WorldWideScience

Sample records for acute immune-mediated thrombocytopenia

  1. Acute immune-mediated thrombocytopenia due to oxaliplatin administration: a case report.

    Science.gov (United States)

    Pietrantonio, Filippo; Di Bartolomeo, Maria; Buzzoni, Roberto; Bajetta, Emilio

    2010-01-01

    Drug-induced acute thrombocytopenia is an extremely rare side effect that may occur immediately after oxaliplatin infusion. This potentially fatal reaction is immune mediated and can be anticipated by mild hemorrhagic signs during previous administrations. This is the first report of acute thrombocytopenia occurring during adjuvant treatment of colorectal cancer with oxaliplatin. Clinicians should be aware of this adverse event in order to prevent possible serious consequences and stop further oxaliplatin administration.

  2. Immune-mediated mechanism for thrombocytopenia after Loxosceles spider bite.

    Science.gov (United States)

    Levin, Carina; Bonstein, Lilach; Lauterbach, Roy; Mader, Rivka; Rozemman, Dganit; Koren, Ariel

    2014-08-01

    Loxoscelism, characterized by high fever, vomiting, malaise, a dermonecrotic lesion, and thrombocytopenia, was diagnosed in a 3-year-old female. Clinical laboratory and dermatological signs are described. Blood test showed a transient hypercoagulable state and the presence of IgG antibodies against platelets, suggesting an immune-mediated mechanism for platelet destruction, in addition to the direct toxic effect of the spider venom. The finding of platelet antibodies after a Loxosceles spider bite has not been previously reported. © 2014 Wiley Periodicals, Inc.

  3. New insights and therapeutics for immune-mediated thrombocytopenia.

    Science.gov (United States)

    Metjian, Ara; Abrams, Charles S

    2008-01-01

    In recent years, great advances have been made in elucidating the pathogenesis of thrombocytopenia and the mechanisms of thrombopoiesis. Drawing upon decades of basic science and clinical research, the pathways behind the immune-mediated destruction of platelets have opened new avenues. This has led to the application of safer and more efficacious immunosuppressive agents, such as the anti-CD20 monoclonal antibody rituximab, or potentially altering the co-stimulatory pathways of the immune system with an anti-CD40L (CD154) monoclonal antibody. This has been coupled with the discoveries of the genetic and molecular pathways in thrombopoiesis, including the identification and cloning of thrombopoietin (TPO) and its receptor. The use of recombinant TPO, such as PEG-rHuMGDF and rhTPO, to treat thrombocytopenia have paved the way for alternative peptidyl and nonpeptidyl thrombopoietic agents that are considered to be nonimmunogenic. Those that have undergone evaluation in humans include the Amgen megakaryopoiesis protein (AMG) 531 compound, eltrombopag, and AKR-501. Additional TPO mimetics show promise in vitro and await future development.

  4. Immune-mediated thrombocytopenia in horses infected with equine infectious anemia virus.

    Science.gov (United States)

    Clabough, D L; Gebhard, D; Flaherty, M T; Whetter, L E; Perry, S T; Coggins, L; Fuller, F J

    1991-11-01

    An adult horse infected with a virulent, cell culture-adapted strain of equine infectious anemia virus (EIAV) developed cyclical thrombocytopenia in which the nadir of platelet counts coincided with peak febrile responses. In order to investigate the mechanism of thrombocytopenia during acute febrile episodes, four adult horses were experimentally infected with the wild-type Wyoming strain of EIAV. Platelet counts decreased from baseline as rectal temperature increased. Serum reverse transcriptase activity increased above background levels in all horses, coincident with increase in rectal temperature. All horses developed an EIAV-specific immune response detectable by Western immunoblot by postinfection day 10. Increases in platelet-associated immunoglobulins G and M were detectable by direct fluorescent-antibody test and flow cytometric assay. Viral replication in bone marrow megakaryocytes was not detectable by in situ hybridization. Results suggest an immune-mediated mechanism of thrombocytopenia in horses infected with EIAV. Despite an inability to identify virion particles in association with platelet-bound antibody, the cyclical nature of the thrombocytopenia and the occurrence of a marked cell-free viremia concomitant with fever and thrombocytopenia suggest immune complex deposition on platelets. We propose that clearance of virus and antibody-coated platelets from the peripheral circulation by hepatic Kupffer cells and splenic macrophages may target infectious virus particles, in the form of immune complexes, to host cells most permissive for in vivo viral replication.

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

    Science.gov (United States)

    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.

  6. Immune-mediated thrombocytopenia associated with angiostrongylus vasorum infection in a jack russell terrier

    Directory of Open Access Journals (Sweden)

    JO'Neill Emma

    2010-07-01

    Full Text Available Abstract A twenty-month-old Jack Russell terrier was presented with a four-day history of thrombocytopenia, echymotic inguinal haemorrhages, coughing and reduced exercise tolerance. Clinical examination revealed several petechial haemorrhages on the gingivae and small echymotic haemorrhages in the inguinal region, along with mild bilateral epistaxis. Haematology confirmed a platelet count of 1.0 × 10/L. Thoracic radiographs revealed a wide-spread mixed alveolar-interstitial lung pattern, apparent throughout the entire lungfield, but particularly marked within the left lung lobes. A presumptive diagnosis of immune-mediated thrombocytopenia was made and the dog was treated with vincristine and immunosuppressive doses of prednisolone. Initially anaemia developed following gastrointestinal haemorrhage; however, after symptomatic treatment the dog showed a marked clinical improvement. Evaluation for an underlying cause of the disease revealed Angiostrongylus vasorum L1 larvae on faecal analysis and treatment with fenbendazole was commenced. The dog made a full clinical recovery with all treatment was withdrawn within five weeks of diagnosis. This is the second report of immune-mediated thrombocytopenia associated with Angiostrongylus vasorum infection and it is the first to be successfully managed. The report highlights that Angiostrongylus vasorum should be considered in young dogs presented with thrombocytopenia.

  7. Immune-mediated thrombocytopenia associated with angiostrongylus vasorum infection in a Jack Russell terrier.

    Science.gov (United States)

    Jo'neill, Emma; Acke, Els; Tobin, Emma; McCarthy, Grainne

    2010-07-01

    A twenty-month-old Jack Russell terrier was presented with a four-day history of thrombocytopenia, echymotic inguinal haemorrhages, coughing and reduced exercise tolerance. Clinical examination revealed several petechial haemorrhages on the gingivae and small echymotic haemorrhages in the inguinal region, along with mild bilateral epistaxis. Haematology confirmed a platelet count of 1.0 × 10/L. Thoracic radiographs revealed a wide-spread mixed alveolar-interstitial lung pattern, apparent throughout the entire lungfield, but particularly marked within the left lung lobes. A presumptive diagnosis of immune-mediated thrombocytopenia was made and the dog was treated with vincristine and immunosuppressive doses of prednisolone. Initially anaemia developed following gastrointestinal haemorrhage; however, after symptomatic treatment the dog showed a marked clinical improvement. Evaluation for an underlying cause of the disease revealed Angiostrongylus vasorum L1 larvae on faecal analysis and treatment with fenbendazole was commenced. The dog made a full clinical recovery with all treatment was withdrawn within five weeks of diagnosis. This is the second report of immune-mediated thrombocytopenia associated with Angiostrongylus vasorum infection and it is the first to be successfully managed. The report highlights that Angiostrongylus vasorum should be considered in young dogs presented with thrombocytopenia.

  8. Immune-mediated thrombocytopenia in horses infected with equine infectious anemia virus.

    OpenAIRE

    Clabough, D L; Gebhard, D; Flaherty, M T; Whetter, L E; Perry, S T; Coggins, L; Fuller, F J

    1991-01-01

    An adult horse infected with a virulent, cell culture-adapted strain of equine infectious anemia virus (EIAV) developed cyclical thrombocytopenia in which the nadir of platelet counts coincided with peak febrile responses. In order to investigate the mechanism of thrombocytopenia during acute febrile episodes, four adult horses were experimentally infected with the wild-type Wyoming strain of EIAV. Platelet counts decreased from baseline as rectal temperature increased. Serum reverse transcri...

  9. Immune-mediated thrombocytopenia associated with angiostrongylus vasorum infection in a Jack Russell terrier

    OpenAIRE

    JO'Neill Emma; Acke Els; Tobin Emma; McCarthy Grainne

    2010-01-01

    Abstract A twenty-month-old Jack Russell terrier was presented with a four-day history of thrombocytopenia, echymotic inguinal haemorrhages, coughing and reduced exercise tolerance. Clinical examination revealed several petechial haemorrhages on the gingivae and small echymotic haemorrhages in the inguinal region, along with mild bilateral epistaxis. Haematology confirmed a platelet count of 1.0 × 10/L. Thoracic radiographs revealed a wide-spread mixed alveolar-interstitial lung pattern, appa...

  10. Acute renal failure and severe thrombocytopenia associated with metamizole

    Directory of Open Access Journals (Sweden)

    Maria Dolores Redondo-Pachon

    2014-01-01

    Full Text Available Metamizole or dipyrone is a pyrazolone derivative that belongs to the non-steroidal anti-inflammatory drugs. Its main side-effect is hematological toxicity. Thrombocytopenia due to metamizole is rare and is usually associated with the involvement of the two other blood series. Drug-induced thrombocytopenia is more frequently related to immune mechanisms, and the diag-nosis is still largely made by exclusion of other causes and by correlation of timing of thrombocytopenia with the administration of drug. Metamizole may cause acute renal failure due to hemodynamic renal failure/acute tubular necrosis and/or acute tubulointerstitial nephritis. We report a case of acute renal failure and severe thrombocytopenia after metamizole. As far as we know, this combination of adverse effects from this drug has not been reported previously.

  11. CFU-MK assay for acute thrombocytopenia.

    Science.gov (United States)

    Parent-Massin, Dominique; Sibiril, Yann

    2008-08-01

    In this unit, protocols to culture human platelet progenitors (Colony Forming Unit-Megakaryocyte; CFU-M) with or without toxicants are described. Platelet progenitors are obtained from human umbilical cord blood. After separation of mononuclear cells, the cell suspension can be cryopreserved or plated immediately. Megakaryocytes are identified by immunocytochemistry. Test chemicals are added to the culture medium before cells are plated. Megakaryocytes are scored after 12 days of culture. IC(10), IC(50) and IC(90) can be calculated by comparison to control cultures. A predictive model is proposed to evaluate the hazard of thrombocytopenia induced by chemicals. When IC(50) and IC(90) are below C(max) in humans, the likelihood of thrombocytopenia is strong.

  12. Anemia and Thrombocytopenia in Acute and Chronic Renal Failure

    OpenAIRE

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

    2013-01-01

    Background 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 ...

  13. Prevention of non-immune mediated transfusion-related acute lung injury; from blood bank to patient.

    Science.gov (United States)

    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 substances that accumulate during storage of cellular blood products. Among these neutrophil priming substances are bioactive lipids, such as lyso-phosphatidylcholines (lysoPCs) and arachidonic acid, soluble CD40L (sCD40L) and possibly other, as yet unidentified substances. The accumulation of these substances during cellular blood product storage and their role in the induction of "non-immune mediated" TRALI pathogenesis are highly relevant for the current debate of the use of longer vs. shorter stored blood products. In this review, the accumulation of these different substances during storage, as well as their mode of action in inducing TRALI are discussed. In addition, different improvements in current blood banking procedures to prevent TRALI due to these non-immune mediators will be proposed.

  14. Acute profound thrombocytopenia secondary to local abciximab infusion

    Science.gov (United States)

    Press, Christopher D.; Moscona, John C.; Syed, Rashad H. Khazi; Katz, Morgan J.; Egan, Alison A.; Bisharat, Mohannad B.; Nijjar, Vikram S.; Anwar, Asif H.

    2012-01-01

    Glycoprotein (GP) IIb/IIIa receptor antagonists are powerful antiplatelet agents that are typically used in percutaneous coronary intervention. All three GP IIb/IIIa agents currently approved for use in the United States cause thrombocytopenia as a rare side effect. Abciximab is unique to the class in that it is a modified monoclonal antibody to the GP IIb/IIIa receptor, a property that can lead to increased platelet destruction. Presented herein is a patient who received a local infusion of abciximab for a lower-extremity thrombus and within 2 hours developed an acute profound thrombocytopenia that likely caused a large retroperitoneal hematoma. This case demonstrates the importance of checking platelet count within 2 to 4 hours after local (in addition to systemic) abciximab administration. Additionally, this report outlines how other causes of acute precipitous platelet drops, such as heparin-induced thrombocytopenia and pseudothrombocytopenia, can be rapidly excluded and allow for the prompt initiation of optimal therapy to minimize bleeding. PMID:23077384

  15. Anemia and Thrombocytopenia in Acute and Chronic Renal Failure

    Science.gov (United States)

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

    2013-01-01

    Background 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. Materials and Methods 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. Results 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 < 0.001). Conclusion It was recommended that in patients with chronic renal failure, to prevent the risk of bleeding, platelet count should be checked periodically. PMID:24505541

  16. Murine model of immune-mediated rejection of the acute lymphoblastic leukemia 70Z/3.

    Science.gov (United States)

    Labbe, Alain; Tran, Anne H; Paige, Christopher J

    2006-05-01

    70Z/3 is a murine pre-B cell leukemia line derived from BDF(1) mice and has been used in the study of signaling pathways in B cells. 70Z/3 cells were initially found to cause widespread disease upon injections in animals. We have isolated 70Z/3 variants divergent in their capacity to lead to morbidity after injections. One variant, 70Z/3-NL, elicits an immune response protecting the animal from tumor growth. Another variant, 70Z/3-L, does not induce an effective immune response and causes morbidity. We demonstrated that both CD4(+) and CD8(+) T cells are required for the rejection of 70Z/3-NL cells. Interestingly, the immune response generated against 70Z/3-NL cells was found to protect against a challenge with the lethal variant, 70Z/3-L. This indicates that although both lines can be recognized and killed by the immune system, only 70Z/3-NL is capable of inducing a protective response. Further observations, using subclones isolated from 70Z/3-NL, demonstrated that immune recognition of a portion of the cells was sufficient for protection. Depletion of CD4(+) and CD8(+) T cells in animals injected previously with 70Z/3-NL cells showed that T cells, and not Abs, were required for the maintenance of the protection initiated by 70Z/3-NL. We tested the capacity of 70Z/3-NL cells to treat mice challenged with 70Z/3-L. We can delay injections of 70Z/3-NL and still provide protection for the animals. We have a model of immune-mediated rejection which will allow us to dissect the requirements for the initiation of immune responses against an ALL tumor cell line.

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

    Science.gov (United States)

    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.

  18. [Immune-mediated neuropathies].

    Science.gov (United States)

    Stoll, G; Reiners, K

    2016-08-01

    The Guillain-Barré syndrome (GBS) and chronic inflammatory demyelinating polyneuropathy (CIDP) are the most common immune-mediated polyneuropathies, which can show variable clinical and electrophysiological manifestations. Rarer immune-mediated neuropathies encompass paraproteinemic neuropathies (PPN), multifocal motor neuropathy (MMN) and vasculitic neuropathies. The diagnosis usually relies on the history of symptom evolution, distribution of nerve dysfunction and particularly on characteristic features in nerve conduction studies, aided by cerebrospinal fluid (CSF) examination and nerve biopsy findings. The therapeutic toolbox encompasses corticosteroids, immunoglobulins and plasmapheresis often accompanied by long-term immunosuppression. It is important to note that immune-mediated neuropathies selectively respond to treatment and contraindications need to be considered. Despite treatment a considerable number of patients suffer from permanent neurological deficits.

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

    Energy Technology Data Exchange (ETDEWEB)

    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.

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

    Directory of Open Access Journals (Sweden)

    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.

  1. Transient leucopenia, thrombocytopenia and anaemia associated with severe acute phenobarbital intoxication in a dog.

    Science.gov (United States)

    Khoutorsky, A; Bruchim, Y

    2008-07-01

    A nine-year-old Labrador retriever dog was admitted to the emergency unit of the Hebrew University Veterinary Teaching Hospital with acute-onset tremors and coma. It had recently ingested a large quantity of phenobarbital and had a high serum phenobarbital concentration. On this basis, a diagnosis of acute phenobarbital intoxication was made. Significant leucopenia, thrombocytopenia and mild anaemia developed on the third day after admission. The leucopenia resolved on day 6 and the thrombocytopenia on day 13. The red blood cell count remained low for the next month. The dog was discharged on day 13 at which time it was ambulatory but weak. It was completely recovered clinically eight days later. In summary, high levels of serum phenobarbital as a result of acute intoxication induced pancytopenia, which improved when the serum phenobarbital level was normalised.

  2. Germline ETV6 Mutations Confer Susceptibility to Acute Lymphoblastic Leukemia and Thrombocytopenia.

    Directory of Open Access Journals (Sweden)

    Sabine Topka

    2015-06-01

    Full Text Available Somatic mutations affecting ETV6 often occur in acute lymphoblastic leukemia (ALL, the most common childhood malignancy. The genetic factors that predispose to ALL remain poorly understood. Here we identify a novel germline ETV6 p. L349P mutation in a kindred affected by thrombocytopenia and ALL. A second ETV6 p. N385fs mutation was identified in an unrelated kindred characterized by thrombocytopenia, ALL and secondary myelodysplasia/acute myeloid leukemia. Leukemic cells from the proband in the second kindred showed deletion of wild type ETV6 with retention of the ETV6 p. N385fs. Enforced expression of the ETV6 mutants revealed normal transcript and protein levels, but impaired nuclear localization. Accordingly, these mutants exhibited significantly reduced ability to regulate the transcription of ETV6 target genes. Our findings highlight a novel role for ETV6 in leukemia predisposition.

  3. Germline ETV6 Mutations Confer Susceptibility to Acute Lymphoblastic Leukemia and Thrombocytopenia.

    Science.gov (United States)

    Topka, Sabine; Vijai, Joseph; Walsh, Michael F; Jacobs, Lauren; Maria, Ann; Villano, Danylo; Gaddam, Pragna; Wu, Gang; McGee, Rose B; Quinn, Emily; Inaba, Hiroto; Hartford, Christine; Pui, Ching-Hon; Pappo, Alberto; Edmonson, Michael; Zhang, Michael Y; Stepensky, Polina; Steinherz, Peter; Schrader, Kasmintan; Lincoln, Anne; Bussel, James; Lipkin, Steve M; Goldgur, Yehuda; Harit, Mira; Stadler, Zsofia K; Mullighan, Charles; Weintraub, Michael; Shimamura, Akiko; Zhang, Jinghui; Downing, James R; Nichols, Kim E; Offit, Kenneth

    2015-06-01

    Somatic mutations affecting ETV6 often occur in acute lymphoblastic leukemia (ALL), the most common childhood malignancy. The genetic factors that predispose to ALL remain poorly understood. Here we identify a novel germline ETV6 p. L349P mutation in a kindred affected by thrombocytopenia and ALL. A second ETV6 p. N385fs mutation was identified in an unrelated kindred characterized by thrombocytopenia, ALL and secondary myelodysplasia/acute myeloid leukemia. Leukemic cells from the proband in the second kindred showed deletion of wild type ETV6 with retention of the ETV6 p. N385fs. Enforced expression of the ETV6 mutants revealed normal transcript and protein levels, but impaired nuclear localization. Accordingly, these mutants exhibited significantly reduced ability to regulate the transcription of ETV6 target genes. Our findings highlight a novel role for ETV6 in leukemia predisposition.

  4. 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.

  5. Persistent thrombocytopenia in a case of equine infectious anemia.

    Science.gov (United States)

    Cohen, N D; Carter, G K

    1991-09-15

    Persistent thrombocytopenia was detected in a horse with equine infectious anemia (EIA). The thrombocytopenia was considered to be immune-mediated, developing secondary to infection with EIA virus. Epistaxis, petechial hemorrhages, subcutaneous hematomas, and edema resolved after treatment with corticosteroids; however, the owners requested that the mare by euthanatized because of infection with EIA virus. Although clinical signs attributable to immune-mediated thrombocytopenia may resolve with appropriate treatment, horses with immune-mediated thrombocytopenia secondary to EIA have a guarded to grave prognosis, because of the risk of recurrence and transmission of the EIA virus.

  6. Thrombocytopenia is associated with acute respiratory distress syndrome mortality: an international study.

    Directory of Open Access Journals (Sweden)

    Tiehua Wang

    Full Text Available BACKGROUND: Early detection of the Acute Respiratory Distress Syndrome (ARDS has the potential to improve the prognosis of critically ill patients admitted to the intensive care unit (ICU. However, no reliable biomarkers are currently available for accurate early detection of ARDS in patients with predisposing conditions. OBJECTIVES: This study examined risk factors and biomarkers for ARDS development and mortality in two prospective cohort studies. METHODS: We examined clinical risk factors for ARDS in a cohort of 178 patients in Beijing, China who were admitted to the ICU and were at high risk for ARDS. Identified biomarkers were then replicated in a second cohort of1,878 patients in Boston, USA. RESULTS: Of 178 patients recruited from participating hospitals in Beijing, 75 developed ARDS. After multivariate adjustment, sepsis (odds ratio [OR]:5.58, 95% CI: 1.70-18.3, pulmonary injury (OR: 3.22; 95% CI: 1.60-6.47, and thrombocytopenia, defined as platelet count <80×10(3/µL, (OR: 2.67; 95% CI: 1.27-5.62were significantly associated with increased risk of developing ARDS. Thrombocytopenia was also associated with increased mortality in patients who developed ARDS (adjusted hazard ratio [AHR]: 1.38, 95% CI: 1.07-1.57 but not in those who did not develop ARDS(AHR: 1.25, 95% CI: 0.96-1.62. The presence of both thrombocytopenia and ARDS substantially increased 60-day mortality. Sensitivity analyses showed that a platelet count of <100×10(3/µL in combination with ARDS provide the highest prognostic value for mortality. These associations were replicated in the cohort of US patients. CONCLUSIONS: This study of ICU patients in both China and US showed that thrombocytopenia is associated with an increased risk of ARDS and platelet count in combination with ARDS had a high predictive value for patient mortality.

  7. Severe Thrombocytopenia after Zika Virus Infection, Guadeloupe, 2016

    Science.gov (United States)

    Boyer Chammard, Timothée; Schepers, Kinda; Breurec, Sébastien; Messiaen, Thierry; Destrem, Anne-Laure; Mahevas, Matthieu; Soulillou, Adrien; Janaud, Ludovic; Curlier, Elodie; Herrmann-Storck, Cécile

    2017-01-01

    Severe thrombocytopenia during or after the course of Zika virus infection has been rarely reported. We report 7 cases of severe thrombocytopenia and hemorrhagic signs and symptoms in Guadeloupe after infection with this virus. Clinical course and laboratory findings strongly suggest a causal link between Zika virus infection and immune-mediated thrombocytopenia. PMID:27997330

  8. Outcomes after acute ischemic stroke in patients with thrombocytopenia or thrombocytosis.

    Science.gov (United States)

    Furlan, Julio C; Fang, Jiming; Silver, Frank L

    2016-03-15

    Thrombocytopenia may be associated with a greater risk of cerebral hemorrhage and thrombocytosis may be associated with a greater risk of cerebral thrombosis. There is a paucity of studies focused on the potential association between blood platelet count (BPC) and outcomes after acute ischemic stroke (AIS). We hypothesized that abnormal BPC is associated with poorer outcomes after AIS. This study included data from the Ontario Stroke Registry on consecutive patients with AIS admitted between July 2003 and March 2008. Patients were divided into groups as follows: low BPC (450,000/mm(3)). Primary outcome measures were the frequency of moderate/severe strokes on admission (Canadian Neurologic Scale: thrombocytosis on the initial admission are associated with higher mortality after AIS. Abnormal BPC does not adversely affect the degree of initial impairment, disability at discharge, or length of stay in the acute care hospital after AIS. Copyright © 2016 Elsevier B.V. All rights reserved.

  9. Acute Thrombocytopenia, Leucopenia, and Multiorgan Dysfunction: The First Case of SFTS Bunyavirus outside China?

    Directory of Open Access Journals (Sweden)

    Srdjan Denic

    2011-01-01

    Full Text Available We report a 57-year-old man with acute thrombocytopenia, leucopenia, and multiorgan dysfunction. Patient was from North Korea and was temporarily working in Dubai, United Arab Emirates, when he fell ill in March 2009. At the same time and unknown to us, many patients with similar clinical manifestations were admitted to hospitals in China. The Chinese cases—identified between March and July 2009—were recently reported to have been infected with a tick-born strain of bunyavirus, a new disease. The virus infection was documented in patients from central China and the region that shares the border with North Korea. The clinical manifestations, the time of disease onset, and geographical link of the patient with the region in which the disease is endemic suggest that the patient had SFTS bunyavirus infection.

  10. Immune mediated liver failure

    OpenAIRE

    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...

  11. [Diagnosis of immune-mediated neuropathies].

    Science.gov (United States)

    Diószeghy, Péter

    2011-09-25

    Separate discussion of immune-mediated neuropathies from other neuropathies is justified by the serious consequences of the natural course of these diseases, like disability and sometimes even life threatening conditions. On the other hand nowadays effective treatments already exist, and with timely and correct diagnosis an appropriately chosen treatment may result in significant improvement of quality of life, occasionally even complete recovery. These are rare diseases, and the increasing number of different variants makes it more difficult to recognize them. Their diagnosis is based on the precise knowledge of clinical signs and symptoms, and it is verified by the help of neurophysiologic and laboratory, first of all CSF examinations. Description of clinical features of the classic acute immune-mediated neuropathy, characterized by ascending paresis and demyelination is followed by a summary of characteristics of newly recognized axonal, regional and functional variants. Chronic immune-mediated demyelinating polyneuropathies are not diagnosed in due number even today. This paper does not only present the classic form but it also introduces the ever increasing special variants, like distal acquired demyelinating sensory neuropathy, Lewis-Sumner syndrome, multifocal motor neuropathy and paraproteinemic neuropathies. Vasculitic neuropathies can be divided into two groups: systemic and non-systemic ones. The first sign of a vasculitic neuropathy is a progressive, painful mononeuropathy; the classic clinical presentation is the mononeuritis multiplex. It is characterized by general signs like fever, loss of weight, fatigue. In systemic vasculitis organ specific symptoms are also present. From the paraneoplastic diseases the subacute sensory neuropathy and the sensory neuronopathy are members of the immune-mediated neuropathies, being most frequently associated with small cell lung cancer.

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

    DEFF Research Database (Denmark)

    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...

  13. Meloxicam-induced thrombocytopenia.

    Science.gov (United States)

    Ranieri, Melissa M; Bradley, Elizabeth F; Simon, Allison B

    2014-02-01

    Immune thrombocytopenia can have several causes including the use of certain drugs. Thrombocytopenia has been documented as a rare adverse effect of some nonsteroidal antiinflammatory drugs (NSAIDs) including diclofenac, naproxen, and ibuprofen. However, only one previously documented case of meloxicam-associated thrombocytopenia has been reported in the literature. We describe an 84-year-old woman who developed a case of immune-mediated thrombocytopenia that was attributed to meloxicam therapy. The patient's platelet count decreased from a baseline of 267 × 10(3) /mm(3) to 2 × 10(3) /mm(3) 1 week after she received her first lifetime dose of meloxicam. She also experienced black stools and bruising that coincided with the meloxicam administration. The almost immediate onset of thrombocytopenia and symptoms after initiation of meloxicam, as well as the marked reduction in her platelet count, suggest an idiosyncratic reaction. According to the Hill criteria for assessing causality of adverse drug events, it is plausible that this reaction was due to meloxicam. Health care providers should be aware of the possibility of thrombocytopenia secondary to NSAID therapy including meloxicam. Immune thrombocytopenia can be life threatening if it is not identified and treated promptly. A thorough medication history is particularly important when patients present with unusual symptoms, with a focus on those drugs that have been recently initiated. Although thrombocytopenia is a rare adverse effect of NSAID therapy, it should be considered a potential cause in patients receiving these drugs who have signs and symptoms consistent with this blood dyscrasia.

  14. Evaluation of a DLA-79 allele associated with multiple immune-mediated diseases in dogs.

    Science.gov (United States)

    Friedenberg, Steven G; Buhrman, Greg; Chdid, Lhoucine; Olby, Natasha J; Olivry, Thierry; Guillaumin, Julien; O'Toole, Theresa; Goggs, Robert; Kennedy, Lorna J; Rose, Robert B; Meurs, Kathryn M

    2016-03-01

    Immune-mediated diseases are common and life-threatening disorders in dogs. Many canine immune-mediated diseases have strong breed predispositions and are believed to be inherited. However, the genetic mutations that cause these diseases are mostly unknown. As many immune-mediated diseases in humans share polymorphisms among a common set of genes, we conducted a candidate gene study of 15 of these genes across four immune-mediated diseases (immune-mediated hemolytic anemia, immune-mediated thrombocytopenia, immune-mediated polyarthritis (IMPA), and atopic dermatitis) in 195 affected and 206 unaffected dogs to assess whether causative or predictive polymorphisms might exist in similar genes in dogs. We demonstrate a strong association (Fisher's exact p = 0.0004 for allelic association, p = 0.0035 for genotypic association) between two polymorphic positions (10 bp apart) in exon 2 of one allele in DLA-79, DLA-79*001:02, and multiple immune-mediated diseases. The frequency of this allele was significantly higher in dogs with immune-mediated disease than in control dogs (0.21 vs. 0.12) and ranged from 0.28 in dogs with IMPA to 0.15 in dogs with atopic dermatitis. This allele has two non-synonymous substitutions (compared with the reference allele, DLA-79*001:01), resulting in F33L and N37D amino acid changes. These mutations occur in the peptide-binding pocket of the protein, and based upon our computational modeling studies, are likely to affect critical interactions with the peptide N-terminus. Further studies are warranted to confirm these findings more broadly and to determine the specific mechanism by which the identified variants alter canine immune system function.

  15. A case of Plasmodium vivax malaria with spontaneous subarachnoid hemorrhage and acute renal failure, severe thrombocytopenia, with anemia

    Directory of Open Access Journals (Sweden)

    Govind S Shiddapur

    2013-01-01

    Full Text Available When we talk about severe malaria, we usually think of Plasmodium falciparum. However, in recent times, Plasmodium vivax has also been reported to cause severe multi-organ dysfunction and life-threatening disease similar to P. falciparum. We report here a case of P. vivax malaria in a young boy from an endemic zone, who developed acute renal failure, severe thrombocytopenia, and anemia and later developed spontaneous subarachnoid hemorrhage. Multisystem involvement in a patient with P. vivax is rare, and subarachnoid hemorrhage is an unusual presentation.

  16. Heparin-induced thrombocytopenia: a general review.

    Science.gov (United States)

    Swanson, Joseph M

    2007-01-01

    Unfractionated heparin is widely used for numerous clinical situations. A well-known adverse effect of heparin exposure is thrombocytopenia. Heparin-induced thrombocytopenia is a clinicopathologic syndrome that can be associated with severe complications and significant mortality. The pathophysiology of heparin-induced thrombocytopenia includes an immune-mediated reaction to heparin that activates platelets and results in an acquired hypercoagulability. Diagnosis of heparin-induced thrombocytopenia should incorporate clinical signs and symptoms and laboratory testing for heparin-induced thrombocytopenia antibodies. Therapy should include discontinuation of heparin, initiation of a direct thrombin inhibitor, and eventually therapy with warfarin (only after the platelet count is at least 100 x 10(9)/L).

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Treatment of immune-mediated, dysimmune neuropathies.

    Science.gov (United States)

    Finsterer, J

    2005-08-01

    This review focuses on the actual status and recent advances in the treatment of immune-mediated neuropathies, including: Guillain-Barre syndrome (GBS) with its subtypes acute inflammatory demyelinating polyradiculoneuropathy, acute motor axonal neuropathy, acute motor and sensory axonal neuropathy, Miller Fisher syndrome, and acute pandysautonomia; chronic inflammatory demyelinating polyneuropathy (CIDP) with its subtypes classical CIDP, CIDP with diabetes, CIDP/monoclonal gammopathy of undetermined significance (MGUS), sensory CIDP, multifocal motor neuropathy (MMN), multifocal acquired demyelinating sensory and motor neuropathy or Lewis-Sumner syndrome, multifocal acquired sensory and motor neuropathy, and distal acquired demyelinating sensory neuropathy; IgM monoclonal gammopathies with its subtypes Waldenstrom's macroglobulinemia, myelin-associated glycoprotein-associated gammopathy, polyneuropathy, organomegaly, endocrinopathy, M-protein, skin changes syndrome, mixed cryoglobulinemia, gait ataxia, late-onset polyneuropathy syndrome, and MGUS. Concerning the treatment of GBS, there is no significant difference between intravenous immunoglobulins (IVIG), plasma exchange or plasma exchange followed by IVIG. Because of convenience and absent invasiveness, IVIG are usually preferred. In treating CIDP corticosteroids, IVIG, or plasma exchange are equally effective. Despite the high costs and relative lack of availability, IVIG are preferentially used. For the one-third of patients, who does not respond, other immunosuppressive options are available. In MMN IVIG are the treatment of choice. Inadequate response in 20% of the patients requires adjunctive immunosuppressive therapies. Neuropathies with IgM monoclonal gammopathy may respond to various chemotherapeutic agents, although the long-term effects are unknown. In addition, such treatment may be associated with serious side effects. Recent data support the use of rituximab, a monoclonal antibody against the B

  19. Congenital Thrombocytopenia

    Institute of Scientific and Technical Information of China (English)

    王兆钺

    2011-01-01

    @@ Platelets are essential for normal hemostasis.Platelets adhere to damaged blood vessels, and then aggregate and promote activation of coagulation factors, resulting to ceasing bleeding.Both quantitative and qualitative abnormalities of platelets can cause bleeding problems.Among them, immune thrombocytopenias are the most common conditions.However, congenital thrombocytopenias are often neglected because of their relative rarity and complex laboratory tests.That causes misdiagnosis and unnecessary and potentially harmful treatments for many patients.

  20. Interferon-α induced severe thrombocytopenia:A case report and review of the literature

    Institute of Scientific and Technical Information of China (English)

    2010-01-01

    We report a case of severe thrombocytopenia following pegylated interferon-α 2a(Peg-IFN-α 2a)treatment of hepatitis C virus infection and summarize the clinical characteristics of 16 cases of IFN-α induced severe thrombocytopenia and its immune-mediated mechanism.Discontinuation of IFN-α and early administration of immunosuppressants are the effective therapy for IFN-αinduced severe thrombocytopenia.

  1. Immune-Mediated Vascular Injury and Dysfunction in Transplant Arteriosclerosis

    Directory of Open Access Journals (Sweden)

    Anna evon Rossum

    2015-01-01

    Full Text Available Solid organ transplantation is the only treatment for end-stage organ failure but this life-saving procedure is limited by immune-mediated rejection of most grafts. Blood vessels within transplanted organs are targeted by the immune system and the resultant vascular damage is a main contributor to acute and chronic graft failure. The vasculature is a unique tissue with specific immunological properties. This review discusses the interactions of the immune system with blood vessels in transplanted organs and how these interactions lead to the development of transplant arteriosclerosis, a leading cause of heart transplant failure.

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

    Directory of Open Access Journals (Sweden)

    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.

  3. 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.

    2016-01-01

    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 in

  4. Immune-mediated canine and feline keratitis.

    Science.gov (United States)

    Andrew, Stacy E

    2008-03-01

    Although the normal cornea is devoid of vasculature and lymphatics, there are still several immune-mediated corneal conditions that can occur in dogs and cats. An overview of corneal immunology is presented. Diseases of dogs, including chronic superficial keratitis, superficial punctate keratitis, and canine adenovirus endotheliitis, as well as feline diseases, including eosinophilic keratitis and herpesvirus-related conditions, are discussed.

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

    Science.gov (United States)

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

    2015-03-12

    Immune-mediated platelet destruction is most frequently caused by allo- or autoantibodies via Fcγ 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 C-reactive protein (CRP), a ligand for Fc receptors on phagocytes, enhances antibody-mediated platelet destruction by human phagocytes in vitro and in vivo in mice. Without antiplatelet antibodies, CRP was found to be inert toward platelets, but it bound to phosphorylcholine exposed after oxidation triggered by antiplatelet antibodies, thereby enhancing platelet phagocytosis. CRP levels were significantly elevated in patients with allo- and autoantibody-mediated thrombocytopenias compared with healthy controls. Within a week, intravenous immunoglobulin treatment in children with newly diagnosed immune thrombocytopenia led to significant decrease of CRP levels, increased platelet numbers, and clinically decreased bleeding severity. Furthermore, the higher the level of CRP at diagnosis, the longer it took before stable platelet counts were reached. These data suggest that CRP amplifies antibody-mediated platelet destruction and may in part explain the aggravation of thrombocytopenia on infections. Hence, targeting CRP could offer new therapeutic opportunities for these patients.

  6. 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.

  7. Immune-Mediated Therapies for Liver Cancer

    Science.gov (United States)

    Aravalli, Rajagopal N.; Steer, Clifford J.

    2017-01-01

    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. PMID:28218682

  8. Immune-Mediated Therapies for Liver Cancer

    OpenAIRE

    Aravalli, Rajagopal N; Steer, Clifford J.

    2017-01-01

    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 ...

  9. 间充质干细胞治疗提升免疫性血小板减少症小鼠的血小板数并影响其外周血单核细胞中 T-bet 和 GATA-3基因表达%Mesenchymal stem cells increase platelet counts in mice with immune-mediated thrombocytopenia and affect T-bet and GATA-3 gene expression

    Institute of Scientific and Technical Information of China (English)

    徐敏; 王椋; 刘国强; 鲁光; 丁慧芳; 邢健; 赵霞; 韩芳; 尚应辉

    2013-01-01

    目的:探讨间充质干细胞( MSC)对原发免疫性血小板减少症( ITP)小鼠血小板数目的影响及其机制。方法采用腹腔注射大鼠抗小鼠CD41抗体( MWReg30单抗)的方法诱导BALB/c小鼠产生ITP后,取20只作为实验组,20只作为对照组。之后通过鼠尾静脉给实验组小鼠注射MSC 2×107个/只。注射后5 d、7 d、14 d,测定实验组与对照组小鼠外周血血小板数;14 d时应用逆转录聚合酶链反应( RT-PCR)检测小鼠外周血单个核细胞( PBMC)中转录因子T-bet和GATA-3 mRNA的表达;应用酶联免疫法测定Th1类细胞因子IFN-γ、IL-2及Th2类细胞因子IL-4、IL-10的水平。结果7 d、14 d后,注射MSC实验组小鼠血小板值[(588.0±81.6)×109/L、(623.0±78.9)×109/L]明显高于未注射MSC对照组[(317.0±90.1)×109/L、(288.0±87.8)×109/L](P<0.05);14 d时,实验组PBMC中T-bet mRNA表达水平低于对照组[(0.04±0.03) vs (0.27±0.05)](P<0.05);GATA-3 mRNA的表达水平高于对照组[(0.14±0.04) vs (0.07±0.05)](P<0.05);实验组Th1类细胞因子IFN-γ、IL-2水平[(3.1±1.7) pg/ml、(3.2±2.1) pg/ml]明显低于对照组[(10.3±4.8) pg/ml、(16.3±5.7) pg/ml](P<0.05);实验组外周血 Th2类细胞因子 IL-4、IL-10水平[(88.6±15.2) pg/ml、(38.3±11.8) pg/ml]明显高于对照组[(32.7±5.7) pg/ml、(22.1±3.4) pg/ml](P<0.05)。结论 MSC可以有效提升ITP小鼠的血小板数,机制可能与抑制了T-bet和GATA-3的表达失常导致的Th1细胞极化有关。%Objective To explore the effects of mesenchymal stem cells ( MSC ) treatment on platelet counts in mice with immune-mediated thrombocytopenia ( ITP) and the possible mechanism .Meth-ods ITP was induced by daily intraperitoneal injection of anti-platelet membrane CD 41 antibody (MWReg30) into

  10. [Heparin-induced thrombocytopenia. New therapeutical options].

    Science.gov (United States)

    Seculini Patiño, Carina E; Tabares, Aldo H

    2016-01-01

    Heparin-induced thrombocytopenia (HIT) is an immune-mediated adverse reaction due to antibodies to a multimolecular complex of heparin and platelet factor 4 (PF4) characterized by moderate thrombocytopenia and paradoxical arterial or venous thrombosis. It is a relatively infrequent complication related to the administration of any type of heparin. In patients undergoing percutaneous coronary revascularization or coronary artery by-pass graft the prevalence of HIT is higher than in other clinical settings. Recognizing clinical and laboratory features of HIT allow immediate discontinuation of heparin and the use of alternative anticoagulants to avoid serious thrombotic complications. In this review, we summarize different therapeutic options for the treatment of HIT with special emphasis on direct oral anticoagulants (DOACS) such as dabigatran, rivaroxaban and apixaban. DOACS might represent a therapeutic alternative for HIT treatment.

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

    Institute of Scientific and Technical Information of China (English)

    Tajeldin; Mohammedien; Abdallah; Omer; Mohammed; Abd; elbagi; Abuelgasim; OsmanKaroum; Abdel; Aziem; Abdallah; Ali

    2014-01-01

    A 25 year-old male patient was admitted to the causality with complaints of fever,joints pain,epislaxis 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 lo 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 55×10~9/L and came up to 180×10~9/L on 12 th day after admission.Brucella-induced immune thrombocytopenia should be considered in patient presenting with bleeding and febrile illness especially in endemic region.

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

    Institute of Scientific and Technical Information of China (English)

    Tajeldin Mohammedien Abdallah; Omer Mohammed Abd elbagi; Abuelgasim OsmanKaroum; Abdel Aziem Abdallah Ali

    2014-01-01

    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 55í109/L and came up to 180í109/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.

  13. Multiple sclerosis and fatigue: A review on the contribution of inflammation and immune-mediated neurodegeneration.

    Science.gov (United States)

    Patejdl, Robert; Penner, Iris K; Noack, Thomas K; Zettl, Uwe K

    2016-03-01

    Multiple sclerosis (MS) is an immune mediated disease of the central nervous system (CNS) and the leading cause of non-traumatic disability among young and middle-aged adults in the western world. One of its most prevalent and debilitating symptoms is fatigue. Despite the general acceptance of the idea of an immune pathogenesis of MS itself, the role of autoimmunity in the course of MS-fatigue is a matter of debate. Both immune-related processes (acute inflammation, chronic inflammation, immune-mediated neurodegeneration, immune-mediated alterations of endocrine functions related to fatigue) and presumably non-immune-mediated disturbances and factors (sleep disturbances, depression, cognitive alterations, chronic infections, adverse effects of medications) contribute to the clinical picture. Data from in vitro and animal experiments has provided evidence for a role of cytokines as IL-1 and TNF-alpha. This association could not be verified directly in blood samples from humans whereas whole blood stimulation protocols gave some indirect evidence for a role of cytokines in MS-fatigue. MRI being able to detect acute and chronic immune mediated damage to the CNS could depict that global atrophy of gray or white matter does not correlate with fatigue. Rather, distinctive clusters of lesions and atrophy at different locations, mostly bifrontal or in subcortical structures, correlate specifically with fatigue. Regardless of the difficulties in pinpointing the immunogenesis of MS-fatigue, an important role of autoimmunity is strongly supported by an indirect route: A growing amount of data shows that the highly effective immunotherapeutics which have been introduced to MS-treatment over the last years effectively and sustainably stabilize and ameliorate fatigue in parallel to their dampening effects on the neuroinflammatory process. This review summarizes the existing data on the relation between inflammation, patterns of CNS-lesions and the effects of immunotherapeutics

  14. 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

  15. Immune-mediated complications in patients with myelodysplastic syndromes--clinical and cytogenetic features.

    Science.gov (United States)

    Billström, R; Johansson, H; Johansson, B; Mitelman, F

    1995-07-01

    It has been recognized in recent years that some patients with myelodysplastic syndromes (MDS) develop immune-mediated complications (IMC), but little is known about the correlations to MDS-specific disease features. In a retrospective study of 82 MDS patients, we identified 10 (12%) with IMC (group A) and compared them to the remaining 72 cases (group B). Group A consisted of 5 patients with biopsy-verified skin vasculitis and 1 case each with temporal arteritis/polymyalgia rheumatica, necrotising panniculitis, Hashimoto's thyroiditis, autoimmune thrombocytopenia, and Sweet's syndrome. Survival times, sex ratio and distribution of MDS subtypes were similar in the two groups. The patients in group A were younger than those in group B (median 66 vs. 76 years, p aberrations, were also observed to be more common in group A (3/9 vs. 8/53). The results indicate that IMC preferentially develop in patients with secondary MDS, in younger MDS cases, and in patients with cytogenetic abnormalities.

  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. Nitrofurantoin-induced immune-mediated lung and liver disease

    Directory of Open Access Journals (Sweden)

    Milić Rade

    2012-01-01

    Full Text Available Introduction. Nitrofurantoin, a furan derivative, introduced in the fifties has widely been used as an effective agent for the treatment and prevention of urinary tract infections (UTI. Spectrum of adverse reactions to nitrofurantoin is wide, ranging from eosinophilic interstitial lung disease, acute hepatitis and granulomatous reaction, to the chronic active hepatitis, a very rare adverse effect, that can lead to cirrhosis and death. Case report. We presented a 55-year-old female patient with eosinophilic interstitial lung disease, severe chronic active hepatitis and several other immune- mediated multisystemic manifestations of prolonged exposure to nitrofurantoin because of the recurrent UTI caused by Escherichia coli. We estimated typical radiographic and laboratory disturbances, also restrictive ventilatory changes, severe reduction of carbon monoxide diffusion capacity and abnormal liver function tests. Lymphocytic-eosinophylic alveolitis was consistent with druginduced reaction. Hepatitis was confirmed by liver biopsy. After withdrawal of nitrofurantoin and application of high dose of glicocorticosteroids, prompt clinical and laboratory recovery was achieved. Conclusion. Adverse drug reactions should be considered in patients with concomitant lung and liver disease. The mainstay of treatment is drug withdrawal and the use of immunosuppressive drugs in severe cases. Consideration should be given to monitor lung and liver function tests during long term nitrofurantoin therapy.

  18. Heparin-induced thrombocytopenia

    Directory of Open Access Journals (Sweden)

    Shaikh Nissar

    2011-01-01

    Full Text Available In the last 7 decades heparin has remained the most commonly used anticoagulant. Its use is increasing, mainly due to the increase in the number of vascular interventions and aging population. The most feared complication of heparin use is heparin-induced thrombocytopenia (HIT. HIT is a clinicopathologic hypercoagulable, procoagulant prothrombotic condition in patients on heparin therapy, and decrease in platelet count by 50% or to less than 100,000, from 5 to 14 days of therapy. This prothrombotic hypercoagulable state in HIT patient is due to the combined effect of various factors, such as platelet activation, mainly the formation of PF4/heparin/IgG complex, stimulation of the intrinsic factor, and loss of anticoagulant effect of heparin. Diagnosis of HIT is done by clinical condition, heparin use, and timing of thrombocytopenia, and it is confirmed by either serotonin release assay or ELISA assay. Complications of HIT are venous/arterial thrombosis, skin gangrene, and acute platelet activation syndrome. Stopping heparin is the basic initial treatment, and Direct Thrombin Inhibitors (DTI are medication of choice in these patients. A few routine but essential procedures performed by using heparin are hemodialysis, Percutaneous Coronary Intervention, and Cardiopulmonary Bypass; but it cannot be used if a patient develops HIT. HIT patients with unstable angina, thromboembolism, or indwelling devices, such as valve replacement or intraaortic balloon pump, will require alternative anticoagulation therapy. HIT can be prevented significantly by keeping heparin therapy shorter, avoiding bovine heparin, using low-molecular weight heparin, and stopping heparin use for flush and heparin lock.

  19. Acute thrombocytopenia caused by ceftizoxime sodium%头孢唑肟钠引起急性血小板减少

    Institute of Scientific and Technical Information of China (English)

    朱颖辉

    2011-01-01

    1例32岁女性患者,因发热腰痛4d入院,诊断为急性肾孟肾炎,予静脉点滴头孢唑肟钠(2g,bid)治疗.用药第2天患者出现血小板急剧下降,无出血,立即停用头孢唑肟钠,患者血小板在1周内逐渐恢复正常.本文分析并总结头孢菌素类药物引起血小板减少的可能发生机制及血小板变化特点,以引起临床关注.%One 32-year-old female patient who was hospitalized as a result of fever and waist pain for 4 days, was diagnosed as acute pyelonephritis. Ceftizoxime sodium injection 2 g twice daily was administered to control the infection. After 2 days, the platelet count of this patient decreased sharply. There was no sign of bleeding in this patient. Ceftizoxime sodium was discontinued immediately. Platelet count of the patient gradually increased to normal within a week. The possible pathogenesis and change characteristics of platelet count in thrombocytopenia caused by cephalosporins were analyzed and summarized, which should be paid more attention to in clinical practice.

  20. [Current treatment of primary immune thrombocytopenia].

    Science.gov (United States)

    Lozano, María L; Vicente, Vicente

    2014-05-06

    Primary immune thrombocytopenia, also termed immune thrombocytopenic purpura (ITP) is an autoimmune disorder characterized by premature platelet destruction and impaired platelet production. Traditional treatment of ITP has predominantly consisted of immune suppression and/or modulation. However, the understanding of the immune mediated impairment of platelet production has led to the development of new treatments that target the thrombopoietin receptor, promoting formation of megakaryocytes and increasing platelet counts. Best practice for the management of ITP has not yet been established because data from comparative studies are lacking. While some disagreement might still remain among experts concerning therapy (when, who, and how should be treated), in recent years different evidence-based practice guidelines have been published to assist healthcare professionals in the diagnosis and treatment of ITP. This review describes the current treatment landscape of ITP. Copyright © 2013 Elsevier España, S.L. All rights reserved.

  1. Immune-Mediated Muscle Diseases of the Horse.

    Science.gov (United States)

    Durward-Akhurst, S A; Valberg, S J

    2017-01-01

    In horses, immune-mediated muscle disorders can arise from an overzealous immune response to concurrent infections or potentially from an inherent immune response to host muscle antigens. Streptococcus equi ss. equi infection or vaccination can result in infarctive purpura hemorrhagica (IPH) in which vascular deposition of IgA-streptococcal M protein complexes produces ischemia and complete focal infarction of skeletal muscle and internal organs. In Quarter Horse-related breeds with immune-mediated myositis, an apparent abnormal immune response to muscle antigens results in upregulation of major histocompatibility complex class (MHC) I and II on muscle cell membranes, lymphocytic infiltration of lumbar and gluteal myofibers, and subsequent gross muscle atrophy. Rarely, an inflammatory event results in myositis with subsequent systemic calcinosis characterized by a pathognomonic hyperphosphatemia and high fatality rate. This review presents an overview of these immune-mediated myopathies and highlights clinical and pathological features as well as the suspected pathophysiology.

  2. Pyrazinamide induced thrombocytopenia

    Directory of Open Access Journals (Sweden)

    Kant Surya

    2010-01-01

    Full Text Available Thrombocytopenia is an uncommon but potentially life-threatening complication of certain antitubercular drugs and is characterized by rapid destruction of platelets whenever offending drug is taken by a susceptible person. We report a case of pyrazinamide-induced thrombocytopenia in a patient receiving anti tubercular drugs.

  3. Autonomic Involvement in Subacute and Chronic Immune-Mediated Neuropathies

    Science.gov (United States)

    Mazzeo, Anna; Stancanelli, Claudia; Vita, Giuseppe

    2013-01-01

    Autonomic function can be impaired in many disorders in which sympathetic, parasympathetic, and enteric arms of the autonomic nervous system are affected. Signs and symptoms of autonomic involvement are related to impairment of cardiovascular, gastrointestinal, urogenital, thermoregulatory, sudomotor, and pupillomotor autonomic functions. Availability of noninvasive, sensitive, and reproducible tests can help to recognize these disorders and to better understand specific mechanisms of some, potentially treatable, immune-mediated autonomic neuropathies. This paper describes autonomic involvement in immune-mediated neuropathies with a subacute or chronic course. PMID:23853716

  4. Relapsing anemia with thrombocytopenia and acute kidney injury%反复发作贫血、血小板减少伴急性肾损伤

    Institute of Scientific and Technical Information of China (English)

    全军肾脏病研究所学术委员会

    2012-01-01

    青年女性,分别先后因少年时不洁饮食及青年期妊娠7月发生急性肾功能不全、微血管病性溶血、血小板减少、癫痫反复发作.第一次肾活检为典型的急性血栓性微血管病变,经甲泼尼龙1.5g冲击、血浆置换2次后血小板升至正常,透析治疗半年后肾功能恢复;第二次发病重复肾活检见肾小球及血管呈慢性化病变,但存在急性肾小管-间质损伤,静脉滴注甲泼尼龙40 mg/d、输注血浆治疗3d后血小板即升至正常,1月后肾功能恢复.两次发病查血管性血友病因子裂解酶13(ADAMTS13)活性均正常、抗ADAMTS13抗体低滴度阳性.最终诊断为获得性血栓性血小板减少性紫癜.%A female patient was admitted for both presenting as acute renal dysfunction, microangiopathic hemolysis, thrombocytopenia ,epilepsia and transient fever separately when she was 14 and 22 years old. In her first onset, renal histoiogiral showed classic acute thrombotic microangiopathies(TMA) .platelet increased to the normal after treatment of Prednisolone 0. 5 g/d for 3 days and plasma exchange twice, her renal function recovered after half-year hemodialysis. Her Second renal biopsy showed that glomcrulus and blood vessel displayed mainly chronic pathological changes, meanwhile obviously acute tubulointerstial injury. Platelet increased and renal function recovered quickly. ADAMTS13 activities were normal,and anti-ADAMTS13 antibodies were positive at her two episodes. Finally,TTP was diagnosed.

