrombocytopenia who subsequently presented with necrotizing enterocolitis and intestinal bleeding. The baby recovered after platelet transfusions were discontinued and the therapy was switched from intravenous ganciclovir to oral valganciclovir. We discuss both measures, speculating on the key role of platelet transfusions.

  14. Discovery of innovative therapies for rare immune-mediated inflammatory diseases via off-label prescription of biologics: the case of IL-6 receptor blockade in Castleman’s disease

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    Anne eMusters

    2015-12-01

    Full Text Available Biologics have revolutionized the field of clinical immunology and proven to be both effective and safe in common immune-mediated inflammatory diseases (IMIDs such as rheumatoid arthritis, inflammatory bowel diseases, and various haematological disorders. However, in patients with rare, severe IMIDs failing on standard therapies it is virtually impossible to conduct randomized controlled trials. Therefore, biologics are usually prescribed off-label in these often severely ill patients. Unfortunately, off-label prescription is sometimes hampered in these diseases due to a lack of reimbursement that is often based on a presumed lack of evidence for effectiveness. In the present article will discuss that off-label prescription of biologics can be a good way to discover new treatments for rare diseases. This will be ilustrated using a case of multicentric Castleman’s disease, an immune-mediated lymphoproliferative disorder, in which off-label tocilizumab (humanized anti-IL-6 receptor blocking antibody treatment resulted in remarkable clinical improvement. Furthermore, we will give recommendations for monitoring efficacy and safety of biologic treatment in rare IMIDs, including the use of registries. In conclusion, we put forward that innovative treatments for rare IMIDs can be discovered via off-label prescription of biologicals, provided that this is based on rational arguments including knowledge of the pathophysiology of the disease.

  15. A cross-sectional study of leukopenia and thrombocytopenia among Chinese adults with newly diagnosed HIV/AIDS.

    Science.gov (United States)

    Shen, Yinzhong; Wang, Jiangrong; Wang, Zhenyan; Shen, Jiayin; Tangkai Qi; Song, Wei; Tang, Yang; Liu, Li; Zhang, Renfang; Zeng, Yi; Lu, Hongzhou

    2015-04-01

    We conducted a cross-sectional study to determine the prevalence and risk factors of leukopenia and thrombocytopenia among Chinese adults with newly diagnosed HIV/AIDS. One thousand nine hundred and forty-eight newly diagnosed HIV-infected patients were enrolled between 2009 and 2010. Serum samples obtained from each individual were collected for complete blood count. Factors associated with the presence of leukopenia and thrombocytopenia were analyzed by multiple logistic regression. The overall prevalence of leukopenia and of thrombocytopenia was 33.2% and 15.6%, respectively. The prevalence of leukopenia was higher among females than among males (39.4% versus 31.2%). The prevalence of leukopenia increased with decreasing CD4 count (8.2%, 26.5%, 33.4%, and 41.5% among patients with CD4 count of ≥ 350, 200-349, 50-199, and leukopenia, and that lower CD4 count, and HIV transmission by blood were significantly associated with an increased risk of thrombocytopenia. The study reflects that leukopenia and thrombocytopenia are common among Chinese adults with newly diagnosed HIV/AIDS; and lower CD4 count is associated with an increased risk of both leukopenia and thrombocytopenia. We propose that a routine assessment of these parameters is necessary for timely and adequate clinical management.

  16. Nanoparticles camouflaged in platelet membrane coating as an antibody decoy for the treatment of immune thrombocytopenia.

    Science.gov (United States)

    Wei, Xiaoli; Gao, Jie; Fang, Ronnie H; Luk, Brian T; Kroll, Ashley V; Dehaini, Diana; Zhou, Jiarong; Kim, Hyeon Woo; Gao, Weiwei; Lu, Weiyue; Zhang, Liangfang

    2016-12-01

    Immune thrombocytopenia purpura (ITP) is characterized by the production of pathological autoantibodies that cause reduction in platelet counts. The disease can have serious medical consequences, leading to uncontrolled bleeding that can be fatal. Current widely used therapies for the treatment of ITP are non-specific and can, at times, result in complications that are more burdensome than the disease itself. In the present study, the use of platelet membrane-coated nanoparticles (PNPs) as a platform for the specific clearance of anti-platelet antibodies is explored. The nanoparticles, whose outer layer displays the full complement of native platelet surface proteins, act as decoys that strongly bind pathological anti-platelet antibodies in order to minimize disease burden. Here, we study the antibody binding properties of PNPs and assess the ability of the nanoparticles to neutralize antibody activity both in vitro and in vivo. Ultimately, we leverage the neutralization capacity of PNPs to therapeutically treat a murine model of antibody-induced thrombocytopenia and demonstrate considerable efficacy as shown in a bleeding time assay. PNPs represent a promising platform for the specific treatment of antibody-mediated immune thrombocytopenia by acting as an alternative target for anti-platelet antibodies, thus preserving circulating platelets with the potential of leaving broader immune function intact. Copyright © 2016 Elsevier Ltd. All rights reserved.

  17. A novel canine model of immune thrombocytopenia: Has ITP gone to the dogs?

    Science.gov (United States)

    LeVine, Dana N; Birkenheuer, Adam J; Brooks, Marjory B; Nordone, Shila K; Bellinger, Dwight A; Jones, Sam L; Fischer, Thomas H; Oglesbee, Stephen E; Frey, Kahlina; Brinson, Nicole S; Peters, Allison Pazandak; Marr, Henry S; Motsinger-Reif, Alison; Gudbrandsdottir, Sif; Bussel, James B; Key, Nigel S

    2014-01-01

    Summary Canine immune thrombocytopenia (ITP) is analogous to human ITP, with similar platelet counts and heterogeneity in bleeding phenotype among affected individuals. With a goal of ultimately investigating this bleeding heterogeneity, a canine model of antibody-mediated ITP was developed. Infusion of healthy dogs with 2F9, a murine IgG2a monoclonal antibody to the canine platelet glycoprotein GPIIb (a common target of autoantibodies in ITP) resulted in profound, dose-dependent thrombocytopenia. Model dogs developed variable bleeding phenotypes, e.g. petechiae and haematuria, despite similar degrees of thrombocytopenia. 2F9 infusion was not associated with systemic inflammation, consumptive coagulopathy, or impairment of platelet function. Unexpectedly however, evaluation of cytokine profiles led to the identification of platelets as a potential source of serum interleukin-8 (IL8) in dogs. This finding was confirmed in humans with ITP, suggesting that platelet IL8 may be a previously unrecognized modulator of platelet-neutrophil crosstalk. The utility of this model will allow future study of bleeding phenotypic heterogeneity including the role of neutrophils and endothelial cells in ITP. PMID:25039744

  18. Petechial-Purpuric Rash, Leukopenia and Thrombocytopenia Associated Parvovirus B19

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    Tugce Tural Kara

    2014-12-01

    Full Text Available Parvovirus B19 can cause different skin rashes like maculopapular, erythematous, petechial, or purpuric lesions. In addition, parvovirus B19 can cause some important hematologic disorders like aplastic anemia, leukopenia, neutropenia, and thrombocytopenia. We report a child who was admitted to the hospital with petechial-purpuric rashes. On laboratory analysis, leukopenia and thrombocytopenia were found and serologic testing of parvovirus B19 IgM was determined to be positive. After the third day of hospitalization, the petechial-purpuric rashes began to decline and laboratory results were in the normal range. We think that the disease was parvovirus B19 infection. The patient was treated with only antipyretic drugs. On follow up, the clinical and laboratory findings had completely returned to normal. In conclusion, parvovirus B19 can cause clinical signs such as petechiae and purpura. Also, hematologic disorders may be a complication. Because of this, it should be considered in the differential diagnosis in patients with rash, thrombocytopenia, and leukopenia.

  19. Gestational Thrombocytopenia: Does It Cause Any Maternal and /or Perinatal Morbidity?

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    Carlo Pafumi

    2013-06-01

    Full Text Available Purpose: The iam of this study was retrospectively evaluate maternal platelet count fluctuation during pregnancy and puerperium and its correlation with the newborn’s platelet levels. Method: A group of 36 patients who have been referred to a haematology-clinic for gestational thrombocytopenia (GT and who delivered at the same hospital during a period of 4 years, from January 2006 to December2009 were included in the study. Mothers and their related foetuses- newborns were evaluated retrospectively for symptoms and/or signs of external and internal haemorrhage throughout pregnancy and early puerperium, even in relationship with mode of delivery (caesarean section versus spontaneous vaginal delivery. Results: All observed cases of GT have an uncomplicated course with no related perinatal and maternal morbidity even in patients with initial platelet count < 75.000/ml independently from the route of delivery. Conclusion: In case of gestational thrombocytopenia a complete normalization of maternal platelet count should be expected during the postpartum period, even if a diagnosis of a concomitant incidental neonatal thrombocytopenia cannot be excluded.No intervention, such as a foetal platelet count or caesarean section, is necessary. [Cukurova Med J 2013; 38(3.000: 349-357

  20. MEGAKARYOCYTIC ALTERATION IN CASES OF THROMBOCYTOPENIA- A BONE MARROW ASPIRATION STUDY

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    Pulok Kutum

    2017-09-01

    Full Text Available BACKGROUND Thrombocytopenia defined as platelet counts less than 1,50,000/μL is commonly found in many haematological practices. The various disorders ranges from benign to malignant conditions. MATERIALS AND METHODS All the bone marrow aspiration smears who presented with thrombocytopenia were retrospectively studied during the period May 2015 to April 2017. The study was conducted in the Department of Pathology, Regional Institute of Medical Sciences, Imphal. All the Leishman stained bone marrow aspirate smears were taken from the archives and studied again with special reference to the megakaryocyte number and the various morphology. The clinical details and the diagnosis were also noted. RESULTS A total of 258 bone marrow aspiration smears were included in the study. The most common cause of thrombocytopenia in the study was AML (53 cases, followed by nutritional anaemia (42 cases and hypoplastic anaemia (38 cases. Various other causes like aplastic anaemia, infective cause and malignant infiltration of the bone marrow were also encountered. In cases of myelodysplasia, dysplastic forms, bare megakaryocytic nuclei, hypogranular forms and micromegakaryocytes were seen. CONCLUSION Giving an undue importance to the morphology and number of megakaryocytes, while reporting bone marrow aspiration smears can help in enabling the diagnostic accuracy of various haematological conditions.

  1. Effect of thrombocytopenia on mode of analgesia/anesthesia and maternal and neonatal outcomes.

    Science.gov (United States)

    Dikman, Daniel; Elstein, Deborah; Levi, Gal Schtrechman; Granovsky-Grisaru, Sorina; Samueloff, Arnon; Gozal, Yaacov; Ioscovich, Alexander

    2014-04-01

    The purpose was to correlate the use of regional analgesia/anasthesia among women with different degrees of thrombocytopenia relative to women with normal platelet counts, and note maternal and neonatal outcome, and mode of delivery. A case-control paradigm was developed based on women who delivered during 2007-2011 with platelet counts ≤80 000/mm(3). For each woman in this "severe" thrombocytopenic group, an age- and parity-matched control was found who delivered a singleton within the same year but whose platelets were either 81 000-150 000/mm(3) ("moderate" thrombocytopenia) or ≥151 000/mm(3) (normal platelet counts). 168 women were identified for each group; mean maternal age (28.4 years), mean gravidity (4.3), mean parity (3.7), mean gestational age (39.2 weeks) and mean birth weight (3283 g) were comparable. However, only in the severe thrombocytopenic women were there very early preterm deliveries, lowest birth weight, lowest Apgar scores, the greatest number with serious post-partum hemorrhage (>500 ml); use of regional analgesia/anesthesia was lowest, and percent cesarean sections highest. This study highlights potential for adverse maternal outcome of post-partum hemorrhage and adverse neonatal outcomes of prematurity, low birth weight, and low Apgar scores (but not neonatal death), and limited regional analgesia/anesthesia in women who present at delivery with severe (≤80 000/mm(3)) thrombocytopenia.

  2. Therapeutic strategies for hepatitis- and other infection-related immune thrombocytopenias.

    Science.gov (United States)

    Stasi, Roberto

    2009-01-01

    Secondary thrombocytopenia may result from autoimmune diseases, lymphoproliferative disorders, infections, myelodysplastic syndromes, common variable immunodeficiency, agammaglobulinemia, hypogammaglobulinemia, immunoglobulin A deficiency, and drugs. The presence of thrombocytopenia may result from chronic infections with hepatitis C virus (HCV), human immunodeficiency virus (HIV), and Helicobacter pylori and should be considered in the differential diagnosis of immune thrombocytopenic purpura (ITP). Studies have shown that upon diagnosis of infections, treatment of the primary disease allows for stabilization of platelet counts. Antiviral therapy with highly active antiretroviral therapy (HAART) for HIV has aided in platelet recovery with a corresponding decrease in circulating viral load. In some cases, the use of a thrombopoietin (TPO) agonist, eltrombopag, normalizes platelet levels in patients with these infections. Thrombocytopenia in the absence of other disease symptoms requires screening for H pylori, especially in regions where there is a high prevalence of the disease, such as in Japan, and in cases where platelets have normalized following eradication therapy. In other regions where these infections are not prevalent, such testing is controversial.

  3. Helicobacter pylori, anemia, iron deficiency and thrombocytopenia among pregnant women at Khartoum, Sudan.

    Science.gov (United States)

    Mubarak, Nahla; Gasim, Gasim I; Khalafalla, Khalifa E; Ali, Naj I; Adam, Ishag

    2014-06-01

    Helicobacter pylori is a common gut pathogen that is linked to many complications of pregnancy such as iron deficiency anemia, pre-eclampsia and thrombocytopenia. There are no published data on H. pylori in Sudan. A cross-sectional study was conducted during the period May-June 2012 at the antenatal care unit of Khartoum Hospital, Sudan, to investigate prevalence of H. pylori and its association, if any, with anemia and thrombocytopenia. Obstetric and medical histories were gathered using questionnaires. Hemoglobin and serum ferritin were measured and H. pylori antibodies (IgA and IgG) investigated using ELISA. Among 179 women, rates of positivity for specific IgG formed against H. pylori were 69.8% (125/179), 94.0% (168/179) and 5.6% (10/179) for IgA, IgG and both IgG and IgA, respectively. There was no association between the expected risk factors (age, parity, education) and H. pylori seropositivity. Of these women, 42/179 (24.3%), 50/179 (28.9%) and 19/179 (11%), respectively, were anemic (hemoglobin Sudan, and it is not associated with anemia or thrombocytopenia. © The Author 2014. Published by Oxford University Press on behalf of Royal Society of Tropical Medicine and Hygiene. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.

  4. Malaria with Acute Renal Failure in a Middle Aged Man: A Case ...

    African Journals Online (AJOL)

    The case of a middle aged(39 years) man admitted with severe malaria in the male ward of the Federal Medical Centre, Owerri, Imo State, Nigeria is reported. The infecting species was Plasmodium falciparum and the patient was febrile, developed acute renal failure, severe thrombocytopenia and hepatic failure. Treatment ...

  5. Recipient-derived HPA-1a antibodies: a cause of prolonged thrombocytopenia after unrelated donor stem cell transplantation.

    Science.gov (United States)

    Lucas, Geoff; Culliford, Steven; Green, Frances; Sidra, Gamal; Calvert, Anthony; Green, Ann; Harrison, Penny; Harvey, John; Allen, Dave; Smillie, David; Masurekar, Ashish; Marks, David; Russell, Nigel; Massey, Edwin

    2010-02-01

    Patients with human platelet antigen (HPA) specific antibodies in cases of neonatal alloimmune thrombocytopenia and platelet (PLT) refractoriness derive clinical benefit from the use of HPA-selected PLTs. This study describes three patients with underlying diagnoses of acute myeloid leukemia, chronic lymphocytic leukemia, and myelodysplasia, respectively, who underwent allogeneic bone marrow transplantation (BMT) with unrelated donors matched at the HLA-A, B, C, Dr, and DQ loci but who failed to achieve an adequate PLT count. Investigation using PLT immunofluorescence test, monoclonal antibody immobilization of PLT antigens assay, and genotyping revealed the presence of recipient-derived HPA-1a antibodies. In two patients, anti-HPA-1a was detected post-BMT and in the third patient, anti-HPA-1a was detected during pre-BMT chemotherapy. Despite apparent 100% engraftment of donor cells, the patients' PLT counts failed to recover 9-10 months posttransplant. The patients remained PLT-transfusion dependent and failed to achieve satisfactory increments following random donor or HLA-matched PLT transfusions. After the identification of HPA-1a antibodies, the patients were supported by HPA-1a(-) PLTs and satisfactory posttransfusion PLT increments were obtained. These cases illustrate that HPA-1a antibodies may remain detectable for 10 months following apparently successful donor engraftment and the disappearance of recipient-derived HLA antibodies. The prolonged persistence of recipient-derived PLT-specific antibodies following BMT has to our knowledge not been described previously. HPA-1a antibodies were associated with protracted PLT-transfusion dependence and significant hemorrhagic complications. Appropriate and timely laboratory investigation for HPA-specific antibodies followed by transfusion support with HPA-selected PLTs provided the cornerstone of the hemostatic management in these cases.

  6. Acute renal failure in a child with thrombocytopenic purpura caused by acute Epstein-Barr virus infection after treatment with anti-D immunoglobulin.

    Science.gov (United States)

    Kossiva, Lydia; Kyriakou, Dimitrios; Mitsioni, Andromachi; Garoufi, Anastasia

    2013-06-01

    Immune thrombocytopenia (ITP) in children is usually a benign, self-limiting disorder. An acute Epstein-Barr virus (EBV) infection usually causes atypical lymphocytosis and mild decrease in platelets. Severe thrombocytopenia is an extremely rare complication. Anti-D immunoglobulin has been used for treatment of ITP in Rh(D)-positive nonsplenectomized patients. Severe hemolysis and acute renal failure are extremely rare complications that may be aggravated by the presence of an acute EBV infection. It is believed that anti-D immunoglobulin triggers an unusual virus-induced immune response causing hemolysis. We present a 4-year-old girl with ITP caused by an acute EBV infection that developed acute kidney injury following treatment with anti-D immunoglobulin. The patient recovered completely from thrombocytopenia and renal dysfunction. Intravascular hemolysis and acute kidney injury are consistent with anti-D immunoglobulin mechanism of action. Pediatric patients treated with anti-D immunoglobulin for ITP should be closely monitored for signs and symptoms of hemolysis that may be aggravated by the presence of EBV infection leading to impaired renal function.

  7. Benign acute childhood myositis.

    Science.gov (United States)

    Rajajee, Sarala; Ezhilarasi, S; Rajarajan, K

    2005-05-01

    To describe the clinical and laboratory features of benign acute childhood myositis. 40 children of BACM were seen during October 2001 to February 2002, 22 (52%) were male with mean age of 5.3 years. Duration of illness was 3.97 days. Preceding symptoms included fever, leg pain, vomiting and inability to walk. A provisional diagnosis of viral myositis was made in 26 (66%). Guillian Barre Syndrome was the most common referral diagnosis. 11 (27.5%) children had leucopenia with lymphocytic response and 16 (40%) had thrombocytopenia. CRP was negative in 32 (80%). CPK was markedly elevated (more than 1000 IU/l) in 18 (45%) and more than 500 IU/l in 11 (27.5%) remaining between 200 to 500 IU/l. Associated features were hepatitis (elevated SGOT & SGPT) in 28 (70%) and shock in 5 (12.5%). Serological test were indicative of dengue virus (Elisa PAN BIO) in 20 (50%) of which 8 (25%) were primary dengue and 12 (30%) were secondary dengue. The outcome of therapy mainly supportive were excellent. Benign acute myositis occurs often in association with viral infection. In the present study, Dengue virus was positive in 20 (50%) children. Benign acute myositis can be differentiated from more serious causes of walking difficulty by presence of calf and thigh muscle tenderness on stretching, normal power and deep tendon reflex and elevated CPK.

  8. Thrombocytopenia from combination treatment with oseltamivir and probenecid: case report, MedWatch data summary, and review of the literature.

    Science.gov (United States)

    Raisch, Dennis W; Straight, Timothy M; Holodniy, Mark

    2009-08-01

    The possibility of an avian flu pandemic has spurred interest in preventive treatments with antivirals such as oseltamivir. Combining treatment with probenecid to delay excretion may extend limited supplies of oseltamivir. We previously conducted a pharmacokinetic study of oseltamivir plus probenecid among healthy volunteers. In this article, we describe a 68-year-old woman who, during the pharmacokinetic study, developed severe thrombocytopenia 2 weeks after starting oseltamivir plus probenecid. She was receiving no other drug therapy at the time. Her platelet count decreased from 200 to 15 x 10(3)/mm(3), although no clinically evident bleeding abnormalities were noted. The two drugs were discontinued. One week later, without any therapeutic intervention, her platelet count returned to normal. By using the Naranjo adverse drug reaction probability scale to assess the strength of the association between the drugs and the adverse event, a score of 7 was derived for both drugs, indicating that the association was probable. We found no previous literature reports of thrombocytopenia associated with either drug. However, a review of the United States Food and Drug Administration's Adverse Event Reporting System database found 93 cases of thrombocytopenia and/or decreased platelet counts associated with oseltamivir and 24 cases associated with probenecid administration. Signal detection analyses were significant for oseltamivir (p=0.001), but not probenecid. The underlying mechanism of thrombocytopenia with these drugs is unknown. Clinicians should be aware that the use of oseltamivir and probenecid has been reported to be associated with thrombocytopenia.

  9. Effect of Carica papaya Leaf Extract Capsule on Platelet Count in Patients of Dengue Fever with Thrombocytopenia.

    Science.gov (United States)

    Gadhwal, Ajeet Kumar; Ankit, B S; Chahar, Chitresh; Tantia, Pankaj; Sirohi, P; Agrawal, R P

    2016-06-01

    Thrombocytopenia in dengue fever is a common and serious complication. However, no specific treatment is available for dengue fever induced thrombocytopenia. In few countries (Pakistan, Malaysia, Sri Lanka and other Asian countries) the leaf extract of Carica papaya has been effectively used for thrombocytopenia. So, the study is planned to access effect of Carica papaya leaf extract on platelet count in dengue fever patients. All participants were randomised into two groups, study group and control group; the study group was given papaya leaf extract capsule of 500 mg once daily and routine supportive treatment for consecutive five days. The controls were given only routine supportive treatment. Daily complete blood counts, platelet counts and haematocrit level, liver function test, renal function test of both groups were observed. On the first day platelet count of study group and control group was (59.82±18.63, 61.06±20.03 thousands, p value 0.36). On the 2nd day platelet count of both study and control groups was not significantly different (61.67±19.46 and 59.93±19.52 thousands, p value 0.20) but on 3rd day platelet count of study group was significantly higher than control group (82.96±16.72, 66.45±17.36 thousands, p value dengue fever without any side effect and prevents the complication of thrombocytopenia. So, it can be used in dengue fever with thrombocytopenia patients.

  10. Thrombocytopenia in Patients with Gastric Varices and the Effect of Balloon-occluded Retrograde Transvenous Obliteration on the Platelet Count

    Directory of Open Access Journals (Sweden)

    W E Saad

    2014-01-01

    Full Text Available Objectives: Gastric varices primarily occur in cirrhotic patients with portal hypertension and splenomegaly and thus are probably associated with thrombocytopenia. However, the prevalence and severity of thrombocytopenia are unknown in this clinical setting. Moreover, one-third of patients after balloon-occluded retrograde transvenous obliteration (BRTO have aggravated splenomegaly, which potentially may cause worsening thrombocytopenia. The aim of the study is to determine the prevalence and degree of thrombocytopenia in patients with gastric varices associated with gastrorenal shunts undergoing BRTO, to determine the prognostic factors of survival after BRTO (platelet count included, and to assess the effect of BRTO on platelet count over a 1-year period. Materials and Methods: This is a retrospective review of 35 patients who underwent BRTO (March 2008-August 2011. Pre- and post-BRTO platelet counts were noted. Potential predictors of bleeding and survival (age, gender, liver disease etiology, platelet count, model for end stage liver disease [MELD]-score, presence of ascites or hepatocellular carcinoma were analyzed (multivariate analysis. A total of 91% (n = 32/35 of patients had thrombocytopenia (90% of patients in patients undergoing BRTO. However, BRTO (with occlusion of the gastrorenal shunt has little effect on the platelet count. Long-term outcomes of BRTO for bleeding gastric varices using sodium tetradecyl sulfate in the USA are impressive with a 4-year variceal rebleed rate and transplant-free survival rate of 9% and 76%, respectively. Platelet count is not a predictor of higher rebleeding or patient survival after BRTO.

