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Sample records for acute immune-mediated thrombocytopenia

  1. Canine pemphigus foliaceus with concurrent immune-mediated thrombocytopenia.

    Kawarai, Shinpei; Hisasue, Masaharu; Matsuura, Shinobu; Ito, Tetsuro; Inoue, Yukari; Neo, Sakurako; Fujii, Yoko; Madarame, Hiroo; Shirota, Kinji; Tsuchiya, Ryo

    2015-01-01

    A 3 yr old wirehaired fox terrier was presented to his primary care veterinarian with fever, thrombocytopenia, and generalized crusting dermatitis. The skin lesion had progressed for at least 18 days, and thrombocytopenia had developed 3 days before presentation. Histopathology and direct immunofluorescence studies of the skin were consistent with pemphigus foliaceus (PF). Immunofluorescence revealed immunoglobulin G deposition around the keratinocytes in the stratum spinosum. A diagnosis of immune-mediated thrombocytopenia (IMT) was confirmed by the presence of platelet surface-associated immunoglobulin using flow cytometry. Systemic immunosuppressive therapy with cyclosporine and azathioprine was effective, and the dog survived for >2 years from the initial presentation. IMT is rarely associated with PF. This appears to be the first detailed report of a definitive diagnosis of concurrent PF and IMT in a dog. The authors' findings indicate that canine PF could be complicated by hematologic immune-mediated diseases such as IMT. PMID:25415212

  2. Immune mediated neutropenia and thrombocytopenia in 3 giant schnauzers.

    Vargo, Cheryl L; Taylor, Susan M; Haines, Deborah M

    2007-11-01

    Neutropenia, thrombocytopenia, and splenomegaly were recognized in 3 adult female giant schnauzers. Antineutrophil antibodies were demonstrated in 2 dogs. Following splenectomy, administration of prednisone and azathioprine resulted in normalization of neutrophil and platelet numbers in all dogs. PMID:18050797

  3. Application of vincristine-loaded platelet therapy in three dogs with refractory immune-mediated thrombocytopenia

    Park, Hyung-Jin; Kim, Ja-Won; Song, Kun-Ho; Seo, Kyoung-Won

    2015-01-01

    Three dogs presented with refractory immune-mediated thrombocytopenia (IMT). All patients failed to respond to prednisone, which is considered a mainstay of immunosuppressive therapy. Vincristine-loaded platelets (VLPs), which act selectively on mononuclear phagocytes,were introduced. After the VLPs were transfused, two dogs responded quickly withimproved clinical signs while the third dogwith recurrent IMT was euthanized due to its deteriorating condition. This case report describesthe effic...

  4. Lameness associated with tarsal haemarthrosis as the sole clinical sign of idiopathic immune-mediated thrombocytopenia in a dog.

    Walton, M B; Mardell, E; Spoor, M; Innes, J

    2014-01-01

    A four-year-old, male Cocker Spaniel was presented for investigation of pelvic limb stiffness. There was palpable effusion of both tarsi, and analysis of synovial fluid from these joints indicated previous haemorrhage. After further investigation a diagnosis of idiopathic immune-mediated thrombocytopenia was made. The dog responded to treatment with prednisolone and azathioprine. To the authors' knowledge, this is the first reported case of confirmed haemarthrosis as the sole presenting clinical sign for canine idiopathic immune-mediated thrombocytopenia. PMID:25327981

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

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

    2015-12-01

    A 4-year-old male Toy Poodle was presented to the Small Animal Veterinary Hospital of the Faculty of Veterinary Medicine of the Autonomous University of Mexico (FMVZ, UNAM) because of depression, lethargy, and hemorrhages involving several areas of the skin and around the eyes. Hematology data and a bone marrow analysis suggested hemolytic anemia and immune-mediated thrombocytopenia. The dog was treated with prednisone, and after one month the hematology variables improved. However, the dog's clinical condition inexplicably worsened and it was euthanized. On necropsy, there were no relevant findings. However, in histology, multifocal lymphoplasmacytic and histiocytic meningoencephalitis and necrosis, and a protozoan cyst in the cerebellum were identified. In addition, moderate multifocal lymphoplasmacytic and necrotizing pancreatitis, hepatitis, myocarditis, and diffuse lymphoplasmacytic enteritis were observed. Immunohistochemistry of the cerebellum, liver, pancreas, and intestine with a specific antibody against Neospora caninum confirmed the diagnosis of systemic neosporosis. The systemic neosporosis in this dog was most likely caused by reactivation of latent parasites due to prednisone administration during the one month of treatment. It should be kept in mind that in dogs being treated with immunosuppressants for immune-mediated conditions, opportunistic parasites, such as Toxoplasma gondii and N caninum, can be reactivated from a latent state, as it probably happened in the present case. PMID:26345698

  6. Acute profound thrombocytopenia with second exposure to eptifibatide associated with a strong antibody reaction

    ATTAYA, SHARIFF; KANTHI, YOGENDRA; ASTER, RICHARD; MCCRAE, KEITH

    2015-01-01

    We present a case of eptifibatide-induced acute profound thrombocytopenia in a 64-year-old male receiving eptifibatide for the second time during percutaneous coronary intervention. Although rare, short and self-limited episodes of acute and profound thrombocytopenia have been associated with eptifibatide exposure. The thrombocytopenia is thought to be immune mediated, and assays are available to test for eptifibatide-induced platelet antibodies. PMID:19172524

  7. Acute profound thrombocytopenia with second exposure to eptifibatide associated with a strong antibody reaction

    ATTAYA, SHARIFF; Kanthi, Yogendra; Aster, Richard; McCrae, Keith

    2009-01-01

    We present a case of eptifibatide-induced acute profound thrombocytopenia in a 64-year-old male receiving eptifibatide for the second time during percutaneous coronary intervention. Although rare, short and self-limited episodes of acute and profound thrombocytopenia have been associated with eptifibatide exposure. The thrombocytopenia is thought to be immune mediated, and assays are available to test for eptifibatide-induced platelet antibodies.

  8. Concurrent immune-mediated haemolytic anaemia and severe thrombocytopenia in 21 dogs.

    Goggs, R; Boag, A K; Chan, D L

    2008-09-13

    The medical records of 21 dogs with concurrent immune-mediated haemolytic anaemia (imha) and severe thrombocytopenia (defined as an automated platelet count of less than 50x10(9)/l, confirmed by the examination of a blood smear) were reviewed. Their mean (sd) age was 5.8 (2.5) years. When compared with the 24,759 dogs in the hospital population for the same period Airedale terriers and dobermanns appeared to be over-represented with odds ratios of 22.5 (95 per cent confidence interval [ci] 5.2 to 97.9) and 7.6 (95 per cent ci 1.8 to 32.7) respectively. The median duration of the dogs' clinical signs was seven days, with a range from one to 17 days. Eleven of the dogs had a history of a tendency to bleed, and 15 had evidence of bleeding when examined. Twenty of the 21 dogs had been treated with glucocorticoids, nine with vincristine, and seven with azathioprine. Their median stay in hospital was four days, with a range from one to 17 days. The median period for which they survived after admission to hospital was five days, with a range from one to 558 days, and 16 of the 21 dogs had died or been euthanased within 30 days of their admission. PMID:18791206

  9. Acute psychosis in children: do not miss immune-mediated causes.

    AlHakeem, Afnan S; Mekki, Mohamed S; AlShahwan, Saad M; Tabarki, Brahim M

    2016-07-01

    New-onset psychosis in children represents a complex presenting symptom. Psychosis can be attributable to a combination of factors and etiologies, and all possible causes must be systematically examined. There is growing evidence that a proportion of psychosis/ psychiatric manifestations in children may be immunemediated, and physicians should consider this etiology in each presentation of first-episode psychosis. Immunemediated encephalopathies/encephalitis are increasingly being recognized in children with antibodies to N-methyl-D-aspartate receptor, Leucine-rich gliomainactivated 1 or other central nervous system antigens such as Contactin-associated protein-like 2, glutamic acid decarboxylase, alpha-amino-3-hydroxy-5-methyl-4isoxazolepropionic acid or Gamma-aminobutyric acid B. In this study, we describe 3 cases of immune-mediated encephalopathy/encephalitis with prominent psychiatric symptoms at presentation, and suggest a practical diagnostic and treatment approach for children with acute psychosis of an immune-mediated cause. PMID:27356658

  10. Acute renal failure and severe thrombocytopenia associated with metamizole

    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. Acute renal failure and severe thrombocytopenia associated with metamizole.

    Redondo-Pachon, Maria Dolores; Enriquez, Ricardo; Sirvent, Ana Esther; Millan, Isabel; Romero, Alberto; Amorós, Francisco

    2014-01-01

    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 diagnosis 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. PMID:24434395

  12. Identifying drugs that cause acute thrombocytopenia: an analysis using 3 distinct methods

    Reese, Jessica A.; Li, Xiaoning; Hauben, Manfred; Aster, Richard H.; Bougie, Daniel W.; Curtis, Brian R.; George, James N.; Vesely, Sara K.

    2010-01-01

    Drug-induced immune thrombocytopenia (DITP) is often suspected in patients with acute thrombocytopenia unexplained by other causes, but documenting that a drug is the cause of thrombocytopenia can be challenging. To provide a resource for diagnosis of DITP and for drug safety surveillance, we analyzed 3 distinct methods for identifying drugs that may cause thrombocytopenia. (1) Published case reports of DITP have described 253 drugs suspected of causing thrombocytopenia; using defined clinica...

  13. Heparin-induced thrombocytopenia associated with acute liver graft failure

    Pannicke, Nadine; Pollok, Joerg-Matthias; Kluge, Stefan; Petzoldt, Martin

    2012-01-01

    An orthotopic liver transplantation (OLT) is of a proven benefit in an acute liver failure (ALF). Heparin-induced thrombocytopenia (HIT) is strongly associated with thromboembolic complications. We present the case of a 56-year-old patient who underwent an OLT owing to an ALF of unknown aetiology. HIT type II with consecutive hepatic and portal vein thrombosis caused progressive graft failure. Total hepatectomy and porto-caval shunt were performed to reduce the toxic effects of liver cell nec...

  14. Borna disease virus induces acute fatal neurological disorders in neonatal gerbils without virus- and immune-mediated cell destructions

    Borna disease virus (BDV) is a noncytolytic, neurotropic RNA virus that is known to cause neurological disturbances in various animal species. Our previous experiment demonstrated that neonate gerbils develop an acute fatal neurological disease following infection with BDV , Virology 282, 65-76). The study suggested that BDV directly causes functional damage of neuronal cells resulting in the lethal disorder in neonatal gerbils. To extend this finding, we examined whether BDV can induce neurological diseases in the absence of virus- and immune-mediated cell destruction, by using cyclosporine A (CsA)-treated neonatal gerbils. Although CsA completely suppressed specific antibody production and brain inflammation in the infected gerbil brains, the fatal neurological disorder was not inhibited by the treatment. Furthermore, we demonstrated that CsA treatment significantly decreased brain levels of cytokines, except interleukin (IL)-1β, in the infected gerbils. These results suggested that BDV replication, as well as brain cytokines, at least IL-1β, rapidly induces fatal disturbances in gerbil brain. We demonstrate here that BDV exhibits a unique neuropathogenesis in neonatal gerbil that may be pathologically and immunologically different from those in two other established rodent models, rats and mice. With this novel rodent model of virus infection it should be possible not only to examine acute neurological disturbances without severe neuroanatomical and immunopathological alterations but also to analyze molecular and cellular damage by virus replication in the central nervous system

  15. Idiopathic thrombocytopenic purpura following successful treatment of acute lymphoblastic leukemia.

    Tannir, N M; Kantarjian, H

    2001-03-01

    Thrombocytopenia is common in patients with acute lymphocytic leukemia (ALL) at diagnosis. It is a universal side effect of dose-intensive regimens employed in the treatment of adult ALL. In patients with ALL who achieve remission, thrombocytopenia frequently indicates relapse. We report three adult patients successfully treated for ALL who developed thrombocytopenia and were found to have immune-mediated thrombocytopenia (ITP). Possible pathophysiologic mechanisms underlying the association of ALL and ITP are discussed. PMID:11342378

  16. A four-point clinical criteria distinguishes immune thrombocytopenia from acute lymphoblastic leukaemia.

    Lum, S H; How, S J; Ariffin, H; Krishnan, S

    2016-02-01

    Immune thrombocytopenia is the most common diagnosis of isolated thrombocytopenia. The dilemma encountered by paediatricians is missing diagnosis of acute leukaemia in children with isolated thrombocytopenia. We demonstrated childhood ITP could be diagnosed using a four point clinical criteria without missing a diagnosis of acute leukaemia. Hence, bone marrow examination is not necessary in children with typical features compatible with ITP prior to steroid therapy. This can encourage paediatricians to choose steroid therapy, which is cheaper and non-blood product, as first line platelet elevating therapy in children with significant haemorrhage. PMID:27130741

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

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

    2013-01-01

    Mice infected with Trypanosoma cruzi, the agent of Chagas disease, rapidly develop anemia and thrombocytopenia. These effects are partially promoted by the parasite trans-sialidase (TS), which is shed in the blood and depletes sialic acid from the platelets, inducing accelerated platelet clearance and causing thrombocytopenia during the acute phase of disease. Here, we demonstrate that oral immunization of C57BL/6 mice with Phytomonas serpens, a phytoflagellate parasite that shares common antigens with T. cruzi but has no TS activity, reduces parasite burden and prevents thrombocytopenia and leukopenia. Immunization also reduces platelet loss after intraperitoneal injection of TS. In addition, passive transfer of immune sera raised in mice against P. serpens prevented platelet clearance. Thus, oral exposure to P. serpens attenuates the progression of thrombocytopenia induced by TS from T. cruzi. These findings are not only important for the understanding of the pathogenesis of T. cruzi infection but also for developing novel approaches of intervention in Chagas disease. PMID:23844182

  18. Acute Thrombocytopenia: An Unusual Complication Occurring After Drug-Eluting Microspheres Transcatheter Hepatic Chemoembolization

    Image-guided transcatheter hepatic chemoembolization (TACE) is accepted worldwide as an effective treatment for patients with unresectable hepatocellular carcinoma and liver metastases from neuroendocrine tumors, colorectal carcinomas, and uveal melanomas. Although the technique is relatively safe, it has been associated with several complications. We report the cases of two patients with colorectal liver metastases who developed acute thrombocytopenia a few hours after TACE. To our knowledge, acute thrombocytopenia occurring after TACE with drug-eluting microspheres has not yet been reported. Here we discuss the hypothetical etiopathogenetic mechanisms.

  19. Successful intravenous thrombolysis in a patient with antiphospholipid syndrome, acute ischemic stroke and severe thrombocytopenia.

    Camara-Lemarroy, Carlos R; Infante-Valenzuela, Adrian; Andrade-Vazquez, Catalina J; Enriquez-Noyola, Raul V; Garcia-Valadez, Erick A; Gongora-Rivera, Fernando

    2016-04-01

    Alteplase is the only approved drug for the treatment of acute ischemic stroke, but it is offered to a minority of patients, not only because of the short therapeutic window but also because of the numerous contraindications associated with thrombolysis, such as thrombocytopenia. There is some controversy on the true risk associated with thrombolysis in patients with thrombocytopenia. Here we report the case of a young patient, who developed an in-hospital acute ischemic stroke involving a large territory of the right middle cerebral artery, who was successfully treated with intravenous alteplase, despite having thrombocytopenia and prolonged prothrombin times due to systemic lupus erythematosus and antiphospholipid syndrome. This case exemplifies the need to reassess contraindications for thrombolysis, many based on expert opinion and not clinical evidence, especially in complex clinical situations. PMID:26575492

  20. Biomarkers for immune thrombocytopenia

    Yu, Lingjia; Zhang, Chunmei; Zhang, Liping; Shi, Yongyu; Ji, Xuebin

    2015-01-01

    Immune thrombocytopenia is an autoimmune disease with abnormal biomarkers. Immune thrombocytopenia pathogenesis is a complicated process in which the patient’s immune system is activated by platelet autoantigens resulting in immune mediated platelet destruction or suppression of platelet production. The autoantibodies produced by autoreactive B cells against self antigens are considered to play a crucial role. In addition, biomarkers such as transforming growth factor-beta1,Toll-like receptor...

  1. Acute profound abciximab induced thrombocytopenia: a correct management of a methodological error.

    Tanzilli, Gaetano; Sordi, Martina; Arrivi, Alessio; Mangieri, Enrico; Scappaticci, Massimiliano

    2009-01-01

    Thrombocytopenia is a rare complication of glycoprotein IIb/IIIa treatment. We report a case of an acute profound abciximab induced thrombocytopenia and its successful management. The patient, presenting with unstable angina, underwent percutaneous coronary intervention with implantation of three drug eluting stents without receiving a clopidogrel loading dose according to guidelines. The rapid drop in the platelet count after abciximab elastomeric pump infusion was treated with drug discontinuation and platelet transfusion. The high risk of stent thrombosis was avoided by a timely readministration of the dual antiplatelet treatment. PMID:21977060

  2. [Immune-mediated neuropathies].

    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. PMID:27474733

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

    Trellopoulos George

    2008-07-01

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

  4. Effect of High Dose of Steroid on Plateletcount in Acute Stage of Dengue Fever with Thrombocytopenia

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

    2013-01-01

    Background: 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)...