  5. Monoclonal IgG can ameliorate immune thrombocytopenia in a murine model of ITP: an alternative to IVIG.

    Science.gov (United States)

    Song, Seng; Crow, Andrew R; Freedman, John; Lazarus, Alan H

    2003-05-01

    Intravenous immunoglobulin (IVIG) is used to treat immune thrombocytopenia resulting from a variety of autoimmune and nonautoimmune diseases such as idiopathic thrombocytopenic purpura (ITP), heparin-induced thrombocytopenia, and posttransfusion purpura. IVIG is a limited resource and although considered safe, may nevertheless carry some risk of transferring disease. Its high cost makes monoclonal antibodies, capable of mimicking the clinical effects of IVIG, highly desirable. We show here, using a murine model of ITP, that selected monoclonal antibodies can protect against thrombocytopenia. SCID mice were pretreated with 1 of 21 monoclonal antibodies before induction of thrombocytopenia by antiplatelet antibody. Four antibodies reacted with the CD24 antigen on erythrocytes. Two antibodies were of the IgM class, and although one IgM antibody caused a minimal degree of anemia (P <.05), neither antibody ameliorated immune thrombocytopenia. One of 2 anti-CD24 antibodies of the IgG class ameliorated immune thrombocytopenia and blocked reticuloendothelial system function at the same doses that protected against thrombocytopenia. Some antibodies reactive with other circulating cell types also protected against immune-mediated thrombocytopenia while no antibody without a distinct target antigen in the mice was protective. Protective monoclonal antibodies significantly prevented thrombocytopenia at down to a 1000-fold lower dose (200 microg/kg) as compared with standard IVIG treatment (2 g/kg). It is concluded that monoclonal IgG with specificity for a circulating cellular target antigen may provide an alternative therapeutic approach to treating immune thrombocytopenia.

  6. Neonatal alloimmune thrombocytopenia

    Directory of Open Access Journals (Sweden)

    Mella MT

    2015-06-01

    Full Text Available Maria Teresa Mella, Keith A Eddleman Department of Obstetrics and Gynecology, Division of Maternal Fetal Medicine, Mount Sinai School of Medicine, New York, NY, USA Abstract: Neonatal alloimmune thrombocytopenia occurs in one in 1,000–1,500 live births and is the most common cause of severe thrombocytopenia and intracranial hemorrhage in term infants. It is the equivalent of red blood cell alloimmunization and is due to transplacental passage of maternal antibodies against paternally derived fetal platelet antigens. A diagnosis of neonatal alloimmune thrombocytopenia should be considered for any neonate with unexplained thrombocytopenia. Once the diagnosis is made, it is known that all subsequent pregnancies are at risk for severe disease. In order to prevent the devastating and potentially life-threatening manifestations of the disease, the goal is to initiate treatment early with serial percutaneous umbilical blood sampling, intravenous immunoglobulin administration, prednisone, and/or fetal platelet transfusions. Timing of delivery is variable with delivery for severe disease recommended at an earlier gestational age. Vaginal delivery can be considered if the fetal platelet count is greater than 50,000–100,000 µL. Thrombocytopenia due to neonatal alloimmune thrombocytopenia usually resolves spontaneously within 1–2 weeks after delivery, but a platelet transfusion may be necessary to prevent a serious hemorrhagic event. In all cases, a multidisciplinary approach to care should be undertaken with delivery at a tertiary care center. Keywords: neonatal thrombocytopenia, fetal therapy, intracranial hemorrhage, intravenous immunoglobulin, alloimmunization

  7. 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.

  8. Immune-mediated diseases in primary sclerosing cholangitis

    NARCIS (Netherlands)

    Lamberts, Laetitia E.; Janse, Marcel; Haagsma, Elizabeth B.; van den Berg, Arie P.; Weersma, Rinse K.

    2011-01-01

    Background: Primary sclerosing cholangitis is a chronic cholestatic liver disease. An immune aetiology is suggested by associations between PSC and inflammatory bowel disease. Data on concomitant prevalence of other immune-mediated diseases is limited. Aim: To assess the prevalence of concomitant im

  9. Immune-mediated diseases in primary sclerosing cholangitis

    NARCIS (Netherlands)

    Lamberts, Laetitia E.; Janse, Marcel; Haagsma, Elizabeth B.; van den Berg, Arie P.; Weersma, Rinse K.

    2011-01-01

    Background: Primary sclerosing cholangitis is a chronic cholestatic liver disease. An immune aetiology is suggested by associations between PSC and inflammatory bowel disease. Data on concomitant prevalence of other immune-mediated diseases is limited. Aim: To assess the prevalence of concomitant

  10. 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

  11. Incidence, severity, prognostic significance of thrombocytopenia in malaria

    Directory of Open Access Journals (Sweden)

    Bezwada Srinivasa Rao

    2015-01-01

    Full Text Available Background: Malaria is an infectious disease caused by plasmodium parasite. P. falciparum account for majority of morbidity and mortality. Thrombocytopenia and anaemia are the most frequently associated hematological complications in malaria. The low platelet count together with acute febrile syndrome emerged as the strongest predictor of malaria a finding that is frequent and present even before anemia and splenomegaly sets in. Severe thrombocytopenia is a good predictor of poor prognosis than mild and moderate thrombocytopenia. The aim is to study the incidence, severity, prognostic significance of thrombocytopenia in malaria. Methods: This was an observational and prospective study. The study enrolled 100 patients with thrombocytopenia and fever who were proven to have malaria either by peripheral smear or Quantitative Buffy Coat (QBC test or malarial antigen assay were included in the study and patients with thrombocytopenia due to other causes were excluded from the study. Platelet count was estimated on a fully automated quantitative analyzer. All the 100 patients were followed during the hospital stay and upto discharge or till the outcome. Results: The incidence of thrombocytopenia was 73% indicating a common association in malaria. Complicated malaria was observed in 58.80% of P. falciparum infection whereas 66% of P. vivax infection was associated with uncomplicated malaria. Severe thrombocytopenia showed positive correlation with severity of malaria. Thrombocytopenic patients with effective anti-malarial treatment showed 95.90% recovery and 3 patients 4.10% had mortality. Patients with severe thrombocytopenia were 8.5 times more likely to have complicated malaria with P <0.001 according to student and lsquo;t' test. Conclusion: Thrombocytopenia is the most common hematological finding in malaria. Severe thrombocytopenia showed positive correlation with complicated malaria and a good predictor of poor prognosis. Patients with classical

  12. 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.

  13. Nonregenerative immune-mediated anemia associated with a diffuse large B-cell lymphoma in a captive jaguar (Panthera onca).

    Science.gov (United States)

    Keresztes, Monika A; Henrich, Manfred; Baloi, Penelope; Gerst, Sascha; Rudnick, Jens-Christian; Langenstein, Judith; Moritz, Andreas; Bauer, Natali

    2017-09-13

    An 18-year-old male castrated jaguar (Panthera onca) was presented with anorexia and continuous bleeding from the oral cavity after a history of fighting with the partner animal. Clinical evaluation revealed ulcerating lesions on the gingiva and hard palate and a hematoma on the tongue. Computed tomography of the head and endoscopic examination of the esophagus and stomach were unremarkable. Hematology and clinical chemistry revealed severe nonregenerative anemia, mild thrombocytopenia, and moderate azotemia. Several PCRs for feline hemotropic mycoplasmas (Mycoplasma haemofelis, M heamominutium, M turicensis), Babesia felis, and Bartonella spp., as well as an FeLV antigen test were negative. The cytologic examination of a bone marrow aspirate was consistent with ineffective erythropoiesis, most likely due to immune-mediated destruction of the erythroid precursor cells. Prednisolone therapy was initiated (1.25 mg/kg/day), and the CBC returned to normal 16 days after the initiation of the therapy. Anemia relapsed after 4 months and severe splenomegaly was noted. A repeat bone marrow aspirate revealed active erythropoiesis in the presence of erythroid precursor phagocytosis suggesting an immune-mediated process. Splenic fine-needle aspiration and tissue biopsies were taken, and all findings including histology and immunohistochemistry were consistent with a diffuse large B-cell lymphoma (DLBCL). Five days later, the clinical condition deteriorated and the jaguar died. Histopathology following necropsy showed infiltration with neoplastic lymphoblasts in the spleen, liver, and abdominal lymph nodes. This case report describes a nonregenerative immune-mediated anemia associated with a DLBCL in a jaguar. © 2017 American Society for Veterinary Clinical Pathology.

  14. Urine metabolome profiling of immune-mediated inflammatory diseases

    OpenAIRE

    Alonso, Arnald; Julià, Antonio; Vinaixa, Maria; Domènech, Eugeni; Fernández-Nebro, Antonio; Cañete, Juan D.; Ferrándiz, Carlos; Tornero, Jesús; Gisbert, Javier P; Nos, Pilar; Casbas, Ana Gutiérrez; Puig, Lluís; González-Álvaro, Isidoro; Pinto-Tasende, José A.; Blanco, Ricardo

    2016-01-01

    Background Immune-mediated inflammatory diseases (IMIDs) are a group of complex and prevalent diseases where disease diagnostic and activity monitoring is highly challenging. The determination of the metabolite profiles of biological samples is becoming a powerful approach to identify new biomarkers of clinical utility. In order to identify new metabolite biomarkers of diagnosis and disease activity, we have performed the first large-scale profiling of the urine metabolome of the six most pre...

  15. Maternal and fetal outcome among pregnant women presenting with thrombocytopenia

    Directory of Open Access Journals (Sweden)

    Vikrant Chauhan

    2016-08-01

    Conclusions: In pregnancy with thrombocytopenia, gestational thrombocytopenia is the commonest and benign condition which does not alter the obstetrical management. Still a vigil should be kept on maternal platelet count in antenatal period to prevent unfavorable outcome in serious conditions that may require specific and urgent management (HELLP syndrome, severe pre-eclampsia, TTP, HUS and acute fatty liver of pregnancy. [Int J Reprod Contracept Obstet Gynecol 2016; 5(8.000: 2736-2743

  16. 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. M

  17. Infection and immune-mediated meningococcal-associated arthritis: combination features in the same patient

    Directory of Open Access Journals (Sweden)

    Karim Yaqub Ibrahim

    2012-04-01

    Full Text Available We present a case of a 16-year-old male patient with sudden-onset, rash, arthritis and meningitis by Neisseria meningitidis one week after an acute upper respiratory infection. On the 10th day of treatment followed by neurological and arthritis clinical improvement, he presented once again a tender and swollen left knee with a moderate effusion, and active and passive range of motion was severely limited secondary to pain, and when he was submitted to surgical drainage and synovial fluid analysis he showed inflammatory characteristics. A non-steroidal anti-inflammatory drug was taken for five days with complete improvement of symptoms. The case is notable for its combination of features of septic and immune-mediated arthritis, which has rarely been reported in the same patient.

  18. Dermatomyositis, polymyositis and immune-mediated necrotising myopathies.

    Science.gov (United States)

    Luo, Yue-Bei; Mastaglia, Frank L

    2015-04-01

    Dermatomyositis, polymyositis and immune-mediated necrotising myopathy are major forms of idiopathic inflammatory myopathy. We review here recent developments in understanding the pathology and pathogenesis of these diseases, and characterisation of autoantibody biomarkers. Dermatomyositis is traditionally considered to be due to a complement-mediated microangiopathy but the factors responsible for complement activation remain uncertain. Recent studies have emphasised the importance of the type I interferon pathway in the pathogenesis of the disease and have identified autoantibodies with specificities for different clinical subgroups of patients. Polymyositis is characterised by a cytotoxic T cell response targeting as yet unidentified muscle antigens presented by MHC Class I molecules, and can occur in isolation but is more often part of a multi-systemic overlap syndrome. The immune-mediated necrotising myopathies are heterogeneous and are distinguished from polymyositis by the sparseness of inflammatory infiltrates and recognition of an association with specific autoantibodies such as anti-SRP and anti-HMGCR in many cases. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis.

  19. 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.

  20. 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......, and certain exposures may have detrimental effects in the earliest life, but no or even beneficial effects later. The human microbiome and infections are candidates as intermediary in the interaction between the host and the environment. The evidence seems inconsistent as infections as well as particular...... colonization patterns in neonates drive both short-term and long-term asthma symptoms, while, on the other hand, the composition of the microbiome in early life may protect against asthma and allergy in later life. This apparent contradiction may be explained by a deeper disease heterogeneity than we...

  1. Characteristic Cytokine and Chemokine Profiles in Encephalitis of Infectious, Immune-Mediated, and Unknown Aetiology.

    Directory of Open Access Journals (Sweden)

    Benedict D Michael

    Full Text Available Encephalitis is parenchymal brain inflammation due to infectious or immune-mediated processes. However, in 15-60% the cause remains unknown. This study aimed to determine if the cytokine/chemokine-mediated host response can distinguish infectious from immune-mediated cases, and whether this may give a clue to aetiology in those of unknown cause.We measured 38 mediators in serum and cerebrospinal fluid (CSF of patients from the Health Protection Agency Encephalitis Study. Of serum from 78 patients, 38 had infectious, 20 immune-mediated, and 20 unknown aetiology. Of CSF from 37 patients, 20 had infectious, nine immune-mediated and eight unknown aetiology.Heat-map analysis of CSF mediator interactions was different for infectious and immune-mediated cases, and that of the unknown aetiology group was similar to the infectious pattern. Higher myeloperoxidase (MPO concentrations were found in infectious than immune-mediated cases, in serum and CSF (p = 0.01 and p = 0.006. Serum MPO was also higher in unknown than immune-mediated cases (p = 0.03. Multivariate analysis selected serum MPO; classifying 31 (91% as infectious (p = 0.008 and 17 (85% as unknown (p = 0.009 as opposed to immune-mediated. CSF data also selected MPO classifying 11 (85% as infectious as opposed to immune-mediated (p = 0.036. CSF neutrophils were detected in eight (62% infective and one (14% immune-mediated cases (p = 0.004; CSF MPO correlated with neutrophils (p<0.0001.Mediator profiles of infectious aetiology differed from immune-mediated encephalitis; and those of unknown cause were similar to infectious cases, raising the hypothesis of a possible undiagnosed infectious cause. Particularly, neutrophils and MPO merit further investigation.

  2. 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.

  3. 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.

  4. Delayed profound thrombocytopenia presenting 7 days after use of abciximab (ReoPro).

    Science.gov (United States)

    Sharma, Sanjiv; Bhambi, Brijesh; Nyitray, William; Sharma, Geetanjali; Shambaugh, Shawn; Antonescu, Adrian; Shukla, Pankaj; Denny, Eileen

    2002-01-01

    A case of a 65-year-old woman presenting with delayed profound thrombocytopenia 7 days after the use of abciximab (ReoPro) in the setting of percutaneous coronary intervention is described. The patient had normal platelet counts for the first 24 hours after the use of abciximab (ReoPro). She presented with petechiae and profound thrombocytopenia 1 week later. The patient was treated successfully with a platelet transfusion and recovered uneventfully. Profound thrombocytopenia occurs acutely within the first few hours after abciximab (ReoPro) use, so this case was unique in that the profound thrombocytopenia presented 1 week after use of abciximab (ReoPro).

  5. Refractory primary immune thrombocytopenia with subsequent del(5q) MDS: complete remission of both after lenalidomide.

    Science.gov (United States)

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

    2017-01-04

    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 features in bone marrow. He remained severely thrombocytopenic, which suggests ongoing immune mediated platelet destruction. After two 3 week cycles of low-dose lenalidomide, complete cytogenetic remission and complete normalisation of platelet count were observed. This suggests that lenalidomide may be a viable treatment option for ITP in the presence of del(5q) not responding to standard treatments.

  6. 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.

  7. [Thrombocytopenia induced by heparin. Diagnosis, treatment, physiopathology: current concepts].

    Science.gov (United States)

    Gruel, Y; Drouet, L

    1986-01-01

    Iatrogenic thrombocytopenia is a rare, but severe complication of treatments with heparin and heparinoids. Mean temporary thrombocytopenia failing to show any complications are usually diagnosed as quite different from acute and delayed thrombocytopenia of which severity depends mainly on thrombotic symptoms demonstrated in 65 p. 100 of cases; the initial evolution of an average thrombocytopenia is not easy to diagnose; it may as well exist a connection between the two diseases, from a physiopathogenic point of view. The diagnosis of severe thrombocytopenia depends:--clinically, on the initial data, delayed as compared with the heparin treatment beginning and existence of arterial and/or venous thrombosis;--biologically, by demonstrating an aggregating activity for platelets in presence of heparin, in the patient plasma. Such an activity requires the suppression of standard heparinotherapy as well as the choice of substitutive anticoagulant treatment in case of evolutive thrombosis. Low molecular weight heparins are prescribed only if in vitro tests of platelet aggregation with the patient's plasma are negative. Antivitamins K are to be used as soon as possible alone or combined with heparin fractions. Antiaggregants are prescribed alone, above all in case of isolated thrombocytopenia and combined with AVK. Treatment of thrombotic complications depends on surgical disobstruction if arterial thrombosis, and use of fibrinolytics if pulmonary embolisms. The acute reaction of some thrombocytopenia to heparin as well as therapeutic difficulties demonstrate the efficiency of an early diagnosis performed thanks to systematic platelet numerations during the first 15 days of a treatment with heparin, as well as to the prevention along with systematic association with aspirin, especially if replaced with AVK.

  8. Factors associated with thrombocytopenia in severe leptospirosis (Weil's disease

    Directory of Open Access Journals (Sweden)

    Elizabeth F. Daher

    2014-02-01

    Full Text Available OBJECTIVE: This study was conducted to investigate factors associated with thrombocytopenia in a large cohort of patients with leptospirosis in an endemic area. METHODS: This retrospective study included 374 consecutive patients with leptospirosis who were admitted to tertiary hospitals in Fortaleza, Brazil. All patients had a diagnosis of severe leptospirosis (Weil's disease. Acute kidney injury was defined according to the RIFLE criteria. Thrombocytopenia was defined as a platelet count <100,000/mm3. RESULTS: A total of 374 patients were included, with a mean age of 36.1±15.5 years, and 83.4% were male. Thrombocytopenia was present at the time of hospital admission in 200 cases (53.5%, and it developed during the hospital stay in 150 cases (40.3%. The patients with thrombocytopenia had higher frequencies of dehydration (53% vs. 35.3%, p = 0.001, epistaxis (5.7% vs. 0.8%, p = 0.033, hematemesis (13% vs. 4.6%, p = 0.006, myalgia (91.5% vs. 84.5%, p = 0.038, hematuria (54.8% vs. 37.6%, p = 0.011, metabolic acidosis (18% vs. 9.2%, p = 0.016 and hypoalbuminemia (17.8% vs. 7.5%, p = 0.005. The independent risk factors associated with thrombocytopenia during the hospital stay were lengthy disease (OR: 1.2, p = 0.001 and acute kidney injury (OR: 6.6, p = 0.004. Mortality was not associated with thrombocytopenia at admission (12.5% vs. 12.6%, p = 1.000 or during the hospital stay (12.6% vs. 11.3%, p = 0.748. CONCLUSIONS: Thrombocytopenia is a frequent complication in leptospirosis, and this condition was present in more than half of patients at the time of hospital admission. Lengthy disease and acute kidney injury are risk factors for thrombocytopenia. There was no significant association between thrombocytopenia and mortality.

  9. Fetal/neonatal alloimmune thrombocytopenia.

    Science.gov (United States)

    Sachs, Ulrich J

    2013-01-01

    In fetal/neonatal alloimmune thrombocytopenia (FNAIT), antibodies against paternal antigens present on fetal platelets are produced by the mother. These antibodies will cross the placenta and can cause thrombocytopenia of the unborn. One severe consequence of thrombocytopenia is intracranial bleeding which may lead to death or severe sequelae. FNAIT index cases in one family are usually detected at birth only since antenatal screening programmes have not been installed so far. Subsequent pregnancies of immunized mothers may require special diagnostic and prophylactic interventions, and interdisciplinary counselling and treatment involving obstetricians, pediatricians and immunohematologists may prove useful for optimized care. This short review covers pathogenesis, clinical presentation, diagnostic, and therapeutic options in FNAIT.

  10. 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

  11. 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

  12. Significance of Anti-cyclic Citrullinated Peptide Autoantibodies in Immune-mediated Inflammatory Skin Disorders with and without Arthritis.

    Science.gov (United States)

    Grover, Chander; Kashyap, Bineeta; Daulatabad, Deepashree; Dhawan, Amit; Kaur, Iqbal R

    2016-01-01

    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. To determine the correlation between anti-CCP, RF, and CRP in immune-mediated inflammatory skin diseases. 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. 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 found to be statistically significant. Although anti-CCP, RF, and CRP levels are

  13. 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

  14. Significance of Anti-cyclic Citrullinated Peptide Autoantibodies in Immune-mediated Inflammatory Skin Disorders with and without Arthritis

    Science.gov (United States)

    Grover, Chander; Kashyap, Bineeta; Daulatabad, Deepashree; Dhawan, Amit; Kaur, Iqbal R

    2016-01-01

    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 found to be

  15. OUTCOME OF NEONATES WITH THROMBOCYTOPENIA

    Directory of Open Access Journals (Sweden)

    Sharangouda

    2014-04-01

    Full Text Available OBJECTIVE: To determine etiology, onset, clinical features and outcome of neonates with thrombocytopenia. METHODS: 140 neonates having bleeding or having platelet count (<1.5lakhs/µl were selected from those admitted to NICU’S attached to MR Medical College, Gulbarga. Initial platelet count was done on admission and counts were repeated 12 hours after any therapeutic intervention. OBSERVATION AND RESULTS: Severe thrombocytopenia (<50000/µl was present in 8.5%, moderate (50, 000-1, 00, 000/µl in 17%. Majority (45.33% were preterm and the major cause was sepsis in 51.3%.Mucosal bleed was the most common presentation. Mortality was 37% in severe and 3.9% in moderate thrombocytopenia group. CONCLUSION: Significant association is observed with maternal PIH, Late onset sepsis, NEC and sepsis with DIC .Prematurity, IUGR, Birth asphyxia were common associated morbidities. Severe thrombocytopenia in sick neonates, in NICU, is a poor prognostic indicator.

  16. 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.

  17. 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

    2017-05-27

    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.

  18. Diagnosis and management of neonatal thrombocytopenia.

    Science.gov (United States)

    Holzhauer, Susanne; Zieger, Barbara

    2011-12-01

    Thrombocytopenia is the most common haematological abnormality in newborns admitted to neonatal care units and serves as an important indicator of underlying pathological processes of mother or child. In most cases thrombocytopenia is mild to moderate and resolves within the first weeks of life without any intervention. However, in some neonates thrombocytopenia is severe or may reflect an inborn platelet disorder. As clinical course and outcome of thrombocytopenia depend on the aetiology of thrombocytopenia, an appropriate work-up is essential to guide therapy in neonates with thrombocytopenia and to avoid severe bleeding.

  19. Romiplostim in thrombocytopenia treatment after allogeneic bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    I. A. Lisukov

    2014-07-01

    Full Text Available Persistent thrombocytopenia is a frequent complication after allogeneic bone marrow transplantation (BMT. The major causes of thrombocytopenia include accelerated platelet destruction by antiplatelet antibodies, microangiopathy, viral infection, drug toxicity,graft`s hypofunction with insufficient production of platelets from megakaryocytes. We have evaluated an efficacy of TPO-receptor agonistromiplostim in treatment of 3 patients with refractory thrombocytopenia after allogeneic BMT. The first 30 years old patient received haploidentical allogeneic stem cell transplantation for refractory AML relapse. He developed graft hypofunction due to CMV infection, acute GVHD and thrombotic thrombocytopenic purpura (TTP with platelet counts 5 × 109/l and bleeding complications. After bone marrow “boost” the patient received romiplostim 1 mkg/kg weekly during 2 weeks and 4 mkg/kg during another 2 weeks. Upon reaching platelet counts 50 × 109/l the romiplostim was stopped, but platelet count decreased to 5–7 × 109/l and romiplostim was administered in dose of 4 mkg/kg weekly during 5 weeks. Platelet counts have achieved 150 × 109/l and thrombocytopenia during further follow-up was not revealed. The second 19 years old AML patient received haploidentical allogeneic stem cell transplantation for second remission consolidation. He developed thrombocytopenia (10 × 109/l due to CMV infection and severe TTP. He received romiplostim 4 mkg/kg weekly and 5 weeks later platelet counts was 50 × 109/l. The administration of romiplostim was allowed to avoid bleeding complications and transfusion dependency. The third 18 years old ALL patient received MUD allogeneic stem cell transplantation for second remission consolidation. He developed profound thrombocytopenia (5 × 109/l with severe hemorrhagic complications and platelet transfusions refractory due to TTP and acute GVHD. He received one dose of romiplostim 1 mkg/kg and two doses of 3 mkg

  20. Romiplostim in thrombocytopenia treatment after allogeneic bone marrow transplantation

    Directory of Open Access Journals (Sweden)

    I. A. Lisukov

    2012-01-01

    Full Text Available Persistent thrombocytopenia is a frequent complication after allogeneic bone marrow transplantation (BMT. The major causes of thrombocytopenia include accelerated platelet destruction by antiplatelet antibodies, microangiopathy, viral infection, drug toxicity,graft`s hypofunction with insufficient production of platelets from megakaryocytes. We have evaluated an efficacy of TPO-receptor agonistromiplostim in treatment of 3 patients with refractory thrombocytopenia after allogeneic BMT. The first 30 years old patient received haploidentical allogeneic stem cell transplantation for refractory AML relapse. He developed graft hypofunction due to CMV infection, acute GVHD and thrombotic thrombocytopenic purpura (TTP with platelet counts 5 × 109/l and bleeding complications. After bone marrow “boost” the patient received romiplostim 1 mkg/kg weekly during 2 weeks and 4 mkg/kg during another 2 weeks. Upon reaching platelet counts 50 × 109/l the romiplostim was stopped, but platelet count decreased to 5–7 × 109/l and romiplostim was administered in dose of 4 mkg/kg weekly during 5 weeks. Platelet counts have achieved 150 × 109/l and thrombocytopenia during further follow-up was not revealed. The second 19 years old AML patient received haploidentical allogeneic stem cell transplantation for second remission consolidation. He developed thrombocytopenia (10 × 109/l due to CMV infection and severe TTP. He received romiplostim 4 mkg/kg weekly and 5 weeks later platelet counts was 50 × 109/l. The administration of romiplostim was allowed to avoid bleeding complications and transfusion dependency. The third 18 years old ALL patient received MUD allogeneic stem cell transplantation for second remission consolidation. He developed profound thrombocytopenia (5 × 109/l with severe hemorrhagic complications and platelet transfusions refractory due to TTP and acute GVHD. He received one dose of romiplostim 1 mkg/kg and two doses of 3 mkg

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

    Science.gov (United States)

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

    2016-01-01

    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 region. Expression QTL studies have shown that these variants affect disease mainly by regulating gene expression. We discuss recent findings on shared genetic loci between infectious and immune-mediated diseases and provide potential clues to explore genetic associations in the context of these infectious agents. We propose that the interdisciplinary studies (genetics-genomics-immunology-infection-bioinformatics) are the future post-GWAS approaches to advance our understanding of the pathogenesis of immune-mediated diseases. PMID:25458995

  2. Subcutaneous immunoglobulins in the treatment of chronic immune-mediated neuropathies

    Science.gov (United States)

    Leussink, Verena I.; Hartung, Hans-Peter; Kieseier, Bernd C.; Stettner, Mark

    2016-01-01

    Intravenous immunoglobulins represent an established therapy for the treatment of chronic immune-mediated neuropathies, specifically chronic inflammatory demyelinating polyradiculoneuropathies (CIDPs) as well as multifocal motor neuropathies (MMNs). For the treatment of antibody deficiency syndromes, subcutaneous immunoglobulins (SCIgs) have represented a mainstay for decades. An emerging body of evidence suggests that SCIg might also exhibit clinical efficacy in CIDP and MMN. This article reviews the current evidence for clinical effectiveness, as well as safety of SCIg for the treatment of immune-mediated neuropathies, and addresses remaining open questions in this context. We conclude that despite the need for controlled long-term studies to demonstrate long-term efficacy of SCIg in immune-mediated neuropathies, SCIg may already represent a potential therapeutic alternative for selected patients. PMID:27366241

  3. Subcutaneous immunoglobulins in the treatment of chronic immune-mediated neuropathies.

    Science.gov (United States)

    Leussink, Verena I; Hartung, Hans-Peter; Kieseier, Bernd C; Stettner, Mark

    2016-07-01

    Intravenous immunoglobulins represent an established therapy for the treatment of chronic immune-mediated neuropathies, specifically chronic inflammatory demyelinating polyradiculoneuropathies (CIDPs) as well as multifocal motor neuropathies (MMNs). For the treatment of antibody deficiency syndromes, subcutaneous immunoglobulins (SCIgs) have represented a mainstay for decades. An emerging body of evidence suggests that SCIg might also exhibit clinical efficacy in CIDP and MMN. This article reviews the current evidence for clinical effectiveness, as well as safety of SCIg for the treatment of immune-mediated neuropathies, and addresses remaining open questions in this context. We conclude that despite the need for controlled long-term studies to demonstrate long-term efficacy of SCIg in immune-mediated neuropathies, SCIg may already represent a potential therapeutic alternative for selected patients.

  4. High ultrasound variability in chronic immune-mediated neuropathies. Review of the literature and personal observations.

    Science.gov (United States)

    Padua, L; Paolasso, I; Pazzaglia, C; Granata, G; Lucchetta, M; Erra, C; Coraci, D; De Franco, P; Briani, C

    2013-12-01

    Chronic immune-mediated neuropathies show high clinical variability. Diagnosis is based on clinical and neurophysiological studies, but recently ultrasound (US) of peripheral nerves has been shown to provide useful morphological information. US has already been shown to crucially influence diagnosis and clinical care in entrapment neuropathies, in traumatic nerve lesions and in tumors. The role of US in the evaluation of polyneuropathies is still not clearly defined, but increasing attention has recently been focused on the immune-mediated neuropathies and specific US measures (namely the intra- and inter-nerve cross-sectional area variability) have been developed. The aim of the current paper is to make a review of the available nerve US studies and provide data from personal observations in the most common chronic immune-mediated neuropathies. Copyright © 2013 Elsevier Masson SAS. All rights reserved.

  5. 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.

  6. 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

  7. 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 b...

  8. 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

  9. 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

  10. Three cases of immune-mediated adnexal skin disease treated with cyclosporin.

    Science.gov (United States)

    Noli, Chiara; Toma, Stefano

    2006-02-01

    Cyclosporin is currently considered a new and interesting drug in veterinary dermatology for the treatment of immune-mediated skin diseases, and a safe and effective alternative to immunosuppressive therapy with glucocorticoids. The authors report a case of granulomatous folliculitis and furunculosis and of sebaceous adenitis in two cats and a case of alopecia areata in a dog, successfully controlled with cyclosporin.

  11. Immune-mediated hemolytic anemia associated with trimethoprim-sulphamethoxazole administration in a horse.

    OpenAIRE

    Thomas, H L; Livesey, M A

    1998-01-01

    A 10-year-old, thoroughbred gelding was administered sulphonamide drugs during surgical treatment of guttural pouch mycosis. The horse became anemic and a diagnosis of immune-mediated hemolytic anemia was made after other causes of anemia had been ruled out. The anemia resolved after the drugs were withdrawn.

  12. Effect of Danggui Buxue Tang on immune-mediated aplastic anemia bone marrow proliferation mice.

    Science.gov (United States)

    Yang, Xian; Huang, Chong-Gang; Du, Shou-Ying; Yang, Shui-Ping; Zhang, Xue; Liu, Jian-Yi; Xian-QinLuo; Xu, Jia-Hong

    2014-04-15

    To investigate the pharmacological effects of Danggui Buxue Tang (DBT) on immune-mediated aplasia anemia mice. The model of immune-mediated aplasia anemia mice was induced by means of (60)Co γ-ray irradiation and mixed cells of thymus and lymphnode of DBA/2 mice infusion through tail vein, the parameters tested indices were as following: blood picture, bone marrow nucleated cell count (BMNC), murine colony-forming unit-megakaryocytes (CFU-GM) of bone marrow cells, murine colony-forming unit-erthroid (CFU-E) and burst forming unit-erythroid (BFU-E). The results showed that DBT could not only withstand significantly decreation of blood cells by immune-mediated, but also stimulate on the growth of bone marrow colony cell and increase the weight of hemopoietic progenitor of bone marrow. Therefore, DBT had an obvious treat effect on immune-mediated aplasia anemia models mice. Copyright © 2013 Elsevier GmbH. All rights reserved.

  13. Autoimmunity : Break-through in the diagnosis and treatment of immune-mediated inflammatory diseases

    NARCIS (Netherlands)

    Kroese, Frans G. M.; Baeten, Dominique; Huizinga, Tom W. J.

    2014-01-01

    The study of fundamental mechanisms of autoimmunity has been instrumental to clinical progress in the diagnosis and treatment of a range of immune-mediated inflammatory disorders. Dutch immunology has made major contributions to these developments, ranging from fundamental studies on immune cells, a

  14. Early intervention in psoriasis and immune-mediated inflammatory diseases: A hypothesis paper

    NARCIS (Netherlands)

    Girolomoni, G.; Griffiths, C.E.; Krueger, J.; Nestle, F.O.; Nicolas, J.F.; Prinz, J.C.; Puig, L.; Stahle, M.; Kerkhof, P.C.M. van de; Allez, M.; Emery, P.; Paul, C.

    2015-01-01

    Psoriasis is an immune-mediated inflammatory disease (IMID) which may have a major impact on a patient's life, especially when the disease is moderate to severe. There is evidence that treatment of psoriasis during the first years is conservative and frequently based on topical agents which rarely c

  15. Childhood immune thrombocytopenia: Clinical presentation and management

    OpenAIRE

    Faki Osman, Mohamed El

    2012-01-01

    Immune thrombocytopenia (ITP) is an acquired hematological disorder that is developed secondary to the production of auto-antibodies against platelets leading to isolated thrombocytopenia, in the absence of other causes of thrombocytopenia such as drugs, infections, malignancy, or other autoimmune diseases [1–6]. ITP commonly affects children between one and seven years of age. Severe life threatening bleeding is rare (0.2–0.9%) [7–12]. Childhood primary ITP usually runs a benign, self-limiti...

  16. Eptifibatide-induced thrombocytopenia: with thrombosis and disseminated intravascular coagulation immediately after left main coronary artery percutaneous coronary angioplasty.

    Science.gov (United States)

    Tempelhof, Michael W; Benzuly, Keith H; Fintel, Dan; Krichavsky, Marc Z

    2012-01-01

    Early clinical trials of eptifibatide did not show a significant association between eptifibatide and the development of thrombocytopenia, thrombosis, or disseminated intravascular coagulation. However, more recent literature has suggested a significant association between eptifibatide and the development of thrombocytopenia and thrombosis. Although the true incidence and the pathophysiology of these associations are unknown, the development of these events can be life-threatening. Herein, we describe the case of a patient who experienced acute onset of profound thrombocytopenia, developing thrombosis, pulmonary emboli, and disseminated intravascular coagulation. This paper adds to the few previous reports of cases that suggested an association between thrombocytopenia, thrombosis, and the administration of eptifibatide. To the best of our knowledge, this is the first case report in the medical literature that associates the new onset of thrombocytopenia, thrombosis, and disseminated intravascular coagulation with the administration of eptifibatide. We also provide a subject review.

  17. 急性心力衰竭应用主动脉内球囊反搏患者血小板减少因素分析%Cause analysis of thrombocytopenia in acute heart failure implanted with intra-aortic balloon pump

    Institute of Scientific and Technical Information of China (English)

    房芳; 李宇

    2016-01-01

    Objective To explore the causes of thrombocytopenia in acute heart failure (AHF) implanted with intra-aortic balloon pump (IABP).Methods Totally 50 cases with AHF implanted with IABP from November 2011 to November 2013 were retrospective enrolled.The time duration of IABP implantion and change of thrombocyte were recorded;the correlations of thrombocytopenia with disease type,size of ballon,gender were analyzed,the influence of thrombocytopenia on hospital mortality rate were assessed.Results The time duration of IABP implantion was (181 ±34) h (32.4-1 136.5 h).There was 27 patients with thrombocytopenia (mild:15 cases,moderate:9 cases,severe:3 cases),the time of the least platelet count was(100 ± 10) h.The incidence of thrombocytopenia in patients with acute myocardial infarction induced AHF was not significantly different from that in patients with other causes induced AHF [51.6% (16/31) vs 57.9% (11/19)] (P > 0.05).The incidence of thrombocytopenia was significantly lower in patients applied with 30 CC balloon than that in patients applied with 40 CC balloon [31.3% (5/16) vs 64.7% (22/34)],was significantly lower in males than that in femals [46.2% (18/39) vs 81.8% (9/11)] (P < 0.05).In 50 patients,17 cases was dead in hospital;the mortality rate in patients with thrombocytopenia was significantly higher than that in patients without thrombocytopenia [48.1% (13/27) vs 17.4% (4/23)] (P <0.05).Conclusion Thrombocytopenia can increase the morality rate in acute heartfailure patients implanted with IABP,which is correlated with the size of implanted balloon and gender.%目的 探讨急性心力衰竭应用主动脉内球囊反搏(IABP)患者血小板减少的原因.方法 回顾性选取首都医科大学附属北京安贞医院2011年11月至2013年11月收治的应用IABP的急性心力衰竭患者50例,记录应用IABP的时间以及应用后患者的血小板变化情况;分析血小板减少和疾病类型、球囊大小、性别的关

  18. PPARγ antagonist attenuates mouse immune-mediated bone marrow failure by inhibition of T cell function.

    Science.gov (United States)

    Sato, Kazuya; Feng, Xingmin; Chen, Jichun; Li, Jungang; Muranski, Pawel; Desierto, Marie J; Keyvanfar, Keyvan; Malide, Daniela; Kajigaya, Sachiko; Young, Neal S

    2016-01-01

    Acquired aplastic anemia is an immune-mediated disease, in which T cells target hematopoietic cells; at presentation, the bone marrow is replaced by fat. It was reported that bone marrow adipocytes were negative regulators of hematopoietic microenvironment. To examine the role of adipocytes in bone marrow failure, we investigated peroxisomal proliferator-activated receptor gamma, a key transcription factor in adipogenesis, utilizing an antagonist of this factor called bisphenol-A-diglycidyl-ether. While bisphenol-A-diglycidyl-ether inhibited adipogenesis as expected, it also suppressed T cell infiltration of bone marrow, reduced plasma inflammatory cytokines, decreased expression of multiple inflammasome genes, and ameliorated marrow failure. In vitro, bisphenol-A-diglycidyl-ether suppressed activation and proliferation, and reduced phospholipase C gamma 1 and nuclear factor of activated T-cells 1 expression, as well as inhibiting calcium flux in T cells. The in vivo effect of bisphenol-A-diglycidyl-ether on T cells was confirmed in a second immune-mediated bone marrow failure model, using different strains and non-major histocompatibility antigen mismatched: bisphenol-A-diglycidyl-ether ameliorated marrow failure by inhibition of T cell infiltration of bone marrow. Our data indicate that peroxisomal proliferator-activated receptor gamma antagonists may attenuate murine immune-mediated bone marrow failure, at least in part, by suppression of T cell activation, which might hold implications in the application of peroxisomal proliferator-activated receptor gamma antagonists in immune-mediated pathophysiologies, both in the laboratory and in the clinic. Genetically "fatless" mice developed bone marrow failure with accumulation of marrow adipocytes in our model, even in the absence of body fat, suggesting different mechanisms of systematic and marrow adipogenesis and physiologic versus pathophysiologic fat accumulation.

  19. Disseminated Scedosporium prolificans infection in a Labrador retriever with immune mediated haemolytic anaemia

    Directory of Open Access Journals (Sweden)

    Amanda Taylor

    2014-10-01

    Full Text Available Disseminated scedosporiosis is rare in dogs and is usually reported in German Shepherds with suspected heritable immunodeficiency. This is the first report of disseminated scedosporiosis due to Scedosporium prolificans in a Labrador retriever dog that was receiving immunosuppressive drug therapy for treatment of immune-mediated haemolytic anaemia. Despite cessation of immunosuppressive medications and an initial response to aggressive treatment with voriconazole and terbinafine the dog developed progressive disease with neurological signs necessitating euthanasia six months from diagnosis.

  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. Early childhood poverty, immune-mediated disease processes, and adult productivity.

    Science.gov (United States)

    Ziol-Guest, Kathleen M; Duncan, Greg J; Kalil, Ariel; Boyce, W Thomas

    2012-10-16

    This study seeks to understand whether poverty very early in life is associated with early-onset adult conditions related to immune-mediated chronic diseases. It also tests the role that these immune-mediated chronic diseases may play in accounting for the associations between early poverty and adult productivity. Data (n = 1,070) come from the US Panel Study of Income Dynamics and include economic conditions in utero and throughout childhood and adolescence coupled with adult (age 30-41 y) self-reports of health and economic productivity. Results show that low income, particularly in very early childhood (between the prenatal and second year of life), is associated with increases in early-adult hypertension, arthritis, and limitations on activities of daily living. Moreover, these relationships and particularly arthritis partially account for the associations between early childhood poverty and adult productivity as measured by adult work hours and earnings. The results suggest that the associations between early childhood poverty and these adult disease states may be immune-mediated.

  2. The diagnostic and prognostic value of neurofilament heavy chain levels in immune-mediated optic neuropathies.

    Science.gov (United States)

    Petzold, Axel; Plant, Gordon T

    2012-01-01

    Background. Loss of visual function differs between immune-mediated optic neuropathies and is related to axonal loss in the optic nerve. This study investigated the diagnostic and prognostic value of a biomarker for neurodegeneration, the neurofilament heavy chain (NfH) in three immune-mediated optic neuropathies. Methods. A prospective, longitudinal study including patients with optic neuritis due to multiple sclerosis (MSON, n = 20), chronic relapsing inflammatory optic neuritis (CRION, n = 19), neuromyelitis optica (NMO, n = 9), and healthy controls (n = 28). Serum NfH-SMI35 levels were quantified by ELISA. Findings. Serum NfH-SMI35 levels were highest in patients with NMO (mean 0.79 ± 1.51 ng/mL) compared to patients with CRION (0.13 ± 0.16 ng/mL, P = 0.007), MSON (0.09 ± 0.09, P = 0.008), and healthy controls (0.01 ± 0.02 ng/mL, P = 0.001). High serum NfH-SMI35 levels were related to poor visual outcome. Conclusions. Blood NfH-SMI35 levels are of moderate diagnostic and more important prognostic value in immune-mediated optic neuropathies. We speculate that longitudinal blood NfH levels may help to identify particular disabling events in relapsing conditions.

  3. Biology of the blood-nerve barrier and its alteration in immune mediated neuropathies.

    Science.gov (United States)

    Kanda, Takashi

    2013-02-01

    The blood-nerve barrier (BNB) is a dynamic and competent interface between the endoneurial microenvironment and the surrounding extracellular space or blood. It is localised at the innermost layer of the multilayered ensheathing perineurium and endoneurial microvessels, and is the key structure that controls the internal milieu of the peripheral nerve parenchyma. Since the endoneurial BNB is the point of entry for pathogenic T cells and various soluble factors, including cytokines, chemokines and immunoglobulins, understanding this structure is important to prevent and treat human immune mediated neuropathies such as Guillain-Barré syndrome, chronic inflammatory demyelinating polyneuropathy, POEMS (polyneuropathy, organomegaly, endocrinopathy, monoclonal protein and skin changes) syndrome and a subset of diabetic neuropathy. However, compared with the blood-brain barrier, only limited knowledge has been accumulated regarding the function, cell biology and clinical significance of the BNB. This review describes the basic structure and functions of the endoneurial BNB, provides an update of the biology of the cells comprising the BNB, and highlights the pathology and pathomechanisms of BNB breakdown in immune mediated neuropathies. The human immortalised cell lines of BNB origin established in our laboratory will facilitate the future development of BNB research. Potential therapeutic strategies for immune mediated neuropathies manipulating the BNB are also discussed.

  4. The Diagnostic and Prognostic Value of Neurofilament Heavy Chain Levels in Immune-Mediated Optic Neuropathies

    Directory of Open Access Journals (Sweden)

    Axel Petzold

    2012-01-01

    Full Text Available Background. Loss of visual function differs between immune-mediated optic neuropathies and is related to axonal loss in the optic nerve. This study investigated the diagnostic and prognostic value of a biomarker for neurodegeneration, the neurofilament heavy chain (NfH in three immune-mediated optic neuropathies. Methods. A prospective, longitudinal study including patients with optic neuritis due to multiple sclerosis (MSON, n=20, chronic relapsing inflammatory optic neuritis (CRION, n=19, neuromyelitis optica (NMO, n=9, and healthy controls (n=28. Serum NfH-SMI35 levels were quantified by ELISA. Findings. Serum NfH-SMI35 levels were highest in patients with NMO (mean 0.79±1.51 ng/mL compared to patients with CRION (0.13±0.16 ng/mL, P=0.007, MSON (0.09±0.09, P=0.008, and healthy controls (0.01±0.02 ng/mL, P=0.001. High serum NfH-SMI35 levels were related to poor visual outcome. Conclusions. Blood NfH-SMI35 levels are of moderate diagnostic and more important prognostic value in immune-mediated optic neuropathies. We speculate that longitudinal blood NfH levels may help to identify particular disabling events in relapsing conditions.

  5. Bleeding complications in immune thrombocytopenia.

    Science.gov (United States)

    Arnold, Donald M

    2015-01-01

    Bleeding manifestations in patients with immune thrombocytopenia (ITP) range from mild skin bruises to life-threatening intracranial hemorrhage (ICH). Severe bleeding is distinctly uncommon when the platelet count is >30 × 10(9)/L and usually only occurs when the platelet count falls administrative databases, the frequency of ICH in patients with ITP is ~0.5% in children and 1.5% in adults. Estimates of severe (non-ICH) bleeding are difficult to obtain because of the lack of standardized case definitions; the lack of a universally accepted, ITP-specific bleeding assessment tool; and the omission of reporting bleeding outcomes in many clinical studies. In practice, the presence of bleeding should dictate whether or not treatment is needed because many patients, especially children, can be safely managed with observation alone. Guiding principles for the management of ITP, based on the bleeding risk are: (1) Decide when treatment is needed and when it can safely be withheld; (2) for patients with chronic ITP, use the least toxic treatment at the lowest dose; (3) emergency treatment of severe thrombocytopenia-associated bleeding requires combination therapy; and (4) early aggressive therapy may result in durable platelet count responses.

  6. Venous Thromboembolism in Patients With Thrombocytopenia

    DEFF Research Database (Denmark)

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

    2017-01-01

    . OBJECTIVES: To identify VTE risk factors and describe treatment and outcome (bleeding episodes and mortality) in patients with thrombocytopenia. PATIENTS/METHODS: Patients with thrombocytopenia (platelet count ... with anticoagulants. There was no difference in bleeding incidence between cases and controls. CONCLUSIONS: Several known VTE risk factors also seems to apply in patients with thrombocytopenia. Also, patients with thrombocytopenia may be VTE risk stratified based on platelet count and comorbidities. Finally, patients......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...

  7. Refractory heparin induced thrombocytopenia with thrombosis (HITT) treated with therapeutic plasma exchange and rituximab as adjuvant therapy.

    Science.gov (United States)

    Schell, Amy M; Petras, Melissa; Szczepiorkowski, Zbigniew M; Ornstein, Deborah L

    2013-10-01

    We report a case of refractory heparin-induced thrombocytopenia with thrombosis (HITT) with prolonged thrombocytopenia and multiple thrombotic complications that failed to improve despite aggressive treatment. A 60 year old female with a prior history of venous thromboembolism was admitted with an acute pulmonary embolism, and developed HITT after several days on heparin therapy. She suffered multiple complications including bilateral venous limb gangrene, acute renal failure, and refractory thrombocytopenia, leading us to use multimodality therapy including therapeutic plasma exchange (TPE) and rituximab immunosuppression. The patient had transient improvements in her thrombocytopenia with TPE, and rituximab was added in an attempt to reduce antibody production. She eventually required bilateral limb amputation, and only after removal of the gangrenous limbs did her platelet count show sustained improvement. We discuss the possible contribution of infection to her prolonged course.

  8. A study of cytological changes in the bone marrow of patients with severe fever with thrombocytopenia syndrome.

    Directory of Open Access Journals (Sweden)

    Xing QuanTai

    Full Text Available BACKGROUND: Peripheral blood leucopenia and thrombocytopenia are the main manifestations in severe fever with thrombocytopenia syndrome (SFTS patients. However, the underlying causes are poorly understood. Therefore, we aimed to investigate cytology of bone marrow samples collected from SFTS patients. METHODS: 10 SFTS patients were identified by typical clinical manifestations, detection of peripheral blood leucopenia and thrombocytopenia, and nucleic acid-based detection of the newly identified bunyavirus. SFTS patients, along with 10 participants with acute aplastic anemia and 10 healthy volunteers were enrolled in this study after written informed consent to undergo bone marrow cytological examination. RESULTS: We observed similar bone marrow properties in SFTS patients and healthy volunteers, significantly different from the characteristics observed in acute aplastic anemia patients. CONCLUSION: Similarities between bone marrow samples collected from SFTS patients and healthy volunteers suggest that peripheral blood leucopenia and thrombocytopenia do not result from bone marrow cell plasticity.

  9. 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.

    2014-01-01

    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

  10. 2, 3, 7, 8-TCDD enhances the sensitivity of mice to concanavalin A immune-mediated liver injury

    OpenAIRE

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

    2012-01-01

    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 30µg/kg TCDD or vehicle cont...

  11. 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.

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

    NARCIS (Netherlands)

    Lisman, Ton; Porte, Robert J.

    2010-01-01

    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 coagulatio

  13. 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

  14. Pseudo-hypoproteinemia in a hyperbilirubinemic dog with immune-mediated hemolytic anemia.

    Science.gov (United States)

    Garner, Bridget C; Priest, Heather; Smith, Jo

    2014-06-01

    A 10-year-old spayed female Miniature Poodle was presented to the University of Georgia veterinary teaching hospital for evaluation of lethargy, vomiting and anorexia of 4 days' duration. Physical examination, history and a minimum database led to a diagnosis of immune-mediated hemolytic anemia accompanied by marked hyperbilirubinemia. Refractometric protein determination was within the reference interval, whereas the biuret method indicated hypoproteinemia. This discrepancy was attributed to interference of bilirubin and biliverdin with the spectrophotometric read-out of the biuret total protein assay. The albumin concentration, determined by bromcresol green, and refractometric total protein were less affected by this interference.

  15. Heparin-Induced Thrombocytopenia Antibody Test

    Science.gov (United States)

    ... Global Sites Search Help? Heparin-induced Thrombocytopenia PF4 Antibody Share this page: Was this page helpful? Also known as: Heparin-PF4 Antibody; HIT Antibody; HIT PF4 Antibody; Heparin Induced Antibody; ...

  16. Risk factors of thrombocytopenia in pregnancy

    Directory of Open Access Journals (Sweden)

    Ayisha Begam

    2017-01-01

    Conclusions: Thrombocytopenia should be evaluated by making a practice of routinely checking the platelet count and peripheral smear in early pregnancy and also in third trimester to enable early diagnosis since most cases may be asymptomatic.

  17. 肾脏病患者血小板减少症的诊治策略%Strategies of diagnosis and treatment for thrombocytopenia in patients with renal diseases

    Institute of Scientific and Technical Information of China (English)

    庄永泽

    2013-01-01

    Apart from accelerating hemostasis,promoting clotting,and maintaining the integrity of capillaries,thrombocytes possess functions of regulating the immune system including gathering leukocytes, capturing and containing pathogens,and killing infected cellular targets directly,etc.Thrombocytopenia may occur in both acute kidney injury (AKI)and chronic kidney disease (CKD)patients,but with differences in etiology and pathophysiology.Thrombocytopenia in AKI is mainly caused by infections,medicine,hemolytic-uremic syndrome (HUS),thrombotic thrombocytopenie purpura (TTP),and syndrome of hemolysis,elevated liver enzymes,and low platelets (HELLP).However,thrombocytopenia in CKD is mostly caused by autoimmune diseases, liver diseases, thrombotic microangiopathy (TMA ), idiopathic thrombocytopenic purpura (ITP),hyper-coagulation consumption,heparin-induced thrombocytopenia (HIT),drug allergies, uremia toxin,blood diseases,and disseminated intravascular coagulation (DIC ),etc.Therapy strategies include etiological treatment,pathogenesis treatment,plasmapheresis,platelet transfusions,promoting platelet formation,and symptomatic treatment.Additional attention should be paid to thrombocytopenia in patients with renal diseases,as it could be an essential clue to the cause of the renal disease,reflecting endothelial dysfunction, immune-mediated damage, thromboembolism, and/or adverse drug reactions. Progressive decrease of platelets may be an important indicator of poor prognosis in patients with renal diseases.%血小板除了止血、促进凝血、维持毛细血管完整性外,还具有调节免疫、募集白细胞、捕获和封存致病原、直接杀死受感染的细胞等功能。急性肾损伤和慢性肾脏病患者均可出现血小板减少症,但两者在病因及病理生理方面存在差异。前者病因主要是感染、药物、溶血尿毒综合征(HUS)、血栓性血小板减少性紫癜(TTP)、溶血、肝酶升高、血小板减少

  18. Immediate transient thrombocytopenia at the time of alemtuzumab infusion in multiple sclerosis.

    Science.gov (United States)

    Ranganathan, Usha; Kaunzner, Ulrike; Foster, Stacyann; Vartanian, Timothy; Perumal, Jai S

    2017-03-01

    Alemtuzumab is a monoclonal antibody approved for relapsing-remitting multiple sclerosis (RRMS). Although Immune thrombocytopenia (ITP) has been reported as a secondary autoimmune phenomenon following alemtuzumab infusion, immediate thrombocytopenia during the infusion has not been reported. We report transient, reversible, self-limiting acute-onset thrombocytopenia during the first course with alemtuzumab. In total, 3 of 22 paitents developed mild self-limited bruising associated with a drop in platelet count from their baseline during the intial 5-day course of alemtuzumab. Upon chart review, all 22 patients who received alemtuzumab developed an immediate mostly asymptomatic drop in platelet count which returned to normal within 2 months post-infusion.

  19. Immune-mediated bone marrow failure in C57BL/6 mice.

    Science.gov (United States)

    Chen, Jichun; Desierto, Marie J; Feng, Xingmin; Biancotto, Angélique; Young, Neal S

    2015-04-01

    We established a model of immune-mediated bone marrow (BM) failure in C57BL/6 (B6) mice with 6.5 G total-body irradiation followed by the infusion of 4-10 × 10(6) lymph node (LN) cells/recipient from Friend leukemia virus B/N (FVB) donors. Forty-three percent of animals succumbed, with surviving animals showing marked declines in blood neutrophils, red blood cells, platelets and total BM cells at 8 to 14 days following LN cell infusion. Lowering the total-body irradiation dose to 5 G or altering the LN source from FVB to BALB/cBy donors failed to produce BM destruction. Affected animals showed significant expansion and activation of CD8 T lymphocytes in both the blood and BM; cytotoxic T cells had elevated Fas ligand expression and were oligoclonal, mainly displaying Vβ7 and Vβ17 T cell receptors. There were significant increases in blood plasma interferon γ and tissue necrosis factor α in affected animals. Chemokine ligands CCL3, CCL4, CCL5, CCL20, CXCL2, and CXCL5 and hematopoietic growth factors G-CSF, M-CSF, GM-CSF, VEGF were also elevated. In B6 mice carrying a Fas gene mutation, BM failure was attenuated when they were infused with FVB LN cells. Our model establishes a useful platform to define the roles of individual genes and their products in immune-mediated BM failure.