  11. Interleukin-11-induced capillary leak syndrome in primary hepatic carcinoma patients with thrombocytopenia

    Directory of Open Access Journals (Sweden)

    Li-Rong Shen

    2011-05-01

    Full Text Available Abstract Background Capillary leak syndrome (CLS is a rare condition characterized by recurrent episodes of generalized edema and severe hypotension associated with hypoproteinemia. Interleukin-11 (IL-11 is a promising therapeutic agent for thrombocytopenia. A direct correlation between IL-11 and CLS has never been reported previously, particularly in patients with hepatic carcinoma. Case presentation We describe two cases of CLS after IL-11 administration in two males with thrombocytopenia. Case 1 was a 46-year-old man with recurrence of hepatic carcinoma who was treated with IL-11 (3 mg per day. After four days of therapy, hypotension and hypoproteinemia were detected. The chest X-ray and B ultrasound of the abdomen showed pleural effusion and ascites. IL-11 was then discontinued, fluid resuscitation was performed, and fresh frozen plasma and packed red blood cells were transfused into this patient. The patient had recovered after 19 days of treatment. Case 2 was a 66-year-old man who had undergone radiofrequency ablation (RFA for hepatic carcinoma. He was treated with IL-11 (3 mg per day for thrombocytopenia. After two days of therapy, this patient complained of dyspnea with bilateral edema of the hands. Laboratory values showed hypoproteinemia. IL-11 was stopped and human albumin was transfused at a rate of 10 g per day. On the 4th day, fluid resuscitation was performed. The patient had recovered after treatment for two weeks. Conclusions The detection of IL-11-induced CLS supports the hypothesis that CLS could be a severe side effect of IL-11 treatment in some patients. These two case reports also demonstrate that patients with hepatic carcinoma who experience this rare form of CLS after treatment with IL-11 seem to respond to a therapeutic regimen that involves hydroxyethyl starch, albumin, and diuretic therapy. Liver cancer patients might be more susceptible to CLS because of poor liver function and hypersplenia. In addition, bleeding

  12. SIRS-associated coagulopathy and organ dysfunction in critically ill patients with thrombocytopenia.

    Science.gov (United States)

    Ogura, Hiroshi; Gando, Satoshi; Iba, Toshiaki; Eguchi, Yutaka; Ohtomo, Yasuhiro; Okamoto, Kohji; Koseki, Kazuhide; Mayumi, Toshihiko; Murata, Atsuo; Ikeda, Toshiaki; Ishikura, Hiroyasu; Ueyama, Masashi; Kushimoto, Shigeki; Saitoh, Daizoh; Endo, Shigeatsu; Shimazaki, Shuji

    2007-10-01

    Coagulopathy and thrombocytopenia often occur in critically ill patients, and disseminated intravascular coagulation (DIC) can lead to multiple organ dysfunction and a poor outcome. However, the relation between coagulopathy and systemic inflammatory response has not been thoroughly clarified. Thus, we evaluated coagulative activity, organ dysfunction, and systemic inflammatory response syndrome (SIRS) in critically ill patients with thrombocytopenia and examined the balance between coagulopathy and systemic inflammation. Two hundred seventy-three patients, who were admitted to 13 critical care centers in Japan and fulfilled the criteria of platelet count of less than 150*10(9)/L, were included. Coagulative variables (platelet count, fibrin/fibrinogen degradation products, and DIC scores), organ dysfunction index (Sequential Organ Failure Assessment [SOFA] score), and SIRS score in each patient were evaluated for 4 consecutive days after fulfilling the above entry criteria. The effect of SIRS on coagulopathy and organ dysfunction was evaluated in these patients. Both the maximum SIRS score and entry SIRS score had significant relation to the maximum SOFA score during the observation period. Coagulation disorders indicated by the minimum platelet count, maximum DIC scores, and positivity for DIC worsened gradually with increases in SIRS scores. Both the minimum platelet count and maximum DIC scores were significantly correlated with the maximum SOFA score, indicating that a relation exists between coagulopathy and organ dysfunction. In critically ill patients with thrombocytopenia, coagulopathy and organ dysfunction progress with significant mutual correlation, depending on the increase in SIRS scores. The SIRS-associated coagulopathy may play a critical role in inducing organ dysfunction after severe insult.

  13. Correlation of thrombocytopenia with grading of esophageal varices in chronic liver disease patients

    International Nuclear Information System (INIS)

    Abbasi, A.; Butt, N.; Bhutto, A.R.; Munir, S.M.

    2010-01-01

    To determine the severity of thrombocytopenia in different grades of esophageal varices. Study Design: Cross-sectional analytical study. Place and Duration of Study: Jinnah Postgraduate Medical Centre, Karachi, Medical Unit-III, Ward-7 from January to December 2008. Methodology: Subjects were eligible if they had a diagnosis of cirrhosis. Patient with advanced cirrhosis (Child-Pugh class C), human immunodeficiency virus (HIV) infection, hepatocellular carcinoma, portal vein thrombosis, parenteral drug addiction, current alcohol abuse and previous or current treatment with b-blockers, diuretics and other vasoactive drugs were excluded from the study. All patients under went upper gastrointestinal endoscopy after consent. On the basis of platelet count patients were divided into four groups. Group I with platelets greater or equal to 20000/mm/sup 3/, Group II with values of 21000- 50000/mm/sup 3/, Group III with count of 51000-99000/mm/sup 3/ and Group IV with count of 100000-150000/mm/sup 3/. Correlation of severity of thrombocytopenia with the grading of esophageal varices was assessed using Spearman's correlation with r-values of 0.01 considered significant. Results: One hundred and two patients with thrombocytopenia and esophageal varices were included in the study. There were 62 (60.8%) males and 40 (39.2%) females. The mean age of onset of the disease in these patients was 49.49 +- 14.3 years with range of 11-85 years. Major causes of cirrhosis were hepatitis C (n=79, 77.5%), hepatitis B (n=12, 11.8%), mixed hepatitis B and C infection (n=8, 7.8%) and Wilson's disease (n=3,2.9%). Seven patients had esophageal grade I, 24 had grade II, 35 had grade III, and 36 had grade IV. Gastric varices were detected in 2 patients. Portal hypertensive gastropathy were detected in 87 patients. There was an inverse correlation of platelet count with grading of esophageal varices (r=-0.321, p < 0.001). Conclusion: The severity of thrombocytopenia increased as the grading of

  14. Robot-assisted laparoscopic prostatectomy performed in a patient with severe thrombocytopenia due to primary myelofibrosis

    Science.gov (United States)

    Khavari, Rose; Stamatakis, Lambros; Miles, Brian

    2009-01-01

    Robot-assisted laparoscopic prostatectomy (RALP) has emerged as a minimally invasive alternative to open radical prostatectomy (ORP) for the treatment of clinically localized prostate cancer. In comparison to the open procedure, there is significantly less intra-operative blood loss during RALP. This benefit has allowed RALP to become a feasible option for patients who would be poor candidates for ORP, including those patients with intrinsic hematological disorders. In this case study, we report a successfully performed RALP in a patient with severe thrombocytopenia in the presence of primary myelofibrosis. PMID:19672431

  15. Neonatal alloimmune thrombocytopenia caused by anti-HLA-A24 alloantibodies.

    Science.gov (United States)

    Starcevic, M; Tomicic, M; Malenica, M; Zah-Matakovic, V

    2010-04-01

    Neonatal alloimmune thrombocytopenia (NAIT) occurs as a result of maternal alloimmunization against paternally inherited antigens on foetal platelets. Platelets express platelet specific antigens (HPA) along with human leucocyte antigens (HLA) class I. Although anti-HLA class I antibodies are often detectable in pregnant women, their role in NAIT is considered controversial. We report a case of NAIT where the most sensitive serological analysis and molecular methods could not detect platelet specific antibodies. Only HLA incompatibility and presence of anti-HLA-A24 antibodies in both the mother's and the newborn's serum were proven. This case supports the idea that some anti-HLA class I antibodies could cause NAIT.

  16. Diagnosis and treatment of MYH9-RD in an Australasian cohort with thrombocytopenia.

    Science.gov (United States)

    Rabbolini, David J; Chun, Yenna; Latimer, Maya; Kunishima, Shinji; Fixter, Kathleen; Valecha, Bhavia; Tan, Peter; Chew, Lee Ping; Kile, Benjamin T; Burt, Rachel; Radhakrishnan, Kottayam; Bird, Robert; Ockelford, Paul; Gabrielli, Sara; Chen, Qiang; Stevenson, William S; Ward, Christopher M; Morel-Kopp, Marie-Christine

    2017-11-01

    MYH9-related disorders (MYH9-RDs) caused by mutation of the MYH9 gene which encodes non-muscle myosin heavy-chain-IIA (NMMHC-IIA), an important motor protein in hemopoietic cells, are the most commonly encountered cause of inherited macrothrombocytopenia. Despite distinguishing features including an autosomal dominant mode of inheritance, giant platelets on the peripheral blood film accompanied by leucocytes with cytoplasmic inclusion bodies (döhle-like bodies), these disorders remain generally under-recognized and often misdiagnosed as immune thrombocytopenia (ITP). This may result in inappropriate treatment with corticosteroids, immunosupressants and in some cases, splenectomy. We explored the efficacy of next generation sequencing (NGS) with a candidate gene panel to establish the aetiology of thrombocytopenia for individuals who had been referred to our center from hematologists in the Australasian region in whom the cause of thrombocytopenia was suspected to be secondary to an inherited condition but which remained uncharacterized despite phenotypic investigations. Pathogenic MYH9 variants were detected in 15 (15/121, 12.4%) individuals and the pathogenecity of a novel variant of uncertain significance was confirmed in a further two related individuals following immunofluorescence (IF) staining performed in our laboratory. Concerningly, only one (1/17) individual diagnosed with MYH9-RD had been referred with this as a presumptive diagnosis, in all other cases (16/17, 94.1%), a diagnosis was not suspected by referring clinicians, indicating a lack of awareness or a failing of our diagnostic approach to these conditions. We examined the mean platelet diameter (MPD) measurements as a means to better identify and quantify platelet size. MPDs in cases with MYH9-RDs were significantly larger than controls (p < 0.001) and in 91% were greater than a previously suggested threshold for platelets in cases of ITP. In addition, we undertook IF staining in a proportion of

  17. Thrombocytopenia and Postpartum Hemorrhage in a Woman with Chromosome 22q11.2 Deletion Syndrome

    Directory of Open Access Journals (Sweden)

    Sarah L. Pachtman

    2016-01-01

    Full Text Available Chromosome 22q11.2 deletion syndrome, also known as DiGeorge or velocardiofacial syndrome, is associated with a wide spectrum of phenotypic features. It is known to be associated with severe macrothrombocytopenia. Postpartum hemorrhage is a leading cause of maternal morbidity and mortality globally. Chromosome 22q11.2 deletion syndrome is rare cause of thrombocytopenia that can be a significant risk factor for life-threatening postpartum hemorrhage. We report a case of postpartum hemorrhage in a woman with 22q11.2 deletion syndrome causing severe macrothrombocytopenia.

  18. Health-related quality of life in children with chronic immune thrombocytopenia in China

    OpenAIRE

    Zhang, Heng; Wang, Li; Quan, Meijie; Huang, Jie; Wu, Peng; Lu, Qin; Fang, Yongjun

    2016-01-01

    Background The concept of health-related quality of life (HRQoL) was brought up decades ago and has been well utilized in many different areas. Regarding immune thrombocytopenia (ITP) management, much work has been done to emphasize the necessity of taking HRQoL into consideration. However, data on HRQoL of children with chronic ITP remain rare. Methods This is a cross-sectional study. Children with chronic ITP aged from 2 to 18 and their parents were recruited. Participants completed the Ped...

  19. Thrombocytopenia and craniotomy for tumor: A National Surgical Quality Improvement Program analysis.

    Science.gov (United States)

    Dasenbrock, Hormuzdiyar H; Devine, Christopher A; Liu, Kevin X; Gormley, William B; Claus, Elizabeth B; Smith, Timothy R; Dunn, Ian F

    2016-06-01

    To the authors' knowledge, the current study is the first national analysis of the association between preoperative platelet count and outcomes after craniotomy. Patients who underwent craniotomy for tumor were extracted from the prospective National Surgical Quality Improvement Program registry (2007-2014) and stratified by preoperative thrombocytopenia, defined as mild (125,000-149,000/μL), moderate (100,000-124,000/μL), severe (75,000-99,000/μL), or very severe (craniotomy for tumor. Cancer 2016;122:1708-17. © 2016 American Cancer Society. © 2016 American Cancer Society.

  20. Vascular- and pregnancy-related outcomes in patients with systemic lupus erythematosus with positive antiphospholipid profile and thrombocytopenia.

    Science.gov (United States)

    Haddad, A; Gladman, D D; Ibañez, D; Urowitz, M B

    2015-07-01

    This study aimed to investigate whether patients with lupus and a positive antiphospholipid profile with thrombocytopenia are at a higher risk for obstetric complications or thrombotic events than patients without thrombocytopenia. We conducted a case-control study matched 3:1 by sex, age of systemic lupus erythematosus diagnosis, age at study start, disease duration and length of follow-up time. Time to first event following study start was compared using Kaplan-Meier curves and log-rank tests and it was not statistically significant. In this study setting and population, thrombocytopenia was not associated with a higher risk for obstetrical complications or thrombotic events. © The Author(s) 2014.

  1. Frank hematuria as the presentation feature of acute leukemia

    Directory of Open Access Journals (Sweden)

    Suriya Owais

    2010-01-01

    Full Text Available Muco-cutaneous bleeding is a common presenting feature of acute leukemias. Mucosal bleeding usually manifests as gum bleeding and/or epistaxis but may occur in any mucosal surface of the body. Hematuria as an isolated or main presenting feature of acute leukemia is rare. We describe two cases of acute leukemia, a 19 year old male with acute lymphoblastic leukemia and a 52 year old male with acute myeloid leukemia, both presenting with gross hematuria. There was no demonstrable leukemic infiltration of the urinary tract on imaging studies. Hematuria in these patients was likely to be due to occult leukemic infiltration of the urinary system, aggravated by thrombocytopenia, as it subsided after starting chemotherapy. Our cases highlight that hematuria should be remembered as a rare presenting feature of acute leukemia.

  2. Immune Thrombocytopenia

    Science.gov (United States)

    ... take part in contact sports, such as boxing, football, or karate. Other sports, such as skiing or horseback riding, also put you at risk for injuries that can cause bleeding. Some safe activities are ...

  3. Oral surgery in a patient with cirrhosis and thrombocytopenia: a case report.

    Science.gov (United States)

    Patel, Seena; Perry, Maureen Munnelly; Spolarich, Ann Eshenaur

    2016-01-01

    While most oral surgical procedures can be safely performed in an outpatient setting, certain medical conditions may present a higher chance of postoperative complications. In particular, those predisposing the patient to bleeding abnormalities pose a potential risk when performing such treatments. The authors report a case involving full-mouth extractions in a patient with cirrhosis and thrombocytopenia after obtaining a platelet transfusion. A 62-year-old Caucasian female presented to a university special care dental clinic requiring extractions. Her pertinent medical history was remarkable for cirrhosis and thrombocytopenia, with a platelet count of 32,000/uL. Upon medical consultation, the patient was appointed for a prophylactic platelet transfusion. The surgery was rendered uneventfully, and the patient achieved adequate hemostasis without hospitalization. Patients with cirrhosis pose a potential bleeding risk with dental surgical procedures. Pre-operative medical consultation, review of pertinent laboratory values, and prophylactic platelet transfusion allow these patients to be managed safely in an outpatient setting. © 2015 Special Care Dentistry Association and Wiley Periodicals, Inc.

  4. Prenatal testing for hemolytic disease of the newborn and fetal neonatal alloimmune thrombocytopenia - current status.

    Science.gov (United States)

    Avent, Neil D

    2014-12-01

    Incompatibility of red cell and platelet antigens can lead to maternal alloimmunization causing hemolytic disease of the fetus & newborn and fetal neonatal alloimmune thrombocytopenia respectively. As the molecular background of these polymorphisms emerged, prenatal testing using initially fetal DNA obtained from invasively obtained amniotic fluid or chorionic villus was implemented. This evolved into testing using maternal plasma as source of fetal DNA, and this is in routine use as a safe non-invasive diagnostic that has no risk to the fetus of alloimmunization or spontaneous miscarriage. These tests were initially applied to high risk pregnancies, but has been applied on a mass scale, to screen fetuses in D-negative pregnant populations as national screening programs. Fetal neonatal alloimmune thrombocytopenia management has had comparatively small take up in non-invasive testing for causative fetal platelet alleles (e.g., HPA-1A), but mass scale genotyping of mothers to identify at risk HPA-1b1b pregnancies and their treatment with prophylactic anti-HPA-1A is being considered in at least one country (Norway).

  5. Thrombocytopenia in the first 24 hours after birth and incidence of patent ductus arteriosus.

    Science.gov (United States)

    Sallmon, Hannes; Weber, Sven C; Hüning, Britta; Stein, Anja; Horn, Peter A; Metze, Boris C; Dame, Christof; Bührer, Christoph; Felderhoff-Müser, Ursula; Hansmann, Georg; Koehne, Petra

    2012-09-01

    Experimental studies suggest that platelet-triggered ductal sealing is critically involved in definite ductus arteriosus closure. Whether thrombocytopenia contributes to persistently patent ductus arteriosus (PDA) in humans is controversial. This was a retrospective study of 1350 very low birth weight (VLBW; gender, and sepsis on PDA was determined by receiver operating characteristic curve, odds ratio, and regression analyses. Platelet numbers within the first 24 hours after birth did not differ between VLBW/ELBW infants with and without spontaneous ductal closure. Platelet numbers were not associated with subsequent PDA treatment. Low platelet counts were not related to failure of pharma-cologic PDA treatment and the need for subsequent surgical ligation. Lower gestational age or birth weight, male gender, and sepsis were linked to the presence of PDA in VLBW infants on day of life 4 to 5. Thrombocytopenia in the first 24 hours after birth was not associated with PDA in this largest VLBW/ELBW infant cohort studied to date. Impaired platelet function, due to immaturity and critical illness, rather than platelet number, might play a role in ductus arteriosus patency.

  6. Significance of Periodontal Health in Primary Immune Thrombocytopenia- A Case Report and Review of Literature

    Directory of Open Access Journals (Sweden)

    Rajinder K Sharma

    2013-01-01

    Full Text Available Primary immune thrombocytopenia is an acquired bleeding disorder with no clinically apparent cause of thrombocytopenia. Clinical indicators of ITP include easy bruising of the skin, prolonged bleeding on injury, mucocutaneous lesions such as petechiae and ecchymosis, epistaxis, gastrointestinal bleeding, hematuria and bleeding from the gums. It is important for a dentist to be aware of the clinical manifestations of ITP as it may not only lead to successful management of the patient, but in some cases it may even lead to formation of a provisional diagnosis of the condition in previously undetected cases. However, very few cases of ITP have been reported in dental practice making it difficult for a dentist to identify the disorder when a patient suffering from ITP reports for dental treatment. A case report of a female patient with ITP is thus described with emphasis on the importance of periodontal health in such patients to prevent consequent unwanted sequelae. It is followed by discussion of oral manifestations of the disorder and dental management of such patients.

  7. Serum thrombopoietin and cMpl expression in thrombocytopenia of different etiologies

    Directory of Open Access Journals (Sweden)

    Fabrizio Vianello

    2014-03-01

    Full Text Available The relationship between thrombopoietin (TPO and its receptor cMpl in thrombocytopenic conditions has not been entirely clarified. To elucidate this interplay may expand the spectrum of indications of TPO mimetics. In this study we have explored the relationship between TPO and cMpl in platelets and megakaryocytes of 43 patients with thrombocytopenia due to idiopathic thrombocytopenic purpura (ITP, bone marrow hypoplasia, myelodysplastic syndromes (MDS, and familial thrombocytopenia. Data were compared to cMpl and TPO in patients with a normal platelet count and in patients with thrombocytosis due to essential thrombocythemia (ET. All but familial patients showed higher TPO compared to controls. All thrombocytopenic states were invariably associated with increased expression of platelet cMPL compared to healthy controls. ET patients showed normal TPO and a trend toward a reduced cMpl expression. Immunofluorescence of bone marrow sections from patients with ITP and MDS failed to show a peculiar pattern compared to controls. Multiple mechanisms regulate TPO and cMpl in thrombocytopenic conditions.

  8. Randomized clinical trial of human interleukin-11 in dengue fever-associated thrombocytopenia

    International Nuclear Information System (INIS)

    Suliman, M.I.; Qayum, I.

    2014-01-01

    Objective: To assess the effectiveness of recombinant human (rh) IL-11 to increase platelets count in patients suffering from Dengue fever (DF). Study Design: Randomized double blind placebo control study. Place and Duration of Study: Farooq Hospital, Lahore, from July to October 2011. Methodology: Forty hospitalized patients suffering from Dengue fever having platelets count A 30000 per micro liter were randomly categorized into two groups, rhIL-11 (test) and distilled water (placebo) groups. The efficacy outcomes (as indicated by step up in platelets count at 48 hours) for the treatment group were compared with the outcomes for the placebo group. Results: The data revealed that the increase in platelet response with recombinant human interleukin 11, 1.5 mg subcutaneously is significantly more brisk than the placebo group. The platelets response in patients with severe thrombocytopenia was greater in the treatment group (50%) at 48 hours as compared to the placebo group (20%) (p=0.047). Response rate was slightly greater among males (6/10, 60%) than females (8/16, 50%); moreover, three-fourth (75%) female responders were in the placebo group, compared to half (50%) male responders in the treatment group. Conclusion: Results of the study suggest that treatment of severe thrombocytopenia accompanying DF with recombinant human interleukin 11 may be a useful therapeutic option. (author)

  9. The role of splenic irradiation in treating HIV-associated immune thrombocytopenia

    International Nuclear Information System (INIS)

    Blauth, Jeanette; Fisher, Scot; Henry, David; Nichini, Franco

    1999-01-01

    Purpose: To evaluate our experience in treating patients with HIV-associated thrombocytopenia using splenic irradiation. Methods and Materials: From 1993 to 1998, 10 patients with HIV-related immune thrombocytopenia (ITP) were treated in our department with low-dose splenic irradiation. All patients had either failed more conventional treatment modalities or possessed some contraindication to them. Results: Nine of 10 patients had at least a small, transient rise in their platelet counts, but only two received a substantial therapeutic benefit. Of these two, one died shortly after completing his course of radiation therapy while the other maintained near normal platelet counts up to approximately 3((1)/(2)) years following treatment. There were no treatment-related morbidities and one patient was treated twice. Conclusion: While most patients with HIV-associated ITP may initially respond favorably to splenic irradiation with small rises in platelet count, few responses are likely to be sustained or provide clinically significant outcomes. Our results support those previously reported by others treating this same condition. What remains to be investigated is whether there are any prognostic indicators to help identify those patients most likely to respond to this treatment, thus enabling us to reserve splenic irradiation for those who might derive a substantial benefit from it

  10. Estudo epidemiológico das doenças dermatológicas imunologicamente mediadas na cavidade oral An epidemiological study of immune-mediated skin diseases affecting the oral cavity

    Directory of Open Access Journals (Sweden)

    Cyntia Helena Pereira de Carvalho

    2011-10-01

    Full Text Available FUNDAMENTO: As doenças dermatológicas imunologicamente mediadas compõem diversas patologias que apresentam formas variadas de manifestação no organismo. OBJETIVO: Foi proposição desta pesquisa, estabelecer a prevalência das principais doenças dermatológicas imunologicamente mediadas que apresentam manifestação oral. MÉTODOS: Foram avaliados laudos histopatológicos de 10.292 casos arquivados no Serviço de Anatomia Patológica da Disciplina de Patologia Oral da Universidade Federal do Rio Grande do Norte, no período de 1988 a 2009. Dos casos diagnosticados como algum tipo de doença em estudo, coletaram-se dados clínicos como sexo, idade, raça, sítio anatômico e sintomatologia das doenças. RESULTADOS: Do total de casos registrados, no serviço supracitado, 82 (0,8% corresponderam a doenças dermato lógicas imunologicamente mediadas com manifestação na cavidade oral. As doenças encontradas neste estudo foram: líquen plano oral, pênfigo vulgar e penfigoide benigno das membranas mucosas, sendo o líquen plano oral a lesão mais prevalente, representando 68,05% dos casos analisados, dos quais 64,3% apresentavam-se em mu lheres, sendo a mucosa jugal o sítio anatômico mais acometido (46,8%. CONCLUSÃO: A ocorrência de doenças dermatológicas imunologicamente mediadas que apresentam manifestação oral ainda é um fato incomum, semelhante ao observado na maioria das regiões mundiais. No entanto, a busca pelo diagnóstico precoce é um requisito essencial para a condução do tratamento dessas doenças, tendo em vista o possível comprometimento sistêmico do organismo nos pacientes.BACKGROUND: Immune-mediated skin diseases encompass a variety of pathologies that present in different forms in the body. OBJECTIVE: The objective of this study was to establish the prevalence of the principal immune-mediated skin diseases affecting the oral cavity. METHODS: A total of 10,292 histopathology reports stored in the archives of the

  11. The role of platelet and plasma markers of antioxidant status and oxidative stress in thrombocytopenia among patients with vivax malaria

    Directory of Open Access Journals (Sweden)

    Claudio F Araujo

    2008-09-01

    Full Text Available Malaria remains an important health problem in tropical countries like Brazil. Thrombocytopenia is the most common hematological disturbance seen in malarial infection. Oxidative stress (OS has been implicated as a possible mediator of thrombocytopenia in patients with malaria. This study aimed to investigate the role of OS in the thrombocytopenia of Plasmodium vivax malaria through the measurement of oxidant and antioxidant biochemical markers in plasma and in isolated platelets. Eighty-six patients with P. vivax malaria were enrolled. Blood samples were analyzed for total antioxidant and oxidant status, albumin, total protein, uric acid, zinc, magnesium, bilirubin, total thiols, glutathione peroxidase (GPx, malondialdehyde (MDA, antibodies against mildly oxidized low-density lipoproteins (LDL-/nLDL ratio and nitrite/nitrate levels in blood plasma and GPx and MDA in isolated platelets. Plasma MDA levels were higher in thrombocytopenic (TCP (median 3.47; range 1.55-12.90 µmol/L compared with the non-thrombocytopenic (NTCP patients (median 2.57; range 1.95-8.60 µmol/L. Moreover, the LDL-/nLDL autoantibody ratio was lower in TCP (median 3.0; range 1.5-14.8 than in NTCP patients (median 4.0; range 1.9-35.5. Finally, GPx and MDA were higher in the platelets of TPC patients. These results suggest that oxidative damage of platelets might be important in the pathogenesis of thrombocytopenia found in P. vivax malaria as indicated by alterations of GPx and MDA.