  5. Immunomodulatory drugs and their application to the management of canine immune-mediated disease.

    Whitley, N T; Day, M J

    2011-02-01

    This review summarises the current understanding of immune response and T cell subsets in the context of development of autoimmunity in the dog. Mode of action and rational usage in immune-mediated disease in the dog are discussed for the following drugs: glucocorticoids, azathioprine, cyclophosphamide, ciclosporin, tacrolimus, human intravenous immunoglobulin, vincristine, danazol, leflunomide, mycophenolate mofetil and liposome-encapsulated clodronate. Disease mechanisms are discussed and published evidence for drug efficacy is scrutinised for five important immune-mediated diseases: immune-mediated haemolytic anaemia, immune-mediated thrombocytopenia, myasthenia gravis, glomerulonephritis and inflammatory bowel disease. Future strategies for more refined manipulation of adverse immune responses are presented. PMID:21265846

  6. Non-surgical contraindication for acute appendicitis with secondary thrombocytopenia: a case report.

    Zhang, Hai-Hong; Gu, Guo-Li; Zhang, Xiang-Yang; Fan, Qin; Wang, Xin-Yan; Wei, Xue-Ming

    2015-03-01

    A 26-year-old man presented with migrated right lower abdominal pain and without any history of hematological systemic diseases. Blood routine test showed a leukocyte count of 22.74 × 10(9)/L, with 91.4% neutrophils, and a platelet count of 4 × 10(9)/L before admission. The case question was whether the team should proceed with surgery. Obviously, a differential diagnosis is essential before making such a decision. Acute appendicitis was easily diagnosed based on clinical findings, including migrating abdominal pain, a leukocyte count of 22.74 × 10(9)/L and the result of abdominal computed tomography scan. However, it was not clear whether the severe thrombocytopenia was primary or secondary. So smear of peripheral blood and aspiration of bone marrow were ordered to exclude hematological diseases. Neither of the tests indicated obvious pathological hematological changes. There was no hepatosplenomegaly found by ultrasound examination of the liver and spleen. Therefore, operative intervention may be a unique clinical scenario in acute severe appendicitis patients with secondary thrombocytopenia. PMID:25759558

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

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

    2015-01-01

    Immune thrombocytopenia (ITP) is an acute self-limited disease of childhood, mostly resolving within 6 months irrespective of whether therapy is given or not. Treatment options when indicated include corticosteroids, intravenous immune globulin (IVIG), and anti-RhD immunoglobulin. We reviewed our 32 years' experience for first-line therapy of acute ITP. Five hundred forty-one children (mean age: 5.3 years) diagnosed and treated for ITP were evaluated retrospectively. Among 491 acute ITP patients, IVIG was used in 27%, high-dose steroids in 27%, low-dose steroids in 20%, anti-D immunoglobulin G (IgG) in 2%, and no therapy in 22%. When the initial response (platelets >50 × 10(9)/L) to first-line treatment modalities were compared, 89%, 84%, and 78% patients treated by low-dose steroids, high-dose steroids, and IVIG responded to treatment, respectively (P > .05). Mean time to recovery of platelets was 16.8, 3.8, and 3.0 days in patients treated with low-dose steroids, high-dose steroids, and IVIG, respectively (P < .0001). Thrombocytopenia recurred in 23% of low-dose steroid, 39% of high-dose steroid, and in 36% of IVIG (P < .0001) treatment groups. Of 108 patients who were observed alone, 4 (3%) had a recurrence on follow-up and only 2 of these required treatment subsequently. Recurrence was significantly less in no therapy group compared with children treated with 1 of the 3 options of pharmacotherapy (P < .0001). Response rates were similar between patients treated by IVIG and low- and high-dose steroids; however, time to response was slower in patients treated with low-dose steroids compared with IVIG and high-dose steroids. PMID:26154620

  8. Corticosteroid responsive prolonged thrombocytopenia in a case of dengue fever

    Verma, Shailendra Prasad; Hamide, Abdoul; Wadhwa, Jyoti; Sivamani, Kalaimani

    2013-01-01

    Thrombocytopenia and bleeding manifestations are consistent features of dengue fever. Usually thrombocytopenia resolves and platelet count normalises by day 10 of fever. Persistent thrombocytopenia is not a feature of dengue fever. Proposed mechanisms behind thrombocytopenia are many. Direct platelet destruction by dengue virus, immune-mediated platelet destruction and even megakaryocytic immune injury have been proposed as underlying mechanisms. We are reporting a case of an old man who pres...

  9. Spleen enlargement is a common finding in acute Puumala hantavirus infection and it does not associate with thrombocytopenia.

    Koskela, Sirpa M; Laine, Outi K; Paakkala, Antti S; Mäkelä, Satu M; Mustonen, Jukka T

    2014-10-01

    The pathogenesis of thrombocytopenia in Puumala hantavirus (PUUV) infection is probably multifactorial. We aimed to evaluate the possible spleen enlargement during acute PUUV infection, and to determine its association with thrombocytopenia and disease severity. Magnetic resonance imaging (MRI) of the spleen was performed in 20 patients with acute PUUV infection. MRI was repeated 5-8 months later. The change in spleen length was compared with markers describing the severity of the disease. In all patients, the spleen length was increased in the acute phase compared with the control phase (median 129 mm vs 111 mm, p < 0.001). The change correlated with maximum C-reactive protein value (r = 0.513, p = 0.021) and inversely with maximum leukocyte count (r = -0.471, p = 0.036), but not with maximum serum creatinine level or minimum platelet count. Enlarged spleen, evaluated by MRI, was shown to be a common finding during acute PUUV infection. However, it does not associate with thrombocytopenia and acute kidney injury. PMID:25119440

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

    Alireza Hosseinnezhad

    2011-05-01

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

  11. Plasma pentraxin-3 and coagulation and fibrinolysis variables during acute Puumala hantavirus infection and associated thrombocytopenia.

    Laine, Outi K; Koskela, Sirpa M; Outinen, Tuula K; Joutsi-Korhonen, Lotta; Huhtala, Heini; Vaheri, Antti; Hurme, Mikko A; Jylhävä, Juulia; Mäkelä, Satu M; Mustonen, Jukka T

    2014-09-01

    Thrombocytopenia and altered coagulation characterize all hantavirus infections. To further assess the newly discovered predictive biomarkers of disease severity during acute Puumala virus (PUUV) infection, we studied the associations between them and the variables reflecting coagulation, fibrinolysis and endothelial activation. Nineteen hospital-treated patients with serologically confirmed acute PUUV infection were included. Acutely, plasma levels of pentraxin-3 (PTX3), cell-free DNA (cf-DNA), complement components SC5b-9 and C3 and interleukin-6 (IL-6) were recorded as well as platelet ligands and markers of coagulation and fibrinolysis. High values of plasma PTX3 associated with thrombin formation (prothrombin fragments F1+2; r = 0.46, P = 0.05), consumption of platelet ligand fibrinogen (r = -0.70, P < 0.001) and natural anticoagulants antithrombin (AT) (r = -0.74, P < 0.001), protein C (r = -0.77, P < 0.001) and protein S free antigen (r = -0.81, P < 0.001) and a decreased endothelial marker ADAMTS13 (a disintegrin and metalloproteinase with a thrombospondin type 1 domain 13) (r = -0.48, P = 0.04). Plasma level of AT associated with C3 (r = 0.76, P < 0.001), IL-6 (r = -0.56, P = 0.01) and cf-DNA (r = -0.47, P = 0.04). High cf-DNA coincided with increased prothrombin fragments F1+2 (r = 0.47, P = 0.04). Low C3 levels reflecting the activation of complement system through the alternative route predicted loss of all natural anticoagulants (for protein C r = 0.53, P = 0.03 and for protein S free antigen r = 0.64, P = 0.004). Variables depicting altered coagulation follow the new predictive biomarkers of disease severity, especially PTX3, in acute PUUV infection. The findings are consistent with the previous observations of these biomarkers also being predictive for low platelet count and underline the cross-talk of inflammation and coagulation systems in acute PUUV infection. PMID:24751477

  12. Immune Thrombocytopenia

    Kistanguri, Gaurav; McCrae, Keith R

    2013-01-01

    Immune thrombocytopenia (ITP) is a common hematologic disorder characterized by isolated thrombocytopenia. ITP presents as a primary form characterized by isolated thrombocytopenia (platelet count < 100 × 109/L) in the absence of other causes or disorders that may be associated with thrombocytopenia, or a secondary form in which immune thrombocytopenia develops in association with another disorder that is usually immune or infectious. ITP may affect individuals of all ages, with peaks during ...

  13. Drug-induced immune thrombocytopenia.

    van den Bemt, Patricia M L A; Meyboom, Ronald H B; Egberts, Antoine C G

    2004-01-01

    Thrombocytopenia can have several causes, including the use of certain drugs. The mechanism behind drug-induced thrombocytopenia is either a decrease in platelet production (bone marrow toxicity) or an increased destruction (immune-mediated thrombocytopenia). In addition, pseudothrombocytopenia, an in vitro effect, has to be distinguished from true drug-induced thrombocytopenia. This article reviews literature on drug-induced immune thrombocytopenia, with the exception of thrombo-haemorrhagic disorders such as thrombotic thrombocytopenic purpura and heparin-induced thrombocytopenia and thrombosis. A literature search in PubMed combined with a check of the reference lists of all the retrieved articles resulted in 108 articles relevant to the subject. The drug classes that are most often associated with drug-induced immune thrombocytopenia are cinchona alkaloid derivatives (quinine, quinidine), sulfonamides, NSAIDs, anticonvulsants, disease modifying antirheumatic drugs and diuretics. Several other drugs are occasionally described in case reports of thrombocytopenia; an updated review of these case reports can be found on the internet. A small number of epidemiological studies, differing largely in the methodology used, describe incidences in the magnitude of 10 cases per 1 000 000 inhabitants per year. No clear risk factors could be identified from these studies. The underlying mechanism of drug-induced immune thrombocytopenia is not completely clarified, but at least three different types of antibodies appear to play a role (hapten-dependent antibodies, drug-induced, platelet-reactive auto-antibodies and drug-dependent antibodies). Targets for drug-dependent antibodies are glycoproteins on the cell membrane of the platelets, such as glycoprotein (GP) Ib/IX and GPIIb/IIIa. Diagnosis of drug-induced immune thrombocytopenia may consist of identifying clinical symptoms (bruising, petechiae, bleeding), a careful evaluation of the causal relationship of the suspected

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

    von Rossum, Anna; Laher, Ismail; Choy, Jonathan C.

    2015-01-01

    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 transpla...

  15. Immunogenetic markers in immune mediated diseases

    Nikitina-Zake, Liene

    2003-01-01

    The aim of this thesis was to study HLA class II markers, as well as other - MHC and non MHC genes in different immune - mediated diseases, namely, cervical intraepithelial neoplasia (CIN), cervical cancer, juvenile idiopathic arthritis (JIA), mixed connective tissue disease (MCTD) and type I diabetes mellitus (T1 DM). HLA class II genes are located on the short arm of chromosome 6 and are known to be important for pathogenesis of immune - mediated diseases due to the fu...

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

    Li, Li; Han, Da-Kang; Lu, Jun

    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-α induced severe thrombocytopenia.

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

    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.

  18. Immune thrombocytopenia.

    Kistangari, Gaurav; McCrae, Keith R

    2013-06-01

    Immune thrombocytopenia (ITP) is a common hematologic disorder characterized by isolated thrombocytopenia. ITP presents as a primary or a secondary form. ITP may affect individuals of all ages, with peaks during childhood and in the elderly, in whom the age-specific incidence of ITP is greatest. Bleeding is the most common clinical manifestation of ITP. The pathogenesis of ITP is complex, involving alterations in humoral and cellular immunity. Corticosteroids remain the most common first line therapy for ITP. This article summarizes the classification and diagnosis of primary and secondary ITP, as well as the pathogenesis and options for treatment. PMID:23714309

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

    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.

  20. Immune thrombocytopenia.

    Maher, George M

    2014-10-01

    Immune thrombocytopenia (ITP) in children is a relatively uncommon and generally benign condition presenting as abrupt onset of bruising, petechiae and thrombocytopenia in an otherwise healthy child due to production of anti-platelet autoantibodies. Diagnosis is largely clinical and laboratory investigation should be kept to a minimum. Indications for treatment have not been standardized and include bleeding, parental anxiety and quality of life. Multiple treatments are available that have been proven to increase the platelet count; the most commonly employed include IVIG, steroids and WinRho (anti-D). Intracranial hemorrhage is the most serious potential complication but is extremely rare and splenectomy is reserved for chronically symptomatic patients who have not responded to other modalities. Identification of molecular targets may be a promising avenue for future research. PMID:25423768

  1. Immune-mediated extrapyramidal movement disorders, including Sydenham chorea.

    Dale, Russell C

    2013-01-01

    Immune-mediated extrapyramidal movement disorders typically occur in previously healthy children. Immune-mediated movement disorders may occur as a postinfectious, paraneoplastic, or idiopathic process. Sydenham chorea (SC) is the classical poststreptococcal movement and psychiatric disorder, and may be associated with other features of rheumatic fever. The outcome is typically good, although residual chorea, psychiatric disturbance, and relapses are possible. Pediatric autoimmune neuropsychiatric disorders associated with streptococcal infections (PANDAS) is a syndrome of streptococcal-induced tics and obsessive-compulsive disorder. Although a number of investigators have reported an association between streptococcal infection and neuropsychiatric syndromes, the PANDAS hypothesis is controversial. Encephalitis lethargica is an encephalitic illness with parkinsonism, dyskinesias, and psychiatric disturbance as dominant features. The exact disease mechanism is not understood, although an autoimmune process is suspected. NMDA-R encephalitis is a new entity characterized by encephalitis with dramatic psychiatric disturbance, dyskinesias, cognitive alteration, and seizures. Patients have autoantibodies against the NMDA-R that appear to be pathogenic: immune therapies appear warranted to minimize disability. Movement disorders are also described associated with systemic lupus erythematosus and antiphospholipid syndrome. The differential diagnosis and investigation approach of acute-onset movement disorders are also discussed. PMID:23622334

  2. Regulatory T cells in immune-mediated renal disease.

    Ghali, Joanna R; Wang, Yuan Min; Holdsworth, Stephen R; Kitching, A Richard

    2016-02-01

    Regulatory T cells (Tregs) are CD4+ T cells that can suppress immune responses by effector T cells, B cells and innate immune cells. This review discusses the role that Tregs play in murine models of immune-mediated renal diseases and acute kidney injury and in human autoimmune kidney disease (such as systemic lupus erythematosus, anti-glomerular basement membrane disease, anti-neutrophil cytoplasmic antibody-associated vasculitis). Current research suggests that Tregs may be reduced in number and/or have impaired regulatory function in these diseases. Tregs possess several mechanisms by which they can limit renal and systemic inflammatory immune responses. Potential therapeutic applications involving Tregs include in vivo induction of Tregs or inducing Tregs from naïve CD4+ T cells or expanding natural Tregs ex vivo, to use as a cellular therapy. At present, the optimal method of generating a phenotypically stable pool of Tregs with long-lasting suppressive effects is not established, but human studies in renal transplantation are underway exploring the therapeutic potential of Tregs as a cellular therapy, and if successful may have a role as a novel therapy in immune-mediated renal diseases. PMID:26206106

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

    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.

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

    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

  5. Prognosis in canine idiopathic immune-mediated haemolytic anaemia

    Piek, C.J.

    2011-01-01

    Canine idiopathic immune-mediated haemolytic anaemia (iIMHA) is one of the most frequently occurring immune-mediated diseases in dogs. A gel-based Coombs' test was shown to perform equally well as a classical Coombs' test. Since the gel-based Coombs' test can be commercially produced and is easy and

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

    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

  7. What Causes Thrombocytopenia?

    ... this page from the NHLBI on Twitter. What Causes Thrombocytopenia? Many factors can cause thrombocytopenia (a low ... known for sure. Rare and Serious Conditions That Cause Blood Clots Some rare and serious conditions can ...

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

    Ostrowski, Sisse R; Johansson, Per Ingemar

    2011-01-01

    Thrombocytopenia in critical illness predicts a poor clinical outcome. Apart from its role in microvascular thrombus formation, it is widely anticipated that this association is indirect rather than causal. Emerging evidence however indicates that platelets are also immune competent cells. Like...... 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...... per se results in immunodeficiency through loss of platelet-mediated immune functions, and propose that thrombocytopenia induced immunodeficiency in critical illness in part explain the negative predictive value of low or declining platelet count. We propose that rethinking the risks of...