  20. Comparison of cytokine responses between dogs with sepsis and dogs with immune-mediated hemolytic anemia.

    Science.gov (United States)

    Johnson, Valerie; Burgess, Brandy; Morley, Paul; Bragg, Ryan; Avery, Anne; Dow, Steven

    2016-11-01

    Cytokine abnormalities have been described previously in dogs with varied immune mediated and inflammatory conditions such as IMHA and sepsis. The purpose of this study was to establish references ranges for cytokine levels in dogs and to compare cytokine levels in normal dogs and dogs with two common inflammatory diseases (sepsis and IMHA). We hypothesized that cytokine response profiles in dogs with sepsis would be significantly different from those in dogs with IMHA due to the very different etiologies of the two diseases. Concentrations of 14 different cytokines in serum were measured and values grouped according to cytokine function. Serum from clinically normal dogs was used to establish cytokine concentration reference ranges. Rank values for each of the 4 cytokine groups were then compared statistically between healthy control, septic and IMHA dogs. This analysis revealed differences in cytokine groups between dogs with sepsis and IMHA when compared to healthy control dogs but no difference between dogs with either of these conditions. In conclustion, dogs in the early stage of sepsis and IMHA have similar circulating cytokines despite different etiologies suggesting activation of common immunologic pathways. This may have implications for immunotherapy of immune mediated diseases in dogs of varying etiology.

  1. 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.

  2. Potential role of NKT regulatory cell ligands for the treatment of immune mediated colitis

    Institute of Scientific and Technical Information of China (English)

    2007-01-01

    Natural killer T lymphocytes (NKT) have been implicated in the regulation of autoimmune processes in both mice and humans. In response to stimuli, this subset of cells rapidly produces large amounts of cytokines thereby provoking immune responses, including protection against autoimmune diseases. NKT cells are present in all lymphoid compartments, but are most abundant in the liver and bone marrow. They are activated by interaction of their T-cell receptor with glycolipids presented by CD1d, a nonpolymorphic, major histocompatibility complex class Mike molecule expressed by antigen presenting cells. Several possible ligands for NKT cells have recently been suggested, p-glucosylceramide, a naturally occurring glycolipid, is a metabolic intermediate in the anabolic and catabolic pathways of complex glycosphingolipids. Like other p-glycolipids, p-glucosylceramide has an immunomodulatory effect in several immune mediated disorders, including immune mediated colitis. Due to the broad impact that NKT cells have on the immune system, there is intense interest in understanding how NKT cells are stimulated and the extent to which NKT cell responses can be controlled. These novel ligands are currently being evaluated in animal models of colitis. Here, we discuss strategies to alter NKT lymphocyte function in various settings and the potential clinical applications of natural glycolipids.

  3. 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.

  4. Drug-induced immune thrombocytopenia: incidence, clinical features, laboratory testing, and pathogenic mechanisms.

    Science.gov (United States)

    Curtis, Brian R

    2014-01-01

    Drug-induced immune thrombocytopenia (DIIT) is a relatively uncommon adverse reaction caused by drug-dependent antibodies (DDAbs) that react with platelet membrane glycoproteins only when the implicated drug is present. Although more than 100 drugs have been associated with causing DIIT, recent reviews of available data show that carbamazepine, eptifibatide, ibuprofen, quinidine, quinine, oxaliplatin, rifampin, sulfamethoxazole, trimethoprim, and vancomycin are probably the most frequently implicated. Patients with DIIT typically present with petechiae, bruising, and epistaxis caused by an acute, severe drop in platelet count (often to transfusion refractoriness, and must be differentiated by temporal association of exposure to a candidate drug with an acute, severe drop in platelet count. Treatment consists of immediate withdrawal of the implicated drug. Criteria for strong evidence of DIIT include (1) exposure to candidate drug-preceded thrombocytopenia; (2) sustained normal platelet levels after discontinuing candidate drug; (3) candidate drug was only drug used before onset of thrombocytopenia or other drugs were continued or reintroduced after resolution of thrombocytopenia, and other causes for thrombocytopenia were excluded; and (4) reexposure to the candidate drug resulted in recurrent thrombocytopenia. Flow cytometry testing for DDAbs can be useful in confirmation of a clinical diagnosis, and monoclonal antibody enzyme-linked immunosorbent assay testing can be used to determine the platelet glycoprotein target(s), usually GPIIb/IIIa or GPIb/IX/V, but testing is not widely available. Several pathogenic mechanisms for DIIT have been proposed, including hapten, autoantibody, neoepitope, drug-specific, and quinine-type drug mechanisms. A recent proposal suggests weakly reactive platelet autoantibodies that develop greatly increased affinity for platelet glycoprotein epitopes through bridging interactions facilitated by the drug is a possible mechanism for the

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

    African Journals Online (AJOL)

    Thrombotic microangiopathies and acute kidney injury induced by artificial termination ... of women with hemolytic anemia, thrombocytopenia and acute kidney injury ... Key words: Acute renal failure, case studies, induced abortion, pregnancy, ...

  6. 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

  7. How Is Immune Thrombocytopenia Treated?

    Science.gov (United States)

    ... counts. Adults who have ITP with very low platelet counts or bleeding problems often are treated. The acute (short-term) type of ITP that occurs in children often goes away within a few weeks or ...

  8. Pharmacologic treatment options in patients with thrombocytopenia.

    Science.gov (United States)

    Demetri, G D

    2000-04-01

    Thrombocytopenia that results from chemotherapy has become an increasingly important issue in the treatment of cancer and remains a difficult clinical problem. The identification of a safe and effective platelet growth factor could significantly improve the management of severe chemotherapy-induced thrombocytopenia. Over the past decade, a number of hematopoietic growth factors with thrombopoietic activity have been identified, including stem-cell factor (c-kit ligand), interleukin (IL)-1, IL-3, IL-6, and IL-11, as well as thrombopoietin (TPO) and its derivatives. Only a few of these agents have shown acceptable tolerability and sufficient ability to stimulate thrombopoiesis to justify testing in randomized clinical trials. Currently, IL-11 is the only cytokine licensed in the United States for treatment of chemotherapy-induced thrombocytopenia. However, its thrombopoietic activity is modest and its use is often associated with unfavorable side effects. Identification of TPO, the c-Mpl ligand, as the primary physiologic regulator of megakaryocyte and platelet development offers important promise for treatment of thrombocytopenia. Preliminary clinical studies of recombinant human TPO (rhTPO), a full-length glycosylated molecule, indicate that it is safe and biologically active in reducing severe chemotherapy-induced thrombocytopenia. In addition to rhTPO, the future may see the development of novel genetically engineered, high-affinity cytokine receptor agonists and c-Mpl ligand mimetic peptides.

  9. 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

    2016-01-01

    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. PMID:27019795

  10. 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.

  11. Neuromyelitis optica-IgG (aquaporin-4) autoantibodies in immune mediated optic neuritis.

    Science.gov (United States)

    Petzold, A; Pittock, S; Lennon, V; Maggiore, C; Weinshenker, B G; Plant, G T

    2010-01-01

    The clinical course of immune mediated optic neuritis (ON) will depend on the specific underlying inflammatory disease. These disorders have traditionally been classified according to clinical and MRI findings. Aquaporin-4 (AQP4) autoantibodies (neuromyelitis optica-IgG (NMO-IgG)) may have diagnostic and prognostic value in patients who present with isolated ON. In this prospective study, NMO-IgG was evaluated in 114 patients with ON in the following contexts: neuromyelitis optica (NMO), multiple sclerosis (MSON), chronic relapsing inflammatory ON (CRION), relapsing isolated ON (RION) and single isolated ON (SION). The proportion seropositive was 56% for NMO (n = 9), 0% for MSON (n = 28) and 5% for the remaining diagnostic categories (CRION (n = 19), RION (n = 17) and SION (n = 41)). Testing for NMO-IgG in patients with recurrent or severe ON who lack convincing evidence of MS may identify patients who would benefit from immunosuppression rather than MS directed immunomodulatory therapies.

  12. 25-Hydroxyvitamin D and Peripheral Immune Mediators: Results from Two Nationwide Danish Pediatric Cohorts.

    Science.gov (United States)

    Thorsen, Steffen U; Pipper, Christian B; Skogstrand, Kristin; Pociot, Flemming; Svensson, Jannet

    2017-04-06

    (1) Background: We aimed to examine if 25-hydroxyvitamin D (25(OH)D) was related to the peripheral immunological and inflammatory signature both at birth, and in newly diagnosed patients with childhood type 1 diabetes (T1D) and their healthy controls; (2) Methods: The birth cohort consisted of 470 patients and 500 healthy controls. Dried blood samples were collected from the neonates in the period 1981-1999. The newly diagnosed cohort consisted of 460 patients and 453 siblings. Serum samples were collected in the period 1997-2005. A variety of peripheral immune mediators were measured and compared to total 25(OH)D levels (25(OH)D₂ + 25(OH)D₃). For each immune mediator, the relative change (RC) in the mean level was modeled by robust log-normal regression and correction for multiple testing was performed; (3) Results: Two associations were identified; there was a negative association between 25(OH)D (10 nmol/L increase) and leptin (RC (95% confidence interval (CI)), 0.98 (0.96; 1.00)), and a positive association between 25(OH)D (10 nmol/L increase) and the chemokine, chemokine (c-x-c motif) ligand (CXCL) 8 (RC (95% CI), 1.07 (1.01; 1.13)); (4) Conclusion: CXCL8 and leptin have significant associations with levels of 25(OH)D in the newly diagnosed cohort. These results do not indicate a strong influence of 25(OH)D on the peripheral immunological or inflammatory signature.

  13. Octreotide-induced thrombocytopenia: a case report

    Directory of Open Access Journals (Sweden)

    Rizvi Nahid

    2011-07-01

    Full Text Available Abstract Introduction Thrombocytopenia is an extremely rare complication of octreotide therapy and can be life threatening in the setting of esophageal variceal bleeding. We report a case of octreotide-induced reversible thrombocytopenia in a 54-year-old Caucasian man with alcohol-induced cirrhosis and upper gastrointestinal bleeding. Case presentation Our patient's platelet count dropped from 155,000/mm3 upon admission to 77,000/mm3 a few hours after initiation of octreotide therapy and stayed low until the drug's administration was discontinued. Significant recovery was achieved quickly after discontinuation of octreotide. Conclusions Thrombocytopenia is a rare but potentially serious side effect of octreotide therapy and may complicate esophageal variceal bleeding. Physicians should be vigilant in identifying this potentially serious condition.

  14. Thrombophilia in patients with chronic immune thrombocytopenia.

    Science.gov (United States)

    Wong, Raymond S M; Bakshi, Kalpana; Brainsky, Andres

    2015-01-01

    An increased risk of thromboembolic events among patients with chronic immune thrombocytopenia has been reported but is still not fully understood. A thrombophilia panel (factors suspected/known to denote a thrombophilic state or indicate activation of the clotting cascade) was measured in previously treated patients with chronic immune thrombocytopenia enrolled in an eltrombopag trial to assess potential thrombophilia risk markers. Of 167 patients, 136 (81%) had abnormal levels of at least 1 known or suspected thrombosis risk marker or coagulation cascade activation marker. Six patients reported thromboembolic events, and all of these patients had at least two abnormal analytes in the thrombophilia panel. The presence of multiple baseline thrombophilia risk markers support the theory that chronic immune thrombocytopenia is a pro-thrombotic disease.

  15. 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.

  16. Genetics Home Reference: thrombocytopenia-absent radius syndrome

    Science.gov (United States)

    ... Genetics Home Health Conditions TAR syndrome thrombocytopenia-absent radius syndrome Enable Javascript to view the expand/collapse ... PDF Open All Close All Description Thrombocytopenia-absent radius (TAR) syndrome is characterized by the absence of ...

  17. Isolated Thrombocytopenia in Thai Children: Etiology and Result of Bone Marrow Aspiration Study

    Directory of Open Access Journals (Sweden)

    Kamon Phuakpet

    2016-05-01

    Full Text Available Background: Isolated thrombocytopenia (IT refers to an entity of low platelet count without abnormalities of other lineages. Previous studies revealed that the main cause of IT in children without atypical features i.e. hepa- tosplenomegaly or adenopathy was immune thrombocytopenia (ITP, while acute leukemia and aplastic anemia (AA were other possible causes. However, there was no previous study in Thailand to identify the cause of IT. Objective: To study the bone marrow aspiration (BMA result in Thai children with IT and to identify the cause of IT in Thai children. Methods: This was a retrospective chart review of children younger than 15 years old with IT who were diag- nosed at Siriraj Hospital during January 1996 to December 2010. All patients had BMA to identify the cause of thrombocytopenia. Demographic data, clinical manifestation, laboratory results including BMA finding, diagnosis and initial treatment were collected and analyzed. Results: One hundred and twenty-nine patients were enrolled to the study. All patients had normal or increased megakaryocytes in their bone marrow, and none of them had more than 5% of blast cells. Most patients (97.7% were diagnosed as acute ITP while 2.3% were diagnosed with neonatal alloimmune thrombocytopenia. None of the patients had acute leukemia or AA. Conclusion: The BMA result of most patients in this study was compatible to that of ITP, that is none of the patients had acute leukemia or AA. The most common cause of IT in Thai children is acute ITP. This result sug- gested that BMA in children with IT before starting treatment is not necessary.

  18. Effect observation of recombinant human thrombopoietin in treatment of thrombocytopenia caused by chemotherapy of acute leukemia%重组人促血小板生成素治疗急性白血病化疗后血小板减少的效果观察

    Institute of Scientific and Technical Information of China (English)

    章志学; 肖牛明; 肖小芳; 谢将; 肖文琼

    2014-01-01

    Objective To investigate the clinical effect of recombinant human thrombopoietin (rhTPO) in the treatment of thrombocytopenia caused by chemotherapy of acute leukemia. Methods Fifty-six patients who received chemothera-py and suffered from thrombocytopenia due to it in our hospital were selected and randomly divided into the observa-tion group (n=28) and the control group (n=28).The observation group received rhTPO treatment and the control group received recombinant human interleukin-11 (rhIL-11) treatment.The efficacy of the two groups was compared. Results After treatment,the platelet level in the observation group was significantly higher than that in the control group,and duration of platelets<50í109/L and time of platelet returning to 70í109/L and 100í109/L in the observation group were significantly shorter than those in the control group (P<0.05).The incidence rate in the the observation group was obvi-ously lower than that in the control group (3.6% vs 42.8%) (P<0.05). Conclusion In the treatment of thrombocytopenia caused by chemotherapy of acute leukemia,rhTPO shows remarkable effects and high safety,thereby it is worthy of clin-ical promotion and application.%目的:探讨重组人促血小板生成素(rhTPO)治疗急性白血病化疗后血小板减少的临床效果。方法选取2012年1月~2014年1月在本院接受化疗治疗且发生血小板减少症的急性白血病患者56例,将其随机分为观察组和对照组,每组各28例。观察组给予rhTPO治疗,对照组给予重组人白介素-11(rhIL-11)治疗,比较两组的疗效。结果观察组治疗后的血小板水平明显高于对照组,且血小板<50×109/L的持续时间、恢复至70×109/L和100×109/L所需时间明显短于对照组(P<0.05);观察组的不良反应发生率明显低于对照组(3.6% vs 42.8%)(P<0.05)。结论 rhTPO治疗急性白血病化疗后血小板减少的效果显著,安全性高,值得临床推广应用。

  19. The use of the rapid osmotic fragility test as an additional test to diagnose canine immune-mediated haemolytic anaemia

    DEFF Research Database (Denmark)

    Paes, Geert; Paepe, Dominique; Meyer, Evelyne

    2013-01-01

    Background: Diagnosing canine immune-mediated haemolytic anaemia (IMHA) is often challenging because all currently available tests have their limitations. Dogs with IMHA often have an increased erythrocyte osmotic fragility (OF), a characteristic that is sometimes used in the diagnosis of IMHA. S...

  20. 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

  1. 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

  2. Are newly discovered drivers of immune-mediated skin disorders expressed in normal skin regenerating from standardized surface injury?

    NARCIS (Netherlands)

    Hendriks, A.G.M.; Keijsers, R.R.M.C.; Seyger, M.M.B.; Erp, P.E.J. van; Kerkhof, P.C.M. van de

    2014-01-01

    Background: In healthy skin, tape stripping induces a transient wave of histological changes resembling immune-mediated skin diseases, such as psoriasis. The response to surface trauma may harbor mechanisms which are also relevant to the development of Koebner-positive skin disorders. However, studi

  3. 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 laboratories

  4. Reliability and responsiveness of a graduated tuning fork in immune mediated polyneuropathies. The Inflammatory Neuropathy Cause and Treatment (INCAT) Group

    NARCIS (Netherlands)

    I.S.J. Merkies (Ingemar); P.I.M. Schmitz (Paul); F.G.A. van der Meché (Frans); P.A. van Doorn (Pieter)

    2000-01-01

    textabstractThe interobserver and intraobserver reliability of the Rydel-Seiffer (RS) graduated tuning fork was evaluated in 113 patients with a clinically stable immune mediated polyneuropathy (83 patients who had had Guillain-Barre syndrome (GBS) in the past, 22 with

  5. Molecular mechanisms of drug-induced thrombocytopenia

    NARCIS (Netherlands)

    Burgess, Janette K.

    2001-01-01

    A wide range of drugs can induce thrombocytopenia. Molecular mechanisms for the formation of specific epitopes for all the drug-dependent antibodies appear to be very similar. A restricted set of glycoproteins on the platelet surface interacts with the drugs to form neoepitopes, to which the drug-de

  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. Severe thrombocytopenia before liver transplantation is associated with delayed recovery of thrombocytopenia regardless of donor type

    Institute of Scientific and Technical Information of China (English)

    Jae Hyuck Chang; Dong Goo Kim; Jong Young Choi; Hyun Young Woo; Jung Hyun Kwon; Chan Ran You; Si Hyun Bae; Seung Kew Yoon; Myung-Gyu Choi; In Sik Chung

    2008-01-01

    AIM: To compare the recovery of thrombocytopenia and splenomegaly during long-term follow-up after liver transplantation in patients receiving a living donor transplant or a cadaveric donor transplant.METHODS: This was a retrospective cohort study of 216 consecutive liver transplant patients who survived for > 6 mo after transplantation; 169 received a liver transplant from a living donor and 47 from a cadaveric donor.The platelet counts or spleen volumes were examined before transplant,1,6,and 12 mo after transplant,and then annually until 5 years after transplant.RESULTS: The mean follow-up period was 49 mo (range,21-66).Platelet counts increased continuously for 5 years after orthotopic liver transplant.The restoration of platelet counts after transplant was significantly slower in patients with severe pretransplant thrombocytopenia (< 50000/μL) until 4 years after transplant (P = 0.005).Donor type did not significantly affect the recovery of platelet count and spleen volume in either patient group.In multivariate analysis,pretransplant severe thrombocytopenia (< 50000/μL)was an independent factor associated with sustained thrombocytopenia (P < 0.001,odds ratio 6.314; confidence interval,2.828-14.095).Thrombocytopenia reappeared after transplant in seven patients with portal flow disturbance near the anastomosis site.CONCLUSION: Our study suggests that severe thrombocytopenia before transplant is closely associated with delayed recovery of platelet count after transplant and donor type did not affect the recovery of thrombocytopenia.The reappearance of thrombocytopenia after transplant should be considered a possible indicator of flow disturbance in the portal vein.

  8. Thrombocytopenia and thrombosis in disseminated intravascular coagulation (DIC).

    Science.gov (United States)

    Kitchens, Craig S

    2009-01-01

    Disseminated intravascular coagulation (DIC) is the physiologic result of pathologic overstimulation of the coagulation system. Despite multiple triggers, a myriad of laboratory abnormalities, and a clinical presentation ranging from gross hemostatic failure to life-threatening thrombosis, or even both simultaneously, a simplified clinical approach augmented by a few readily available tests allows prompt identification of the process and elucidation of treatment opportunities. Platelet counts in DIC may be low, especially in acute sepsis-associated DIC, yet increased in malignancy-associated chronic DIC. Thrombotic risk is not a function of the platelet count, and thrombocytopenia does not protect the patient from thrombosis. The stratification of both thrombotic risk and hemorrhagic risk will be addressed.

  9. 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

  10. 重组人白介素11对儿童急性淋巴细胞白血病化疗后血小板减少的疗效观察%Effects of recombinant human interleukin 11 treatment on thrombocytopenia induced by chemotherapy in children with acute lymphoblastic leukemia

    Institute of Scientific and Technical Information of China (English)

    梁卉; 刘华林; 宋亮

    2011-01-01

    Objective To investigate the effects of recombinant human interleukin-11 (rhIL-11 ) treatment on thrombocytopenia in childhood acute lymphoblastic leukemia (ALL) after chemotherapy. Methods Total of 36 patients of childhood ALL suffering thrombocytopenia were randomly divided into treatment group and control group. Twenty-four hours after chemotherapy, only patients of the treatment group were given daily subcutaneous injection of rhIL-11 for 5 days. Changes of the platelet count were observed, the amount of platelet transfusion and adverse reactions were recorded. Results Compared with the control group, recovery time of platelet count was shorter, platelet transfusion was less in the treatment group, and the differences were statistically significant, while adverse reaction was mild.Conclusions Application of rhIL-11 can improve platelet count obviously after chemotherapy of ALL children, reduce platelet transfusion, and it is clinically safe and affordable.%目的 观察重组人白介素11(rhIL-11)对急性淋巴细胞白血病(ALL)患儿化疗后血小板减少的疗效和安全性.方法 选取36例ALL化疗后血小板减少患儿,随机分为治疗组和对照组,治疗组患儿在化疗结束后24 h每日皮下注射rhIL-11,应用5 d;对照组不用rhIL-11.观察两组患儿血小板数值变化,记录血小板输注量及治疗组不良反应.结果 治疗组较对照组血小板恢复时间短,输注血小板少,差异有统计学意义.治疗组rhIL-11不良反应轻微.结论 rhIL-11能明显提高儿童ALL化疗后血小板数量,减少血小板输注,临床应用安全,综合临床费用降低.

  11. Glycan elongation beyond the mucin associated Tn antigen protects tumor cells from immune-mediated killing.

    Directory of Open Access Journals (Sweden)

    Caroline B Madsen

    Full Text Available Membrane bound mucins are up-regulated and aberrantly glycosylated during malignant transformation in many cancer cells. This results in a negatively charged glycoprotein coat which may protect cancer cells from immune surveillance. However, only limited data have so far demonstrated the critical steps in glycan elongation that make aberrantly glycosylated mucins affect the interaction between cancer cells and cytotoxic effector cells of the immune system. Tn (GalNAc-Ser/Thr, STn (NeuAcα2-6GalNAc-Ser/Thr, T (Galβ1-3GalNAc-Ser/Thr, and ST (NeuAcα2-6Galβ1-3GalNAc-Ser/Thr antigens are recognized as cancer associated truncated glycans, and are expressed in many adenocarcinomas, e.g. breast- and pancreatic cancer cells. To investigate the role of the cancer associated glycan truncations in immune-mediated killing we created glyco-engineered breast- and pancreatic cancer cells expressing only the shortest possible mucin-like glycans (Tn and STn. Glyco-engineering was performed by zinc finger nuclease (ZFN knockout (KO of the Core 1 enzyme chaperone COSMC, thereby preventing glycan elongation beyond the initial GalNAc residue in O-linked glycans. We find that COSMC KO in the breast and pancreatic cancer cell lines T47D and Capan-1 increases sensitivity to both NK cell mediated antibody-dependent cellular-cytotoxicity (ADCC and cytotoxic T lymphocyte (CTL-mediated killing. In addition, we investigated the association between total cell surface expression of MUC1/MUC16 and NK or CTL mediated killing, and observed an inverse correlation between MUC16/MUC1 expression and the sensitivity to ADCC and CTL-mediated killing. Together, these data suggest that up-regulation of membrane bound mucins protects cells from immune mediated killing, and that particular glycosylation steps, as demonstrated for glycan elongation beyond Tn and STn, can be important for fine tuning of the immune escape mechanisms in cancer cells.

  12. Evaluation of the diagnostic performance of platelet-derived indices for the differential diagnosis of thrombocytopenia in pediatrics

    Directory of Open Access Journals (Sweden)

    Nelson Hernando Aponte-Barrios

    2014-10-01

    Full Text Available Background. Platelet-derived indices have a well-established correlation with the differential diagnosis of thrombocytopenia in adult-based research. These indices include mean platelet volume, platelet distribution width, and platelet-large cell ratio. Objective. To determine the values of platelet-derived indices in a pediatric population with diagnoses of thrombocytopenia and their etiologic correlation. Materials and methods. Analytic observational diagnostic-test study. The population for this analytical study was pediatric patients between 6 months and 18 years of age who had thrombocytopenia (<100x10(9/L. The study period was 18 months long. Results. Of 54 subjects, 18 (33.3% were diagnosed with idiopathic thrombocytopenic purpura, and 36 (66.7% were diagnosed with acute leukemia. Mean age was 7.4 years and 6.8 years for immune thrombocytopenic purpura and acute leukemia, respectively. Mean platelet distribution width values for immune thrombocytopenic purpura and acute leukemia were 15.08 fL and 10.73, respectively. Mean MPV for immune thrombocytopenic purpura and acute leukemia was 11.7 fL and 9.8 fL, respectively. Mean platelet-large cell ratio was 38.26% and 24.97% for idiopathic thrombocytopenic purpura and acute leukemia, respectively. Differences in these three distinct platelet indices between idiopathic thrombocytopenic purpura and acute leukemia were statistically significant (p=0.00. The area under the ROC curve for platelet-derived indices showed that they were adequate for defining the causes of thrombocytopenia. MPV and platelet-large cell ratio had an area under the curve of 0.89 and 0.88, respectively, while platelet size deviation width had an area under the curve of 0.903. Conclusions. Platelet-derived indices could be useful in the initial approach for the differential diagnosis of pediatric patients with thrombocytopenia.

  13. The levels of IL-17A and of the cytokines involved in Th17 cell commitment are increased in patients with chronic immune thrombocytopenia

    Science.gov (United States)

    Rocha, Andreia Maria Camargos; Souza, Cláudia; Rocha, Gifone Aguiar; de Melo, Fabrício Freire; Clementino, Nelma Cristina Diogo; Marino, Marília Campos Abreu; Bozzi, Adriana; Silva, Maria Luiza; Martins Filho, Olindo Assis; Queiroz, Dulciene Maria Magalhães

    2011-01-01

    Th17 cells have been associated with immune-mediated diseases in humans but it has still not been determined whether they play a role in immune thrombocytopenia. We evaluated representative cytokines of the Th17, Th1, Th2 and Treg cell commitment in the serum of patients with chronic immune thrombocytopenia, as well as the cell source of IL-17A. Higher levels of IL-17A and Th17-related cytokines, and an increased percentage of IL-17A producing CD4+ and neutrophils were observed in patients. The levels of cytokines involved in Th1 cell commitment IFN-γ, IL-2, IL12-p70 and the percentages of Th1 cells were also increased, but IL-4 was not detected. Although the concentrations of IL-10 were higher, the levels of TGF-β were similar in both groups. In conclusion, our results point to a putative role for Th-17 cells/IL-17A cytokine in the pathogenesis of chronic immune thrombocytopenia. PMID:21972211

  14. 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.

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

    Science.gov (United States)

    de Azeredo, Elzinandes Leal; Monteiro, Robson Q; de-Oliveira Pinto, Luzia Maria

    2015-01-01

    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.

  16. Adalimumab for the treatment of immune-mediated diseases: an update on old and recent indications.

    Science.gov (United States)

    Murdaca, G; Colombo, B M; Puppo, F

    2011-04-01

    Ongoing progress in understanding the pathogenic mechanisms regulating various immune-mediated and inflammatory diseases, as well as the availability of innovative biotechnological approaches, have lead to the development of new drugs that add to conventional treatments. Among these, tumor necrosis factor (TNF)-α inhibitors such as infliximab, adalimumab, etanercept, golimumab and certolizumab pegol, are now available for clinical use. Adalimumab is a fully recombinant human immunoglobulin G1 monoclonal antibody that specifically binds with high affinity to human TNF-α and inhibits its binding to TNF receptors. Adalimumab was approved by the U.S. FDA in 2002 and was granted approval from the European Medicines Agency in September 2003 for the treatment of moderate to severe rheumatoid arthritis and subsequently for the treatment of ankylosing spondylitis, chronic plaque psoriasis, psoriatic arthritis, juvenile idiopathic arthritis and Crohn's disease. In this paper, we will briefly review the structure and biological effects of TNF-α, the old and recent indications of adalimumab, the pretreatment considerations, the reported adverse events and finally, the recommendations for its use in pregnancy.

  17. 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.

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

    Science.gov (United States)

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

    2011-06-01

    Identifying disease-associated variants can improve the predictive models of disease risk and provide mechanistic insights into disease development. Coeliac disease (CD) is the only autoimmune trait with a known environmental trigger, which makes it an excellent model for studying the complexity of genetic and environmental factors in the development of autoimmunity. In this review, we will focus on the genetic loci that have recently been associated with CD and that contain genes involved in innate and adaptive immunity. Some of these loci are shared with other immune-mediated diseases, suggesting an overlap of the genetic mechanisms involved in the development of such diseases. Some therapies, e.g. tumour necrosis factor inhibitors or a gluten-free diet, are already proving effective for more than one autoimmune disease. Follow-up of individuals with a high genetic risk of CD and other autoimmune diseases could help to elucidate the role of environmental factors (such as infectious agents or alterations in the microbiome) and prevent disease development. © 2011 The Association for the Publication of the Journal of Internal Medicine.

  19. Immune-mediated bile duct injury: The case of primary biliary cirrhosis

    Science.gov (United States)

    Selmi, Carlo; Affronti, Andrea; Ferrari, Laura; Invernizzi, Pietro

    2010-01-01

    Autoimmune cholangitis would be the appropriate name to define the immune-mediated bile duct injury following the breakdown of tolerance to mitochondrial proteins and the appearance of serum autoantibodies and autoreactive T cells. Nevertheless, the condition is universally named primary biliary cirrhosis (PBC). The disease etiology and pathogenesis remain largely unknown despite the proposed lines of evidence. One twin study and numerous epidemiology reports suggest that both a susceptible genetic background and environmental factors determine disease onset while a recent genome-wide association study proposed highly significant associations with several common genetic polymorphisms in subgroups of patients. Specific infectious agents and chemicals may contribute to the disease onset and perpetuation in a genetically susceptible host, possibly through molecular mimicry. Importantly, several murine models have been proposed and include strains in which PBC is genetically determined or induced by immunization with chemicals and bacteria. From a pathogenetic standpoint, new exciting data have demonstrated the unique apoptotic features of bile duct cells that allow the mitochondrial autoantigens to be taken up in their intact form within apoptotic blebs. We are convinced that the application of the most recent molecular techniques will soon provide developments in PBC etiology and pathogenesis with likely implications in diagnostics and therapeutics. PMID:21607152

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    Rogier M Thurlings

    Full Text Available BACKGROUND: 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. METHODS/PRINCIPAL FINDINGS: 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. CONCLUSIONS/SIGNIFICANCE: 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.

  3. [Diagnosis and treatment of heparin-induced thrombocytopenia (HIT) based on its atypical immunological features].

    Science.gov (United States)

    Miyata, Shigeki; Maeda, Takuma

    2016-03-01

    Heparin-induced thrombocytopenia (HIT) is a prothrombotic side effect of heparin therapy caused by HIT antibodies, i.e., anti-platelet factor 4 (PF4)/heparin IgG with platelet-activating properties. For serological diagnosis, antigen immunoassays are commonly used worldwide. However, such assays do not indicate their platelet-activating properties, leading to low specificity for the HIT diagnosis. Therefore, over-diagnosis is currently the most serious problem associated with HIT. The detection of platelet-activating antibodies using a washed platelet activation assay is crucial for appropriate HIT diagnosis. Recent advances in our understanding of the pathogenesis of HIT include it having several clinical features atypical for an immune-mediated disease. Heparin-naïve patients can develop IgG antibodies as early as day 4, as in a secondary immune response. Evidence for an anamnestic response on heparin re-exposure is lacking. In addition, HIT antibodies are relatively short-lived, unlike those in a secondary immune response. These lines of evidence suggest that the mechanisms underlying HIT antibody formation may be compatible with a non-T cell-dependent immune reaction. These atypical clinical and serological features should be carefully considered while endeavoring to accurately diagnose HIT, which leads to appropriate therapies such as immediate administration of an alternative anticoagulant to prevent thromboembolic events and re-administration of heparin during surgery involving cardiopulmonary bypass when HIT antibodies are no longer detectable.

  4. Proteins Encoded in Genomic Regions Associated with Immune-Mediated Disease Physically Interact and Suggest Underlying Biology

    DEFF Research Database (Denmark)

    Rossin, Elizabeth J.; Hansen, Kasper Lage; Raychaudhuri, Soumya

    2011-01-01

    Genome-wide association studies (GWAS) have defined over 150 genomic regions unequivocally containing variation predisposing to immune-mediated disease. Inferring disease biology from these observations, however, hinges on our ability to discover the molecular processes being perturbed by these r......Genome-wide association studies (GWAS) have defined over 150 genomic regions unequivocally containing variation predisposing to immune-mediated disease. Inferring disease biology from these observations, however, hinges on our ability to discover the molecular processes being perturbed......-immune traits to assess its applicability to complex traits in general. We find that genes in loci associated to height and lipid levels assemble into significantly connected networks but did not detect excess connectivity among Type 2 Diabetes (T2D) loci beyond chance. Taken together, our results constitute...

  5. Current management of heparin-induced thrombocytopenia.

    Science.gov (United States)

    Cosmi, Benilde

    2015-12-01

    Heparin-induced thrombocytopenia (HIT) is an immune adverse reaction to heparin (both unfractionated and low-molecular-weight), which is mediated by the formation of IgG antibodies against platelet factor 4-heparin complexes. The IgG/platelet factor 4 immunocomplexes activate platelets with resulting thrombocytopenia, which is not associated with bleeding, but with paradoxical life-threatening thrombotic complications, for coagulation activation. HIT diagnosis requires the assessment of pre-test clinical probability in combination with the measurement of platelet activating antibodies against platelet factor 4-heparin complexes with immunological and functional assays. When HIT is diagnosed, any form of heparin should be stopped and a non-heparin alternative anticoagulant should be started. Argatroban and danaparoid are currently the only drugs licensed for HIT, with different country availability. Bivalirudin is an option in cardiac surgery and procedures in HIT patients.

  6. Immunological HCV-Associated Thrombocytopenia: Short Review

    Directory of Open Access Journals (Sweden)

    Dimitrios Dimitroulis

    2012-01-01

    Full Text Available Infection with Hepatitis C virus (HCV is affecting about 3% of the world's population, leading to liver damage, end-stage liver disease, and development of hepatocellular carcinoma, being thus the first indication for liver transplantation in the USA. Apart from the cirrhotic-liver-derived clinical signs and symptoms several conditions with immunological origin can also arise, such as, glomerulonephritis, pulmonary fibrosis, and thrombocytopenia. HCV-related autoimmune thrombocytopenia shows specific pathogenetic characteristics as well as symptoms and signs that differ in severity and frequency from symptoms in patients that are not HCV infected. Aim of this short paper is to estimate the epidemiological characteristics of the disease, to investigate the pathogenesis and clinical manifestation, and to propose treatment strategies according to the pertinent literature.

  7. 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.

  8. Treatment of chronic immune-mediated neuropathies: chronic inflammatory demyelinating polyradiculoneuropathy, multifocal motor neuropathy, and the Lewis-Sumner syndrome.

    Science.gov (United States)

    Sederholm, Benson H

    2010-09-01

    Current treatment approaches for the management of chronic immune-mediated peripheral neuropathies are reviewed, including chronic inflammatory demyelinating polyradiculoneuropathy (CIDP), multifocal motor neuropathy (MMN), and the Lewis-Sumner syndrome (LSS). A summary of existing evidence for commonly used treatment modalities, such as corticosteroids, intravenous immune globulin (IVIG), and plasma exchange is provided. Evidence for the use of additional immunosuppressant and immunomodulatory agents is also reviewed.

  9. Immune-Mediated Cytotoxicity に対するグリチルリチンの作用

    OpenAIRE

    豊原, 眞久

    2000-01-01

    Intravenous administration of glycyrrhizin (GL) is known to decrease elevated plasma transaminase levels in patients with chronic viral hepatits, in which immune-mediated cytotoxicity by cytotoxic T lymphocytes and tumor necrosis factor alpha (TNFα) is considered to play an important pathogenic role. However, im- munological interpretation of the transaminase-lowering action by GL is not clear. Studies were made to elucidate this action immunologically by assessing the effects of GL on immune...

  10. Thrombocytopenia during pregnancy: an institutional based study

    Directory of Open Access Journals (Sweden)

    Rajshree Dayanand Katke

    2014-08-01

    Methods: The study was conducted in this tertiary institute over a period of two years and three months. 103 pregnant patients with a platelet count of or less than 100000/mL were included. The course of pregnancy was studied and the investigation profile was monitored. Results: Out of 103 cases of thrombocytopenia, 73 (70.9% patients had moderate, 30 (29.1% patients had severe thrombocytopenia. In this study 35% cases were primigravidas, 32% cases were gravida 2, 33% cases were gravida 3 to 5. Gestational thrombocytopenia was the most common etiological factor with 30.1% cases, 27.2% cases due to hypertensive disorders, 18.4% cases due to malaria followed by 12.6% cases due to dengue. In the study group the mean gestational age was 33 +/- 5.139, maximum cases belonged to gestational age 30 to and #8805;40. 14 patients (14.1% had still births. 9 patients (8.7% had Neonatal deaths (NNDs. Conclusions: The challenge to the clinician is to weigh the risks of maternal and fetal bleeding complications against the benefits of diagnostic tests and interventions. [Int J Reprod Contracept Obstet Gynecol 2014; 3(4.000: 947-951

  11. Ipilimumab and immune-mediated adverse events: a case report of anti-CTLA4 induced ileitis.

    Science.gov (United States)

    Venditti, Olga; De Lisi, Delia; Caricato, Marco; Caputo, Damiano; Capolupo, Gabriella Teresa; Taffon, Chiara; Pagliara, Elisa; Battisi, Sofia; Frezza, Anna Maria; Onetti Muda, Andrea; Tonini, Giuseppe; Santini, Daniele

    2015-03-01

    Ipilimumab is a fully human monoclonal antibody directed against cytotoxic T-lymphocyte antigen-4 , a key negative regulator of T-cell activation approved by the Food and Drug Administration as of March 2011 for the treatment of metastatic melanoma. As a result of the up-regulation of the immune system, several immune-mediated adverse effects have been reported including colitis, dermatitis, hepatitis and rarely hypophysitis. The most frequent immune-mediated adverse effects described in literature include gastrointestinal toxicity such as diarrhea, colitis and case of colitis and ileitis. In this paper we report an interesting case of immune-mediate ileitis without colitis in a 54 years old woman with metastatic melanoma treated with ipilimumab. We also discuss about case management and the possible pathological mechanisms considering also previous reports. The aim of this article is to support further investigations concerning epigenetic and genetic analysis in order to personalize biological therapy and to reduce immune related adverse events observed after ipilimumab administration.

  12. The Association of Specific Constituents of the Fecal Microbiota with Immune-Mediated Brain Disease in Dogs

    Science.gov (United States)

    Jeffery, Nick D.; Barker, Andrew K.; Alcott, Cody J.; Levine, Jon M.; Meren, Ilyssa; Wengert, Jane; Jergens, Albert E.; Suchodolski, Jan S.

    2017-01-01

    Meningoencephalomyelitis of unknown origin (MUO) is a common, naturally-occurring, clinical disease of pet dogs. It is an immune-mediated condition that has many similarities with experimental autoimmune encephalitis (EAE) in rodents and so investigation of its pathogenesis may aid in understanding factors that contribute to development of multiple sclerosis in people. Gut microbiota are known to modulate immune responses that influence susceptibility to immune-mediated brain disease. In this study we aimed to compare abundance of specific constituents of the fecal microbiota, namely Faecalibacterium prausnitzii and Prevotellaceae, between dogs diagnosed with MUO and matched controls. Fecal samples were obtained from 20 dogs diagnosed with MUO and 20 control dogs matched for breed, age and gender. Bacterial abundance was measured using qPCR and 16S rRNA sequencing. We found that Prevotellaceae were significantly less abundant in cases compared with controls (p = 0.003) but there was no difference in abundance of F.prausnitzii. There was no evidence of other differences in gut microbiota between groups. These data, derived from this naturally-occurring canine clinical model, provide strong corroborative evidence that high abundance of Prevotellaceae in the gut is associated with reduced risk for developing immune-mediated brain disease. PMID:28125651

  13. Association Between Genetic Traits for Immune-Mediated Diseases and Alzheimer Disease.

    Science.gov (United States)

    Yokoyama, Jennifer S; Wang, Yunpeng; Schork, Andrew J; Thompson, Wesley K; Karch, Celeste M; Cruchaga, Carlos; McEvoy, Linda K; Witoelar, Aree; Chen, Chi-Hua; Holland, Dominic; Brewer, James B; Franke, Andre; Dillon, William P; Wilson, David M; Mukherjee, Pratik; Hess, Christopher P; Miller, Zachary; Bonham, Luke W; Shen, Jeffrey; Rabinovici, Gil D; Rosen, Howard J; Miller, Bruce L; Hyman, Bradley T; Schellenberg, Gerard D; Karlsen, Tom H; Andreassen, Ole A; Dale, Anders M; Desikan, Rahul S

    2016-06-01

    allelic effect between AD and the immune-mediated diseases. Both rs2516049 and rs12570088 were significantly associated with neurofibrillary tangle pathology (P = .01352 and .03151, respectively); rs2516049 additionally correlated with longitudinal decline on Alzheimer's Disease Assessment Scale cognitive subscale scores (β [SE], 0.405 [0.190]; P = .03). Regarding gene expression, HLA-DRA and IPMK transcript expression was significantly altered in AD brains compared with control brains (HLA-DRA: β [SE], 0.155 [0.024]; P = 1.97 × 10-10; IPMK: β [SE], -0.096 [0.013]; P = 7.57 × 10-13). Our findings demonstrate genetic overlap between AD and immune-mediated diseases and suggest that immune system processes influence AD pathogenesis and progression.

  14. Syndromic mental retardation with thrombocytopenia due to 21q22.11q22.12 deletion: Report of three patients.

    Science.gov (United States)

    Katzaki, Eleni; Morin, Gilles; Pollazzon, Marzia; Papa, Filomena Tiziana; Buoni, Sabrina; Hayek, Joussef; Andrieux, Joris; Lecerf, Laure; Popovici, Cornel; Receveur, Aline; Mathieu-Dramard, Michèle; Renieri, Alessandra; Mari, Francesca; Philip, Nicole

    2010-07-01

    During the last few years, an increasing number of microdeletion/microduplication syndromes have been delineated. This rapid evolution is mainly due to the availability of microarray technology as a routine diagnostic tool. Microdeletions of the 21q22.11q22.12 region encompassing the RUNX1 gene have been reported in nine patients presenting with syndromic thrombocytopenia and mental retardation. RUNX1 gene is responsible for an autosomal dominant platelet disorder with predisposition to acute myelogenous leukemia. We report on three novel patients with an overlapping "de novo" interstitial deletion involving the band 21q22 characterized by array-CGH. All our patients presented with severe developmental delay, dysmorphic features, behavioral problems, and thrombocytopenia. Comparing the clinical features of our patients with the overlapping ones already reported two potential phenotypes related to 21q22 microdeletion including RUNX1 were highlighted: thrombocytopenia with +/- mild dysmorphic features and syndromic thrombocytopenia with growth and developmental delay.

  15. 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.

  16. Tumor-induced CD11b(+) Gr-1(+) myeloid-derived suppressor cells exacerbate immune-mediated hepatitis in mice in a CD40-dependent manner.

    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

    2015-04-01

    Immunosuppressive CD11b(+) Gr-1(+) myeloid-derived suppressor cells (MDSCs) accumulate in the livers of tumor-bearing (TB) mice. We studied hepatic MDSCs in two murine models of immune-mediated hepatitis. Unexpectedly, treatment of TB mice with Concanavalin A (Con A) or α-galactosylceramide resulted in increased alanine aminotransferase (ALT) and aspartate aminotransferase (AST) serum levels in comparison to tumor-free mice. Adoptive transfer of hepatic MDSCs into naïve mice exacerbated Con A induced liver damage. Hepatic CD11b(+) Gr-1(+) cells revealed a polarized proinflammatory gene signature after Con A treatment. An IFN-γ-dependent upregulation of CD40 on hepatic CD11b(+) Gr-1(+) cells along with an upregulation of CD80, CD86, and CD1d after Con A treatment was observed. Con A treatment resulted in a loss of suppressor function by tumor-induced CD11b(+) Gr-1(+) MDSCs as well as enhanced reactive oxygen species (ROS)-mediated hepatotoxicity. CD40 knockdown in hepatic MDSCs led to increased arginase activity upon Con 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 ROS production in vivo. Our findings indicate that in a setting of acute hepatitis, tumor-induced hepatic MDSCs act as proinflammatory immune effector cells capable of killing hepatocytes in a CD40-dependent manner.

  17. A rare case of infantile cerebellar pilocytic astrocytoma and thrombocytopenia presenting with intratumoral hemorrhage

    Directory of Open Access Journals (Sweden)

    Shashank R Ramdurg

    2016-01-01

    Full Text Available Incidence of gliomas presenting with hemorrhage is around 3.7–7.2%. Low-grade gliomas account for <1% tumor with hemorrhage. Infants presenting with cerebellar pilocytic astrocytomas (PAs and hemorrhage with thrombocytopenia have not been reported. We report an interesting case of a 9-month-old infant who presented to the emergency department in a drowsy state with recurrent vomiting. Laboratory investigations showed anemia, thrombocytopenia, and coagulopathy. Radiological evaluation showed a large PA with bleed. The patient was treated with retromastoid suboccipital craniotomy and tumor excision and improved postoperatively. Cerebellar PA with bleed and coagulopathy in infants has not been reported in literature till date. Their presentation seems to be acute in nature, and high index of suspicion is required for the diagnosis of these posterior fossa tumors, which can deteriorate rapidly in infants.

  18. Ustekinumab in chronic immune-mediated diseases: a review of long term safety and patient improvement

    Directory of Open Access Journals (Sweden)

    Toussirot E

    2013-04-01

    Full Text Available Éric Toussirot,1–4 Fabrice Michel,5 Matthieu Béreau,6 Delphine Binda1,7 1Clinical Investigation Center – Biotherapy CBT-506, University Hospital of Besançon, Besançon, France; 2Department of Rheumatology, University Hospital of Besançon, Besançon, France; 3Department of Therapeutics, University of Franche-Comté, Besançon, France; 4Equipe d'Acceuil 4266 Pathogens and Inflammation, Structure Fédérative de Recherche–Fédération de Recherche 4234, University of Franche-Comté, Besançon, France; 5Department of Physical Medicine and Rehabilitation, University Hospital of Besançon, Besançon, France; 6Department of Neurology, University Hospital of Besançon, Besançon, France; 7Institut National de la Santé et de la Recherche Médicale Unité Mixte de Recherche 1098, Blood Transfusion Center, Besançon, France Abstract: Ustekinumab is a fully human monoclonal antibody targeting the common p40 subunit shared by interleukin (IL-12 and IL-23. Ustekinumab prevents the interaction of IL-12 and IL-23 with their cell surface receptors, and thus blocks T helper (Th-1 IL-12 and Th-17 IL-23 inflammatory pathways. Ustekinumab has been evaluated in the treatment of various chronic immune-mediated diseases including, psoriasis, psoriatic arthritis, Crohn's disease, and multiple sclerosis. It led to a rapid and durable improvement in psoriasis area and severity index in patients with moderate to severe psoriasis. Ustekinumab also improved joint symptoms of psoriatic arthritis. Results in Crohn's disease were more mitigated, albeit with a symptomatic improvement in patients refractory to tumor necrosis factor-α inhibitors. Ustekinumab did not reduce the number of magnetic resonance imaging brain lesions in multiple sclerosis. The most common adverse events to have been observed during clinical trials are mild in intensity, and include respiratory tract infections, nasopharyngitis, headaches, and injection site reactions. A pooled analysis of

  19. 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

  20. Bone marrow pathology in dogs and cats with non-regenerative immune-mediated haemolytic anaemia and pure red cell aplasia.

    Science.gov (United States)

    Weiss, D J

    2008-01-01

    Many dogs and cats with immune-mediated haemolytic anaemia (IMHA) lack a bone marrow erythroid regenerative response. To better understand the failure of the bone marrow to respond to the anaemia, bone marrow pathology associated with non-regenerative IMHA and pure red cell aplasia (PRCA) was reviewed. Eighty-two affected dogs and 57 affected cats were identified from a population presenting to a referral hospital over a 10-year period. Fifty-five dogs had non-regenerative IMHA (38 had bone marrow erythroid hyperplasia and 17 had erythroid maturation arrest) and 27 had pure red cell aplasia (PRCA). Twenty-eight cats had non-regenerative IMHA (24 had erythroid hyperplasia and 4 had erythroid maturation arrest) and 29 had PRCA. A variety of pathological changes were observed in bone marrow aspirates and core biopsy specimens taken from these animals. These changes included dysmyelopoiesis, myelonecrosis, myelofibrosis, interstitial oedema, haemorrhage, acute inflammation, haemophagocytic syndrome, lymphocyte aggregation, and lymphocyte or plasma cell hyperplasia. In both dogs and cats, dysmyelopoiesis, myelonecrosis, myelofibrosis, interstitial oedema, haemorrhage, acute inflammation and haemophagocytic syndrome were primarily noted in bone marrow specimens where there was evidence of erythroid hyperplasia. These animals were also more often neutropenic and thrombocytopenic, and had decreased 60 day survival when compared with dogs or cats with non-regenerative anaemia associated with erythroid maturation arrest or PRCA. Therefore, the pathogenesis of the non-regenerative anaemia in non-regenerative IMHA may involve both antibody-mediated destruction of bone marrow precursor cells and pathological events within the bone marrow that result in ineffective erythropoiesis.

  1. Linezolid-associated thrombocytopenia: prevention and treatment%利奈唑胺致血小板减少及其防治

    Institute of Scientific and Technical Information of China (English)

    王博雅; 闫素英

    2011-01-01

    Linezolid is an oxazolidinone antibacterial used for the treatment of Gram-positive infection of the respiratory tract and skin, including those due to vancomycin resistant enterocooci. The common adverse reactions are diarrhea, nausea, vomiting, headache, and rash. Linezolid may cause thrombocytopenia, and the risk factors for thrombocytopenia are prolonged use of linezolid, advanced age, and renal insufficiency. The mechanism of thrombocytopenia induced by linezolid might be linked to bone marrow suppression or immune-mediated platelet decrease. The measures for prevention and treatment of thrombocytopenia are as follows: high-dose and prolonged use of linezolid should be avoided; platelet count should be closely monitored during linezolid therapy; linezolid combined with drugs that produce bone marrow suppression should be avoided; linezolid therapy should be discontinued in patients who developed thrombocytopenia, and transfusion of platelets should be considered in patients having severe thrombocytopenia.%利奈唑胺为恶唑烷酮类抗生素,主要用于革兰阳性细菌引起的呼吸道和皮肤感染以及耐万古霉素肠球菌引起的感染.利奈唑胺的常见不良反应为腹泻、恶心、呕吐、头痛、皮疹等.利奈唑胺可致血小板减少,其危险因素为长时间治疗、高龄以及肾功能不全.利奈唑胺所致血小板减少的机制可能与骨髓抑制或免疫介导致血小板减少有关.防治血小板减少的措施:避免大剂量和长时间应用利奈唑胺;用药期间严密监测血小板水平;避免将利奈唑胺与抑制骨髓的药物联用;患者出现血小板减少应立即停药,严重患者可考虑输注血小板.

  2. Acute lymphoblastic leukemia presenting with gross hematuria

    OpenAIRE

    Kalbani, Naifain Al; Weitzman, Sheila; Abdelhaleem, Mohamed; Carcao, Manuel; Abla, Oussama

    2007-01-01

    A case of a six-year-old boy presenting with gross hematuria is reported. Investigations revealed the etiology of the hematuria to be thrombocytopenia in the setting of newly diagnosed acute lymphoblastic leukemia. The diagnosis of leukemia was confirmed by bone marrow examination. The patient’s hematuria completely resolved with platelet transfusions. Although thrombocytopenia is a very common presenting feature of acute lymphoblastic leukemia, gross hematuria is exceedingly rare. Thus, thro...

  3. 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].

  4. 2,3,7,8-TCDD enhances the sensitivity of mice to concanavalin A immune-mediated liver injury.

    Science.gov (United States)

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

    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.