  12. A pilot study to assess the hemostatic function of pathogen-reduced platelets in patients with thrombocytopenia

    DEFF Research Database (Denmark)

    Johansson, Pär I; Simonsen, Anne Catrine; Brown, Peter de Nully

    2013-01-01

    Platelet (PLT) support is critical to the care of patients with thrombocytopenia, but allogeneic transfusions carry risk. Pathogen reduction mitigates some transfusion risks, but effects on PLT function remain a concern. This clinical pilot study assessed the effect of pathogen reduction technolo...... with riboflavin plus ultraviolet light using thrombelastography (TEG)....

  13. Drug-induced haemolysis, renal failure, thrombocytopenia and lactic acidosis in patients with HIV and cryptococcal meningitis: a diagnostic challenge.

    Science.gov (United States)

    Camara-Lemarroy, Carlos R; Flores-Cantu, Hazael; Calderon-Hernandez, Hector J; Diaz-Torres, Marco A; Villareal-Velazquez, Hector J

    2015-12-01

    Patients with HIV are at risk of both primary and secondary haematological disorders. We report two cases of patients with HIV and cryptococcal meningitis who developed severe haemolytic anaemia, thrombocytopenia, renal failure and lactic acidosis while on treatment with amphotericin B and co-trimoxazole. © The Author(s) 2015.

  14. Glycosylation pattern of anti-platelet IgG is stable during pregnancy and predicts clinical outcome in alloimmune thrombocytopenia

    NARCIS (Netherlands)

    Sonneveld, Myrthe E.; Natunen, Suvi; Sainio, Susanna; Koeleman, Carolien A. M.; Holst, Stephanie; Dekkers, Gillian; Koelewijn, Joke; Partanen, Jukka; van der Schoot, C. Ellen; Wuhrer, Manfred; Vidarsson, Gestur

    2016-01-01

    Fetal or neonatal alloimmune thrombocytopenia (FNAIT) is a potentially life-threatening disease where fetal platelets are destroyed by maternal anti-platelet IgG alloantibodies. The clinical outcome varies from asymptomatic, to petechiae or intracranial haemorrhage, but no marker has shown reliable

  15. Assessing risk of liver enzyme elevation in patients with immune-mediated diseases and different hepatitis B virus serostatus receiving anti-TNF agents: a nested case-control study.

    Science.gov (United States)

    Chiu, Ying-Ming; Lai, Mei-Shu; Chan, K Arnold

    2017-11-01

    Liver enzyme elevation is an important and common adverse effect among patients with immune-mediated diseases who receive tumour necrosis factor inhibitors (anti-TNF), and has various causes. Hence, we evaluated the relative risks of developing liver enzyme elevation in anti-TNF users with differing hepatitis B virus (HBV) infection status. At a hospital in central Taiwan, 407 patients with rheumatoid arthritis, ankylosing spondylitis, or psoriasis/psoriatic arthritis received anti-TNF therapy between 1 January 2004 and 30 June 2012. We performed a nested case-control study (n = 368) of cases with serum alanine aminotransferase (ALT) > 40 international units/L ≤ 12 months after starting anti-TNF therapy, and corresponding controls without liver enzyme elevation. Conditional logistic regression was used to evaluate associations between liver enzyme elevation and HBV serostatus, as well as other risk factors. Thirty cases were compared to 338 controls. After adjustment for potential confounders, HBV surface antigen-positive (HBsAg + ) serostatus was associated with substantially higher likelihood of developing elevated ALT (adjusted odds ratio 7.91, 95% confidence interval (CI) 2.16-31.31) relative to those with an uninfected HBV status; no such association was observed among HBsAg-negative/HBV core antibody-positive (HBsAg - /HBcAb + ) patients (adjusted odds ratio 1.00, 95% CI 0.33-3.25). Increased risk of ALT elevation was associated with methotrexate used alone, without folic acid (adjusted odds ratio 11.60, 95% CI 2.52-56.46), and history of ALT elevation (adjusted odds ratio 13.71, 95% CI 4.32-45.75). HBsAg + patients with immune-mediated diseases who received anti-TNF therapy had an approximately eight-fold higher likelihood of liver enzyme elevation than those without HBV infection, whereas patients with HBsAg - /HBcAb + serostatus had a risk similar to that of uninfected patients.

  16. Correlation between serum levels of interleukins 10 and 12 and thrombocytopenia in hepatitis C cirrhotic (class A patients

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    N Abdallah

    2010-01-01

    Full Text Available Hepatitis C virus (HCV patients commonly have low platelet counts; however, the exact role of HCV infection in thrombocytopenia is unknown. This work aimed to study the serum levels of interleukins (IL 10 and 12 in patients with mild and moderate thrombocytopenia associated with chronic hepatitis C infection. Our study included 15 patients with chronic HCV infection and newly diagnosed isolated autoimmune thrombocytopenia (Group I and 15 patients with chronic HCV infection and normal platelet count as controls (Group II. All patients were examined for personal history and clinical aspects, complete blood count, bone marrow aspiration, liver function tests, HCV antibody assay by ELISA and polymerase chain reaction (PCR, abdominal ultrasound, Helicobacter pylori stool antigen test, evaluation of serum levels of IL-10, IL-12 and platelet specific antibodies. Our results revealed that eight patients from Group l had mild thrombocytopenia and seven patients had moderate thrombocytopenia. Serum IL-10 level was significantly elevated (t = 9.301, p < 0.001 while serum IL-12 showed a significant decrease (t = 6.502, p < 0.001 in Group I compared to the control group. No correlation was detected between platelet counts and the serum levels of either IL-10 [r = 0.454, p = 0.089 (Group I, r = 0.038, p = 0.89 (Group II] or IL-12 [r = 0.497, p = 0.06 (Group I, r = 0.499, p = 0.058 (Group II]. However, in Group I, a significant correlation was present only between moderate thrombocytopenia and serum levels of either IL-10 (r = 0.794, p = 0.033 or IL-12 (r = 0.967, p = 0.001, while no correlation was detected between these interleukin parameters and mild thrombocytopenia (r = 0.311 and p = 0.453 for IL-10 and r = -0.08 and p = 0.851 for IL-12. Based on our data, we may conclude that interleukins 10 and 12 are involved in low platelet levels.

  17. Downregulation of Interferon-β and Inhibition of TLR3 Expression are associated with Fatal Outcome of Severe Fever with Thrombocytopenia Syndrome.

    Science.gov (United States)

    Song, Peixin; Zheng, Nan; Zhang, Li; Liu, Yong; Chen, Taoyu; Bao, Changjun; Li, Zhifeng; Yong, Wei; Zhang, Yongyang; Wu, Chao; Wu, Zhiwei

    2017-07-26

    Severe Fever with Thrombocytopenia Syndrome (SFTS) is an emerging infectious disease with high mortality and increasing prevalence in the East Asia. Though the etiological agent has been identified as a novel Bunyavirus, cellular mechanisms of viral pathogenesis and host immune response to SFTS virus infection remain unknown. A comprehensive study was conducted on a cohort of 70 patients on clinical manifestations, viral loads, modulation of cytokines, serum interferon level, immune related gene expression in peripheral blood cells, and dynamic changes of circulating dendritic cells during the acute phase of SFTSV infection. We found that high level viremia, reduced platelets, coagulation dysfunction, multi-organ injuries, elevated IL-6 and TNF-α were closely associated with the aggravation of SFTS. In addition, we demonstrated strong correlations between disease severity and the decline of serum IFN-β and IL-1β level, reduction of myeloid dendritic cells (mDCs) and suppressed Toll like receptor 3 expression in monocytes and mDCs. In general, dysfunction of innate immune response and cytokine storm are both involved in the pathogenesis of SFTS. Reduction of myeloid DCs contributes to the fatal outcome of SFTS virus infection, and the regulation of TLR3 could probably be the mechanism.

  18. Comparison between IV immune globulin (IVIG) and anti-D globulin for treatment of immune thrombocytopenia: a randomized open-label study.

    Science.gov (United States)

    Eghbali, Aziz; Azadmanesh, Peyman; Bagheri, Bahador; Taherahmadi, Hasan; Sadeghi Sedeh, Bahman

    2016-08-01

    To compare the effect of IV immune globulin (IVIG) and anti-D globulin (anti-D) for treatment of immune thrombocytopenia (ITP) in children. A randomized, open-label, single-center clinical trial was carried out in Amir-Kabir Hospital (Arak, Iran). The study was performed on 60 children with acute and chronic ITP, aged from 1 to 15 years. Patients were randomly assigned (1:1) to 50 μg/kg anti-D or 1 g/kg IVIG. Platelet counting was performed at baseline and at 3, 7, and 14 days after treatment termination. Safety assessment was performed in all patients. Anti-D caused a quicker response on the 3rd day of treatment (P anti-D had lower rate of side effects including fever (P anti-D was associated with rapid rise of platelets compared to IVIG. In addition, anti-D treatment had acceptable safety profile. © 2016 Société Française de Pharmacologie et de Thérapeutique.

  19. Pathophysiology and management of thrombocytopenia in bone marrow failure: possible clinical applications of TPO receptor agonists in aplastic anemia and myelodysplastic syndromes.

    Science.gov (United States)

    Townsley, Danielle M; Desmond, Ronan; Dunbar, Cynthia E; Young, Neal S

    2013-07-01

    Aplastic anemia is a bone marrow failure syndrome that causes pancytopenia and can lead to life-threatening complications. Bone marrow transplantation remains the standard of care for younger patients and those with a good performance status but many patients may not have a suitable donor. Immunosuppressive therapy is able to resolve cytopenias in a majority of patients with aplastic anemia but relapses are not uncommon and some patients remain refractory to this approach. Patients may require frequent blood and platelet transfusion support which is expensive and inconvenient. Life-threatening bleeding complications still occur despite prophylactic platelet transfusion. Thrombopoietin (TPO) mimetics, such as romiplostim and eltrombopag, were developed to treat patients with refractory immune thrombocytopenia but are now being investigated for the treatment of bone marrow failure syndromes. TPO is the main regulator for platelet production and its receptor (c-Mpl) is present on megakaryocytes and hematopoietic stem cells. Trilineage hematopoietic responses were observed in a recent clinical trial using eltrombopag in patients with severe aplastic anemia refractory to immunosuppression suggesting that these agents can provide a new therapeutic option for enhancing blood production. In this review, we discuss these recent results and ongoing investigation of TPO mimetics for aplastic anemia and other bone marrow failure states like myelodysplastic syndromes. Clonal evolution or progression to acute myeloid leukemia remains a concern when using these drugs in bone marrow failure and patients should only be treated in the setting of a clinical trial.

  20. Selected topics of the 4th International Cooperative Study Group meeting on immune thrombocytopenia revisited.

    Science.gov (United States)

    Nydegger, Urs E; Risch, Lorenz

    2013-01-01

    The Intercontinental Cooperative immune thrombocytopenia (ITP) Study Group (ICIS) held its 4th Expert Meeting in September 2012 in Montreux, Switzerland. The program reunited researchers and clinicians from all over the globe and was organized with lectures and seminars for real-time exchange of latest information. Platelets target victims of autoimmune disease on their own, participating under physiological conditions in the immune network; these small cells are more immunologically savvy than previously thought. Currently, researchers focus their attention on regulatory T and regulatory B cells, ie, cells that might have a decisive impact on how ITP spontaneously resolves or evolves into chronic disease. Diagnostic criteria and prognosis are increasingly benefiting from molecular biological tests, and therapy has evolved with the availability of biosimilar agents and recombinant hormones or blockers of their receptors. Copyright © 2013 Elsevier Inc. All rights reserved.

  1. Effects of maternal thrombocytopenia on platelet counts of pre- and postnatal mice

    Energy Technology Data Exchange (ETDEWEB)

    McDonald, T.P.; Clift, R.; Dunn, C.D.R.

    1977-10-15

    The effects of maternal thrombocytopenia on platelet counts of pre- and postnatal mice were determined. Platelet counts of gravid mice were reduced at 2 to 3 days before parturition by injection of rabbit anti-mouse platelet serum (RAMPS). Marked rebound-thrombocytosis was observed after 4 to 6 days. Platelet counts of pre- and postnatal mice whose mothers were injected with RAMPS 3 days before parturition were unaltered except at 1 day before and at the time of birth when they were significantly (P less than 0.005) reduced. The results of immunodiffusion techniques showed that RAMPS crossed the placental barrier resulting in reduced platelet counts of the fetuses, but significant fetal rebound-thrombocytosis was not observed.

  2. Case report of an SGA infant with jaundice, direct hyperbilirubinemia, hepatosplenomegaly, thrombocytopenia, and a negative VDRL.

    Science.gov (United States)

    Dalgleish, Stacey; Premji, Shahirose; Young, Sandra; Kamaluddeen, Majeeda

    2004-04-01

    This case report highlights the presentation of syphilis in a small-for-gestational age (SGA) female infant who was born to a mother with no prenatal care. In the first 2 days of life, the infant developed hepatosplenomegaly, conjugated hyperbilirubinemia, thrombocytopenia, and hemolysis. After extensive diagnostic investigation, the case was solved on the infant's day of life (DOL) 12. In retrospect, the health care team had obtained a diagnostic result that could potentially have solved the case on DOL 2. Although this infant suffered no long-term sequelae secondary to the delayed diagnosis, the review of this case presentation may assist other clinicians in an early identification of a potentially lethal diagnosis.

  3. The centenary of Immune Thrombocytopenia – Part 1: revising nomenclature and pathogenesis

    Directory of Open Access Journals (Sweden)

    Rita Consolini

    2016-10-01

    Full Text Available The natural history of the Immune Thrombocytopenia (ITP is interesting and intriguing because it traces different steps underlying autoimmune diseases. The review points out the main steps that have accompanied the stages of its history and the consequential changes related to its terminology. ITP is an autoimmune disease resulting from platelet antibody- mediated destruction and impaired megakaryocyte (MK and platelet production. However, research advances highlight that a complex dysregulation of the immune system is involved in the pathogenesis of this condition. The review examines the role of the multiple immune components involved in the autoimmunity process, focusing on the more recent mechanisms which could be new promising therapeutic targets for ITP patients.

  4. Her-2 Positive Gastric Cancer Presented with Thrombocytopenia and Skin Involvement: A Case Report

    Directory of Open Access Journals (Sweden)

    Deniz Arslan

    2014-01-01

    Full Text Available Gastric cancer is the 5th most frequent cancer around the world and the 3rd most frequent reason of deaths due to cancer. Every year, about 1 million new cases are taking place, with varying geographical distribution. Gastric cancer is often metastatic to liver, lungs, and bones in hematogenous way, to peripheral lymph nodes in lymphogenous way, and to peripheral tissues in adjacency way, yet bone marrow (BM and cutaneous metastasis are quite seldom. Pancytopenia is a more frequent finding identified in BM metastasis of solid organ cancers, and isolated thrombocytopenia is less often. The human epidermal growth factor 2 (HER-2 is positive in gastric cancer at a rate of 7–34%. Here, we have presented our HER-2 positive gastric cancer incident which presented with BM and cutaneous metastasis, and has no 18F-fluoro-2-deoxi-D-glucose (FDG involvement except bone metastases.

  5. [A double antibody sandwich ELISA based assay for titration of severe fever with thrombocytopenia syndrome virus].

    Science.gov (United States)

    Liu, Lin; Zhang, Quan-Fu; Li, Chuan; Li, Jian-Dong; Jiang, Xiao-Lin; Zhang, Fu-Shun; Wu, Wei; Liang, Mi-Fang; Li, De-Xin

    2013-06-01

    To develop an assay for titration of severe fever with thrombocytopenia syndrome virus (SFTSV) based on double antibody sandwich ELISA. A double antibody sandwich ELISA was developed for detection of SFTSV based on SFTSV nucleocapsid (N) protein specific poly- and monoclonal antibodies, procedures were optimized and evaluated. This ELISA based titration assay was compared with fluorescence assasy and plaque assay based titration method. The results suggested that the titers obtained by ELISA based method are consistent with those obtained by IFA based method (R = 0.999) and the plaque assay titration method (R = 0.949). The novel ELISA based titration method with high sensitivity and specificity is easy to manage and perform, and can overcome the subjectivity associated with result determination of the fluorescence assay and plaque assay based methods. The novel ELISA based titration method can also be applied to high throughput detection.

  6. Romiplostim for the Emergency Management of Severe Immune Thrombocytopenia with Intracerebral Hemorrhage

    Directory of Open Access Journals (Sweden)

    Romain Gellens

    2018-01-01

    Full Text Available Currently, we lack well-established guidelines for the emergency management of severe immune thrombocytopenia (ITP with life-threatening bleeding. We now report the management of two patients with severe ITP, complicated by substantial cerebral hemorrhage, requiring urgent surgery due to refractory intracranial hypertension. To rapidly boost platelet counts (PCs, corticosteroids, intravenous immunoglobulin, and iterative platelet transfusions were given; all were ineffectual. Romiplostim, a thrombopoietin receptor agonist, was then administered as an “on demand therapy,” with the result that a rapid and sustained increase of PCs was achieved, thus allowing for postoperative hemostasis. Both patients recovered good neurological condition, suggesting the potential utility of romiplostim, in combined therapy, for the emergency management of severe ITP.

  7. Partial splenic embolization in a child with Gaucher disease, massive splenomegaly and severe thrombocytopenia

    Energy Technology Data Exchange (ETDEWEB)

    Pena, Andres H.; Clevac, Egor; Marie Cahill, Anne [Children' s Hospital of Philadelphia, Department of Radiology, Philadelphia, PA (United States); Kaplan, Paige; Ganesh, Jaya [Children' s Hospital of Philadelphia, Division of Metabolic Diseases, Philadelphia, PA (United States)

    2009-09-15

    A 13-month-old boy with Gaucher disease presented with severe thrombocytopenia, anemia and massive splenomegaly. In addition he had significant respiratory compromise caused by abdominal compartment syndrome, requiring mechanical ventilation. Because of the degree of respiratory compromise and his existing bone marrow suppression, splenic artery embolization was chosen as an alternative to splenectomy. Splenic artery embolization was performed using 355-500-{mu}m polyvinyl alcohol particles, with 70% ablation achieved. Within 24 h of the procedure the platelet count had risen to greater than 70,000/mm{sup 3} and to more than 170,000/mm{sup 3} on postoperative day 4. At the 8-month follow-up the splenic size had decreased from 18 cm to 8 cm, with a platelet count of 578,000/mm{sup 3}. Partial splenic embolization provides a minimally invasive alternative to splenectomy in patients with Gaucher disease with massive splenomegaly and bone marrow suppression. (orig.)

  8. Use of Heparin and The Related Incidence of HeparinInduced Thrombocytopenia in an Education and Research Hospital in Turkey

    Directory of Open Access Journals (Sweden)

    Nibal Abunahlah

    2017-09-01

    Full Text Available Objective: We analyzed the incidence of heparin-induced thrombocytopenia in a group of patients who received heparin (LMWH, UFH in an education and research hospital using the 4T test score as a diagnostic tool. Patients and Methods: A retrospective descriptive study analyzing patients using heparin preparations within the years 2015 and 2016. The risk for heparin-induced thrombocytopenia was calculated using the 4T test score system and also the monitoring of platelet counts of each patient. Results: Of 19.257 patients who used either UFH or LMWH and were admitted to the hospital within 2015 and 2016, 308 patients were suspected to have thrombocytopenia based on their individual platelet counts by excluding only patients with thrombocytopenia. 100 patients were determined to probably have heparin-induced thrombocytopenia and were further evaluated using the 4t test score. Overall risk was calculated to be 0.5%. Incidence was calculated to be 0.15% (29 out of 19257. For patients with high-risk scores, the incidence was 0.01% (2 out of 19257. Patients who had a high 4T test score were using ranitidine. In 29 patients who had intermediate and high-risk probability for HIT, mean starting day of HIT was 6.24±3.68 days; mean withdrawal day of heparin was 9,55±5,86 days and mean delay of heparin withdrawal was 3.31±3.39 days. Conclusion: Although the use of LMWH is being favored in the hospital when compared to UFH, health care practitioners should still remain vigilant about the occurrence of HIT as a complication of heparin therapy in hospitalized patients most especially within the first few weeks following heparin administration.

  9. Weight loss, leukopenia and thrombocytopenia associated with sustained virologic response to Hepatitis C treatment.

    Science.gov (United States)

    Suwantarat, Nuntra; Tice, Alan D; Khawcharoenporn, Thana; Chow, Dominic C

    2010-01-22

    To identify apparent adverse effects of treatment of chronic hepatitis C and their relationship to sustained virologic response (SVR). A retrospective study was conducted of all Hepatitis C virus (HCV)-infected patients treated with pegylated interferon and ribavirin in an academic ambulatory infectious disease practice. Clinical and laboratory characteristics were compared between patients with SVR and without SVR. Fifty-four patients completed therapy with the overall SVR rate of 76%. SVR was associated with genotype non-1 (P=0.01), weight loss more than 5 kilograms (P=0.04), end of treatment leukopenia (P=0.02) and thrombocytopenia (P=0.05). In multivariate analysis, SVR was significant associated with HCV genotype non-1 (Adjusted Odd Ratio [AOR] 15.22; CI 1.55 to 149.72; P=0.02), weight loss more than 5 kilograms, (AOR 5.74; CI 1.24 to 26.32; P=0.04), and end of treatment white blood cell count level less than 3 X 10(3) cells/microl (AOR 9.09; CI 1.59 to 52.63; P=0.02). Thrombocytopenia was not significant after adjustment. Other factors including age, gender, ethnicity, injection drug use, viral load, anemia, alanine transaminase level, and liver histology did not reach statistical significance. Besides non-1 genotype, SVR was found to be independently associated with weight loss during therapy, and leukopenia at the end of HCV treatment. These correlations suggest continuation of therapy despite adverse effects, may be of benefit.

  10. [Epidemiological characteristics of severe fever with thrombocytopenia syndrome in Zhoushan, Zhejiang, 2011-2013].

    Science.gov (United States)

    Wu, Hui; Wang, Jianyue; Tong, Zhendong; Tang, An; Ren, Feilin; Ye, Ling; Wang, Chengwei

    2014-12-01

    To analyze the epidemiological characteristics of severe fever cases, with thrombocytopenia syndrome (SFTS) in Zhoushan,Zhejiang, 2011-2013 and to provide evidence for the development of related strategies for prevention and control of the disease. Data was collected from the studies and related demography of the cases with SFTS in Zhoushan, 2011-2013. Clinical and epidemiological characteristics of the cases with SFTS were analyzed descriptively. During 2011-2013, 45 SFTS cases were reported in Zhoushan city, with fatality rate as 11.11% (5/45), including 41 cases(91.11%)reported in Daishan county. Most cases aged 50 or over, residing in hilly regions (93.33%). The epidemic peak was seen from May to July (84.44%). Incidence rates of the disease did not show significant statistical differences between males and females. Most cases were farmers (42.22% ) and housewives (31.11% ). Most patients complained of fever (97.78%), anorexia (91.11%), fatigue (62.22%), chill (44.44%) and other non-specific clinical manifestations but all appeared progressive thrombocytopenia and leucopenia. Sanitation condition of the patients was generally poor. 68.89% (31/45) of cases had farmed, mowed or involved in other outdoor activities in the previous two weeks, with some of them reported having exposed to tick bites. Three events were reported, epidemiologically. SFTS in Zhoushan was a infectious disease with natural foci and caused by SFTSV. Ticks might serve as the main vectors for SFTSV, and might cause direct transmission between humans. Improving the environment for living and carrying out essential protective measures in outdoor activities seemed to be significant in decreasing the incidence rate of the disease.