  9. Heparin-induced thrombocytopenia: pathophysiology and new treatment options.

    Harenberg, J; Jörg, I; Fenyvesi, T

    2002-01-01

    Heparin induced thrombocytopenia (HIT) is a severe complication of heparin therapy. It is generally accompanied by a paradoxical decrease in platelets leading to activation of platelets and of the coagulation system. HIT type I is a mild, transient, non-immune disorder. HIT type II is an immune-mediated reaction towards neo-antigen on PF4, which is platelet factor 4 (PF4) that is exposed upon binding to heparins. A low sulfated octasaccharide is required for binding to PF4. The generated immunoglobulines bridge platelets by binding to the FcgRIIa-receptor. In patients with HIT type II heparin/LMW-heparin has to be discontinued immediately upon clinical suspicion. Diagnosis can be confirmed by laboratory tests. As patients are at high risk for or because they have developed thromboembolism, anticoagulation is mandatory, despite thrombocytopenia. Treatment options are danaparoid, r-hirudin, bivalirudin, argatroban, dextransulfate, and dermatansulfate. In future, fondaparinux and ximelagatran may be considered for treatment. PMID:13679659

  10. Mechanisms of conduction block in immune-mediated polyneuropathies

    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. Immune-mediated diseases in primary sclerosing cholangitis

    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

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

    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

  13. Fetal thrombocytopenia : preventive strategies.

    Akker, Eline van den

    2008-01-01

    Intracranial haemorrhage (ICH) among term neonates is associated with neonatal death or lifelong disability. Between all the proposed aetiological mechanisms, including impairments in coagulation, hypoxic-ischemic injury and birth related trauma, thrombocytopenia seems to be the most important predi

  14. Thrombocytopenia - drug induced

    ... the condition is called drug-induced immune thrombocytopenia. Heparin, a blood thinner, is the most common cause ... bleeding Bleeding when you brush your teeth Easy bruising Pinpoint red spots on the skin ( petechiae )

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

    Ken-Ichiro Inoue; Hirohisa Takano

    2011-01-01

    Although the adverse health effects of nanoparticles have been proposed and are being clarified, their aggravating effects on pre-existing pathological conditions have not been fully investigated. In this review, we provide insights into the immunotoxicity of both airborne and engineered nanoparticles as an exacerbating factor on hypersusceptible subjects, especially those with immune-mediated pulmonary inflammation, using our in vivo experimental model. First, we exhibit the effects of nanop...

  16. Mechanisms of conduction block in immune-mediated polyneuropathies

    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 of conduction block plays an important role. Conduction block may originate from demyelination, Na-channel damage at the node of Ranvier, and permanently changed resting membrane potential. Better...

  17. Vaccinations in patients with immune-mediated inflammatory diseases

    Rahier, Jean-Francois; Moutschen, Michel; Van Gompel, Alfons; Van Ranst, Marc; Louis, Edouard; Segaert, Siegfried; Masson, Pierre; De Keyser, Filip

    2010-01-01

    Patients with immune-mediated inflammatory diseases (IMID) such as RA, IBD or psoriasis, are at increased risk of infection, partially because of the disease itself, but mostly because of treatment with immunomodulatory or immunosuppressive drugs. In spite of their elevated risk for vaccine-preventable disease, vaccination coverage in IMID patients is surprisingly low. This review summarizes current literature data on vaccine safety and efficacy in IMID patients treated with immunosuppressive...

  18. Primary immune-mediated neutropenia in a cat

    Waugh, Carly E.; Scott, Katherine D.; Bryan, Laura K.

    2014-01-01

    An 18-month-old male castrated indoor Himalayan cat was presented for recurrent fever, lethargy, and uveitis. Persistent neutropenia was identified and tests for infectious disease and bone marrow cytology were performed. Primary immune-mediated neutropenia was diagnosed and successfully treated. At the time of writing this report, 24 mo after the initial diagnosis. the patient was clinically normal and not receiving therapy.

  19. Thrombocytopenia Associated with Levodopa Treatment

    Ku-Eun Lee

    2013-05-01

    Full Text Available There were few cases of thrombocytopenia associated with levodopa. Herein, we report a patient with Parkinson’s disease, who suffered thrombocytopenia related to long-term use of levodopa.

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

    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

  1. From Lipid Retention to Immune-Mediate Inflammation and Associated Angiogenesis in the Pathogenesis of Atherosclerosis.

    Usman, Ammara; Ribatti, Domenico; Sadat, Umar; Gillard, Jonathan H

    2015-08-26

    Atherosclerosis is a leading cause of mortality and long-term morbidity worldwide. It is a lipoprotein-driven disease that leads to plaque formation at focal areas in the arterial blood vessels through intimal inflammation, necrosis, fibrosis, and calcification. Adventitial and intimal angiogenesis contributes to the progression of intimal hyperplasia and the development of a necrotic core. The volatile nature of an atheromatous plaque is responsible for approximately 60% of symptomatic carotid artery diseases and about 75% of acute coronary events. In this review the pathogenesis of atherosclerosis is discussed from the initial step of lipid retention to advanced stages of immune-mediate inflammation and associated angiogenesis. Mechanisms of plaque rupture are also discussed. PMID:26156748

  2. Novel oral anticoagulants for heparin-induced thrombocytopenia.

    Skelley, Jessica W; Kyle, Jeffrey A; Roberts, Rachel A

    2016-08-01

    To review the use of the novel oral anticoagulant (NOAC) agents for the treatment of heparin-induced thrombocytopenia (HIT) from relevant clinical trial data. A MEDLINE, International Pharmaceutical Abstracts, ClinicalTrials.gov, and Google-Scholar searches (1966-March 2016) were conducted using the keywords: thrombocytopenia, NOACs, dabigatran, apixaban, rivaroxaban, edoxaban, Xa inhibitor, direct thrombin inhibitor. Articles evaluating the new oral anticoagulants for thrombocytopenia published in English and using human subjects were selected. Eight clinical trials were identified. References cited in identified articles were used for additional citations. Approximately 12 million hospitalized patients each year are exposed to heparin for thromboprophylaxis. HIT, an immune-mediated, prothrombotic adverse reaction is a potential complication of heparin therapy. As a result, heparin products must be immediately withdrawn and replaced by alternative anticoagulants to compensate for the thrombotic risk associated with HIT. Limitations exist with the only currently FDA approved heparin alternative, argatroban. NOACs have been considered as potential alternatives to traditional agents based on their pharmacologic activity. Case reports have indicated positive results in patients, with clinical outcomes and tolerability supporting the use of the NOACs as alternative agents in the treatment of HIT. Positive results have been reported for the use of NOACs in the treatment of HIT. Further robust studies are needed for definitive decision making by clinicians. PMID:27102287

  3. Repurposing miltefosine for the treatment of immune-mediated disease?

    Verhaar, Auke P; Wildenberg, Manon E; Peppelenbosch, Maikel P; Hommes, Daniel W; van den Brink, Gijs R

    2014-08-01

    Miltefosine is an ether lipid that was initially developed for cancer treatment in the early 1980s. Miltefosine largely failed development for oncology, although it was approved for the topical treatment of breast cancer metastasis. It was subsequently discovered that miltefosine is a highly effective treatment of visceral Leishmaniasis, a parasitic disease that affects millions worldwide and causes an estimated 30,000 fatalities each year. Oral treatment with miltefosine is generally well tolerated and has relatively few adverse effects. The exact mechanism of action of miltefosine treatment is still under investigation. Its close resemblance to phospholipids allows it to be quickly taken up by cell membranes and affect related processes, such as lipid metabolism and signaling through lipid rafts. These processes play an important role in the immune response and it comes as no surprise that miltefosine has been successfully tested for the treatment of a number of immune-mediated diseases in preclinical models of disease. Drug repurposing of miltefosine for immune-mediated diseases may provide an opportunity to expand the limited number of drugs that are currently available for therapeutic use. PMID:24833702

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

    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.

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

    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.

  6. Immune Thrombocytopenia in Pregnancy

    Stavrou, Evi; McCrae, Keith R

    2009-01-01

    Management of ITP in pregnancy can be a complex and challenging task, and may be complicated by fetal/neonatal thrombocytopenia. Though fetal intracranial hemorrhage is a rare complication of ITP in pregnancy, invasive studies designed to determine the fetal platelet count before delivery are associated with greater risk than that of fetal intracranial hemorrhage, and therefore are discouraged. Moreover, the risk of neonatal bleeding complications does not correlate with the mode of delivery,...

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

    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.

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

    Bisgaard, H; Bønnelykke, K; Stokholm, Jacob

    2014-01-01

    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 are...... currently able to discriminate, and in particular, the indiscriminate lumping together of different diseases into one atopic disease category. Also, the microbiome needs a differentiated understanding, considering balance between microbial groups, diversity and microbial genetic capability. Furthermore, the......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...

  9. Immune Thrombocytopenia in Pregnancy

    Stavrou, Evi; McCrae, Keith R.

    2009-01-01

    SYNOPSIS Management of ITP in pregnancy can be a complex and challenging task, and may be complicated by fetal/neonatal thrombocytopenia. Though fetal intracranial hemorrhage is a rare complication of ITP in pregnancy, invasive studies designed to determine the fetal platelet count before delivery are associated with greater risk than that of fetal intracranial hemorrhage, and therefore are discouraged. Moreover, the risk of neonatal bleeding complications does not correlate with the mode of delivery, and thus cesarean section should be reserved for obstetric indications only. PMID:19932435

  10. Malaria-induced immune thrombocytopenia

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

    1984-01-01

    On return from Liberia, a previously healthy 36-year-old man showed signs of malaria accompanied by severe haemolysis and slight thrombocytopenia. We found evidence of a platelet-associated IgG being responsible for the thrombocytopenia, inasmuch as the direct platelet suspension immunofluorescen...

  11. The Gut Microbiota in Immune-Mediated Inflammatory Diseases

    Forbes, Jessica D.; Van Domselaar, Gary; Bernstein, Charles N.

    2016-01-01

    The collection of microbes and their genes that exist within and on the human body, collectively known as the microbiome has emerged as a principal factor in human health and disease. Humans and microbes have established a symbiotic association over time, and perturbations in this association have been linked to several immune-mediated inflammatory diseases (IMID) including inflammatory bowel disease, rheumatoid arthritis, and multiple sclerosis. IMID is a term used to describe a group of chronic, highly disabling diseases that affect different organ systems. Though a cornerstone commonality between IMID is the idiopathic nature of disease, a considerable portion of their pathobiology overlaps including epidemiological co-occurrence, genetic susceptibility loci and environmental risk factors. At present, it is clear that persons with an IMID are at an increased risk for developing comorbidities, including additional IMID. Advancements in sequencing technologies and a parallel explosion of 16S rDNA and metagenomics community profiling studies have allowed for the characterization of microbiomes throughout the human body including the gut, in a myriad of human diseases and in health. The main challenge now is to determine if alterations of gut flora are common between IMID or, if particular changes in the gut community are in fact specific to a single disease. Herein, we review and discuss the relationships between the gut microbiota and IMID. PMID:27462309

  12. The Gut Microbiota in Immune-Mediated Inflammatory Diseases.

    Forbes, Jessica D; Van Domselaar, Gary; Bernstein, Charles N

    2016-01-01

    The collection of microbes and their genes that exist within and on the human body, collectively known as the microbiome has emerged as a principal factor in human health and disease. Humans and microbes have established a symbiotic association over time, and perturbations in this association have been linked to several immune-mediated inflammatory diseases (IMID) including inflammatory bowel disease, rheumatoid arthritis, and multiple sclerosis. IMID is a term used to describe a group of chronic, highly disabling diseases that affect different organ systems. Though a cornerstone commonality between IMID is the idiopathic nature of disease, a considerable portion of their pathobiology overlaps including epidemiological co-occurrence, genetic susceptibility loci and environmental risk factors. At present, it is clear that persons with an IMID are at an increased risk for developing comorbidities, including additional IMID. Advancements in sequencing technologies and a parallel explosion of 16S rDNA and metagenomics community profiling studies have allowed for the characterization of microbiomes throughout the human body including the gut, in a myriad of human diseases and in health. The main challenge now is to determine if alterations of gut flora are common between IMID or, if particular changes in the gut community are in fact specific to a single disease. Herein, we review and discuss the relationships between the gut microbiota and IMID. PMID:27462309

  13. Eosinophilic esophagitis: an immune-mediated esophageal disease.

    Weinbrand-Goichberg, Jenny; Segal, Idit; Ovadia, Adi; Levine, Arie; Dalal, Ilan

    2013-07-01

    Eosinophilic esophagitis (EoE) is an emerging disease defined by esophageal dysfunction, by typical endoscopic findings and by abnormal eosinophilic inflammation within the esophagus. Eosinophilic accumulation in the esophagus occurs as a result of esophageal overexpression of pro-inflammatory mediators, including T cells and mast cells, cytokines such as interleukin (IL)-13, IL-5 and IL-15, as well as chemoattractants (eotaxin and transforming growth factor-β1, fibroblast growth factor and the newly characterized gene--thymic stromal lymphopoietin, which is a key regulator of allergic sensitization initiation). The role of allergy, particularly food allergy in EoE is indisputable, as elimination diet is a proven commonly used treatment for the disease. However, unlike classical immediate IgE-mediated reaction to allergen, EoE is associated with an altered immune response, characterized by a combination of IgE-mediated and non-IgE-mediated mechanisms. In this review, we aim to discuss the many typical aspects of EoE as opposed to other entities involving the esophagus, with focusing on the aberrant immune-mediated key players contributing to the pathogenesis of this unique disease. PMID:23579771

  14. Treatment of immune-mediated hemolytic anemia in dogs with cyclophosphamide.

    Burgess, K; Moore, A; Rand, W; Cotter, S M

    2000-01-01

    A review of 60 cases of immune-mediated hemolytic anemia (IMHA) in the dog was performed in order to characterize the disease and to identify potential prognostic indicators. Dogs ranged in age from 1 to 13 years, with a mean age of 6.5 years. The 2 most commonly affected breeds were Cocker Spaniels and Labrador Retrievers. Fifty-two of the 60 dogs tested (87%) were autoagglutination positive and spherocytes were present in 45 (75%). Forty-one (89%) of 46 patients tested positive for the presence of immunoglobulin on the red blood cell surface (Coombs assay). The most common clinical signs at presentation were lethargy, weakness, pale mucous membranes, icterus, hemoglobinuria, and anorexia. PCV less than 25% was present in 59 (98%) dogs. At the time of presentation, 35 dogs (58%) had a nonregenerative anemia, whereas 25 patients (42%) had a regenerative response. Thrombocytopenia was seen in 41 (68%) dogs. Nine of 34 dogs (26%) had a prolonged prothrombin time, 19 of 34 (56%) had a prolonged activated partial thromboplastin clotting time, and 12 of 34 (35%) had abnormal fibrinogen concentrations. All dogs received prednisone at immunosuppressive doses (2.2-4.4 mg/kg PO as a single or divided dose every 24 hours) and cyclophosphamide as primary therapy. Forty-one dogs (63%) received cyclophosphamide at 50 mg/m2 q24h for 4 days, whereas 9 dogs (15%) received an initial high dose (200 mg/m2) followed by 3 days of a lower dose (50 mg/m2 q24h). No statistical difference in survival times was found for either protocol. Thirteen dogs were treated with azathioprine in addition to cyclophosphamide and prednisone. The median survival time of dogs that received all 3 drugs was 370 days as compared to 9 days for those dogs that were treated with cyclophosphamide and prednisone alone. Thirty-one (52%) dogs died from the disease, 13 (22%) dogs were alive, and 15 (25%) dogs were lost to follow-up. The median length of survival for all dogs was 21 days. Eight dogs that were

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

    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

  16. Mesenchymal Stem Cells in Immune-Mediated Bone Marrow Failure Syndromes

    Maria-Christina Kastrinaki; Konstantia Pavlaki; Batsali, Aristea K.; Elisavet Kouvidi; Irene Mavroudi; Charalampos Pontikoglou; Papadaki, Helen A

    2013-01-01

    Immune-mediated bone marrow failure syndromes (BMFS) are characterized by ineffective marrow haemopoiesis and subsequent peripheral cytopenias. Ineffective haemopoiesis is the result of a complex marrow deregulation including genetic, epigenetic, and immune-mediated alterations in haemopoietic stem/progenitor cells, as well as abnormal haemopoietic-to-stromal cell interactions, with abnormal release of haemopoietic growth factors, chemokines, and inhibitors. Mesenchymal stem/stromal cells (MS...

  17. CXCL9, but not CXCL10, Promotes CXCR3-Dependent Immune-Mediated Kidney Disease

    Menke, Julia; Zeller, Geraldine C.; Kikawada, Eriya; Means, Terry K.; Huang, Xiao R; Lan, Han Y.; Lu, Bao; Farber, Joshua; Luster, Andrew D.; Kelley, Vicki R.

    2008-01-01

    Chemokines are instrumental in macrophage- and T cell–dependent diseases. The chemokine CCL2 promotes kidney disease in two models of immune-mediated nephritis (MRL-Faslpr mice and the nephrotoxic serum nephritis model), but evidence suggests that multiple chemokines are involved. For identification of additional therapeutic targets for immune-mediated nephritis, chemokine ligands and receptors in CCL2−/− and wild-type (WT) MRL-Faslpr kidneys were profiled. The focus was on intrarenal chemoki...

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

    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.

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

    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. PMID:27366241

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

    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.

  1. Thrombocytopenia and leptospirosis Trombocitopenia e leptospirose

    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

  2. Hantavirus Infection: A Neglected Diagnosis in Thrombocytopenia and Fever?

    Denecke, Barbara; Bigalke, Boris; Haap, Michael; Overkamp, Dietrich; Lehnert, Hendrik; Haas, Christian S.

    2010-01-01

    Thrombocytopenia, fever, and acute renal failure are characteristic features of nephropathia epidemica, the predominant hantavirus infection in Europe. However, clinical presentation and blood cell counts may point to other disorders, such as a hematologic disease, particularly when impairment of renal function is not evident. This differential diagnosis often results in further extensive and unnecessary testing. We describe 3 patients with hantavirus infection with no renal failure, in whom ...