  5. Immune-Mediated Nephropathy and Systemic Autoimmunity in Mice Does Not Require Receptor Interacting Protein Kinase 3 (RIPK3)

    Science.gov (United States)

    Corradetti, Chelsea; Jog, Neelakshi R.; Gallucci, Stefania; Madaio, Michael; Balachandran, Siddharth

    2016-01-01

    Immune mediated nephropathy is one of the most serious manifestations of lupus and is characterized by severe inflammation and necrosis that, if untreated, eventually leads to renal failure. Although lupus has a higher incidence in women, both sexes can develop lupus glomerulonephritis; nephritis in men develops earlier and is more severe than in women. It is therefore important to understand the cellular and molecular mechanisms mediating nephritis in each sex. Previous work by our lab found that the absence or pharmacological inhibition of Poly [ADP-ribose] polymerase 1 (PARP-1), an enzyme involved in DNA repair and necrotic cell death, affects only male mice and results in milder nephritis, with less in situ inflammation, and diminished incidence of necrotic lesions, allowing for higher survival rates. A second pathway mediating necrosis involves Receptor-Interacting Serine-Threonine Kinase 3 (RIPK3); in this study we sought to investigate the impact of RIPK3 on the development of lupus and nephritis in both sexes. To this end, we used two inducible murine models of lupus: chronic graft versus host disease (cGvHD) and pristane-induced lupus; and nephrotoxic serum (NTS)-induced nephritis as a model of immune mediated nephropathy. We found that the absence of RIPK3 has neither positive nor negative impact on the disease development or progression of lupus and nephritis in all three models, and in both male and female mice. We conclude that RIPK3 is dispensable for the pathogenesis of lupus and immune mediated nephropathy as to accelerate, worsen or ameliorate the disease. PMID:27669412

  6. Analysis of polymorphisms in 16 genes in type 1 diabetes that have been associated with other immune-mediated diseases

    Directory of Open Access Journals (Sweden)

    Walker Neil M

    2006-03-01

    Full Text Available Abstract Background The identification of the HLA class II, insulin (INS, CTLA-4 and PTPN22 genes as determinants of type 1 diabetes (T1D susceptibility indicates that fine tuning of the immune system is centrally involved in disease development. Some genes have been shown to affect several immune-mediated diseases. Therefore, we tested the hypothesis that alleles of susceptibility genes previously associated with other immune-mediated diseases might perturb immune homeostasis, and hence also associate with predisposition to T1D. Methods We resequenced and genotyped tag single nucleotide polymorphisms (SNPs from two genes, CRP and FCER1B, and genotyped 27 disease-associated polymorphisms from thirteen gene regions, namely FCRL3, CFH, SLC9A3R1, PADI4, RUNX1, SPINK5, IL1RN, IL1RA, CARD15, IBD5-locus (including SLC22A4, LAG3, ADAM33 and NFKB1. These genes have been associated previously with susceptibility to a range of immune-mediated diseases including rheumatoid arthritis (RA, systemic lupus erythematosus (SLE, Graves' disease (GD, psoriasis, psoriatic arthritis (PA, atopy, asthma, Crohn disease and multiple sclerosis (MS. Our T1D collections are divided into three sample subsets, consisting of set 1 families (up to 754 families, set 2 families (up to 743 families, and a case-control collection (ranging from 1,500 to 4,400 cases and 1,500 to 4,600 controls. Each SNP was genotyped in one or more of these subsets. Our study typically had approximately 80% statistical power for a minor allele frequency (MAF >5% and odds ratios (OR of 1.5 with the type 1 error rate, α = 0.05. Results We found no evidence of association with T1D at most of the loci studied 0.02 P ADAM33, rs2787094, was any evidence of association obtained, P = 0.0004 in set 1 families (relative risk (RR = 0.78, but further support was not observed in the 4,326 cases and 4,610 controls, P = 0.57 (OR = 1.02. Conclusion Polymorphisms in a variety of genes previously associated with

  7. Intrahepatic cholestasis of pregnancy and cancer, immune-mediated and cardiovascular diseases: A population-based cohort study.

    Science.gov (United States)

    Wikström Shemer, Elisabeth A; Stephansson, Olof; Thuresson, Marcus; Thorsell, Malin; Ludvigsson, Jonas F; Marschall, Hanns-Ulrich

    2015-08-01

    Intrahepatic cholestasis of pregnancy (ICP) is the most common liver disease in pregnancy. It is associated with hepatobiliary diseases that might predispose to cancer and also with gestational diabetes and preeclampsia. In this study, we examined associations between ICP and cancer, and immune-mediated and cardiovascular diseases. By linking the Swedish Medical Birth Register and the Swedish Patient Register, we identified 11,388 women with ICP and 113,893 matched women without ICP who gave birth between 1973 and 2009. Diagnoses of cancer and immune-mediated and cardiovascular diseases both before and after delivery were obtained from the Patient Register. The main outcome measures were hazard ratios (HRs), calculated through Cox regression, for the indicated diseases after delivery. ICP was not associated with later overall cancer (HR 1.07, 95% confidence interval [CI] 0.94-1.21), but it was associated with later liver and biliary tree cancer (HR 3.61, 95% CI 1.68-7.77, and 2.62, 95% CI 1.26-5.46, respectively). ICP was also associated with later immune-mediated diseases (HR 1.28, 95% CI 1.19-1.38), and specifically diabetes mellitus (HR 1.47, 95% CI 1.26-1.72), thyroid disease (HR 1.30, 95% CI 1.14-1.47), psoriasis (HR 1.27, 95% CI 1.07-1.51), inflammatory polyarthropathies (HR 1.32, 95% CI 1.11-1.58) and Crohn's disease (HR 1.55, 95% CI 1.14-2.10), but not ulcerative colitis (HR 1.21, 95% CI 0.93-1.58). Women with ICP also had a small increased risk of later cardiovascular disease (HR 1.12, 95% CI 1.06-1.19). Women with ICP have increased risk of later hepatobiliary cancer and immune-mediated and cardiovascular diseases. Copyright © 2015 European Association for the Study of the Liver. Published by Elsevier B.V. All rights reserved.

  8. 脂联素与免疫性皮肤病%Adiponectin and immune-mediated skin diseases

    Institute of Scientific and Technical Information of China (English)

    罗丽敏; 何春涤

    2016-01-01

    脂联素是一种主要由脂肪细胞分泌的内源性生物活性蛋白质,以三聚体、六聚体和高分子量多聚体3种不同的形式存在于外周血中.脂联素与其受体结合后,通过激活下游的信号通路,发挥调控新陈代谢、调节免疫平衡、抑制细胞增殖和炎症反应、维持血管稳态等重要作用,而其免疫调节作用日益成为研究的焦点.近年来研究表明,脂联素积极参与免疫性皮肤病的进程,随着对脂联素免疫调节作用研究的不断深入,其与免疫性皮肤病的关系亦取得了较大进展.拟为今后免疫性皮肤病的临床治疗及用药提供新的方法和思路.概述脂联素与银屑病、系统性红斑狼疮、硬皮病及干燥综合征等免疫性皮肤病的关系.%Adiponectin is an endogenous bioactive protein secreted mainly by adipocytes, and exists in peripheral blood in three forms, including trimers, hexamers and high-molecular weight multimers.By binding to its receptor and activating downstream signaling pathways, it plays an important role in regulating metabolism and immune balance, inhibiting cell proliferation and inflammatory reaction, and maintaining vascular homeostasis.The immunoregulatory effect of adiponectin has been gradually becoming a focus of researches.Recent studies have indicated that adiponectin is actively involved in the development of immune-mediated skin diseases.With further insights into the immunoregulatory effect of adiponectin, great progress has been made in elucidating the relationship between adiponectin and immune-mediated skin diseases, which will provide new methods and ideas for clinical treatment of immune-mediated skin diseases.This review summarizes the relationship between adiponectin and immune-mediated skin diseases, such as psoriasis, systemic lupus erythematosus, scleroderma and Sj(o)gren's syndrome.

  9. Study of thrombopoietin for gene therapy of thrombocytopenia

    Institute of Scientific and Technical Information of China (English)

    崇松; 卢大儒; 李昌本; 邱信芳; 薛京伦

    1999-01-01

    Thrombopoietin (TPO) is likely to be a potent, specific and reliable medication in the treatment of thrombocytopenia. A TPO-highly-expressed plasmid pcDNA3-TPO was constructed and a primary study was made on the expression of TPO cDNA in vitro and gene transfer study for thrombocytopenia in vivo. rhTPO showed complete and stable bioactivity by a series of indicators. High expression of TPO was detected in plasma from healthy mice or thrombocytopenia mice model receiving direct intramuscular injection of pcDNA3-TPO. And the platelet level of healthy mice peaked to 1.9-fold of baseline. Mice with CTX-induced thrombocytopenia achieved profound nadirs, acceleration of recovery, even 1.8—2.0-fold supranormal levels of peripheral platelet counts. The results offered experimental support for clinical application of gene therapy for thrombocytopenia via direct intramuscular injection of TPO cDNA.

  10. Management of thrombocytopenia in the ICU (pregnancy excluded).

    Science.gov (United States)

    Van der Linden, Thierry; Souweine, Bertrand; Dupic, Laurent; Soufir, Lilia; Meyer, Pascal

    2012-08-28

    Thrombocytopenia is a very frequent disorder in the intensive care unit. Many etiologies should be searched, and therapeutic approaches differ according to these different causes. However, no guideline exists regarding optimum practices for these situations in critically ill patients. We present recommendations for the management of thrombocytopenia in intensive care unit, excluding pregnancy, developed by an expert group of the French-Language Society of Intensive Care (Société de Réanimation de Langue Française (SRLF), the French Language Group of Paediatric Intensive Care and Emergencies (GFRUP) and of the Haemostasis and Thrombosis Study Group (GEHT) of the French Society of Haematology (SFH). The recommendations cover six fields of application: definition, epidemiology, and prognosis; diagnostic approach; therapeutic aspects; thrombocytopenia and sepsis; iatrogenic thrombocytopenia, with a special focus on heparin-induced thrombocytopenia; and thrombotic microangiopathy.

  11. Fatal immune-mediated pancytopenia and a TRALI-like syndrome associated with high titers of recipient-type antibodies against donor-derived peripheral blood cells after allogeneic bone marrow transplantation following dose reduced conditioning.

    Science.gov (United States)

    Knop, Stefan; Bux, Juergen; Kroeber, Stefan M; Bader, Peter; Hebart, Holger; Kanz, Lothar; Einsele, Hermann

    2004-05-01

    Pancytopenia occurring after bone marrow transplantation is a rare complication. A 47 year old patient with progression of multiple myeloma after standard therapy received an allogeneic marrow graft from a matched unrelated donor. The non-myeloablative conditioning regimen consisted of fludarabine, cyclophosphamide, rabbit anti-thymocyte globulin and total body irradiation. GVHD prophylaxis consisted of cyclosporine. Neutrophil engraftment was as expected and the patient was discharged without signs of acute GvHD. On day +34 the patient presented with clinical and laboratory findings consistent with severe pancytopenia. Antibodies against red cells, platelets, lymphocytes and granulocytes were detected in extremely high titers. Immune-mediated pancytopenia was refractory on multiple immunosuppressive treatment strategies. Proliferation of polyclonal plasma cells of recipient-type that was documented postmortem, was most likely responsible for excessive antibody formation.

  12. Perioperative use of iloprost in cardiac surgery patients diagnosed with heparin-induced thrombocytopenia-reactive antibodies or with true HIT (HIT-reactive antibodies plus thrombocytopenia): An 11-year experience.

    Science.gov (United States)

    Palatianos, George; Michalis, Alkiviadis; Alivizatos, Petros; Lacoumenda, Stavroula; Geroulanos, Stefanos; Karabinis, Andreas; Iliopoulou, Eugenia; Soufla, Giannoula; Kanthou, Chryso; Khoury, Mazen; Sfyrakis, Petros; Stavridis, George; Astras, George; Vassili, Maria; Antzaka, Christina; Marathias, Katerina; Kriaras, Ioannis; Tasouli, Androniki; Papadopoulos, Kyrillos; Katafygioti, Marina; Matoula, Nikoletta; Angelidis, Antonios; Melissari, Euthemia

    2015-07-01

    Thrombocytopenia and thromboembolism(s) may develop in heparin immune-mediated thrombocytopenia (HIT) patients after reexposure to heparin. At the Onassis Cardiac Surgery Center, 530 out of 17,000 patients requiring heart surgery over an 11-year period underwent preoperative HIT assessment by ELISA and a three-point heparin-induced platelet aggregation assay (HIPAG). The screening identified 110 patients with HIT-reactive antibodies, out of which 46 were also thrombocytopenic (true HIT). Cardiac surgery was performed in HIT-positive patients under heparin anticoagulation and iloprost infusion. A control group of 118 HIT-negative patients received heparin but no iloprost during surgery. For the first 20 patients, the dose of iloprost diminishing the HIPAG test to ≤5% was determined prior to surgery by in vitro titration using the patients' own plasma and donor platelets. In parallel, the iloprost "target dose" was also established for each patient intraoperatively, but before heparin administration. Iloprost was infused initially at 3 ng/kg/mL and further adjusted intraoperatively, until ex vivo aggregation reached ≤5%. As a close correlation was observed between the "target dose" identified before surgery and that established intraoperatively, the remaining 90 patients were administered iloprost starting at the presurgery identified "target dose." This process significantly reduced the number of intraoperative HIPAG reassessments needed to determine the iloprost target dose, and reduced surgical time, while maintaining similar primary clinical outcomes to controls. Therefore, infusion of iloprost throughout surgery, under continuous titration, allows cardiac surgery to be undertaken safely using heparin, while avoiding life-threatening iloprost-induced hypotension in patients diagnosed with HIT-reactive antibodies or true HIT. © 2015 Wiley Periodicals, Inc.

  13. Evaluation of the immature platelet fraction in the diagnosis and prognosis of childhood immune thrombocytopenia.

    Science.gov (United States)

    Adly, Amira Abdel Moneam; Ragab, Iman Ahmed; Ismail, Eman Abdel Rahman; Farahat, Mona Mohammed

    2015-01-01

    Rapid assessment of platelet production would distinguish between thrombocytopenia due to decreased platelet production or increased peripheral platelet destruction. We evaluated the value of immature platelet fraction (IPF) in differentiating immune thrombocytopenia (ITP) from thrombocytopenia secondary to bone marrow failure and its potential use as a prognostic marker. Forty-one young patients with ITP were compared with 14 patients with hematological malignancies under chemotherapy, representing a control group with thrombocytopenia due to bone marrow suppression and 30 age- and sex-matched healthy controls. Patients were studied stressing on bleeding manifestations, organomegaly/lymphadenopathy and therapy. Complete blood count including IPF was performed using Sysmex XE-2100. ITP patients were classified into two subgroups: acute ITP with spontaneous resolution within 3 months from diagnosis and chronic ITP that lasted ≥ 1 year from diagnosis. Median IPF was 11.8% in patients with ITP, 7% in those with hematological malignancy and 3% in the control group (p < 0.001). ITP patients had significantly higher mean platelet volume (MPV), platelet distribution width (PDW), platelet large cell ratio (P-LCR) and IPF compared with patients with malignancy or healthy controls, while plateletcrit (PCT) was significantly lower in ITP patients than other groups (p < 0.001). IPF was increased in patients with chronic ITP compared with acute ITP group (p < 0.001). Patients with active ITP had the highest IPF followed by those in partial remission, while ITP patients in remission had the lowest IPF. IPF was positively correlated to the number of lines of treatment used, MPV, PDW and P-LCR, while negatively correlated to platelet count and PCT among ITP patients (p < 0.001). Multiple regression analysis showed that platelet count and P-LCR were independently related to IPF. ROC curve analysis revealed that the cut-off value of IPF at 9.4% could be diagnostic for ITP patients

  14. Topical TLR7 agonist imiquimod can induce immune-mediated rejection of skin metastases in patients with breast cancer.

    Science.gov (United States)

    Adams, Sylvia; Kozhaya, Lina; Martiniuk, Frank; Meng, Tze-Chiang; Chiriboga, Luis; Liebes, Leonard; Hochman, Tsivia; Shuman, Nicholas; Axelrod, Deborah; Speyer, James; Novik, Yelena; Tiersten, Amy; Goldberg, Judith D; Formenti, Silvia C; Bhardwaj, Nina; Unutmaz, Derya; Demaria, Sandra

    2012-12-15

    Skin metastases of breast cancer remain a therapeutic challenge. Toll-like receptor 7 agonist imiquimod is an immune response modifier and can induce immune-mediated rejection of primary skin malignancies when topically applied. Here we tested the hypothesis that topical imiquimod stimulates local antitumor immunity and induces the regression of breast cancer skin metastases. A prospective clinical trial was designed to evaluate the local tumor response rate of breast cancer skin metastases treated with topical imiquimod, applied 5 d/wk for 8 weeks. Safety and immunologic correlates were secondary objectives. Ten patients were enrolled and completed the study. Imiquimod treatment was well tolerated, with only grade 1 to 2 transient local and systemic side effects consistent with imiquimod's immunomodulatory effects. Two patients achieved a partial response [20%; 95% confidence interval (CI), 3%-56%]. Responders showed histologic tumor regression with evidence of an immune-mediated response, showed by changes in the tumor lymphocytic infiltrate and locally produced cytokines. Topical imiquimod is a beneficial treatment modality for breast cancer metastatic to skin/chest wall and is well tolerated. Importantly, imiquimod can promote a proimmunogenic tumor microenvironment in breast cancer. Preclinical data generated by our group suggest superior results with a combination of imiquimod and ionizing radiation and we are currently testing in patients whether the combination can further improve antitumor immune and clinical responses. ©2012 AACR.

  15. Interplay among cytokines and T cell subsets in the progression and control of immune-mediated diseases.

    Science.gov (United States)

    Moudgil, Kamal D

    2015-07-01

    Cytokines serve as key mediators of inflammation and tissue damage in a variety of immune-mediated disorders. The induction, progression, and resolution of inflammation in such disorders are characterized by a dynamic balance between both the pro-inflammatory and anti-inflammatory cytokines as well as the pathogenic and protective T cell subsets. Over the past two decades, the roles of the interleukin-17 (IL-17) /IL-23 axis and the T helper 17 (Th17)/ T regulatory (Treg) cell balance in the pathogenesis of autoimmunity and other inflammatory diseases have extensively been analyzed, and their significance validated. However, these studies, coupled with others devoted to well-established Th1/Th2 cytokines, have unraveled some challenging issues including the dual action of cytokines and the plasticity of T cell subsets. Nevertheless, major positive advances have also been made regarding cytokines and T cell subsets as therapeutic targets/agents. In this special issue, "Cytokines in Immune Pathology and Therapy," leading experts have shared their research work and perspectives on the roles of cytokines in the development and control of immune-mediated diseases. An outline of 14 articles in the first volume is presented here. The second volume will follow soon.

  16. THROMBOCYTOPENIA & RUPTURED CORPUS LUTEAL CYST : A DEADLY COMBINATION: A CASE REPORT

    Directory of Open Access Journals (Sweden)

    Baidya

    2015-07-01

    Full Text Available Ovarian corpus luteal cyst occurs during reproductive years, at end of menstrual cycle, or during pregnancy. The presentation of ruptured luteal cyst may vary from no symptoms to symptoms and signs of acute abdomen . 1 Ruptured corpus luteal cyst in some instances causes massive intraperitoneal hemorrhage leading to death in patient , 2 particularly those with bleeding diathesis. Fitzgerald & Berrigan (1959 called it an “ovarian accident”& it is rarely accurately diagnosed before operation . 3 In this case report, we will depict a case of ruptured corpus luteal cyst which became catastrophic for the patient with thrombocytopenia.

  17. Thrombocytopenia in Preterm Infants with Intrauterine Growth Restriction

    Directory of Open Access Journals (Sweden)

    Matsuda,Miwa

    2008-10-01

    Full Text Available Sick preterm infants often have thrombocytopenia at birth, and this is often associated with intrauterine growth restriction (IUGR, or birth weights less than the 10th percentile. The pathogenesis of the thrombocytopenia and its importance in IUGR are still unclear. We studied the characteristics of preterm IUGR infants with thrombocytopenia. Twenty-seven singleton Japanese preterm IUGR infants were born between January 2002 and June 2007 at Okayama University Hospital. Infants with malformation, chromosomal abnormalities, alloimmune thrombocytopenia, sepsis, and maternal aspirin ingestion were excluded. The infants were divided into group A (n=8, which had thrombocytopenia within 72h after birth, and group B (n=19, which did not. There were significant differences in birth weight, head circumference, umbilical artery (UA-pulsatility index (PI, middle cerebral artery-PI, UA-pH, UA-pO2, and UA-pCO2. The infants in group A were smaller, had abnormal blood flow patterns, and were hypoxic at birth. We speculate that the infants with thrombocytopenia were more severely growth-restricted by chronic hypoxia. Thrombocytopenia is an important parameter for chronic hypoxia in the uterine.

  18. Immune Thrombocytopenia and Obesity: Predictive Relationship

    Science.gov (United States)

    Hanafy, Ehab; Pakra, Mohammed Al

    2017-01-01

    Background: Chronic refractory immune thrombocytopenia (ITP) is defined as the failure of any modality to maintain the platelet count above 20 × 103/μL for an appreciable time without unacceptable toxicity. To date, certain predictive factors have been associated with refractory ITP. However, none of the published studies has declared the possible association between obesity and refractory ITP. Case Reports: We present the cases of 3 children with ITP who failed to achieve remission on different therapeutic approaches including rituximab, vincristine, and romiplostim. The 3 children had obesity as a common feature. Conclusion: We present these cases to propose a possible association between obesity and refractoriness of ITP to different therapeutic approaches and to emphasize the need for further study to establish whether a causal relationship exists.

  19. 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

  20. Acute Renal Failure: Unusual Complication of Epstein-Barr Virus-Induced Infectious Mononucleosis

    National Research Council Canada - National Science Library

    Paul S. Lei; Amy Lowichik; Wain Allen; Teri Jo Mauch

    2000-01-01

    A 17-year-old boy with juvenile rheumatoid arthritis presented with jaundice, confusion, hemolytic anemia, thrombocytopenia, and acute renal failure secondary to titer-confirmed acute Epstein-Barr virus (EBV...

  1. Co-stimulation with LPS or Poly I:C markedly enhances the anti-platelet immune response and severity of fetal and neonatal alloimmune thrombocytopenia.

    Science.gov (United States)

    Li, Conglei; Chen, Pingguo; Vadasz, Brian; Ma, Li; Zhou, Hui; Lang, Sean; Freedman, John; Ni, Heyu

    2013-12-01

    Fetal and neonatal alloimmune thrombocytopenia (FNAIT) is a life-threatening bleeding disorder caused by maternal antibodies against fetal/neonatal platelets. FNAIT is also linked with miscarriages, although the incidence and mechanisms of fetal death have not been well studied. IntegrinαIIbβ3 (GPIIbIIIa) and the GPIbα complex are major glycoproteins expressed on platelets and are also major antigens targeted in autoimmune thrombocytopenia (ITP), but reported cases of anti-GPIb-mediated FNAIT are rare. Bacterial and viral infections have been causally linked with the pathogenesis of immune-mediated thrombocytopenia (ITP); however, it is unknown whether these infections contribute to the severity of FNAIT. Here, immune responses against platelet antigens were examined by transfusing wild-type (WT) mouse platelets into β3-/- or GPIbα-/- mice. To mimic bacterial or viral infections, lipopolysaccharide (LPS) or polyinosinic:polycytidylic acid (Poly I:C) were injected intraperitoneally following platelet transfusions. The FNAIT model was established by breeding the immunised female mice with WT male mice. We demonstrated for the first time that the platelet GPIbα has lower immunogenicity compared to β3 integrin. Interestingly, co-stimulation with LPS or Poly I:C markedly enhanced the immune response against platelet GPIbα and caused severe pathology of FNAIT (i.e. miscarriages). LPS or Poly I:C also enhanced the immune response against platelet β3 integrin. Our data suggest that bacterial and viral infections facilitate the anti-platelet GPIbα response, which may lead to a severe non-classical FNAIT (i.e. miscarriage but not neonatal bleeding) that has not been adequately reported in humans.

  2. 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

  3. 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

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

    Directory of Open Access Journals (Sweden)

    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.

  5. Retrospective study on clinical features and interventional therapy of acute deep venous thrombosis of lower extremity combined with type Ⅱ heparin-induced thrombocytopenia%急性下肢深静脉血栓形成合并Ⅱ型肝素诱导血小板减少症的临床特征及介入综合治疗效果

    Institute of Scientific and Technical Information of China (English)

    苏浩波; 赵伯翔; 黄昊; 楼文胜; 顾建平; 何旭; 陈亮; 陈国平; 宋进华; 施万印; 汪涛

    2015-01-01

    此类患者深静脉血栓介入治疗效果。%Objective To explore the clinical features, diagnosis and interventional management of acute deep venous thrombosis of lower extremity (LEDVT)combined with type Ⅱ heparin-induced thrombocytopenia (HITⅡ) and to improve the knowledge of this disease. Methods A retrospective review and analysis of the clinical data of the patients with acute LEDVT combined with HIT Ⅱ enrolled from January 2010 to June 2014. All of them underwent anticoagulation with low molecular weight heparin (LMWH) and the comprehensive interventional therapy at the beginning of treatment.When HIT Ⅱ was identified, all forms of heparin and LMWH were avoided . Alternative anticoagulation was commenced with argatrobam. Adjustments in interventional therapy were taken while the short-term low-dose glucocorticoid treatment were used.The clinical manifestations, changes of PLT, 4Ts score (Warkentin 4T scoring system, 4Ts) , HIT antibody assay (ELISA) and response to therapy of the patients were analyzed and the treatment effect was observed . The efficacy of interventional therapy was evaluated according to the improvement clinical symptoms and venography. Results The incidence of acute LEDVT combined with HIT Ⅱ was 1.9%(8/416). There were 4 males and 4 females with a median age of 24 years in this study. The median time between their initiation exposure to heparin and onset of thrombocytopenia was 5 days (range,3 to 8 days). The median platelet counts prior to HIT Ⅱ was 218 × 109/L( range,122 × 109/L to 254 × 109/L ). Platelet counts decreased to the lowest level range from 20 × 109/L to 51 × 109/L(median 32 × 109/L). After alternative anticoagulation, the interval period which PLT recovered to the basic level was range from 3 to 7 days (median 3.5 days) . According to the score of 4Ts , there were 2 cases score 6 and 6 cases score 8. HIT antibody assay (ELISA) was detected in 6 patients which the results were positive. During heparin

  6. Leptin inhibitors from fungal endophytes (LIFEs): Will be novel therapeutic drugs for obesity and its associated immune mediated diseases.

    Science.gov (United States)

    Chandra Mouli, K; Pragathi, D; Naga Jyothi, U; Shanmuga Kumar, V; Himalaya Naik, M; Balananda, P; Suman, B; Seshadri Reddy, V; Vijaya, T

    2016-07-01

    Treatment of obesity and its associated immune mediated diseases is challenging due to impaired function of leptin system. Thus leptin is providing an interesting target for therapeutic intervention. Leptin, an adipose tissue-derived adipokine, displays a variety of immune functions, and regulate both innate and adaptive immune responses. The increased secretion of leptin (hyperleptinemia) and production of proinflammatory cytokines has been implicated in the pathogenesis of obesity-related immune diseases such as diabetes mellitus, hypertension, atherosclerosis, cancer, systemic lupus erythematosus, rheumatoid arthritis, crohn's disease and multiple sclerosis. These disorders are managed through antibiotics and by cytokines replacement. However, the effectiveness of cytokines coupled to the complexity of the cytokine network leads to severe side-effects, which can still occur after careful preclinical evaluation. In addition, synthetic immunotherapeutics carries a degree of risk, is time-consuming and expensive. Hence, the complexity of existing therapy and adverse effects emphasizes the need of an alternative approach for the management of immune dysfunction associated with obesity and its related diseases. For the aforementioned diseases that are related to leptin overabundance, new drugs blocking leptin signaling need to be generated. The research on the discovery of clinically important novel compounds from natural source is expanding due to their safety and no side effect. The fungal endophytes are the microbes that colonize internal tissue of plants without causing negative effects to the host. They produce plethora of substances of potential use to modern medicinal and pharmaceutical industry. The increasing body of evidence associated with application of bioactive metabolites derived from fungal endophytes in diverse disease states merits its use as therapeutic drugs. In particular, the saponins have been extensively proved to modulate the immune system

  7. Idiopathic Mediastinal Fibrosis: a Systemic Immune-Mediated Disorder. A Case Series and a Review of the Literature.

    Science.gov (United States)

    Rossi, Giovanni M; Emmi, Giacomo; Corradi, Domenico; Urban, Maria L; Maritati, Federica; Landini, Federica; Galli, Paola; Palmisano, Alessandra; Vaglio, Augusto

    2017-06-01

    Mediastinal fibrosis is a rare disease characterised by fibrous proliferation in the mediastinum. It can be idiopathic or secondary to several conditions such as infections and malignancies. Anecdotal reports have described idiopathic mediastinal fibrosis (IMF) in association with other fibro-inflammatory or autoimmune diseases. We report nine new IMF cases recently seen at our Fibro-Inflammatory Disease Clinic and reviewed the IMF cases reported in the English language literature throughout 2006-2016. The purposes of our literature search were to assess the frequency of the association between IMF and other immune-mediated disorders and to analyse which disorders most often coexist with IMF. Of our nine IMF cases, one was associated with anti-neutrophil cytoplasmic antibody (ANCA)-associated vasculitis, one with large-vessel arteritis, three with idiopathic retroperitoneal fibrosis (one of which was IgG4-related), one with pancreatitis and one with IgG4-related seminal vesicle involvement. The remaining two cases, in which IMF was not associated with any other disease, were both classifiable as IgG4-related. The literature review showed that, of the 84 IMF cases identified, 27 (32 %) were associated with other idiopathic autoimmune or fibro-inflammatory disorders, particularly small-vessel vasculitis, Behçet disease, retroperitoneal fibrosis and other conditions belonging to the IgG4-related disease spectrum. Based on our own data and the literature review, we conclude that IMF is often associated with other autoimmune or fibro-inflammatory diseases; therefore, its clinical management requires an accurate screening of associated conditions. Immune-mediated mechanisms may be shared by these disorders.

  8. Thrombocytopenia after therapeutic hypothermia in severe traumatic brain injury

    Institute of Scientific and Technical Information of China (English)

    QIU Wu-si; WANG Wei-min; DU Hong-ying; LIU Wei-guo; SHEN Hong; SHEN Lei-fen; ZHU Ming-lan

    2006-01-01

    Objective: To investigate the clinical characteristics and significance of thrombocytopenia after therapeutic hypothermia in severe traumatic brain injury (TBI).Methods: Ninety-six inpatients with severe brain injury were randomized into three groups: SBC (selective brain cooling ) group (n =24), MSH ( mild systemic hypothermia ) group ( n = 30), and control (normothermia) group ( n = 42). The platelet counts and prognosis were retrospectively analyzed.Results: Thrombocytopenia was present in 18 (75 % ), 23 (77 % ) and 15 (36 % ) patients in SBC group,MSH group and control group, respectively (P <0.01 ).Thrombocytopenia, in which the minimum platelet count was seen 3 days after hypothermia, showed no significant difference between SBC and MSH group (P > 0.05). Most platelet counts (37 cases, 90% ) in hypothermia group were returned to normal level after 1 to 2 days of natural rewarming. The platelet count in SBC group reduced by 16%, 27% and 29% at day 1, 3 and 5 respectively compared with the baseline value. Good recovery (GOS score 4-5) rate of thrombocytopenia 1 year after injury for hypothermia group ( 17 cases, 37 % ) was significantly lower than that of control group (P <0.01).Conclusions: Therapeutic hypothermia increases the incidence of thrombocytopenia in severe TBI, and patients with thrombocytopenia after therapeutic hypothermia are associated with unfavorable neurological prognosis.

  9. Efalizumab-induced severe thrombocytopenia can be resolved

    Directory of Open Access Journals (Sweden)

    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

  10. A STUDY OF THROMBOCYTOPENIA IN PATIENTS WITH P. VIVAX MALARIA

    Directory of Open Access Journals (Sweden)

    Apte

    2013-12-01

    Full Text Available ABSTRACT: BACKGROUND: Malaria is commonly associated with various degrees of haematological complications most frequently with anaemia and thrombocytopenia. However there are contrasting reports about frequency of thrombocytopenia in P. vivax infection. MATERIAL AND METHODS: A total of 140 patients were included in the study. The details of the patients history along with their clinical f eatures, laboratory reports were recorded in a standard proforma. Sample of venous blood were collected for haematological examination like Haemoglobin, total and differential count and platelet count, which was done under automated cell counter. RESULTS: Out of 140, there were 119(85% patients who had thrombocytopenia, of them 75(54% patients had mild, 38(27% patients had moderate and 6(4% patients had severe thrombocytopenia., 30(21% out of 140 patients had leucopenia. Significant inverse association was seen between degree of parasitemia and platelet count. CONCLUSION: Various theories have been postulated for the cause of thrombocytopenia in P. Vivax infection but none of them is conclusive. Frequency or severity of thrombocytopenia doesn’t appear t o be any particular strain of plasmodium infection.

  11. Beyond the platelet count: immature platelet fraction and thromboelastometry correlate with bleeding in patients with immune thrombocytopenia.

    Science.gov (United States)

    Greene, Lindsey A; Chen, Siqi; Seery, Caroline; Imahiyerobo, Allison M; Bussel, James B

    2014-08-01

    Platelet counts (PC) estimate bleeding risk in Immune Thrombocytopenia (ITP). We investigated whether measures of thromboelastometry and absolute immature platelet fraction (A-IPF) would correlate better with acute bleeding score (ABS) than PC or mean platelet volume (MPV). Simultaneous determination of ABS, complete blood count and thromboelastometry was performed in 141 ITP patients; 112 underwent A-IPF testing. Subgroup analyses were performed for paediatric subjects, PC children with PC children and children with PC platelet function, contribute to ITP bleeding pathophysiology. Thromboelastometry, A-IPF and ABS can be incorporated into routine or acute visits.

  12. Hashimoto's Encephalopathy Presenting with Acute Cognitive Dysfunction and Convulsion.

    Science.gov (United States)

    Kang, Woo-Hyuk; Na, Ju-Young; Kim, Meyung-Kug; Yoo, Bong-Goo

    2013-12-01

    Hashimoto's encephalopathy is an immune-mediated disorder characterized by acute or subacute encephalopathy related to increased anti-thyroid antibodies. Clinical manifestations of Hashimoto's encephalopathy may include stroke-like episodes, altered consciousness, psychosis, myoclonus, abnormal movements, seizures, and cognitive dysfunction. Acute cognitive dysfunction with convulsion as initial clinical manifestations of Hashimoto's encephalopathy is very rare. We report a 65-year-old man who developed acute onset of cognitive decline and convulsion due to Hashimoto's encephalopathy.

  13. 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.

  14. Short-course oral prednisone treatment in children with acute immune thrombocytopenia%大剂量短疗程泼尼松治疗儿童急性免疫性血小板减少症的疗效观察

    Institute of Scientific and Technical Information of China (English)

    王娴静; 邹湘; 赵晓武

    2013-01-01

    目的 观察大剂量短疗程泼尼松(Pred)疗法对儿童急性免疫性血小板减少症(ITP)的疗效.方法 162例ITP患儿根据治疗方法不同随机分为大剂量静脉丙种球蛋白+甲基泼尼松龙组(IVIG+MP)、静脉丙种球蛋白组(IVIG)、甲基泼尼松龙组(MP)与Predl组.IVIG+MP组41例,采用IVIG(1g/kg,共1次)+MP[10 mg/(kg·d),每3天减半量,共9 d]冲击治疗,继之口服Pred[1.5~2.0 mg/(kg·d)],并逐渐减量维持治疗;IVIG组39例,采用丙种球蛋白(1 g/kg,共1次)冲击治疗,继之口服Pred[1.5~2.0 mg/(kg·d)]并逐渐减量维持治疗;MP组40例,采用MP[10 mg/(kg·d),每3天减半量,共9 d]冲击治疗,继之口服Pred[1.5~2.0 mg/(kg·d)]并逐渐减量维持治疗;Pred组42例,采用口服Pred[4 mg/(kg·d),共4 d]治疗后停药,无减量维持治疗.比较各组治疗前后血小板数、治疗有效率、不良反应发生率及药费支出.结果 各治疗组治疗前后血小板数及治疗有效率差异无显著性,IVIG+MP组、IVIG组、MP组治疗不良反应发生率及药费支出均高于Pred组.结论 大剂量短疗程Pred疗法治疗儿童急性ITP能有效提升血小板计数,有效率与IVIG及MP冲击治疗相比差异无显著性,不良反应少,花费低.%Objective To analyze the effects of large dose of short-course oral prednisone on the childhood acute immune thrombocytopenia ( ITP) . Methods We conducted 162 children with primary acute ITP and randomized divided them into 4 groups; IVIG + MP group, IVIG group, MP group and prednisone group. For IVIG + MP group, 41 children with ITP were treated with intravenous immunoglobulin G ( IVIG) 1 g/kg once and methylprednisolone ( MP) 10 mg/( kg · d) for 3 days, and with tapering and discontinuation of prednisone by 4 ~6 months. For IVIG group, 39 children with ITP were treated with IVIG 1g/kg once, and with tapering and discontinuation of prednisone by 4 ~ 6 months. For the MP group, 40 children with ITP were treated with MP 10 mg/( kg · d

  15. 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

  16. Improving and standardising assessment of patients with immune-mediated neuropathies: Peripheral Neuropathy outcome measures Standardisation study (PeriNomS study – part 1)

    NARCIS (Netherlands)

    S.I. van Nes (Sonja)

    2012-01-01

    textabstractIn this thesis, the outline and the results of the fi rst part of the Peripheral Neuropathy outcome measures Standardisation (PeriNomS) study are described. The PeriNomS study aims to improve and standardise the assessment of patients with immune-mediated neuropathies. These disorders

  17. Thrombocytopenia is not mandatory to diagnose haemolytic and uremic syndrome

    Directory of Open Access Journals (Sweden)

    Sallée Marion

    2013-01-01

    Full Text Available Abstract Background Hemolytic and uremic syndrome (HUS diagnosis involves association of non immune hemolytic anemia, thrombocytopenia, and renal failure. HUS without thrombocytopenia has been observed, we call it partial HUS. Its real frequency and outcome are unknown. The aim of this study was to determine the prevalence of patients with normal platelets count in two HUS cohorts and to compare their outcome to patients with thrombocytopenia. Methods We retrospectively identified HUS diagnosis in two different cohorts. The first cohort was from a single center and consisted of all cases of HUS whatever the aetiology, the second was multicentric and consisted of atypical HUS patients. These cohorts were divided into two groups depending on the presence or absence of thrombocytopenia. Clinical and biological data were compared between thrombopenic and non thrombopenic group. Results We identified 13% (20/150 of patients with normal platelets count: 10 episodes (18% of HUS in six patients (14% in the monocentric cohort and 14 patients (13% with 17 episodes (12% in the multicentric cohort of atypical HUS. Groups differed in platelets count and LDH level. In both cohorts, renal outcome was similar to patient presenting with thrombocytopenia. Conclusion HUS with normal platelets count is not infrequent. Relative to classical clinical presentation of HUS, partial HUS has similar characteristics and identical poor renal outcome and so must be treated in the same way.

  18. A study of thrombocytopenia in hospitalized vivax malaria patients

    Directory of Open Access Journals (Sweden)

    Hassan Abu Zaid

    2012-09-01

    Full Text Available Objective: To assess the occurrence and severity of thrombocytopenia in hospitalized vivax malaria patients.Design and setting:Retrospective and descriptive hospital based case series from March 2005 to March 2007, conducted in the medical unit of Al Khor Hospital.Patients and methods: 78 patients with peripheral smear positive were enrolled in the study. Peripheral smear examination for malaria parasites was used as the method of choice for the diagnosis of malaria. Hematological parameters were determined by using an automated analyzer. Low platelet counts were re-evaluated by manual methods.Results:Study sample was 78 patients, of which 65 patients (83.3% were thrombocytopenic. Of these, 41 patients (52.6% had mild thrombocytopenia, 23 patients (29.5% had moderate thrombocytopenia and 1 patient (1.3% had severe thrombocytopenia. All patients (100% were male.Conclusion:High prevalence of thrombocytopenia was seen in vivax malaria patients, making it a common hematological feature in vivax malaria.

  19. 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.

  20. 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

  1. Effect of Moringa oleifera Lam. seed extract on toluene diisocyanate-induced immune-mediated inflammatory responses in rats.

    Science.gov (United States)

    Mahajan, Shailaja G; Mali, Ravindra G; Mehta, Anita A

    2007-04-01

    Moringa oleifera Lam. is a small tree cultivated throughout India. We have investigated the effect of ethanolic extract of seeds of Moringa oleifera (MOEE, an herbal remedy) on the potential prevention of immune-mediated inflammatory responses in toluene diisocyanate (TDI as antigen)-induced asthma in Wistar rats. Rats were divided into five different groups (n = 8/group): Group-I = unsensitized control; Group-II = TDI control/vehicle; Group-III = dexamethasone (DXM) 2.5 mg/kg; and, Groups IV and V = 100 mg/kg and 200 mg/kg body weight [BW] of MOEE, respectively. All rats (except unsensitized controls) were sensitized by intranasal application of 10% TDI to induce airway hypersensitivity. Animals in Groups II-V were given their respective drug treatment per os from 1 wk prior to initiation of sensitization until the day of final provocation with 5% TDI. After this last challenge, all rats were examined for hyperreactivity symptoms and then sacrificed to determine their total and differential leucocytes in blood and bronchoalveolar (BAL) fluid and levels of TNF proportional, variant, IL-4, and IL-6 in their BAL and serum. Homogenates of one lung lobe from each animal were utilized to assess oxidative stress; a separate lobe underwent histologic examination to assess airway inflammatory status. The results suggest that asthmatic symptoms were found in TDI control rats only, while both MOEE- and DXM-treated rats did not manifest any airway abnormality. In MOEE- and DXM-treated rats, neutrophil and eosinophil levels in the blood were decreased significantly; levels of total cells and each different cell in their BAL fluid were markedly decreased as compared to those in TDI controls. TNF alpha, IL-4, and IL-6 were predominant in serum as well as in BAL fluids in TDI controls, but these levels were reduced significantly by MOEE treatment. The antioxidant activity in relation to antiinflammatory activity of the extract and histopathological observations also reflected a

  2. Relapsed hydroxychloroquine induced thrombocytopenia in a systemic lupus erythematosus patient.

    Science.gov (United States)

    Antón Vázquez, Vanesa; Pascual, Luis; Corominas, Héctor; Giménez Torrecilla, Isabel

    Hydroxychloroquine is used in the long-term therapy of systemic lupus erythematosus (SLE). Although considered to be a safe treatment, side effects have been documented. An uncommon side effect is thrombocytopenia. In order to establish the diagnosis of thrombocytopenia secondary to Hydroxychloroquine, non-pharmacological causes must be ruled out and it is necessary to determine a recurrence after re-exposure to the drug. We present one case of severe thrombocytopenia occurring in a patient with SLE undergoing treatment with Hydroxychloroquine. Copyright © 2016 Elsevier España, S.L.U. and Sociedad Española de Reumatología y Colegio Mexicano de Reumatología. All rights reserved.

  3. Simultaneous occurrence of fetal and neonatal alloimmune thrombocytopenia and neonatal neutropenia due to maternal neutrophilic autoantibodies

    DEFF Research Database (Denmark)

    Taaning, Ellen; 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...

  4. Thrombocytopenia in Systemic Lupus Erythematosus: Clinical Manifestations, Treatment, and Prognosis in 230 Patients

    National Research Council Canada - National Science Library

    Jung, Jin-Hee; Soh, Moon-Seung; Ahn, Young-Hwan; Um, Yoo-Jin; Jung, Ju-Yang; Suh, Chang-Hee; Kim, Hyoun-Ah

    2016-01-01

    The aim of the study was to examine the clinical characteristics and prognosis according to severity of thrombocytopenia and response to treatment for thrombocytopenia in patients with systemic lupus erythematosus (SLE...

  5. 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....

  6. Genetic Associations in Acquired Immune-Mediated Bone Marrow Failure Syndromes: Insights in Aplastic Anemia and Chronic Idiopathic Neutropenia

    Directory of Open Access Journals (Sweden)

    Irene Mavroudi

    2012-01-01

    Full Text Available Increasing interest on the field of autoimmune diseases has unveiled a plethora of genetic factors that predispose to these diseases. However, in immune-mediated bone marrow failure syndromes, such as acquired aplastic anemia and chronic idiopathic neutropenia, in which the pathophysiology results from a myelosuppressive bone marrow microenvironment mainly due to the presence of activated T lymphocytes, leading to the accelerated apoptotic death of the hematopoietic stem and progenitor cells, such genetic associations have been very limited. Various alleles and haplotypes of human leucocyte antigen (HLA molecules have been implicated in the predisposition of developing the above diseases, as well as polymorphisms of inhibitory cytokines such as interferon-γ, tumor necrosis factor-α, and transforming growth factor-β1 along with polymorphisms on molecules of the immune system including the T-bet transcription factor and signal transducers and activators of transcription. In some cases, specific polymorphisms have been implicated in the outcome of treatment on those patients.

  7. Heparin-Induced Thrombocytopenia: A Comprehensive Clinical Review.

    Science.gov (United States)

    Salter, Benjamin S; Weiner, Menachem M; Trinh, Muoi A; Heller, Joshua; Evans, Adam S; Adams, David H; Fischer, Gregory W

    2016-05-31

    Heparin-induced thrombocytopenia is a profoundly dangerous, potentially lethal, immunologically mediated adverse drug reaction to unfractionated heparin or, less commonly, to low-molecular weight heparin. In this comprehensive review, the authors highlight heparin-induced thrombocytopenia's risk factors, clinical presentation, pathophysiology, diagnostic principles, and treatment. The authors place special emphasis on the management of patients requiring procedures using cardiopulmonary bypass or interventions in the catheterization laboratory. Clinical vigilance of this disease process is important to ensure its recognition, diagnosis, and treatment. Misdiagnosis of the syndrome, as well as misunderstanding of the disease process, continues to contribute to its morbidity and mortality.

  8. Tuberculous splenic abscess in a neonate with thrombocytopenia

    Energy Technology Data Exchange (ETDEWEB)

    Amodio, John; Biskup, Darius; Rivera, Rafael; Fefferman, Nancy [New York University Medical Center, Department of Radiology, NY (United States); Shah, Shetal [New York University Medical Center, Division of Neonatology, Department of Pediatrics, Avenue, NY (United States)

    2005-09-01

    We present a case of a premature neonate who presented with anemia and persistent thrombocytopenia. The patient was ultimately diagnosed with disseminated tuberculosis. Initial sonographic evaluation of the abdomen revealed a heterogeneous but predominately hypoechoic spleen; there was subsequent evolution of a splenic abscess. The patient was treated medically with anti-tubercular drugs. Follow-up post-treatment sonograms of the spleen showed diminution of the abscess and the evolution of multiple calcifications compatible with calcified granulomas. This case is an unusual presentation of tuberculosis in an infant with splenic abscess associated with thrombocytopenia and anemia. (orig.)

  9. 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...... sporadically in the material. CONCLUSIONS: The spectrum of drugs reported as causing drug-induced thrombocytopenia is broadening and changing progressively, reflecting changes in drug consumption. The most frequently reported drugs at present are valproic acid and measlesmumps-rubella vaccine....

  10. Significant correlation between spleen volume and thrombocytopenia in liver transplant patients: a concept for predicting persistent thrombocytopenia.

    Science.gov (United States)

    Ohira, Masahiro; Ishifuro, Minoru; Ide, Kentaro; Irei, Toshimitsu; Tashiro, Hirotaka; Itamoto, Toshiyuki; Ito, Katsuhide; Chayama, Kazuaki; Asahara, Toshimasa; Ohdan, Hideki

    2009-02-01

    Interferon (IFN) therapy with or without ribavirin treatment is well established as a standard antiviral treatment for hepatitis C virus (HCV)-infected patients. However, susceptibility to thrombocytopenia is a major obstacle for initiating or continuing this therapy, particularly in liver transplant (LTx) recipients with HCV. Studies have reported that splenectomy performed concurrently with LTx is a feasible strategy for conditioning patients for anti-HCV IFN therapy. However, the relationship between the severity of splenomegaly and alterations in the blood cytopenia in LTx recipients remains to be clarified. Here, we analyzed the relationship between spleen volume (SV) and thrombocytopenia in 45 patients who underwent LTx at Hiroshima University Hospital. The extent of pre-LTx splenomegaly [the SV to body surface area (BSA) ratio in an individual] was inversely correlated with both the post-LTx white blood cell count and platelet (PLT) count (P or= 400), persistent thrombocytopenia is predictable after LTx.

  11. Cerebrospinal fluid neopterin analysis in neuropediatric patients: establishment of a new cut off-value for the identification of inflammatory-immune mediated processes.

    Directory of Open Access Journals (Sweden)

    Marta Molero-Luis

    Full Text Available OBJECTIVE: A high level of cerebrospinal fluid (CSF neopterin is a marker of central nervous system inflammatory-immune mediated processes. We aimed to assess data from 606 neuropediatric patients, describing the clinical and biochemical features of those neurological disorders presenting CSF neopterin values above a new cut-off value that was defined in our laboratory. METHODS: To establish the new CSF neopterin cut-off value, we studied two groups of patients: Group 1 comprised 68 patients with meningoencephalitis, and Group 2 comprised 52 children with a confirmed peripheral infection and no central nervous system involvement. We studied 606 CSF samples from neuropediatric patients who were classified into 3 groups: genetic diagnosis (A, acquired/unknown etiologic neurologic diseases (B and inflammatory-immune mediated processes (C. RESULTS: The CSF neopterin cut-off value was 61 nmol/L. Out of 606 cases, 56 presented a CSF neopterin level above this value. Group C had significantly higher CSF neopterin, protein and leukocyte values than the other groups. Sixteen of twenty-three patients in this group had a CSF neopterin level above the cut-off, whereas three and seven patients presented increased leukocyte and protein values, respectively. A significant association was found among CSF neopterin, proteins and leukocytes in the 606 patients. White matter disturbances were associated with high CSF neopterin concentrations. CONCLUSIONS: Although children with inflammatory-immune mediated processes presented higher CSF neopterin values, patients with other neurological disorders also showed increased CSF neopterin concentrations. These results stress the importance of CSF neopterin analysis for the identification of inflammatory-immune mediated processes.

  12. Altered distribution of regulatory lymphocytes by oral administration of soy-extracts exerts a hepatoprotective effect alleviating immune mediated liver injury, non-alcoholic steatohepatitis and insulin resistance

    Science.gov (United States)

    Khoury, Tawfik; Ben Ya'acov, Ami; Shabat, Yehudit; Zolotarovya, Lidya; Snir, Ram; Ilan, Yaron

    2015-01-01

    AIM: To determine the immune-modulatory and the hepatoprotective effects of oral administration of two soy extracts in immune mediated liver injury and non-alcoholic steatohepatitis (NASH). METHODS: Two soy extracts, M1 and OS, were orally administered to mice with concanavalin A (ConA) immune-mediated hepatitis, to high-fat diet (HFD) mice and to methionine and choline reduced diet combined with HFD mice. Animals were followed for disease and immune biomarkers. RESULTS: Oral administration of OS and M1 had an additive effect in alleviating ConA hepatitis manifested by a decrease in alanine aminotransferase and aspartate aminotransferase serum levels. Oral administration of the OS and M1 soy derived fractions, ameliorated liver injury in the high fat diet model of NASH, manifested by a decrease in hepatic triglyceride levels, improvement in liver histology, decreased serum cholesterol and triglycerides and improved insulin resistance. In the methionine and choline reduced diet combined with the high fat diet model, we noted a decrease in hepatic triglycerides and improvement in blood glucose levels and liver histology. The effects were associated with reduced serum tumor necrosis factor alpha and alteration of regulatory T cell distribution. CONCLUSION: Oral administration of the combination of OS and M1 soy derived extracts exerted an adjuvant effect in the gut-immune system, altering the distribution of regulatory T cells, and alleviating immune mediated liver injury, hyperlipidemia and insulin resistance. PMID:26139990

  13. Thrombocytopenia, bleeding, and use of platelet transfusions in sick neonates.

    Science.gov (United States)

    Stanworth, Simon J

    2012-01-01

    Survival rates for infants born prematurely have improved significantly, in part due to better supportive care such as RBC transfusion. The role of platelet transfusions in neonates is more controversial. Neonatal thrombocytopenia is common in premature infants. The primary causal factors are intrauterine growth restriction/maternal hypertension, in which the infant presents with thrombocytopenia soon after birth, and sepsis/necrotizing enterocolitis, which are the common morbidities associated with thrombocytopenia in neonates > 72 hours of age. There is no evidence of a relationship between platelet count and occurrence of major hemorrhage, and cardiorespiratory problems are considered the main etiological factors in the development of intraventricular and periventricular hemorrhage in the neonatal period. Platelet transfusions are used commonly as prophylaxis in premature neonates with thrombocytopenia. However, there is widespread variation in the pretransfusion thresholds for platelet count and evidence of marked disparities in platelet transfusion practice between hospitals and countries. Platelet transfusions are biological agents and as such are associated with risks. Unlike other patient groups, specifically patients with hematological malignancies, there have been no recent clinical trials undertaken comparing different thresholds for platelet transfusion in premature neonates. Therefore, there is no evidence base with which to inform safe and effective practice for prophylactic platelet transfusions. There is a need for randomized controlled trials to define the optimal use of platelet transfusions in premature neonates, who at present are transfused heavily with platelets.

  14. 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...

  15. A patient with Graves' disease, thrombocytopenia and chronic hepatitis B.

    OpenAIRE

    Szeto, C C; Chow, C C; Ko, G. T.; K. Y. LI; Yeung, V. T.; Cockram, C S

    1997-01-01

    A 22-year-old Chinese man, a HBsAg carrier, presented with relapse of thyrotoxic Graves' disease complicated by thrombocytopenia and hepatitis. Platelet count and liver enzymes gradually improved following successful treatment of the thyrotoxicosis with radioactive iodine. Possible pathogenetic links and therapeutic implications are discussed.

  16. Salmonella enteritidis from a case of fever with thrombocytopenia

    Institute of Scientific and Technical Information of China (English)

    Shamma Arora; Naveen Gupta; Ashwani Kumar; IR Kaur

    2011-01-01

    Non typhoidalSalmonella species are thought to be potentially infectious to humans. We isolated Salmonella enteritidis from a 10-year-old boy with fever and thrombocytopenia. We reviewed the literature concerning infections caused bySalmonella but we could not find any such case report from India.

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

    Directory of Open Access Journals (Sweden)

    Deepak 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. DiscussionNeonatal 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

  18. 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

  19. A study on association of thrombocytopenia with pregnancy induced hypertension

    Directory of Open Access Journals (Sweden)

    Kasturi V. Donimath

    2016-03-01

    Conclusions: Thrombocytopenia is the most common complications of PIH and at times is life threatening. Therefore, platelet count can be used as an early, simple, and rapid test to assess the severity of pre eclampsia and prevent progression to HELLP syndrome and DIC. [Int J Reprod Contracept Obstet Gynecol 2016; 5(3.000: 808-812

  20. Intracerebral hemorrhage caused by varicella-induced thrombocytopenia.

    Science.gov (United States)

    Lizarazo, Jairo; Castellanos, María Fernanda; Omaña, Claudia Rosa; Chaín, Miguel; Villamizar, Sergio

    2016-02-16

    We present the case of a previously healthy 44-years-old man with chickenpox, severe thrombocytopenia, mucosal hemorrhage, and intracerebral hemorrhage in the right hemisphere. The patient was treated with platelets and high doses of steroids. He recovered although with persistent left homonymous hemianopsia and epilepsy, which were controlled with medication.