  11. Evolutionary and molecular analysis of the emergent severe fever with thrombocytopenia syndrome virus.

    Science.gov (United States)

    Lam, Tommy Tsan-Yuk; Liu, Wei; Bowden, Thomas A; Cui, Ning; Zhuang, Lu; Liu, Kun; Zhang, Yao-Yun; Cao, Wu-Chun; Pybus, Oliver G

    2013-03-01

    In 2009, a novel Bunyavirus, called severe fever with thrombocytopenia syndrome virus (SFTSV) was identified in the vicinity of Huaiyangshan, China. Clinical symptoms of this zoonotic virus included severe fever, thrombocytopenia, and leukocytopenia, with a mortality rate of ~10%. By the end of 2011 the disease associated with this pathogen had been reported from eleven Chinese provinces and human-to-human transmission suspected. However, current understanding of the evolution and molecular epidemiology of SFTSV before and after its identification is limited. To address this we undertake phylogenetic, evolutionary and structural analyses of all available SFTSV genetic sequences, including a new SFTSV complete genome isolated from a patient from Henan in 2011. Our discovery of a mosaic L segment sequence, which is descended from two major circulating lineages of SFTSV in China, represents the first evidence that homologous recombination plays a role in SFTSV evolution. Selection analyses indicate that negative selection is predominant in SFTSV genes, yet differences in selective forces among genes are consistent between Phlebovirus species. Further analysis reveals structural conservation between SFTSV and Rift Valley fever virus in the residues of their nucleocapsids that are responsible for oligomerisation and RNA-binding, suggesting the viruses share similar modes of higher-order assembly. We reconstruct the epidemic history of SFTSV using molecular clock and coalescent-based methods, revealing that the extant SFTSV lineages originated 50-150 years ago, and that the viral population experienced a recent growth phase that concurs with and extends the earliest serological reports of SFTSV infection. Taken together, our combined structural and phylogenetic analyses shed light into the evolutionary behaviour of SFTSV in the context of other, better-known, pathogenic Phleboviruses. Copyright © 2012 Elsevier B.V. All rights reserved.

  12. Long-term outcome of otherwise healthy individuals with incidentally discovered borderline thrombocytopenia.

    Directory of Open Access Journals (Sweden)

    Roberto Stasi

    2006-03-01

    Full Text Available BACKGROUND: The long-term outcome of individuals with mild degrees of thrombocytopenia is unknown. METHODS AND FINDINGS: In a prospective study conducted between August 1992 and December 2002, 260 apparently healthy individuals with incidentally discovered platelet counts between 100 x 10(9/l and 150 x 10(9/l were monitored for 6 mo to determine whether their condition persisted. The monitoring period was completed in 217 cases, of whom 191 (88% maintained stable platelet counts. These 191 individuals were included in a long-term follow-up study to gain knowledge of their natural history. With a median time of observation of 64 mo, the thrombocytopenia resolved spontaneously or persisted with no other disorders becoming apparent in 64% of cases. The most frequent event during the study period was the subsequent development of an autoimmune disease. The 10-y probability of developing idiopathic thrombocytopenic purpura (ITP, as defined by platelet counts persistently below 100 x 10(9/l, was 6.9% (95% confidence interval [CI]: 4.0%-12.0%. The 10-y probability of developing autoimmune disorders other than ITP was 12.0% (95% CI: 6.9%-20.8%. Most of the cases (85% of autoimmune disease occurred in women. CONCLUSIONS: Healthy individuals with a sustained platelet count between 100 x 10(9/l and 150 x 10(9/l have a 10-y probability of developing autoimmune disorders of 12%. Further investigation is required to establish whether this risk is higher than in the general population and whether an intensive follow-up results in an improvement of prognosis.

  13. A rare case of thrombotic microangiopathy triggered by acute pancreatitis.

    Science.gov (United States)

    Singh, Kevin; Nadeem, Ahmed Jamal; Doratotaj, Behzad

    2017-05-15

    Thrombotic microangiopathy (TMA) occurring after acute pancreatitis is rarely described. Without prompt intervention, TMA can be, and often is, lethal, so prompt recognition is important. Here, we present a case of a 61-year-old woman with a history of alcohol misuse who presented with epigastric pain, nausea and vomiting after binge drinking. Elevated serum lipase and imaging were suggestive of acute-on-chronic pancreatitis. Although the patient's symptoms of acute pancreatitis subsided, her anaemia, thrombocytopenia and acute kidney injury worsened. A peripheral blood smear revealed schistocytes, prompting suspicion for TMA. Therapeutic plasma exchange (TPE) was promptly initiated and she completed 10 TPE sessions that improved her anaemia and serum creatinine and resolved the thrombocytopenia. Since TPE was effective and the ADAMTS13 assay revealed 55% activity in the absence of anti-ADAMTS13 IgG prior to initiation of therapy, a confident diagnosis of TMA caused by acute pancreatitis was made. There was no evidence of relapse 2 years later. © BMJ Publishing Group Ltd (unless otherwise stated in the text of the article) 2017. All rights reserved. No commercial use is permitted unless otherwise expressly granted.

  14. Management of an acute outbreak of diarrhoea-associated haemolytic uraemic syndrome with early plasma exchange in adults from southern Denmark: an observational study

    DEFF Research Database (Denmark)

    Colic, Edin; Dieperink, Hans; Titlestad, Kjell

    2011-01-01

    Diarrhoea-associated haemolytic uraemic syndrome in adults is a life-threatening, but rare multisystem disorder that is characterised by acute haemolytic anaemia, thrombocytopenia, and renal insufficiency. We aimed to assess the success of management of this disorder with plasma exchange therapy....

  15. Influence of immune-mediated hemolytic anemia on flow velocities in the portal vein and caudal vena cava measured by use of pulsed-wave Doppler ultrasonography in dogs.

    Science.gov (United States)

    Smith, Rachel Policelli; Koenigshof, Amy M; Smith, Daniel J; Strom, Phillip R; Nelson, Nathan C

    2018-05-01

    OBJECTIVE To compare blood flow velocities of the portal vein (PV) and caudal vena cava (CVC) measured by use of pulsed-wave Doppler ultrasonography in clinically normal dogs and dogs with primary immune-mediated hemolytic anemia (IMHA). ANIMALS 11 client-owned dogs admitted to a veterinary teaching hospital for management of primary IMHA and 21 staff- or student-owned clinically normal dogs. PROCEDURES Flow velocities in the PV and CVC at the porta hepatis were evaluated in conscious unsedated dogs with concurrent ECG monitoring; evaluations were performed before dogs with IMHA received heparin or blood transfusions. Three measurements of peak velocity at end expiration were obtained for each vessel, and the mean was calculated. Results were compared between IMHA and control groups. RESULTS Mean ± SD blood flow velocity in the CVC differed between control (63.0 ± 18.6 cm/s) and IMHA (104 ± 36.9 cm/s) groups. Variance in dogs with IMHA was significantly greater than that for the clinically normal dogs. No significant difference in blood flow velocity in the PV was detected between IMHA and control dogs. CONCLUSIONS AND CLINICAL RELEVANCE Higher blood flow velocities were detected by use of pulsed-wave Doppler ultrasonography in the CVC of dogs with naturally occurring IMHA and may be used to predict anemia in patients suspected of having IMHA.

  16. Acute Motor Axonal Neuropathy in Association with Hepatitis E

    Directory of Open Access Journals (Sweden)

    Araz Al-Saffar

    2018-02-01

    Full Text Available Guillain–Barré syndrome (GBS is an acute peripheral neuropathy that develops as a result of post-infectious immune-mediated nerve injury. It can be classified into classic and variant GBS. Acute motor axonal neuropathy (AMAN is a subtype of GBS with the key clinical features of pure motor weakness, areflexia, absence of sensory symptoms, and lack of neurophysiologic evidence of demyelination. We reported a case of acute motor axonal neuropathy in association with hepatitis E infection. A young woman was referred to us after a period of nausea, fever, and diarrhea. She had unexplained muscle weakness at admission and has been diagnosed with acute hepatitis E infection. A rigorous clinical neurological assessment revealed bilateral symmetrical weakness, which affects the lower limbs more than the upper limbs, with no evidence of sensory involvement. Neurophysiological measurements indicated acute axonal injury without clues to demyelination. A diagnosis of acute motor axonal neuropathy subtype has been made, to which she only received supportive therapy. The symptoms resolved spontaneously and full recovery of motor function was attained after 35 days of weakness onset with complete normalization of neurophysiologic parameters.

  17. Nye behandlingsmuligheder ved primær immun trombocytopeni

    DEFF Research Database (Denmark)

    Gudbrandsdottir, Sif; Frederiksen, Henrik; Birgens, Henrik Sverre

    2011-01-01

    Primary immune thrombocytopenia (ITP)--formerly known as idiopathic thrombocytopenic purpura--is an autoimmune disorder characterized by immune mediated thrombocytopenia. The aetiology of ITP remains unknown, but studies have shown that multiple immunological mechanisms are involved...

  18. Patofysiologien ved primær immun trombocytopeni

    DEFF Research Database (Denmark)

    Gudbrandsdottir, Sif; Frederiksen, Henrik; Birgens, Henrik Sverre

    2011-01-01

    Primary immune thrombocytopenia (ITP)--formerly known as idiopathic thrombocytopenic purpura--is an autoimmune disorder characterized by immune-mediated thrombocytopenia. The aetiology of ITP remains unknown, but studies have shown that multiple immunological mechanisms are involved...

  19. Nye behandlingsmuligheder ved primær immun trombocytopeni

    DEFF Research Database (Denmark)

    Gudbrandsdottir, Sif; Frederiksen, Henrik; Birgens, Henrik Sverre

    2011-01-01

    Primary immune thrombocytopenia (ITP)--formerly known as idiopathic thrombocytopenic purpura--is an autoimmune disorder characterized by immune mediated thrombocytopenia. The aetiology of ITP remains unknown, but studies have shown that multiple immunological mechanisms are involved in the pathog...

  20. Acute pancreatitis

    Science.gov (United States)

    ... its blood vessels. This problem is called acute pancreatitis. Acute pancreatitis affects men more often than women. Certain ... well it can be treated. Complications of acute pancreatitis may include: Acute kidney failure Long-term lung damage (ARDS) Buildup ...

  1. Nye behandlingsmuligheder ved primær immun trombocytopeni

    DEFF Research Database (Denmark)

    Gudbrandsdottir, Sif; Frederiksen, Henrik; Birgens, Henrik Sverre

    2011-01-01

    Primary immune thrombocytopenia (ITP)--formerly known as idiopathic thrombocytopenic purpura--is an autoimmune disorder characterized by immune mediated thrombocytopenia. The aetiology of ITP remains unknown, but studies have shown that multiple immunological mechanisms are involved in the pathog......Primary immune thrombocytopenia (ITP)--formerly known as idiopathic thrombocytopenic purpura--is an autoimmune disorder characterized by immune mediated thrombocytopenia. The aetiology of ITP remains unknown, but studies have shown that multiple immunological mechanisms are involved...

  2. Patofysiologien ved primær immun trombocytopeni

    DEFF Research Database (Denmark)

    Gudbrandsdottir, Sif; Frederiksen, Henrik; Birgens, Henrik Sverre

    2011-01-01

    Primary immune thrombocytopenia (ITP)--formerly known as idiopathic thrombocytopenic purpura--is an autoimmune disorder characterized by immune-mediated thrombocytopenia. The aetiology of ITP remains unknown, but studies have shown that multiple immunological mechanisms are involved in the pathog......Primary immune thrombocytopenia (ITP)--formerly known as idiopathic thrombocytopenic purpura--is an autoimmune disorder characterized by immune-mediated thrombocytopenia. The aetiology of ITP remains unknown, but studies have shown that multiple immunological mechanisms are involved...

  3. Thrombotic thrombocytopenic purpura or immune thrombocytopenia in a sickle cell/β+-thalassemia patient: a rare and challenging condition.

    Science.gov (United States)

    Vlachaki, Efthymia; Agapidou, Aleka; Neokleous, Nikolaos; Adamidou, Despoina; Vetsiou, Evaggelia; Boura, Panagiota

    2014-10-01

    The diagnosis of thrombotic thrombocytopenic purpura is one of the possible diagnosis when a patient is admitted with unexpected micro-angiopathic hemolytic anemia and thrombocytopenia. The combination of sickle cell/β(+)-thalassemia and thrombotic thrombocytopenic purpura is rare and triggering. This article describes the poor outcome of a patient with sickle cell/β(+)-thalassemia presenting with gingival bleeding, severe thrombocytopenia and anemia. The patient had normal renal function, no neurological deficit and he was initially treated as immune thrombocytopenic purpura. He eventually died due to multi-organ failure and brain hemorrhage even though he had started plasma exchange sessions. The co-existence of thrombotic thrombocytopenic purpura and sickle cell anemia is making the diagnosis of the former difficult. Early and rapid intervention is critical to the outcome. Copyright © 2014 Elsevier Ltd. All rights reserved.

  4. A Case of Thrombotic Thrombocytopenia Purpura Associated with Systemic Lupus Erythematosus: Diagnostic Utility of ADAMTS-13 Activity

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    Risa Yamada

    2011-01-01

    Full Text Available Thrombotic thrombocytopenia purpura (TTP caused by a deficiency in ADAMTS-13 activity is considered to involve a subset of thrombotic microangiopathy (TMA. Although concept of TTP is included under the umbrella of TMA, discrimination of TTP from TMA is occasionally difficult in an autoimmune disorder. Herein, we report a case with TTP associated with systemic lupus erythematosus (SLE. In this case, it was difficult to discriminate TTP from TMA and the measurement of ADAMTS-13 activity was useful for obtaining an accurate diagnosis. SLE patients having thrombocytopenia in complication with anemia should be considered a monitoring of ADAMTS-13 activity even though the patients lacked symptoms of TTP related to the microvascular coagulation.

  5. Genetic Variability in Platelet Integrin α2β1 Density: Possible Contributor to Plasmodium vivax–induced Severe Thrombocytopenia

    Science.gov (United States)

    Campos, Fernanda M. F.; Santos, Marina L. S.; Kano, Flora S.; Fontes, Cor J. F.; Lacerda, Marcus V. G.; Brito, Cristiana F. A.; Carvalho, Luzia H.

    2013-01-01

    Understanding the pathogenesis of Plasmodium vivax malaria is challenging. We hypothesized that susceptibility to P. vivax-induced thrombocytopenia could be associated with polymorphisms on relevant platelet membrane integrins: integrin α2 (C807T), and integrin β3 (T1565C). Although β3 polymorphism was not related with P. vivax malaria, α2 807T carriers, which show high levels of integrin α2β1, had a higher probability for severe thrombocytopenia than wild-type carriers. This evidence of the association of integrin polymorphism and P. vivax morbidity was further demonstrated by a moderate but significant correlation between clinical disease and surface levels of the integrin α2β1. PMID:23249684

  6. Acute ciprofloxacin-induced crystal nephropathy with granulomatous interstitial nephritis

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    R Goli

    2017-01-01

    Full Text Available Crystal-induced acute kidney injury (AKI is caused by the intratubular precipitation of crystals, which results in obstruction and kidney injury. Ciprofloxacin, a commonly used antibiotic, causes AKI secondary to immune-mediated interstitial injury. Rare mechanisms of ciprofloxacin-induced renal injury include crystalluria, rhabdomyolysis, and granulomatous interstitial nephritis. Clinical and experimental studies have suggested that crystalluria and crystal nephropathy due to ciprofloxacin occur in alkaline urine. Preexisting kidney function impairment, high dose of the medication, and advanced age predispose to this complication. We report a case of ciprofloxacin-induced crystal nephropathy and granulomatous interstitial nephritis in a young patient with no other predisposing factors. The patient responded to conservative treatment without the need for glucocorticoids.

  7. Assessing single-stranded oligonucleotide drug-induced effects in vitro reveals key risk factors for thrombocytopenia.

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    Sabine Sewing

    Full Text Available Single-stranded oligonucleotides (ON comprise a promising therapeutic platform that enables selective modulation of currently undruggable targets. The development of novel ON drug candidates has demonstrated excellent efficacy, but in certain cases also some safety liabilities were reported. Among them are events of thrombocytopenia, which have recently been evident in late stage trials with ON drugs. The underlying mechanisms are poorly understood and the risk for ON candidates causing such events cannot be sufficiently assessed pre-clinically. We investigated potential thrombocytopenia risk factors of ONs and implemented a set of in vitro assays to assess these risks. Our findings support previous observations that phosphorothioate (PS-ONs can bind to platelet proteins such as platelet collagen receptor glycoprotein VI (GPVI and activate human platelets in vitro to various extents. We also show that these PS-ONs can bind to platelet factor 4 (PF4. Binding to platelet proteins and subsequent activation correlates with ON length and connected to this, the number of PS in the backbone of the molecule. Moreover, we demonstrate that locked nucleic acid (LNA ribosyl modifications in the wings of the PS-ONs strongly suppress binding to GPVI and PF4, paralleled by markedly reduced platelet activation. In addition, we provide evidence that PS-ONs do not directly affect hematopoietic cell differentiation in culture but at higher concentrations show a pro-inflammatory potential, which might contribute to platelet activation. Overall, our data confirm that certain molecular attributes of ONs are associated with a higher risk for thrombocytopenia. We propose that applying the in vitro assays discussed here during the lead optimization phase may aid in deprioritizing ONs with a potential to induce thrombocytopenia.

  8. Thrombocytopenia in pregnant women with Plasmodium falciparum malaria in an area of unstable malaria transmission in eastern Sudan

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    Adam Mayyada B

    2012-08-01

    Full Text Available Abstract Background Blood platelet levels are being evaluated as predictive and prognostic indicators of the severity of malaria infections in humans. However, there are few studies on platelets and Plasmodium falciparum malaria during pregnancy. Methods A case–control study was conducted at Gadarif Hospital in Eastern Sudan, an area characterized by unstable malaria transmission. The aim of the study was to investigate thrombocytopenia in pregnant women with P. falciparum malaria (cases and healthy pregnant women (controls. Results The median (interquartile platelet counts were significantly lower in patients with malaria (N = 60 than in the controls (N = 60, 61, 000 (43,000–85,000 vs. 249,000 (204,000–300,000/μL, respectively, p P. falciparum malaria (N = 12 compared with those patients with uncomplicated P. falciparum malaria (N = 48, 68, 000 (33,000-88,000/μL vs. 61, 000 (45,000–85,000/μL, respectively, p = 0.8. While none of the control group had thrombocytopenia (platelet count p P. falciparum malaria, compared with the pregnant healthy control group, were at higher risk (OR = 10.1, 95% CI = 4.1–25.18; p  Conclusion P. falciparum malaria is associated with thrombocytopenia in pregnant women in this setting. More research is needed.

  9. Acute pancreatitis-induced thrombotic thrombocytopenic purpura with recurrent acute pancreatitis.

    Science.gov (United States)

    Fujino, Yasuhisa; Inoue, Yoshihiro; Onodera, Makoto; Kikuchi, Satoshi; Sato, Masayuki; Kojika, Masahiro; Sato, Hisaho; Suzuki, Keijiro; Matsumoto, Masanori

    2016-04-01

    Recent successive reports on acute pancreatitis-induced thrombotic thrombocytopenic purpura (TTP) have revealed that TTP-related microvascular damage is an aggravating factor of acute pancreatitis. Here, we report the case of a 26-year-old man diagnosed with acute pancreatitis due to high alcohol consumption. The patient was unconscious as he had taken an overdose of medication, and presented with fever and renal failure due to acute pancreatitis on admission. Although the pancreatitis subsequently improved, the symptoms were still observed; on the next day, he exhibited hemoglobinuria, anemia, and thrombocytopenia. Moreover, general blood examinations indicated the presence of schistocytes and reduced activity of ADAMTS13 (a disintegrin-like metalloproteinase with thrombospondin type 1 motif 13) to 47 %. Thus, the patient was diagnosed with TTP, and plasma exchange was performed. After the development of TTP, the acute pancreatitis recurred, but a severe pathogenesis was prevented by plasma exchange. Thus, ADAMTS13 activity may be useful for predicting a severe pathogenesis of acute pancreatitis. In ADAMTS13-deficient cases, plasma exchange may be an effective technique for preventing aggravation of acute pancreatitis.

  10. Neonatal alloimmune thrombocytopenia caused by human leucocyte antigen-B27 antibody.

    Science.gov (United States)

    Thude, H; Schorner, U; Helfricht, C; Loth, M; Maak, B; Barz, D

    2006-04-01

    Neonatal alloimmune thrombocytopenia (NAIT) occurs when maternal alloantibodies to antigens presented on foetal platelets cause their immune destruction. Whether human leucocyte antigen (HLA) antibodies can cause NAIT is controversial. Here, a patient was described who suffered from a NAIT caused by an HLA-B27 antibody. Sera from the mother and the newborn were tested for human platelet antigen antibodies and HLA antibodies by monoclonal antibody-specific immobilization of platelet antigens (MAIPA) assay, solid phase-linked immunosorbent assay (ELISA), lymphocytotoxicity assay (LCT) and flow cytometric analysis. No antibodies against cluster designation (CD)109 and platelet glycoproteins of the father were found in patient's and mother's serum. However, HLA ELISA was used to identify HLA antibody in both sera. The antibody was specified as HLA-B27 antibody. Typing results showed that the father descended HLA-B27 antigen on patient and his brother. The mother was HLA-B27 negative. It is most conceivable that the previous pregnancy of the mother induced the production of anti-HLA-B27 antibody, which crossed the placenta and subsequently caused an NAIT in the case presented.

  11. Anti-D treatment for pediatric immune thrombocytopenia: Is the bad reputation justified?

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    Yacobovich, Joanne; Abu-Ahmed, Sabreen; Steinberg-Shemer, Orna; Goldberg, Tracie; Cohen, Miriam; Tamary, Hannah

    2016-04-01

    The purpose of this study was to assess the efficacy and side effect profile of the repeated use of anti-D for the treatment of pediatric immune thrombocytopenia (ITP) in a large pediatric hematology center. We performed a retrospective analysis of patient records for children (aged 4 months-18 years) treated for ITP at Schneider Children's Medical Center of Israel from 1995-2015. Demographic and clinical data, reported adverse events, and therapy response were extracted from written and electronic files for all patients having received anti-D. Therapy response was defined as time to platelet count >30 x 10(9)/L. Thirty-six patients received 170 treatments of anti-D at a dose of 75 μg/kg. The majority were previously treated with corticosteroids and/or intravenous immunoglobulin (IVIG). Minimal adverse events were recorded including fever (3.5%), vomiting (2.9%), and headaches (1.7%). Notably only 1/170 treatments required blood transfusion and no life-threatening events occurred. The average time to platelets >30 x 10(9)/L was 2.3 days, with a median of 1 day, range 1-12 days. Despite the reported severe adverse events in mainly elderly patients, the use of anti-D can be safe and effective in carefully chosen, low-risk pediatric patients with ITP. Copyright © 2016 Elsevier Inc. All rights reserved.

  12. A Non-Invasive Strategy for Neonatal Alloimmune Thrombocytopenia Diagnosis: Newborn Platelet Genotyping with Buccal Swabs

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    Gérald Bertrand

    2016-07-01

    Full Text Available Neonatal alloimmune thrombocytopenia results from the maternal immune response against fetal-specific antigens inherited from the father. The diagnosis is ascertained only when the maternal alloantibody and the offending antigen present in the newborn are identified. Up until now most laboratories perform DNA extraction for neonatal genotyping from newborn blood samplings. In order to avoid such an invasive procedure, two protocols of DNA extraction from buccal swabs were developed: a manual protocol using the QIAamp mini blood kit (Qiagen, and an automated procedure with the MagNA Pure Compact instrument (Roche. Both EDTA-blood and buccal swabs from thrombocytopenic newborns were genotyped manually (14 samples, automatically (15 samples or both manually and automatically (two samples. Human Platelet Antigen (HPA genotyping was performed using the BeadChip assay (BioArray, Immucor. Concordant genotypings were obtained for all samples except for one swab with the manual method. The automated DNA extraction from newborn buccal swabs with the MagNA Pure Compact instrument was chosen as the first-line strategy, with a significant gain of time in processing buccal swabs.

  13. A scoring model for predicting prognosis of patients with severe fever with thrombocytopenia syndrome.

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    Bei Jia

    2017-09-01

    Full Text Available Severe fever with thrombocytopenia syndrome (SFTS is an emerging epidemic infectious disease caused by the SFTS bunyavirus (SFTSV with an estimated high case-fatality rate of 12.7% to 32.6%. Currently, the disease has been reported in mainland China, Japan, Korea, and the United States. At present, there is no specific antiviral therapy for SFTSV infection. Considering the higher mortality rate and rapid clinical progress of SFTS, supporting the appropriate treatment in time to SFTS patients is critical. Therefore, it is very important for clinicians to predict these SFTS cases who are more likely to have a poor prognosis or even more likely to decease. In the present study, we established a simple and feasible model for assessing the severity and predicting the prognosis of SFTS patients with high sensitivity and specificity. This model may aid the physicians to immediately initiate prompt treatment to block the rapid development of the illness and reduce the fatality of SFTS patients.

  14. Thrombocytopenia as a surrogate marker of hepatosplenic schistosomiasis in endemic areas for Schistosomiasis mansoni

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    Sandra Costa Drummond

    2014-04-01

    Full Text Available Introduction This study aimed to evaluate whether a low platelet count is a good surrogate marker of hepatosplenic schistosomiasis (HSS in a rural area of Brazil. A small district in southeastern Brazil, with a population of 1,543 individuals and a 23% prevalence of schistosomiasis, was selected for this investigation. Methods In July 2012, 384 volunteers were subjected to clinical, ultrasonography (US, and laboratory examinations, including stool sample analysis. The HSS patients were classified into four groups: Group 1 consisted of patients with a spleen >13cm and liver fibrosis; Group 2 consisted of patients with a palpable spleen and spleen>13cm measured by US; Group 3 consisted of patients with a spleen >13cm measured by US; and Group 4 consisted of patients with a palpable spleen. Results Eight patients were in Group 1 (2.1%, twenty-one were in Group 2 (5.5%, eight were in Group 3 (2.1%, and eighteen were in Group 4 (4.7%. A significant difference in the mean platelet counts was observed between the patients with and without HSS (p<0.01. Based on the receiver operating characteristic (ROC curve (platelet count <143,000/mm3, the sensitivity was greater than 92% in all groups, and the specificity varied from 44.4% to 75%. Conclusions We concluded that in endemic areas, thrombocytopenia demonstrates good sensitivity for detecting HSS and may be used as a screening tool to identify patients with HSS.