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

    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...

  4. Efficacy observation of recombinant human interleukin-11 (Ⅰ) in treatment of chemotherapy induced thrombocytopenia in patients with acute leukemia%重组人白介素-11(Ⅰ)治疗急性白血病化疗后血小板减少的疗效观察

    蒋锐; 谢明; 王龙; 杨波; 江炳东

    2012-01-01

    目的 观察重组人白介素-11(Ⅰ)治疗急性白血病化疗后血小板减少的疗效及安全性.方法 68例急性白血病患者强化治疗后出现血小板减少,分为治疗组35例,对照组33例.治疗组使用重组人白介素-11(Ⅰ)治疗,25μg/kg·d皮下注射,直至血小板连续2 d>50×109/L或>100×109/L.对照组不使用任何升血小板药物.结果 治疗组血小板减少持续时间缩短,血小板输注量减少,血小板绝对值较对照组高,差异有显著性.主要不良反应为乏力、头痛、肌痛和浮肿.结论 重组人白介素-11(Ⅰ)治疗急性白血病化疗后血小板减少疗效显著,且不良反应轻微,值得推广.%[Objective] To observe the effectiveness and safety of recombinant human interleukin-11 ( I ) in the treatment of chemotherapy induced thrombocytopenia in patients with acute leukemia. [Methods] Sixty-eight patients with chemotherapy induced thrombocytopenia after intensive treatment of acute leukemia were divided into treatment group including thirty-five patients and control group including thirty-three patients. Patients in treatment group were given subcutaneous injection of recombinant human interleukin-11 (Ⅰ) at the dose of 25 μg/kg·d. Drug withdrawal was conducted after platelet count being on two consecutive days than 50×109/L or higher than 100×109/ L. Patients in control group were not use any elevating platelet drugs. [Results] In treatment group ,the thrombocytopenia duration was shortened; the platelet transfusion volume was reduced; the platelet absolute value was higher than the control group. The difference was statistically significant. The main ADR were fatigue, headache, muscle pain, dropsy. [Conclusion] Recombinant human interleukin 11(Ⅰ) is effective in the treatment group of chemotherapy induced thrombocytopenia in patients with acute leukemia and its adverse reactions are slight. It is worth promoting.

  5. Management of symptomatic thrombocytopenia associated with dengue haemorrhagic fever

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

  6. Complete Penile Necrosis in a Patient With Heparin-induced Thrombocytopenia: A Case Report*

    Blais, Anne-Sophie; Deschênes Rompré, Marie-Pier; Lacombe, Louis

    2014-01-01

    Penile necrosis is a rare condition that has been mostly described in association with diabetes mellitus and end-stage renal disease. We report an unusual case of acute penile necrosis because of heparin-induced thrombocytopenia. A 75-year-old man presented with acute renal failure and experienced cardiac complications during the hospitalization. The patient was treated twice with intravenous heparin. He developed symptoms of penile necrosis 4 days after the reintroduction of heparin. At that moment, the platelet count dropped by 61%, and the analysis of heparin-pf4 antibodies was positive for heparin-induced thrombocytopenia. The patient underwent a total penectomy and a perineal urethrostomy. PMID:26954936

  7. Heparin-Induced Thrombocytopenia Antibody Test

    ... Thrombocytopenia Platelet Factor 4 Antibody Related tests: Complete Blood Count , Platelet Count , Serotonin Release Assay, Heparin-induced Platelet Aggregation All content on Lab Tests Online has been ...

  8. Immune-mediated haemolytic anaemia associated with a sarcoma in a flat-coated retriever.

    Mellanby, R J; Holloway, A; Chantrey, J; Herrtage, M E; Dobson, J M

    2004-01-01

    A seven-year-old flat-coated retriever presented with a history of lethargy, dyspnoea and inappetence of several days' duration. Clinical examination revealed pale mucous membranes and tachypnoea, and haematology demonstrated marked autoagglutination. Thoracic radiographs revealed an increased opacity in the perihilar region. The owners declined further evaluation and the dog was treated symptomatically with immunosuppressive doses of prednisolone and azathioprine. The dog's demeanour improved, although it was eventually euthanased seven weeks later because of dysphagia and worsening dyspnoea. Postmortem examination revealed a widespread, poorly differentiated sarcoma involving the lungs, pericardium, thoracic lymph nodes and spleen. Immune-mediated haemolytic anaemia is a well recognised condition in dogs and is occasionally associated with neoplastic conditions. This is the first case report to describe immune-mediated haemolytic anaemia associated with a diffuse, poorly differentiated sarcoma. PMID:14756205

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

    Madsen, Caroline B; Lavrsen, Kirstine; Steentoft, Catharina; Vester-Christensen, Malene B; Clausen, Henrik; Wandall, Hans H; Pedersen, Anders Elm

    2013-01-01

    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...... 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...

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

    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.

  11. Bilateral regulatory action of corticotropin-releasing hormone on immune-mediated inflammation

    YANG Ce; JIANG Jian-xin

    2009-01-01

    @@ In trauma, infection and hemorrhagic shock derived stress, primary and secondary injury may result in severe derangement in the internal environment. The abnormal changes of immune-mediated inflammation interfere its pathogenesis and development directly. In recent years, various aspects of neuroendocrine responses, especially the regulatory effects of hypothalamic-pituitary-adrenal and sympathetico-adrenomedullary axes in inflammatory diseases have been the focus of research.

  12. Adalimumab safety and mortality rates from global clinical trials of six immune-mediated inflammatory diseases

    Burmester, G R; Mease, P; Dijkmans, B A C; Gordon, K; Lovell, D; Panaccione, R.; J. Perez; Pangan, A L

    2009-01-01

    Objectives: Clinical trials of tumour necrosis factor antagonists have raised questions about the potential risk of certain serious adverse events (SAE). To assess the safety of adalimumab in rheumatoid arthritis (RA) over time and across five other immune-mediated inflammatory diseases and to compare adalimumab malignancy and mortality rates with data on the general population. Methods: This analysis included 19 041 patients exposed to adalimumab in 36 global clinical trials in RA, psoriatic...

  13. The relationship between intestinal parasites and some immune-mediated intestinal conditions

    Mohammadi, Rasoul; Hosseini-Safa, Ahmad; Ehsani Ardakani, Mohammad Javad; Rostami-Nejad, Mohammad

    2015-01-01

    Over the last decades, the incidence of infestation by minor parasites has decreased in developed countries. Infectious agents can also suppress autoimmune and allergic disorders. Some investigations show that various protozoa and helminthes are connected with the main immune-mediated intestinal conditions including celiac disease (CD), inflammatory bowel diseases (IBD) and irritable bowel syndrome (IBS). Celiac disease is a digestive and autoimmune disorder that can damage the small intestin...

  14. Immune-mediated haemolytic anaemia : possible association with Ancylostoma caninum infection in three dogs : case report

    Lobetti, R. G.; T. Schoeman

    2001-01-01

    Immune-mediated haemolytic anaemia (IMHA) may be primary or secondary. In primary IMHA, no underlying cause can be found, whereas secondary IMHA is triggered by an underlying cause, such as neoplasia, infectious diseases, or drugs. This paper describes 3 dogs with typical signs of IMHA that was possibly associated with the intestinal parasite Ancylostoma caninum. As intestinal helminths can be difficult to diagnose on faecal examination, it would be pertinent to performmultiple faecal examina...

  15. Immune-mediated keratoconjunctivitis sicca in dogs: current perspectives on management

    Dodi PL

    2015-01-01

    Pier Luigi Dodi Department of Veterinary Medicine Sciences, University of Parma, Parma, Italy Abstract: Keratoconjunctivitis sicca (KCS) is a frequent canine ophthalmic disease, resulting from the deficiency of one or more elements in the precorneal tear film. There are different known causes of KCS in dogs, including congenital, metabolic, infectious, drug induced, neurogenic, radiation, iatrogenic, idiopathic, and immune mediated, though the last one is the most prevalent form in dogs. Ini...

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

    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

  17. Antiplatelet antibodies in oxaliplatin-induced immune thrombocytopenia

    McNamara, Michael J; Curtis, Brian R; McCrae, Keith R

    2014-01-01

    Lesson Drug-induced immune thrombocytopenia may be potentially fatal; here we report the development of severe thrombocytopenia with strong oxaliplatin-dependent antiplatelet antibodies. PMID:25057402

  18. Incidence of Thrombocytopenia in Idiopathic Hyperbilirubinemic Newborns

    Hassan Boskabadi

    2014-06-01

    Conclusion: This study determines higher rate of thrombocytopenia among idiopathic hyperbilirubinemic neonates (36% and helps the practitioner to be aware of this association and avoid unnecessary investigations.We did not find a significant correlation between serum bilirubin values and thrombocytopenia.

  19. Noninvasive low-level laser therapy for thrombocytopenia.

    Zhang, Qi; Dong, Tingting; Li, Peiyu; Wu, Mei X

    2016-07-27

    Thrombocytopenia is a common hematologic disorder that is managed primarily by platelet transfusions. We report here that noninvasive whole-body illumination with a special near-infrared laser cures acute thrombocytopenia triggered by γ-irradiation within 2 weeks in mice, as opposed to a 5-week recovery time required in controls. The low-level laser (LLL) also greatly accelerated platelet regeneration in the presence of anti-CD41 antibody that binds and depletes platelets, and prevented a severe drop in platelet count caused by a common chemotherapeutic drug. Mechanistically, LLL stimulated mitochondrial biogenesis specifically in megakaryocytes owing to polyploidy of the cells. LLL also protected megakaryocytes from mitochondrial injury and apoptosis under stress. The multifaceted effects of LLL on mitochondria bolstered megakaryocyte maturation; facilitated elongation, branching, and formation of proplatelets; and doubled the number of platelets generated from individual megakaryocytes in mice. LLL-mediated platelet biogenesis depended on megakaryopoiesis and was inversely correlated with platelet counts, which kept platelet biogenesis in check and effectively averted thrombosis even after repeated uses, in sharp contrast to all current agents that stimulate the differentiation of megakaryocyte progenitors from hematopoietic stem cells independently of platelet counts. This safe, drug-free, donor-independent modality represents a paradigm shift in the prophylaxis and treatment of thrombocytopenia. PMID:27464749

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

    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.

  1. Fatal anaphylactoid reaction associated with heparin-induced thrombocytopenia.

    Singla, Atul; Amini, Mohammad R; Alpert, Martin A; Gornik, Heather L

    2013-06-01

    Acute systemic (anaphylaxis and anaphylactoid) reactions have been well described in patients with heparin-induced thrombocytopenia (HIT). Both necrotizing and non-necrotizing skin lesions at heparin injection sites have been reported and may occur in 10-20% of patients with HIT. We report herein a patient treated with subcutaneous enoxaparin sodium who developed non-necrotizing erythematous skin lesions at enoxaparin sodium injection sites. A subsequent intravenous bolus of unfractionated heparin produced a fatal anaphylactoid reaction. This suggests that caution should be exercised in the administration of intravenous heparin to patients with non-necrotizing erythematous skin lesions at prior heparin injection sites. PMID:23579400

  2. How we manage patients with heparin induced thrombocytopenia.

    Scully, Marie; Gates, Carolyn; Neave, Lucy

    2016-07-01

    Heparin induced thrombocytopenia (HIT) remains a rare, but significant, condition related to mortality and morbidity. The incidence has decreased with reduced use of unfractionated heparin, with the exception of cardiac surgery. Due to the high risk of thrombosis, a switch to a non-heparin anticoagulant is required, until platelet counts normalize. Within the acute setting, argatroban, fondaparinux and direct acting oral anticoagulants (DOACS) are therapeutic options. In patients with HIT-associated thrombosis or who require long-term anticoagulation, warfarin remains the preference, but DOACs are attractive alternatives. PMID:27097741

  3. Effector CD4+ T cell expression signatures and immune-mediated disease associated genes.

    Wei Zhang

    Full Text Available Genome-wide association studies (GWAS in immune-mediated diseases have identified over 150 associated genomic loci. Many of these loci play a role in T cell responses, and regulation of T cell differentiation plays a critical role in immune-mediated diseases; however, the relationship between implicated disease loci and T cell differentiation is incompletely understood. To further address this relationship, we examined differential gene expression in naïve human CD4+ T cells, as well as in in vitro differentiated Th1, memory Th17-negative and Th17-enriched CD4+ T cells subsets using microarray and RNASeq. We observed a marked enrichment for increased expression in memory CD4+ compared to naïve CD4+ T cells of genes contained among immune-mediated disease loci. Within memory T cells, expression of disease-associated genes was typically increased in Th17-enriched compared to Th17-negative cells. Utilizing RNASeq and promoter methylation studies, we identified a differential regulation pattern for genes solely expressed in Th17 cells (IL17A and CCL20 compared to genes expressed in both Th17 and Th1 cells (IL23R and IL12RB2, where high levels of promoter methylation are correlated to near zero RNASeq levels for IL17A and CCL20. These findings have implications for human Th17 celI plasticity and for the regulation of Th17-Th1 expression signatures. Importantly, utilizing RNASeq we found an abundant isoform of IL23R terminating before the transmembrane domain that was enriched in Th17 cells. In addition to molecular resolution, we find that RNASeq provides significantly improved power to define differential gene expression and identify alternative gene variants relative to microarray analysis. The comprehensive integration of differential gene expression between cell subsets with disease-association signals, and functional pathways provides insight into disease pathogenesis.

  4. Pulmonary thromboembolism associated with immune-mediated hemolytic anemia in dogs: ten cases (1982-1987)

    Pulmonary thromboembolism was confirmed at necropsy in 10 (32.2%) of 31 dogs treated for immune-mediated hemolytic anemia. Radiographic findings associated with thromboembolism included pronounced interstitial lung pattern and small amounts of pleural effusion. Variables associated with significantly higher incidence of pulmonary thromboembolism included hyperbilirubinemia (P = 0.023), negative Coombs test result (P = 0.032), and presence of an indwelling catheter (P = 0.04). There was a tendency (P = 0.06) for association of higher number of whole blood transfusions with pulmonary thromboembolism

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

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

    2014-01-01

    We established a model of immune-mediated bone marrow (BM) failure in C57BL/6 (B6) mice with 6.5 Gy total body irradiation (TBI) followed by the infusion of 4–10 × 106 lymph node (LN) cells/recipient from FVB/N (FVB) donors. Forty-three percent 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 TBI dose to 5 Gys or altering the LN source from FVB to BALB/...

  6. Thrombocytopenia in Brucellosis: A Case Report

    A Nikavar; Z Kalbasi

    1997-01-01

    A 6-year old is presented with fever, ecchymosis and knee pain. Positive Wright and 2ME tests were in favor of Brucellosis. Blood culture for Brucella was also positive. Blood cells count showed a Thrombocytopenia of 35.000. Platelets returned to normal by mere antibiotic treatment of Brucellosis. Pancytopenia or any isolated deficiency of hematologic cell lines can be a complication of Brucellosis. This urges the clinicians to think of Brucellosis in patients with Thrombocytopenia.

  7. Thrombocytopenia in Brucellosis: A Case Report

    A Nikavar

    1997-05-01

    Full Text Available A 6-year old is presented with fever, ecchymosis and knee pain. Positive Wright and 2ME tests were in favor of Brucellosis. Blood culture for Brucella was also positive. Blood cells count showed a Thrombocytopenia of 35.000. Platelets returned to normal by mere antibiotic treatment of Brucellosis. Pancytopenia or any isolated deficiency of hematologic cell lines can be a complication of Brucellosis. This urges the clinicians to think of Brucellosis in patients with Thrombocytopenia.

  8. Practice Bulletin No. 166: Thrombocytopenia in Pregnancy.

    2016-09-01

    Thrombocytopenia in pregnant women is diagnosed frequently by obstetricians because platelet counts are included with automated complete blood cell counts (CBCs) obtained during routine prenatal screening (). Although most U.S. health care providers are trained using U.S. Conventional Units, most scientists, journals, and countries use Système International (SI) units. The laboratory results reported in U.S. Conventional Units can be converted to SI Units or vice versa by using a conversion factor. The conversion factor for platelet count results is 1.0 (ie, to convert from x 103/µL, multiply by 1.0, to get x 109/L). Thrombocytopenia, defined as a platelet count of less than 150 x 109/L, is common and occurs in 7-12% of pregnancies (). Thrombocytopenia can result from a variety of physiologic or pathologic conditions, several of which are unique to pregnancy. Some causes of thrombocytopenia are serious medical disorders that have the potential for maternal and fetal morbidity. In contrast, other conditions, such as gestational thrombocytopenia, are benign and pose no maternal or fetal risks. Because of the increased recognition of maternal and fetal thrombocytopenia, there are numerous controversies about obstetric management of this condition. Clinicians must weigh the risks of maternal and fetal bleeding complications against the costs and morbidity of diagnostic tests and invasive interventions. PMID:27548554

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

    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.

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

    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.

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

    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. PMID:25555453

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

    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

  13. Immune mediated mechanism for thrombosis: antiphospholipid antibody binding to platelet membranes.

    M. A. Khamashta; Harris, E N; Gharavi, A E; Derue, G; Gil, A.; Vázquez, J. J.; Hughes, G R

    1988-01-01

    Because thrombocytopenia occurs frequently in patients with anticardiolipin (aCL) antibodies and thrombosis, some investigators have proposed that aCL antibodies may play a direct part in thrombosis by binding and activating platelets. To test this proposal experiments were performed to determine whether aCL antibodies can bind platelets. Preincubation of aCL positive sera with freeze-thawed platelets caused significant inhibition of aCL activity in four serum samples tested. Antibodies with ...