  1. Mechanisms of action of intravenous immunoglobulin in the treatment of immune thrombocytopenia.

    Science.gov (United States)

    Crow, Andrew R; Song, Seng; Siragam, Vinayakumar; Lazarus, Alan H

    2006-10-15

    Intravenous immunoglobulin (IVIG) is currently used to treat a multitude of autoimmune disorders including immune thrombocytopenic purpura (ITP), yet the mechanism of action of IVIG remains unresolved. Using a murine model of ITP in which IVIG functions therapeutically, our laboratory has addressed such theories as blockade/inhibition of the mononuclear phagocytic system, cytokine regulation, and neutralization of pathogenic autoantibodies mediated by anti-idiotypic antibodies, and these findings will be discussed herein. We have also demonstrated that soluble immune complexes can completely recapitulate the therapeutic effects of IVIG in ITP, and recent work from us has identified activating Fcgamma receptors on CD11c+ dendritic cells as the relevant molecular target of IVIG in the acute resolution of murine immune thrombocytopenia. This and other work to devise antibody-based IVIG alternative therapies will also be addressed. Copyright (c) 2006 Wiley-Liss, Inc.

  2. IFN-γ-mediated hematopoietic cell destruction in murine models of immune-mediated bone marrow failure.

    Science.gov (United States)

    Chen, Jichun; Feng, Xingmin; Desierto, Marie J; Keyvanfar, Keyvan; Young, Neal S

    2015-12-10

    Interferon gamma (IFN-γ) has been reported to have both negative and positive activity on hematopoietic cells, adding complexity to the interpretation of its pleiotropic functions. We examined the effects of IFN-γ on murine hematopoietic stem cells (HSCs) and progenitors in vitro and in vivo by using mouse models. IFN-γ treatment expanded bone marrow (BM) c-Kit(+)Sca1(+)Lin(-) (KSL) cell number but reduced BM KLCD150(+) and KLCD150(+)CD48(-) cells. IFN-γ-expanded KSL cells engrafted poorly when tested by competitive repopulation in vivo. KSL, KLCD150(+), and KLCD150(+)CD48(-) cells from IFN-γ-treated animals all showed significant upregulation in Fas expression. When cocultured with activated T cells in vitro, KSL and KLCD150(+) cells from IFN-γ-treated donors showed increased apoptosis relative to those from untreated animals, and infusion of activated CD8 T cells into IFN-γ-injected animals in vivo led to partial elimination of KSL cells. Exposure of BM cells or KSL cells to IFN-γ increased expression of Fas, caspases, and related proapoptotic genes and decreased expression of Ets-1 and other hematopoietic genes. In mouse models of BM failure, mice genetically deficient in IFN-γ receptor expression showed attenuation of immune-mediated marrow destruction, whereas effector lymphocytes from IFN-γ-deficient donors were much less potent in initiating BM damage. We conclude that the activity of IFN-γ on murine hematopoiesis is context dependent. IFN-γ-augmented apoptotic gene expression facilitates destruction of HSCs and progenitors in the presence of activated cytotoxic T cells, as occurs in human BM failure.

  3. Changes in Vaginal Microbiota and Immune Mediators in HIV-1-Seronegative Kenyan Women Initiating Depot Medroxyprogesterone Acetate.

    Science.gov (United States)

    Roxby, Alison C; Fredricks, David N; Odem-Davis, Katherine; Ásbjörnsdóttir, Kristjana; Masese, Linnet; Fiedler, Tina L; De Rosa, Stephen; Jaoko, Walter; Kiarie, James N; Overbaugh, Julie; McClelland, R Scott

    2016-04-01

    Depot medroxyprogesterone acetate (DMPA) is associated with HIV acquisition. We studied changes in vaginal microbiota and inflammatory milieu after DMPA initiation. In a cohort of HIV-negative Kenyan women, we collected monthly vaginal swabs over 1 year before and after DMPA. Using quantitative polymerase chain reaction, we compared quantities of Lactobacillus crispatus, Lactobacillus jensenii, Lactobacillus iners, Gardnerella vaginalis, and total bacterial load (16S ribosomal RNA gene levels). Six vaginal immune mediators were measured with enzyme-linked immunosorbent assay. Trends in the detection and quantity of bacteria were estimated by logistic and linear mixed-effects regression. From 2010 to 2012, 15 HIV-seronegative women initiated DMPA, contributing 85 visits (median, 6 visits/woman; range, 3-8 visits/woman). The median time of DMPA-exposed follow-up was 8.4 months (range, 1.5-11.6 months). Seven women (46%) had bacterial vaginosis within 70 days before DMPA start. L. iners was detected in 13 women (87%) before DMPA start, but other lactobacilli were rarely detected. Gardnerella vaginalis decreased by 0.21 log10 copies per swab per month after DMPA exposure (P = 0.01). Total bacterial load decreased by 0.08 log10 copies per swab per month of DMPA (P = 0.02). Sustained decreases in interleukin (IL)-6 (P = 0.03), IL-8 (P = 0.04), and IL-1 receptor antagonist (P < 0.001) were also noted. Nine women (60%) had L. crispatus detected post-DMPA, which significantly correlated with reduced IL-6 (P < 0.01) and IL-8 (P = 0.02). Initiation of DMPA led to sustained shifts in vaginal bacterial concentrations and levels of inflammatory mediators. Further studies are warranted to outline components of the vaginal microbiota influenced by DMPA use and impact on HIV susceptibility.

  4. Targeting B cells in immune-mediated inflammatory disease: a comprehensive review of mechanisms of action and identification of biomarkers.

    Science.gov (United States)

    Dörner, Thomas; Kinnman, Nils; Tak, Paul P

    2010-03-01

    B cell-depletion therapy, particularly using anti-CD20 treatment, has provided proof of concept that targeting B cells and the humoral response may result in clinical improvements in immune-mediated inflammatory disease. In this review, the mechanisms of action of B cell-targeting drugs are investigated, and potential biomarkers associated with response to treatment in patients with autoimmune diseases are identified. Most available data relate to B cell depletion using anti-CD20 therapy (rituximab) in patients with rheumatoid arthritis (RA). Treatment leads to significant clinical benefit, but apparently fails to deplete long-lived plasma cells, and discontinuation is associated with relapse. Biomarkers commonly used in studies of B cell-targeted therapies include rheumatoid factor, anti-citrullinated peptide antibodies, and immunoglobulin (Ig) levels. More recently, there has been interest in markers such as B cell phenotype analysis, and B lymphocyte stimulator (BLyS)/a proliferation-inducing ligand (APRIL), the latter particularly in studies of the IgG Fc-transmembrane activator and CAML interactor (TACI) fusion protein (atacicept) and anti-BLyS therapy (belimumab). Data from clinical trials of B cell-depleting agents in RA suggest that specific autoantibodies, BLyS, APRIL, and circulating and synovial B lineage cell levels may have potential as biomarkers predictive of response to treatment. Further trials validating these markers against clinical outcomes in RA are required. In patients with systemic lupus erythematosus, Fc receptors and levels of circulating immune cells (including B cells and natural killer cells) may be relevant markers.

  5. Comprehensive analysis of inflammatory immune mediators of the intraocular fluid aspirated from the foldable capsular vitreous body filled-eyes.

    Directory of Open Access Journals (Sweden)

    Peijuan Wang

    Full Text Available PURPOSE: To analyze the level of human inflammatory immune mediators in the intraocular fluid aspirated from foldable capsular vitreous body (FCVB filled-eyes during FCVB removal surgery, 3 months after implantation. METHODS: 8 samples of intra-FCVB fluids (n = 8 were collected from 8 FCVB filled patients in our previous FCVB exploratory clinical trial. The intra-FCVB fluids were aspirated from the FCVB filled-eyes during the FCVB removal surgeries at the third month. For the control groups, the vitreous fluids were collected from patients with idiopathic macular hole (n = 9 or rhegmatogenous retinal detachment (n = 6 during pars plana vitrectomy. A multiplex immunoassay was used to determine levels of 9 cytokines (IL-1β, IL-2, IL-6, IL-8, IL-10, IL-17, TNF-α, IFN-γ and VEGF in these samples. The VEGF level of some intra-FCVB fluids (n = 6 were re-tested using enzyme-linked immunosorbent assay (ELISA. RESULTS: In the intra-FCVB fluids, 9 cytokines concentrations of most samples (n = 5 measured by Multiplex immunoassay showed low values, except for Patient 02, 06, and 09. The VEGF concentrations of some intra-FCVB fluids (n = 6 tested by ELISA were in accordance with Multiplex immunoassay results. For all eight patients (n = 8, the concentrations of IL-1β, IL-2, IL-6, TNF-α, IFN-γ and VEGF were slightly higher as compared to the idiopathic macular hole control group. While, the concentrations of IL-8, IL-10, and IL-17 were not statistically significant different compared with the idiopathic macular hole control samples. Most cytokines concentrations (IL-2, IL-6, IL-8, IL-10, IL-17, TNF-α, IFN-γ, VEGF were not statistically significant different compared to the rhegmatogenous retinal detachment control group except IL-1β. CONCLUSIONS: The FCVB had sufficient porosity to allow cytokines to pass through. This study first discovered that the FCVB possesses favorable permeability of proteins in the human eye.

  6. Immune-mediated bone marrow failure syndromes of progenitor and stem cells: molecular analysis of cytotoxic T cell clones.

    Directory of Open Access Journals (Sweden)

    Ramon Tiu

    2007-03-01

    Full Text Available The unique structure of the T cell receptor (TCR enables molecular identification of individual T cell clones and provides an unique opportunity for the design of molecular diagnostic tests based on the structure of the rearranged TCR chain e.g., using the TCR CDR3 region. Initially, clonal T cell malignancies, including T cell large granular lymphocyte leukemia (T-LGL, mucosis fungoides and peripheral T cell lymphoma were targets for the TCR-based analytic assays such as detection of clonality by T-gamma rearrangement using y-chain-specific PCR or Southern Blotting. Study of these disorders facilitated further analytic concepts and application of rational methods of TCR analysis to investigations of polyclonal T cell-mediated diseases. In hematology, such conditions include graft versus host disease (GvHD and immune-mediated bone marrow failure syndromes. In aplastic anemia (AA, myelodysplastic syndrome (MDS or paroxysmal nocturnal hemoglobinuria (PNH, cytotoxic T cell responses may be directed against certain antigens located on stem or more lineage-restricted progenitor cells in single lineage cytopenias. The nature of the antigenic targets driving polyclonal CTL responses remains unclear. Novel methods of TCR repertoire analysis, include VB flow cytometry, peptide-specific tetramer staining, in vitro stimulation assays and TCR CDR3-specific PCR. Such PCR assay can be either VB family-specific or multiplexed for all VB families. Amplified products can be characterized and quantitated to facilitate detection of the most immunodominant clonotypes. Such clonotypes may serve as markers for the global polyclonal T cell response. Identification of these clonotypes can be performed in blood and tissue biopsy material by various methods. Once immunodominant clonotypes corresponding to pathogenic CTL clones are identified they can serve as surrogate markers for the activity of the pathophysiologic process or even indicate the presence of specific

  7. 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

  8. 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.

  9. 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.

  10. ANAEMIC RETINOPATHY WITH THROMBOCYTOPENIA: AN INTERESTING CASE REPORT

    Directory of Open Access Journals (Sweden)

    Parul

    2014-07-01

    Full Text Available Anemia is a group of disorders characterized by decrease in number of circulating red blood cells, decrease in amount of hemoglobin in each cell or both. We report an interesting case of young female who presented to us with clinical presentation of anemic retinopathy with thrombocytopenia. History of bleeding gums with menorrhagia was present. She had short history of diminish vision in both eyes. Fundus changes were very typical of anemic retinopathy with presence of Roth spots as characteristic finding. Disc pallor and venous tortousity was also present in both eyes. Fundus picture showed marked improvement with blood transfusion. Our case confirms the association of anemic retinopathy in patients suffering with severe anemia with coexisting thrombocytopenia

  11. Acquired amegakaryocytic thrombocytopenia: Three case reports and a literature review

    Directory of Open Access Journals (Sweden)

    Antonijević Nebojša

    2004-01-01

    Full Text Available Introduction Acquired amegakaryocytic thrombocytopenia (AAT is a rare disease characterized by thrombocytopenia due to selective reduction/absence of bone marrow (BM megakaryocytes. In the BM culture isolated reduction of colony-forming units-megakaryocyte (CFU-Mk may occur. Material and methods BM aspirates and trephine biopsies were obtained from all patients and processed by routine methods. In vitro BM culture and cytogenetic analysis was performed in one patient. Results This article presents three patients with manifested signs of hemorrhagic syndrome due to severe thrombocytopenia caused by an absence/significant reduction of BM megakaryocytes. Eexistence of systemic or any other disease was excluded in all patients. BM culture of the second patient showed reduction of all hematopoietic progenitors. In the subsequent course of the disease in this patient, signs of dysplastic erythrocytic series and megakaryocytes were also noted, although there were no positive proofs of evolution into myelodysplastic syndrome. Discussion AAT is a disease of hematopoietic stem cells manifesting in a certain period as amegakaryocytic thrombocytopenia which subsequently may progress into aplastic anemia or myelodysplastic syndrome. Patients were treated with corticosteroids, lithium carbonate, androgens, vincristine, immunoglobulins, folic acid, platelet and erythrocyte transfusions along with plasma substitution. The first patient reacted positively to the therapy. In two other patients a minimal, short-term therapeutic effect was achieved, followed by improvement of hemorrhagic syndrome and an insignificant increase in platelet count. In one patient the treatment was stopped after 4 months and the other died of bleeding after 4 months. Conclusion AAT is a rare disease with unpredictable course. This is a case report of three patients with AAT and different therapeutic effects.

  12. Sports Participation in Children and Adolescents with Immune Thrombocytopenia (ITP).

    Science.gov (United States)

    Kumar, Manjusha; Lambert, Michele P; Breakey, Vicky; Buchanan, George R; Neier, Michelle; Neufeld, Ellis J; Kempert, Pamela; Neunert, Cindy E; Nottage, Kerri; Klaassen, Robert J

    2015-12-01

    We surveyed 278 pediatric hematologists/oncologists regarding how children with immune thrombocytopenia (ITP) are counseled for participation in sports. Results show substantial variation in physician perception of contact risk for different sports, and the advice offered about restriction of sport activities of affected children. Many physicians recommend restriction of sports when platelet counts are under 50 × 10(9) /L. Such restriction may affect the child's quality of life despite their having an overall benign disease.

  13. Effect of recombinant human thrombopoietin on exsanguine thrombocytopenia mice

    Institute of Scientific and Technical Information of China (English)

    2001-01-01

    AIM:To investigate effect of recombinant human thrombopoietin on exsanguine thrombocytopenia mice. METHODS:Normal peripheral platelet counts were performed on sample obtained from the tail vein of purebred Babl/c mice including experimental and control groups before experimentation. rhTPO was injected into the mice by intraperitoneal injection once a day for 7 days. On the seventh and the fourteenth day, the mice were phlebotomized from the supra-obitalis vein in order to make exsanguine thrombocytopenia animal model. At the same time, we observed the biological activity of recombinant human thrombopoietin in vivo and the mice's death rate. RESULTS: On the seventh day and the fourteenth day, platelet counts of mice treated by rhTPO were higher than those by PBS (P<0.05). Moreover the platelet counts of mice in experimental group of rhTPO showed increasing tendency following experimental days. In addition, death happened in two groups after those mice were phlebotomized from the supra-obitalis vein, but the death rate in negative control group was evidently higher than that in experimental group (P<0.05). CONCLUSION:rhTPO had obvious biological activity in increasing platelet production, which resulted in the drop in thrombocytopenia mice's death rate.

  14. Trombocitopenia induzida por heparina Heparin-induced thrombocytopenia

    Directory of Open Access Journals (Sweden)

    Fernanda Longhi

    2001-08-01

    Full Text Available O objetivo deste relato é fazer uma revisão a fim de obter informações atualizadas sobre trombocitopenia induzida por heparina, suas manifestações clínicas, seu diagnóstico e seu manejo terapêutico. Após, concluímos que a trombocitopenia induzida por heparina é uma complicação comum em pacientes submetidos a tratamento com heparina, indiferentemente da doença de base. Complicações trombóticas potencialmente fatais têm sido descritas. Por essa razão, se houver suspeita de trombocitopenia induzida por heparina, uma abordagem adequada incluindo suspensão precoce da heparina é mandatória. Produtos que substituem a heparina incluem hirudina e danaparóide sódico. Heparina de baixo peso molecular é contra-indicada.The aim of this paper is to review current information about the clinical manifestations, diagnosis and management of heparin-induced thrombocytopenia. This was achieved by a bibliographic review using Public Medline and consulting Hematology textbooks. From this study we concluded that heparin-induced thrombocytopenia is a common complication of patients exposed to heparin therapy regardless of underlying conditions. Potentially fatal thrombotic complications have been reported. Therefore, if heparin-induced thrombocytopenia is suspected, an adequate approach including early heparin discontinuation is mandatory. Alternative products for heparin include hirudin and danaparoid sodium. Low-molecular-weight heparin is contraindicated.

  15. Hepatitis B Leading to Megaloblastic Anemia and Catastrophic Peripheral Thrombocytopenia.

    Science.gov (United States)

    Hafeez, Muhammad; Sarfraz, Tariq; Khan, Raja Ghayas; Rafe, Abdul; Rasool, Ghulam; Ahmed, Kamran Nazir

    2016-12-01

    Hepatitis B virus (HBV) typically causes chronic hepatitis, cirrhosis, and hepatocellular carcinoma. It is associated with a variety of extrahepatic complications. We herein, present a rare extrahepatic complication of HBV infection. A 32-year man presented with melena, bleeding from gums and fever. Peripheral blood examination revealed anemia, macrocytosis and severe thrombocytopenia. His hepatitis B surface antigen (HBsAg) was positive but deoxyribonucleic acid (HBV DNA) by polymerase chain reaction (PCR) was negative. Other hepatitis, human immune deficiency virus (HIV), dengue, and autoimmune serology were negative. Bone marrow examination revealed megaloblastic erythropoiesis. There was mild to moderate reduction of megakaryocytes in bone marrow, which was not compatible with severe peripheral thrombocytopenia. His response to cyanocobalamin and folic acid was remarkable for myeloid cell lines and moderate for erythroid cell lines, but poor to platelet counts. Platelet counts gradually improved to safe limits with eltrombopag, likely reflecting autoimmune pathogenesis for thrombocytopenia. This case report highlights multiple targets of HBV infection with associated multiple pathogenetic mechanisms.

  16. 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.

  17. Platelet activation determines the severity of thrombocytopenia in dengue infection

    Science.gov (United States)

    Ojha, Amrita; Nandi, Dipika; Batra, Harish; Singhal, Rashi; Annarapu, Gowtham K.; Bhattacharyya, Sankar; Seth, Tulika; Dar, Lalit; Medigeshi, Guruprasad R.; Vrati, Sudhanshu; Vikram, Naval K.; Guchhait, Prasenjit

    2017-01-01

    Thrombocytopenia is common in patients with dengue virus (DENV) infections. With a focus on understanding the possible mechanism of thrombocytopenia in DENV infections we described a direct correlation between activation and depletion of platelets in patients. Our data showed a sharp decrease in platelet counts at day 4 of fever in patients. The high DENV genome copies in platelets correlated directly with the elevated platelet activation along with increased binding of complement factor C3 and IgG on their surface at day 4. Recovery in platelet count was observed on day 10 through day 6 and 8 with simultaneous decrease in platelet activation markers. Further, our in vitro data supported the above observations describing a concentration-dependent increase in platelet activation by DENV serotype-2. The high copy number of DENV2 genome in the platelet pellet correlated directly with platelet activation, microparticle generation and clot formation. Furthermore the DENV2-activated platelets were phagocytosed in large numbers by the monocytes. The DENV2-mediated lysis and clearance of platelets were abrogated in presence of platelet activation inhibitor, prostacyclin. These observations collectively suggest that platelet activation status is an important determinant of thrombocytopenia in dengue infections. A careful strategy of inactivation of platelets may rescue them from rapid destruction during DENV infections. PMID:28139770

  18. Report: Heparin-induced thrombocytopenia associated with cardiopulmonary bypass: Preliminary attempt with recombinant human thrombopoietin therapy.

    Science.gov (United States)

    Yuan, Shi-Min

    2015-09-01

    Recombinant human thrombopoietin (rhTPO) is popularly used for the treatment of chemotherapy-induced thrombocytopenia. However, rhTPO therapy for heparin-induced thrombocytopenia relating to cardiopulmonary bypass has not been previously described. A young patient developed heparin-induced thrombocytopenia during open-heart surgery. Postoperative rhTPO therapy (15000 units injection hypodermatica once daily for consecutive 3 days) made a quick platelet recovery without any side effects. Heparin-induced thrombocytopenia associated with cardiopulmonary bypass is more likely to be benign, and is curable to rhTPO therapy. The preliminary rhTPO administration of heparin-induced thrombocytopenia in association with cardiopulmonary bypass shows satisfactory pharmaceutical effects with lower dose, shorter duration treatment and shorter platelet increase time and recovery time in comparison with those for the treatment of chemotherapy-induced thrombocytopenia. rhTPO therapy does not produce any side effects and it could avoid or minimize necessary blood product infusions.

  19. Cutaneous angiosarcoma of the buttock complicated by severe thrombocytopenia: A case report

    OpenAIRE

    Nagao, Kaoru; Suzuki, Kayo; Yasuda, Taketoshi; HORI, TAKESHI; HACHINODA, JUN; Kanamori, Masahiko; Kimura, Tomoatsu

    2013-01-01

    Angiosarcoma (AS) is an aggressive, malignant endothelial cell tumor of vascular or lymphatic origin, the presentation and clinical behavior of which may vary according to its location. This is the case report of a 56-year-old woman with cutaneous angiosarcoma (CAS) of the buttock complicated by severe thrombocytopenia. A review of the literature revealed that only nine cases of CAS with thrombocytopenia have been previously reported. The prognosis of CAS complicated by thrombocytopenia is po...

  20. 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.

  1. Heparin-Induced Thrombocytopenia in a Patient with Essential Thrombocythemia: A Case Based Update

    Directory of Open Access Journals (Sweden)

    Edva Noel

    2015-01-01

    Full Text Available Vascular thrombosis is a common clinical feature of both essential thrombocythemia (ET and heparin-induced thrombocytopenia (HIT. The development of HIT in a patient with ET is rare and underrecognized. We report the case of a 77-year-old woman with preexisting ET, who was admitted with acute coronary syndrome, and IV heparin was started. She was exposed to unfractionated heparin (UFH 5 days prior to this admission. Decrease in platelet count was noted, and HIT panel was sent. Heparin was discontinued. Patient developed atrial fibrillation, and Dabigatran was started. On day three, patient also developed multiple tiny cerebral infarctions and acute right popliteal DVT. On day ten of admission, HIT panel was positive, and Dabigatran was changed to Lepirudin. Two days later, Lepirudin was also discontinued because patient developed pseudoaneurysm on the right common femoral artery at the site of cardiac catheterization access. A progressive increase in the platelet count was noted after discontinuing heparin. Physicians should be aware of the coexistence of HIT and ET, accompanied challenges of the prompt diagnosis, and initiation of appropriate treatment.

  2. 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.

    Science.gov (United States)

    Musters, Anne; Assaf, Amira; Gerlag, Danielle M; Tak, Paul P; Tas, Sander W

    2015-01-01

    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 hematological 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, we will discuss that off-label prescription of biologics can be a good way to discover new treatments for rare diseases. This will be illustrated 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.

  3. Bleeding After Endoscopic Procedures in Patients With Chronic Hematologic Thrombocytopenia.

    Science.gov (United States)

    Oh, Hyun Jin; Park, Jae Myung; Yoon, Seung Bae; Lee, Han Hee; Lim, Chul-Hyun; Kim, Jin Su; Cho, Yu Kyung; Lee, Bo-In; Cho, Young-Seok; Choi, Myung-Gyu

    2017-03-01

    Procedure-induced bleeding is a major complication after endoscopic intervention. The aim of this study was to investigate the risk of endoscopy-related bleeding in patients with chronic hematologic thrombocytopenia. We investigated endoscopy-related bleeding in 175 procedures performed on 108 patients with immune thrombocytopenic purpura or aplastic anemia. The outcomes were compared with those of 350 procedures on age-, sex-, and procedure-matched control subjects. Endoscopic interventions included low-risk procedures such as endoscopic biopsy and high-risk procedures including polypectomy, endoscopic resection, and endoscopic retrograde cholangiopancreatogram with sphincterotomy. Bleeding occurred in 17 (9.7%) procedures among the patients with thrombocytopenia. This rate was significantly higher than that in procedures on controls (3.1%, P = 0.003). About 60% of all bleeding events were observed within 24 h after the endoscopic procedure. Bleeding after endoscopic biopsy developed more frequently in the patient group than in the control group (7.1 vs. 0.7%; P Bleeding occurred after 20% of all high-risk procedures. The incidence of bleeding was significantly elevated in patients with a platelet count less than 50 × 10(3)/μl. Multivariate analysis revealed that high-risk procedures and low platelet count (less than 50 × 10(3)/μl) were significantly related to procedure-related bleeding. All bleeding events stopped spontaneously or were controlled with endoscopic hemostasis. Endoscopic procedure-related bleeding develops frequently in patients with chronic hematologic thrombocytopenia. Post-procedural bleeding should be observed carefully in these patients, especially when the platelet count is less than 50 × 10(3)/μl or high-risk endoscopic procedures are planned.

  4. View Point on Severe Fever with Thrombocytopenia Syndrome

    Institute of Scientific and Technical Information of China (English)

    2013-01-01

    Severe fever with thrombocytopenia syndrome (SFTS), a new disease of zoonotic natural foci has been increasing in recent years. In this review, the disease of human granulocytic anaplasmosis infection due to tick-borne and new Bunia virus infection, have similar clinical symptoms. Total of 11 articles were retrieved. The emergence, etiology, nomenclature and pathogenic mechanisms, clinical diagnosis and genotyping of SFTS were summarized, and the current situation of treatment was also evaluated. In conclusion, early detection, identiifcation and treatment are the key points to SFTS, but how to reduce the mortality of critically ill patients is still the focus in the future.

  5. Resolution of chronic severe refractory thrombocytopenia after treatment of hypothyroidism

    Science.gov (United States)

    Bowles, K M; Turner, G E; Wimperis, J Z

    2004-01-01

    The case of a 52 year old woman with chronic severe refractory thrombocytopenia is presented. Over a three year period, her platelet count was persistently less than 20 × 109/litre (normal range, 150–400). She required repeated hospital admission for management of bleeding and received multiple blood transfusions. She was given repeated courses of steroids, immunosuppression, immunoglobulin, and splenectomy, without success, in an attempt to stop the chronic blood loss. Eventually, she was found to be profoundly hypothyroid. On correction of her thyroid deficiency the platelet count returned to the normal range and all bleeding stopped. The platelet count remains in the normal range three years later. PMID:15333667

  6. Acute Hepatitis Induced by Alpha-Interferon in a Patient with Chronic Hepatitis C

    Directory of Open Access Journals (Sweden)

    Ivan Kraus

    2001-01-01

    Full Text Available Hepatic adverse effects occur very rarely with alpha-interferon therapy. A case of acute hepatitis induced by alpha-interferon in a 33-year-old man with chronic hepatitis C is described. The patient developed acute hepatitis with very high aminotransferase activity and jaundice. After discontinuing alpha-interferon therapy, hepatitis resolved rapidly. The immune-mediated mechanism is the most probable cause of this hepatitis.

  7. Hashimoto’s Encephalopathy Presenting with Acute Cognitive Dysfunction and Convulsion

    OpenAIRE

    Kang, Woo-Hyuk; Na, Ju-Young; Kim, Meyung-Kug; Yoo, Bong-Goo

    2013-01-01

    Hashimoto’s encephalopathy is an immune-mediated disorder characterized by acute or subacute encephalopathy related to increased anti-thyroid antibodies. Clinical manifestations of Hashimoto’s encephalopathy may include stroke-like episodes, altered consciousness, psychosis, myoclonus, abnormal movements, seizures, and cognitive dysfunction. Acute cognitive dysfunction with convulsion as initial clinical manifestations of Hashimoto’s encephalopathy is very rare. We report a 65-year-old man wh...

  8. Acute Hepatitis Induced by Alpha-Interferon in a Patient with Chronic Hepatitis C

    OpenAIRE

    Ivan Kraus; Dinko Vitezic

    2001-01-01

    Hepatic adverse effects occur very rarely with alpha-interferon therapy. A case of acute hepatitis induced by alpha-interferon in a 33-year-old man with chronic hepatitis C is described. The patient developed acute hepatitis with very high aminotransferase activity and jaundice. After discontinuing alpha-interferon therapy, hepatitis resolved rapidly. The immune-mediated mechanism is the most probable cause of this hepatitis.

  9. Gestational Thrombocytopenia Complicated with Macrosomia, Failure to Progress in Active Labor, and Postpartum Hemorrhage

    Directory of Open Access Journals (Sweden)

    Shih-Peng Mao

    2007-06-01

    Conclusion: Gestational thrombocytopenia does not usually require treatment if there is no bleeding tendency. However, when other bleeding complications are present, it may exacerbate coagulopathy and exhaust the platelet reserve, thereby worsening the condition. If surgical intervention cannot be avoided, blood and platelet transfusion before a cesarean delivery is highly recommended in severe gestational thrombocytopenia.

  10. Acute Disseminated Encephalomyelitis Following Typhoid Fever: A Case Report

    Directory of Open Access Journals (Sweden)

    R Adhikari

    2014-04-01

    Full Text Available The involvement of central nervous system in children with typhoid fever is common. Acute disseminated encephalomyelitis is a rare immune mediated and demyelinating disease of the central nervous system that usually affects children. We report a 7-year-old child with typhoid fever who developed acute cerebellar syndrome due to acute disseminated encephalomyelitis.Journal of College of Medical Sciences-Nepal, 2013, Vol-9, No-4, 55-58 DOI: http://dx.doi.org/10.3126/jcmsn.v9i4.10237

  11. Fatal thrombocytopenia: A rare case with possible explanation

    Science.gov (United States)

    Barik, Ramachandra; Patnaik, A. N.; Gulati, A. S.

    2012-01-01

    A 22 year old male presented with breathlessness on exertion, ecchymosis, jaundice and features of worsening right heart failure for the last fifteen days. On physical examination, he had a mid diastolic murmur in the tricuspid area and an ejection systolic murmur in the pulmonary area. Bone marrow histopathology report showed an increased in megakaryocytes count. Routine investigations reports were normal. Echocardiography and computerized tomography (CT) revealed a single mobile large intra cardiac mass originating from the right atrium and causing dynamic obstruction of the right ventricular inflow and outflow tract. Associated fatal thrombocytopenia did not respond to intravenous steroids or platelet transfusion. Patient could not be operated because of very low platelet count, and died during hospital stay before excision biopsy could be done. Pathological autopsy was not done. This is a rare case, as the fatal thrombocytopenia observed here was the result of mechanical effects like frictional and shear force, which can be attributed to the physical presence of a large intra cardiac mass resulting in obstruction to flow. PMID:22629036

  12. Invasive thymoma with pure red cell aplasia and amegakaryocytic thrombocytopenia

    Directory of Open Access Journals (Sweden)

    Takuya Onuki

    2016-12-01

    Full Text Available We here describe a case involving a 67-yearold female patient who was referred to our hospital due to severe anemia (hemoglobin, 5.0 g/dL, thrombocytopenia (platelet count, 0.6×104/μL, and a mediastinal shadow with calcification noted on X-ray. On admission, an anterior mediastinal tumor was detected, and bone marrow biopsy revealed few megakaryocytes and severely reduced numbers of erythroid cells. The diagnosis was thymoma with pure red cell aplasia (PRCA and acquired amegakaryocytic thrombocytopenia (AAMT. On Day 8 of admission, the patient received immunosuppressive therapy together with cyclosporine for the 2 severe hematologic diseases, which were stabilized within 2 months. Subsequently, total thymectomy was performed. The diagnosis of the tumor invading the left lung was invasive thymoma, Masaoka- Koga stage III. The histological diagnosis was World Health Organization type AB. Thymoma accompanied with PRCA and AAMT is very rare, and, based on our case, immunotherapeutic therapy for the hematologic disorders should precede surgical intervention.

  13. Clinical and research issues in neonatal anemia and thrombocytopenia.

    Science.gov (United States)

    Sallmon, Hannes; Sola-Visner, Martha

    2012-02-01

    Anemia and thrombocytopenia are the most common hematological problems in neonates. Red blood cell (RBC) and platelet transfusions are the mainstays of therapy, but data to guide neonatal transfusion practices have been sparse. Recombinant hematopoietic growth factors represent another therapeutic alternative, but their use in this population requires a solid understanding of the developmental differences between fetal and adult hematopoiesis. Recently, follow-up studies from children randomized as neonates to either liberal or restrictive RBC transfusion approaches were published. Results of these studies have so far been contradictory and have generated more questions than answers. New developmental stage-specific problems associated with RBC transfusions were also uncovered, such as the transfusion-associated necrotizing enterocolitis. Finally, two thrombopoietin (Tpo) mimetics were approved by the FDA for the treatment of adults with chronic immune thrombocytopenia, thus offering a novel potential therapeutic alternative for thrombocytopenic neonates. In this review, we will discuss the currently available data regarding neonatal RBC and platelet transfusion thresholds, as well as the potential limitations, and concerns associated with the use of erythropoietin and Tpo mimetics in this patient population. Finally, we will point out specific areas wherein additional research is critically needed.

  14. Prolonged thrombocytopenia in a child with severe neonatal alloimmune reaction and Noonan syndrome.

    Science.gov (United States)

    Salva, Inês; Batalha, Sara; Maia, Raquel; Kjollerstrom, Paula

    2016-06-01

    Fetomaternal alloimmune thrombocytopenia (FMAIT) caused by maternal antibodies is the leading cause of severe neonatal thrombocytopenia. A 1-month-old Caucasian girl was referred to our Hematology Clinic for persistent thrombocytopenia diagnosed after a bleeding episode. Diagnostic tests suggested FMAIT. Mild thrombocytopenia persisted for 18 months, and subsequent findings of dysmorphic facies, short stature and mild pulmonary stenosis led to the hypothesis of Noonan syndrome (NS), which was confirmed by genetic test. Other hematological abnormalities were excluded and she had no further bleeding episodes. This case illustrates the possibility of different diagnoses with the same clinical manifestations. The persistence of thrombocytopenia longer than expected associated with typical physical features led to the diagnosis of NS.

  15. Bilateral lower extremity gangrene requiring amputation associated with heparin-induced thrombocytopenia: a case report.

    Science.gov (United States)

    Dickinson, Brian P; Lawrence, Peter F

    2007-01-01

    Heparin is a common cause of thrombocytopenia in hospitalized patients. Between 10% and 15% of patients receiving therapeutic doses of heparin develop thrombocytopenia. Heparin-induced thrombocytopenia (HIT) can cause severe bleeding and thrombosis owing to intravascular platelet aggregation. HIT must be distinguished from other causes of thrombocytopenia. Importantly, heparin use is often associated with an early fall in the platelet count that usually occurs within the first 4 days of initiation and recovers without cessation of heparin treatment. This nonimmune heparin-associated thrombocytopenia has not been found to be associated with thrombosis and does not necessitate discontinuation of heparin. The authors present a case report of a 70-year-old man who received heparin therapy following aortic tissue valve replacement and aortic root repair with graft and developed bilateral lower extremity arterial clots 6 days postoperatively in the setting of positive heparin antibody titers. Ultimately the patient required bilateral above-knee amputations.

  16. Thrombocytopenia and absent radii (TAR syndrome associated with bilateral congenital cataract: a case report

    Directory of Open Access Journals (Sweden)

    Omran Ahmed

    2012-06-01

    Full Text Available Abstract Introduction Thrombocytopenia with absent radii is a rare congenital defect with hypomegakaryocytic thrombocytopenia and bilateral radial aplasia that may have additional anomalies. We report the case of a girl baby with thrombocytopenia and absent radii syndrome and bilateral congenital cataract. This anomaly has not been previously reported in the children of a non- consanguineous marriage. Case presentation This case report describes a two-day-old girl baby of Arab origin with thrombocytopenia and absent radii syndrome and bilateral congenital cataract. Conclusions This report describes a finding of bilateral congenital cataract associated with thrombocytopenia and absent radii syndrome that has been reported only once before in the literature. This case report highlights a new ocular manifestation in one of the bone marrow failure syndromes.

  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. Elevated Plasma P-Selectin Autoantibodies in Primary Sjögren Syndrome Patients with Thrombocytopenia.

    Science.gov (United States)

    Hu, Ya-Hui; Zhou, Peng-Fei; Long, Guang-Feng; Tian, Xin; Guo, Yu-Fan; Pang, Ai-Ming; Di, Ran; Shen, Yan-Na; Liu, Yun-De; Cui, Yu-Jie

    2015-11-28

    BACKGROUND Primary Sjögren's syndrome (pSS) is one of the most common chronic systemic autoimmune diseases, and thrombocytopenia is one of the hematological manifestations of pSS. When platelet and endothelial cells are activated, P-selectin is expressed on the cell surface. This study aimed to investigate the role of P-selectin autoantibodies in the pathogenesis of thrombocytopenia in pSS. MATERIAL AND METHODS P-selectin autoantibodies were measured by enzyme-linked immunosorbent assay (ELISA) in 38 pSS patients without thrombocytopenia and 32 pSS patients with thrombocytopenia, 32 idiopathic thrombocytopenic purpura (ITP) patients, and 35 healthy controls. RESULTS The plasma P-selectin autoantibodies (A490) in ITP patients and pSS patients with/without thrombocytopenia were significantly higher than those in healthy controls, but there were no significant differences between ITP patients and pSS patients with thrombocytopenia. The positive rate of P-selectin autoantibodies in pSS patients with thrombocytopenia was significantly higher than that in ITP patients. The platelet count was lower in P-selectin autoantibodies-positive patients, while among pSS patients with thrombocytopenia, the platelet count was lower in P-selectin autoantibodies-positive patients than in P-selectin autoantibodies-negative patients. In ITP patients and pSS patients with thrombocytopenia, the platelet count was lower in P-selectin autoantibodies-positive patients. CONCLUSIONS Elevated plasma P-selectin autoantibodies may play a role in the pathogenesis of thrombocytopenia in pSS patients.

  19. 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.

  20. The role of the Th1 transcription factor T-bet in a mouse model of immune-mediated bone-marrow failure.

    Science.gov (United States)

    Tang, Yong; Desierto, Marie J; Chen, Jichun; Young, Neal S

    2010-01-21

    The transcription factor T-bet is a key regulator of type 1 immune responses. We examined the role of T-bet in an animal model of immune-mediated bone marrow (BM) failure using mice carrying a germline T-bet gene deletion (T-bet(-/-)). In comparison with normal C57BL6 (B6) control mice, T-bet(-/-) mice had normal cellular composition in lymphohematopoietic tissues, but T-bet(-/-) lymphocytes were functionally defective. Infusion of 5 x 10(6) T-bet(-/-) lymph node (LN) cells into sublethally irradiated, major histocompatibility complex-mismatched CByB6F1 (F1) recipients failed to induce the severe marrow hypoplasia and fatal pancytopenia that is produced by injection of similar numbers of B6 LN cells. Increasing T-bet(-/-) LN-cell dose to 10 to 23 x 10(6) per recipient led to only mild hematopoietic deficiency. Recipients of T-bet(-/-) LN cells had no expansion in T cells or interferon-gamma-producing T cells but showed a significant increase in Lin(-)Sca1(+)CD117(+)CD34(-) BM cells. Plasma transforming growth factor-beta and interleukin-17 concentrations were increased in T-bet(-/-) LN-cell recipients, possibly a compensatory up-regulation of the Th17 immune response. Continuous infusion of interferon-gamma resulted in hematopoietic suppression but did not cause T-bet(-/-) LN-cell expansion or BM destruction. Our data provided fresh evidence demonstrating a critical role of T-bet in immune-mediated BM failure.

  1. Histologic and cytologic bone marrow findings in dogs with suspected precursor-targeted immune-mediated anemia and associated phagocytosis of erythroid precursors.

    Science.gov (United States)

    Lucidi, Cynthia de A; de Rezende, Christian L E; Jutkowitz, L Ari; Scott, Michael A

    2017-09-01

    Precursor-targeted immune-mediated anemia (PIMA) has been suspected in dogs with nonregenerative anemia and bone marrow findings varying from erythroid hyperplasia to pure red cell aplasia. Phagocytosis of erythroid precursors/rubriphagocytosis (RP) reported in some affected dogs suggests a destructive component to the pathogenesis of PIMA. The purpose of the study was to characterize laboratory and clinical findings in dogs with suspected PIMA and RP, with emphasis on cytologic and histologic bone marrow findings. Dogs with PIMA and RP were identified by review of paired bone marrow aspirate and core biopsy slides collected over a 4-year period. Samples were systematically assessed and characterized along with other pertinent laboratory data and clinical findings. Twenty-five dogs met criteria for PIMA and had RP that was relatively stage-selective. Erythropoiesis was expanded to the stage of erythroid precursors undergoing most prominent phagocytosis, yielding patterns characterized by a hypo-, normo-, or hypercellular erythroid lineage. A 4(th) pattern involved severe collagen myelofibrosis, and there was a spectrum of mild to severe collagen myelofibrosis overall. Evidence of immune-mediated hemolysis was rare. Immunosuppressive therapy was associated with remission in 77% of dogs treated for at least the median response time of 2 months. Bone marrow patterns in dogs fulfilling criteria for PIMA were aligned with stage-selective phagocytosis of erythroid precursors and the development of collagen myelofibrosis, common in dogs with PIMA. Recognition of these patterns and detection of RP facilitates diagnosis of PIMA, and slow response to immunosuppressive therapy warrants further investigation into its pathogenesis. © 2017 American Society for Veterinary Clinical Pathology.

  2. Cytokine and chemokine levels in patients with severe fever with thrombocytopenia syndrome virus.

    Directory of Open Access Journals (Sweden)

    Baocheng Deng

    Full Text Available BACKGROUND: Severe fever with thrombocytopenia syndrome virus (SFTSV, which can cause hemorrhagic fever-like illness, is a newly discovered bunyavirus in China. The pathogenesis of SFTSV infection is poorly understood. However, it has been suggested that immune mechanisms, including cytokines and chemokines, play an important role in disease pathogenesis. In the present study, we investigated host cytokine and chemokine profiles in serum samples of patients with SFTSV infection from Northeast China and explored a possible correlation between cytokine levels and disease severity. METHODS AND PRINCIPAL FINDINGS: Acute phase serum samples from 40 patients, diagnosed with SFTSV infection were included. Patients were divided into two groups--severe or non-severe--based on disease severity. Levels of tumor necrosis factor (TNF-α, transforming growth factor (TGF-β, interleukin-6, interferon (IFN-γ, IFN- γ-induced protein (IP-10 and RANTES were measured in the serum samples with commercial ELISAs. Statistical analysis showed that increases in TNF-α, IP-10 and IFN-γ were associated with disease severity. CONCLUSIONS: We suggest that a cytokine-mediated inflammatory response, characterized by cytokine and chemokine production imbalance, might be in part responsible for the disease progression of patients with SFTSV infection.

  3. Consensus Paper-ICIS Expert Meeting Basel 2009 treatment milestones in immune thrombocytopenia.

    Science.gov (United States)

    Tamary, Hannah; Roganovic, Jelena; Chitlur, Meera; Nugent, Diane J

    2010-07-01

    The rarity of severe complications of this disease in children makes randomized clinical trials in immune thrombocytopenia (ITP) unfeasible. Therefore, the current management recommendations for ITP are largely dependent on clinical expertise and observations. As part of its discussions during the Intercontinental Cooperative ITP Study Group Expert Meeting in Basel, the Management working group recommended that the decision to treat an ITP patient be individualized and based mainly on bleeding symptoms and not on the actual platelet count number and should be supported by bleeding scores using a validated assessment tool. The group stressed the need to develop a uniform validated bleeding score system and to explore new measures to evaluate bleeding risk in thrombocytopenic patients-the role of rituximab as a splenectomy-sparing agent in resistant disease was also discussed. Given the apparently high recurrence rate to rituximab therapy in children and the drug's possible toxicity, the group felt that until more data are available, a conservative approach may be considered, reserving rituximab for patients who failed splenectomy. More studies of the effectiveness and side effects of drugs to treat refractory patients, such as TPO mimetics, cyclosporine, mycophenolate mofetil, and cytotoxic agents are required, as are long-term data on post-splenectomy complications. In the patient with either acute or chronic ITP, using a more personalized approach to treatment based on bleeding symptoms rather than platelet count should result in less toxicity and empower both physicians and families to focus on quality-of-life.

  4. RhIG for the treatment of immune thrombocytopenia: consensus and controversy (CME).

    Science.gov (United States)

    Despotovic, Jenny M; Lambert, Michele P; Herman, Jay H; Gernsheimer, Terry B; McCrae, Keith R; Tarantino, Michael D; Bussel, James B

    2012-05-01

    Anti-D immune globulin (RhIG) is a front-line option in North America for the treatment of immune thrombocytopenia (ITP) in children and adults. Recently, addition of a Food and Drug Administration-mandated black box warning highlighted the risks of intravascular hemolysis, renal failure, and disseminated intravascular coagulation after anti-D infusion, prompting concern within the medical community regarding its use. A working group convened in response to this warning to prepare a consensus document regarding the safety of RhIG because there has been no increased incidence of adverse events since the initial discovery of these reactions many years ago. The efficacy of anti-D is well documented and only briefly reviewed. The estimated incidence and proposed mechanisms for the rare, major treatment-related complications are discussed, and signal detection data associated with heightened risk of acute hemolytic reactions are presented. The importance of considering host factors, given the rarity of severe reactions, is emphasized. Safety profiles of parallel treatment options are reviewed. The working group consensus is that RhIG has comparable safety and efficacy to other front-line agents for the treatment of children and adults with ITP. Safety may be further improved by careful patient selection.

  5. Thrombocytopenia in Plasmodium vivax malaria is related to platelets phagocytosis.

    Directory of Open Access Journals (Sweden)

    Helena Cristina C Coelho

    Full Text Available BACKGROUND: Although thrombocytopenia is a hematological disorder commonly reported in malarial patients, its mechanisms are still poorly understood, with only a few studies focusing on the role of platelets phagocytosis. METHODS AND FINDINGS: Thirty-five malaria vivax patients and eight healthy volunteers (HV were enrolled in the study. Among vivax malaria patients, thrombocytopenia (<150,000 platelets/µL was found in 62.9% (22/35. Mean platelet volume (MPV was higher in thrombocytopenic patients as compared to non-thrombocytopenic patients (p = 0.017 and a negative correlation was found between platelet count and MPV (r = -0.483; p = 0.003. Platelets from HV or patients were labeled with 5-chloromethyl fluorescein diacetate (CMFDA, incubated with human monocytic cell line (THP-1 and platelet phagocytosis index was analyzed by flow cytometry. The phagocytosis index was higher in thrombocytopenic patients compared to non-thrombocytopenic patients (p = 0.042 and HV (p = 0.048. A negative correlation was observed between platelet count and phagocytosis index (r = -0.402; p = 0.016. Platelet activation was assessed measuring the expression of P-selectin (CD62-P in platelets' surface by flow cytometry. No significant difference was found in the expression of P-selectin between thrombocytopenic patients and HV (p = 0.092. After evaluating the cytokine profile (IL-2, IL-4, IL-6, IL-10, TNF-α, IFN-γ and IL-17 in the patients' sera, levels of IL-6, IL-10 and IFN-γ were elevated in malaria patients compared to HV. Moreover, IL-6 and IL-10 values were higher in thrombocytopenic patients than non-thrombocytopenic ones (p = 0.044 and p = 0.017, respectively. In contrast, TNF-α levels were not different between the three groups, but a positive correlation was found between TNF-α and phagocytosis index (r = -0.305; p = 0.037. CONCLUSION/SIGNIFICANCE: Collectively, our findings indicate that platelet

  6. Emergence of infectious malignant thrombocytopenia in Japanese macaques (Macaca fuscata) by SRV-4 after transmission to a novel host

    Science.gov (United States)

    Okamoto, Munehiro; Miyazawa, Takayuki; Morikawa, Shigeru; Ono, Fumiko; Nakamura, Shota; Sato, Eiji; Yoshida, Tomoyuki; Yoshikawa, Rokusuke; Sakai, Kouji; Mizutani, Tetsuya; Nagata, Noriyo; Takano, Jun-ichiro; Okabayashi, Sachi; Hamano, Masataka; Fujimoto, Koji; Nakaya, Takaaki; Iida, Tetsuya; Horii, Toshihiro; Miyabe-Nishiwaki, Takako; Watanabe, Akino; Kaneko, Akihisa; Saito, Akatsuki; Matsui, Atsushi; Hayakawa, Toshiyuki; Suzuki, Juri; Akari, Hirofumi; Matsuzawa, Tetsuro; Hirai, Hirohisa

    2015-01-01

    We discovered a lethal hemorrhagic syndrome arising from severe thrombocytopenia in Japanese macaques kept at the Primate Research Institute, Kyoto University. Extensive investigation identified that simian retrovirus type 4 (SRV-4) was the causative agent of the disease. SRV-4 had previously been isolated only from cynomolgus macaques in which it is usually asymptomatic. We consider that the SRV-4 crossed the so-called species barrier between cynomolgus and Japanese macaques, leading to extremely severe acute symptoms in the latter. Infectious agents that cross the species barrier occasionally amplify in virulence, which is not observed in the original hosts. In such cases, the new hosts are usually distantly related to the original hosts. However, Japanese macaques are closely related to cynomolgus macaques, and can even hybridize when given the opportunity. This lethal outbreak of a novel pathogen in Japanese macaques highlights the need to modify our expectations about virulence with regards crossing species barriers. PMID:25743183

  7. [Electronic platelet counting with particular reference to thrombocytopenias (author's transl)].

    Science.gov (United States)

    Kuse, R; Burmeister, H; Hausmann, K

    1977-09-29

    Platelet counts in platelet-rich plasma without hematocrit dependent correction were performed by following rapid and simple steps: 1. pre-dilution of 20 microliter of whole blood by an isotonic solution 1:25; 2. stabilized low-speed centrifugation with 55 g for 5 minutes; 3. final dilution 1 : 5000; 4. enumeration by use of a TOA platelet counter PL-100 which has been technically improved in comparison to similar machines. Erroneously high results were obtained after a too short or too low centrifugation. As reason for this artifical small pulses due to disturbances of the flow patterns around the aperture (so-called vortex-effect) can be assumed having been caused by large-volumed erythrocytes and leukocytes in the suspension. The routinely used procedure was reliable for all platelet ranges, especially in thrombocytopenias between 100 X 10(9)/l and 25 X 10(9)l. In lower ranges comparisons with visual counts are essential.

  8. 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.

  9. The Incidence of Thrombocytopenia in Children with Cornelia de Lange Syndrome

    Science.gov (United States)

    Lambert, Michele P.; Jackson, Laird G.; Clark, Dinah; Kaur, Mani; Krantz, Ian D.; Deardorff, Matthew A.

    2010-01-01

    Thrombocytopenia was first reported in Cornelia de Lange Syndrome (CdLS) by Froster in 1993. Despite early reports, thrombocytopenia has been rarely reported in this disorder. We performed a retrospective analysis of a large cohort of patients with CdLS. We calculated prevalence of thrombocytopenia in 3 subsets of this cohort: the entire cohort (n=1740), a subset of subjects with substantial clinical records (n=695) and a subset of subjects with clinical information regarding platelet counts (n=85). This analysis revealed that 15 have had thrombocytopenia (18% of those with available blood counts); seven had Immune ThrombocytoPenia (ITP). The reported prevalence of pediatric ITP is between 5-13 per 100,000 persons. The prevalence of ITP in this cohort is between 7/1740 and 7/85, giving a relative risk of ITP of between 30 (CI 12 to 77) and 633 (CI 259-1549). Contrary to the reported cases in the literature, none of our patients have had progression of the thrombocytopenia nor have they developed other cytopenias. All 15 patients with thromobocytopenia had CdLS based on clinical criteria. Of the 10 patients tested for mutations in NIBPL, eight had mutations identified. These data support an increased incidence of thrombocytopenia and ITP in CdLS. Subsequently, patients are at risk for spontaneous hemorrhage, and likely increased risk secondary to the high frequency of self-injurious behavior. Although further studies are needed to better define the scope of the problem and to define the mechanisms of thrombocytopenia in CdLS, we would recommend screening for thrombocytopenia upon diagnosis and at five-year intervals thereafter. PMID:21204208

  10. The Incidence, Clinical Outcomes, and Risk Factors of Thrombocytopenia in Intra-Abdominal Infection Patients: A Retrospective Cohort Study.

    Directory of Open Access Journals (Sweden)

    Qin Wu

    Full Text Available Studies on the incidence and risk factors of thrombocytopenia among intra-abdominal infection patients remain absent, hindering efficacy assessments regarding thrombocytopenia prevention strategies.We retrospectively studied 267 consecutively enrolled patients with intra-abdominal infections. Occurrence of thrombocytopenia was scanned for all patients. All-cause 28-day mortality was recorded. Variables from univariate analyses that were associated with occurrence of hospital-acquired thrombocytopenia were included in a multivariable logistic regression analysis to determine thrombocytopenia predictors.Median APACHE II score and SOFA score of the whole cohort was 12 and 3 respectively. The overall ICU mortality was 7.87% and the 28-day mortality was 8.98%. The incidence of thrombocytopenia among intra-abdominal infection patients was 21.73%. Regardless of preexisting or hospital-acquired one, thrombocytopenia is associated with an increased ICU mortality and 28-day mortality as well as length of ICU or hospital stay. A higher SOFA and ISTH score at admission were significant hospital-acquired thrombocytopenia risk factors.This is the first study to identify a high incidence of thrombocytopenia in patients with intra-abdominal infections. Our findings suggest that the inflammatory milieu of intra-abdominal infections may uniquely predispose those patients to thrombocytopenia. More effective thrombocytopenia prevention strategies are necessary in intra-abdominal infection patients.

  11. Recurrent febrile neutropenia and thrombocytopenia in a chronic cocaine user: a case of levamisole induced complications.

    Science.gov (United States)

    Martinez, Eduardo; Alvi, Raza; Venkatram, Sindhaghatta; Diaz-Fuentes, Gilda

    2015-01-01

    Cocaine is used by approximately 1.5 million Americans each month and up to 69% of the cocaine seized contains levamisole. The real incidence of cocaine-levamisole induced neutropenia is unclear but probably underestimated. Associated complications include fever, thrombocytopenia, skin-vasculitis disorders, and rarely kidney injury. We present a young male, with chronic active cocaine use presenting with recurrent episodes of febrile neutropenia and thrombocytopenia. He underwent extensive work-up and was treated with many antibiotics and we suspect that his neutropenia and thrombocytopenia were caused by recurrent cocaine-levamisole use.