  15. Dapsone salvage therapy for adult patients with immune thrombocytopenia relapsed or refractory to steroid and rituximab.

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    Zaja, Francesco; Marin, Luciana; Chiozzotto, Marianna; Puglisi, Simona; Volpetti, Stefano; Fanin, Renato

    2012-03-01

    Dapsone is an antibacterial sulfonamide with anti-inflammatory property, which showed therapeutic activity in patients with immune thrombocytopenia (ITP); the activity in patients who showed refractoriness to rituximab is unknown. We evaluated the effect of dapsone in 20 consecutive adult patients, median age 51 years, with primary ITP previously treated at least with steroids and rituximab. Median baseline platelet count was 19 × 10⁹/L, and the median interval between diagnosis of ITP and dapsone therapy was 46 months. Response (platelet count ≥ 30 × 10⁹/L) and complete response (CR; platelet count ≥ 100 × 10⁹/L) were 55 and 20%, respectively; median time to response (TTR) was 1 month. All responders were able to interrupt any other specific anti-ITP treatment. The median duration of dapsone therapy in responders and the median response duration were 31 and 42 months, respectively. None of responders lost response during treatment. One patient in CR interrupted dapsone after 9 months and still maintained the response after 48 months. None of the patients interrupted the treatment for toxicity. All the patients were screened for normal glucose-6-phosphate-dehydrogenase (G6PD); two patients showed mild increase of methemoglobin (MHb). These results highlight the therapeutic activity and good safety profile of dapsone in patients with ITP who previously failed rituximab treatment.

  16. Thrombocytopenia is associated with an increased risk of cancer during treated HIV disease

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    Borges, Alvaro Humberto Diniz; Lundgren, Jens D; Ridolfo, Annalisa

    2014-01-01

    OBJECTIVE: To assess the relationship between platelet counts and risk of AIDS and non-AIDS-defining events.DESIGN: Prospective cohort.METHODS: EuroSIDA patients with at least one platelet count were followed from baseline (first platelet ≥ 1 January 2005) until last visit or death. Multivariate...... Poisson regression was used to assess the relationship between current platelet counts and the incidence of non-AIDS-defining (pancreatitis, end-stage liver/renal disease, cancer, cardiovascular disease) and AIDS-defining events.RESULTS: There were 62 898 person-years of follow-up (PYFU) among 12 279...... patients, including 1168 non-AIDS-defining events [crude incidence 18.6/1000 PYFU, 95% confidence interval (CI) 17.5-19.6] and 735 AIDS-defining events (crude incidence 11.7/1000 PYFU, 95% CI 10.8-12.5). Patients with thrombocytopenia (platelet count ≤100 × 10/l) had a slightly increased incidence of AIDS...

  17. Epidemiological characteristics of severe fever with thrombocytopenia syndrome in Zhejiang Province, China.

    Science.gov (United States)

    Sun, Jimin; Chai, Chengliang; Lv, Huakun; Lin, Junfen; Wang, Chengwei; Chen, Enfu; Zhang, Yanjun; Chen, Zhiping; Liu, Shelan; Gong, Zhenyu; Jiang, Jianmin

    2014-08-01

    To summarize the epidemiological characteristics of severe fever with thrombocytopenia syndrome (SFTS) in Zhejiang Province, China. A standardized questionnaire was used to collect information on demographic features, exposure history, clinical symptoms, and timelines of medical visits. Descriptive statistics were used to analyze the characteristics of SFTS. A total of 65 cases of SFTS were identified in Zhejiang Province from 2011 to 2013, of whom 34 were male and 31 were female. The median age was 66 years and 60 cases occurred in persons aged ≥ 50 years. The majority (91%) of SFTS cases occurred between May and August. With regard to exposure history, patients had pursued outdoor activities (63%), had a history of exposure to a tick (68%) or tick bite (29%), bred domestic animals (31%), or had a history of exposure to a mouse (57%), and some patients had a multi-exposure history. Approximately 98.46% of patients were hospitalized, and symptoms of the illness included fever (98%), fatigue (71%), chills (51%), etc. Two family clusters occurred, although there was no person-to-person transmission. In Zhejiang Province, SFTS is prevalent between May and August among elderly persons who live in hilly areas, and clinical features are not specific. More emphasis should be given to this disease and further training of medical personnel should be carried out to prevent misdiagnosis. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  18. Placental histological lesions in fetal and neonatal alloimmune thrombocytopenia: A retrospective cohort study of 21 cases.

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    Dubruc, Estelle; Lebreton, Frédérique; Giannoli, Catherine; Rabilloud, Muriel; Huissoud, Cyril; Devouassoux-Shisheboran, Mojgan; Allias, Fabienne

    2016-12-01

    Alloimmunization against human platelet antigens (HPAs) can occur prenatally and induce fetal/neonatal alloimmune thrombocytopenia (FNAIT). The aim of this study was to identify placental histological features associated with platelet alloimmunization and their clinical significance. This study examined 21 placentas from FNAIT-affected pregnancies and 42 age-matched control cases, all collected from pathology departments in the Rhône-Alpes region. Clinical and laboratory findings were collected for each FNAIT case. Two pathologists reviewed the placental slides of each FNAIT and control case. Histological features, with special emphasis on chronic inflammatory lesions, were evaluated. Differences between the two groups were calculated with odds ratios (ORs) and assessed with Wald's chi-square. FNAIT was associated with a significantly higher frequency of chronic chorioamnionitis (CC) (OR 14, 95%CI 1.7-113.8), basal chronic villitis (BCV) (OR 17, 95%CI 2-145.6) and chronic intervillositis (CIV). Chronic villitis (CV) (OR 3.7, 95%CI 0.9-15.2) and chronic deciduitis (CD) (OR 4.7, 95%CI 0.79-28.2) were also more frequent in the FNAIT than the control group, but these differences were not statistically significant. FNAIT is significantly associated with CC, BCV, and CIV. This chronic inflammatory reaction is preferentially localized on the maternofetal interface. Anti-HPA alloimmunization may trigger an immunological conflict similar to graft-versus-host disease. Copyright © 2016 Elsevier Ltd. All rights reserved.

  19. Ecological niche modeling for predicting the potential risk areas of severe fever with thrombocytopenia syndrome.

    Science.gov (United States)

    Du, Zhaohui; Wang, Zhiqiang; Liu, Yunxia; Wang, Hao; Xue, Fuzhong; Liu, Yanxun

    2014-09-01

    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel bunyavirus. The spatial distribution has continued to expand, while the areas at potential high risk of SFTS have, to date, remained unclear. Using ecological factors as predictors, the MaxEnt model was first trained based on the locations of human SFTS occurrence in Shandong Province. The risk prediction map of China was then created by projecting the training model onto the whole country. The performance of the model was assessed using the known locations of disease occurrence in China. The key environmental factors affecting SFTS occurrence were temperature, precipitation, land cover, normalized difference vegetation index (NDVI), and duration of sunshine. The risk prediction maps suggested that central, southwestern, northeastern, and the eastern coast of China are potential areas at high risk of SFTS. The potential high risk SFTS areas are distributed widely in China. The epidemiological surveillance system should be enhanced in these high risk regions. Copyright © 2014 The Authors. Published by Elsevier Ltd.. All rights reserved.

  20. Pulsed high-dose dexamethasone modulates Th1-/Th2-chemokine imbalance in immune thrombocytopenia.

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    Liu, Zongtang; Wang, Meiying; Zhou, Shufen; Ma, Ji; Shi, Yan; Peng, Jun; Hou, Ming; Guo, Chengshan

    2016-10-24

    Chemokines and chemokine receptors play important roles in autoimmune diseases; however, their role in immune thrombocytopenia (ITP) is unclear. High-dose dexamethasone (HD-DXM) may become a first-line therapy for adult patients with ITP, but the effect of HD-DXM on chemokines in ITP patients is unknown. Our aim was to investigate the mechanism of pulsed HD-DXM for management of ITP, specifically regarding the chemokine pathways. Th1-/Th2-associated chemokine and chemokine receptor profiles in ITP patients before and after pulsed HD-DXM was studied. Plasma levels of CCL5 and CXCL11 (Th1-associated) and of CCL11 (Th2-associated) were determined by ELISA. Gene expression of these three chemokines and their corresponding receptors CCR5, CXCR3, and CCR3, in peripheral blood mononuclear cells (PBMCs) was determined by quantitative RT-PCR. Thirty-three of the thirty-eight ITP patients responded effectively to HD-DXM (oral, 40 mg/day, 4 days). In ITP patients, plasma CXCL11 levels increased, while CCL11 and CCL5 decreased compared to controls (P Th1-/Th2-associated chemokines and chemokine receptors may play important roles in the pathogenesis of ITP. Importantly, regulating Th1 polarization by pulsed HD-DXM may represent a novel approach for immunoregulation in ITP.

  1. Reduced PTEN involved in primary immune thrombocytopenia via contributing to B cell hyper-responsiveness.

    Science.gov (United States)

    Wang, Shixuan; Guan, Yue; Wang, Yunlong; Li, Huiyuan; Zhang, Donglei; Ju, Mankai; Hao, Yating; Song, Xuewen; Sun, Boyang; Dou, Xueqing; Yang, Renchi

    2018-01-01

    Phosphatase and tensin homolog (PTEN) is thought to mediate B cell activation by negatively regulating the phosphoinositide 3-kinase (PI3K) signaling pathway. This pathway is important for activation, growth, and proliferation. Although enhanced B cell receptor (BCR) signaling contributes to increased B cell activity in immune thrombocytopenia (ITP), the role of PTEN is unclear. In this study, we analyzed B cells of ITP patients using flow cytometry and found that all B cell subsets, excluding memory B cells, showed lower PTEN expression than cells from healthy controls (HCs). PTEN expression was also positively-correlated with blood platelet count, although levels were lower in patients who were platelet autoantibody-positive compared with those who were negative. We next evaluated the effects of IL-21, anti-IgM, and CD40L on PTEN expression, demonstrating that they were potent inducers of PTEN expression in normal B cells. Induction of PTEN expression was lower in B cells of ITP patients. We also found that IL-21 increased the proportion of plasma cells in peripheral blood mononuclear cells (PBMCs) of ITP patients, independent of BCR signaling. This effect was reproducible using PTEN inhibitors with cells from HCs. In summary, defective PTEN expression, regulation, and function all contribute to the B cell hyper-responsiveness that associates with ITP. Copyright © 2017 Elsevier Ltd. All rights reserved.

  2. Prognostic Factors for Immune Thrombocytopenia Outcome in Greek Children: A Retrospective Single-Centered Analysis.

    Science.gov (United States)

    Makis, Alexandros; Gkoutsias, Athanasios; Palianopoulos, Theodoros; Pappa, Eleni; Papapetrou, Evangelia; Tsaousi, Christina; Hatzimichael, Eleftheria; Chaliasos, Nikolaos

    2017-01-01

    Immune thrombocytopenia (ITP) in children has a varied course and according to duration is distinguished as newly diagnosed (12) types. Several studies have evaluated the prognostic factors for the progression of the disease, but similar works have yet to be performed in Greece. We aimed to identify prognostic markers for the three forms of the disease in 57 Greek children during a 13-year period. Information regarding age, gender, preceding infection, bleeding type, duration of symptoms and platelets at diagnosis, treatment, disease course, and immunological markers was recorded. 39 children had newly diagnosed, 4 persistent, and 14 chronic disease. Chronic ITP children were more likely to be of age > 10 years ( p = 0.015) and have gradual initiation of the disease ( p = 0.001), platelets > 10 × 10 9 /L ( p = 0.01), and impaired immunological markers ( p < 0.003) compared to newly diagnosed/persistent groups. Recent history of infection was found mainly in the newly diagnosed/persistent group ( p = 0.013). None of the children exhibited severe spontaneous bleeding. Conclusion . Even though ITP in children usually has a self-limited course, with rare serious bleeding complications, the chronic form of the disease is characterized by different predictive parameters, which can be used in clinical practice.

  3. Prognostic Factors for Immune Thrombocytopenia Outcome in Greek Children: A Retrospective Single-Centered Analysis

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    Alexandros Makis

    2017-01-01

    Full Text Available Immune thrombocytopenia (ITP in children has a varied course and according to duration is distinguished as newly diagnosed (12 types. Several studies have evaluated the prognostic factors for the progression of the disease, but similar works have yet to be performed in Greece. We aimed to identify prognostic markers for the three forms of the disease in 57 Greek children during a 13-year period. Information regarding age, gender, preceding infection, bleeding type, duration of symptoms and platelets at diagnosis, treatment, disease course, and immunological markers was recorded. 39 children had newly diagnosed, 4 persistent, and 14 chronic disease. Chronic ITP children were more likely to be of age > 10 years (p=0.015 and have gradual initiation of the disease (p=0.001, platelets > 10 × 109/L (p=0.01, and impaired immunological markers (p<0.003 compared to newly diagnosed/persistent groups. Recent history of infection was found mainly in the newly diagnosed/persistent group (p=0.013. None of the children exhibited severe spontaneous bleeding. Conclusion. Even though ITP in children usually has a self-limited course, with rare serious bleeding complications, the chronic form of the disease is characterized by different predictive parameters, which can be used in clinical practice.

  4. Current perspectives on fetal and neonatal alloimmune thrombocytopenia – increasing clinical concerns and new treatment opportunities

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    Tiller H

    2017-04-01

    Full Text Available Heidi Tiller,1 Anne Husebekk,1 Maria Therese Ahlen,2 Tor B Stuge,1 Bjørn Skogen3 1Immunology Research Group, Faculty of Health Sciences, UiT, The Arctic University of Norway, 2Division of Diagnostic Services, Department of Laboratory Medicine, 3Department of Laboratory Medicine, Norwegian National Unit for Platelet Immunology, University Hospital of North Norway, Tromsø, Norway Abstract: Differences in platelet type between the fetus and the mother can lead to maternal immunization and destruction of the fetal platelets, a condition named fetal and neonatal alloimmune thrombocytopenia (FNAIT. FNAIT is reported to occur in ~1 per 1,000 live born neonates. The major risk is intracranial hemorrhage in the fetus or newborn, which is associated with severe neurological complications or death. Since no countries have yet implemented a screening program to detect pregnancies at risk, the diagnosis is typically established after the birth of a child with symptoms. Reports on broader clinical impact have increased clinical concern and awareness. Along with new treatment options for FNAIT, the debate around antenatal screening to detect pregnancies at risk of FNAIT has been revitalized. Keywords: antibodies, screening, alloimmunization, platelets, newborn, pregnancy

  5. Predictive factors for resolution of childhood immune thrombocytopenia: Experience from a single tertiary center in Thailand.

    Science.gov (United States)

    Chotsampancharoen, Thirachit; Sripornsawan, Pornpun; Duangchoo, Sarapee; Wongchanchailert, Malai; McNeil, Edward

    2017-01-01

    Initial clinical factors that can reliably predict a successful within-1-year resolution of childhood immune thrombocytopenia (ITP) are still unclear. This study aimed to determine factors associated with within-12-month resolution of newly diagnosed childhood ITP. The hospital records of 417 consecutive children aged less than 15 years with ITP were reviewed retrospectively and data related to the initial presentation were noted. Logistic regression analysis was used to determine which presenting features were associated with a favorable outcome within 12 months. Significant clinical and laboratory predictors for resolution of newly diagnosed childhood ITP within 12 months were abrupt onset less than 14 days, age less than 5 years, and platelet count at 4 weeks postdiagnosis of at least 100 × 10 9 l -1 . With these three significant predictors, the rate of within-1-year recovery was more than 97.2%, with a positive predictive value of 97.8% for newly diagnosed childhood ITP. Age less than 5 years, onset of bleeding less than 14 days, and follow-up platelet count at 4 weeks of at least 100 × 10 9 l -1 are significant predictive factors for disease resolution among children with newly diagnosed ITP. © 2016 Wiley Periodicals, Inc.

  6. Rituximab Leads to Long Remissions in Patients with Chronic Immune Thrombocytopenia

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    Khalid Al-Habsi

    2015-03-01

    Full Text Available Objectives: To assess the response rate and duration of response in patients with chronic immune thrombocytopenia (ITP receiving rituximab. Methods: We retrospectively analyzed 32 consecutive patients with chronic ITP who were treated in two tertiary centers in Oman. Response assessment was based on the American Society of Hematology criteria. Results: Nineteen patients (59% had an initial response. However, six of the 19 patients lost their response leaving 13 patients with long-lasting remissions. The median age at diagnosis was 25 years (range 14–58. The median time from diagnosis to rituximab therapy was 21 months. The median follow-up after starting rituximab was 26 months. The overall cumulative response rate was 59% (complete response 44%, partial response 15% and the median time to respond was 30 days with a response rate of 44% at four weeks. In all responders, the cumulative rate of loss of response was 32% with a median time to lose response of 54 months. Conclusions: The use of rituximab in ITP achieves high response rate and long remission duration. Our study was limited by the small sample size and further larger prospective studies are recommended.

  7. Mucoepidermoid carcinoma of the lung with initial presentation of microangiopathic hemolytic anemia and thrombocytopenia

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    Yuan-Chun Huang

    2017-12-01

    Full Text Available Mucoepidermoid carcinoma is a rare entity of lung malignancy that is subclassified into high-grade or low-grade types according to its histological features. High-grade mucoepidermoid carcinoma is a more aggressive form of malignancy, with a tendency towards lymph node involvement and distant metastasis. Cancer-related microangiopathic hemolytic anemia as a less common situation of paraneoplastic syndrome may be encountered with metastatic malignancy, but has not been reported previously in mucoepidermoid carcinoma of the lung. Herein, we report a 78-year-old male patient who presented with hemoptysis for one day. Laboratory tests showed microangiopathic hemolytic anemia and thrombocytopenia. A chest X-ray demonstrated consolidation in the left lung field. Chest computed tomography revealed a mass in the left upper lobe, and a subsequent bronchoscopic biopsy was performed. The histopathological results indicated a high-grade mucoepidermoid carcinoma. Magnetic resonance imaging of the brain demonstrated leptomeningeal carcinomatosis. The patient refused systemic chemotherapy, and palliative radiation therapy only was conducted for local disease control. The patient has performed well for 12 months to date since diagnosis of the tumor.

  8. Rapid and simple IgG specific test for the exclusion of heparin induced thrombocytopenia (HIT).

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    Kolde, Hans-Jürgen; Dostatni, Ralf; Mauracher, Susanne

    2011-08-29

    The exclusion of heparin induced thrombocytopenia (HIT) is required for selecting the most appropriate anticoagulation therapy in affected patients. It requires the combination of clinical data with the detection of antibodies directed against platelet factor 4 (PF4) in complex with polyanions (PA) such as heparin. We developed a lateral flow immunoassay (LFIA) for PF4/PA complex specific IgG antibodies based on gold nanoparticles. Unlike most other assays, the initial immune reaction takes place in the liquid phase. The sensitivity of the assay has been adjusted with clinical samples aiming in the reliable detection of sera which are positive in a functional platelet activation assay. Sera from 60 patients with suspected HIT were investigated. LFIA identified correctly all samples (n=20) which were positive in a functional assay (HIPA) and an IgG specific ELISA. It correlated with ELISA, but false positive results were less frequent (7 samples were negative with LFIA and HIPA but positive with ELISA). The LFIA may be a suitable tool for the rapid exclusion of HIT within 10 min.

  9. Prevalence of severe fever with thrombocytopenia syndrome virus in Haemaphysalis longicornis ticks in South Korea.

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    Park, Sun-Whan; Song, Bong Gu; Shin, E-Hyun; Yun, Seok-Min; Han, Myung-Guk; Park, Mi Yeoun; Park, Chan; Ryou, Jungsang

    2014-10-01

    Haemaphysalis longicornis a vector that harbors severe fever with thrombocytopenia syndrome virus (SFTSV) is a major species of tick in South Korea. To investigate the existence and prevalence of SFTSV in Korea, we collected ticks from nine provinces in South Korea for detecting SFTSV. In all, we collected 13,053 ticks, and H. longicornis (90.8%, 11,856/13,053) was the most abundant among them. The minimum infection rate (MIR) of SFTSV in H. longicornis was 0.46% (55 pools). SFTSV was detected in ticks during all the developmental stages, showing MIR in larvae (2/350, 0.57%), nymphs (38/10,436, 0.36%), males (2/221, 0.90%), and females (13/849, 1.53%), respectively. Viruses were detected in ticks collected between April and September. A higher MIR was detected in ticks from the southern part of the country. We amplified the M and S segment partial genes from a sample and analyzed the nucleotide sequence. The results showed a 93-98% homology to Chinese and Japanese strains registered in Genbank. In this study, we confirmed the existence of SFTSV for the first time in South Korea. The SFTSV prevalence data from the studies are essential for raising the awareness of SFTS in South Korea. Copyright © 2014 Elsevier GmbH. All rights reserved.

  10. A novel recombinant human thrombopoietin therapy for the management of immune thrombocytopenia in pregnancy.

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    Kong, Zhangyuan; Qin, Ping; Xiao, Shan; Zhou, Hai; Li, Hong; Yang, Renchi; Liu, Xiaofan; Luo, Jianmin; Li, Zhichun; Ji, Guochao; Cui, Zhongguang; Bai, Yusheng; Wu, Yuxia; Shao, Linlin; Peng, Jun; Ma, Jun; Hou, Ming

    2017-08-31

    The aim of this study was to determine the safety and efficacy of recombinant human thrombopoietin (rhTPO) for the management of immune thrombocytopenia (ITP) during pregnancy. Pregnant patients with ITP were enrolled in the study if they had a platelet count less than 30 × 10 9 /L, were experiencing bleeding manifestations, had failed to respond to corticosteroids and/or intravenous immunoglobulin (IVIG), and had developed refractoriness to platelet transfusion. Thirty-one patients received rhTPO at an initial dose of 300 U/kg once daily for 14 days. Twenty-three patients responded (74.2%), including 10 complete responders (>100 × 10 9 /L) and 13 responders (30-100 × 10 9 /L). It appears that rhTPO ameliorated the bleeding symptoms remarkably, even in the nonresponders. rhTPO was well tolerated. Dizziness, fatigue, and pain at an injection site were reported in 1 patient each. No congenital disease or developmental delays were observed in the infants in a median follow-up of 53 (range, 39-68) weeks. In conclusion, rhTPO is a potentially safe and effective treatment choice for patients with ITP during pregnancy. Our work has paved the way for further study on the clinical application of rhTPO and other thrombopoietic agents for the management of ITP during pregnancy. This study is registered at www.clinicaltrials.gov as NCT02391272. © 2017 by The American Society of Hematology.

  11. Severe fever with thrombocytopenia syndrome, an emerging tick-borne zoonosis.

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    Liu, Quan; He, Biao; Huang, Si-Yang; Wei, Feng; Zhu, Xing-Quan

    2014-08-01

    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging haemorrhagic fever that was first described in rural areas of China. The causative agent, SFTS virus (SFTSV), is a novel phlebovirus in the Bunyaviridae family. Since the first report in 2010, SFTS has been found in 11 provinces of China, with about 2500 reported cases, and an average case-fatality rate of 7·3%. The disease was also reported in Japan and Korea in 2012; Heartland virus, another phlebovirus genetically closely related to SFTSV, was isolated from two patients in the USA. The disease has become a substantial risk to public health, not only in China, but also in other parts of the world. The virus could undergo rapid evolution by gene mutation, reassortment, and homologous recombination in tick vectors and vertebrate reservoir hosts. No specific treatment of SFTS is available, and avoiding tick bites is an important measure to prevent the infection and transmission of SFTSV. This Review provides information on the molecular characteristics and ecology of this emerging tick-borne virus and describes the epidemiology, clinical signs, pathogenesis, diagnosis, treatment, and prevention of human infection with SFTSV. Copyright © 2014 Elsevier Ltd. All rights reserved.

  12. Feasibility of an Isometric Maximal Voluntary Contraction Test in Hematological Cancer Patients during Thrombocytopenia

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    Philipp Zimmer

    2013-01-01

    Full Text Available Introduction. Resistance training is rarely offered to hemato-oncological patients in the daily clinical routine due to its potential harmful impact on the cardiovascular system and the long periods of thrombocytopenia experienced by these patients. Therefore, it is important to determine a valid assessment to define and control resistance training. In this study, the feasibility of a maximal voluntary contraction (MVC test was investigated in hemato-oncological patients. This inexpensive assessment may be a practicable alternative to the one repetition maximum test which is currently described as the gold standard. Methods. 29 hemato-oncological patients with platelet counts between 30000/μL and 70000/μL were recruited for this pilot study. Complications like petechial bleedings, muscle convulsion, and pain were assessed using the Brief Pain Inventory before and 48 hours after the MVC test, which was performed unidirectionally for the quadriceps muscle. Results. We did not detect any statistically significant test-related exacerbations or pain development. Discussion. MVC testing seems to be a feasible method to control a resistance training program in hemato-oncological patients. Further studies need to extend their methods and, for example, compare the MVC test with the one repetition maximum test.