  14. Genetic associations and functional characterization of M1 aminopeptidases and immune-mediated diseases.

    Agrawal, N; Brown, M A

    2014-12-01

    Endosplasmic reticulum aminopeptidase 1 (ERAP1), endoplasmic reticulum aminopeptidase 2 (ERAP2) and puromycin-sensitive aminopeptidase (NPEPPS) are key zinc metallopeptidases that belong to the oxytocinase subfamily of M1 aminopeptidase family. NPEPPS catalyzes the processing of proteosome-derived peptide repertoire followed by trimming of antigenic peptides by ERAP1 and ERAP2 for presentation on major histocompatibility complex (MHC) Class I molecules. A series of genome-wide association studies have demonstrated associations of these aminopeptidases with a range of immune-mediated diseases such as ankylosing spondylitis, psoriasis, Behçet's disease, inflammatory bowel disease and type I diabetes, and significantly, genetic interaction between some aminopeptidases and HLA Class I loci with which these diseases are strongly associated. In this review, we highlight the current state of understanding of the genetic associations of this class of genes, their functional role in disease, and potential as therapeutic targets. PMID:25142031

  15. Interventions to Improve Adherence in Patients with Immune-Mediated Inflammatory Disorders: A Systematic Review.

    Fanny Depont

    Full Text Available In patients with immune-mediated inflammatory disorders, poor adherence to medication is associated with increased healthcare costs, decreased patient satisfaction, reduced quality of life and unfavorable treatment outcomes.To determine the impact of different interventions on medication adherence in patients with immune-mediated inflammatory disorders.Systematic review.MEDLINE, EMBASE and Cochrane Library.Included studies were clinical trials and observational studies in adult outpatients treated for psoriasis, Crohn's disease, ulcerative colitis, rheumatoid arthritis, spondyloarthritis, psoriatic arthritis or multiple sclerosis.Intervention approaches were classified into four categories: educational, behavioral, cognitive behavioral, and multicomponent interventions. The risk of bias/study limitations of each study was assessed using the GRADE system.Fifteen studies (14 clinical trials and one observational study met eligibility criteria and enrolled a total of 1958 patients. Forty percent of the studies (6/15 was conducted in patients with inflammatory bowel disease, half (7/15 in rheumatoid arthritis patients, one in psoriasis patients and one in multiple sclerosis patients. Seven out of 15 interventions were classified as multicomponent, four as educational, two as behavioral and two as cognitive behavioral. Nine studies, of which five were multicomponent interventions, had no serious limitations according to GRADE criteria. Nine out of 15 interventions showed an improvement of adherence: three multicomponent interventions in inflammatory bowel disease; one intervention of each category in rheumatoid arthritis; one multicomponent in psoriasis and one multicomponent in multiple sclerosis.The assessment of interventions designed for increasing medication adherence in IMID is rare in the literature and their methodological quality may be improved in upcoming studies. Nonetheless, multicomponent interventions showed the strongest evidence for

  16. Molecular tracking of antigen-specific T cell clones in neurological immune-mediated disorders

    Muraro, Paolo A.; Wandinger, Klaus-Peter; Bielekova, Bibiana; Gran, Bruno; Marques, Adriana; Utz, Ursula; McFarland, Henry F.; Jacobson, Steve; Martin, Roland

    2016-01-01

    Summary T cells recognizing self or microbial antigens may trigger or reactivate immune-mediated diseases. Monitoring the frequency of specific T cell clonotypes to assess a possible link with the course of disease has been a difficult task with currently available technology. Our goal was to track individual candidate pathogenic T cell clones, selected on the basis of previous extensive studies from patients with immune-mediated disorders of the CNS, including multiple sclerosis, HTLV-I associated myelopathy/tropical spastic paraparesis (HAM/ TSP) and chronic Lyme neuroborreliosis. We developed and applied a highly specific and sensitive technique to track single CD4+ and CD8+ T cell clones through the detection and quantification of T cell receptor (TCR) α or β chain complementarity-determining region 3 transcripts by real-time reverse transcriptase (RT)-PCR. We examined the frequency of the candidate pathogenic T cell clones in the peripheral blood and CSF during the course of neurological disease. Using this approach, we detected variations of clonal frequencies that appeared to be related to clinical course, significant enrichment in the CSF, or both. By integrating clono-type tracking with direct visualization of antigen-specific staining, we showed that a single T cell clone contributed substantially to the overall recognition of the viral peptide/MHC complex in a patient with HAM/ TSP. T cell clonotype tracking is a powerful new technology enabling further elucidation of the dynamics of expansion of autoreactive or pathogen-specific T cells that mediate pathological or protective immune responses in neurological disorders. PMID:12477694

  17. Plasma Kallikrein-Kinin system mediates immune-mediated renal injury in trichloroethylene-sensitized mice.

    Wang, Hui; Zhang, Jia-Xiang; Ye, Liang-Ping; Li, Shu-Long; Wang, Feng; Zha, Wan-Sheng; Shen, Tong; Wu, Changhao; Zhu, Qi-Xing

    2016-07-01

    Trichloroethylene (TCE) is a major environmental pollutant. An immunological response is a newly-recognized mechanism for TCE-induced kidney damage. However, the role of the plasma kallikrein-kinin system (KKS) in immune-mediated kidney injury has never been examined. This study aimed to explore the role of the key components of the KKS, i.e. plasma kallikrein (PK), bradykinin (BK) and its receptors B1R and B2R, in TCE-induced kidney injury. A mouse model of skin sensitization was used to explore the mechanism of injury with or without a PK inhibitor PKSI. Kidney function was evaluated by measuring blood urea nitrogen (BUN) and creatinine (Cr) in conjunction with histopathologic characterization. Plasma BK was determined by ELISA; Renal C5b-9 membrane attack complex was evaluated by immunohistochemistry. Expression of BK and PK in the kidney was detected by immunofluorescence. mRNA and protein levels of B1R and B2R were assessed by real-time qPCR and Western blot. As expected, numerous inflammatory cell infiltration and tubular epithelial cell vacuolar degeneration were observed in TCE-sensitized mice. Moreover, serum BUN and Cr and plasma BK were increased. In addition, deposition of BK, PK and C5b-9 were observed and B1R and B2R mRNA and proteins levels were up-regulated. Pre-treatment with PKSI, a highly selective inhibitor of PK, alleviated TCE-induced renal damage. In addition, PKSI attenuated TCE-induced up-regulation of BK, PK and its receptors and C5b-9. These results provided the first evidence that activation of the KKS contributed to immune-mediated renal injury induced by TCE and also helped to identify the KKS as a potential therapeutic target for mitigating chemical sensitization-induced renal damage. PMID:27027470

  18. Octreotide-induced thrombocytopenia: a case report

    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.

  19. Alleviating anemia and thrombocytopenia in myelofibrosis patients.

    Cervantes, Francisco; Correa, Juan-Gonzalo; Hernandez-Boluda, Juan Carlos

    2016-05-01

    Anemia and thrombocytopenia are frequent clinical manifestations of myelofibrosis as well as important prognostic factors of the disease. Concerning the treatment of anemia, the first step should be the correction of reversible contributing factors, such as possible iron, folate and vitamin B12 deficiency. Then, treatment options include erythropoiesis stimulating agents, androgens, immunomodulating drugs, corticosteroids, and splenectomy. Anemia responses may also be observed in some patients treated with JAK inhibitors. However, most patients eventually fail to such therapies and become transfusion dependent. Some of the aforementioned therapies can also improve thrombocytopenia, but the responses are usually observed in patients with moderate platelet count decrease. Allogeneic hematopoietic stem cell transplantation, the only curative treatment of myelofibrosis, can be an alternative for selected patients with cytopenias who are refractory to conventional therapies. However, for the majority of patients, the management of anemia and severe thrombocytopenia remains an unmet need. PMID:26891375

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

    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

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

    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...

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

    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

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

    T. Dörner; N. Kinnman; P.P. Tak

    2010-01-01

    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 investig

  4. Pathobiology and Treatment of Hepatitis Virus-Related Thrombocytopenia

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

    2009-01-01

    Thrombocytopenia is a well recognized complication of infections, including those from hepatotropic viruses. Thrombocytopenia may actually be the only manifestation of vital hepatitis, which should therefore be considered in the differential diagnosis of primary immune thrombocytopenia (ITP). The mechanisms of thrombocytopenia associated with viral hepatitis vary widely depending on the specific infectious agent and the severity of liver disease. Most of the studies have described thrombocyto...

  5. [Cerebellar hemangioblastoma and thrombocytopenia: Report of one case].

    Patiño G, Santiago

    2016-04-01

    The association between vascular tumors and thrombocytopenia is rare. Kasabach-Merritt Syndrome is seen in childhood and is characterized by hemangiomas and thrombocytopenia. A 42 years-old man with a cerebellar hemangioblastoma and thrombocytopenia, admitted with a subarachnoid hemorrhage is reported. The patient was operated and required a splenectomy to manage the thrombocytopenia. After the splenectomy the patient developed a subdural hematoma that was operated. Despite the surgical treatment, the patient died. PMID:27401386

  6. Complete Penile Necrosis in a Patient With Heparin-induced Thrombocytopenia: A Case Report

    Anne-Sophie Blais

    2014-01-01

    Full Text Available Penile necrosis is a rare condition that has been mostly described in association with diabetes mellitus and end-stage renal disease. We report an unusual case of acute penile necrosis because of heparin-induced thrombocytopenia. A 75-year-old man presented with acute renal failure and experienced cardiac complications during the hospitalization. The patient was treated twice with intravenous heparin. He developed symptoms of penile necrosis 4 days after the reintroduction of heparin. At that moment, the platelet count dropped by 61%, and the analysis of heparin-pf4 antibodies was positive for heparin-induced thrombocytopenia. The patient underwent a total penectomy and a perineal urethrostomy.

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

    Mojgan Karahmadi; Elmira Layegh; Samira Layegh; Maryam Keypour

    2011-01-01

    Background: Anorexia nervosa (AN) is a difficult-to-treat psychosomatic disease. Very few cases of acute liver failure associated with AN have been described. We describe one patient who was affected by AN and presented high level increase of serum liver enzymes, along with sever thrombocytopenia. Then, we discuss the possible etiopathogenic factors. Methods: A 14-year-old boy with AN was admitted in the pediatric psychiatric emergency department of Alzahra Hospital with impaired electrol...

  8. Frequency of thrombocytopenia in plasmodium vivax malaria

    Objective: To determine the frequency of thrombocytopenia in Plasmodium vivax (P.vivax) malaria cases at two hospitals. Study Design: Cross-sectional descriptive study. Place and Duration of Study: The study was conducted at the departments of Pathology, Combined Military Hospitals Malir and Sibi, Pakistan from Jul 2011 to Mar 2012. Patients and Methods: A total of 2709 samples were collected from febrile patients for detection of malaria parasite (944 from CMH Malir and 1765 from CMH Sibi). Cases having infection with P. falciparum alone or having mixed infection with P. Vivax and P. falciparum were excluded from the study. Both thick and thin film microscopy and immunochromatographic method (OptiMA L-IT) were used for detection of malarial parasite. Platelet counts were done using automated haematology analyser (Sysmex KX 21) with re-evaluation of low counts with manual methods. Results: Total of 170 patients were found positive for P. vivax malaria (44 from CMH Malir and 126 from CMH Sibi). Platelet counts ranged from 21 - 457 * 10/sub 9/ with a mean of 134 * 10/sub 9/. Ninety five (2.1%) from CMH Malir and 4.2% from CMH Sibi out of 170 patients had thrombocytopenia, and the difference in thrombocytopenia at the two hospitals was insignificant (0.017). Conclusion: Thrombocytopenia in patients with P. vivax infection is equally prevalent in the two hospitals, representing a widely different geographical area and should prompt a more thorough search for malaria parasite. (author)

  9. Lessons in platelet production from inherited thrombocytopenias.

    Pecci, Alessandro; Balduini, Carlo L

    2014-04-01

    Our knowledge of the cellular and molecular mechanisms of platelet production has greatly expanded in recent years due to the opportunity to culture in vitro megakaryocytes and to create transgenic animals with specific genetic defects that interfere with platelet biogenesis. However, in vitro models do not reproduce the complexity of the bone marrow microenvironment where megakaryopoiesis takes place, and experience shows that what is seen in animals does not always happen in humans. So, these experimental models tell us what might happen in humans, but does not assure us that these events really occur. In contrast, inherited thrombocytopenias offer the unique opportunity to verify in humans the actual effects of abnormalities in specific molecules on platelet production. There are currently 20 genes whose defects are known to result in thrombocytopenia and, on this basis, this review tries to outline a model of megakaryopoiesis based on firm evidence. Inherited thrombocytopenias have not yet yielded all the information they can provide, because nearly half of patients have forms that do not fit with any known disorder. So, further investigation of inherited thrombocytopenias will advance not only the knowledge of human illnesses, but also our understanding of human platelet production. PMID:24480030

  10. Clinical practice: immune thrombocytopenia in paediatrics.

    Labarque, Veerle; Van Geet, Chris

    2014-02-01

    Immune thrombocytopenia (ITP) is a disease affecting both children and adults. It is defined as acquired isolated thrombocytopenia caused by the autoimmune production of anti-platelet antibodies. Childhood ITP most frequently occurs in young children who have been previously well, although a viral respiratory tract infection often precedes thrombocytopenia. A benign and self-limiting course is common, but major bleeding complications such as intracranial haemorrhage may occur. Yet one cannot predict which child will have a prolonged course of thrombocytopenia and who will develop an intracranial haemorrhage. In children without atypical characteristics, only minimal diagnostic investigations are needed, and most paediatric ITP patients do not need platelet-enhancing therapy even though various treatment options are available. A "watch and wait" strategy should be considered in paediatric patients with mild disease. Steroids, intravenous immunoglobulin G or anti-D immunoglobulin are the current first-line therapeutic measures for children at risk for severe bleeding. When life-threatening bleeding occurs, a combination of therapies is needed. In this review, we summarise the current knowledge on primary ITP in children and adolescents. PMID:24390128

  11. Wilson disease with thrombocytopenia (case report).

    Zhvania, M; Gogberashvili, K; Gagoshidze, M; Uberi, E

    2014-12-01

    We present an adolescent patient with WD accompanied with secondary amenorrhea, and thrombocytopenia. NK, a 14 year-old girl, had amenorrhea for 5 months despite having had regular menses for 2 years. An abdominal ultrasound scan revealed ascitis and some ovarian cysts. On physical examination: slight jaundice, edema of lower extremities, skin purpuric rash, enlarged abdomen, dry skin. She had no hepatomegaly and no splenomegaly. Breast and pubic hair development was concomitant with Tanner stage 4. There was performed laboratory and instrumental investigations. The patient was diagnosed as WD owing to the low level of ceruloplasmin, with increased level of copper in 24-hour urine excretion and in dry liver tissue. The needle biopsy of liver showed severe hepatocellular necrosis, inflammatory changes and fibrosis. The platelet count was found to be low with lack of increased number of megakaryocytes in the bone marrow aspiration suggesting the thrombocytopenia was not exclusively owing to hypersplenism. The absence of antithrombocyte and other autoimmune and viral antibodies excluded respectively the diagnosis of autoimmune thrombocytopenia, other autoimmune diseases and viral infections. Thus, we support the recommendation that adolescents with amenorrhea or children with thrombocytopenia without any obvious cause should be evaluated for WD, because the early detection and treatment of WD is capable of reversing described changes and restoring a normal liver function. PMID:25617103

  12. REFRACTORY THROMBOCYTOPENIA AND NEUTROPENIA: A DIAGNOSTIC CHALLENGE

    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.

  13. The Heparin-Induced Thrombocytopenia and Thrombosis Syndrome: Treatment with Intraarterial Urokinase and Systemic Platelet Aggregation Inhibitors

    We report a case of the heparin-induced thrombocytopenia and thrombosis syndrome presenting with acute ischemia of a lower limb. The patient was successfully treated by withdrawal of heparin products, intraarterial urokinase, and platelet anti-aggregation therapy consisting of Dextran and aspirin

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

    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

  15. Cancer-associated immune-mediated syndromes: Pathogenic values and clinical implementation.

    Suchkov, S V; Petrunin, D D; Kostalevskaya, A V; Kachkov, I A; Elbeik, T; Matsuura, E; Paltsev, M A

    2007-07-01

    The ability of tumors to provoke formation of cancer-associated secondary immunodeficiency (CASID) with predominant suppression of CMI and cancer-associated secondary immunodeficiency with clinical autoimmunity syndrome (CASICAS) with triggering of a set of the autoimmune deviations is appearing to be a key event in the restriction of hosts' anti-tumor immunity. Earlier the existence of the above-mentioned syndromes was demonstrated in BCC and GBM patients. In order to reach a point where immunological phenotypes in GBM and BCC can be clarified clinically and, partly, pathogenically, we have conducted a series of studies of typical and atypical types of immune responsiveness in patients with GBM and BCC. For GBM and BCC three scenarios of the involvement of the immune responsiveness have been established in a series of our studies, i.e., (i) malignancy with no immunopathology, (ii) malignancy as CASID, and (iii) malignancy as CASICAS. All of those scenarios demonstrated significant differences in their immune-mediated manifestations which, in turn, were proven to reveal close associative relationships with a specific clinicopathologic type and clinical manifestations of the tumor. CASID and CASICAS share two common features, i.e., (i) signs of immunodeficiency and (ii) a tandem of the deviations within the adaptive and innate links of the host immune responsiveness. At the same time, CASID and CASICAS are distinct pathogenically and clinically, and in terms of depth of the immune deviations observed, CASID patients manifest a breakage in both links, whereas in CASICAS patients, a breakage in the adaptive link would dominate. To get these differences clarified, we summarized major types of the immune imbalances and sets of clinical and clinicopathologic manifestations to illustrate the above-mentioned features in CASID and CASICAS patients. There are distinct close correlations between clinicopathologic features of the disease course and sets of the immune-mediated

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

    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.