  12. Recurrent Febrile Neutropenia and Thrombocytopenia in a Chronic Cocaine User: A Case of Levamisole Induced Complications

    Directory of Open Access Journals (Sweden)

    Eduardo Martinez

    2015-01-01

    Full Text Available Cocaine is used by approximately 1.5 million Americans each month and up to 69% of the cocaine seized contains levamisole. The real incidence of cocaine-levamisole induced neutropenia is unclear but probably underestimated. Associated complications include fever, thrombocytopenia, skin-vasculitis disorders, and rarely kidney injury. We present a young male, with chronic active cocaine use presenting with recurrent episodes of febrile neutropenia and thrombocytopenia. He underwent extensive work-up and was treated with many antibiotics and we suspect that his neutropenia and thrombocytopenia were caused by recurrent cocaine-levamisole use.

  13. An inducible transgenic mouse model for immune mediated hepatitis showing clearance of antigen expressing hepatocytes by CD8+ T cells.

    Directory of Open Access Journals (Sweden)

    Marcin Cebula

    Full Text Available The liver has the ability to prime immune responses against neo antigens provided upon infections. However, T cell immunity in liver is uniquely modulated by the complex tolerogenic property of this organ that has to also cope with foreign agents such as endotoxins or food antigens. In this respect, the nature of intrahepatic T cell responses remains to be fully characterized. To gain deeper insight into the mechanisms that regulate the CD8+ T cell responses in the liver, we established a novel OVA_X_CreER(T2 mouse model. Upon tamoxifen administration OVA antigen expression is observed in a fraction of hepatocytes, resulting in a mosaic expression pattern. To elucidate the cross-talk of CD8+ T cells with antigen-expressing hepatocytes, we adoptively transferred K(b/OVA257-264-specific OT-I T cells to OVA_X_CreER(T2 mice or generated triple transgenic OVA_X CreER(T2_X_OT-I mice. OT-I T cells become activated in OVA_X_CreER(T2 mice and induce an acute and transient hepatitis accompanied by liver damage. In OVA_X_CreER(T2_X_OT-I mice, OVA induction triggers an OT-I T cell mediated, fulminant hepatitis resulting in 50% mortality. Surviving mice manifest a long lasting hepatitis, and recover after 9 weeks. In these experimental settings, recovery from hepatitis correlates with a complete loss of OVA expression indicating efficient clearance of the antigen-expressing hepatocytes. Moreover, a relapse of hepatitis can be induced upon re-induction of cured OVA_X_CreER(T2_X_OT-I mice indicating absence of tolerogenic mechanisms. This pathogen-free, conditional mouse model has the advantage of tamoxifen inducible tissue specific antigen expression that reflects the heterogeneity of viral antigen expression and enables the study of intrahepatic immune responses to both de novo and persistent antigen. It allows following the course of intrahepatic immune responses: initiation, the acute phase and antigen clearance.

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

    Directory of Open Access Journals (Sweden)

    Joonhee Cho

    Full Text Available BACKGROUND AND AIMS: 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. METHODS: 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. RESULTS: 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. CONCLUSIONS: 17β-estradiol and IL-6 may act synergistically to promote sex bias in experimental DILI by reducing Tregs. Modulating Treg numbers may provide a

  15. The clinical characteristics of 169 cases of severe fever with thrombocytopenia syndrome

    Institute of Scientific and Technical Information of China (English)

    崔宁

    2012-01-01

    Objective To analyze the clinical characteristics of severe fever with thrombocytopenia syndrome(SFTS) so as to improve the recognition of the emerging infectious disease. Methods A retrospective analysis was performed upon clinical manifestations,laboratory test results and

  16. Bilateral lower extremity gangrene requiring amputation associated with heparin-induced thrombocytopenia--a case report.

    Science.gov (United States)

    Dickinson, Brian P; De Ugarte, Daniel A; Reil, Todd D; Beseth, Bryce D; Lawrence, Peter F

    2006-01-01

    Heparin use, both prophylactically and therapeutically, is prevalent among hospitalized patients. Patients on heparin may develop a thrombocytopenia that is self-limited. Fewer patients develop a heparin-induced thrombocytopenia that can cause severe bleeding and thrombosis owing to intravascular platelet aggregation. The authors present a case report of heparin-induced thrombocytopenia in a patient who underwent aortic arch and aortic valve replacement that resulted in bilateral above-knee amputations. The patient developed limb ischemia related to heparin-associated thrombosis, but had a delay in antibody seroconversion. Early and accurate diagnosis of heparin-induced thrombocytopenia requires a high clinical suspicion and may be present despite the absence of serum antibodies.

  17. Wiskott-Aldrich syndrome mutation in two Turkish siblings with X-linked thrombocytopenia

    Directory of Open Access Journals (Sweden)

    Göksel Leblebisatan

    2011-06-01

    Full Text Available Wiskott-Aldrich syndrome (WAS is a clinical condition characterized by thrombocytopenia, eczema, and life-threatening infections. In some cases autoimmunity-related problems and even malignancy might be seen; however, some patients have milder clinical manifestations due to mutations in the same gene family, such as in X-linked thrombocytopenia (XLT, which is generally not associated with serious symptoms of disease, except for thrombocytopenia. Herein we report 2 siblings with chronic thrombocytopenia that were diagnosed with XLT based on a missense mutation in the WASP gene (223G>A, Val75Met. To the best of our knowledge this mutation has not been previously reported in a Turkish patient with XLT.

  18. 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 preva

  19. The potential of antimicrobials to induce thrombocytopenia in critically ill patients

    DEFF Research Database (Denmark)

    Johansen, Maria Egede; Jensen, Jens Ulrik Stæhr; Bestle, Morten Heiberg

    2013-01-01

    Antimicrobial-induced thrombocytopenia is frequently described in the literature among critically ill patients. Several antimicrobials have been implicated, although experimental evidence to demonstrate causality is limited. We report, using a randomized trial, the potential of antimicrobials to ...

  20. Prevalence of Thrombocytopenia among Chinese Adult Antiretroviral-naïve HIV-positive Patients

    Directory of Open Access Journals (Sweden)

    Hong-Wei Fan

    2015-01-01

    Full Text Available Background: The prevalence of thrombocytopenia among Chinese antiretroviral therapy (ART-naïve HIV-infected adults has not been well-described. The aim of this study was to investigate the prevalence and associated risk factors of thrombocytopenia among Chinese ART-naïve HIV-infected adults. Methods: We performed a cross-sectional study of Chinese adult ART-naïve HIV-infected patients from September 2005 through August 2014. Socio-demographic variables and laboratory results including platelets, CD4+ cell count, and viral load were obtained from medical records. Factors and outcomes associated with thrombocytopenia were assessed using logistic regression. Results: A total of 1730 adult ART-naïve HIV-infected patients was included. The mean age was 38 years. The prevalence of thrombocytopenia was 4.5%. There were significant differences in the prevalence of thrombocytopenia between patients 350 cells/mm 3 (2.8% compared with patients with CD4+ counts of 50-199 cells/mm 3 (7.1% (P = 0.002 and P = 0.005, respectively. The prevalence of thrombocytopenia was significantly different by hepatitis C virus antibody (HCV-Ab seropositivity (10.2% for HCV-Ab positive vs. 3.9% for HCV-Ab negative, P = 0.001. We observed differences in prevalence of thrombocytopenia by mode of transmission of HIV infection: Blood transmission (10.7% versus men who have sex with men (3.9% (P = 0.002 and versus heterosexual transmission (3.9% (P = 0.001. In binary logistic regression analyses, age ≥50 years, HCV-Ab positivity and having a CD4+ cell count of 50-199 cells/mm 3 were significantly associated with thrombocytopenia with adjusted odds ratio of 2.482 (95% confidence interval [CI]: 1.167, 5.281, P = 0.018, 2.091 (95% CI: 1.078, 4.055, P = 0.029 and 2.259 (95% CI: 1.028, 4.962, P = 0.042, respectively. Conclusions: Thrombocytopenia is not common among adult ART-naïve HIV-infected patients in China. Older age (age over 50 years, HCV-Ab positivity and lower CD4

  1. Can we predict neonatal thrombocytopenia in offspring of women with idiopathic thrombocytopenic purpura?

    OpenAIRE

    Hachisuga, Kazuhisa; Hidaka, Nobuhiro; Fujita, Yasuyuki; Fukushima, Kotaro; Kato, Kiyoko

    2014-01-01

    Background We aimed to investigate which factors in the clinical profile of mothers with idiopathic thrombocytopenic purpura (ITP) can predict neonatal risk of thrombocytopenia. Methods Data was retrospectively collected from all pregnant women with ITP who presented to our institution between 2001 and 2013. Neonatal offspring of these women were classified into 2 groups based on the presence or absence of neonatal thrombocytopenia (platelet count

  2. Prevalence of cirrhosis in patients with thrombocytopenia who receive bone marrow biopsy

    Directory of Open Access Journals (Sweden)

    Muhammad Y Sheikh

    2012-01-01

    Full Text Available Background/Aim: Thrombocytopenia is a common finding in patients with cirrhosis and may lead to unnecessary referral for bone marrow (BM biopsy. To date, the prevalence of cirrhosis in patients with thrombocytopenia who receive BM biopsy is largely unknown. Materials and Methods: Between fiscal years 2006-2010, 744 patients (≥18 years who underwent BM biopsies for thrombocytopenia at our hospital were identified retrospectively. 541 patients were excluded who had hematologic malignancies and received chemotherapy. Remaining 203 patients with predominant isolated thrombocytopenia were included in the study. Results: Of 203 patients, 136 (67% had a normal and 67 (33% had an abnormal BM examination. Prevalence of cirrhosis in the study population was 35% (95% CI: 28.4-41.9. 51% patients with normal BM were found to have cirrhosis compared to 3% of patients with abnormal BM exam (P < 0.0001. Common causes of cirrhosis were nonalcoholic steatohepatitis (NASH (47%, followed by alcohol and Hepatitis C virus infection. Idiopathic thrombocytopenia and myelodysplastic syndrome were most frequent causes of thrombocytopenia in patients without cirrhosis. Patients with NASH had higher body mass index (BMI (33.4 vs. 25.8, P < 0.001 and lower MELD scores (11.1 vs. 16, P = 0.028 when compared to non-NASH patients with cirrhosis. Conclusion: Approximately, one third (35% of patients with cirrhosis induced thrombocytopenia may undergo unwarranted BM biopsies. Clinical diagnosis of cirrhosis is still a challenge for many physicians, particularly with underlying NASH. We propose cirrhosis to be the prime cause of isolated thrombocytopenia.

  3. Thrombocytopenia in Paediatric ICU: Incidence, Transfusion Requirement and Role as Prognostic Indicator

    Science.gov (United States)

    Sethi, Gurmeet Kaur; Goyal, Ram Kumar; Kaur, Avneet; Kaur, Rupinderjeet; Dhir, Shashi Kant; Gupta, Harshvardhan

    2015-01-01

    Introduction Thrombocytopenia is defined as platelet count less than 150×109/L, it has a greater incidence in Intensive Care Units (ICUs) compared to wards and its most common cause is increased platelet consumption. Aims To investigate incidence of thrombocytopenia, platelet transfusions requirement, associated diseases and relationship between thrombocytopenia and mortality. Materials and Methods Eleven months hospital records between October 2013 and August 2014 of the PICU in a tertiary care teaching hospital was investigated retrospectively and 275 critically ill children formed the sample. Statistical analysis Odds ratio with 95% confidence interval was used. Probability value (p-value) of less than 0.05 was considered statistically significant. Results were confirmed using χ2 test. Results Out of 275 patients {168 males (61.09%) and 107 females (38.91%)}, 89 patients had thrombocytopenia. Out of these 89 patients, 43 patients (48.31%) had severe, 24 patients (27.91%) had moderate and 22 patients (24.72%) had mild thrombocytopenia. The 43 patients having severe thrombocytopenia received platelet transfusion and out of these 43 patients 24 (55.81%) received more than one transfusion and 18 (41.86%) of the transfused patients expired. Among thrombocytopaenic patients, Sepsis (25.84%) was the most common diagnosis followed by Pneumonia (19.10%), Meningitis (13.48%), Diabetic Ketoacidosis (5.62%), Enteric fever (7.86%), Tubercular Meningitis (3.37%), Infantile Tremor Syndrome (2.25%), Congenital heart disease (5.62%), Burns(3.37%), Brain Haemorrhage (2.25%%), Hepatic abscess (1.12%), Chronic Renal Failure (3.37%), Malaria (2.25%) and Hepatitis (4.49%). There is a statistically significant association between thrombocytopenia and mortality. A significant association was established between mortality in thrombocytopenic patients of sepsis. Conclusion Thrombocytopenia is commonly associated with sepsis. Mortality rate is higher in thrombocytopenic patients. PMID

  4. 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.

  5. Thrombocytopenia absent radius syndrome with Tetralogy of Fallot: a rare association

    Directory of Open Access Journals (Sweden)

    Kumar C

    2015-03-01

    Full Text Available Chetan Kumar,1 Deepak Sharma,2 Aakash Pandita,2 Sanjay Bhalerao1 1Department of Pediatrics, Madras Institute of Orthopedic and Trauma, Manapakkam, Chennai, India; 2Department of Neonatology, Fernandez Hospital, Hyderabad, India Abstract: Thrombocytopenia absent radius (TAR syndrome is a very rare and infrequently seen congenital disorder with an approximate frequency of 0.42/100,000 live births. It is associated with bilateral absence of radii, hypo-megakaryocytic thrombocytopenia, and presence of both thumbs. The other systems which are affected by TAR syndrome include skeletal, hematologic, and cardiac systems. Intracranial hemorrhages due to thrombocytopenia and cardiac disorders are a common association usually seen with this syndrome and are usual cause of death. We describe a 3-month-old infant who was diagnosed with TAR syndrome on the basis of clinical features (thrombocytopenia and bilateral absent radius bone and confirmed by genetic analysis. The patient was diagnosed to have Tetralogy of Fallot, for which the infant was managed with definitive repair and thrombocytopenia was managed with platelet transfusion. Infants with TAR syndrome should be assessed for other associated malformations of various systems and followed up regularly and parents should be counseled for associated expected complications in these patients. We report an infant with TAR syndrome with Tetralogy of Fallot, which has not been reported in medical literature until now and this is the first case of its type. Keywords: thrombocytopenia absent radius syndrome, Tetralogy of Fallot, microdeletion 1q21.1, RBM8A

  6. Lack of evidence of a beneficial effect of azathioprine in dogs treated with prednisolone for idiopathic immune-mediated hemolytic anemia: a retrospective cohort study

    Directory of Open Access Journals (Sweden)

    Junius Greet

    2011-04-01

    Full Text Available Abstract 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 treated with a protocol that included azathioprine and prednisolone versus a protocol that included prednisolone alone. Results The study included 222 dogs with a hematocrit lower than 0.30 L/L and either a positive Coombs' test or spherocytosis and no evidence of diseases that could trigger IMHA. The clinical and laboratory data at the time of diagnosis and the response to therapy and survival were compared in dogs treated according to the prednisolone and azathioprine protocol (AP protocol; n = 149 and dogs treated according to the prednisolone protocol (P protocol; n = 73. At study entry, the two groups were comparable, except that thrombocyte counts were significantly lower and clinical signs had been present significantly longer in the AP protocol group. No significant difference in survival was found between the two groups: the 1-year survival was 64% (95% CI 54 - 77% in the P protocol group and 69% (95% CI 59-80% in the AP protocol group, respectively. Conclusions Azathioprine would appear not to be beneficial as standard treatment for all cases of IMHA; however, a blinded, randomized clinical trial is needed to establish whether outcome is different with the two treatment protocols.

  7. Possible Involvement of Foxp3+ Regulatory T Cells in the Development of Immune-Mediated Pancreatitis in MRL/Mp Mice Treated with Polyinosinic:Polycytidylic Acid

    Directory of Open Access Journals (Sweden)

    Masanori Koyabu

    2013-01-01

    Full Text Available Objectives. This study was conducted to clarify whether or not Tregs are involved in the development of immune-mediated pancreatitis in MRL/Mp mice as an AIP (autoimmune pancreatitis model, in order to understand more clearly the pathogenic mechanism of AIP. Methods. We compared the immunohistochemical features of pancreatic forkhead box P3 (Foxp3 in the administration of poly I:C in MRL/Mp mice and two types of control mice (BALB/c and C57BL/6. As a contrast, we analyzed three mouse models of pancreatitis without autoimmune mechanism (Cerulein-, Ligation-, and Ligation + Cerulein-treated mice. After staining these specimens, we compared the ratios of Foxp3-positive cells to infiltrated mononuclear cells (Foxp3/Mono. Results. Our immunohistochemical study of Foxp3 revealed that the infiltration of Foxp3-positive cells increased in poly I:C-treated MRL/Mp mice. The histopathological score of pancreatitis showed no difference among poly I:C-treated MRL/Mp, Ligation-, and Ligation + Cerulein-treated mice; however, the Foxp3/Mono ratio in poly I:C-treated MRL/Mp mice was significantly increased compared with Ligation- and Ligation + Cerulein-treated mice. Conclusions. MRL/Mp mice treated with poly I:C showed early development of pancreatitis with abundant infiltration of Foxp3-positive cells. There may be a possibility that Tregs are involved in the development of pancreatitis in these mice.

  8. 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.

  9. The IL23R R381Q gene variant protects against immune-mediated diseases by impairing IL-23-induced Th17 effector response in humans.

    Directory of Open Access Journals (Sweden)

    Paola Di Meglio

    Full Text Available IL-23 and Th17 cells are key players in tissue immunosurveillance and are implicated in human immune-mediated diseases. Genome-wide association studies have shown that the IL23R R381Q gene variant protects against psoriasis, Crohn's disease and ankylosing spondylitis. We investigated the immunological consequences of the protective IL23R R381Q gene variant in healthy donors. The IL23R R381Q gene variant had no major effect on Th17 cell differentiation as the frequency of circulating Th17 cells was similar in carriers of the IL23R protective (A and common (G allele. Accordingly, Th17 cells generated from A and G donors produced similar amounts of Th17 cytokines. However, IL-23-mediated Th17 cell effector function was impaired, as Th17 cells from A allele carriers had significantly reduced IL-23-induced IL-17A production and STAT3 phosphorylation compared to G allele carriers. Our functional analysis of a human disease-associated gene variant demonstrates that IL23R R381Q exerts its protective effects through selective attenuation of IL-23-induced Th17 cell effector function without interfering with Th17 differentiation, and highlights its importance in the protection against IL-23-induced tissue pathologies.

  10. Women's health and fertility, family planning and pregnancy in immune-mediated rheumatic diseases: a report from a south-eastern European Expert Meeting.

    Science.gov (United States)

    Ntali, Stella; Damjanov, Nemanja; Drakakis, Peter; Ionescu, Ruxandra; Kalinova, Desislava; Rashkov, Rasho; Malamitsi-Puchner, Ariadne; Mantzaris, Gerassimos; Michala, Lina; Pamfil, Cristina; Rednic, Simona; Tektonidou, Maria G; Tsiodras, Sotirios; Vassilopoulos, Dimitrios; Vojinovic, Jelena; Bertsias, George K; Boumpas, Dimitrios T

    2014-01-01

    With current advances in medical treatment, reproductive issues have become more important for women with chronic immune-mediated diseases. Most, if not all, patients report that their disease affects their personal relationships, their decision to have children, and the size of their family. These decisions are multi-factorial, influenced mainly by concerns over the effect of pregnancy on the rheumatic disease, the impact of disease activity during pregnancy on foetal health, the patient's ability to care for the child, and the possible harmful effects medication could have on the child, both pre- and post-natally during breastfeeding. Apart from that, women's health issues tend to be overlooked in favour of the management of the underlying rheumatic disease. To this end, we convened an expert panel to review the published literature on women's health and reproductive issues and provide evidence- and eminence-based points to consider for the treating physicians. We conclude that there is a need for a change in mind-set from one which 'cautions against pregnancy' to one which 'embraces pregnancy' through the practice of individualised, pre- and post-conceptual, multi-disciplinary care.

  11. Immune thrombocytopenia of childhood responsive to tonsillectomy in the setting of chronic tonsillitis: A case report and literature review.

    Science.gov (United States)

    Thompson, Richard William; Gungor, Anil

    2016-11-23

    Immune thrombocytopenia of childhood (platelet count children. Patients typically present with bruising and bleeding in the setting of thrombocytopenia. Although it is usually short-lived, some cases persist and are unresponsive to treatment. This can lead to exposure to a variety of treatment regimens including immunosuppressants and splenectomy. The goal of this report is to present a case of chronic ITP of childhood that responded to tonsillectomy addressing the tonsils as a source of chronic infection and inflammation triggering ITP. A 4-year-old male with ITP of childhood presented with enlarged tonsils and obstructive sleep apnea. History and physical were consistent with chronic tonsillitis/adenoiditis including malaise, poor oral intake, congestion, rhinorrhea, tonsil hypertrophy, and lymphadenopathy persisting despite antibiotic therapy. Tonsillectomy and adenoidectomy were performed. One, six, and eighteen weeks post-operatively the platelet count was 371, 215, and 205 respectively. Although at 12months two relapses had occurred, during the observed period, he had decreased incidence and severity of disease. In around 60% of ITP there is a history of prior infection within the last month but no systemic symptoms at time of diagnosis. Additionally, chronic ITP is characterized by relapses coinciding with infection. This case is unique because the patient had chronic ITP and a clinical history and physical exam concerning for a subclinical, indolent inflammatory process that responded to surgical intervention. Given that chronic ITP exacerbation has been associated with recurrent acute infections it seems probable that chronic tonsillitis could serve as a trigger for relapse or contribute to a prolonged and/or more severe disease course. Therefore, tonsillectomy may result in earlier treatment and/or an altered disease course with avoidance of the expense and morbidity associated with frequent exacerbations and multiple treatment regimens. Copyright © 2016

  12. 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.

  13. Decreased IL-35 levels in patients with immune thrombocytopenia.

    Science.gov (United States)

    Yang, Yanhui; Xuan, Min; Zhang, Xian; Zhang, Donglei; Fu, Rongfeng; Zhou, Fangfang; Ma, Li; Li, Huiyuan; Xue, Feng; Zhang, Lei; Yang, Renchi

    2014-08-01

    IL-35 is a novel heterodimeric anti-inflammatory cytokine consisting of Epstein-Barr virus-induced gene 3 (EBI3) and the p35 subunit of IL-12. IL-35 has been shown to possess the potency of inhibiting the CD4+ effector T cells and alleviating autoimmune diseases. In the study we investigated the levels of IL-35 as well as its prospective role in immune thrombocytopenia (ITP).ELISA was adopted to measure plasma IL-35, TGF-β and IL-10 levels. The mRNA expression levels of P35 and EBI3 in peripheral blood mononuclear cells (PBMCs) were studied based on real-time quantitative PCR. The correlation between plasma cytokine levels and clinical parameters was analyzed. Significantly lower plasma IL-35 levels were found in active ITP patients compared with those in remission (p = 0.017) and the healthy controls (p IL-35 levels displayed a significantly positive correlation with platelet counts (r = 0.5335, p IL-35 levels in ITP patients, suggesting that IL-35 may be involved in the pathogenesis of ITP.

  14. Cyclosporin A for persistent or chronic immune thrombocytopenia in children.

    Science.gov (United States)

    Liu, Anthony P Y; Cheuk, Daniel K L; Lee, Ana H Y; Lee, Pamela P W; Chiang, Alan K S; Ha, S Y; Tsoi, W C; Chan, Godfrey C F

    2016-10-01

    Twenty percent of children with immune thrombocytopenia (ITP) develop a chronic course where treatment strategy is less established. Cyclosporin A (CSA) has been shown to be effective in small series of children with chronic ITP and might reduce the need for chronic steroid therapy and/or splenectomy. We reviewed consecutive patients below 18 years old with persistent or chronic ITP treated with CSA in our unit between January 1998 and June 2015. Thirty patients (14 boys and 16 girls) were included. The median age at initial diagnosis of ITP was 5 years (range 0.5-16.2 years). CSA was started at a median of 13.9 months (range 3.4-124 months) after initial diagnosis and given for a median duration of 9.3 months (range 0.2-63.9 months). The median platelet count before commencement was 12 × 10(9)/L (range 4-199 × 10(9)/L). The median dose of CSA was 6 mg/kg/day (range 2.4-7.5 mg/kg/day). Complete response (CR) or response (R) was achieved in 17 patients (57 %), and 7 (23 %) had sustained response. Side effects (most commonly hirsutism) were tolerable and reversible. CSA appeared effective in about half of persistent or chronic ITP patients and safe as a second-line agent in managing these children.

  15. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  17. 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.

  18. CLINICAL AND LABORATORY MANIFESTATIONS OF THROMBOCYTOPENIA IN PATIENTS WITH SYSTEMIC LUPUS ERYTHEMATOSUS

    Directory of Open Access Journals (Sweden)

    I. Salehi.

    1997-06-01

    Full Text Available In systemic lupus erythematosus- (SLE various antibodies are produced against cells including platelets and result in thrombocytopenia. In the literature, the incidence of thrombocytopenia varied from 7% to 52%, in seven series of SLE patients with a mean cumulative percentage of 14.5% (1-5. SLE patients referred to the Lupus Unit of the Rheumatology Research Center, Tehran University for Medical Sciences (Shariati Hospital during the period of 1975 to 1977 were included in this study. T/irombocytopenic patients were selected and 72 items were studied. Tiie incidence of thrombocytopenia in Iranian SLE patients was 16.6%, which is similar to the mean cumulative percentage mentioned above. There was no difference in sex ratio between thrombocytopenic ami nonthrombocytopenic patients: Tiie same was true for the mean age at the onset of the disease. In 70% of patients there was mild to moderate thrombocytopenia (platelet from 50000 to lS0000/mm3. the remaining (30% had severe to very severe thrombocytopenia. In 1.9% of patients had a previous diagnosis of idiopathic thrombocytopenic purpura (ITP. the following symptoms were seen more oflen in thrombocy¬topenic patients than in others: Hemolytic anemia (p<0.001, leukopenia (p<0.001, lymphopenia (p<0.001, splenomegaly (p<0.00007, and abortion (p<0.0006. For the fallowings the p value was less than 0.05: ESR> 700, positive FANA, positive Anti-dsDNA antibodies, positive VDRL, and positive anticardiolipin antibodies. All thrombocytopenic patients' except one (previously sptenectomized were controlled by the medical treatment. Severe and very severe thrombocytopenia were controlled in 86% of cases by moderate to high dose steroids, with or without cytotoxic drugs: In 10% of cases, thrombocytopenia was controlled by a combination of chloroquine and low dose steroid (< 15 mg prednisolone daily. In 4%, other medical treatments (Danazol, etc. were needed.

  19. Successful treatment of post-transplant thrombocytopenia with romiplostim in a pediatric patient with X-linked chronic granulomatous disease.

    Science.gov (United States)

    Buchbinder, David; Hsieh, Loan; Krance, Robert; Nugent, Diane J

    2014-11-01

    Thrombocytopenia is a frequent complication following HSCT in pediatric patients. Romiplostim is a TPO receptor agonist that has been utilized successfully in the treatment of pediatric patients with immune thrombocytopenia. We describe a three-yr-old male with X-linked CGD treated with an unrelated donor bone marrow transplant. His course was complicated by the development of symptomatic thrombocytopenia. He was started on romiplostim with prompt improvement in his thrombocytopenia. We found the use of romiplostim to be an effective and safe alternative to the potential complications as well as morbidity and mortality associated with the use of immunosuppressive agents such as corticosteroids.

  20. 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.

  1. 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.

  2. Refractor y thrombotic thrombocytopenic pur pura following acute pancreatitis

    OpenAIRE

    Ebisa Bekele; Bethel Shiferaw; Alexandra Sokolova; Arpan Shah; Phillip Saunders; Alida Podrumar; Javed Iqbal

    2016-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a rare blood disorder with an estimated incidence of 4–5 cases per million people per year. It is characterized by small-vessel platelet-rich thrombi that cause thrombocytopenia, microangiopathic hemolytic anemia and organ damage. There are reports in literature that TTP and acute pancreatitis are associated, indicating each can be the cause of the other. However, acute pancreatitis triggering TTP is very rare. A 71 years old female ...

  3. [Significance of regulatory B cells in nosogenesis of immune thrombocytopenia].

    Science.gov (United States)

    Li, Xin; Wang, Fang; Ding, Kai Yang; Dai, Lan

    2014-04-01

    This study was aimed to investigate the role of regulatory B cells (Breg) in pathogenesis of immune thrombocytopenia (ITP) and its clinical significance. A total of 35 ITP patients and 20 normal controls were enrolled in this study. The expression of CD19(+)CD24(hi)CD38(hi) B cells was detected by flow cytometry and the expression of IL-10 mRNA and TGF-β1 mRNA was assayed by RT-PCR. The results indicated that the expression level of CD19(+)CD24(hi)CD38(hi) B cells in peripheral blood of newly diagnosed ITP patients was obviously lower than that in normal controls (P < 0.05); the expression level of CD19(+)CD24(hi)CD38(hi) B cells in ITP patients with increased platelet count after treatment was higher than that before treatment (P < 0.05); the expression level of IL-10 mRNA in newly diagnosed ITP patients was significantly lower than that the in normal controls (P < 0.05), the expression level of TGF-β1 mRNA in newly diagnosed ITP patients increases as compared with normal controls (P < 0.05), after treatment with DXM the expression of IL-10 mRNA was enhanced, the expression of TGF-β1 mRNA was reduced as compared with expression level before treatment (P < 0.05). It is concluded that the Breg cells may play an important role in the pathogenesis of ITP via humoral immunity and its regulation of T lymphocytes.

  4. Rituximab for children with immune thrombocytopenia: a systematic review.

    Directory of Open Access Journals (Sweden)

    Yi Liang

    Full Text Available BACKGROUND: Rituximab has been widely used off-label as a second line treatment for children with immune thrombocytopenia (ITP. However, its role in the management of pediatric ITP requires clarification. To understand and interpret the available evidence, we conducted a systematic review to assess the efficacy and safety of rituximab for children with ITP. METHODOLOGY/PRINCIPAL FINDINGS: We searched MEDLINE, EMBASE, Cochrane Library, CBM, CNKI, abstract databases of American Society of Hematology, American Society of Clinical Oncology and Pediatric Academic Society. Clinical studies published in full text or abstract only in any language that met predefined inclusion criteria were eligible. Efficacy analysis was restricted to studies enrolling 5 or more patients. Safety was evaluated from all studies that reported data of toxicity. 14 studies (323 patients were included for efficacy assessment in children with primary ITP. The pooled complete response (platelet count ≥ 100 × 10(9/L and response (platelet count ≥ 30 × 10(9/L rate after rituximab treatment were 39% (95% CI, 30% to 49% and 68% (95%CI, 58% to 77%, respectively, with median response duration of 12.8 month. 4 studies (29 patients were included for efficacy assessment in children with secondary ITP. 11 (64.7% of 17 patients associated with Evans syndrome achieved response. All 6 patients with systemic lupus erythematosus associated ITP and all 6 patients with autoimmune lymphoproliferative syndrome associated ITP achieved response. 91 patients experienced 108 adverse events associated with rituximab, among that, 91 (84.3% were mild to moderate, and no death was reported. CONCLUSIONS/SIGNIFICANCE: Randomized controlled studies on effect of rituximab for children with ITP are urgently needed, although a series of uncontrolled studies found that rituximab resulted in a good platelet count response both in children with primary and children secondary ITP. Most adverse events

  5. An improbable and unusual case of thrombotic thrombocytopenia purpura

    Directory of Open Access Journals (Sweden)

    Jaymon Patel

    2016-09-01

    Full Text Available Thrombotic thrombocytopenic purpura (TTP is a life-threatening medical emergency which may be difficult to recognize given the wide spectrum in which it presents. A delay in treatment may be catastrophic as untreated cases of TTP have a mortality rate exceeding 90%. Given the high fatality rate of untreated TTP and its range of presenting symptoms, we present our unusual case of TTP in a post-splenectomy patient with early treatment and positive outcome. This case describes a 54-year-old female who presented with hematuria and gingival bleeding, followed by the development of a bilateral lower extremity petechial rash. Her past medical history was significant for multiple episodes of TTP, the last of which resulted in a splenectomy and a 20-year history of remission thereafter. On exam, she was alert, well appearing, and neurologically intact. Her only significant finding was a bilateral lower extremity petechial rash. Laboratory studies revealed mild anemia and thrombocytopenia, an elevated lactate dehydrogenase, and a decreased haptoglobin. Peripheral smear showed poikilocytosis, helmet cells, and schistocytes. Corticosteroid therapy was promptly initiated, her platelets were monitored closely, and she underwent urgent therapeutic plasma exchange. Due to the risk of significant morbidity and mortality that may result from delayed treatment of TTP as well as the significant variations of presentation, TTP requires a consistently high index of suspicion. Our patient suffered multiple relapses of TTP within a 30-year span, underwent splenectomy in early adulthood, and presented with atypical symptoms during her most recent relapse illustrating how persistent TTP can be as well as how unusually it may present. Providers should be aware of the vast spectrum of presentation and remember that TTP may recur following splenectomy despite prolonged remission.

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

    Directory of Open Access Journals (Sweden)

    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.

  7. MHC class II up-regulation and co-localization with Fas in experimental models of immune-mediated bone marrow failure

    Science.gov (United States)

    Erie, Andrew J.; Samsel, Leigh; Takaku, Tomoiku; Desierto, Marie J.; Keyvanfar, Keyvan; McCoy, J. Philip; Young, Neal S.; Chen, Jichun

    2011-01-01

    Objective To test the hypothesis that gamma interferon (IFN-γ) promotes MHC class II expression on bone marrow (BM) cell targets that facilitates T cell-mediated BM destruction in immune-mediated BM failure. Materials and Methods Allogeneic lymph node (LN) cells were infused into MHC or minor histocompatibility antigen (minor-H) mismatched hosts to induce BM failure. MHC class II and Fas expression and cell apoptosis were analyzed by flow cytometry. MHC class II-Fas co-localization was detected by ImageStream Imaging Flow Cytometry and other cell-cell associations were visualized by confocal microscopy. T cell-mediated BM cell apoptosis and effects of IFN-γ on MHC class II-Fas co-localization on normal BM cells were studied using cell culture in vitro followed by conventional and imaging flow cytometry. Results BM failure animals had significantly up-regulated MHC class II expression on CD4−CD8−CD11b−CD45R− residual BM cells and significantly increased MHC class II-Fas co-localization on BM CD150+ and CD34+ hematopoietic cells. MHC class II+Fas+ BM cells were closely associated with CD4+ T cells in the BM of affected animals, and they were significantly more responsive to T-cell mediated cell apoptosis relative to MHC class II−Fas− BM cells. Infusion of IFN-γ-deficient LN cells into minor-H mismatched recipients resulted in no MHC class II-Fas up-regulation and no clinically overt BM failure. Treatment with recombinant IFN-γ significantly increased both MHC class II-Fas co-expression and co-localization on normal BM cells. Conclusion Elevation of the inflammatory cytokine IFN-γ stimulated MHC class II expression and MHC class II-Fas co-localization, which may facilitate T-cell mediated cell destruction. PMID:21635935

  8. Immune-mediated hemolytic anemia - report of three cases / Anemia hemolítica imunomediada em cães - relato de três casos

    Directory of Open Access Journals (Sweden)

    Luciana Curotto Nolasco de Carvalho

    Full Text Available Immune-mediated hemolytic anemia (IMHA is a common type of anemia in dogs and cats. The disease é most common in middle-aged female dogs, especially American Cocker Spaniel. The clinical signs are associated with severe anemia. There is no pathognomonic test for IMHA, but the presence of hemolytic anemia in a young adult or middle age, autoagglutination and spherocytosis or positive results of Coombs test, elimination of any other underlying cause of anemia and an appropriate response to immunosuppressive therapy are suggestive of it. The aim of the present paper is to report of three cases of serious IMHA, and highlighting the therapeutic modalities and prognosis associated with them.A anemia hemolítica imunomediada (AHIM é um tipo comum de anemia em cães e gatos. A doença é mais comum em fêmeas caninas de meia-idade, especialmente Cocker Spaniel Americano. Os sinais clínicos estão associados com a anemia severa. Não há achados patognomônicos, mas a presença de anemia hemolítica em um cão jovem ou de meia idade, auto-aglutinação e esferócitos ou teste de Coombs positivo, eliminação de outros diagnósticos diferenciais e a resposta apropriada a terapia imunossupressora indicam AHIM. Apesar de inúmeras opções terapêuticas, os índices de mortalidade permanecem elevados. O objetivo do presente trabalho é relatar três casos graves de AHIM, ressaltando as modalidades terapêuticas e o prognóstico associado a elas.

  9. 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.

  10. 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

  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. Indispensable roles of OX40L-derived signal and epistatic genetic effect in immune-mediated pathogenesis of spontaneous pulmonary hypertension

    Directory of Open Access Journals (Sweden)

    Rabieyousefi Moloud

    2011-12-01

    Full Text Available Abstract Background Pulmonary hypertension (PH refers to a spectrum of diseases with elevated pulmonary artery pressure. Pulmonary arterial hypertension (PAH is a disease category that clinically presents with severe PH and that is histopathologically characterized by the occlusion of pulmonary arterioles, medial muscular hypertrophy, and/or intimal fibrosis. PAH occurs with a secondary as well as a primary onset. Secondary PAH is known to be complicated with immunological disorders. The aim of the present study is to histopathologically and genetically characterize a new animal model of PAH and clarify the role of OX40 ligand in the pathogenesis of PAH. Results Spontaneous onset of PAH was stably identified in mice with immune abnormality because of overexpression of the tumor necrosis factor (TNF family molecule OX40 ligand (OX40L. Histopathological and physical examinations revealed the onset of PAH-like disorders in the C57BL/6 (B6 strain of OX40L transgenic mice (B6.TgL. Comparative analysis performed using different strains of transgenic mice showed that this onset depends on the presence of OX40L in the B6 genetic background. Genetic analyses demonstrated a susceptibility locus of a B6 allele to this onset on chromosome 5. Immunological analyses revealed that the excessive OX40 signals in TgL mice attenuates expansion of regulatory T cells the B6 genetic background, suggesting an impact of the B6 genetic background on the differentiation of regulatory T cells. Conclusion Present findings suggest a role for the OX40L-derived immune response and epistatic genetic effect in immune-mediated pathogenesis of PAH.

  13. 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.

  14. Anti-HMGCR antibodies as a biomarker for immune-mediated necrotizing myopathies: A history of statins and experience from a large international multi-center study.

    Science.gov (United States)

    Musset, Lucile; Allenbach, Yves; Benveniste, Olivier; Boyer, Olivier; Bossuyt, Xavier; Bentow, Chelsea; Phillips, Joe; Mammen, Andrew; Van Damme, Philip; Westhovens, René; Ghirardello, Anna; Doria, Andrea; Choi, May Y; Fritzler, Marvin J; Schmeling, Heinrike; Muro, Yoshinao; García-De La Torre, Ignacio; Ortiz-Villalvazo, Miguel A; Bizzaro, Nicola; Infantino, Maria; Imbastaro, Tiziana; Peng, Qinglin; Wang, Guochun; Vencovský, Jiří; Klein, Martin; Krystufkova, Olga; Franceschini, Franco; Fredi, Micaela; Hue, Sophie; Belmondo, Thibaut; Danko, Katalin; Mahler, Michael

    2016-10-01

    In an effort to find naturally occurring substances that reduce cholesterol by inhibiting 3-hydroxy-3-methylglutaryl-coenzyme A reductase (HMGCR), statins were first discovered by Endo in 1972. With the widespread prescription and use of statins to decrease morbidity from myocardial infarction and stroke, it was noted that approximately 5% of all statin users experienced muscle pain and weakness during treatment. In a smaller proportion of patients, the myopathy progressed to severe morbidity marked by proximal weakness and severe muscle wasting. Remarkably, Mammen and colleagues were the first to discover that the molecular target of statins, 3-hydroxy-3-methylglutaryl coenzyme A reductase (HMGCR), is an autoantibody target in patients that develop an immune-mediated necrotizing myopathy (IMNM). These observations have been confirmed in a number of studies but, until today, a multi-center, international study of IMNM, related idiopathic inflammatory myopathies (IIM), other auto-inflammatory conditions and controls has not been published. Accordingly, an international, multi-center study investigated the utility of anti-HMGCR antibodies in the diagnosis of statin-associated IMNM in comparison to different forms of IIM and controls. This study included samples from patients with different forms of IIM (n=1250) and patients with other diseases (n=656) that were collected from twelve sites and tested for anti-HMGCR antibodies by ELISA. This study confirmed that anti-HMGCR autoantibodies, when found in conjunction with statin use, characterize a subset of IIM who are older and have necrosis on muscle biopsy. Taken together, the data to date indicates that testing for anti-HMGCR antibodies is important in the differential diagnosis of IIM and might be considered for future classification criteria.

  15. 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.

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

    Science.gov (United States)

    Danish, Fazal-I-Akbar; Yasmin, Saeeda

    2013-01-01

    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."

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

    Directory of Open Access Journals (Sweden)

    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. Whole exome sequencing identifies genetic variants in inherited thrombocytopenia with secondary qualitative function defects

    Science.gov (United States)

    Johnson, Ben; Lowe, Gillian C.; Futterer, Jane; Lordkipanidzé, Marie; MacDonald, David; Simpson, Michael A.; Sanchez-Guiú, Isabel; Drake, Sian; Bem, Danai; Leo, Vincenzo; Fletcher, Sarah J.; Dawood, Ban; Rivera, José; Allsup, David; Biss, Tina; Bolton-Maggs, Paula HB; Collins, Peter; Curry, Nicola; Grimley, Charlotte; James, Beki; Makris, Mike; Motwani, Jayashree; Pavord, Sue; Talks, Katherine; Thachil, Jecko; Wilde, Jonathan; Williams, Mike; Harrison, Paul; Gissen, Paul; Mundell, Stuart; Mumford, Andrew; Daly, Martina E.; Watson, Steve P.; Morgan, Neil V.

    2016-01-01

    Inherited thrombocytopenias are a heterogeneous group of disorders characterized by abnormally low platelet counts which can be associated with abnormal bleeding. Next-generation sequencing has previously been employed in these disorders for the confirmation of suspected genetic abnormalities, and more recently in the discovery of novel disease-causing genes. However its full potential has not yet been exploited. Over the past 6 years we have sequenced the exomes from 55 patients, including 37 index cases and 18 additional family members, all of whom were recruited to the UK Genotyping and Phenotyping of Platelets study. All patients had inherited or sustained thrombocytopenia of unknown etiology with platelet counts varying from 11×109/L to 186×109/L. Of the 51 patients phenotypically tested, 37 (73%), had an additional secondary qualitative platelet defect. Using whole exome sequencing analysis we have identified “pathogenic” or “likely pathogenic” variants in 46% (17/37) of our index patients with thrombocytopenia. In addition, we report variants of uncertain significance in 12 index cases, including novel candidate genetic variants in previously unreported genes in four index cases. These results demonstrate that whole exome sequencing is an efficient method for elucidating potential pathogenic genetic variants in inherited thrombocytopenia. Whole exome sequencing also has the added benefit of discovering potentially pathogenic genetic variants for further study in novel genes not previously implicated in inherited thrombocytopenia. PMID:27479822

  19. Management of Thrombocytopenia in Chronic Liver Disease: Focus on Pharmacotherapeutic Strategies.

    Science.gov (United States)

    Maan, Raoel; de Knegt, Robert J; Veldt, Bart J

    2015-11-01

    Thrombocytopenia (platelet count management of these patients. The prevalence of this manifestation ranges from 6% among non-cirrhotic patients with chronic liver disease to 70% among patients with liver cirrhosis. It has also been shown that the severity of liver disease is associated with both prevalence and level of thrombocytopenia. Its development is often multifactorial, although thrombopoietin is thought to be a major factor. The discovery of and ability to clone thrombopoietin led to new treatment opportunities for this clinical manifestation. This review discusses data on the three most important thrombopoietin receptor agonists: eltrombopag, avatrombopag, and romiplostim. Currently, only eltrombopag is approved for usage among patients with thrombocytopenia and chronic hepatitis C virus infection in order to initiate and maintain interferon-based antiviral treatment. Nevertheless, the optimal management of hematologic abnormalities among patients with chronic liver disease, and its risk for bleeding complications, is still a matter of discussion. Thrombocytopenia definitely contributes to hemostatic defects but is often counterbalanced by the enhanced presence of procoagulant factors. Therefore, a thorough assessment of the patient's risk for thrombotic events is essential when the use of thrombopoietin receptor agonists is considered among patients with chronic liver disease and thrombocytopenia.

  20. 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.

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

    Directory of Open Access Journals (Sweden)

    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

  2. Antiphospholipid syndrome in a pregnant female presenting with severe thrombocytopenia and bleeding.

    Science.gov (United States)

    Mahajan, Kunal; Katyal, Virender; Arya, Suvrat; Shrama, Meha

    2015-01-01

    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.

  3. Delayed-onset heparin-induced thrombocytopenia presenting with multiple arteriovenous thromboses: case report

    Directory of Open Access Journals (Sweden)

    Omran Abbas

    2007-11-01

    Full Text Available Abstract Background Delayed-onset heparin-induced thrombocytopenia with thrombosis, albeit rare, is a severe side effect of heparin exposure. It can occur within one month after coronary artery bypass grafting (CABG with manifestation of different thrombotic events. Case presentation A 59-year-old man presented with weakness, malaise, bilateral lower limb pitting edema and a suspected diagnosis of deep vein thrombosis 18 days after CABG. Heparin infusion was administered as an anticoagulant. Clinical and paraclinical work-up revealed multiple thrombotic events (stroke, renal failure, deep vein thrombosis, large clots in heart chambers and 48 ×103/μl platelet count, whereupon heparin-induced thrombocytopenia was suspected. Heparin was discontinued immediately and an alternative anticoagulant agent was administered, as a result of which platelet count recovered. Heparin-induced thrombocytopenia, which causes thrombosis, is a serious side effect of heparin therapy. It is worthy of note that no case of delayed-onset heparin-induced thrombocytopenia with thrombosis associated with cardiopulmonary bypass surgery has thus far been reported in Iran. Conclusion Delayed-onset heparin-induced thrombocytopenia should be suspected in any patient presenting with arterial or venous thromboembolic disorders after recent heparin therapy, even though the heparin exposure dates back to more than a week prior to presentation; and it should be ruled-out before the initiation of heparin therapy.

  4. 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.

  5. Immune-mediated hemolytic anemia.

    Science.gov (United States)

    Rosse, Wendell F; Hillmen, Peter; Schreiber, Alan D

    2004-01-01

    Hemolytic anemia due to immune function is one of the major causes of acquired hemolytic anemia. In recent years, as more is known about the immune system, these entities have become better understood and their treatment improved. In this section, we will discuss three areas in which this progress has been apparent. In Section I, Dr. Peter Hillmen outlines the recent findings in the pathogenesis of paroxysmal nocturnal hemoglobinuria (PNH), relating the biochemical defect (the lack of glycosylphosphatidylinositol [GPI]-linked proteins on the cell surface) to the clinical manifestations, particularly hemolysis (and its effects) and thrombosis. He discusses the pathogenesis of the disorder in the face of marrow dysfunction insofar as it is known. His major emphasis is on innovative therapies that are designed to decrease the effectiveness of complement activation, since the lack of cellular modulation of this system is the primary cause of the pathology of the disease. He recounts his considerable experience with a humanized monoclonal antibody against C5, which has a remarkable effect in controlling the manifestations of the disease. Other means of controlling the action of complement include replacing the missing modulatory proteins on the cell surface; these studies are not as developed as the former agent. In Section II, Dr. Alan Schreiber describes the biochemistry, genetics, and function of the Fc gamma receptors and their role in the pathobiology of autoimmune hemolytic anemia and idiopathic thrombocytopenic purpura due to IgG antibodies. He outlines the complex varieties of these molecules, showing how they vary in genetic origin and in function. These variations can be related to three-dimensional topography, which is known in some detail. Liganding IgG results in the transduction of a signal through the tyrosine-based activation motif and Syk signaling. The role of these receptors in the pathogenesis of hematological diseases due to IgG antibodies is outlined and the potential of therapy of these diseases by regulation of these receptors is discussed. In Section III, Dr. Wendell Rosse discusses the forms of autoimmune hemolytic anemia characterized by antibodies that react preferentially in the cold-cold agglutinin disease and paroxysmal cold hemoglobinuria (PCH). The former is due to IgM antibodies with a common but particular structure that reacts primarily with carbohydrate or carbohydrate-containing antigens, an interaction that is diminished at body temperature. PCH is a less common but probably underdiagnosed illness due to an IgG antibody reacting with a carbohydrate antigen; improved techniques for the diagnosis of PCH are described. Therapy for the two disorders differs somewhat because of the differences in isotype of the antibody. Since the hemolysis in both is primarily due to complement activation, the potential role of its control, as by the monoclonal antibody described by Dr. Hillmen, is discussed.

  6. Severe thrombocytopenia in a child with typhoid fever: a case report.

    Science.gov (United States)

    Al Reesi, Mohammed; Stephens, Glenn; McMullan, Brendan

    2016-11-30

    Although thrombocytopenia is common in typhoid fever, its course, response to treatment, and need for specific therapies such as platelet transfusion are not well characterized. We report a case of typhoid fever in a 4-year-old Asian male returned traveler, admitted with prolonged fever and found to have severe thrombocytopenia (platelets 16 × 10(9)/L). Despite appropriate antibiotic therapy, his platelet recovery was slow, but did not lead to complications and he did not require platelet transfusion. There is no consensus in the medical literature guiding the optimal management of severe thrombocytopenia in typhoid fever, but it may improve with conservative management, as in our case. The epidemiology and management of this condition merits further research to guide clinical practice.

  7. Severe thrombocytopenia in a child with typhoid fever: a case report

    Directory of Open Access Journals (Sweden)

    Mohammed Al Reesi

    2016-11-01

    Full Text Available Abstract Background Although thrombocytopenia is common in typhoid fever, its course, response to treatment, and need for specific therapies such as platelet transfusion are not well characterized. Case presentation We report a case of typhoid fever in a 4-year-old Asian male returned traveler, admitted with prolonged fever and found to have severe thrombocytopenia (platelets 16 × 109/L. Despite appropriate antibiotic therapy, his platelet recovery was slow, but did not lead to complications and he did not require platelet transfusion. Conclusions There is no consensus in the medical literature guiding the optimal management of severe thrombocytopenia in typhoid fever, but it may improve with conservative management, as in our case. The epidemiology and management of this condition merits further research to guide clinical practice.

  8. Detection of antiplatelet antibody in serum and on megakaryocytes of dogs with autoimmune thrombocytopenia.

    Science.gov (United States)

    Joshi, B C; Jain, N C

    1976-06-01

    Blood and bone marrow samples from 13 thrombocytopenic dogs were examined to determine whether immunologic thrombocytopenia existed. Antiplatelet antibody was detected in serum of 8 of the dogs by platelet factor 3 test or its modification. Moderate to strong immunofluorescence of megakaryocytes was noticed in bone marrow smears stained with rabbit anticanine globulin conjugated with fluorescin isothiocyanate. Negative results were obtained with serum and bone marrow samples collected from 6 of the dogs during therapy for autoimmune thrombocytopenia. Clinical and laboratory findings varied in individual patients with circulating antiplatelet antibodies. Thrombocytopenia was present in all the dogs, with platelet counts ranging from less than 3,000 to 20,000/mu1 of blood. Signs of bleeding in tissues and body cavities were present in all dogs, but anemia was evidenced in only 3 dogs. Differential leukocyte counts were variable. Morphologic abnormalities such as vacuolation and reduced or absence of granulation of the cytoplasm and nuclear fragmentation were seen in some megakaryocytes.

  9. ST-Elevation Myocardial Infarction and Myelodysplastic Syndrome with Acute Myeloid Leukemia Transformation

    OpenAIRE

    2014-01-01

    Acute myocardial infarction and acute myeloid leukemia are rarely reported as concomitant conditions. The management of ST-elevation myocardial infarction (STEMI) in patients who have acute myeloid leukemia is challenging: the leukemia-related thrombocytopenia, platelet dysfunction, and systemic coagulopathy increase the risk of bleeding, and the administration of thrombolytic agents can be fatal. We report the case of a 76-year-old man who presented emergently with STEMI, myelodysplastic syn...

  10. Hepatitis C virus-associated thrombocytopenia is not related to serum thrombopoietin levels

    Directory of Open Access Journals (Sweden)

    Afifi Ola

    2007-01-01

    Full Text Available Objective: Hepatitis C virus (HCV infection is one of the most important health problems in Egypt. Thrombocytopenia is a common finding in subjects with chronic hepatitis. The precise etiology of this thrombocytopenia is still obscure. There is increasing interest in the potential role of thrombopoietin (TPO as a cause of this thrombocytopenia. The aim of this work was to determine serum TPO levels in HCV-positive patients and to test the assumption that HCV-associated thrombocytopenia could be due to low TPO levels. Materials and Methods: Forty patients with HCV infection were included in this study and classified into three groups according to the degree of thrombocytopenia (IA-mild, IB-moderate, II-none. Twenty five healthy volunteers served as control (Group III. All patients and controls had undergone full clinical assessment and the following laboratory investigations: complete blood count, liver function tests, prothrombin time and concentration and serum TPO level. Results: TPO levels were significantly elevated in Group IA as compared to the control group ( P < 0.05. No significant difference was found between groups IA and II. TPO in Group IB was slightly, but insignificantly reduced compared to Group IA but did not differ statistically from the control or Group II. Significant negative correlation was found between serum TPO levels and platelet counts in Groups IA, IB and II (r=-0.421, P < 0.05. No correlations were found between serum TPO levels and liver function tests or hematological parameters. Conclusion: An impaired TPO production did not explain the development of thrombocytopenia in HCV and other mechanisms must be involved.