  13. Family Cluster Analysis of Severe Fever with Thrombocytopenia Syndrome Virus Infection in Korea.

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    Yoo, Jeong Rae; Heo, Sang Taek; Park, Dahee; Kim, Hyemin; Fukuma, Aiko; Fukushi, Shuetsu; Shimojima, Masayuki; Lee, Keun Hwa

    2016-12-07

    Severe fever with thrombocytopenia syndrome (SFTS) is tick-borne viral disease that was first suspected in China in 2009. The causative virus (SFTSV) was isolated in 2009 and reported in 2011, and SFTSV expanded its geographic distribution in 2012-2013, from China to South Korea and Japan. Most SFTSV infections occur through Haemaphysalis longicornis However, SFTSV infection can also occur between family members, and nosocomial transmission of SFTSV is also possible through close contact with a patient. In this study, we first analyzed clinical, epidemiological, and laboratory data for SFTS patients and family members of an index patient in Korea. The S segment of SFTSV was amplified from the sera of three patients, and the S segment of SFTSV and IgG specific to SFTSV were detected in the serum from one family member; although this individual had no history of exposure to H. longicornis, she frequently had close contact with the index patient. In Korea, SFTSV infection among family members does not have to be reported, and we suggest that person-to-person transmission of SFTSV among family members is possible in Korea. © The American Society of Tropical Medicine and Hygiene.

  14. Assessment of Th17/Treg cells and Th cytokines in an improved immune thrombocytopenia mouse model.

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    Zhang, Guoyang; Zhang, Ping; Liu, Hongyun; Liu, Xiaoyan; Xie, Shuangfeng; Wang, Xiuju; Wu, Yudan; Chang, Jianxing; Ma, Liping

    2017-09-01

    The improved passive immune thrombocytopenia (ITP) mouse model has been extensively utilized for the study of ITP. However, how closely this model matches the human inflammation state and immune background is unclear. Our study aimed to explore the profile of Th cytokines and Th17/Treg cells in the model. We induced the ITP mouse model by dose-escalation injection of MWReg30. The serum levels of cytokines (IFN-γ, IL-2, IL-4, IL-10, IL-17A, and TGF-β1) were measured by enzyme-linked immunosorbent assay and the frequency of Th17 and Treg cells was measured by flow cytometry. The mRNA expression of Foxp3 and RORrt was measured by real-time PCR. The serum levels of cytokines IFN-γ, TGF-β1, IL-4, and IL-10 were significantly lower in ITP mice. The secretion of serum proinflammatory cytokines IL-2 and IL-17A and the percentage of Th17 cells showed no statistically significant increase. In ITP mice the frequency of Treg cells and mRNA expression of Foxp3 was significantly lower in splenocytes. Our data suggest that the improved passive ITP mouse model does not mimic the autoimmune inflammatory process of human ITP. Compared with human ITP, this model has a similar change in frequency of Treg cells, which may directly or indirectly result from antibody-mediated platelet destruction due to attenuated release of TGF-β.

  15. Long-term outcomes of laparoscopic versus open splenectomy for immune thrombocytopenia.

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    Tada, Kazuhiro; Ohta, Masayuki; Saga, Kunihiro; Takayama, Hiroomi; Hirashita, Teijiro; Endo, Yuichi; Uchida, Hiroki; Iwashita, Yukio; Inomata, Masafumi

    2018-02-01

    Splenectomy is the standard therapy for medically refractory immune thrombocytopenia (ITP). Laparoscopic splenectomy (LS) has gained wide acceptance; however, the long-term outcomes of LS versus open splenectomy (OS) for patients with ITP remain unclear. We analyzed, retrospectively, 32 patients who underwent splenectomy, as LS in 22 and OS in 10, for refractory ITP at our institute. Data were evaluated based on the American Society of Hematology 2011 evidence-based practice guidelines for ITP. Although the operation time was significantly longer in the LS group (p < 0.01), LS was associated with less blood loss (p < 0.01), infrequent blood transfusion during surgery (p < 0.01), quicker resumption of oral intake (p < 0.01), and shorter hospital stay (p < 0.01) than OS. Positive responses, including complete and partial remission, were achieved in 90% of the OS group patients and 77% of the LS group patients. The mean follow-up periods were 183 and 92 months, respectively. Relapse-free survival rates, 15 years after the operation were 63% in the OS group and 94% in the LS group. LS can provide better short-term results and comparable long-term results to those of OS for ITP.

  16. Splenectomy and the incidence of venous thromboembolism and sepsis in patients with immune thrombocytopenia

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    Boyle, Soames; White, Richard H.; Brunson, Ann

    2013-01-01

    Patients with immune thrombocytopenia (ITP) who relapse after an initial trial of corticosteroid treatment present a therapeutic challenge. Current guidelines recommend consideration of splenectomy, despite the known risks associated with surgery and the postsplenectomy state. To better define these risks, we identified a cohort of 9976 patients with ITP, 1762 of whom underwent splenectomy. The cumulative incidence of abdominal venous thromboembolism (AbVTE) was 1.6% compared with 1% in patients who did not undergo splenectomy; venous thromboembolism (VTE) (deep venous thrombosis and pulmonary embolus) after splenectomy was 4.3% compared with 1.7% in patients who did not undergo splenectomy. There was increased risk of AbVTE early (splenectomy. There was increased risk of VTE both early (HR 5.2 [CI, 3.2-8.5]) and late (HR 2.7 [CI, 1.9-3.8]) after splenectomy. The cumulative incidence of sepsis was 11.1% among the ITP patients who underwent splenectomy and 10.1% among the patients who did not. Splenectomy was associated with a higher adjusted risk of sepsis, both early (HR 3.3 [CI, 2.4-4.6]) and late (HR 1.6 or 3.1, depending on comorbidities). We conclude that ITP patients post splenectomy are at increased risk for AbVTE, VTE, and sepsis. PMID:23637127

  17. Long-term results of splenectomy in adult chronic immune thrombocytopenia.

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    Guan, Yue; Wang, Shixuan; Xue, Feng; Liu, Xiaofan; Zhang, Lei; Li, Huiyuan; Yang, Renchi

    2017-03-01

    We performed this study in adult patients with chronic primary immune thrombocytopenia to explore the long-term efficacy and safety of splenectomy. Data of 174 patients who underwent splenectomy in our hospital from 1994 to 2014 were analyzed. After splenectomy, 126 (72.4%) patients achieved a complete response (CR) and 28 (16.1%) achieved a response (R). Thirty-two (20.8%) responders relapsed with a median time of 24 months. Compared with non-responders and recurrent patients, the stable responders were younger and had higher preoperation and postoperation peak platelet count, later peak platelet count emergence time, and more megakaryocytes. Corticosteroid-dependent patients were more likely to response to splenectomy than those refractory to corticosteroid. We performed a relapse-free survival analysis among the 154 responders. In univariate analyses, corticosteroid dependent and time from diagnosis to splenectomy ≤24 months showed predictive value to persistent response. But only corticosteroid dependent was a significant predictor in multivariate analysis. The 30-d complication rate after the surgery was 25.9%. There were five (2.9%) patients experienced thrombosis and three (1.7%) refractory patients died during follow-up. Splenectomy was a safe treatment with a cure rate of 58.0%. Corticosteroid dependent showed predictive value to persistent response. © 2016 John Wiley & Sons A/S. Published by John Wiley & Sons Ltd.

  18. Is B-cell depletion still a good strategy for treating immune thrombocytopenia?

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    Godeau, Bertrand; Stasi, Roberto

    2014-04-01

    B cells play an important role in the pathophysiology of immune thrombocytopenia (ITP). Thus, a rational approach to ITP treatment involves B-cell depletion such as with rituximab. More than 10 years after the first reports of data suggesting that anti-CD20 MoAbs could be effective treatment for ITP, we have now a clear view of its efficacy, with an overall response in about 60% of patients. The report of fatal opportunistic infections was initially a matter of concern, but to date, reassuring data have been reported and rituximab appears well tolerated with an acceptable risk of infection. In view of these data, rituximab may always be a valid option for ITP. However, relapses are frequent, and the long-term response appears modest. Therefore, strategies to ameliorate the long-term efficacy of the treatment must be developed. Several options may be tested including giving rituximab upfront or early on after ITP diagnosis, maintenance treatment with repeated infusions, and combining rituximab with other treatments able to modulate T-cell compartment to achieve a synergistic effect. New generations of B-cell targeted treatment, including new-generations anti-CD20 MoAbs, may be also tested. Copyright © 2014. Published by Elsevier Masson SAS.

  19. Narcolepsy as an Immune-Mediated Disease

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    Alberto K. De la Herrán-Arita

    2014-01-01

    Full Text Available Narcolepsy is a neurological disorder characterized by excessive daytime sleepiness, cataplexy, hypnagonic hallucinations, sleep paralysis, and disturbed nocturnal sleep patterns. This disease is secondary to the specific loss of hypothalamic hypocretin (orexin-producing neurons in the lateral hypothalamus. An autoimmune basis for the disease has long been suspected based on its strong association with the genetic marker DQB1*06:02, and current studies greatly support this hypothesis. Narcolepsy with hypocretin deficiency is associated with human leukocyte antigen (HLA and T cell receptor (TCR polymorphisms, suggesting that an autoimmune process targets a peptide unique to hypocretin-producing neurons via specific HLA-peptide-TCR interactions. This concept has gained a lot of notoriety after the increase of childhood narcolepsy in 2010 following the 2009 H1N1 pandemic (pH1N1 in China and vaccination with Pandemrix, an adjuvanted H1N1 vaccine that was used in Scandinavia. The surge of narcolepsy cases subsequent to influenza A H1N1 infection and H1N1 vaccination suggests that processes such as molecular mimicry or bystander activation might be crucial for disease development.

  20. Cancer as an immune-mediated disease

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    Shurin MR

    2012-06-01

    Full Text Available Michael R ShurinDepartments of Pathology and Immunology, University of Pittsburgh Medical Center, Pittsburgh, PA, USAAbstract: The link between oncology and immunology has a long history and its development is forced by the necessity to develop innovative and highly efficient modalities for immunological destruction of malignant cells. The limited efficacy of surgery, chemotherapy and radiation also exemplify these issues, as these treatments do not eliminate all cancerous cells, do not address the immunosuppressive nature of the disease and can further impair the patient's immune response weakening patient's resistance to the cancer. Multidisciplinary analysis of the interaction between the immune system and cancer in preclinical and clinical settings suggests that the immune system is closely intertwined with both cancer pathogenesis and treatment. On the one hand, cancer is a manifestation of malfunctions in immunity, as malignant cells manage to escape recognition and elimination by the immune system. Chronic infections and inflammation associated with limited or polarized immune responses also contribute to carcinogenesis and tumor progression. The tumor immunoenvironment represents specific conditions and elements that support cancerous cell survival, proliferation and spreading. On the other hand, the specificity and strength of antitumor immunity is a powerful and efficient tool that can be used to recognize and destroy neoplastic cells or their supporting microenvironment. Understanding the role of the immune system in controlling and supporting tumor initiation, formation, growth and progression has crucial implications for cancer therapy and will therefore guide the future development of cancer immunotherapy and its combination with conventional therapies to achieve optimal antitumor effects in patients with different types of cancer.Keywords: tumor immunology and immunotherapy, tumor immunoenvironment, cancer, immunosuppression, regulatory immune cells

  1. Thrombosis in adult patients with acute leukemia.

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    Del Principe, Maria Ilaria; Del Principe, Domenico; Venditti, Adriano

    2017-11-01

    Recent studies indicate that the risk of thrombosis in hematologic patients may be similar or even higher than that found in patients with solid tumors. However, available information about pathogenesis and incidence of thrombosis in acute leukemia is limited. This review focuses on mechanisms underlying thrombosis in acute leukemia and discusses recent literature data. In the last few years, proofs have been provided that leukemic cells release free prothrombotic products, such as micro-vesicles, tissue factors, circulating free DNA and RNA. Furthermore, leukemic blasts can activate the procoagulant population of platelets, which initiate and amplify coagulation, causing thrombosis. In addition to factors produced by acute leukemia itself, others concur to trigger thrombosis. Some drugs, infections and insertion of central venous catheter have been described to increase risk of thrombosis in patients with acute leukemia. Thrombosis represents a serious complication in patients affected by myeloid and lymphoid acute leukemia. A proper knowledge of its pathophysiology and of the predisposing risk factors may allow to implement strategies of prevention. Improving prevention of thrombosis appears a major goal in patients whose frequent conditions of thrombocytopenia impede an adequate delivery of anticoagulant therapy.

  2. Incidence of leukopenia and thrombocytopenia with cisplatin plus mitomycin-c versus melphalan in patients undergoing cytoreductive surgery (CRS) and hyperthermic intraperitoneal chemotherapy (HIPEC).

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    Hakeam, Hakeam A; Arab, Amal; Azzam, Ayman; Alyahya, Zyad; Eldali, Abdelmoneim M; Amin, Tarek

    2018-02-10

    Cytopenia after hyperthermic intraperitoneal chemotherapy (HIPEC) with cytoreductive surgery (CRS) has been reported in non-comparative studies with various chemotherapeutic regimens. This study compared the incidence of leukopenia and thrombocytopenia in patients who underwent CRS/HIPEC and received melphalan or cisplatin plus mitomycin-c (CIS + MMC). This retrospective study included patients who underwent CRS/HIPEC at King Faisal Specialist Hospital and Research Centre, Riyadh, Saudi Arabia from March 2011 to March 2017 and received melphalan 60 mg/m 2 or CIS 100 mg/m 2 combined with MMC 30 mg/m 2 . Incidences and severity of leukopenia, neutropenia, thrombocytopenia, and anemia were compared between groups. This study included 46 patients who received CIS + MMC and 35 patients who received melphalan. The leukopenia incidence was 25.7% in the melphalan group and 17.3% in the CIS + MMC group (P = 0.362), with one patient (2.8%) in the melphalan group developed grade V leukopenia. The number of days to leukocyte nadir was 32.8 days for CIS + MMC group compared to 9.8 days for melphalan group(P = 0.035). Thrombocytopenia occurred at a similar rate in the melphalan (60%) and CIS + MMC (68.8%) groups (P = 0.4). Grade III thrombocytopenia developed in 3.2% and 5% of patients in the melphalan and the CIS + MMC groups, respectively. Neutropenia did not occur in any patient. In multivariate analysis, leukopenia predictors were female gender (P = 0.047) and baseline leukocyte counts (P = 0.029). Baseline platelet count predicted thrombocytopenia (P leukopenia and thrombocytopenia. Severe leukopenia and severe thrombocytopenia were rare following CRS/HIPEC using both chemotherapy regimens.

  3. Esophageal Candidiasis as the Initial Manifestation of Acute Myeloid Leukemia.

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    Komeno, Yukiko; Uryu, Hideki; Iwata, Yuko; Hatada, Yasumasa; Sakamoto, Jumpei; Iihara, Kuniko; Ryu, Tomiko

    2015-01-01

    A 47-year-old woman presented with persistent dysphagia. A gastroendoscopy revealed massive esophageal candidiasis, and oral miconazole was prescribed. Three weeks later, she returned to our hospital without symptomatic improvement. She was febrile, and blood tests showed leukocytosis (137,150 /μL, blast 85%), anemia and thrombocytopenia. She was diagnosed with acute myeloid leukemia (AML). She received chemotherapy and antimicrobial agents. During the recovery from the nadir, bilateral ocular candidiasis was detected, suggesting the presence of preceding candidemia. Thus, esophageal candidiasis can be an initial manifestation of AML. Thorough examination to detect systemic candidiasis is strongly recommended when neutropenic patients exhibit local candidiasis prior to chemotherapy.

  4. LOW FREQUENCY HUMAN PLATELET ANTIGENS (HPA) AS TRIGGERS FOR NEONATAL ALLOIMMUNE THROMBOCYTOPENIA (NAIT)

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    Peterson, Julie A.; Gitter, Maria; Bougie, Daniel W.; Pechauer, Shannon; Hopp, Kathleen A.; Pietz, Brad; Szabo, Aniko; Curtis, Brian R.; McFarland, Janice; Aster, Richard H.

    2013-01-01

    Background Twenty-four low frequency platelet antigens (HPAs) have been implicated as immunogens in neonatal alloimmune thrombocytopenia (NAIT). We performed studies to define more fully how often these antigens trigger maternal immunization leading to NAIT. Study design and methods In a Phase 1 study, fathers of selected NAIT cases not resolved by serologic testing but thought to have a high likelihood of NAIT on clinical and serologic grounds were typed for low frequency HPAs (LFHPAs) by DNA sequencing. In a Phase 2 study, high-throughput methods were used to type fathers of 1067 consecutive unresolved NAIT cases for LFHPAs. Mothers of 1338 unresolved cases were also typed to assess the prevalence of LFHPAs in a population racially/ethnically similar to the fathers. Results In Phase 1, LFHPAs were identified in 16 of 244 fathers (6.55%). In Phase 2, LFPAs were found in only 28 of 1067 fathers (2.62%). LFHPAs were identified in 27 of 1338 maternal samples (2.01%). HPA-9bw was by far the most common LFHPA identified in the populations studied and was the only LFHPA that was significantly more common in fathers than in mothers of affected infants (P=0.02). Conclusions Maternal immunization against recognized LFHPAs accounts for only a small fraction of the cases of apparent NAIT not resolved by standard serologic testing. Typing of the fathers of such cases for LFHPAs is likely to be rewarding only when a maternal antibody specific for a paternal platelet glycoprotein is demonstrated and/or there is compelling clinical evidence for NAIT. PMID:24128174

  5. DNA Methyltransferase 3B Gene Promoter and Interleukin-1 Receptor Antagonist Polymorphisms in Childhood Immune Thrombocytopenia

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    Margarita Pesmatzoglou

    2012-01-01

    Full Text Available Primary immune thrombocytopenia (ITP is one of the most common blood diseases as well as the commonest acquired bleeding disorder in childhood. Although the etiology of ITP is unclear, in the pathogenesis of the disease, both environmental and genetic factors including polymorphisms of TNF-a, IL-10, and IL-4 genes have been suggested to be involved. In this study, we investigated the rs2424913 single-nucleotide polymorphism (SNP (C46359T in DNA methyltransferase 3B (DNMT3B gene promoter and the VNTR polymorphism of IL-1 receptor antagonist (IL-1 Ra intron-2 in 32 children (17 boys with the diagnosis of ITP and 64 healthy individuals. No significant differences were found in the genotype distribution of DNMT3B polymorphism between the children with ITP and the control group, whereas the frequency of allele T appeared significantly increased in children with ITP (P = 0.03, OR = 2, 95% CI: 1.06–3.94. In case of IL-1 Ra polymorphism, children with ITP had a significantly higher frequency of genotype I/II, compared to control group (P = 0.043, OR = 2.60, 95% CI: 1.02–6.50. Moreover, genotype I/I as well as allele I was overrepresented in the control group, suggesting that allele I may have a decreased risk for development of ITP. Our findings suggest that rs2424913 DNMT3B SNP as well as IL-1 Ra VNTR polymorphism may contribute to the susceptibility to ITP.

  6. Extensive severe fever with thrombocytopenia syndrome virus contamination in surrounding environment in patient rooms.

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    Ryu, B-H; Kim, J Y; Kim, T; Kim, M-C; Kim, M J; Chong, Y-P; Lee, S-O; Choi, S-H; Kim, Y S; Woo, J H; Kim, S-H

    2018-01-31

    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging tick-borne disease in Korea and China. Although there is previous evidence of person-to-person transmission via direct contact with body fluids, the role of environmental contamination by SFTS virus (SFTSV) in healthcare settings has not been established. We therefore investigated the contamination of the healthcare environment by SFTSV. We investigated the possible contamination of hospital air and surfaces with SFTSV transmission by collecting air and swabbing environmental surface samples in two hospitals treating six SFTS patients between March and September 2017. The samples were tested using real-time RT-PCR for SFTS M and S segments. Of the six SFTS patients, four received mechanical ventilation and three died. Five rooms were occupied by those using mechanical ventilation or total plasma exchange therapy in isolation rooms without negative pressure and one room was occupied by a patient bedridden due to SFTS. SFTSV was detected in 14 (21%) of 67 swab samples. Five of 24 swab samples were obtained from fomites including stethoscopes, and 9 of 43 were obtained from fixed structures including doorknobs and bed guardrails. Some samples from fixed structures such as television monitors and sink tables were obtained in areas remote from the patients. SFTSV RNA was not detected in five air samples from three patients' rooms. Our data suggest that SFTSV contamination was extensive in surrounding environments in SFTS patients' rooms. Therefore, more strict isolation methods and disinfecting procedures should be considered when managing SFTS patients. Copyright © 2018 European Society of Clinical Microbiology and Infectious Diseases. Published by Elsevier Ltd. All rights reserved.

  7. Severe Fever with Thrombocytopenia Syndrome in South Korea, 2013-2015.

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    Seong Jin Choi

    2016-12-01

    Full Text Available Severe fever with thrombocytopenia syndrome (SFTS is an emerging infectious disease that was recently identified in China, South Korea and Japan. The objective of the study was to evaluate the epidemiologic and clinical characteristics of SFTS in South Korea.SFTS is a reportable disease in South Korea. We included all SFTS cases reported to the Korea Centers for Disease Control and Prevention (KCDC from January 2013 to December 2015. Clinical information was gathered by reviewing medical records, and epidemiologic characteristics were analyzed using both KCDC surveillance data and patient medical records. Risk factors for mortality in patients with SFTS were assessed. A total of 172 SFTS cases were reported during the study period. SFTS occurred throughout the country, except in urban areas. Hilly areas in the eastern and southeastern regions and Jeju island (incidence, 1.26 cases /105 person-years were the main endemic areas. The yearly incidence increased from 36 cases in 2013 to 81 cases in 2015. Most cases occurred from May to October. The overall case fatality ratio was 32.6%. The clinical progression was similar to the 3 phases reported in China: fever, multi-organ dysfunction, and convalescence. Confusion, elevated C-reactive protein, and prolonged activated partial thromboplastin times were associated with mortality in patients with SFTS. Two outbreaks of nosocomial SFTS transmission were observed.SFTS is an endemic disease in South Korea, with a nationwide distribution and a high case-fatality ratio. Confusion, elevated levels of C-reactive protein, and prolonged activated partial thromboplastin times were associated with mortality in patients with SFTS.

  8. Age is a critical risk factor for severe fever with thrombocytopenia syndrome.

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    Shujun Ding

    Full Text Available Severe Fever with Thrombocytopenia Syndrome (SFTS is an emerging infectious disease in East Asia. SFTS is a tick borne hemorrhagic fever caused by SFTSV, a new bunyavirus named after the syndrome. We investigated the epidemiology of SFTS in Laizhou County, Shandong Province, China.We collected serum specimens of all patients who were clinically diagnosed as suspected SFTS cases in 2010 and 2011 in Laizhou County. The patients' serum specimens were tested for SFTSV by real time fluorescence quantitative PCR (RT-qPCR. We collected 1,060 serum specimens from healthy human volunteers by random sampling in Laizhou County in 2011. Healthy persons' serum specimens were tested for specific SFTSV IgG antibody by ELISA.71 SFTS cases were diagnosed in Laizhou County in 2010 and 2011, which resulted in the incidence rate of 4.1/100,000 annually. The patients ranged from 15 years old to 87 years old and the median age of the patients were 59 years old. The incidence rate of SFTS was significantly higher in patients over 40 years old and fatal cases only occurred in patients over 50 years old. 3.3% (35/1,060 of healthy people were positive to SFTSV IgG antibody. The SFTSV antibody positive rate was not significantly different among people at different age groups.Our results revealed that seroprevalence of SFTSV in healthy people in Laizhou County was not significantly different among age groups, but SFTS patients were mainly elderly people, suggesting that age is the critical risk factor or determinant for SFTS morbidity and mortality.

  9. A case of refractory immune thrombocytopenia in pregnancy managed with elthrombopag

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    Jyothis Purushothaman

    2016-01-01

    Full Text Available Immune thrombocytopenic purpura is a common acquired autoimmune disorder defined by a low platelet count secondary to accelerated platelet destruction or impaired thrombopoesis by anti-platelet antibodies. Thrombopoietin (TPO-mimetic drugs such as eltrombopag and romiplostim have been used successfully in many nonpregnant individuals with immune thrombocytopenia (ITP but studies based on its effects in pregnancy are limited. A 27-year-old multigravida who is a known case of ITP with bad obstetric history was referred to the Department of Obstetrics and Gynecology at 26 weeks of gestation with complaints of mucosal bleeding and recurrent abortions. After 2 weeks of hospital stay, the patient did not respond to treatment with steroid and immunosuppressant. There was a rapid decline in platelet count with mucosal bleeds for which she required frequent platelet transfusions. Due to high costs, short action periods, and other potential maternal and fetal side effects of intravenous immunoglobulin (IVIgG and anti-D, it was decided that TPO-mimetic drug eltrombopag would be given. After starting treatment with eltrombopag, the patient's platelet count could be maintained between 30,000/μl and 50,000/μl. At 36 weeks of gestation following preterm-induced vaginal delivery, she delivered a male active baby weighing 1.86 kg with an Apgar score of 8/10. After delivery, her platelet count was 60,000/μl. Eltrombopag is a thrombopoietin receptor agonist. It has been assigned to pregnancy category C by the Food and Drug Administration (FDA. There are no adequate and well-controlled studies of use of eltrombopag in pregnancy. In our case, the drug was given in the last trimester of pregnancy and the mother and baby were in good health at the time of discharge from the hospital and during follow-up.