  17. Acute Disseminated Encephalomyelitis

    Kambiz Sotoudeh

    Full Text Available Acute disseminated encephalomyelitis (ADEM is an acute, inflammatory, monophasic, demyelinating and immune-mediated disorder of central nervous system; occurs mostly in children after systemic viral infections or vaccinations. Acute polysymptomatic neurologic signs such as encephalopathy, paralysis of limbs, cranial nerve involvement, ataxia and optic neuritis are common manifestations. Brain magnetic resonance imaging study is essential for diagnosis and enabling prompt diagnosis and treatment. Evidence of multifocal lesions of demyelination in subcortical white matter are seen. They are usually bilateral and asymmetrical. Treatment optins have included steroids, immunoglobulins, and plasmapheresis. ADEM is treatable and prognosis is good.

  18. Hyperbaric oxygen reduces delayed immune-mediated neuropathology in experimental carbon monoxide toxicity

    The goal of this investigation was to determine whether exposure to hyperbaric oxygen (HBO2) would ameliorate biochemical and functional brain abnormalities in an animal model of carbon monoxide (CO) poisoning. In this model, CO-mediated oxidative stress causes chemical alterations in myelin basic protein (MBP), which initiates an adaptive immunological response that leads to a functional deficit. CO-exposed rats do not show improvements in task performance in a radial maze. We found that HBO2 given after CO poisoning will prevent this deficit, but not eliminate all of the CO-mediated biochemical alterations in MBP. MBP from HBO2 treated CO-exposed rats is recognized normally by a battery of antibodies, but exhibits an abnormal charge pattern. Lymphocytes from HBO2-treated and control rats do not become activated when incubated with MBP, immunohistological evidence of microglial activation is not apparent, and functional deficits did not occur, unlike untreated CO-exposed rats. The results indicate that HBO2 prevents immune-mediated delayed neurological dysfunction following CO poisoning

  19. Subcutaneous IgG in immune-mediate diseases: proposed mechanisms of action and literature review.

    Danieli, Maria Giovanna; Gelardi, Chiara; Pedini, Veronica; Moretti, Romina; Gabrielli, Armando; Logullo, Francesco

    2014-12-01

    Intravenous immunoglobulin (IVIg) constitutes a relevant treatment option in various immune-mediated disorders, such as chronic inflammatory neuropathies and idiopathic inflammatory myopathies (IIM). Several advantages are linked to IVIg immunomodulatory and steroid sparing effects and to the possibility to withdraw the immunosuppressant therapy. However, the use of IVIg is not always easy to manage. It is associated with the need of an intravenous route of administration, high costs, and the risk of serious systemic adverse effects. More recently, the subcutaneous administration of immunoglobulin (SCIg) has been used in immunological practice as an alternative to IVIg, administered at lower dosages and more frequent intervals. This results in higher and more stable IgG serum levels and may prevent end-of-dose reduction and adverse effects caused by sudden IgG serum elevation. Moreover, the use of SCIg is more feasible, patient-friendly and cost-effective compared to the intravenous administration. In this context we compared IVIg and SCIg long term efficacy in the treatment of chronic inflammatory neuropathies and IIM, by reviewing the current literature and reporting the data obtained from our clinical experience about the use of SCIg in patients with myositis. We also described the most recent evidence on the immunomodulatory role of immunoglobulin, the pharmacokinetic properties of SCIg compared to the IVIg treatment, and the consequent clinical, laboratory and immunological implications. PMID:25172241

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

    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.

  1. The relationship between intestinal parasites and some immune-mediated intestinal conditions.

    Mohammadi, Rasoul; Hosseini-Safa, Ahmad; Ehsani Ardakani, Mohammad Javad; Rostami-Nejad, Mohammad

    2015-01-01

    Over the last decades, the incidence of infestation by minor parasites has decreased in developed countries. Infectious agents can also suppress autoimmune and allergic disorders. Some investigations show that various protozoa and helminthes are connected with the main immune-mediated intestinal conditions including celiac disease (CD), inflammatory bowel diseases (IBD) and irritable bowel syndrome (IBS). Celiac disease is a digestive and autoimmune disorder that can damage the small intestine and characterized by a multitude gastrointestinal (GI) and extra GI symptoms. IBD (including ulcerative colitis and Crohn's disease) is a group of inflammatory conditions of the small intestine and colon. The etiology of IBD is unknown, but it may be related to instability in the intestinal microflora that leading to an immoderate inflammatory response to commensal microbiota. Irritable bowel syndrome (IBS) is a common, long-term condition of the digestive system. Bloating, diarrhoea and/or constipation are nonspecific symptoms of IBS. Various studies have shown that some intestinal parasites can effect on immune system of infected hosts and in some cases, they are able to modify and change the host's immune responses, particularly in autoimmune disorders like celiac disease and IBD. The main objective of this review is to investigate the relationship between intestinal parasites and different inflammatory bowel disorders. PMID:25926937

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

    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. PMID:21573251

  3. Immune-mediated keratoconjunctivitis sicca in dogs: current perspectives on management

    Dodi PL

    2015-10-01

    Full Text Available Pier Luigi Dodi Department of Veterinary Medicine Sciences, University of Parma, Parma, Italy Abstract: Keratoconjunctivitis sicca (KCS is a frequent canine ophthalmic disease, resulting from the deficiency of one or more elements in the precorneal tear film. There are different known causes of KCS in dogs, including congenital, metabolic, infectious, drug induced, neurogenic, radiation, iatrogenic, idiopathic, and immune mediated, though the last one is the most prevalent form in dogs. Initially, clinical signs of KCS include blepharospasm caused by ocular pain, mucoid to mucopurulent ocular discharge, and conjunctival hyperemia; secondary bacterial infection may also occur, with chronicity, corneal epithelial hyperplasia, pigmentation, neovascularization, and corneal ulceration. The diagnosis of KCS is based on the presence of consistent clinical signs and measurement of decreased aqueous tear production using the Schirmer tear test. Therapy is based on administering the following topical drugs: ocular lubricant, mucolytics, antibiotics, corticosteroids, pilocarpine, and immunomodulators. These last drugs (eg, cyclosporine, pimecrolimus, and tacrolimus have immunosuppressive activity and stimulate tear production. Furthermore, the nerve growth factor is a new subject matter of the research. Although these therapies are advantageous, stimulation of natural tear production seems to provide the highest recovery in clinical signs and prevention of vision loss. The goal of the following article is to describe the recent developments about KCS in dogs emphasizing the use of new therapies. Keywords: dogs, keratoconjunctivitis sicca, treatment, NGF

  4. Nodular Scleritis Associated with Herpes Zoster Virus: An Infectious and Immune-Mediated Process.

    Loureiro, Mónica; Rothwell, Renata; Fonseca, Sofia

    2016-01-01

    Purpose. To describe a case of anterior nodular scleritis, preceded by an anterior hypertensive uveitis, which was primarily caused by varicella zoster virus (VZV). Case Report. A 54-year-old woman presented with anterior uveitis of the right eye presumably caused by herpetic viral disease and was successfully treated. Two months later, she developed a nodular scleritis and started oral nonsteroidal anti-inflammatory without effect. A complete laboratory workup revealed positivity for HLA-B27; the infectious workup was negative. Therapy was changed to oral prednisolone and an incomplete improvement occurred. Therefore, a diagnostic anterior paracentesis was performed and the polymerase chain reaction (PCR) analysis revealed VZV. She was treated with valacyclovir and the oral prednisolone began to decrease; however, a marked worsening of the scleritis occurred with the reduction of the daily dose; subsequently, methotrexate was introduced allowing the suspension of the prednisolone and led to clinical resolution of the scleritis. Conclusion. This report of anterior nodular scleritis caused by VZV argues in favor of an underlying immune-mediated component, requiring immunosuppressive therapy for clinical resolution. The PCR analysis of the aqueous humor was revealed to be a valuable technique and should be considered in cases of scleritis with poor response to treatment. PMID:27298747

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

    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.

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

    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.

  7. Immune thrombocytopenia: No longer ‘idiopathic’

    McCRAE, KEITH

    2012-01-01

    Immune thrombocytopenia (ITP) is a common hematologic disorder. Its pathogenesis involves both accelerated platelet destruction and impaired platelet production. First-line agents are usually effective initially but do not provide long-term responses. Splenectomy remains an effective long-term therapy, as does rituximab (Rituxan) in a subset of patients. Thrombopoietic agents offer a new alternative, although their place in the overall management of ITP remains uncertain. PMID:21632906

  8. Immune thrombocytopenia: No longer ‘idiopathic’

    McCrae, Keith

    2011-01-01

    Immune thrombocytopenia (ITP) is a common hematologic disorder. Its pathogenesis involves both accelerated platelet destruction and impaired platelet production. First-line agents are usually effective initially but do not provide long-term responses. Splenectomy remains an effective long-term therapy, as does rituximab (Rituxan) in a subset of patients. Thrombopoietic agents offer a new alternative, although their place in the overall management of ITP remains uncertain.

  9. Thrombocytopenia during pregnancy: an institutional based study

    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

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

    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). PMID:26437745

  11. Use of serum C-reactive protein as an early marker of inflammatory activity in canine type II immune-mediated polyarthritis: case report

    Kristensen Annemarie T; Jessen Lisbeth; Houser Geoffrey A; Jensen Asger; Kjelgaard-Hansen Mads

    2006-01-01

    Abstract Background Monitoring systemic inflammatory activity during steroid therapy of canine immune-mediated polyarthritis (IMPA) is difficult and mainly relies on clinical signs. Case presentation Canine serum C-reactive protein (CRP) was measured serially and blinded during a 27-week follow-up period of a case of Anaplasma phagocytophilia induced type II immune-mediated polyarthritis. Conclusion WBC was, as expected, observed not to reflect the inflammatory activity during steroid treatme...

  12. Effect of vitamin E on thrombocytopenia in dengue fever

    Arvind Vaish; Sudhir Verma; Abhishek Agarwal; Lokesh Gupta; Manish Gutch

    2012-01-01

    Context: Dengue fever frequently causes thrombocytopenia for which there is no satisfactory treatment. Aim: To evaluate the effect of vitamin E on thrombocytopenia in dengue fever. Settings and Design: A tertiary teaching hospital during a recent outbreak of dengue fever in the area. Materials and Methods: Patients of dengue fever (as per WHO criteria) with thrombocytopenia and platelet counts between 10 × 10 3 /mm 3 and 100 × 10 3 /mm 3 seen during September 1, 2010 to November 30, 2010 were...

  13. Heparin induced thrombocytopenia type ii and myocardial infarction: Two case reports

    Antonijević Nebojša

    2004-01-01

    Full Text Available Heparin-induced thrombocytopenia (HIT type II is an acquired thrombophylic state and life-threatening immune complication of a heparin treatment mainly clinically manifested by marked thrombocytopenia, frequently by arterial and venous thrombosis, and sometimes by skin changes. Functional assay as heparin aggregation test and 14C-serotonin release assays are used in diagnostics as well as antigen assays of which detection tests for heparin-platelet factor 4 antibodies are most frequently used. Considering the fact that there is no single reliable assays for HIT II detection available, sometimes it is necessary to combine both of the above-mentioned types of assays. We present the case of a 57-year-old patient with an acute anterior myocardial infarction with cardiac insufficiency of III and IV degree according to Killip, recurrent ventricular fibrillation and diabetes mellitus type II developing thrombocytopenia to 37x10 9/l accompanied with typical skin changes. The diagnosis was confirmed by the heparin aggregation test. The second patient aged 70 undergoing the treatment for anteroseptal myocardial infarction and reinfarction of the inferior wall complicated by a cardiogenic shock and acute right bundle branch block developed thrombocytopenia 59x10 9/I on the third day of the heparin therapy, with the remark that he had received a heparin therapy during the first infarction as well. Antibodies against heparin-platelet factor 4 were detected by particle gel ID-HPF4 immunoassay. In both patients, the disease had a lethal outcome despite all then available therapeutic measures applied. Further on we discuss advantages of certain types of tests, a therapy doctrine, need for urgent therapeutic measures, inclusive of the administration of anitithrombins, avoidance of harmful procedures like low-molecular-weight heparins administration and prophylactic platelet transfusion as well as preventive measures.

  14. Transfusion-Related Acute Lung Injured (TRALI): Current Concepts

    Álvarez, P; Carrasco, R; Romero-Dapueto, C; Castillo, R.L

    2015-01-01

    Transfusion-related acute lung injury (TRALI) is a life-threatening intervention that develops within 6 hours of transfusion of one or more units of blood, and is an important cause of morbidity and mortality resulting from transfusion. It is necessary to dismiss other causes of acute lung injury (ALI), like sepsis, acute cardiogenic edema, acute respiratory distress syndrome (ARDS) or bacterial infection. There are two mechanisms that lead to the development of this syndrome: immune-mediated...

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

    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.

    2016-01-01

    .096 [0.013]; P = 7.57 × 10−13). CONCLUSIONS AND RELEVANCE Our findings demonstrate genetic overlap between AD and immune-mediated diseases and suggest that immune system processes influence AD pathogenesis and progression. PMID:27088644

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

    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

  17. Thrombocytopenia in leptospirosis and role of platelet transfusion

    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

  18. Pathogenesis of the delayed phase of Rauscher virus-induced thrombocytopenia

    BALB/c (H-2/sup d/) mice injected with Rauscher murine leukemia virus (RMuLV) developed two phases of thrombocytopenia: an acute phase, probably due to direct virus-platelet interactions, and a delayed phase, starting 2 to 3 wk after virus injection, which was associated with the infection of megakaryocytes by RMuLV and with the expression of RMuLV gp70 and p30 antigens on platelet membranes. This study was concerned with the pathogenesis of this second phase of thrombocytopenia. During this period, the number of marrow megakaryocytes was increased. A peripheral platelet destruction was further indicated by reduced platelet life span. It was shown that radiolabeled platelets, either normal or infected, were submitted to a more rapid clearance in infected recipients than in normal recipients. This might be due to the splenomegaly observed in infected recipients. However, the immediate clearance of gp70+ platelets was more accelerated in infected recipients with high titers of serum anti-gp70 antibodies than in infected recipients without detectable serum anti-gp70 antibodies. These results suggest that specific clearance of gp70+ platelets in the presence of significant amounts of serum antiviral antibodies and nonspecific hypersplenism play a role in the development of delayed thrombocytopenia in RMuLV-infected mice

  19. Study of thrombopoietin for gene therapy of thrombocytopenia

    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.

  20. Anti-RhD immunoglobulin in the treatment of immune thrombocytopenia

    Eric Cheung

    2009-01-01

    Full Text Available Eric Cheung, Howard A LiebmanJane Anne Nohl Division of Hematology and Center for the Study of Blood Diseases, University of Southern California-Keck School of Medicine, Los Angeles, CA, USAAbstract: Immune thrombocytopenia (ITP is an acquired bleeding autoimmune disorder characterized by a markedly decreased blood platelet count. The disorder is variable, frequently having an acute onset of limited duration in children and a more chronic course in adults. A number of therapeutic agents have demonstrated efficacy in increasing the platelet counts in both children and adults. Anti-RhD immunoglobulin (anti-D is one such agent, and has been successfully used in the setting of both acute and chronic immune thrombocytopenia. In this report we review the use of anti-D in the management of ITP. While the FDA-approved dose of 50 mg/kg has documented efficacy in increasing platelet counts in approximately 80% of children and 70% of adults, a higher dose of 75 μg/kg has been shown to result in a more rapid increase in platelet count without a greater reduction in hemoglobin. Anti-D is generally ineffective in patients who have failed splenectomy. Anti-RhD therapy has been shown capable of delaying splenectomy in adult patients, but does not significantly increase the total number of patients in whom the procedure can be avoided. Anti-D therapy appears to inhibit macrophage phagocytosis by a combination of both FcR blockade and inflammatory cytokine inhibition of platelet phagocytosis within the spleen. Anti-RhD treatment is associated with mild to moderate infusion toxicities. Rare life-threatening toxicities such as hemoglobinuria, acute renal failure and disseminated intravascular coagulation have been reported. Recommendations have been proposed to reduce the risk of these complications. Anti-D immunoglobulin can be an effective option for rapidly increasing platelet counts in patients with symptomatic ITP.Keywords: immune thrombocytopenia, Rh

  1. Simultaneous Manifestation of Chronic Myelomonocytic Leukemia and Multiple Myeloma during Treatment by Prednisolone and Eltrombopag for Immune-Mediated Thrombocytopenic Purpura.