  11. Results of a randomized, double-blind study of romiplostim versus placebo in patients with low/intermediate-1–risk myelodysplastic syndrome and thrombocytopenia

    Science.gov (United States)

    Giagounidis, Aristoteles; Mufti, Ghulam J; Fenaux, Pierre; Sekeres, Mikkael A; Szer, Jeffrey; Platzbecker, Uwe; Kuendgen, Andrea; Gaidano, Gianluca; Wiktor-Jedrzejczak, Wieslaw; Hu, Kuolung; Woodard, Paul; Yang, Allen S; Kantarjian, Hagop M

    2014-01-01

    BACKGROUND Thrombocytopenia in patients with myelodysplastic syndrome (MDS) is associated with shortened survival and an increased risk of evolution to acute myeloid leukemia (AML). In this study, the authors evaluated the efficacy of romiplostim in patients who had thrombocytopenia with low-risk/intermediate-1–risk MDS. METHODS Patients who had thrombocytopenia with low-risk/intermediate-1–risk MDS (N = 250) were randomized 2:1 to receive romiplostim or placebo weekly for 58 weeks. RESULTS The primary endpoint— the number of clinically significant bleeding events (CSBEs) per patient—had a hazard ratio for romiplostim:placebo of 0.83 (95% confidence interval, 0.66-1.05; P = .13). CSBEs were reduced significantly in the romiplostim group for patients who had baseline platelet counts ≥20 × 109/L (P < .0001). For patients who had baseline platelet counts <20 × 109/L, there was no difference in the number of CSBEs, but the platelet transfusion rates were higher in the placebo group (P < .0001), which may have affected the overall CSBE results in this group with severe thrombocytopenia. The incidence of bleeding events was reduced significantly in the romiplostim group (relative risk, 0.92), as were protocol-defined platelet transfusions (relative risk, 0.77). Platelet response rates according to 2006 International Working Group criteria were higher for the group that received romiplostim (odds ratio, 15.6). On the basis of interim data, an independent data monitoring committee advised halting study drug because of concerns regarding excess blasts and AML rates with romiplostim (interim hazard ratio, 2.51). At 58 weeks, the AML rates were 6% in the romiplostim group and 4.9% in the placebo group (hazard ratio, 1.20; 95% confidence interval, 0.38-3.84), and the overall survival rates were similar. CONCLUSIONS Romiplostim treatment in patients with low-risk/intermediate-1–risk MDS increased platelet counts and decreased the number of

  12. 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

  13. Congenital amegakaryocytic thrombocytopenia: a case report of pediatric twins undergoing matched unrelated bone marrow transplantation.

    Science.gov (United States)

    Rao, Amulya A N; Gourde, Julia A; Marri, Preethi; Galardy, Paul J; Khan, Shakila P; Rodriguez, Vilmarie

    2015-05-01

    Congenital amegakaryocytic thrombocytopenia (CAMT) is a rare inherited disorder that presents with thrombocytopenia in infancy and evolves into bone marrow failure over time. Allogeneic hematopoietic stem cell transplant remains the only curative treatment option. We report our experience with identical twin sisters diagnosed with CAMT and treated successfully with matched unrelated donor bone marrow transplants. Before the transplant, 1 twin developed pancytopenia, whereas the other had a relatively benign clinical course. Choice of conditioning regimens was based on their pretransplant bone marrow cellularity and presence or absence of panyhypoplasia. Both twins tolerated the procedure well with no significant complications.

  14. Homing in on Acute Graft vs. Host Disease: Tissue-Specific T Regulatory and Th17 Cells

    OpenAIRE

    Engelhardt, Brian G.; Crowe, James E.

    2010-01-01

    Acute graft vs. host disease (aGVHD) is a major limitation of hematopoietic stem cell transplantation (HSCT), and it causes significant morbidity and mortality for this patient population. This immune-mediated injury occurs unpredictably and is caused by donor-derived T cells reacting to recipient alloantigens. Although donor Th1 cells play a critical role in aGVHD generation, numerous arms of both the innate and the adaptive immune systems along with determinants of lymphocyte trafficking ar...

  15. 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.

  16. Gender and the treatment of immune-mediated chronic inflammatory diseases: rheumatoid arthritis, inflammatory bowel disease and psoriasis: an observational study

    Directory of Open Access Journals (Sweden)

    Lesuis Nienke

    2012-08-01

    Full Text Available Abstract Background Rheumatoid arthritis (RA, inflammatory bowel disease (IBD, and psoriasis are immune-mediated inflammatory diseases with similarities in pathophysiology, and all can be treated with similar biological agents. Previous studies have shown that there are gender differences with regard to disease characteristics in RA and IBD, with women generally having worse scores on pain and quality of life measurements. The relationship is less clear for psoriasis. Because treatment differences between men and women could explain the dissimilarities, we investigated gender differences in the disease characteristics before treatment initiation and in the biologic treatment prescribed. Methods Data on patients with RA or IBD were collected from two registries in which patients treated with biologic medication were enrolled. Basic demographic data and disease activity parameters were collected from a time point just before the initiation of the biologic treatment. For patients with psoriasis, the data were taken from the 2010 annual report of the Swedish Psoriasis Register for systemic treatment, which included also non-biologic treatment. For all three diseases, the prescribed treatment and disease characteristics were compared between men and women. Results In total, 4493 adult patients were included in the study (1912 with RA, 131 with IBD, and 2450 with psoriasis. Most of the treated patients with RA were women, whereas most of the patients with IBD or psoriasis were men. There were no significant differences between men and women in the choice of biologics. At treatment start, significant gender differences were seen in the subjective disease measurements for both RA and psoriasis, with women having higher (that is, worse scores than men. No differences in objective measurements were found for RA, but for psoriasis men had higher (that is, worse scores for objective disease activity measures. A similar trend to RA was seen in IBD

  17. Advances in fetal immune mediated atrioventricular block%胎儿免疫性房室传导阻滞研究进展

    Institute of Scientific and Technical Information of China (English)

    严华林; 李一飞(综述); 周开宇; 华益民(审校)

    2015-01-01

    Fetal atrioventricular block (AVB) is a type of fetal bradyarrhythmias. The reported incidence of fetal complete atrioventricular block (CAVB) and mortality of perinatal fetuses and neonates are signiifcantly higher in pregnancies of anti-SSA/Ro-positive mothers than that of anti-SSA/Ro-negative mothers. The auto-antibodies in maternal serum that can be transported into fetal circulation through placenta may damage fetal cardiac conductive system and eventually result in fetal AVB. There are evidences that early diagnosis and proper treatment can improve the prognosis and survival rate of affected fetuses. In this article, the pathogenesis, risk factors, prenatal diagnosis, treatment and prognosis of fetal immune mediated AVB is reviewed.%胎儿房室传导阻滞属于胎儿缓慢性心律失常。当母体血清抗-SSA/Ro、抗-SSB/La抗体阳性时,胎儿完全性房室传导阻滞发病率和相关围生期胎儿/新生儿死亡率显著升高。母体血清自身抗体可经胎盘转运进入胎儿体内,可能导致胎儿心脏传导系统免疫损伤,从而引起房室传导阻滞发生。如果能进行胎儿免疫性房室传导阻滞的早期诊断和及时干预,可能阻止病情进展,改善免疫性房室传导阻滞胎儿的预后并提高其生存率。文章综述胎儿免疫性房室传导阻滞的发病机制、危险因素、产前诊断、胎儿期干预及预后等。

  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. Prevalence of Thrombocytopenia among Chinese Adult Antiretroviral-na(i)ve HIV-positive Patients

    Institute of Scientific and Technical Information of China (English)

    Hong-Wei Fan; Fu-Ping Guo; Yi-Jia Li; Ning Li; Tai-Sheng Li

    2015-01-01

    Background:The prevalence ofthrombocytopenia among Chinese antiretroviral therapy (ART)-na(i)ve HIV-infected adults has not been well-described.The aim of this study was to investigate the prevalence and associated risk factors of thrombocytopenia among Chinese ART-na(i)ve HIV-infected adults.Methods:We performed a cross-sectional study of Chinese adult ART-na(i)ve HIV-infected patients from September 2005 through August 2014.Socio-demographic variables and laboratory results including platelets,CD4+ cell count,and viral load were obtained from medical records.Factors and outcomes associated with thrombocytopenia were assessed using logistic regression.Results:A total of 1730 adult ART-na(i)ve HIV-infected patients was included.The mean age was 38 years.The prevalence of thrombocytopenia was 4.5%.There were significant differences in the prevalence of thrombocytopenia between patients <30 years of age (2.8%) and 30-39 years (4.0%) compared with patients greater than 50 years (7.0%) (P =0.006 and P =0.044,respectively).The prevalence of thrombocytopenia was also significantly different between patients with CD4+ counts of 200-349 cells/mm3 (3.3%) and >350 cells/mm3 (2.8%) compared with patients with CD4+ counts of50-199 cells/mm3 (7.1%) (P =0.002 and P =0.005,respectively).The prevalence of thrombocytopenia was significantly different by hepatitis C virus antibody (HCV-Ab) seropositivity (10.2% for HCV-Ab positive vs.3.9% for HCV-Ab negative,P =0.001).We observed differences in prevalence of thrombocytopenia by mode of transmission of HIV infection:Blood transmission (10.7%) versus men who have sex with men (3.9%) (P =0.002) and versus heterosexual transmission (3.9%) (P =0.001).In binary logistic regression analyses,age ≥>50 years,HCV-Ab positivity and having a CD4+ cell count of 50-199 cells/mm3 were significantly associated with thrombocytopenia with adjusted odds ratio of 2.482 (95% confidence interval [CI]:1.167,5.281,P=0

  20. A case of neonatal HPA-1b allo-immune thrombocytopenia

    NARCIS (Netherlands)

    van der Vlugt, AH; Hepkema, BG; Tamminga, RYJ

    1999-01-01

    We present a case of a newborn with neonatal alloimmune thrombocytopenia (NAIT) due to fete-maternal incompatibility for the thrombocyte allo-antigen HPA-1b. We discuss the policy of platelet transfusions and suggest to treat NAIT early on with thrombocytes transfusions from selected compatible

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

    Directory of Open Access Journals (Sweden)

    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.

  2. Effect of recombinant human thrombopoietin in nonhuman primates with chemotherapy-induced thrombocytopenia.

    Science.gov (United States)

    Akahori, H; Shibuya, K; Obuchi, M; Nishizawa, Y; Tsuji, A; Kabaya, K; Kusaka, M; Ohashi, H; Tsumura, H; Kato, T; Miyazaki, H

    1996-09-01

    We examined the effects of recombinant human thrombopoietin (rhTPO) on myelosuppressive chemotherapy-induced thrombocytopenia in cynomolgus monkeys. After treatment with nimustine (ACNU) on day 0, the monkeys intravenously received rhTPO at a dose of 0.04, 0.2 or 1 microgram/kg/d or monkey's serum once each day from day 1 to day 28. Administration of rhTPO reduced the severity of thrombocytopenia and accelerated the rate of platelet recovery in a dose-dependent fashion. Treatment with the highest rhTPO dose completely prevented thrombocytopenia and stimulated a marked increase in platelet counts over the normal values. Animals treated with ACNU also became neutropenic and slightly anaemic. Administration of rhTPO following ACNU treatment significantly improved neutropenia with increasing doses of rhTPO, but had no effect on anaemia. Compared to the control animals, rhTPO-treated animals exhibited no significant changes in several serum parameters. C-reactive protein concentration and some blood coagulation profiles within the study period. These results suggest a therapeutic efficacy of rhTPO in improving chemotherapy-induced thrombocytopenia.

  3. Fcγ receptor expression on splenic macrophages in adult immune thrombocytopenia

    NARCIS (Netherlands)

    Audia, S; Santegoets, K; Laarhoven, A G; Vidarsson, G; Facy, O; Ortega-Deballon, P; Samson, M; Janikashvili, N; Saas, P; Bonnotte, B; Radstake, T R

    2017-01-01

    Splenic macrophages play a key role in immune thrombocytopenia (ITP) pathogenesis by clearing opsonized platelets. Fcγ receptors (FcγR) participate in this phenomenon, but their expression on splenic macrophages and their modulation by treatment have scarcely been studied in human ITP. We aimed to

  4. The clinical usefulness of the platelet aggregation test for the diagnosis of heparin-induced thrombocytopenia

    NARCIS (Netherlands)

    Chong, B H; Burgess, J; Ismail, F

    1993-01-01

    The platelet aggregation test is widely used for the diagnosis of heparin-induced thrombocytopenia (HIT), a potentially serious complication of heparin therapy. We have evaluated its sensitivity and specificity in comparison with those of the 14C-serotonin release test. The sensitivity of the platel

  5. Thrombocytopenia in pregnancy in a tertiary care hospital: a retrospective study

    Directory of Open Access Journals (Sweden)

    Shiny Varghese

    2016-05-01

    Conclusions: Commonest cause of thrombocytopenia in pregnancy is GT, followed by preeclampsia, eclampsia and HELLP syndrome. ITP is a rare cause of this disorder in pregnancy. Early detection and treatment of expected complications is the key focus in management of such cases. [Int J Reprod Contracept Obstet Gynecol 2016; 5(5.000: 1532-1535

  6. 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 rema

  7. Pharmacokinetic-pharmacodynamic analysis of sunitinib-induced thrombocytopenia in Japanese patients with renal cell carcinoma.

    Science.gov (United States)

    Nagata, Masashi; Ishiwata, Yasuyoshi; Takahashi, Yutaka; Takahashi, Hiromitsu; Saito, Kazutaka; Fujii, Yasuhisa; Kihara, Kazunori; Yasuhara, Masato

    2015-01-01

    The aim of the present study was to clarify the therapeutic range and adequate dose of sunitinib in Japanese renal cell carcinoma patients by means of a pharmacokinetic-pharmacodynamic analysis of sunitinib-induced thrombocytopenia. Six patients with renal cell carcinoma were enrolled in this study. After starting the sunitinib treatment, between three and seven blood samples were obtained from each patient just before the administration of sunitinib. Serum concentrations of sunitinib and its active metabolite N-desethyl-sunitinib were fit to the 1-compartment model with first-order absorption. Changes in platelet counts were fit to the pharmacokinetic-pharmacodynamic model, in which the proliferation of platelet progenitor cells was assumed to be linearly inhibited by sunitinib and its metabolite. All patients using 50 mg as an initial dose of sunitinib developed grade 2 or 3 thrombocytopenia. The pharmacokinetic-pharmacodynamic model created successfully described the time course of sunitinib-induced thrombocytopenia and could predict changes in platelet counts after alterations to the dosage of sunitinib administered. The simulation results indicated that the total trough level of sunitinib to avoid severe thrombocytopenia should be Japanese patients. In addition to the pharmacokinetic-guided dosage adjustment, the careful monitoring of platelet counts is required for the safe use of sunitinib.

  8. Analysis of 339 pregnancies in 181 women with 13 different forms of inherited thrombocytopenia

    Science.gov (United States)

    Noris, Patrizia; Schlegel, Nicole; Klersy, Catherine; Heller, Paula G.; Civaschi, Elisa; Pujol-Moix, Nuria; Fabris, Fabrizio; Favier, Remi; Gresele, Paolo; Latger-Cannard, Véronique; Cuker, Adam; Nurden, Paquita; Greinacher, Andreas; Cattaneo, Marco; De Candia, Erica; Pecci, Alessandro; Hurtaud-Roux, Marie-Françoise; Glembotsky, Ana C.; Muñiz-Diaz, Eduardo; Randi, Maria Luigia; Trillot, Nathalie; Bury, Loredana; Lecompte, Thomas; Marconi, Caterina; Savoia, Anna; Balduini, Carlo L.; Bayart, Sophie; Bauters, Anne; Benabdallah-Guedira, Schéhérazade; Boehlen, Françoise; Borg, Jeanne-Yvonne; Bottega, Roberta; Bussel, James; De Rocco, Daniela; de Maistre, Emmanuel; Faleschini, Michela; Falcinelli, Emanuela; Ferrari, Silvia; Ferster, Alina; Fierro, Tiziana; Fleury, Dominique; Fontana, Pierre; James, Chloé; Lanza, Francois; Le Cam Duchez, Véronique; Loffredo, Giuseppe; Magini, Pamela; Martin-Coignard, Dominique; Menard, Fanny; Mercier, Sandra; Mezzasoma, Annamaria; Minuz, Pietro; Nichele, Ilaria; Notarangelo, Lucia D.; Pippucci, Tommaso; Podda, Gian Marco; Pouymayou, Catherine; Rigouzzo, Agnes; Royer, Bruno; Sie, Pierre; Siguret, Virginie; Trichet, Catherine; Tucci, Alessandra; Saposnik, Béatrice; Veneri, Dino

    2014-01-01

    Pregnancy in women with inherited thrombocytopenias is a major matter of concern as both the mothers and the newborns are potentially at risk of bleeding. However, medical management of this condition cannot be based on evidence because of the lack of consistent information in the literature. To advance knowledge on this matter, we performed a multicentric, retrospective study evaluating 339 pregnancies in 181 women with 13 different forms of inherited thrombocytopenia. Neither the degree of thrombocytopenia nor the severity of bleeding tendency worsened during pregnancy and the course of pregnancy did not differ from that of healthy subjects in terms of miscarriages, fetal bleeding and pre-term births. The degree of thrombocytopenia in the babies was similar to that in the mother. Only 7 of 156 affected newborns had delivery-related bleeding, but 2 of them died of cerebral hemorrhage. The frequency of delivery-related maternal bleeding ranged from 6.8% to 14.2% depending on the definition of abnormal blood loss, suggesting that the risk of abnormal blood loss was increased with respect to the general population. However, no mother died or had to undergo hysterectomy to arrest bleeding. The search for parameters predicting delivery-related bleeding in the mother suggested that hemorrhages requiring blood transfusion were more frequent in women with history of severe bleedings before pregnancy and with platelet count at delivery below 50 × 109/L. PMID:24763399

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

    Science.gov (United States)

    Ayadi, Imene Dahmane; Ben Hamida, Emira; Boukhris, Mohamed Riadh; Bezzine, Ahlem; Chaouachi, Sihem; Marrakchi, Zahra

    2015-01-01

    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 tissue disease. Pregnancy was uneventful. The postnatal examination was normal. On the first day of life, blood cells count showed thrombocytopenia at 40 x 10(9)/L. Within the second day of life, platelet level dropped to 20 x 10(9)/L. The management of thrombocytopenia included platelet transfusion and human immunoglobulin infusion. On the fifth day of life, there has been a drop in platelet count to 10 x 10(9)/L requiring renewed platelet transfusion and human immunoglobulin infusion. On the 10(th) of life platelets rate was stable around 60 x 10(9)/L. The infant had no evidence of cardiac, dermatologic or hepatobilary involvement initially or throughout follow up.

  10. Thrombocytopenia is associated with a dysregulated host response in critically ill sepsis patients

    NARCIS (Netherlands)

    Claushuis, Theodora A M; van Vught, Lonneke A; Scicluna, Brendon P; Wiewel, Maryse A; Klein Klouwenberg, Peter M C; Hoogendijk, Arie J; Ong, David S Y; Cremer, Olaf L; Horn, Janneke; Franitza, Marek; Toliat, Mohammad R; Nürnberg, Peter; Zwinderman, Aeilko H; Bonten, Marc J M; Schultz, Marcus J; van der Poll, Tom

    2016-01-01

    Preclinical studies have suggested that platelets influence the host response during sepsis. We sought to assess the association of admission thrombocytopenia with the presentation, outcome, and host response in patients with sepsis. Nine hundred thirty-one consecutive sepsis patients were stratifie

  11. 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.

  12. Severe fever with thrombocytopenia syndrome virus in ticks collected from humans, South Korea, 2013.

    Science.gov (United States)

    Yun, Seok-Min; Lee, Wook-Gyo; Ryou, Jungsang; Yang, Sung-Chan; Park, Sun-Whan; Roh, Jong Yeol; Lee, Ye-Ji; Park, Chan; Han, Myung Guk

    2014-08-01

    We investigated the infection rate for severe fever with thrombocytopenia syndrome virus (SFTSV) among ticks collected from humans during May-October 2013 in South Korea. Haemaphysalis longicornis ticks have been considered the SFTSV vector. However, we detected the virus in H. longicornis, Amblyomma testudinarium, and Ixodes nipponensis ticks, indicating additional potential SFTSV vectors.

  13. Reduced corticosteroid use in adult patients with primary immune thrombocytopenia receiving romiplostim

    NARCIS (Netherlands)

    M. Michel (Marc); P.A.W. te Boekhorst (Peter); A. Janssens (Andre); I. Pabinger-Fasching (Ingrid); M.A. Sanz (Miguel Angel); K. Nie (Kun); G. Kreuzbauer (Georg)

    2011-01-01

    textabstractAdult patients with primary immune thrombocytopenia requiring first-line treatment typically receive corticosteroids, which are associated with low response rates and many potential side effects. In a retrospective analysis of two 6-month, placebo-controlled, phase III trials, corticoste

  14. 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...

  15. 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.

  16. 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...

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

    Directory of Open Access Journals (Sweden)

    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.

  18. Study Progress on Pathogenesis of Primary immune thrombocytopenia%原发免疫性血小板减少症发病机制的研究进展

    Institute of Scientific and Technical Information of China (English)

    薛晗; 贾瑞萍

    2013-01-01

    Primary immune thrombocytopenia (ITP), is the most common clinical autoimmune disorder and the pathogenesis is not completely clear, which clinical features are mucocutaneous bleeding and visceral hemorrhage.The main Pathogenesis of ITP includes humoral and cellular immunity-mediated platelet destruction,abnormal magakaryoyte quantity and quality, suppressed platelet production.In recenct years, The opinions of complement system and T fol icular helper cells has caused more attention, This review wil be made to sum up the study progress on the pathogenesisof ITP.%原发免疫性血小板减少症(Primary immune thrombocytopenic purpura ITP)是一种常见的以皮肤黏膜、内脏出血为主要临床表现的自身免疫性疾病,其发病机制尚未完全明确。目前认为体液和细胞免疫介导的血小板过度破坏、巨核细胞数量和质量异常、血小板生成不足是该病的主要发病机制。近年来,随着对ITP发病机制的不断深入研究,补体作用、滤泡辅助性T细胞的异常等许多观点引起了越来越多的关注,本文将对ITP的发病机制的研究进展做一综述。

  19. Successful liver transplantation in a patient with splanchnic vein thrombosis and pulmonary embolism due to polycythemia vera with Jak2v617f mutation and heparin-induced thrombocytopenia.

    Science.gov (United States)

    Biagioni, Emanuela; Pedrazzi, Paola; Marietta, Marco; Di Benedetto, Fabrizio; Villa, Erica; Luppi, Mario; Girardis, Massimo

    2013-10-01

    Heparin-induced thrombocytopenia (HIT) is a rare complication of heparin treatment resulting in a severe acquired thrombophilic condition with an associated mortality of about 10 %. We report the first case of successful urgent liver transplantation (LT) in a patient with end-stage liver disease due to a Budd-Chiari syndrome, portal vein thrombosis and pulmonary embolism due to acquired thrombophilia associated to polycythemia vera carrying JAK2V617F gene mutation and HIT in the acute phase. Lepirudin was used to provide anticoagulation in the LT perioperative period that was performed without haemorrhagic and thrombotic complications despite the donor received heparin during liver explantation.

  20. 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.

  1. Actively induced platelet-bound IgG associated with thrombocytopenia in the marmoset

    Energy Technology Data Exchange (ETDEWEB)

    Gengozian, N.; McLaughlin, C.L.

    1978-06-01

    Interspecies platelet immunizations among marmosets lead to antibody formation to the donor platelets and a profound thrombocytopenia, which when associated with anemia may result in death of the animal. This actively induced immonologic thrombocytopenia closely resembles two clinical disease entities manifesting autoimmune thrombocytopenia, posttransfusion purpura and idiopathic thrombocytopenic purpura. Although antibody to donor-type platelets could be demonstrated readily, antihost activity was most often nondetectable or, when present, was in very low titer. A consistent finding was the appearance of IgG on the host's platelets shortly after immunization and concomitant with the appearance of antidonor platelet antibody. In 3 of 13 immunized animals thromoocytopenia did not occur even though antibody was formed and the host's platelets became IgG positive. In those animals that recovered from the induced thrombocytopenia IgG-positive platelets were found for periods ranging from 30 to greater than 100 days. Splenectomy before or after immunization did not alter the sequential development of antibody formation, appearance of IgG-positive platelets, and thrombocytopenia. Eluates prepared from IgG-positive platelets contained IgG and platelet antigens; the eluted IgG could attach nonspecifically to platelets of host or donor (immunizing) type, in contrast to the species specificity demonstrated for IgG eluted from platelets that had been reacted in vitro with specific antibody. Platelets in a few normal, nonimmunized marmosets were found to have signficant amounts of IgG on their surface, comparable to that observed in the immunized animal; interestingly, such IgG-positive platelets were found among imported but not laboratory-bred marmosets.

  2. 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

  3. 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.

  4. Flavonoid-induced acute nephropathy by Cupressus funebris Endl (Mourning Cypress).

    Science.gov (United States)

    Lee, Jia-Jung; Chen, Hung-Chun

    2006-11-01

    Worldwide use of herbal therapy has increased dramatically in recent years. Most herbal therapies were not regulated as medicines, and their adverse effects often were underreported. We report a patient who developed acute renal failure, acute hepatic failure, autoimmune hemolytic anemia, and thrombocytopenia after oral intake of hot-water extract of Cupressus funebris Endl (Mourning Cypress), which is rich in flavonoids. Her renal biopsy showed acute tubular necrosis, interstitial nephritis, and hemoglobin casts. The clinical course and pathological findings were consistent with flavonoid-induced acute nephropathy. We emphasize that flavonoids are not harmless and may induce acute life-threatening renal damage.

  5. 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

    Directory of Open Access Journals (Sweden)

    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.

  6. Clinical Analysis of 38 Pregnancies with Thrombocytopenia%妊娠合并血小板减少症38例临床分析

    Institute of Scientific and Technical Information of China (English)

    刘桂玲; 邹青

    2011-01-01

    目的 探讨妊娠合并血小板减少症的病因、临床特征和诊治.方法 选取蚌埠第三人民医院2004年1月-2011年6月间就诊的38例妊娠合并血小板减少症患者进行回顾性分析.结果 妊娠合并血小板减少症的病因为妊娠相关性血小板减少(PAT)24例,免疫性血小板减少症(ITP)7例,再生障碍性贫血2例,营养性巨幼细胞性贫血2例,急性白血病1例,系统性红斑狼疮2例.治疗方法是给予糖皮质激素或丙种球蛋白或输注血小板等,其中23例行剖宫产,有1例出现产后出血,所有患者均未出现新生儿颅内出血及新生儿死亡.结论 妊娠期血小板减少原因较多并且多发生于妊娠中晚期,应积极治疗合并症和并发症,预防出血倾向及加强胎儿监护.对于血小板<50×109/L或有严重出血倾向的患者可予以糖皮质激素和(或)人血丙种球蛋白治疗,产前适当提高血小板水平,可以减少并发症的出现.%Objective To study the pathogeny,clinical characteristic,diagnosis and treatment of thrombocytopenia in pregnancy. Methods The clinical data of 38 pregnancies with thrombocytopenia from Jan. 2004 to Jun. 2011 in our hospital was analyzed retrospectively. Results In all 38 cases,24 were with pregnancy-associated thrombocytopenia (PAT) ,7 with immune thrombocytopenia,2 with aplastic anemia( AA) ,2 with nutritional megaloblastic anemia, 1 with acute leukemia(AL) ,2 with systemic lupus erythematosus( SLE). Glucocorticoid, immunoglobulin or platelet transfusion was selectively administered. The cesarean section was performed in 23 cases, and 1 case was with posrpartum hemorrhage. There was no intracranial hemorrhage of the newborn and perinatal mortality. Conclusion A number of causes may result in thrombocytopenia in pregnancy that mostly occurred in the middle-late pregnancy. More attentions should be paid on the treatment of complication to prevent the haemorrhage and carefully neonatal intensive care. For the

  7. ST-elevation myocardial infarction and myelodysplastic syndrome with acute myeloid leukemia transformation.

    Science.gov (United States)

    Jao, Geoffrey T; Knovich, Mary Ann; Savage, Rodney W; Sane, David C

    2014-04-01

    Acute myocardial infarction and acute myeloid leukemia are rarely reported as concomitant conditions. The management of ST-elevation myocardial infarction (STEMI) in patients who have acute myeloid leukemia is challenging: the leukemia-related thrombocytopenia, platelet dysfunction, and systemic coagulopathy increase the risk of bleeding, and the administration of thrombolytic agents can be fatal. We report the case of a 76-year-old man who presented emergently with STEMI, myelodysplastic syndrome, and newly recognized acute myeloid leukemia transformation. Standard antiplatelet and anticoagulation therapy were contraindicated by the patient's thrombocytopenia and by his reported ecchymosis and gingival bleeding upon admission. He declined cardiac catheterization, was provided palliative care, and died 2 hours after hospital admission. We searched the English-language medical literature, found 8 relevant reports, and determined that the prognosis for patients with concomitant STEMI and acute myeloid leukemia is clearly worse than that for either individual condition. No guidelines exist to direct the management of STEMI and concomitant acute myeloid leukemia. In 2 reports, dual antiplatelet therapy, anticoagulation, and drug-eluting stent implantation were used without an increased risk of bleeding in the short term, even in the presence of thrombocytopenia. However, we think that a more conservative approach--balloon angioplasty with the provisional use of bare-metal stents--might be safer. Simultaneous chemotherapy for the acute myeloid leukemia is crucial. Older age seems to be a major risk factor: patients too frail for emergent treatment can die within hours or days.

  8. Haemolytic Uraemic Syndrome Following Acute Pancreatitis

    Directory of Open Access Journals (Sweden)

    Sinha A

    2005-07-01

    Full Text Available CONTEXT: Haemolytic uraemic syndrome is a common cause of renal failure in children but it is a rare condition in adults. Acute pancreatitis in adult as a cause of haemolytic uraemic syndrome is very rare. CASE REPORT: A 19-year-old male presented with symptom and signs suggestive of acute pancreatitis which was confirmed as his serum amylase was significantly raised. Within three days of admission he developed acute renal failure with evidence of haemolytic anaemia and thrombocytopenia. A clinical diagnosis of haemolytic uraemic syndrome was made and he was treated with plasma exchange. He made a complete recovery. CONCLUSION: Renal failure in a patient with acute pancreatitis is rarely due to haemolytic uraemic syndrome. But it is important to consider this differential diagnosis so that early treatment can be instituted to prevent mortality.

  9. Arterial and venous thromboses in patients with idiopathic (immunological) thrombocytopenia: a possible contributing role of cortisone-induced hypercoagulable state.

    Science.gov (United States)

    Girolami, Antonio; de Marinis, Gulia Berti; Bonamigo, Emanuela; Treleani, Martina; Vettore, Silvia

    2013-01-01

    Immunological thrombocytopenias, as other forms of thrombocytopenia, are associated with bleeding. Occasionally, these patients manifest thrombotic events. A total of at least 29 patients were reported to have had either arterial (20 cases) or venous (9 cases) thrombosis while platelet count was less than 50 × 10(3)/μL. The most frequent clinical manifestation was a myocardial infarction. Thrombosis occurred in the large majority of patients during prednisone therapy. Patients receiving cortisone or patients with Cushing syndrome show a hypercoagulable state characterized by elevated factor VIII levels, decreased fibrinolysis, and abnormal von Willebrand factor multimers composition. The same is probably true for prednisone-treated patients with thrombocytopenia. However, the 2 conditions are not identical since prednisone is a mainly glycoactive compound, whereas cortisol produced in excess in Cushing syndrome is mainly mineraloactive. The presence of large, young, hyperactive platelets may also play a role. Prednisone-treated patients with thrombocytopenia have to be considered as potentially thrombophilic.

  10. Primary anti-phospholipid antibody syndrome causing recurrent venous thrombosis and thrombocytopenia in a patient with Addison's disease.

    Science.gov (United States)

    Elebrashy, Ibrahim; Yousief, Elham; Saif, Aasem

    2014-12-01

    We report a case of Addison's disease presenting with recurrent deep venous thrombosis and thrombocytopenia and proved to have primary anti-phospholipid antibody syndrome. The case report highlights the shared autoimmune nature of both diseases.

  11. Functional promoter haplotypes of the human FAS gene are associated with the phenotype of SLE characterized by thrombocytopenia

    DEFF Research Database (Denmark)

    Nolsøe, R L; Kelly, J A; Pociot, F;

    2005-01-01

    to SLE or subphenotypes in 126 multiplex American SLE pedigrees and found association of the FAS codon214 AC(C/T) as well as the FAS-670G>A'-codon214 AC(C/T)' haplotype to thrombocytopenia in SLE. Furthermore we have functionally characterized the FAS/FASL promoter polymorphisms associated with SLE...... variant, determines the promoter activity. We conclude that the FAS/FASL promoter haplotypes are functional and that polymorphisms in FAS may contribute to thrombocytopenia in SLE....

  12. 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.

  13. Mild Clinical Course of Severe Fever with Thrombocytopenia Syndrome Virus Infection in an Elderly Japanese Patient

    Directory of Open Access Journals (Sweden)

    Yuko Ohagi

    2014-01-01

    Full Text Available Severe fever with thrombocytopenia syndrome (SFTS is an emerging infectious and hemorrhagic disease recently described in China and western Japan. A 71-year-old healthy Japanese woman noticed a tick biting her after harvesting in an orchard and removed it herself. She developed diarrhea, anorexia, and chills eight days later. Because these symptoms continued, she visited a primary care physician 6 days after the onset. Laboratory data revealed thrombocytopenia, leukocytopenia, and elevated liver enzymes. She was then referred to our hospital. Although not completely fulfilling the diagnostic criteria used in a retrospective study in Japan, SFTS was suspected, and we detected SFTS virus in the patient’s blood using RT-PCR. However, she recovered without intensive treatment and severe complications 13 days after the onset. In this report, we present a mild clinical course of SFTS virus infection in Japan in detail.

  14. Acute Renal Failure, Microangiopathic Haemolytic Anemia, and Secondary Oxalosis in a Young Female Patient

    OpenAIRE

    Stepien, Karolina M; Peter Prinsloo; Tony Hitch; McCulloch, Thomas A.; Rebecca Sims

    2011-01-01

    A 29-year old female presented with a one-week history of vomiting, diarrhoea, abdominal pain, and headache. On admission, she had acute renal failure requiring dialysis. Tests revealed a hemolytic anemia with thrombocytopenia. An initial diagnosis of thrombotic thrombocytopenic microangiopathy was made and plasma exchange was instigated. However, renal biopsy did not show thrombotic microangiopathy but instead revealed acute kidney injury with mild tubulointerstitial nephritis and numerous o...

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

    OpenAIRE

    Danish FA; Yasmin S

    2013-01-01

    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 hepati...

  16. TAR (THROMBOCYTOPENIA WITH ABSENT RADIUS) SYNDROME WITH CONGENITAL ACYANOTIC HEART DISEASE: A RARE CASE REPORT

    OpenAIRE

    Ashok S; Ankit; Aundhakar; Lekha; Umardand

    2016-01-01

    It is a rare genetic disorder characterized by the absence of the radius bone in the forearm and a dramatically reduced platelet count. This syndrome may occur as a part of the 1q21.1 deletion syndrome. Symptoms of thrombocytopenia or a lowered platelet count leads to bruising and potentially life-threatening haemorrhage. Affected children who survive this period and do not have damaging haemorrhages in the brain usually have a normal life expectancy and normal intellectual develo...

  17. Thrombocytopenia is associated with an increased risk of cancer during treated HIV disease

    DEFF Research Database (Denmark)

    Borges, Alvaro Humberto Diniz; Lundgren, Jens D; Ridolfo, Annalisa

    2014-01-01

    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...... the pathophysiological processes underlying thrombocytopenia are associated with the development of cancer during treated HIV disease....

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

    Science.gov (United States)

    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 simultaneously taking care of the patient as a whole. PMID:27006850

  19. 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.

  20. Haemaphysalis longicornis Ticks as Reservoir and Vector of Severe Fever with Thrombocytopenia Syndrome Virus in China

    OpenAIRE

    Luo, Li-mei; Zhao, Li; Wen, Hong-Ling; Zhang, Zhen-Tang; Liu, Jian-Wei; Fang, Li-Zhu; Xue, Zai-Feng; Ma, Dong-Qiang; Zhang, Xiao-Shuang; Ding, Shu-Jun; Lei, Xiao-Ying; Yu, Xue-jie

    2015-01-01

    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging hemorrhagic fever in East Asia caused by SFTS virus (SFTSV), a newly discovered phlebovirus. The Haemaphysalis longicornis tick has been suspected to be the vector of SFTSV. To determine whether SFTSV can be transmitted among ticks, from ticks to animals, and from animals to ticks, we conducted transmission studies between developmental stages of H. longicornis ticks and between ticks and mice. Using reverse transcription PCR, ...

  1. Steroid-resistant autoimmune thrombocytopenia in systemic lupus erythematosus treated with rituximab

    Directory of Open Access Journals (Sweden)

    Vasudha V Sardesai

    2015-01-01

    Full Text Available Systemic Lupus Erythematosus (SLE is a multisystem disorder characterized by production of numerous autoantibodies, some of which have pathogenic consequences and result in considerable morbidity. Herein, we present a case of 48-year-old female with SLE having autoimmune hemolytic anemia, autoimmune thrombocytopenia, renal involvement, and recurrent flares of skin manifestations. She did not respond to the conventional therapy and was controlled and treated with Rituximab, a chimeric, monoclonal antiCD20 antibody, which specifically depletes B lymphocytes.

  2. Hyperferritinemia as a Diagnostic Marker for Severe Fever with Thrombocytopenia Syndrome

    Science.gov (United States)

    Kim, Uh Jin; Oh, Tae hoon; Kim, Bansuk; Kim, Seong Eun; Kang, Seung-Ji; Park, Kyung-Hwa; Jung, Sook-In

    2017-01-01

    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging viral disease in East Asia with high mortality. Few studies have examined markers that suggest SFTS in febrile patients. To determine useful biochemical markers for SFTS, patients aged 18 years or older with SFTS or microbiologically confirmed community-onset bacteremia with thrombocytopenia (BT) at presentation between June 2013 and December 2015 were included from two tertiary university hospitals in Republic of Korea retrospectively. Eleven patients with SFTS and 62 patients with bacteremia and thrombocytopenia were identified in the study period. Age and sex did not show significant difference among two groups. Fever was more commonly observed but comorbidities were less common in SFTS than in BT (P < 0.05, each). The areas under the curves of serum ferritin, C-reactive protein, white blood cell count, serum procalcitonin, and fibrinogen were above 0.9, indicating the discriminative power of these biomarkers (1.000, 0.991, 0.963, 0.931, and 0.934, resp., all P < 0.05). The optimal cutoff value of serum ferritin was 3,822 ng/mL in this study. These results suggest that hyperferritinemia is a typical laboratory feature of SFTS, and the serum ferritin level can be used as a marker for clinicians suspecting SFTS.

  3. Level of RUNX1 activity is critical for leukemic predisposition but not for thrombocytopenia.

    Science.gov (United States)

    Antony-Debré, Iléana; Manchev, Vladimir T; Balayn, Nathalie; Bluteau, Dominique; Tomowiak, Cécile; Legrand, Céline; Langlois, Thierry; Bawa, Olivia; Tosca, Lucie; Tachdjian, Gérard; Leheup, Bruno; Debili, Najet; Plo, Isabelle; Mills, Jason A; French, Deborah L; Weiss, Mitchell J; Solary, Eric; Favier, Remi; Vainchenker, William; Raslova, Hana

    2015-02-01

    To explore how RUNX1 mutations predispose to leukemia, we generated induced pluripotent stem cells (iPSCs) from 2 pedigrees with germline RUNX1 mutations. The first, carrying a missense R174Q mutation, which acts as a dominant-negative mutant, is associated with thrombocytopenia and leukemia, and the second, carrying a monoallelic gene deletion inducing a haploinsufficiency, presents only as thrombocytopenia. Hematopoietic differentiation of these iPSC clones demonstrated profound defects in erythropoiesis and megakaryopoiesis and deregulated expression of RUNX1 targets. iPSC clones from patients with the R174Q mutation specifically generated an increased amount of granulomonocytes, a phenotype reproduced by an 80% RUNX1 knockdown in the H9 human embryonic stem cell line, and a genomic instability. This phenotype, found only with a lower dosage of RUNX1, may account for development of leukemia in patients. Altogether, RUNX1 dosage could explain the differential phenotype according to RUNX1 mutations, with a haploinsufficiency leading to thrombocytopenia alone in a majority of cases whereas a more complete gene deletion predisposes to leukemia.

  4. Long-term safety and efficacy of romiplostim for treatment of immune thrombocytopenia

    Directory of Open Access Journals (Sweden)

    Vishnu P

    2016-05-01

    Full Text Available Prakash Vishnu,1 David M Aboulafia1,2 1Floyd and Delores Jones Cancer Institute at Virginia Mason Medical Center, 2Division of Hematology, University of Washington, Seattle, WA, USA Abstract: Inhibition of platelet production and mediated by antiplatelet antibodies is a well-known mechanism causing low platelet counts in immune thrombocytopenia (ITP. Use of thrombopoietin receptor agonists increases platelet counts and decreases the risk of bleeding in patients with ITP. Two such thrombopoietin receptor agonists, romiplostim and eltrombopag, are approved by the US Food and Drug Administration to treat thrombocytopenia in adults, and most recently, children with persistent or chronic ITP. This review focuses on the efficacy data and safety analysis of the pooled data from the clinical trials evaluating romiplostim for treatment of adults with ITP. The rates of hemorrhage, thrombosis, hematologic and nonhematologic cancers, and myelodysplastic syndrome were not overrepresented among the groups who received romiplostim versus placebo or other standard-of-care treatments. Yet, as after-market experience with thrombopoietin receptor agonists increases, there are emerging reports of increased incidence of thrombosis and bone marrow reticulin among patients who are treated with long-term use of these agents. Ongoing clinical research will continue to evaluate romiplostim’s efficacy and safety in other primary and secondary thrombocytopenic states. Keywords: thrombopoietin receptor agonists, romiplostim, randomized clinical trials, immune thrombocytopenia, long-term efficacy, safety

  5. Small Cell Lung Cancer Presenting as Severe Thrombocytopenia and Refractory Hypokalemia

    Directory of Open Access Journals (Sweden)

    Rohan Mandaliya

    2014-01-01

    Full Text Available A 70-year-old female with a history of mild cirrhosis was referred by her primary care provider for a platelet count of 36,000/μL which had dropped from 47,000/μL in a week along with mild pain in extremities. Serum potassium was low (2.9 mEq/L in spite of the patient being recently started on potassium supplement on outpatient for hypokalemia. Initially thrombocytopenia was attributed to cirrhosis. However, platelet counts continued to drop to a nadir of 9000/μL in spite of several platelet transfusions. Hypokalemia was refractory to potassium supplements. Subsequent bone marrow biopsy revealed extensive marrow necrosis with a focus of small cell tumor cells of pulmonary origin. CT scan of the chest showed a spiculated left lung mass. The ACTH level was high, with normal rennin and aldosterone levels. The patient likely had ectopic ACTH syndrome from small cell lung cancer. She died within few days of diagnosis. Severe thrombocytopenia and refractory hypokalemia can rarely be initial presentations of small cell lung cancer. Thrombocytopenia should prompt an evaluation for bone marrow metastases and a search for undiagnosed systemic malignancy. In severe cases of metastases, bone marrow necrosis can be present. Refractory hypokalemia can be the sole presentation of ectopic ACTH production.

  6. Emergency Splenectomy in a patient with primary immune thrombocytopenia and hemoperitoneum

    Directory of Open Access Journals (Sweden)

    Liermis Michael Dita Salabert

    2013-08-01

    Full Text Available Primary immune thrombocytopenia is an acquired autoimmune disease, with a very variable clinical course, which causes an accelerated destruction by antibodies and an impaired platelet production. A case of a 40 year-old female patient of rural origin with a history of mitral stenosis and atrial fibrillation, diagnosed two months prior to her admission to the Dr. Gustavo Aldereguía Lima University General Hospital in Cienfuegos, is presented. She attended the hospital with ecchymosis and petechiae on the lower and upper limbs. After confirming a severe thrombocytopenia (5x109/ l, she was admitted to the Hematology Department. Possible primary immune thrombocytopenia was found. During her stay in the hospital, her clinical condition was complicated by hemoperitoneum. The patient underwent surgery which confirmed the presence of four liters of blood in the abdominal cavity with few clots, bleeding and fissure in the left ovary and adherent clots. An early clamping of the splenic artery, evacuation of the hemoperitoneum, left adnexectomy, splenectomy and resection of accessory spleen were performed. The patient progressed satisfactorily.

  7. Tpl2 kinase regulates FcγR signaling and immune thrombocytopenia in mice.

    Science.gov (United States)

    Kyrmizi, Irene; Ioannou, Marianna; Hatziapostolou, Maria; Tsichlis, Philip N; Boumpas, Dimitrios T; Tassiulas, Ioannis

    2013-10-01

    The MAPK3 Tpl2 controls innate and adaptive immunity by regulating TLR, TNF-α, and GPCR signaling in a variety of cell types. Its ablation gives rise to an anti-inflammatory phenotype characterized by resistance to LPS-induced endotoxin shock, DSS-induced colitis, and TNF-α-induced IBD. Here, we address the role of Tpl2 in autoimmunity. Our data show that the ablation and the pharmacological inhibition of Tpl2 protect mice from antiplatelet antibody-induced thrombocytopenia, a model of ITP. Thrombocytopenia in this model and in ITP is caused by phagocytosis of platelets opsonized with antiplatelet antibodies and depends on FcγR activation in splenic and hepatic myeloid cells. Further studies explained how Tpl2 inhibition protects from antibody-induced thrombocytopenia, by showing that Tpl2 is activated by FcγR signals in macrophages and that its activation by these signals is required for ERK activation, cytoplasmic Ca(2+) influx, the induction of cytokine and coreceptor gene expression, and phagocytosis.

  8. Nonstructural Protein 2 (nsP2) of Chikungunya Virus (CHIKV) Enhances Protective Immunity Mediated by a CHIKV Envelope Protein Expressing DNA Vaccine

    OpenAIRE

    Bao, Huihui; Ramanathan, Aarti A.; Kawalakar, Omkar; Sundaram, Senthil G.; Tingey, Colleen; Bian, Charoran B.; Muruganandam, Nagarajan; Vijayachari, Paluru; Sardesai, Niranjan Y.; Weiner, David B.; Ugen, Kenneth E; Muthumani, Karuppiah

    2013-01-01

    Chikungunya virus (CHIKV) is an important emerging mosquito-borne alphavirus, indigenous to tropical Africa and Asia. It can cause epidemic fever and acute illness characterized by fever and arthralgias. The epidemic cycle of this infection is similar to dengue and urban yellow fever viral infections. The generation of an efficient vaccine against CHIKV is necessary to prevent and/or control the disease manifestations of the infection. In this report, we studied immune response against a CHIK...

  9. 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.

  10. Thrombocytopenia in the experimental leptospirosis of guinea pig is not related to disseminated intravascular coagulation

    Directory of Open Access Journals (Sweden)

    HU Bao-Yu

    2006-02-01

    Full Text Available Abstract Background Thrombocytopenia is commonly observed in severe leptospirosis. However, previous studies on coagulation alterations during leptospirosis resulted in inconsistent conclusions. Some findings showed that the prominent levels of thrombocytopenia observed in severe leptospirosis did not reflect the occurrence of disseminated intravascular coagulation (DIC syndrome, while the others reached the conclusion that the hemorrhages observed in leptospirosis were due to DIC. The aim of this study is to elucidate whether DIC is an important feature of leptospirosis. Methods The leptospirosis model of guinea pig was established by intraperitoneal inoculation of Leptospira interrogans strain Lai. Hematoxylin and eosin (HE staining, electron microscopy and immunohistochemistry staining were used to detect the pathologic changes. Platelet thrombus or fibrin thrombus was detected by HE, Martius Scarlet Blue (MSB staining and electron microscopy. Hemostatic molecular markers such as 11-dehydrogenate thromboxane B2 (11-DH-TXB2, thrombomodulin (TM, thrombin-antithrombin III complex (TAT, D-Dimer and fibrin (ogen degradation products (FDPs in the plasma were examined by quantitative enzyme-linked immunosorbent assay (ELISA to evaluate the hematological coagulative alterations in leptospirosis models. Results Pulmonary hemorrhage appeared in the model guinea pig 24 hours after leptospires intraperitoneal inoculation, progressing to a peak at 96 hours after the infection. Leptospires were detected 24 hours post-inoculation in the liver, 48 hours in the lung and 72 hours in the kidney by immunohistochemistry staining. Spiral form of the bacteria was initially observed in the liver, lung and kidney suggestive of intact leptospires, granular form of leptospires was seen as the severity increased. Platelet aggregation in hepatic sinusoid as well as phagocytosis of erythrocytes and platelets by Kupffer cells were both observed. Neither platelet thrombus

  11. Heparin-induced thrombocytopenia type II: Innovations in diagnostics and treatment

    Directory of Open Access Journals (Sweden)

    Antonijević Nebojša

    2003-01-01

    Full Text Available Heparin-induced thrombocytopenia (HIT Management of heparin-induced thrombocytopenia (HIT and treatment options have significantly changed recently. Heparin may induce two types of thrombocytopenia. Type I, occurring earlier with a much higher rate of incidence (5-30%, is characterized by mild thrombocytopenia without significant clinical manifestations. Type II is less frequent (0.5-2%, life threatening immune type, develops following a period of minimum 5-7 days upon introduction of heparin therapy (patients earlier treated with heparin are excluded. Type II heparin-induced thrombocytopenia with severely reduced platelet count may be clinically manifested by thrombosis in 20-50% cases within the period of 30 days. HIT is suspected in persons resistant to heparin with relatively reduced platelet count, though HIT is described in person with normal platelet counts, as well. None of available assays used for HIT detection is completely reliable Sensitivity of a highly specific platelet aggregation assay is only 36% sensitivity and specificity of 14C-serotonin release assays amounts to 95% while ELISA using a heparin/platelet factor-4 target has a sensitivity of 85%. Thus, it is sometimes necessary to combine functional and antigen assays. Furthermore, new classes of antigen assays, like antibody detection tests of complexes between heparin and neutrophil-activating peptide-2 as well as those between heparin and interleukin-8, have been used. Current therapy options Current therapy options exclude formerly applied low-molecular-weight heparins due to the existing cross-reactivity of 80–100%. Danaparoid sodium exhibits in vitro cross-reactivity of 10–61%, clinically manifested in less than 5% of patients. Two drugs are drugs of choice in HIT type II treatment: lepirudin, especially in patients without renal failure and argatroban, particularly in patients with renal failure. The following procedures and agents are also efficient: asmapheresis

  12. 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.

  13. 免疫介导性坏死性肌肉病四例临床病理分析及随访%The clinical pathological characteristics and follow-up of 4 cases of immune-mediated necrotizing myopathy

    Institute of Scientific and Technical Information of China (English)

    张英爽; 孙阿萍; 陈璐; 董荣芳; 钟延丰; 樊东升

    2015-01-01

    Objective To characterize the clinical,electrophysiology and neuropathological features of 4 cases with immune-mediated necrotizing myopathy (IMNM).Methods We retrospectively analyzed the clinical,electrophysiology,neuropathological characteristics of 4 IMNM patients with muscular and skin biopsy in our department during 4 years (from January 2011 to January 2014).Results Among these 4 patients,2 were men and 2 were women (aged 37 to 58 years) with disease duration ranging from 1 month to 60 months.Two patients were with acute onset and 2 with chronic onset.All 4 patients had proximal muscle weakness with three patients with cervical flexor muscle weakness and one with respiratory muscles weakness and noninvasive ventilator assisted respiration.One patient had interstitial lung disease.The anti-signal recognition particle antibodies were strong positive in all 4 patients.Muscle biopsy showed group necrotizing and regenerating fibers in one patient and few scattered necrotizing and regenerating fibers in the other 3 patients.Both muscle fiber hypertrophy and muscle fiber atrophy together with proliferation of connective tissue on endomysium could be viewed in all 4 patients.However,very few inflammatory cells were detectable in patients.One patient was treated with corticosteroids and the other three were treated with combination of corticosteroids and immunosuppressant drugs.Conclusions IMNM is characterized by heterogeneity at disease onset,severity and ilnvolvement of muscles with,however,similary pathological changes including the presence of numerous necrotic and regenerating fibers with little or none inflammation.Corticosteroid and/or immunosuppressant is effective for patients.%目的 总结免疫介导性坏死性肌肉病(IMNM)患者的临床、电生理和骨骼肌病理改变特点.方法 回顾性分析北京大学第三医院2011年1月—2014年1月的4例IMNM患者的临床、电生理特点及肌肉、皮肤活检的病理特点和

  14. Immune-mediated severe hemolytic crisis with a hemoglobin level of 1.6 g/dl caused by anti-piperacillin antibodies in a patient with cystic fibrosis.

    Science.gov (United States)

    Kunzmann, S; Thomas, W; Mayer, B; Kuhn, S; Hebestreit, H

    2010-04-01

    We report a 23-year-old female patient with cystic fibrosis developing severe intravascular hemolysis with a minimal hemoglobin level of 1.6 g/dl after 7 days of treatment with piperacillin, consistent with an immune-mediated hemolytic crisis. Twenty days later, the patient could leave the hospital in good condition without any neurological deficit. To our knowledge, this is the lowest reported hemoglobin value caused by hemolytic anemia with intact survival. As piperacillin is commonly used in patients with cystic fibrosis, it is important to monitor the full-blood counts of patients during treatment with piperacillin and to be aware of the potential for hemolytic anemia to develop. Anti-piperacillin antibodies should be considered whenever these patients develop hemolytic anemia or a positive direct antiglobulin test (DAT). Furthermore, drug-fever under piperacillin application could be a warning sign for the development of hemolytic anemia.

  15. 蠕虫对免疫相关性疾病的防治研究%The impact of helminth on the prevention and treatment of immune-mediated diseases

    Institute of Scientific and Technical Information of China (English)

    姚雪洁; 吴小平

    2013-01-01

    随着现代生活及医疗水平的提高,蠕虫感染率逐渐下降,缺乏蠕虫的暴露可能是免疫相关性疾病发病日益增多的一个重要环境因素.蠕虫对过敏性疾病及自身免疫性疾病的预防及治疗作用近年受到重视,得到了较多流行病学、实验及临床研究的支持.本文就蠕虫与过敏性疾病、炎症性肠病、多发性硬化、Ⅰ型糖尿病、类风湿性关节炎等免疫性疾病防治方面的研究进展作一综述.%The lack of exposure to helminth infections, as a result of improved living standards and medical conditions, may have contributed to the increased incidence of immune-mediated diseases as an important environmental factor. Basically the increasing epidemiologic studies, experimental and clinical date all support the preventive and therapeutic potential of helminth infections in allergic and autoimmune diseases. In this review, we will introduce the latest research progress on the role of helminth in the prevention and treatment of immune-mediated diseases such as allergic disease, inflammatory bowel disease, multiple sclerosis, type 1 diabetes and rheumatoid arthritis.