  10. Flow cytometric immunobead assay for quantitative detection of platelet autoantibodies in immune thrombocytopenia patients.

    Science.gov (United States)

    Zhai, Juping; Ding, Mengyuan; Yang, Tianjie; Zuo, Bin; Weng, Zhen; Zhao, Yunxiao; He, Jun; Wu, Qingyu; Ruan, Changgeng; He, Yang

    2017-10-23

    Platelet autoantibody detection is critical for immune thrombocytopenia (ITP) diagnosis and prognosis. Therefore, we aimed to establish a quantitative flow cytometric immunobead assay (FCIA) for ITP platelet autoantibodies evaluation. Capture microbeads coupled with anti-GPIX, -GPIb, -GPIIb, -GPIIIa and P-selectin antibodies were used to bind the platelet-bound autoantibodies complex generated from plasma samples of 250 ITP patients, 163 non-ITP patients and 243 healthy controls, a fluorescein isothiocyanate (FITC)-conjugated secondary antibody was the detector reagent and mean fluorescence intensity (MFI) signals were recorded by flow cytometry. Intra- and inter-assay variations of the quantitative FCIA assay were assessed. Comparisons of the specificity, sensitivity and accuracy between quantitative and qualitative FCIA or monoclonal antibody immobilization of platelet antigen (MAIPA) assay were performed. Finally, treatment process was monitored by our quantitative FCIA in 8 newly diagnosed ITPs. The coefficient of variations (CV) of the quantitative FCIA assay were respectively 9.4, 3.8, 5.4, 5.1 and 5.8% for anti-GPIX, -GPIb, -GPIIIa, -GPIIb and -P-selectin autoantibodies. Elevated levels of autoantibodies against platelet glycoproteins GPIX, GPIb, GPIIIa, GPIIb and P-selectin were detected by our quantitative FCIA in ITP patients compared to non-ITP patients or healthy controls. The sensitivity, specificity and accuracy of our quantitative assay were respectively 73.13, 81.98 and 78.65% when combining all 5 autoantibodies, while the sensitivity, specificity and accuracy of MAIPA assay were respectively 41.46, 90.41 and 72.81%. A quantitative FCIA assay was established. Reduced levels of platelet autoantibodies could be confirmed by our quantitative FCIA in ITP patients after corticosteroid treatment. Our quantitative assay is not only good for ITP diagnosis but also for ITP treatment monitoring.

  11. Survival, bacterial clearance and thrombocytopenia are improved in polymicrobial sepsis by targeting nuclear transport shuttles.

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    Ruth Ann Veach

    Full Text Available The rising tide of sepsis, a leading cause of death in the US and globally, is not adequately controlled by current antimicrobial therapies and supportive measures, thereby requiring new adjunctive treatments. Severe microvascular injury and multiple organ failure in sepsis are attributed to a "genomic storm" resulting from changes in microbial and host genomes encoding virulence factors and endogenous inflammatory mediators, respectively. This storm is mediated by stress-responsive transcription factors that are ferried to the nucleus by nuclear transport shuttles importins/karyopherins. We studied the impact of simultaneously targeting two of these shuttles, importin alpha 5 (Imp α5 and importin beta 1 (Imp β1, with a cell-penetrating Nuclear Transport Modifier (NTM in a mouse model of polymicrobial sepsis. NTM reduced nuclear import of stress-responsive transcription factors nuclear factor kappa B, signal transducer and activator of transcription 1 alpha, and activator protein 1 in liver, which was also protected from sepsis-associated metabolic changes. Strikingly, NTM without antimicrobial therapy improved bacterial clearance in blood, spleen, and lungs, wherein a 700-fold reduction in bacterial burden was achieved while production of proinflammatory cytokines and chemokines in blood plasma was suppressed. Furthermore, NTM significantly improved thrombocytopenia, a prominent sign of microvascular injury in sepsis, inhibited neutrophil infiltration in the liver, decreased L-selectin, and normalized plasma levels of E-selectin and P-selectin, indicating reduced microvascular injury. Importantly, NTM combined with antimicrobial therapy extended the median time to death from 42 to 83 hours and increased survival from 30% to 55% (p = 0.022 as compared to antimicrobial therapy alone. This study documents the fundamental role of nuclear signaling mediated by Imp α5 and Imp β1 in the mechanism of polymicrobial sepsis and highlights the

  12. Safety and Feasibility of Transradial Access for Visceral Interventions in Patients with Thrombocytopenia

    Energy Technology Data Exchange (ETDEWEB)

    Titano, J. J., E-mail: joseph.titano@mountsinai.org; Biederman, D. M., E-mail: derek.biederman@mountsinai.org; Marinelli, B. S., E-mail: brett.marinelli@exchange.mssm.edu; Patel, R. S., E-mail: rahul.patel@mountsinai.org; Kim, E., E-mail: edward.kim@mountsinai.org; Tabori, N. E., E-mail: nora.tabori@mountsinai.org; Nowakowski, F. S., E-mail: scott.nowakowski@mountsinai.org; Lookstein, R. A., E-mail: robert.lookstein@mountsinai.org; Fischman, A. M., E-mail: aaron.fischman@mountsinai.org [Icahn School of Medicine at Mount Sinai, Department of Interventional Radiology (United States)

    2016-05-15

    PurposeTransradial access (TRA) has shown lower morbidity and decreased bleeding complications compared to transfemoral access. This study evaluates the safety and feasibility of TRA in thrombocytopenic patients undergoing visceral interventions.Methods and MaterialsPatients who underwent visceral interventions via the radial artery with platelet count less than or equal to 50,000/µL were included in the study. Outcome variables included technical success, access site, bleeding, transfusion, and neurological complications.ResultsFrom July 1, 2012, to May 31, 2015, a total of 1353 peripheral interventions via TRA were performed, of which 85 procedures were performed in 64 patients (mean age 62.2 years) with a platelet count <50,000/µL (median 39,000/µL). Interventions included chemoembolization (n = 46), selective internal radiation therapy (n = 30), and visceral embolization (n = 9). Technical success was 97.6 % with two cases of severe vessel spasm requiring ipsilateral femoral crossover. There was no major access site, bleeding, or neurological adverse events at 30 days. Minor access site hematomas occurred in five cases (5.9 %) and were treated conservatively in all cases. Pre-procedural platelet transfusions were administered in 23 (27.1 %) cases. There was no statistically significant difference in access site or bleeding complications between the transfused and nontransfused groups.ConclusionsTransradial visceral interventions in patients with thrombocytopenia are both feasible and safe, possibly without the need for platelet transfusions.

  13. Cytokine changes in response to TPO receptor agonist treatment in primary immune thrombocytopenia.

    Science.gov (United States)

    Qu, Ming-Ming; Liu, Xue-Na; Liu, Xin-Guang; Feng, Qi; Liu, Yang; Zhang, Xu; Liu, Shuang; Zhang, Lei; Li, Guo-Sheng; Zhu, Yuan-Yuan; Lv, Ming-Yun; Peng, Jun; Hou, Ming

    2017-04-01

    Thrombopoietin receptor agonists (TPO-RAs) have been clinically used in primary immune thrombocytopenia (ITP) with favorable outcomes, while their effect on cytokine regulation in ITP remains unknown. In the present study, plasma and mRNA expression levels of interleukin (IL)-2, interferon gamma (IFN-γ), IL-4, IL-17A, and transforming growth factor-β1 (TGF-β1) were determined by ELISA and real-time quantitative PCR in 26 corticosteroid-resistant/relapsed ITP patients receiving eltrombopag or rhTPO therapy and 15 healthy controls (HCs). Results showed that plasma and mRNA levels of IL-2, IFN-γ, IL-4, and IL-17A in ITP patients did not change significantly after TPO-RA treatment, whereas TGF-β1 levels increased remarkably. The pre- and post-treatment plasma and mRNA levels of IFN-γ and IL-2 were significantly higher, while the pre- and post-treatment IL-4 levels as well as the pre-treatment TGF-β1 levels were remarkably lower in ITP patients compared with HCs. There was no significant difference in TGF-β1 levels between TPO-RA-treated ITP patients and HCs. No statistical difference was found in plasma levels of IL-17A between ITP patients before or after treatment and HCs. However, the pre- and post-treatment mRNA expression of IL-17A and retinoic orphan receptor (ROR) γt in ITP patients were higher than that in HCs. Overall, these findings indicated that TPO-RA treatment could promote the secretion of TGF-β1, while it could not correct the Th1 and Th17 polarization in ITP patients. This study might improve our understanding of the mechanism of action of TPO-RAs and provide important information for optimizing therapeutic strategies for ITP. Copyright © 2017 Elsevier Ltd. All rights reserved.

  14. Severe Fever with Thrombocytopenia Syndrome in South Korea, 2013-2015.

    Science.gov (United States)

    Choi, Seong Jin; Park, Sang-Won; Bae, In-Gyu; Kim, Sung-Han; Ryu, Seong Yeol; Kim, Hyun Ah; Jang, Hee-Chang; Hur, Jian; Jun, Jae-Bum; Jung, Younghee; Chang, Hyun-Ha; Kim, Young Keun; Yi, Jongyoun; Kim, Kye-Hyung; Hwang, Jeong-Hwan; Kim, Yeon-Sook; Jeong, Hye Won; Song, Kyoung-Ho; Park, Wan Beom; Kim, Eu Suk; Oh, Myoung-Don

    2016-12-01

    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that was recently identified in China, South Korea and Japan. The objective of the study was to evaluate the epidemiologic and clinical characteristics of SFTS in South Korea. SFTS is a reportable disease in South Korea. We included all SFTS cases reported to the Korea Centers for Disease Control and Prevention (KCDC) from January 2013 to December 2015. Clinical information was gathered by reviewing medical records, and epidemiologic characteristics were analyzed using both KCDC surveillance data and patient medical records. Risk factors for mortality in patients with SFTS were assessed. A total of 172 SFTS cases were reported during the study period. SFTS occurred throughout the country, except in urban areas. Hilly areas in the eastern and southeastern regions and Jeju island (incidence, 1.26 cases /105 person-years) were the main endemic areas. The yearly incidence increased from 36 cases in 2013 to 81 cases in 2015. Most cases occurred from May to October. The overall case fatality ratio was 32.6%. The clinical progression was similar to the 3 phases reported in China: fever, multi-organ dysfunction, and convalescence. Confusion, elevated C-reactive protein, and prolonged activated partial thromboplastin times were associated with mortality in patients with SFTS. Two outbreaks of nosocomial SFTS transmission were observed. SFTS is an endemic disease in South Korea, with a nationwide distribution and a high case-fatality ratio. Confusion, elevated levels of C-reactive protein, and prolonged activated partial thromboplastin times were associated with mortality in patients with SFTS.

  15. Effect of premedication and other factors on the occurrence of acute transfusion reactions in dogs.

    Science.gov (United States)

    Bruce, Joshua A; Kriese-Anderson, Lisa; Bruce, Ashley M; Pittman, Jennifer R

    2015-01-01

    To evaluate the effect of premedication on transfusion reactions (TRs) within 24 hours after blood product transfusions in dogs. Retrospective study between 2008 and 2011. Private veterinary referral hospital. Nine hundred and thirty-five transfusion events in 558 dogs. None. Medical records of dogs receiving blood product transfusions were reviewed. Information collected included signalment, weight, transfusion product type, reason for transfusion, first or subsequent transfusion, whether an acute reaction occurred, type of reaction, whether the reaction was treated, premedication prior to the transfusion and the premedication used, other medications the animal was given, whether the animal had an immune-mediated process, and whether the transfusion was administered in the perioperative period. A total of 144 (15%) acute TRs were documented in 136 dogs. The most common TRs were fever alone (77/144 [53%]) and vomiting alone (26/144 [18%]). Six dogs died due to the TR (4%). TR was not associated with age (P = 0.257), sex (P = 0.754), weight (P = 0.829), or premedication (P = 0.312). The type of blood product transfused (P reactions were documented following transfusions given in the perioperative period (P = 0.023). While most TRs were mild, there were some serious reactions observed including hemolysis, dyspnea, and 6 deaths. Immune-mediated disease was associated with development of a TR, while transfusion during the perioperative period was associated with lower likelihood of reaction. Packed RBC transfusions were associated with development of acute TRs. Overall occurrence of TR was not significantly altered with premedication; however, when evaluated alone, antihistamines decreased the incidence of acute allergic reactions. © Veterinary Emergency and Critical Care Society 2015.

  16. Quadro seroproteico como auxílio diagnóstico na anemia hemolítica imunomediada em cães Serum proteic profile as diagnosis aids in immune-mediated hemolytic anemia in dogs

    Directory of Open Access Journals (Sweden)

    Patrícia Mendes Pereira

    2010-04-01

    maior nestes. Tais achados analisados em conjunto agregam informações adicionais úteis à elucidação das AHIMs em cães.This assay aimed to determine the serum protein - via polyacrylamide gel electrophoresis, which contained duodecil sodium sulfate (SDS-PAGE - in 120 dogs, with different breeds and ages, seen by the Veterinary Hospital "Governor Laudo Natel." These animals were grouped into five experimental groups: Group 1 - group control with 20 dogs, group 2 - 28 dogs with regenerative anemia; group 3 - 27 dogs with arregenarative; anemia group 4 - 10 dogs with primary immune-mediated hemolytic anemia (AHIM 1.rd; group 5 - 35 dogs with secondary immune-mediated hemolytic anemia (AHIM 2.rd. The technique allowed the SDS-PAGE fractionation of 24 protein, whose molecular weights (PM ranged from 18,000 to 165,000 daltons (Da. The dogs with 1st and 2nd AHIM showed 24 protein fractions in their tracks electrophoretic, while other groups of dogs showed 23 fractions of protein, whose molecular protein weight of 68,000Da was not found. Thus, twenty-three proteins were common to proteinograms of the five experimental groups. From these, it was possible to identify eleven protein fractions nominally, and others were identified by their molecular weights. For control dogs, the anemic (groups 2, 3, 4 and 5 showed higher concentrations of serum transferrin and between them, the animals carrying the primary IMHA. All groups of dogs showed anemic levels of serum haptoglobin and phosphorylase significantly higher than the control dogs, while the serum ceruloplasmin was lower in anemic dogs. These findings provide additional information to the elucidation of the AHIMs in dogs.

  17. Association of beta2-glycoprotein I IgG and IgM antibodies with thrombosis and thrombocytopenia

    DEFF Research Database (Denmark)

    Voss, Anne-Sofie Boertmann; Jacobsen, Søren; Heegaard, Niels Henrik Helweg

    2001-01-01

    Antiphospholipid antibodies (APA) have been known for decades. Their relation to clinical manifestations, primarily thromboses and thrombocytopenia, was recognised in the 1980s. In this clinical study two cohorts of patients, a population-based (84 patients with systemic lupus erythematosus (SLE......)) and a hospital-based (87 patients with SLE and 53 with other connective tissue diseases) were investigated for APA and associated clinical manifestations. Anticardiolipin antibodies (ACA) of IgG and IgM classes were found in 13 and 38% of the population-based patients and in 29 and 58% of the hospital...

  18. Task Force on Catastrophic Antiphospholipid Syndrome (APS) and Non-criteria APS Manifestations (II): thrombocytopenia and skin manifestations.

    Science.gov (United States)

    Cervera, R; Tektonidou, M G; Espinosa, G; Cabral, A R; González, E B; Erkan, D; Vadya, S; Adrogué, H E; Solomon, M; Zandman-Goddard, G; Shoenfeld, Y

    2011-02-01

    The objectives of the 'Task Force on Catastrophic Antiphospholipid Syndrome (APS) and Non-criteria APS Manifestations' were to assess the clinical utility of the international consensus statement on classification criteria and treatment guidelines for the catastrophic APS, to identify and grade the studies that analyze the relationship between the antiphospholipid antibodies and the non-criteria APS manifestations, and to present the current evidence regarding the accuracy of these non-criteria APS manifestations for the detection of patients with APS. This article summarizes the studies analyzed on thrombocytopenia and skin manifestations, and presents the recommendations elaborated by the Task Force after this analysis.

  19. Acute Bronchitis

    Science.gov (United States)

    ... Table of Contents1. Overview2. Symptoms3. Diagnosis4. Prevention5. Treatment6. Everyday Life7. Questions8. Resources What is acute bronchitis? Acute ... heartburn, you can get acute bronchitis when stomach acid gets into the bronchial tree. How is acute ...

  20. Acute thrombosis in superior mesenteric artery as first symptom in a AML patient

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    Yan Liu

    2008-07-01

    Full Text Available Yan Liu1, Xangshan Chao1, Weiying Gu1, Xiaoying Hua1, Ning Xu21Department of Hematology, The Third Affiliated Hospital, Suzhou University, Changzhou, China; 2Division of Clinical Chemistry and Pharmacology, Department of Laboratory Medicine, Lund University, Lund, SwedenAbstract: It is well known that acute leukemia may accompany thromboembolic events; even severe thrombocytopenia does not prevent thrombosis. Coagulation dysfunction is the major pathophysiological background for thromboembolism in these patients. Most thromboembolism is localized in venous vessels in acute leukemic patients and it happens rarely in the artery. We report a case of acute thrombosis in the superior mesenteric artery as the first symptom in a patient suffering from acute myeloid leukemia (FAB M4.Keywords: acute leukemia, thromboembolism, pathogenesis

  1. Correlation Between HLA-A, B and DRB1 Alleles and Severe Fever with Thrombocytopenia Syndrome.

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    Shu-Jun Ding

    2016-10-01

    Full Text Available Severe fever with thrombocytopenia syndrome (SFTS is an emerging hemorrhagic fever caused by a tick-borne bunyavirus (SFTSV in East Asian countries. The role of human leukocyte antigen (HLA in resistance and susceptibility to SFTSV is not known. We investigated the correlation of HLA locus A, B and DRB1 alleles with the occurrence of SFTS.A total of 84 confirmed SFTS patients (patient group and 501 unrelated non-SFTS patients (healthy individuals as control group from Shandong Province were genotyped by PCR-sequence specific oligonucleotide probe (PCR-SSOP for HLA-A, B and DRB1 loci.Allele frequency was calculated and compared using χ2 test or the Fisher's exact test. A corrected P value was calculated with a bonferronis correction. Odds Ratio (OR and 95% confidence intervals (CI were calculated by Woolf's method.A total of 11 HLA-A, 23 HLA-B and 12 HLA-DRB1 alleles were identified in the patient group, whereas 15 HLA-A, 30 HLA-B and 13 HLA-DRB1 alleles were detected in the control group. The frequencies of A*30 and B*13 in the SFTS patient group were lower than that in the control group (P = 0.0341 and 0.0085, Pc = 0.5115 and 0.252. The ORs of A*30 and B*13 in the SFTS patient group were 0.54 and 0.49, respectively. The frequency of two-locus haplotype A*30-B*13 was lower in the patient group than in the control group(5.59% versus 12.27%, P = 0.037,OR = 0.41, 95%CI = 0.18-0.96 without significance(Pc>0.05. A*30-B*13-DRB1*07 and A*02-B*15-DRB1*04 had strong associations with SFTS resistance and susceptibility respectively (Pc = 0.0412 and 0.0001,OR = 0.43 and 5.07.The host HLA class I polymorphism might play an important role with the occurrence of SFTS. Negative associations were observed with HLA-A*30, HLA-B*13 and Haplotype A*30-B*13, although the associations were not statistically significant. A*30-B*13-DRB1*07 had negative correlation with the occurrence of SFTS; in contrast, haplotype A*02-B*15-DRB1*04 was positively correlated with SFTS.

  2. [Thrombosis during thrombopoietin receptor agonist treatment for immune thrombocytopenia. A French multicentric observational study].

    Science.gov (United States)

    Weber, E; Moulis, G; Mahévas, M; Guy, C; Lioger, B; Durieu, I; Hunault, M; Ramanantsoa, M; Royer, B; Default, A; Pérault-Pochat, M-C; Moachon, L; Bernard, N; Bardy, G; Jonville-Bera, A-P; Geniaux, H; Godeau, B; Cathébras, P

    2017-03-01

    Thrombopoietin-receptor agonists (TPO-RA) are marketed for immune thrombocytopenia (ITP). They have been associated to thrombosis occurrence in randomized controlled trials. However, the characteristics of these thromboses in the real-life practice as well as their management are poorly known. The objectives of this study were to determine the risk factors, circumstances and management of thrombosis occurring during exposure to TPO-RA in ITP. We carried out a multicentre retrospective study in France. Moreover, all cases reported to the French pharmacovigilance system were also analyzed. Overall, 41 thrombosis (13 arterial) in 36 ITP patients (14 males and 22 females, mean age: 59 years) were recorded between January 2009 and October 2015. Twenty patients were treated with romiplostim, 15 with eltrombopag and 1 was treated by both medications. Thirty-three (92%) of the patients had another risk factor for thrombosis. Ten (28%) had an history of thrombosis and 13 (36%) received immunoglobulin in the month preceding the thrombotic event. Three had antiphospholipid antibodies; congenital low-risk thrombophilia was found in 4 cases; 18 patients (50%) were splenectomized. Median platelet count at the time of thrombosis was 172G/l (1-1049G/l). In 22 patients (56%), a good prognosis was associated with the thrombosis and was not linked with TPO-RA withdrawal. Bleeding events occurred in 14% of the patients treated with antiplatelet or anticoagulant drug, including 5% serious events (1 death of intracranial haemorrhage, 1 death of haemorrhagic shock). The thrombotic risk may be carefully assessed before starting TPO-RA in ITP patients. The impact of antiphospholipid antibodies and of congenital thrombophilia remains to be defined. Thrombosis evolution seems independent of TPO-RA management. Bleeding manifestations seem rare. Poor prognosis was mainly due to ischemic sequelae. Copyright © 2016 Société Nationale Française de Médecine Interne (SNFMI

  3. Health-related quality of life in children with chronic immune thrombocytopenia in China.

    Science.gov (United States)

    Zhang, Heng; Wang, Li; Quan, Meijie; Huang, Jie; Wu, Peng; Lu, Qin; Fang, Yongjun

    2016-03-15

    The concept of health-related quality of life (HRQoL) was brought up decades ago and has been well utilized in many different areas. Regarding immune thrombocytopenia (ITP) management, much work has been done to emphasize the necessity of taking HRQoL into consideration. However, data on HRQoL of children with chronic ITP remain rare. This is a cross-sectional study. Children with chronic ITP aged from 2 to 18 and their parents were recruited. Participants completed the Pediatric Quality of Life Inventory™ (PedsQL™) and Kids' ITP Tools (KIT) questionnaires at only one time. The Pearson's correlation was examined between these measures for the pooled samples. A total of 42 families participated. Mean child self-report scores of KIT and PedsQL™ were 78.60 (SD = 12.40) and 85.13 (SD = 14.12), respectively, corresponding to parent proxy report scores, which were 73.40 (SD = 19.96) and 85.10 (SD = 13.56), respectively. Mean score of KIT parent impact report was only 40.39 (SD = 19.96). Significantly higher KIT scores (self-report and parent proxy) were observed in children with PLT more than 30 × 10*9/L compared to others, and this difference was even more noticeable in the PedsQL™ parent proxy report group (p corticosteroids had no impact on the KIT and PedsQL™ scores here. Internal consistency reliability was demonstrated with Cronbach's alpha for all scales above the acceptable level of 0.89 (range from 0.88 to 0.97). There was a substantial concordance (p < 0.001) between the child and parent proxy scores (ICC for KIT is 0.59, ICC for PedsQL™ is 0.85). Meanwhile, KIT scores are correlated with PedsQL™ (r = 0.75 for child self report, r = 0.61 for parent proxy report). ITP affects HRQoL of children and parents. Parents are much more concerned with the disease than their children, which seriously influence their HRQoL as a result. The cross-culture translated KIT is reliable and valid with acceptable correlation to the PedsQL™. KIT provides valuable

  4. Treatment of patients with refractory immune thrombocytopenia: literature review and case report

    Directory of Open Access Journals (Sweden)

    V. V. Ptushkin

    2014-07-01

    with severe bleeding. Patient received 1 mg/kg of romiplostim and a week later platelet count was 250  10 9/l. Successfully tumor resection was done. No romiplostim side effects or thrombotic complications during postoperative period were found. The obtained data together with similar case reports of successful surgery after TPO-agonists administration allow considering romiplostim as an effective method of thrombocytopenia therapy before surgery in ITP patients.

  5. Trends in the prevalence of thrombocytopenia among individuals iInfected with hepatitis C Virus in the United States, 1999-2008

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    Kauf Teresa L

    2012-03-01

    Full Text Available Abstract Background Thrombocytopenia is associated with the natural history of hepatitis C virus (HCV infection and anti-viral therapy. Recent, national estimates of the clinical burden of thrombocytopenia among HCV-infected individuals in the United States are unavailable. Bi-yearly data from the 1999-2000 to 2007-2008 National Health and Nutrition Examination Surveys (NHANES were used to examine the prevalence of thrombocytopenia among HCV-infected individuals in the United States. Results Among 467 HCV-infected individuals in the survey (weighted population = 3,597,039, mean weighted age was 46.7 years (standard deviation = 15.5 and 61.7% were male. Overall, 7.6% met the study definition of TCP at the 150 × 109/L threshold; 4.5%, 2.0%, and 0.8% had platelet counts below 125, 100, and 75 × 109/L, respectively. The 2-year weighted prevalences of thrombocytopenia (150 × 109/L threshold from 1999-2008 were 4.9%, 8.6%, 6.5%, 4.1%, and 12.9%. The unadjusted biannual time trend (odds ratio was 1.16 (95% confidence interval = 0.82-1.64. In the two adjusted models, the odds by time ranged from 1.24-1.40, depending on whether the model included demographic or laboratory variables or both, but did not reach statistical significance. Age was positively and significantly related to thrombocytopenia status. Conclusions As the HCV-infected population ages, the prevalence of thrombocytopenia is expected to rise. This study provides limited evidence of such an effect at the national level.