    Hagihara, Masao; Inoue, Morihiro; Kodama, Kenichiro; Uchida, Tomoyuki; Hua, Jian

    2016-01-01

    An 80-year-old man was admitted to our hospital because of severe thrombocytopenia. He was diagnosed with idiopathic thrombocytopenia, and prednisolone together with eltrombopag was started, leading to significant improvement of platelet counts. Four years later, there was a prominent increase of peripheral blood monocytes, which was accompanied by recurrence of thrombocytopenia. Bone marrow aspirates and serum electrophoresis revealed coexistence of chronic myelomonocytic leukemia (CMML) and multiple myeloma (MM). The patient received lenalidomide plus dexamethasone therapy but died due to exacerbation of the disorder. It was supposed that thrombocytopenia was secondarily caused by CMML and MM developed at a later period. PMID:27597907

  2. Phenotypic analysis of bone marrow lymphocytes from children with acute thrombocytopenic purpura.

    Guiziry, Dalai E L; El, Gendy Wessam; Farahat, Nahla; Hassab, Hoda

    2005-01-01

    Hematogones are benign immature B cells that commonly populate the bone marrow of children. Their presence has been noted to interfere with the flow-cytometric analysis of acute lymphoblastic leukemia (ALL), because their immunophenotype is similar to B-precursor cell lymphoblasts. Immune-mediated thrombocytopenia is a clinical condition characterized by increased platelet destruction due to sensitization of platelets by autoantibodies. The aim of this study was to determine the incidence and clinical impact of bone marrow hematogones in cases of acute immune thrombocytopenic purpura (ITP) among children. This was done by immunophenotyping of bone marrow lymphocytes of ITP cases and controls and follow up of cases. This study was done on 25 cases of ITP, 12 females and 13 males, their age ranged from 2 to 13 years. A control group was included in the study, 15 cases of apparently healthy children with matching age and sex taken from among bone marrow donors. Cases and controls were subjected to bone marrow lymphocyte immunophenotyping with flow-cytometry to verify the presence of hematogones. A statistically significant increase in the percentage of hematogones was demonstrated in their bone marrows. An increased percentage of CD10+ lymphocytes was demonstrated; with a mean of 18+/-15.2%, CD19+ with a mean of 27+/-16.3% and CD34+ with a mean of 3.7+/-3.2%. No correlation was found between the percentage of hematogones and peripheral platelet count or bone marrow lymphocytic count. In conclusion, there is an increase in the bone marrow hematogones in ITP cases in comparison to normal controls. This could be the sequence of an immunological response to the cause which determined the disease, or the regeneration of the stem cell compartment following transient damage. PMID:16734134

  3. Heparin-induced thrombocytopenia in solid organ transplant recipients: The current scientific knowledge.

    Assfalg, Volker; Hüser, Norbert

    2016-03-24

    Exposure to heparin is associated with a high incidence of immunization against platelet factor 4 (PF4)/heparin complexes. A subgroup of immunized patients is at risk of developing heparin-induced thrombocytopenia (HIT), an immune mediated prothrombotic adverse drug effect. Transplant recipients are frequently exposed to heparin either due to the underlying end-stage disease, which leads to listing and transplantation or during the transplant procedure and the perioperative period. To review the current scientific knowledge on anti-heparin/PF4 antibodies and HIT in transplant recipients a systematic PubMed literature search on articles in English language was performed. The definition of HIT is inconsistent amongst the publications. Overall, six studies and 15 case reports have been published on HIT before or after heart, liver, kidney, and lung transplantation, respectively. The frequency of seroconversion for anti-PF4/heparin antibodies ranged between 1.9% and 57.9%. However, different methods to detect anti-PF4/heparin antibodies were applied. In none of the studies HIT-associated thromboembolic events or fatalities were observed. More importantly, in patients with a history of HIT, reexposure to heparin during transplantation was not associated with thrombotic complications. Taken together, the overall incidence of HIT after solid organ transplantation seems to be very low. However, according to the current knowledge, cardiac transplant recipients may have the highest risk to develop HIT. Different alternative suggestions for heparin-free anticoagulation have been reported for recipients with suspected HIT albeit no official recommendations on management have been published for this special collective so far. PMID:27011914

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

    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.

  5. Pathophysiology of acute small bowel disease with CT correlation

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

  6. Pathophysiology of acute small bowel disease with CT correlation

    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.

  7. NCIDENCE OF BLEEDING MANIFESTATIONS IN FEVER WITH THROMBOCYTOPENIA CASES

    Putta

    2015-04-01

    Full Text Available INTRODUCTION: Fever is the cardinal manifestation of infection. Platelets are necessary to prevent bleeding manifestations. Certain infections cause thrombocytopenia and bleeding manifestations. AIMS AND OBJECTIVES: To study the incidence of bleeding manifestations in i nfections which cause fever and thrombocytopenia. MATERIALS AND METHODS: INCLUSION CRITERIA: Patients who were admitted with fever and thrombocytopenia, aged above 12 years, in S.V.R.R.G.G.H, Tirupati were taken for the study. EXCLUSION CRITERIA: Patients who are admitted with thrombocytopenia and without fever were excluded. Patients who are admitted with fever and normal platelet count were excluded. RESULTS AND CONCLUSI ON: Fever with thrombocytopenia is the commonest presenting problem in the medical war ds. In the present study the commonest infectious etiology of fever with thrombocytopenia was malaria fever (36%, followed by undiagnosed fevers (28%, dengue fever (26%, typhoid fever (6% and scrub typhus (4%. In the present study bleeding manifestati ons were seen in 16 cases (32% and bleeding manifestations were not seen in 34 cases (68%. The commonest bleeding manifestation was cutaneous, followed by hematemesis, malena, bleeding gums, hematuria and epistaxis. Bleeding manifestation was commonly se en in thrombocytopenia with dengue fever (14%, followed by malaria (8%, undiagnosed cases (8% and typhoid (2%.

  8. Thrombocytopenia in Preterm Infants with Intrauterine Growth Restriction

    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.

  9. Drug-induced immune thrombocytopenia due to moxifloxacin

    Coker, Timothy J

    2013-01-01

    A 39-year-old woman with 1 day of oral petechiae, leg ecchymoses and epistaxis was found to have isolated thrombocytopenia. She had recently completed a 10-day course of moxifloxacin for an upper respiratory infection. On further questioning, she had developed thrombocytopenia 2 years earlier after a treatment course with moxifloxacin. After ruling out other causes, drug-induced immune thrombocytopenia due to moxifloxacin was diagnosed. Her platelets returned to normal range 15 days after fin...

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

    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

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

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

    2013-01-15

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

  12. Use of serum C-reactive protein as an early marker of inflammatory activity in canine type II immune-mediated polyarthritis: case report

    Kristensen Annemarie T

    2006-06-01

    Full Text Available Abstract Background Monitoring systemic inflammatory activity during steroid therapy of canine immune-mediated polyarthritis (IMPA is difficult and mainly relies on clinical signs. Case presentation Canine serum C-reactive protein (CRP was measured serially and blinded during a 27-week follow-up period of a case of Anaplasma phagocytophilia induced type II immune-mediated polyarthritis. Conclusion WBC was, as expected, observed not to reflect the inflammatory activity during steroid treatment in a clinical useful manner, whereas, CRP is suggested a valuable unbiased marker of inflammatory activity during steroid treatment in this case.

  13. Use of serum C-reactive protein as an early marker of inflammatory activity in canine type II immune-mediated polyarthritis: case report

    Kjelgaard-Hansen, Mads; Jensen, Asger Lundorff; Houser, Geoffrey A; Jessen, Lisbeth Rem; Kristensen, Annemarie T

    2006-01-01

    Background Monitoring systemic inflammatory activity during steroid therapy of canine immune-mediated polyarthritis (IMPA) is difficult and mainly relies on clinical signs. Case presentation Canine serum C-reactive protein (CRP) was measured serially and blinded during a 27-week follow-up period of a case of Anaplasma phagocytophilia induced type II immune-mediated polyarthritis. Conclusion WBC was, as expected, observed not to reflect the inflammatory activity during steroid treatment in a clinical useful manner, whereas, CRP is suggested a valuable unbiased marker of inflammatory activity during steroid treatment in this case. PMID:16987405

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

    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...... that the RA and CD networks have predictive power by demonstrating that proteins in these networks, not encoded in the confirmed list of disease associated loci, are significantly enriched for association to the phenotypes in question in extended GWAS analysis. Finally, we test our method in 3 non-immune...... risk variants. It has previously been observed that different genes harboring causal mutations for the same Mendelian disease often physically interact. We sought to evaluate the degree to which this is true of genes within strongly associated loci in complex disease. Using sets of loci defined in...

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

    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.

  16. Effect of a single plasma transfusion on thromboembolism in 13 dogs with primary immune-mediated hemolytic anemia.

    Thompson, Mary F; Scott-Moncrieff, J Catharine; Brooks, Marjory B

    2004-01-01

    Thirteen dogs with primary immune-mediated hemolytic anemia received fresh-frozen plasma within 12 hours of admission, in addition to unfractionated heparin and other therapies, such as prednisone, azathioprine, and packed red blood cell transfusion. Antithrombin activity was quantified prior to transfusion and at 30 minutes and 48 hours after transfusion. Plasma antithrombin activity did not change significantly after a single plasma transfusion. There were no deaths in the first 48 hours of treatment. Thromboembolism was identified at necropsy in six of 10 dogs that died within 12 months of admission. There was no significant difference in the incidence of thromboembolism between the current treatment group and a historical control group. PMID:15533964

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

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

    2002-10-01

    The pathogenesis of Crohn's disease involves a mucosal inflammatory response affecting the barrier function of the gut. Myofibroblasts directly underlining the intestinal epithelium may have a regulatory role in immune-mediated barrier disruption. A coculture system of T84 epithelial and CCD-18Co myofibroblasts was established in order to mimic the in situ spatial interactions between these cell types and to evaluate their role in barrier: integrity. Lamina propria mononuclear cells (LPMC) were introduced in co- and monocultures. Effects of immune cells on barrier integrity was determined by measuring resistance and permeability for macromolecules. Introduction of LPMC in both culture systems caused a time-dependent decrease in barrier integrity. This was found to be less pronounced in cocultures indicating a regulatory role for mesenchymal cells. The effects were also found to depend on the route of LPMC stimulation. Additional analyses suggested that the regulatory role of myofibroblasts in barrier integrity involves production of growth factors. PMID:12395905

  18. Data correlations between gender, cytomegalovirus infection and T cells, NK cells, and soluble immune mediators in elderly humans.

    Al-Attar, Ahmad; Presnell, Steven R; Peterson, Charlotte A; Thomas, D Travis; Lutz, Charles T

    2016-09-01

    We describe a cohort of 50 elderly subjects, age at least 70 years. We present gender-specific findings in T lymphocyte markers and soluble immune mediators. We show the correlation between cytomegalovirus infection status with CD56(dim) NK cell responses to a variety of stimuli and with CD56(bright)/CD56(dim) NK cell ratio. We also present the correlation of retinol binding protein (RBP)-4 plasma levels with NK cell responses and we explore the relationship between gender and adiponectin, 25(OH)D (vitamin D), and RBP4 in affecting CD56(dim) NK cell responses. These data are discussed in Al-Attar et al. (2016) [1]. PMID:27508213

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

    Ostrowski, Sisse R; Johansson, Per Ingemar

    2011-01-01

    Thrombocytopenia in critical illness predicts a poor clinical outcome. Apart from its role in microvascular thrombus formation, it is widely anticipated that this association is indirect rather than causal. Emerging evidence however indicates that platelets are also immune competent cells. Like...... per se results in immunodeficiency through loss of platelet-mediated immune functions, and propose that thrombocytopenia induced immunodeficiency in critical illness in part explain the negative predictive value of low or declining platelet count. We propose that rethinking the risks of...... thrombocytopenia to include not only bleeding but also immunodeficiency and immune dysregulation along with the conduct of studies investigating mechanisms contributing to thrombocytopenia induced poor non-hemorrhagic outcome in critical illness, may be means to improve outcome in these patients through...

  20. Idelalisib given front-line for treatment of chronic lymphocytic leukemia causes frequent immune-mediated hepatotoxicity.

    Lampson, Benjamin L; Kasar, Siddha N; Matos, Tiago R; Morgan, Elizabeth A; Rassenti, Laura; Davids, Matthew S; Fisher, David C; Freedman, Arnold S; Jacobson, Caron A; Armand, Philippe; Abramson, Jeremy S; Arnason, Jon E; Kipps, Thomas J; Fein, Joshua; Fernandes, Stacey; Hanna, John; Ritz, Jerome; Kim, Haesook T; Brown, Jennifer R

    2016-07-14

    Idelalisib is a small-molecule inhibitor of PI3Kδ with demonstrated efficacy for the treatment of relapsed/refractory chronic lymphocytic leukemia (CLL). To evaluate idelalisib as front-line therapy, we enrolled 24 subjects in a phase 2 study consisting of 2 months of idelalisib monotherapy followed by 6 months of combination therapy with idelalisib and the anti-CD20 antibody ofatumumab. After a median follow-up period of 14.7 months, hepatotoxicity was found to be a frequent and often severe adverse event. A total of 19 subjects (79%) experienced either grade ≥1 ALT or AST elevation during the study, and 13 subjects (54%) experienced grade ≥3 transaminitis. The median time to development of transaminitis was 28 days, occurring before ofatumumab introduction. Younger age and mutated immunoglobulin heavy chain status were significant risk factors for the development of hepatotoxicity. Multiple lines of evidence suggest that this hepatotoxicity was immune mediated. A lymphocytic infiltrate was seen on liver biopsy specimens taken from 2 subjects with transaminitis, and levels of the proinflammatory cytokines CCL-3 and CCL-4 were higher in subjects experiencing hepatotoxicity. All cases of transaminitis resolved either by holding the drug, initiating immunosuppressants, or both, and rates of recurrent toxicity were lower in patients taking steroids when idelalisib was reinitiated. A decrease in peripheral blood regulatory T cells was seen in patients experiencing toxicity on therapy, which is consistent with an immune-mediated mechanism. These results suggest that caution should be taken as drugs within this class are developed for CLL, particularly in younger patients who have not received prior disease-specific therapy. This study was registered at www.clinicaltrials.gov as #NCT02135133. PMID:27247136

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

    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

  2. Natural history of severe thrombocytopenia in infectious mononucleosis

    Wong, Su Yong; Bennett, Bruce

    1982-01-01

    The natural history of severe thrombocytopenia in two patients with infectious mononucleosis (minimum platelet counts under 10 × 109 and 17 × 109/l respectively) is described. In both, the platelet count rose rapidly and spontaneously, reaching approximately 100 × 109/l on the seventh day. Bleeding symptoms were also transient and never life-threatening. The possibility of very rapid spontaneous recovery from severe thrombocytopenia must be borne in mind in assessing the effect of any drug in...

  3. Efalizumab-induced severe thrombocytopenia can be resolved

    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

  4. Practice Bulletin No 166 Summary : Thrombocytopenia in Pregnancy.

    2016-09-01

    Thrombocytopenia in pregnant women is diagnosed frequently by obstetricians because platelet counts are included with automated complete blood cell counts (CBCs) obtained during routine prenatal screening (1). Although most U.S. health care providers are trained using U.S. Conventional Units, most scientists, journals, and countries use Système International (SI) units. The laboratory results reported in U.S. Conventional Units can be converted to SI Units or vice versa by using a conversion factor. The conversion factor for platelet count results is 1.0 (ie, to convert from x 103/μL, multiply by 1.0, to get x 109/L). Thrombocytopenia, defined as a platelet count of less than 150 x 109/L, is common and occurs in 7-12% of pregnancies (2, 3). Thrombocytopenia can result from a variety of physiologic or pathologic conditions, several of which are unique to pregnancy. Some causes of thrombocytopenia are serious medical disorders that have the potential for maternal and fetal morbidity. In contrast, other conditions, such as gestational thrombocytopenia, are benign and pose no maternal or fetal risks. Because of the increased recognition of maternal and fetal thrombocytopenia, there are numerous controversies about obstetric management of this condition. Clinicians must weigh the risks of maternal and fetal bleeding complications against the costs and morbidity of diagnostic tests and invasive interventions. PMID:27548548

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

    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

  6. The pathophysiology of thrombocytopenia in chronic liver disease

    Mitchell O

    2016-04-01

    Full Text Available Oscar Mitchell,1 David M Feldman,1,2 Marla Diakow,1 Samuel H Sigal3 1Department of Medicine, 2Division of Gastroenterology and Liver Diseases, New York University School of Medicine, Langone Medical Center, New York, 3Division of Gastroenterology and Liver Diseases, Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA Abstract: Thrombocytopenia is the most common hematological abnormality encountered in patients with chronic liver disease (CLD. In addition to being an indicator of advanced disease and poor prognosis, it frequently prevents crucial interventions. Historically, thrombocytopenia has been attributed to hypersplenism, which is the increased pooling of platelets in a spleen enlarged by congestive splenomegaly secondary to portal hypertension. Over the past decade, however, there have been significant advances in the understanding of thrombopoiesis, which, in turn, has led to an improved understanding of thrombocytopenia in cirrhosis. Multiple factors contribute to the development of thrombocytopenia and these can broadly be divided into those that cause decreased production, splenic sequestration, and increased destruction. Depressed thrombopoietin levels in CLD, together with direct bone marrow suppression, result in a reduced rate of platelet production. Thrombopoietin regulates both platelet production and maturation and is impaired in CLD. Bone marrow suppression can be caused by viruses, alcohol, iron overload, and medications. Splenic sequestration results from hypersplenism. The increased rate of platelet destruction in cirrhosis also occurs through a number of pathways: increased shear stress, increased fibrinolysis, bacterial translocation, and infection result in an increased rate of platelet aggregation, while autoimmune disease and raised titers of antiplatelet immunoglobulin result in the immunologic destruction of platelets. An in-depth understanding of the complex

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

    Federico Pasin

    2014-02-01

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

  8. Leptin concentrations and the immune-mediated reduction of feed intake in sheep infected with the nematode Trichostrongylus colubriformis.