  16. PAIgG and PAIgM levels in secondary dengue virus infections lead to thrombocytopenia in patients from KP, Pakistan

    Institute of Scientific and Technical Information of China (English)

    Ibrar Alam; Said Hassan; Iftikhar Alam; Rahmat Gul; Farhad Ali; Ijaz Ali; Sana Ullah; Imtiaz Ali Khan; Aasif Awan

    2015-01-01

    Objective:To understand the impact of platelet associated immunoglobulin G (PAIgG)/ platelet associated immunoglobulin M (PAIgM) on severity of dengue virus infection leading to thrombocytopenia. Methods: In this study we examined a total of 52 patients who were having secondary infection of dengue in acute phase by using competitive ELISA. Results: A decrease in the platelet count was observed at the acute phase of infection while all along the recovery stage the count of platelet was significantly increased. A significant decrease was observed inPAIgG andPAIgM in these subjects. Inverse correlation was found between platelets count andPAIgG/PAIgM among the subjects studied. In the platelets elution from ten subjects, anti-dengue virus immunoglobulin G and immunoglobulin M were observed.PAIgG andPAIgM with inclined levels were higher in dengue hemorrhagic fever than the classical dengue fever. In the development of dengue hemorrhagic feverPAIgM inclined level was independently associated with high specificity, showing a possible indication of dengue hemorrhagic fever. Conclusions: This study suggests that in secondary dengue virus infection, thePAIgGand PAIgM levels, and the activity of anti-dengue virus play key roles, both in the development and severity of the disease.

  17. PAIgG and PAIgM levels in secondary dengue virus infections lead to thrombocytopenia in patients from KP, Pakistan简

    Institute of Scientific and Technical Information of China (English)

    Ibrar; Alam; Said; Hassan; Iftikhar; Alam; Rahmat; Gul; Farhad; Ali; Ijaz; Ali; Sana; Ullah; Imtiaz; Ali; Khan; Aasif; Awan

    2015-01-01

    Objective: To understand the impact of platelet associated immunoglobulin G(PAIg G)/platelet associated immunoglobulin M(PAIg M) on severity of dengue virus infection leading to thrombocytopenia.Methods: In this study we examined a total of 52 patients who were having secondary infection of dengue in acute phase by using competitive ELISA.Results: A decrease in the platelet count was observed at the acute phase of infection while all along the recovery stage the count of platelet was significantly increased. A significant decrease was observed in PAIg G and PAIg M in these subjects. Inverse correlation was found between platelets count and PAIg G/PAIg M among the subjects studied. In the platelets elution from ten subjects, anti-dengue virus immunoglobulin G and immunoglobulin M were observed. PAIg G and PAIg M with inclined levels were higher in dengue hemorrhagic fever than the classical dengue fever. In the development of dengue hemorrhagic fever PAIg M inclined level was independently associated with high specificity, showing a possible indication of dengue hemorrhagic fever.Conclusions: This study suggests that in secondary dengue virus infection, the PAIg G and PAIg M levels, and the activity of anti-dengue virus play key roles, both in the development and severity of the disease.

  18. Multiple myeloma presenting as acute pancreatitis.

    Science.gov (United States)

    Mishra, Shakti Bedanta; Azim, Afzal; Mukherjee, Arindam

    2017-09-01

    A 36 year old male presented to the emergency department with severe epigastric pain, nausea, vomiting without hematemesis, diarrhea and anorexia. He presented with respiratory distress, shock and fever at the emergency. He was intubated and shifted to the intensive care unit with the diagnosis of acute pancreatitis with hypercalcemia and an elevated amylase and lipase's well as thrombocytopenia and elevated creatinine. CT scan of abdomen was done which showed lytic bone lesions in the spine and necrosis of the pancrease. He was evaluated for multiple myeloma and it was confirmed in a bone marrow biopsy. Multiple myeloma usually is seen in patients aged more than 60 yrs. The typical presentation of multiple myeloma is anemia, back pain, and an elevated sedimentation rate. Patients with multiple myeloma have hypercalcemia but it's rarely manifested as acute pancreatitis. This case shows a rare presentation of multiple myeloma as acute pancreatitis in a younger adult. Copyright © 2017 Elsevier Inc. All rights reserved.

  19. The potential of antimicrobials to induce thrombocytopenia in critically ill patients: data from a randomized controlled trial.

    Directory of Open Access Journals (Sweden)

    Maria Egede Johansen

    Full Text Available BACKGROUND: Antimicrobial-induced thrombocytopenia is frequently described in the literature among critically ill patients. Several antimicrobials have been implicated, although experimental evidence to demonstrate causality is limited. We report, using a randomized trial, the potential of antimicrobials to induce thrombocytopenia. METHODS: Randomized trial allocated patients to antimicrobial treatment according to standard- of-care (SOC group or drug-escalation in case of procalcitonin increases (high-exposure group. Patients were followed until death or day 28. Thrombocytopenia defined as absolute (platelet count ≤ 100 x 109/L or relative (≥ 20% decrease in platelet count. Analyses were performed in the two randomized groups and as a merged cohort. RESULTS: Of the 1147 patients with platelet data available, 18% had absolute thrombocytopenia within the first 24 hours after admission to intensive care unit and additional 17% developed this complication during follow-up; 57% developed relative thrombocytopenia during follow-up. Absolute and relative thrombocytopenia day 1-4 was associated with increased mortality (HR: 1.67 [95% CI: 1.30 to 2.14]; 1.71 [95% CI: 1.30 to 2.30], P<0.0001, respectively. Patients in the high-exposure group received more antimicrobials including piperacillin/tazobactam, meropenem and ciprofloxacin compared with the SOC group, whereas cefuroxime was used more frequently in the SOC group (p<0.05. Risk of absolute and relative thrombocytopenia (RR: 0.9 [0.7-1.3], p=0.7439; 1.2 [1.0-1.4], p=0.06; respectively, as well as absolute platelet count (daily difference, high-exposure vs. SOC -1.7 [-3.8-0.5], p=0.14 was comparable between groups. In observational analyses, use of ciprofloxacin and piperacillin/tazobactam predicted risk of relative thrombocytopenia (vs. cefuroxime, RR: 2.08 [1.48-2.92]; 1.44 [1.10-1.89], respectively, however only ciprofloxacin were associated with a reduction in absolute platelet count (p=0

  20. 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.

  1. Spotlight on romiplostim in the treatment of children with chronic immune thrombocytopenia: design, development, and potential place in therapy

    Directory of Open Access Journals (Sweden)

    Buchbinder D

    2017-03-01

    Full Text Available David Buchbinder, Diane Nugent, Loan Hsieh Division of Hematology, CHOC Children’s Hospital and UC Irvine Medical Center, CA, USA Abstract: Primary immune thrombocytopenia (ITP is an autoimmune disorder characterized by isolated thrombocytopenia. In approximately one-third of cases, the duration of thrombocytopenia will extend beyond 12 months consistent with a diagnosis of chronic ITP. Minor bleeding manifestations are common in chronic ITP while severe or life-threatening bleeding complications are uncommon. Moreover, spontaneous resolution occurs in the majority of children with chronic ITP necessitating treatment in only those children with ongoing bleeding manifestations or impairment in health-related quality of life (HRQOL. The characterization of thrombopoietin (TPO and remarkable advancements in our understanding of the pathophysiology of ITP has led to the development of a new class of agents, the TPO-receptor agonists that have documented efficacy in the amelioration of thrombocytopenia and bleeding manifestations in chronic ITP. Romiplostim is a second-generation TPO-receptor agonist that has undergone limited evaluation in the treatment of chronic ITP in children. Evolving data suggest that romiplostim may be a safe and effective agent in the treatment of chronic ITP in children. Additional data are needed to confirm its ability to increase platelet counts, decrease bleeding manifestation, and improve the HRQOL of children and caregivers impacted by chronic ITP. Keywords: thrombocytopenia, chronic, thrombopoietin, childhood

  2. 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.

  3. Acute Limb Ischemia and Coronary Artery Disease in a Case of Kimura’s Disease

    Science.gov (United States)

    Heo, Woon; Jun, Hee Jae; Kang, Do Kyun; Min, Ho-Ki; Hwang, Youn-Ho; Kim, Ji Yong; Nam, Kyung Han

    2017-01-01

    Kimura disease (KD) is an immune-mediated chronic inflammatory disease of unknown etiology. KD has many complications associated with hypereosinophilia, including various forms of allergic reactions and eosinophilic lung disease. Additionally, hypereosinophilia is associated with hypercoagulability, which may lead to thromboembolic events. A 36-year-old man with KD presented with acute limb ischemia and coronary artery occlusion. He underwent thrombectomy, partial endarterectomy of both popliteal arteries, and coronary artery stent insertion. KD is a systemic disease that affects many organs and presents with thromboembolism and vasculitis. In a patient with KD, physicians should evaluate the vascular system, including the coronary arteries. PMID:28382271

  4. Clinical experience with recombinant human thrombopoietin in chemotherapy-induced thrombocytopenia.

    Science.gov (United States)

    Vadhan-Raj, S

    2000-04-01

    Since the identification and cloning of c-Mpl ligand, two forms of recombinant human thrombopoietin have undergone clinical development. Both the full-length molecule, known as rhTPO, and the truncated version of the molecule, known as pegylated recombinant human megakaryocyte growth and development factor (PEG-rHuMGDF), have been evaluated in phase I/II clinical trials in cancer patients receiving myelosuppressive chemotherapy. Early clinical trials with PEG-rHuMGDF in cancer patients demonstrated its clinical safety and platelet-stimulating activity. However, the development of neutralizing antibodies and clinically significant thrombocytopenia in some patients and normal donors who received PEG-rHuMGDF have led to discontinuation of clinical trials with this molecule in the United States. Clinical experience with rhTPO so far indicates that this full-length glycosylated molecule is remarkably well tolerated and has a favorable safety profile. In these studies, rhTPO exhibited dose-dependent increases in circulating platelet counts and bone marrow megakaryocytes before chemotherapy. In addition, there was an increase in the frequency and proliferation of bone marrow progenitor cells and mobilization of progenitors into the peripheral blood. Early results also showed that rhTPO can attenuate chemotherapy-induced severe thrombocytopenia and reduce the need for platelet transfusions. However, in this setting, the optimal schedule of rhTPO administration may depend on the length of the regimen and anticipated timing of the platelet nadir. These initial results indicate that rhTPO is a safe and potentially useful agent in the prevention and management of chemotherapy-induced thrombocytopenia. Results of larger randomized clinical trials will determine the therapeutic potential of this novel growth factor in various clinical settings.

  5. Oxidative stress in severe dengue viral infection: association of thrombocytopenia with lipid peroxidation.

    Science.gov (United States)

    Soundravally, R; Sankar, P; Bobby, Z; Hoti, S L

    2008-09-01

    Oxidative stress in viral infections has been suggested. The study was carried out to assess the oxidative stress in the different clinical spectrums of dengue infection and to evaluate if thrombocytopenia is associated with lipid and protein oxidative injury. Twenty-seven dengue fever (DF), 32 dengue hemorrhagic fever (DHF) and 21 dengue shock syndrome (DSS) cases were studied at 3, 5 and 7 days of illness. Sixty-three healthy subjects were selected as controls. Serum protein carbonyls (PCOs), malendialdehyde (MDA) and total antioxidant status (TAS) were estimated in blood. Dengue infected individuals had significantly high levels of PCOs and MDA on the three days tested in comparison to controls. In DF cases, no significant changes in the levels of MDA and PCOs were found in course of time. However, among DHF and DSS, significant increase in MDA levels was found in the fifth and seventh day samples in comparison to their respective third day sample (P platelet count and plasma lipid peroxidation levels among DHF and DSS on all three days tested [day 3 (DHF r = -0.392; p = 0.012 and DSS r = -0.453; p = 0.004), day 5 (DHF r = -0.592; p viral infection. The level of oxidative stress was maximal in DSS followed by DHF and its severity was minimal in DF. The thrombocytopenia of dengue infection was associated with the extent of lipid peroxidation. Future studies might be carried out to find the role of oxidative damage in the ethiopathogenesis of thrombocytopenia and vascular leakage in dengue infection.

  6. A whole blood model of thrombocytopenia that controls platelet count and hematocrit.

    Science.gov (United States)

    Bercovitz, R S; Brenner, M K; Newman, D K

    2016-10-01

    In patients with thrombocytopenia, it can be difficult to predict a patient's bleeding risk based on platelet count alone. Platelet reactivity may provide additional information; however, current clinical assays cannot reliably assess platelet function in the setting of thrombocytopenia. New methods to study platelet reactivity in thrombocytopenic samples are needed. In this study, we sought to develop a laboratory model of thrombocytopenia using blood from healthy subjects that preserves the whole blood environment and reproducibly produces samples with a specific platelet count and hematocrit. We compared the activation state of unstimulated and agonist-stimulated platelets in thrombocytopenic samples derived from this method with normocytic controls. Whole blood was diluted with autologous red blood cell concentrate and platelet-poor plasma, which were obtained via centrifugation, in specific ratios to attain a final sample with a predetermined platelet count and hematocrit. P-selectin exposure and GPIIbIIIa activation in unstimulated platelets and platelets stimulated with collagen-related peptide (CRP) or adenosine diphosphate (ADP) in thrombocytopenic samples and the normocytic control from which they were derived were quantified by flow cytometry. Our methodology reliably produced thrombocytopenic samples with a platelet count ≤50,000/μL and an accurately and precisely controlled hematocrit. P-selectin exposure and GPIIbIIIa activation on unstimulated platelets or on ADP- or CRP-stimulated platelets did not differ in thrombocytopenic samples compared to normocytic controls. We describe a new method for creating thrombocytopenic blood that can be used to better understand the contributions of platelet number and function to hemostasis.

  7. Incidence of thrombocytopenia and changes in various platelet parameters, in blood culture positive neonatal sepsis

    Directory of Open Access Journals (Sweden)

    Sartaj Bhat

    2015-07-01

    Full Text Available Abstract Objective: To assess the incidence of thrombocytopenia and changes in various platelet parameters, in culture positive neonatal sepsis. Methods: This was prospective study conducted over a period of one year from December 2009 to November 2010 in neonatal intensive care unit of DDUH Hospital, a tertiary care hospital in Delhi, North India. All babies who were admitted during this period were evaluated prospectively for evidence of sepsis. Results: sepsis was diagnosed in 560 neonates. Among 560 neonates, 80/560 (14.28% had Culture positive sepsis. Out of 80 blood culture positive neonates 73 were term neonates and 7 were near term. Gram positive sepsis occurred in 21/80 (26.25%, gram negative sepsis in 54/80 (67.5%, and fungal sepsis in 5/80 (6.25%. Incidence of thrombocytopenia in Gram negative sepsis was (35/54 64.81%, in gram positive sepsis (15/21 71.41% and in fungal sepsis was (3/5 60%. Mean platelet count at the onset of sepsis in all the patients was 123287.5±49428.68. The mean duration of thrombocytopenia in gram positive sepsis was 4.66 ±2.6 days, in gram negative sepsis 4.39 ± 2.22 days and in fungal sepsis 5.2±1.3 days. MPV at the time of onset of sepsis (MPV was high in gram positive sepsis than in gram negative sepsis (11.57±0.88 Vs 11.29 ± 0.76. The MPV of thrombocytopenic neonates was significantly higher than that of non-thrombocytopenic neonates (p < 0.01.

  8. 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.

  9. Thrombocytopenia and Postpartum Hemorrhage in a Woman with Chromosome 22q11.2 Deletion Syndrome

    Science.gov (United States)

    Deng, Kathy; Nanda, Deepak

    2016-01-01

    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. PMID:27366335

  10. [Heparin immune thrombocytopenia in a hemodialysis patient. A case report. Literature review].

    Science.gov (United States)

    Benítez, M; González Gómez, I; González Carmelo, I; Palma, A; Cruz, S; Rodríguez, E; Amián, A; Fernández M, F; Merino, M J; Fernández G, F; Suárez, C; Onaindía, J M; González, J

    2007-01-01

    Heparin-induced thrombocytopenia (HIT) is an important side effect of heparin therapy associated with significant morbidity and mortality if unrecognized. The platelet count typically falls below 150,000/ll 5-14 days after heparin is started. Thrombosis is the major clinical complication. We present the case gives a patient that develops a deep vein thrombosis ilio-femoral left, with trombocytopenia, one week after beginning treatment with haemodialysis in which Ac anti heparin is detected by test PaGIA (Particle Gel Inmuno Assay.

  11. Sterile water injection labour analgesia in a parturient with preeclampsia with thrombocytopenia

    Directory of Open Access Journals (Sweden)

    Shivali Panwar

    2017-01-01

    Full Text Available Pregnancy induced hypertension is one of the most common causes of maternal morbidity and mortality. A G2L1A1 female with period of gestation 36 weeks presented in our hospital with early labour pains. She was a known case of pregnancy induced hypertension with thrombocytopenia and had been operated on the lumbar spine for Potts spine. She was administered intradermal sterile water injection labour analgesia every 3 hours. The labour was uneventful and patient had a normal vaginal delivery of a male baby. The postnatal course was uneventful and patient was satisfied with the labour analgesia.

  12. Value of autoantibody detection for illness assessment in systemic lupus erythematosus patients with refractory thrombocytopenia

    Institute of Scientific and Technical Information of China (English)

    Xiao-Liang Wu

    2016-01-01

    Objective:To analyze the value of autoantibody detection for illness assessment in systemic lupus erythematosus patients with refractory thrombocytopenia.Methods:A total of 60 cases of systemic lupus erythematosus (SLE) with refractory thrombocytopenia were the observation group A, 58 cases of patients with SLE alone were the observation group B, and 66 cases of healthy people who received physical examination were control group. Peripheral circulating blood was drawn from research subjects to detect the levels of autoantibody, illness-related factors, Th17, Th1 and Th2 cytokines, complements, and so on, and then the correlation between specific antibody positive rate and disease severity in SLE patients with refractory thrombocytopenia was further analyzed.Results:Anti-RNP antibody, anti-Sm antibody, anti-Scl-70 antibody, anti-AnuA antibody, anti-His antibody and anti-ds-DNA antibody positive rates of observation group A were higher than those of observation group B and control group (P<0.05); sICAM-1, PTM, sCD30L and MCP-1 values of observation group A were higher than those of observation group B and control group (P<0.05); serum IL-17, IL-23, IFN-γ, TNF-α, IL-4, IL-5 and IL-6 values of observation group A were higher than those of observation group B and control group (P<0.05); serum C1qAg, C3, C4 and CFH values of observation group A were lower than those of observation group B and control group while C1qAb value was higher than that of observation group B and control group (P<0.05); anti-Sm antibody and anti-ds-DNA antibody positive rates of SLE patients were positively correlated with serum sICAM-1, PTM, sCD30L, MCP-1, IL-17, IL-23, IFN-γ, TNF- , IL-4, IL-5, IL-6 and C1qAb values, and negatively correlated with C1qAg, C3, C4 and CFH values (P<0.05). Conclusions:Specific autoantibody positive rates are high in systemic lupus erythematosus patients with refractory thrombocytopenia, have direct correlation with the disease severity and can be used as the

  13. Successful Management of Heparin-Induced Thrombocytopenia Using Argatroban in a Very Old Woman: A Case Report

    Directory of Open Access Journals (Sweden)

    A. Putot

    2013-01-01

    Full Text Available Thrombosis due to heparin-induced thrombocytopenia (HIT is rare but has a severe prognosis. Its management is not always easy, particularly in old patients with renal insufficiency. A 95-year-old woman was hospitalized for dyspnea. Curative treatment with unfractionated heparin was started because pulmonary embolism was suspected. Disseminated intravascular coagulation was then suspected because of thrombocytopenia, hypoprothrombinemia, hypofibrinogenemia, and a positive ethanol gelation test. The first immunoassay for HIT was negative. On the 12th day of hospitalization, bilateral cyanosis of the toes occurred associated with recent deep bilateral venous and arterial thrombosis at duplex ultrasound. New biological tests confirmed HIT and led us to stop heparin and to start argatroban with a positive clinical and biological evolution. Venous and arterial thrombosis associated with thrombocytopenia during heparin treatment must be considered HIT whatever the biological test results are. Argatroban is a good alternative treatment in the elderly.

  14. Nonstructural protein 2 (nsP2) of Chikungunya virus (CHIKV) enhances protective immunity mediated by a CHIKV envelope protein expressing DNA Vaccine.

    Science.gov (United States)

    Bao, Huihui; Ramanathan, Aarti A; Kawalakar, Omkar; Sundaram, Senthil G; Tingey, Colleen; Bian, Charoran B; Muruganandam, Nagarajan; Vijayachari, Paluru; Sardesai, Niranjan Y; Weiner, David B; Ugen, Kenneth E; Muthumani, Karuppiah

    2013-02-01

    Chikungunya virus (CHIKV) is an important emerging mosquito-borne alphavirus, indigenous to tropical Africa and Asia. It can cause epidemic fever and acute illness characterized by fever and arthralgias. The epidemic cycle of this infection is similar to dengue and urban yellow fever viral infections. The generation of an efficient vaccine against CHIKV is necessary to prevent and/or control the disease manifestations of the infection. In this report, we studied immune response against a CHIKV-envelope DNA vaccine (pEnv) and the role of the CHIKV nonstructural gene 2 (nsP2) as an adjuvant for the induction of protective immune responses in a relevant mouse challenge model. When injected with the CHIKV pEnv alone, 70% of the immunized mice survived CHIKV challenge, whereas when co-injected with pEnv+pnsP2, 90% of the mice survived viral challenge. Mice also exhibited a delayed onset signs of illness, and a marked decrease in morbidity, suggesting a nsP2 mediated adjuvant effect. Co-injection of the pnsP2 adjuvant with pEnv also qualitatively and quantitatively increased antigen specific neutralizing antibody responses compared to vaccination with pEnv alone. In sum, these novel data imply that the addition of nsP2 to the pEnv vaccine enhances anti-CHIKV-Env immune responses and maybe useful to include in future CHIKV clinical vaccination strategies.

  15. Incidence and diagnosis of EDTA-dependent pseudothrombocytopenia in a consecutive outpatient population referred for isolated thrombocytopenia.

    Science.gov (United States)

    Silvestri, F; Virgolini, L; Savignano, C; Zaja, F; Velisig, M; Baccarani, M

    1995-01-01

    Among 111 patients referred to our outpatient clinic for isolated thrombocytopenia during a 24-month period, 17 (15.3%) cases of EDTA-dependent pseudothrombocytopenia (EDTA-PTCP) were identified. EDTA-PTCP represented the second most frequent cause of thrombocytopenia in this population. The diagnosis was confirmed by the following findings: (a) normal platelet numbers immediately after blood withdrawal; (b) progressive fall of platelet counts and evident platelet clumping over time, only in EDTA-anticoagulated blood. A simple, inexpensive and quick diagnostic method was devised, that consists in evaluating the platelet number in a blood sample anticoagulated with EDTA immediately after blood withdrawal and 4 h later.

  16. 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

  17. 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).

  18. 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.

  19. Heparin-induced thrombocytopenia: a review of concepts regarding a dangerous adverse drug reaction.

    Science.gov (United States)

    Junqueira, Daniela Rezende Garcia; Carvalho, Maria das Graças; Perini, Edson

    2013-01-01

    Heparin is a natural agent with antithrombotic action, commercially available for therapeutic use as unfractionated heparin and low molecular weight heparin. Heparin-induced thrombocytopenia (HIT) is a serious adverse reaction to heparin that promotes antibody-mediated platelet activation. HIT is defined as a relative reduction in platelet count of 50% (even when the platelet count at its lowest level is above>150 x 10(9)/L) occurring within five to 14 days after initiation of the therapy. Thrombocytopenia is the main feature that directs the clinical suspicion of the reaction and the increased risk of thromboembolic complications is the most important and paradoxical consequence. The diagnosis is a delicate issue, and requires a combination of clinical probability and laboratory tests for the detection of platelet activation induced by HIT antibodies. The absolute risk of HIT has been estimated between 1% and 5% under treatment with unfractionated heparin, and less than 1% with low molecular weight heparin. However, high-quality evidence about the risk of HIT from randomized clinical trials is scarce. In addition, information on the frequency of HIT in developing countries is not widely available. This review aims to provide a better understanding of the key features of this reaction and updated information on its frequency to health professionals and other interested parties. Knowledge, familiarity, and access to therapeutic options for the treatment of this adverse reaction are mandatory to minimize the associated risks, improving patient safety.

  20. Successful laparoscopic splenectomy after living-donor liver transplantation for thrombocytopenia caused by antiviral therapy

    Institute of Scientific and Technical Information of China (English)

    2008-01-01

    Although interferon (IFN) based therapy for recurrent hepatitis C virus (HCV) infection after liver transplantation has been widely accepted, it induces various adverse effects such as thrombocytopenia, resulting in its interruption. Recently, concomitant splenectomy at the time of living donor liver transplantation (LDLT) has been tried to overcome this problem, but this procedure leads to several complications such as excessive intraoperative bleeding and serious infection. A 60-year-old female received LDLT using a left lobe graft from her second son for liver failure caused by hepatitis C-related cirrhosis. Six months after LDLT, she was diagnosed as recurrent HCV infection by liver biopsy. IFN monotherapy was started from 7 mo after LDLT and her platelet count decreased to less than 50000/μL, which thus made it necessary to discontinue the treatment. We decided to attempt laparoscopic splenectomy (LS) under general anesthesia. Since intra-abdominal findings did not show any adhesion formations around the spleen, LS could be successfully performed. After LS, since her platelet count immediately increased to 225000/μL 14 d after operation, IFN therapy was restarted and we could convert the combination therapy of IFN and ribavirin, resulting in no detectable viral marker. In conclusion, LS can be performed safely even after LDLT, and LS after LDLT is a feasible and less invasive modality for thrombocytopenia caused by antiviral therapy.

  1. Treatment-associated severe thrombocytopenia affects survival rate in esophageal cancer patients undergoing concurrent chemoradiotherapy

    Directory of Open Access Journals (Sweden)

    Y M Huang

    2015-01-01

    Full Text Available Background: Esophageal cancer is commonly treated with surgery, concurrent chemoradiotherapy (CCRT, or a combination of both. The correlation between the hematological parameters during CCRT and early survival of esophageal cancer has not been fully evaluated. Materials And Methods: We analyzed the records of 65 esophageal cancer patients treated by CCRT between 2007 and 2010 retrospectively. The association between CCRT-associated myelosuppression, demographic variables, and survival rates were analyzed by univariate and multivariate analysis. Results: The univariate analysis showed that tumor extent of T3-4, a higher stage of tumor, a lower albumin level, grade 3 or higher anemia and thrombocytopenia, and interruptions in treatment affected survival rates. Further, the multivariate analysis revealed that stage IV (P = 0.030 is an independently negative prognostic factor for a one-year survival rate. Stage IV (P = 0.035, tumor extent of T3-4 (P = 0.002, and grade 3-4 thrombocytopenia (P = 0.015 are independently negative prognostic factors for a two-year survival rate. Conclusions: Severe decrease in platelet count during CCRT independently affects survival of esophageal cancer patients in addition to stage of the tumor.

  2. Systematic review of severe fever with thrombocytopenia syndrome: virology, epidemiology, and clinical characteristics.

    Science.gov (United States)

    Liu, Shelan; Chai, Chengliang; Wang, Chengmin; Amer, Said; Lv, Huakun; He, Hongxuan; Sun, Jimin; Lin, Junfen

    2014-03-01

    Severe fever with thrombocytopenia syndrome (SFTS) was firstly discovered in China in 2010, followed by several reports from many other countries worldwide. SFTS virus (SFTSV) has been identified as the causative agent of the disease and has been recognized as a public health threat. This novel Bunyavirus belongs to the Phlebovirus genus in the family Bunyaviridae. This review also describes the different aspects of virology, pathogenesis, epidemiology, and clinical symptoms on the basis of the published article surveillance data and phylogenetic analyses of viral sequences of large, medium, and small segments retrieved from database using mega 5.05, simplot 3.5.1, network 4.611, and epi information system 3.5.3 software. SFTS presents with fever, thrombocytopenia, leukocytopenia, and considerable changes in several serum biomarkers. The disease has 10~15% mortality rate, commonly because of multiorgan dysfunction. SFTSV is mainly reported in the rural areas of Central and North-Eastern China, with seasonal occurrence from May to September, mainly targeting those of ≥50 years of age. A wide range of domesticated animals, including sheep, goats, cattle, pigs, dogs, and chickens have been proven seropositive for SFTSV. Ticks, especially Haemaphysalis longicornis, are suspected to be the potential vector, which have a broad animal host range in the world. More studies are needed to elucidate the vector-animal-human ecological cycle, the pathogenic mechanisms in high level animal models and vaccine development.

  3. 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.

  4. 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....

  5. 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.

  6. 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.

  7. Experience of off-label use of Eltrombopag in the treatment of thrombocytopenia associated with solid tumors

    Directory of Open Access Journals (Sweden)

    María Henar García Lagunar

    2015-02-01

    Full Text Available Purpose: To describe the results of the off-label use of eltrombopag in patients with solid tumors and thrombocytopenia that limits chemotherapy. Methods: Retrospective observational study including all patients with solid tumors who were treated with eltrombopag for thrombocytopenia during the chemotherapy treatment between January 2012 and December 2014. Results: Six patients, with solid tumors and thrombocytopenia that limits chemotherapy treatment, received eltrombopag during the study and it was observed a decrease in the delay of chemotherapy cycles (4.83 ± 4.79 delayed cycles before starting eltrombopag vs 2.50 ± 4.32 delayed cycles during the treatment with eltrombopag, p=0.492 and an increase in the percentage of administrated dosage (89.29 ± 13.36% vs 91.43 ± 10.69%, p=0.682. Also, there was an increase in platelet nadir (55.29 ± 16.45x109/L vs 76.14 ± 36.38x109/L, p=0.248 without platelet transfusion support in any patient during treatment with eltrombopag. Conclusions: eltrombopag has resulted to be an alternative in the treatment of patients with thrombocytopenia that limits chemotherapy, clinical trials with more number or patients are needed to confirm these results

  8. An unusual cause of mismanagement in an acute myocardial infarction case: pseudothrombocytopenia.

    Science.gov (United States)

    Kocum, Tolga H; Katircibasi, Tuna M; Sezgin, Alpay T; Atalay, Hakan

    2008-07-01

    Thrombocytopenia determined by an automated counter may represent a benign, incidental finding in an asymptomatic patient or a potentially life-threatening disorder. Even if the low platelet count actually is a benign condition itself, in some conditions, any delay resulting from this condition consequently may be seriously hazardous. Low platelet count may alter the decision of heparin administration, which is an essential part of management during acute coronary syndromes. EDTA-dependent pseudothrombocytopenia (PTCP) is reported to have a prevalence of 0.1% in a general hospital; however, it is also reported that around 15% of the patients referred for a specialized center for isolated thrombocytopenia are actually cases of PTCP. In this report, we describe a patient with PTCP who could not receive reperfusion therapy during acute myocardial infarction because of the low platelet counts reported by an automated counter.

  9. Correlation between serum levels of interleukins 10 and 12 and thrombocytopenia in hepatitis C cirrhotic (class A patients

    Directory of Open Access Journals (Sweden)

    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.

  10. 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...

  11. Refractory thrombotic thrombocytopenic purpura following acute pancreatitis

    Institute of Scientific and Technical Information of China (English)

    Ebisa Bekele; Bethel Shiferaw; Alexandra Sokolova; Arpan Shah; Phillip Saunders; Alida Podrumar; Javed Iqbal

    2016-01-01

    Thrombotic thrombocytopenic purpura (TTP) is a rare blood disorder with an estimated incidence of 4–5 cases per million people per year. It is characterized by small-vessel platelet-rich thrombi that cause thrombocytopenia, microangiopathic hemolytic anemia and organ damage. There are reports in literature that TTP and acute pancreatitis are associated, indicating each can be the cause of the other. However, acute pancreatitis triggering TTP is very rare. A 71 years old female presented with abdominal pain of 3 days, followed by dark urine. She had icteric sclera, petechial rash and mild epigastric tenderness. Lab findings were significant for hemolytic anemia, thrombocytopenia and elevated lipase. CT of abdomen showed evidence of pancreatitis and cholelithiasis. After admission, patient developed symptoms of stroke. Further investigation showed elevated lactate dehydrogenase and normal coagulation studied with peripheral blood smear showed 5–6 schistocytes/high power field. Disintegrin and metalloproteinase with thrombospondin motifs-13 (ADAMTS13) activity showed less than 3% with high ADAMTS13 inhibitor 2.2. Patient required 6–7 weeks of daily plasmapheresis until she showed complete response. Our patient presented with clinical features of pancreatitis prior to having dark urine and petechial rash. Therefore, we strongly believe that our patient had pancreatitis which was followed by TTP. Patient's ADMTS13 activity was 6%after 10 plasma exchanges, signifying refractory TTP and higher risk for morbidity and mortality. There are limited data and consensus on the management of refractory TTP. TTP and acute pancreatitis are associated. However, refractory TTP following acute pancreatitis is rarely mentioned in the literature. We would like to emphasize the importance of having higher clinical suspicion of the association of both disease entities.

  12. Recent progress in understanding the pathogenesis of fetal and neonatal alloimmune thrombocytopenia.

    Science.gov (United States)

    Curtis, Brian R

    2015-12-01

    Fetal and neonatal alloimmune thrombocytopenia (FNAIT) occurs in c. 1 in 1000 births and is caused by maternal antibodies against human platelet alloantigens that bind incompatible fetal platelets and promote their clearance from the circulation. Affected infants can experience bleeding, bruising and, in severe cases, intracranial haemorrhage and even death. As maternal screening is not routinely performed, and first pregnancies can be affected, most cases are diagnosed at delivery of a first affected pregnancy. Unlike its erythrocyte counterpart, Haemolytic Disease of the Fetus and Newborn, there is no prophylactic treatment for FNAIT. This report will review recent advances made in understanding the pathogenesis of FNAIT: the platelet alloantigens involved, maternal exposure and sensitization to fetal platelet antigens, properties of platelet Immunoglobulin G antibodies, maternal-fetal antibody transport mechanisms and efforts to develop an effective FNAIT prophylaxis.

  13. Her-2 Positive Gastric Cancer Presented with Thrombocytopenia and Skin Involvement: A Case Report

    Science.gov (United States)

    Arslan, Deniz; Tatlı, Ali Murat; Goksu, Sema Sezgin; Başsorgun, Cumhur İbrahim; Coskun, Hasan Senol; Bozcuk, Hakan; Savaş, Burhan

    2014-01-01

    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. PMID:25045559

  14. Molecular detection of severe fever with thrombocytopenia syndrome virus (SFTSV) in feral cats from Seoul, Korea.

    Science.gov (United States)

    Hwang, Jusun; Kang, Jun-Gu; Oh, Sung-Suck; Chae, Jeong-Byoung; Cho, Yun-Kyung; Cho, Young-Sun; Lee, Hang; Chae, Joon-Seok

    2017-01-01

    This study tested serum samples of feral cats from a highly urbanized habitat, Seoul, Korea to determine the infection to severe fever with thrombocytopenia syndrome virus (SFTSV). From 126 samples tested, SFTSV was detected by RT-PCR in 22 (17.5%) cats from various sites of Seoul. Sequences identified from this study were grouped with clusters from China and Japan. Our result provides data that SFTSV may have been circulating in settings that were suspected to have relatively low risk, such as highly urbanized habitats. Thus it warrants further study to investigate the ecology of SFTSV in urban-dwelling animals including ticks, human and other potential host species. Copyright © 2016 Elsevier GmbH. All rights reserved.

  15. 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.

  16. Childhood immune thrombocytopenia: role of rituximab, recombinant thrombopoietin, and other new therapeutics.

    Science.gov (United States)

    Journeycake, Janna M

    2012-01-01

    Childhood immune thrombocytopenia (ITP) is often considered a benign hematologic disorder. However, 30% of affected children will have a prolonged course and 5%-10% will develop chronic severe refractory disease. Until recently, the only proven therapeutic option for chronic severe ITP was splenectomy, but newer alternatives are now being studied. However, because immunosuppressive agents such as rituximab are not approved for use in ITP and the thrombopoietin receptor agonists are not yet approved in children, the decision to use alternatives to splenectomy needs to be considered carefully. This review describes the factors that should affect decisions to treat ITP at diagnosis and compares the options for the occasional child in whom ITP does not resolve within the first year.

  17. 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.

  18. 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.)

  19. More on false thrombocytopenias: EDTA-dependent pseudothrombocytopenia associated with a congenital platelet release defect.

    Science.gov (United States)

    Silvestri, F; Masotti, A; Pradella, P; Zaja, F; Barillari, G; De Marco, L

    1996-01-01

    We report herein the case of a 54-year-old woman with a moderate bleeding tendency, diagnosed as an EDTA-dependent pseudothrombocytopenia associated with a congenital platelet release defect. The patient, at the age of 12, had a misleading diagnosis of idiopathic thrombocytopenic purpura and all the recurrent bleeding problems she had during her life were referred to that disease. The recent correct diagnosis of a false thrombocytopenia stimulated further laboratory investigation on the cause of the patient's bleeding tendency with the consequent identification of a congenital platelet deficiency of the arachidonic acid pathway. This finding is of relevant importance for the management of the patient in case of elective surgery or hemorrhagic emergency.

  20. Hereditary Haemorrhagic Telangiectasia with Thrombocytopenia - A Rare Association with an Atypical Presentation

    Directory of Open Access Journals (Sweden)

    Padmakumar R

    2015-04-01

    Full Text Available Hereditary Haemorrhagic Telangiectasia (Osler-Rendu-Weber disease is a rare autosomal dominant disorder commonly a ecting small vessels of skin and mucosa. It is usually misdiagnosed because of its atypical presentation. This disease frequently presents as epistaxis, GI bleed and visceral arterio venous malformations. Patient may present with stroke or migraine but presentation due to predominant respiratory symptoms may occur in the presence of pulmonary A-V stula. We present a 9 yr old male with dyspnoea on exertion and cyanosis and clubbing. He had a past history of intracerebral bleed with thrombocytopenia and he was being treated as ITP. Contrast echo revealed ndings suggestive of pulmonary arterio venous stula which led to subsequent investigations and retrospective evaluation and hence achieving the final diagnosis.

  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. Acute liver failure caused by drug-induced hypersensitivity syndrome associated with hyperferritinemia

    Institute of Scientific and Technical Information of China (English)

    Masayuki Miyazaki; Masatake Tanaka; Akihiro Ueda; Tsuyoshi Yoshimoto; Masaki Kato; Makoto Nakamuta; Kazuhiro Kotoh; Ryoichi Takayanagi

    2011-01-01

    Drug-induced hypersensitivity syndrome (DIHS) is a se-vere reaction usually characterized by fever, rash, and multiorgan failure, occurring 2-6 wk after drug introduction.It is an immune-mediated reaction involving macrophage and T-lymphocyte activation and cytokine release. A 54-year-old woman was diagnosed with rheumatic arthritis and initiated salazosulfapyridine by mouth. About 10 d later, she had a high fever, skin rash and liver dysfunction. She was admitted to hospital and diagnosed with a drug eruption. She was treated with oral prednisolone 30 mg/d; however, she developed high fever again and her blood tests showed acute liver failure and cytopenia associated with hyperferritinemia. She was diagnosed with acute liver failure and hemophagocytosis caused by DIHS. She was transferred to the Department of Medicine and Bioregulatory Science, Kyushu University, where she was treated with arterial steroid injection therapy. Following this treatment, her liver function improved and serum ferritin immediately decreased. We hypothesized that an immune-mediated reaction in DIHS may have generated over-activation of macrophages and T-lymphocytes, followed by a cytokine storm that affected various organs. The measurement of serum ferritin might be a useful marker of the severity of DIHS.

  4. 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.

  5. Weight loss, leukopenia and thrombocytopenia associated with sustained virologic response to Hepatitis C treatment

    Directory of Open Access Journals (Sweden)

    Nuntra Suwantarat, Alan D. Tice, Thana Khawcharoenporn, Dominic C. Chow

    2010-01-01

    Full Text Available OBJECTIVE: To identify apparent adverse effects of treatment of chronic hepatitis C and their relationship to sustained virologic response (SVR. METHODS: 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. RESULTS: 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 103 cells/µl (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. CONCLUSION: 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.

  6. Autoimmune thrombocytopenia in response to splenectomy in cirrhotic patients with accompanying hepatitis C

    Institute of Scientific and Technical Information of China (English)

    Tetsuro Sekiguchi; Takeaki Nagamine; Hitoshi Takagi; Masatomo Mori

    2006-01-01

    AIM: To estimate the contribution of autoimmune thrombocytopenia to hepatitis C virus-related liver cirrhosis (type C cirrhosis), we evaluated the influence of splenectomy upon platelet-associated immunoglobulin G (PAIgG) levels and platelet numbers.METHODS: PAIgG titers and immune markers were determined in 24 type C cirrhotic patients with an intact spleen, 17 type C cirrhotic patients submitted to splenectomy, and 21 non-C cirrhosis with an intact spleen.RESULTS: Thrombocytopenia (PLT<15×104/μL) in type C cirrhosis was diagnosed in all patients with an intact spleen, 8 patients submitted to splenectomy, and in 19 non-C cirrhosis with intact spleen. Elevated titers of PAIgG at more than 25.0 ng/107 cells were detected in all cirrhotic patients except for one splenectomized patient.PAIgG titers (ng/107 cells) were significantly higher in the type C cirrhosis with an intact spleen (247.9 ± 197.0)compared with the splenectomized patients (125.6±87.8)or non-C cirrhosis (152.4± 127.4). PAIgG titers were negatively correlated with platelet counts in type C cirrhotic patients with an intact spleen. In comparison with the type C cirrhosis with an intact spleen, the splenectomized patients had a reduced CD4/CD8 ratio and serum neopterin levels. The spleen index (cm2) was negatively correlated with platelet counts in the non-C cirrhosis, but not in the type C cirrhosis.CONCLUSION: Our data indicate that the autoimmune mechanism plays an important role in thrombocytosis complicated by HCV-positive cirrhosis. In addition,splenectomy may impair T ceils function through, at least in part, a reduction of CD4/CD8 ratio, consequently suppressing PAIgG production.

  7. Characterization of severe fever with thrombocytopenia syndrome in rural regions of Zhejiang, China.

    Science.gov (United States)

    Zhang, Lei; Ye, Ling; Ojcius, David M; Lou, Xiuyu; Wang, Chengwei; feng, Cen; Sun, Yi; Wang, Zhongfa; Li, Shibo; Zhang, Yanjun

    2014-01-01

    Severe fever with thrombocytopenia syndrome virus (SFTSV) infections have recently been found in rural regions of Zhejiang. A severe fever with thrombocytopenia syndrome (SFTS) surveillance and sero-epidemiological investigation was conducted in the districts with outbreaks. During the study period of 2011-2014, a total of 51 SFTSV infection cases were identified and the case fatality rate was 12% (6/51). Ninety two percent of the patients (47/51) were over 50 years of age, and 63% (32/51) of laboratory confirmed cases occurred from May to July. Nine percent (11/120) of the serum samples from local healthy people without symptoms were found to be positive for antibodies to the SFTS virus. SFTSV strains were isolated by culture using Vero, and the whole genomic sequences of two SFTSV strains (01 and Zhao) were sequenced and submitted to the GenBank. Homology analysis showed that the similarity of the target nucleocapsid gene from the SFTSV strains from different geographic areas was 94.2-100%. From the constructed phylogenetic tree, it was found that all the SFTSV strains diverged into two main clusters. Only the SFTSV strains from the Zhejiang (Daishan) region of China and the Yamaguchi, Miyazakj regions of Japan, were clustered into lineage II, consistent with both of these regions being isolated areas with similar geographic features. Two out of eight predicted linear B cell epitopes from the nucleocapsid protein showed mutations between the SFTSV strains of different clusters, but did not contribute to the binding ability of the specific SFTSV antibodies. This study confirmed that SFTSV has been circulating naturally and can cause a seasonal prevalence in Daishan, China. The results also suggest that the molecular characteristics of SFTSV are associated with the geographic region and all SFTSV strains can be divided into two genotypes.

  8. Clinical features and factors associated with severity and fatality among patients with severe fever with thrombocytopenia syndrome Bunyavirus infection in Northeast China.

    Directory of Open Access Journals (Sweden)

    Baocheng Deng

    Full Text Available BACKGROUND: In 2009, severe fever with thrombocytopenia syndrome virus (SFTSV was identified as a novel member of the genus phlebovirus in the Bunyaviridae family in China. The detailed clinical features of cases with SFTSV infection have not been well described, and the risk factors for severity among patients and fatality among severe patients remain to be determined. METHODOLOGY/PRINCIPAL FINDINGS: Clinical and laboratory features of 115 hospitalized patients with SFTSV infection during the period from June 2010 to December 2011 in Northeast China were retrospectively reviewed. We assessed the risk factors associated with severity in confirmed cases and fatality in severe cases by multivariate analysis. One hundred and three (89.6% of 115 patients presented with multiple organ dysfunction, and 22 (19.1% of 115 proceeded to the stage of life threatening multiple organ failure. Of the 115 patients, 14 fatalities (12.2% were reported. Multivariate analysis demonstrated that the independent predictors of risk for severity were: albumin ≤ 30 g/l (OR, 8.09; 95% CI, 2.58-25.32, APTT ≥ 66 seconds (OR, 14.28; 95% CI, 3.28-62.24, sodium ≤ 130 mmol/l (OR, 5.44; 95% CI, 1.38-21.40, and presence of neurological manifestations (OR, 7.70; 95% CI, 1.91-31.12. Among patients with severe disease, presence of acute lung injury/acute respiratory distress syndrome (HR, 4.59; 95% CI, 1.48-14.19 and disseminated intravascular coagulation (HR, 4.24; 95% CI, 1.38-13.03 were independently associated with fatality. CONCLUSIONS/SIGNIFICANCE: SFTSV infection may present with more severe symptoms and laboratory abnormalities than hitherto reported. Due to infection with a novel bunyavirus, the patients may sufferer multiple organ dysfunction and die of multiple organ failure. In the clinical assessment of any case of SFTS, independent factors relating to prognosis need to be taken into account by clinicians.

  9. Acute autonomic, sensory and motor neuropathy associated with meningoencephalitis.

    Science.gov (United States)

    Kinoshita, Satoko; Sugie, Kazuma; Kataoka, Hiroshi; Sugie, Miho; Hirano, Makito; Ueno, Satoshi

    2009-01-01

    We report the first case of acute autonomic, motor and sensory neuropathy (AASMN) associated with meningoencephalitis. A 62-year-old man presented with fever, neck stiffness, and coma. Respiratory failure developed. Magnetic resonance images showed an abnormality in the medial temporal lobe. Cerebrospinal fluid analysis revealed pleocytosis with a high protein level. Intensive care gradually improved the consciousness level, but paralysis of the four extremities persisted. Nerve conduction studies revealed demyelinating sensory and motor polyneuropathy. Severe orthostatic hypotension, urinary retention, and constipation were also present. Clinical autonomic tests suggested both sympathetic and parasympathetic dysfunction. After intravenous immunoglobulin therapy, motor and sensory symptoms resolved rapidly; dysautonomia resolved gradually over the next 2 months. The response to immunological therapy and the presence of antecedent infection suggest that AASMN is a postinfectious, immune-mediated, autonomic, sensory and motor nervous system dysfunction.

  10. Acute ciprofloxacin-induced crystal nephropathy with granulomatous interstitial nephritis

    Directory of Open Access Journals (Sweden)

    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.

  11. Acute pancreatitis

    Science.gov (United States)

    ... its blood vessels. This problem is called acute pancreatitis. Acute pancreatitis affects men more often than women. Certain ... pancreatitis; Pancreas - inflammation Images Digestive system Endocrine glands Pancreatitis, acute - CT scan Pancreatitis - series References Forsmark CE. Pancreatitis. ...

  12. Cystitis - acute

    Science.gov (United States)

    Uncomplicated urinary tract infection; UTI - acute cystitis; Acute bladder infection; Acute bacterial cystitis ... cause. Menopause also increases the risk for a urinary tract infection. The following also increase your chances of having ...

  13. 利妥昔单抗在治疗免疫介导的肾小球肾炎中的应用%Rituximab for the treatment of immune-mediated glomerular diseases

    Institute of Scientific and Technical Information of China (English)

    姜玲(综述); 李世军(审校)

    2015-01-01

    Rituximab ( RTX) is a monoclonal antibody to the CD 20 antigen on B-cells that was initially designed and approved for the treatment of non-Hodgkin′s B-cell lymphoma and has emerged as a potent immunosuppressant for many immune -mediated disea-ses.Given its efficacy , tolerability and safety profile in comparison to more conventional treatment regimens , RTX is rapidly emerging as a critical therapeutic modality for glomerular disease .The paper reviews the role of RTX in the treatment of ANCA-associated vascul-itis, lupus nephritis , mixed cryoglobulinemia , membranous nephropathy , minimal change disease , and focal segmental glomeruloscle-rosis.%利妥昔单抗( Rituximab, RTX)是用于治疗非霍奇金淋巴瘤的抗CD20人/鼠嵌合型单克隆抗体,也是一种有效治疗自身免疫性疾病的药物。其疗效确切,耐受性及安全性较好,已逐渐成为治疗肾小球肾炎的重要药物之一。文中主要对RTX在抗中性粒细胞胞浆抗体( antineutrophil cytoplasmic antibody , ANCA)相关小血管炎、狼疮性肾炎、混合性冷球蛋白血症、膜性肾病、微小病变肾病和局灶节段性肾小球硬化中的应用作一综述。

  14. MOG抗体在不同类型免疫介导性视神经炎血清中的表达%Anti-MOG antibody in different types of immune-mediated optic neuritis

    Institute of Scientific and Technical Information of China (English)

    孔秀云; 彭静婷; 刘丽娟; 颜榕; 张晓君

    2012-01-01

    目的 初步探索抗髓鞘少突胶质细胞糖蛋白抗体(MOG-Ab)在不同临床类型免疫介导性视神经炎(IM-ON)患者血清中的表达.方法 采用临床病例横断面研究.2010年5月至2011年2月至北京同仁医院神经内科就诊的免疫介导性视神经炎患者(IM-ON) 129例,根据其临床特点分为以下5组:多发性硬化相关视神经炎(MS-ON) 20例,视神经脊髓炎相关视神经炎(NMO-ON) 13例,自身免疫病相关视神经炎(AON) 33例,复发性孤立性视神经炎(RION) 43例及单发性孤立性视神经炎(SION)20例.用ELISA方法对其血清中MOG-Ab进行检测,应用SPSS17.0软件,采用x2检验及方差分析、t检验方法对数据进行统计学分析,比较其阳性率与抗体滴度在不同组间的区别.结果 所有129例IM-ON患者中12例(9.3%)患者的血清MOG-Ab阳性.其中MS-ON组血清MOG-Ab阳性者5例(5/20),NMO-ON组0例(0/13),AON组4例(4/33),RION组2例(2/43),SION组1例(1/20).5组间阳性率差异无统计学意义(Fisher确切概率法,x2=7.051,P=0.088).将除MS-ON组之外的其余4组合并为“视神经脊髓炎(NMO)谱系视神经炎”后与MS-ON组比较发现,MS-ON组的MOG-Ab阳性率和抗体滴度均明显高于“NMO谱系视神经炎”组.结论 MOG抗体见于除NMO-ON之外的各种类型的IM-ON,在MS-ON患者血清中的表达明显高于“NMO谱系视神经炎”.%Objective To investigate the expression of anti-myelin oligodendrocyte glycoprotein antibody (MOG-Ab) in different types of immune-mediated optic neuritis (IM-ON).Methods Case-control and cross section study.The serum of 129 consecutive cases of immune-mediated optic neuritis (IM-ON group) seen in Neuro-ophthalmology clinic in Department of Neurology,Beijing Tongren Hospital during May 2010 and February 2011 were collected.All IM-ON cases were further classified into five different types as:20 cases of multiple sclerosis related ON (MS-ON),13 cases of neuromyelitis optica related ON (NMO-ON),33 cases of

  15. Rapid response of advanced squamous non-small cell lung cancer with thrombocytopenia after first-line treatment with pembrolizumab plus autologous cytokine-induced killer cells

    Directory of Open Access Journals (Sweden)

    Zhenzhen eHui

    2015-12-01

    Full Text Available We present the first clinical evidence of advanced squamous non-small cell lung cancer with severe thrombocytopenia showing dramatic improvement after first-line treatment with pembrolizumab plus cytokine-induced killer cells.

  16. Narcolepsy as an Immune-Mediated Disease

    Directory of Open Access Journals (Sweden)

    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.

  17. Cancer as an immune-mediated disease

    Directory of Open Access Journals (Sweden)

    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

  18. Pathogenesis of immune-mediated neuropathies.

    Science.gov (United States)

    Dalakas, Marinos C

    2015-04-01

    Autoimmune neuropathies occur when immunologic tolerance to myelin or axonal antigens is lost. Even though the triggering factors and the underling immunopathology have not been fully elucidated in all neuropathy subsets, immunological studies on the patients' nerves, transfer experiments with the patients' serum or intraneural injections, and molecular fingerprinting on circulating autoantibodies or autoreactive T cells, indicate that cellular and humoral factors, either independently or in concert with each other, play a fundamental role in their cause. The review is focused on the main subtypes of autoimmune neuropathies, mainly the Guillain-Barré syndrome(s), the Chronic Inflammatory Demyelinating Polyneuropathy (CIDP), the Multifocal Motor Neuropathy (MMN), and the IgM anti-MAG-antibody mediated neuropathy. It addresses the factors associated with breaking tolerance, examines the T cell activation process including co-stimulatory molecules and key cytokines, and discusses the role of antibodies against peripheral nerve glycolipids or glycoproteins. Special attention is given to the newly identified proteins in the nodal, paranodal and juxtaparanodal regions as potential antigenic targets that could best explain conduction failure and rapid recovery. New biological agents against T cells, cytokines, B cells, transmigration and transduction molecules involved in their immunopathologic network, are discussed as future therapeutic options in difficult cases. This article is part of a Special Issue entitled: Neuromuscular Diseases: Pathology and Molecular Pathogenesis.

  19. Esophageal Candidiasis as the Initial Manifestation of Acute Myeloid Leukemia.

    Science.gov (United States)

    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.

  20. A Case of Thrombotic Thrombocytopenia Purpura Associated with Systemic Lupus Erythematosus: Diagnostic Utility of ADAMTS-13 Activity

    Directory of Open Access Journals (Sweden)

    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.