  6. Hymenoptera Stings and the Acute Kidney Injury

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    Yashad Dongol

    2013-07-01

    Full Text Available Hymenoptera stings are a health concern. Apidae (bees, Vespidae (hornets, yellow jackets and wasps and Formicidae (ants are medically-important stinging insects under the order Hymenoptera. Clinical features from simple skin manifestations to severe and fatal organ injury are due to the hypersensitivity reactions and/ or the toxic effects of the venom inoculated. Here we discuss on Hymenoptera stings involving apids (honey bees and vespids (wasps, hornets and yellow jackets and their effect on renal function and associated morphological changes in the kidney. Despite the differences in venom composition and quantity released per sting in two insect groups, both lead to similar medical consequences, such as localised normal allergic reactions, mild to severe anaphylaxis and shock and multiple organ and tissue injury leading to multiple organ failure. Acute kidney injury (AKI is one of the unusual complications of Hymenoptera stings and has the basis of both immune-mediated and toxic effects. Evidence has proven that supportive therapy along with the standard medication is very efficient in completely restoring the kidney function without any recurrence.

  7. Thrombosis and antiphospholipid antibody syndrome during acute Q fever

    Science.gov (United States)

    Million, Matthieu; Bardin, Nathalie; Bessis, Simon; Nouiakh, Nadia; Douliery, Charlaine; Edouard, Sophie; Angelakis, Emmanouil; Bosseray, Annick; Epaulard, Olivier; Branger, Stéphanie; Chaudier, Bernard; Blanc-Laserre, Karine; Ferreira-Maldent, Nicole; Demonchy, Elisa; Roblot, France; Reynes, Jacques; Djossou, Felix; Protopopescu, Camelia; Carrieri, Patrizia; Camoin-Jau, Laurence; Mege, Jean-Louis; Raoult, Didier

    2017-01-01

    Abstract Q fever is a neglected and potentially fatal disease. During acute Q fever, antiphospholipid antibodies are very prevalent and have been associated with fever, thrombocytopenia, acquired heart valve disease, and progression to chronic endocarditis. However, thrombosis, the main clinical criterion of the 2006 updated classification of the antiphospholipid syndrome, has not been assessed in this context. To test whether thrombosis is associated with antiphospholipid antibodies and whether the criteria for antiphospholipid syndrome can be met in patients with acute Q fever, we conducted a cross-sectional study at the French National Referral Center for Q fever. Patients included were diagnosed with acute Q fever in our Center between January 2007 and December 2015. Each patient's history and clinical characteristics were recorded with a standardized questionnaire. Predictive factors associated with thrombosis were assessed using a rare events logistic regression model. IgG anticardiolipin antibodies (IgG aCL) assessed by an enzyme-linked immunosorbent assay were tested on the Q fever diagnostic serum. A dose-dependent relationship between IgG aCL levels and thrombosis was tested using a receiver operating characteristic (ROC) analysis. Of the 664 patients identified for inclusion in the study, 313 (47.1%) had positive IgG aCL and 13 (1.9%) were diagnosed with thrombosis. Three patients fulfilled the antiphospholipid syndrome criteria. After multiple adjustments, only positive IgG aCL (relative risk, 14.46 [1.85–113.14], P = .011) were independently associated with thrombosis. ROC analysis identified a dose-dependent relationship between IgG aCL levels and occurrence of thrombosis (area under curve, 0.83, 95%CI [0.73–0.93], P antiphospholipid antibodies are associated with thrombosis, thrombocytopenia, and acquired valvular heart disease. Antiphospholipid antibodies should be systematically assessed in acute Q fever patients. Hydroxychloroquine

  8. Flow cytometric assessment of activation of peripheral blood platelets in dogs with normal platelet count and asymptomatic thrombocytopenia.

    Science.gov (United States)

    Żmigrodzka, M; Guzera, M; Winnicka, A

    2016-01-01

    Platelets play a crucial role in hemostasis. Their activation has not yet been evaluated in healthy dogs with a normal and low platelet count. The aim of this study was to determine the influence of activators on platelet activation in dogs with a normal platelet count and asymptomatic thrombocytopenia. 72 clinically healthy dogs were enrolled. Patients were allocated into three groups. Group 1 consisted of 30 dogs with a normal platelet count, group 2 included 22 dogs with a platelet count between 100 and 200×109/l and group 3 consisted of 20 dogs with a platelet count lower than 100×109/l. Platelet rich-plasma (PRP) was obtained from peripheral blood samples using tripotassium ethylenediaminetetraacetic acid (K3-EDTA) as anticoagulant. Next, platelets were stimulated using phorbol-12-myristate-13-acetate or thrombin, stabilized using procaine or left unstimulated. The expression of CD51 and CD41/CD61 was evaluated. Co-expression of CD41/CD61 and Annexin V served as a marker of platelet activation. The expression of CD41/CD61 and CD51 did not differ between the 3 groups. Thrombin-stimulated platelets had a significantly higher activity in dogs with a normal platelet count than in dogs with asymptomatic thrombocytopenia. Procaine inhibited platelet activity in all groups. In conclusion, activation of platelets of healthy dogs in vitro varied depending on the platelet count and platelet activator.

  9. Spatial Analysis of Severe Fever with Thrombocytopenia Syndrome Virus in China Using a Geographically Weighted Logistic Regression Model

    Directory of Open Access Journals (Sweden)

    Liang Wu

    2016-11-01

    Full Text Available Severe fever with thrombocytopenia syndrome (SFTS is caused by severe fever with thrombocytopenia syndrome virus (SFTSV, which has had a serious impact on public health in parts of Asia. There is no specific antiviral drug or vaccine for SFTSV and, therefore, it is important to determine the factors that influence the occurrence of SFTSV infections. This study aimed to explore the spatial associations between SFTSV infections and several potential determinants, and to predict the high-risk areas in mainland China. The analysis was carried out at the level of provinces in mainland China. The potential explanatory variables that were investigated consisted of meteorological factors (average temperature, average monthly precipitation and average relative humidity, the average proportion of rural population and the average proportion of primary industries over three years (2010–2012. We constructed a geographically weighted logistic regression (GWLR model in order to explore the associations between the selected variables and confirmed cases of SFTSV. The study showed that: (1 meteorological factors have a strong influence on the SFTSV cover; (2 a GWLR model is suitable for exploring SFTSV cover in mainland China; (3 our findings can be used for predicting high-risk areas and highlighting when meteorological factors pose a risk in order to aid in the implementation of public health strategies.

  10. Clinical and laboratory characteristics in congenital ANKRD26 mutation-associated thrombocytopenia: A detailed phenotypic study of a family.

    Science.gov (United States)

    Perez Botero, Juliana; Chen, Dong; He, Rong; Viswanatha, David S; Majerus, Julie A; Coon, Lea M; Nguyen, Phuong L; Reichard, Karen K; Oliveira, Jennifer L; Tefferi, Ayalew; Gangat, Naseema; Pruthi, Rajiv K; Patnaik, Mrinal M

    2016-11-01

    The clinical and laboratory characteristics of patients with non-syndromic, autosomal dominant thrombocytopenia secondary to germ line ANKRD26 mutations appear to be heterogeneous. Except for a targeted molecular genotyping approach, there is no distinct clinical or laboratory phenotype that has been specifically associated with this particular gene mutation. Such heterogeneity could be due to variations in mutation and genetic background in different families. To understand the phenotypic heterogeneity, we thoroughly studied one affected family using the International Society for Thrombosis and Haemostasis bleeding assessment tool and both clinically validated standard and esoteric platelet testing (electron microscopy (EM) and flow cytometry). We found that decreased platelet aggregation with arachidonic acid and epinephrine agonists was common in affected family members. EM studies demonstrated persistent borderline low mean dense granules per platelet, decreased alpha granules and an increased canalicular network pattern in all affected members. Since these characteristics are subtle or non-pathognomonic, molecular testing for ANKRD26 mutation remains the most reliable test to render a diagnosis and should be considered when evaluating a patient or family with congenital thrombocytopenia, particularly if there is a history of myeloid neoplasms.

  11. Partial response to sorafenib treatment associated with transient grade 3 thrombocytopenia in a patient with locally advanced thyroid cancer

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    Pitoia Fabian; Abelleira, Erika; Jerkovich, Fernando; Urciuoli, Carolina; Cross, Graciela, E-mail: fpitoia@intramed.net [Division de Endocrinologia, Hospital de Clinicas, Universidad de Buenos Aires Buenos Aires (Argentina)

    2015-08-15

    Advanced radioactive refractory and progressive or symptomatic differentiated thyroid carcinoma (DTC) is a rare condition. Sorafenib was recently approved for the treatment of these patients. We present the case of a 67 year old woman diagnosed with DTC who underwent a total thyroidectomy with central, lateral-compartment neck dissection and shaving of the trachea and esophagus due to tumor infiltration. A local recurrence was detected 14 months later requiring, additionally, two tracheal rings resection. The patient received a cumulative {sup 131}I dose of 650 mCi and developed dysphagia and dyspnea 63 months after initial surgery. A {sup 18}FGD-PET/CT showed progression of the local mass associated to hypermetabolic pulmonary nodules. Sorafenib 800 mg/day was then prescribed. A dose reduction to 400 mg/day was necessary due to grade 3 thrombocytopenia that appeared four months after drug prescription. Platelet count went to normal after this dose reduction. Five months after initiation of sorafenib, a partial response of the local mass with significant intra-tumoral necrosis was observed. We conclude that sorafenib is a valid option for locally advanced DTC and that the platelet count should be evaluated regularly because it seems that thrombocytopenia might be more frequently observed in DTC than in other types of tumors. (author)

  12. Frequency of human platelet antigens in oncohematological patients with thrombocytopenia and the probability of incompatibility to platelet transfusions.

    Science.gov (United States)

    Bianchi, Juliana Vieira Dos Santos; de Azevedo, Maria Regina Andrade; Jens, Eduardo; Nukui, Youko; Chamone, Dalton Alencar Ficher

    2012-01-01

    The objective of this study was to evaluate the frequencies of human platelet antigens in oncohematological patients with thrombocytopenia and to analyze the probability of their incompatibility with platelet transfusions. Platelet antigen genotyping was performed by sequence-specific primer polymerase chain reaction (SSP-PCR) for the HPA-1a, HPA-1b, HPA-2a, HPA-2b, HPA-3a, HPA-3b, HPA-4a, HPA-4b, HPA-5a, HPA-5b; HPA-15a, HPA-15b alleles in 150 patients of the Hematology Service of the Hospital das Clínicas (FMUSP). THE ALLELE FREQUENCIES FOUND WERE: HPA-1a: 0.837; HPA-1b: 0.163; HPA-2a: 0.830; HPA-2b: 0.170; HPA-3a: 0.700; HPA-3b: 0.300; HPA-4a: 1; HPA-4b: 0; HPA-5a: 0.887; HPA-5b: 0.113; HPA-15a: 0.457 and HPA-15b: 0.543. Data from the present study showed that the A allele is more common in the population than the B allele, except for HPA-15. This suggests that patients homozygous for the B allele are more predisposed to present alloimmunization and refractoriness to platelet transfusions by immune causes. Platelet genotyping could be of great value in the diagnosis of alloimmune thrombocytopenia and to provide compatible platelet concentrates for these patients.

  13. Determination of human platelet antigen typing by molecular methods: Importance in diagnosis and early treatment of neonatal alloimmune thrombocytopenia.

    Science.gov (United States)

    Arinsburg, Suzanne A; Shaz, Beth H; Westhoff, Connie; Cushing, Melissa M

    2012-05-01

    Neonatal alloimmune thrombocytopenia (NAIT) is the most common cause of severe thrombocytopenia and intracranial hemorrhage in the perinatal period. While the gold standard for making a diagnosis of NAIT is detection of a human platelet antigen (HPA)-specific antibody in maternal serum, together with identifying an incompatibility between the parents for the cognate HPA antigen, platelet genotyping is the gold standard method for HPA typing. Platelet genotyping is critical in screening at-risk fetuses for the presence ofthe HPA corresponding to the maternal antibody. In addition, platelet genotyping may play a role in population screening to identify women at risk for sensitization, and thus, fetuses at risk for NAIT. The most commonly used methods of platelet genotyping are sequence-specific primer-polymerase chain reaction (PCR-SSP), restriction fragment length polymorphism-PCR (PCR-RFLP), and TaqMan real-time PCR. PCR-SSP and PCR-RFLP are relatively inexpensive and technically simple methods, but they are not easily automated and require expertise for reliable interpretation of results. Newer methods that allow for multiplexing, automation, and easily interpretable results, such as bead arrays, are currently in development and available for research purposes. Copyright © 2012 Wiley Periodicals, Inc.

  14. Pentadecapeptide BPC 157 Reduces Bleeding and Thrombocytopenia after Amputation in Rats Treated with Heparin, Warfarin, L-NAME and L-Arginine

    Science.gov (United States)

    Stupnisek, Mirjana; Kokot, Antonio; Drmic, Domagoj; Hrelec Patrlj, Masa; Zenko Sever, Anita; Kolenc, Danijela; Radic, Bozo; Suran, Jelena; Bojic, Davor; Vcev, Aleksandar; Seiwerth, Sven; Sikiric, Predrag

    2015-01-01

    Background BPC 157 is a stable gastric pentadecapeptide recently implicated with a role in hemostasis. While NO is largely implicated in hemostatic mechanisms, in tail-amputation-models under heparin- and warfarin-administration, both the NO-synthase (NOS)-blocker, L-NAME (prothrombotic) and the NOS-substrate L-arginine (antithrombotic), were little investigated. Objective. To investigate the effect of L-NAME and L-arginine on hemostatic parameters, and to reveal the effects of BPC 157 on the L-NAME- and L-arginine-induced hemostatic actions under different pathological condition: tail amputation without or with anticoagulants, heparin or warfarin. Methods Tail amputation, and/or i.v.-heparin (10 mg/kg), i.g.-warfarin (1.5 mg/kg/day for 3 days) were used in rats. Treatment includes BPC 157, L-NAME, L-arginine, per se and their combination. Results After (tail) amputation, with or without i.v.-heparin or i.g.-warfarin, BPC 157 (10 μg/kg, 10 ng/kg, i.p., i.v. (heparin), 10 μg/kg i.g. (warfarin)) always reduced bleeding time and/or haemorrhage and counteracted thrombocytopenia. As for L-NAME and/or L-arginine, we noted: L-arginine (100 mg/kg i.p.)–rats: more bleeding, less/no thrombocytopenia; L-NAME (5 mg/kg i.p.)-rats: less bleeding (amputation only), but present thrombocytopenia; L-NAME+L-arginine-rats also exhibited thrombocytopenia: L-NAME counteracted L-arginine-increased bleeding, L-arginine did not counteract L-NAME-thrombocytopenia. All animals receiving BPC 157 in addition (BPC 157μg+L-NAME; BPC 157μg+L-arginine, BPC 157μg+L-NAME+L-arginine), exhibited decreased haemorrhage and markedly counteracted thrombocytopenia. Conclusions L-NAME (thrombocytopenia), L-arginine (increased haemorrhage) counteraction and BPC 157 (decreased haemorrhage, counteracted thrombocytopenia) with rescue against two different anticoagulants, implicate a BPC 157 modulatory and balancing role with rescued NO-hemostatic mechanisms. PMID:25897838

  15. [Immunization against a new, infrequent alloantigen (Iy) on the platelet glycoprotein Ib/IX as a cause of a serious case of neonatal alloimmune thrombocytopenia].

    Science.gov (United States)

    Kiefel, V; Vicariot, M; Breitfeld, C; Giptner, A; Schlüter, C; Böhringer, M; Santoso, S; Kroll, H; Mueller-Eckhardt, C

    1994-01-01

    Neonatal alloimmune thrombocytopenia is the consequence of maternal alloimmunization against platelet-specific alloantigens, usually PIA1 or Br(a). The clinical picture is characterized by signs of haemorrhagic diathesis as a result of marked thrombocytopenia. In the last years, rare cases of immunization against 'low-frequency' or 'private' platelet alloantigens on the platelet glycoprotein (GP) complex IIb/IIIa have been found. This is the first report on NAIT due to maternal immunization against a low-frequency platelet alloantigen ('Iy') localized on platelet GP Ib/IX.

  16. Safety of live vaccinations on immunosuppressive therapy in patients with immune-mediated inflammatory diseases, solid organ transplantation or after bone-marrow transplantation - A systematic review of randomized trials, observational studies and case reports.

    Science.gov (United States)

    Croce, Evelina; Hatz, Christoph; Jonker, Emile F; Visser, L G; Jaeger, Veronika K; Bühler, Silja

    2017-03-01

    Live vaccines are generally contraindicated on immunosuppressive therapy due to safety concerns. However, data are limited to corroborate this practice. To estimate the safety of live vaccinations in patients with immune-mediated inflammatory diseases (IMID) or solid organ transplantation (SOT) on immunosuppressive treatment and in patients after bone-marrow transplantation (BMT). A search was conducted in electronic databases (Cochrane, Pubmed, Embase) and additional literature was identified by targeted searches. Randomized trials, observational studies and case reports. Patients with IMID or SOT on immunosuppressive treatment and BMT patients vaccinations: mumps, measles, rubella (MMR), yellow fever (YF), varicella vaccine (VV), herpes zoster (HZ), oral typhoid, oral polio, rotavirus, Bacillus Calmette-Guérin (BCG), smallpox. One author performed the data extraction using predefined data fields. It was cross-checked by two other authors. 7305 articles were identified and 64 articles were included: 40 on IMID, 16 on SOT and 8 on BMT patients. In most studies, the administration of live vaccines was safe. However, some serious vaccine-related adverse events occurred. 32 participants developed an infection with the vaccine strain; in most cases the infection was mild. However, in two patients fatal infections were reported: a patient with RA/SLE overlap who started MTX/dexamethasone treatment four days after the YFV developed a yellow fever vaccine-associated viscerotropic disease (YEL-AVD) and died. The particular vaccine lot was found to be associated with a more than 20 times risk of YEL-AVD. One infant whose mother was under infliximab treatment during pregnancy received the BCG vaccine at the age of three months and developed disseminated BCG infection and died. An immunogenicity assessment was performed in 43 studies. In most cases the patients developed satisfactory seroprotection rates. In the IMID group, YFV and VV demonstrated high seroconversion rates

  17. Acute Renal Failure in Dengue Infection.

    Science.gov (United States)

    Vakrani, Girish Pamappa; Subramanyam, Nambakam Tanuja

    2017-01-01

    Acute Renal Failure (RF) is a rare but well recognized complication of Dengue Infection (DI). There has been paucity of published data regarding renal involvement in DI. The aim of the present study was to elucidate different clinical presentations, disease outcomes of DI. To study the frequency, severity and predictors of RF in DI. Patients diagnosed either as Dengue Fever (DF) or Dengue Haemorrhagic Fever/Dengue Shock Syndrome (DHF/DSS) respectively were enrolled for this study. The diagnostic criteria for DI were febrile illness associated with one of the following: 1) detection of dengue-specific IgM capture antibody or Non-Structural Protein1 (NS1) antigen; or 2) a four-fold or greater increase of dengue-specific IgG capture antibody by ELISA and haemoagglutination inhibition assay. Patients were diagnosed as having Acute RF, if serum creatinine was >1.2 mg/dl or who showed improvement by 50% in serum creatinine from the initial value. It is an observational study of medical charts, data of age, gender, and medical history of any underlying diseases in association with the severity of DI of each patient recorded. All of the laboratory results were collected. Parameters that influenced the clinical presentations and outcomes for development of classical DF or DHF/DSS in patients with or without RF were analysed and compared. Descriptive and inferential statistical analysis was carried. The Statistical software namely SAS 9.2, SPSS 15.0, Stata 10.1, Med Calc 9.0.1, Systat 12.0 and R environment ver.2.11.1 were used. Most common symptoms were fever followed by headache and pain in abdomen. Among the patients with RF, all patients had recovery. The patients with DHF/DSS were more susceptible to develop renal failure compared to DF group. There were statistically significant higher frequencies of renal failure, haemoconcentration, thrombocytopenia, low serum cholesterol. Patients in the RF group also had significantly higher percentages of shock, haemoconcentration

  18. Acute Pancreatitis and Pregnancy

    Science.gov (United States)

    ... Information Acute Pancreatitis Acute Pancreatitis and Pregnancy Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is ... of acute pancreatitis in pregnancy. Reasons for Acute Pancreatitis and Pregnancy While acute pancreatitis is responsible for ...

  19. Outcomes after heparin-induced thrombocytopenia in patients with Propaten vascular grafts.

    Science.gov (United States)

    Kasirajan, Karthikeshwar

    2012-08-01

    Heparin-induced thrombocytopenia (HIT) can result in a life- or limb-threatening condition that can be reversed with early detection and prompt discontinuation of systemic heparin. The advent of heparin-bonded grafts may introduce a new level of complexity in some patients with a suspected diagnosis of HIT. This review evaluates the outcomes of patients who received the Gore Propaten vascular graft with a subsequent suspicion of HIT. This is a retrospective analysis of cases with suspected type II HIT after implant of the Propaten vascular graft that were reported to W.L. Gore & Associates. Data reviewed included clinical studies, including physician-sponsored studies, both inside and outside the United States; published literature; and Gore's product surveillance records. Overall, as of June 2011, there have been 27 cases (27 patients and 30 vascular grafts) of suspected HIT after graft implant. Of these 27 patients, 18 were tested for HIT antibodies (enzyme-linked immunosorbent assay, heparin-induced platelet activation test, serotonin release assay, drug-induced platelet activation test, platelet aggregation test, an HIT panel, or an unknown HIT test), with a positive test result in 17 of the 18 cases. In 5 of the 18 cases, patients were tested with two distinct HIT assays, resulting in one positive and one negative test. Among patients with available data, the mean preoperative heparin dose was 4850 ± 1634 U, and four patients had a postoperative heparin drip. The mean preoperative platelet count was 227,000 ± 71,616. Mean platelet count at time of diagnosis of HIT was 53,429 ± 36,832. For the majority of those patients known to have had heparin discontinued once HIT was suspected, Argatroban was the anticoagulant of choice. Sixteen patients had grafts that remained implanted and in circulation, eight patients had grafts that were explanted, two patients had grafts that were ligated in situ, and the outcome was unknown for one patient. Among the 16 patients

  20. Inhibition of Megakaryocyte Differentiation by Antibody-Drug Conjugates (ADCs) is Mediated by Macropinocytosis: Implications for ADC-induced Thrombocytopenia.

    Science.gov (United States)

    Zhao, Hui; Gulesserian, Sara; Ganesan, Sathish Kumar; Ou, Jimmy; Morrison, Karen; Zeng, Zhilan; Robles, Veronica; Snyder, Josh; Do, Lisa; Aviña, Hector; Karki, Sher; Stover, David R; Doñate, Fernando

    2017-09-01

    Thrombocytopenia is a common adverse event in cancer patients treated with antibody-drug conjugates (ADC), including AGS-16C3F, an ADC targeting ENPP3 (ectonucleotide pyrophosphatase/phosphodiesterase-3) and trastuzumab emtansine (T-DM1). This study aims to elucidate the mechanism of action of ADC-induced thrombocytopenia. ENPP3 expression in platelets and megakaryocytes (MK) was investigated and shown to be negative. The direct effect of AGS-16C3F on platelets was evaluated using platelet rich plasma following the expression of platelet activation markers. Effects of AGS-16C3F, T-DM1, and control ADCs on maturing megakaryocytes were evaluated in an in vitro system in which human hematopoietic stem cells (HSC) were differentiated into MKs. AGS-16C3F, like T-DM1, did not affect platelets directly, but inhibited MK differentiation by the activity of Cys-mcMMAF, its active metabolite. FcγRIIA did not appear to play an important role in ADC cytotoxicity to differentiating MKs. AGS-16C3F, cytotoxic to MKs, did not bind to FcγRIIA on MKs. Blocking the interaction of T-DM1 with FcγRIIA did not prevent the inhibition of MK differentiation and IgG1-mcMMAF was not as cytotoxic to MKs despite binding to FcγRIIA. Several lines of evidence suggest that internalization of AGS-16C3F into MKs is mediated by macropinocytosis. Macropinocytosis activity of differentiating HSCs correlated with cell sensitivity to AGS-16C3F. AGS-16C3F was colocalized with a macropinocytosis marker, dextran-Texas Red in differentiating MKs. Ethyl isopropyl amiloride (EIPA), a macropinocytosis inhibitor, blocked internalization of dextran-Texas Red and AGS-16C3F. These data support the notion that inhibition of MK differentiation via macropinocytosis-mediated internalization plays a role in ADC-induced thrombocytopenia. Mol Cancer Ther; 16(9); 1877-86. ©2017 AACR See related article by Zhao et al., p. 1866 . ©2017 American Association for Cancer Research.