    Greer, Andrew W; Boisclair, Yves R; Stankiewicz, Miroslaw; McAnulty, Robin W; Jay, Nigel P; Sykes, Andrew R

    2009-10-01

    The hypothesis that increases in the concentration of the anorectic peptide leptin may be responsible for the immune-mediated reduction in feed intake (FI) during gastrointestinal parasitism in sheep was investigated. In a 2 x 2 x 2 factorial design, the first factor was age at the start of infection (5 months old v. 17 months old). The second factor was parasite infection (no infection v. administration of eighty L3 infective Trichostrongylus colubriformis larvae/kg live weight (LW) per d three times per week for 77 d). The third factor was immunosuppressive therapy with a corticosteroid (no therapy or weekly intramuscular injection of 40 mg methylprednisolone acetate/30 kg LW). Relative to their uninfected counterparts, a 20 % reduction in FI per unit LW (FI/LW; g DM/kg LW) was observed in infected non-suppressed 5-month-old lambs from 21 to 63 d post-infection (P 0.05 for all), allowing the suggestion that the anorexia was a consequence of the developing immune response. The reduction in FI/LW in 5-month-old lambs was not associated with an increase in plasma leptin concentration. Furthermore, plasma leptin concentrations were greater in corticosteroid-treated animals (P anorexia in lambs during T. colubriformis infection. PMID:19785931

  9. Deletion of macrophage migration inhibitory factor inhibits murine oral carcinogenesis: Potential role for chronic pro-inflammatory immune mediators.

    Oghumu, Steve; Knobloch, Thomas J; Terrazas, Cesar; Varikuti, Sanjay; Ahn-Jarvis, Jennifer; Bollinger, Claire E; Iwenofu, Hans; Weghorst, Christopher M; Satoskar, Abhay R

    2016-09-15

    Oral cancer kills about 1 person every hour each day in the United States and is the sixth most prevalent cancer worldwide. The pro-inflammatory cytokine 'macrophage migration inhibitory factor' (MIF) has been shown to be expressed in oral cancer patients, yet its precise role in oral carcinogenesis is not clear. In this study, we examined the impact of global Mif deletion on the cellular and molecular process occurring during oral carcinogenesis using a well-established mouse model of oral cancer with the carcinogen 4-nitroquinoline-1-oxide (4NQO). C57BL/6 Wild-type (WT) and Mif knock-out mice were administered with 4NQO in drinking water for 16 weeks, then regular drinking water for 8 weeks. Mif knock-out mice displayed fewer oral tumor incidence and multiplicity, accompanied by a significant reduction in the expression of pro-inflammatory cytokines Il-1β, Tnf-α, chemokines Cxcl1, Cxcl6 and Ccl3 and other molecular biomarkers of oral carcinogenesis Mmp1 and Ptgs2. Further, systemic accumulation of myeloid-derived tumor promoting immune cells was inhibited in Mif knock-out mice. Our results demonstrate that genetic Mif deletion reduces the incidence and severity of oral carcinogenesis, by inhibiting the expression of chronic pro-inflammatory immune mediators. Thus, targeting MIF is a promising strategy for the prevention or therapy of oral cancer. PMID:27164411

  10. Retrospective study of reticulocyte indices as indicators of iron-restricted erythropoiesis in dogs with immune-mediated hemolytic anemia.

    Schaefer, Deanna M W; Stokol, Tracy

    2016-05-01

    Iron-restricted erythropoiesis can occur as a result of an absolute deficiency of iron stores, inflammation-mediated iron sequestration, or functional iron deficiency (in which release of stored iron is slower than the iron uptake by erythroid precursors during intense erythropoiesis). Reticulocyte indices are used to identify iron-restricted erythropoiesis, with the reticulocyte hemoglobin content (CHr) being the most commonly used index in human patients. Dogs with immune-mediated hemolytic anemia (IMHA) may have iron-restricted erythropoiesis caused by inflammation-mediated iron sequestration and/or functional iron deficiency, which could contribute to anemia severity and blunt the regenerative response in some dogs. To investigate this possibility, reticulocyte indices were examined retrospectively in 14 dogs (2-15 years of age; 9 spayed females, 1 intact female, 4 neutered males) with IMHA, and no clinical evidence of blood loss was found to suggest absolute iron deficiency. Five dogs (34%) had CHr below the preestablished lower reference limit (24.5 pg), and hematocrit was significantly lower in these dogs (p = 0.042, nonpaired t-test). Our results suggest that some dogs with IMHA may have iron-restricted erythropoiesis as a result of functional iron deficiency, inflammation-mediated iron sequestration, or (less likely) absolute iron deficiency. Further study is warranted to evaluate if dogs with IMHA may benefit from parenteral iron therapy. PMID:27034340

  11. Disease patterns and incidence of immune-mediated disease in insured Swedish Nova Scotia Duck Tolling Retrievers.

    Bremer, H D; Vilson, Å; Bonnett, B N; Hansson-Hamlin, H

    2015-07-18

    In this study, morbidity in insured Nova Scotia Duck Tolling Retriever (NSDTR) dogs from Sweden was investigated and compared with all other breeds and other retriever breeds. In addition to describing common morbidities in NSDTRs, the hypotheses that NSDTRs are predisposed to lymphoma, immune-mediated rheumatic disease (IMRD) and steroid-responsive meningitis-arteritis (SRMA) were tested. Included in the study were 445,336 dogs; of which, 2890 were NSDTRs that had been covered by veterinary insurance from the Agria Insurance Company (Stockholm, Sweden) at some point during the years 1995-2006. Incidences of various health problems were calculated using the number of veterinary visits as the numerator and the exact time at risk as the denominator. Overall, morbidity was higher in NSDTRs compared with all other breeds, but similar compared with other retriever breeds. The most common causes of veterinary visits in NSDTRs were injuries, gastrointestinal disease and locomotor disorders, with NSDTRs at increased risk of these compared with all other breeds. The incidences for IMRD, SRMA and lymphoma were significantly higher in NSDTRs than in all other dog breeds and all other retriever breeds. The study describes morbidity in NSDTRs, and identifies several disorders to which the breed is predisposed. PMID:26089352

  12. Quinine-induced thrombocytopenia following intravenous use of heroin

    Profound thrombocytopenia developed in a 22-year-old man after intravenous use of heroin. A high-titer, quinine-dependent, platelet-specific antibody was detected in his serum using lysis of normal platelets labeled with chromium 51 and an electroimmunoassay for measurement of platelet-associated IgG. The antibody was specific for quinine and failed to react with platelets in the presence of quinidine hydrochloride or two structural analogues of heroin. Quinine, a common adulterant found in heroin, was detected in the patient's blood and urine. On the basis of these observations, the patient was judged to have quinine-induced immunologic thrombocytopenia. To our knowledge, this report is the first to confirm that quinine used as an adulterant can induce immunologic thrombocytopenia following an injection of heroin

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

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

    2014-01-01

    Although various haematologic abnormalities are known to occur with tuberculosis, association of immune thrombocytopenia with tuberculosis is uncommon. We report a case of retroperitoneal lymph node tuberculosis who presented with ITP. A 76 year old female was admitted to our hospital with oral mucosal bleed and petechial lesions over extremities and abdomen. A diagnosis of immune thrombocytopenia (ITP) was established. Intravenous Anti-D immunoglobulin and Dexamethasone therapy was started, but failed to elicit any sustained platelet response. CT abdomen revealed multiple retroperitoneal lymph nodes with central necrosis. Histopathology (HPE) of these revealed caseating lymphadenitis suggestive of tuberculosis. After 2 months of anti-tuberculous therapy, the platelet counts returned to normal and patient was off all therapy for ITP thereby suggesting likely association between tuberculosis and immune thrombocytopenia. PMID:25327103

  14. Intravenous Immunoglobulin Responsive Persistent Thrombocytopenia after Dengue Haemorrhagic Fever.

    Kumar, Prabhat; Charaniya, Riyaz; Ghosh, Anindya; Sahoo, Ratnakar

    2016-04-01

    Dengue outbreak is common in Indian subcontinent and causes significant morbidity and mortality. Year 2015 has witnessed yet another Dengue epidemic in northern India and the number of cases this year is maximum in a decade. Dengue infection is a viral disease and there are 4 different serotypes DENV1, DENV2, DENV3 and DENV4. This year DENV2 and DENV4 have been isolated from most of the patients. Thrombocytopenia is hallmark of dengue infection and generally recovers within ten days of onset of symptoms. We report a case of dengue haemorrhagic fever in which thrombocytopenia persisted for almost a month and improved after Intravenous immunoglobulin (IVIG) administration. This is the first case where IVIG has been successfully used for treating persisting thrombocytopenia after dengue infection. PMID:27190868

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

    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; Schultz, Marcus J; van der Poll, Tom

    2016-06-16

    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 stratified according to platelet counts (very low <50 × 10(9)/L, intermediate-low 50 × 10(9) to 99 × 10(9)/L, low 100 × 10(9) to 149 × 10(9)/L, or normal 150 × 10(9) to 399 × 10(9)/L) on admission to the intensive care unit. Sepsis patients with platelet counts <50 × 10(9)/L and 50 × 10(9) to 99 × 10(9)/L presented with higher Acute Physiology and Chronic Health Evaluation scores and more shock. Both levels of thrombocytopenia were independently associated with increased 30-day mortality (hazard ratios with 95% confidence intervals 2.00 [1.32-3.05] and 1.72 [1.22-2.44], respectively). To account for baseline differences besides platelet counts, propensity matching was performed, after which the association between thrombocytopenia and the host response was tested, as evaluated by measuring 17 plasma biomarkers indicative of activation and/or dysregulation of pathways implicated in sepsis pathogenesis and by whole genome blood leukocyte expression profiling. In the propensity matched cohort, platelet counts < 50 × 10(9)/L were associated with increased cytokine levels and enhanced endothelial cell activation. All thrombocytopenic groups showed evidence of impaired vascular integrity, whereas coagulation activation was similar between groups. Blood microarray analysis revealed a distinct gene expression pattern in sepsis patients with <50 × 10(9)/L platelets, showing reduced signaling in leukocyte adhesion and diapedesis and increased complement signaling. These data show that admission thrombocytopenia is associated with enhanced mortality and a more disturbed host response during sepsis independent of disease severity, thereby providing clinical validity to animal

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

    Mojgan Karahmadi

    2011-01-01

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

  17. Adult-onset congenital erythropoietic porphyria (Günther's disease) presenting with thrombocytopenia.

    Murphy, A.; Gibson, G; Elder, G H; Otridge, B A; Murphy, G M

    1995-01-01

    Cutaneous signs of Günther's disease (congenital erythropoietic porphyria) developing 5 years after the onset of symptomatic thrombocytopenia are described in a 65-year-old man. Persistent thrombocytopenia unresponsive to corticosteroids and immunoglobulin necessitated a splenectomy.

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

    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...

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

    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....

  20. Rapid-Onset Thrombocytopenia Following Piperacillin-Tazobactam Reexposure.

    Nguyen, Van Dong; Tourigny, Jean-François; Roy, Renaud; Brouillette, Denis

    2015-12-01

    Drug-induced thrombocytopenia is a rare but serious adverse event that has been associated with multiple drugs including β-lactams. Although it mostly occurs with prolonged medication use, some cases of rapid-onset thrombocytopenia have been reported. We describe the case of a 69-year-old man who developed severe and immediate thrombocytopenia following reexposure to piperacillin-tazobactam in the critical care setting. He received a 6-day course of piperacillin-tazobactam for a possible pneumonia immediately after cardiac surgery. During this course of therapy, his platelet count decreased (fluctuating between 69 × 10(3) /mm(3) and 104 × 10(3) /mm(3) ) and then progressively increased after completion of the antibiotic to 340 × 10(3) /mm(3) on postoperative day 15. Ten days after the antibiotic course was completed (postoperative day 16), the patient developed new signs of infection (fever and neutrophilia), and piperacillin-tazobactam was restarted. Eight hours after reintroducing the antibiotic, his platelet count dropped from 317 × 10(3) /mm(3) to 7 × 10(3) /mm(3) . After reviewing all the medications administered to the patient as well as other potential causes of thrombocytopenia, and given the chronology of events, piperacillin-tazobactam was suspected as the most likely offending agent and was therefore replaced by meropenem on postoperative day 17. The patient's platelet count began to rise 2 days after discontinuation of piperacillin-tazobactam and reached 245 × 10(3) /mm(3) by postoperative day 30. No spontaneous bleeding or thrombosis occurred while the patient was thrombocytopenic. Use of the Naranjo Adverse Drug Reaction Probability Scale indicated a probable relationship (score of 6) between the patient's development of thrombocytopenia and piperacillin-tazobactam therapy. This case highlights the severity and swiftness in which drug-induced thrombocytopenia may present in the context of cardiac surgery. PMID:26684560

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

    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. PMID:27230048

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

    Federico Pasin; Emanuela Porro; Francesco Frattini; Pierpaolo Vescovi; Massimo Franchini; Paolo Sansoni

    2014-01-01

    Thrombocytopenia is a well-recognized adverse effect of many drugs. The association of thrombocytopenia with herbal remedies, nutritional supplements, foods and beverages, complementary or alternative medicines, has been rarely described. There are reports of thrombocytopenia caused by quinine-containing beverages, cow�s milk, cranberry juice, Jui, a Chinese herbal tea, Lupinus termis bean and tahini. A definite evidence of a causal association with thrombocytopenia is warranted; nevertheless...

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

    Afifi Ola; Sewify Eman; El-Attar Madiha; Taie Amal; Mostafa Ahmad

    2007-01-01

    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 cou...

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

    Zöller Bengt; Li Xinjun; Sundquist Jan; Sundquist Kristina

    2012-01-01

    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 ...

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

    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.

  6. CORRELATION OF LIVER FUNCTION TEST ABNORMALITIES WITH CLINICAL OUTCOMES IN PATIENT S WITH FEBRILE THROMBOCYTOPENIA : A CROSS SECTIONAL STUDY

    Prakash Kikkeri

    2015-07-01

    Full Text Available Febrile thrombocytopenia is a common clinical condition encountered in medical wards especially so during Dengue fever epidemics. Hepatic dysfunction is a well - recognized feature of dengue infection manifested by mild to moderate increases in transaminase levels, although jaundice and acute liver failure are generally uncommon. We undertook this cross sectional clinical study to find out the pattern of liver function test abnormalities in patients with febrile thrombocytopenia and to know whether it has any adverse clinical outcome. One hundred patients aged 18 years and above with established fever and a platelet count of <1,00,000 w ho were admitted to medical wards of Victoria hospital, Bangalore during the dengue epidemic between May 2013 and August 2013 were enrolled into this study. Relevant laboratory tests were done including dengue serology to establish the cause of fever and to rule out liver disorders, ITP and other hematological disorders. There were 71 male patients and 29 females with majority in the age group 21 to 40 years. 65 patients tested positive on dengue serology (IgM antibody, NS1 antigen or both, and in 24 patients no cause of fever could be established. Liver function tests were normal in 54(54% patients. Among 46 patients who had LFT abnormalities, raised SGOT and raised ALP were the most common abnormalities present in 30% each of the patients. Raised total bilirubin was present in only 4% patients. There was no statistically significant difference in severity of thrombocytopenia in patients with LFT abnormalities as well as duration of hospital stay and requirement for platelet transfusions, when compared to patients with normal liver function. Derangement of LFT could be one manifestation of a systemic infective/ inflammatory process without any serious adverse clinical outcomes in patients with febrile thrombocytopenia.

  7. Salmonella enteritidis from a case of fever with thrombocytopenia

    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.

  8. Eltrombopag for Treatment of Thrombocytopenia after Allogeneic Hematopoietic Cell Transplantation.

    Tanaka, Takashi; Inamoto, Yoshihiro; Yamashita, Takuya; Fuji, Shigeo; Okinaka, Keiji; Kurosawa, Saiko; Kim, Sung-Won; Tanosaki, Ryuji; Fukuda, Takahiro

    2016-05-01

    Persistent thrombocytopenia is a common complication after allogeneic hematopoietic cell transplantation (HCT). Eltrombopag is an oral thrombopoietin receptor agonist whose efficacy against persistent thrombocytopenia after allogeneic HCT has not been well characterized. This retrospective study evaluated the safety and efficacy of eltrombopag in 12 consecutive patients with persistent thrombocytopenia after allogeneic HCT. Eltrombopag was started at 12.5 mg once daily and the dose was increased by 12.5 mg daily every week until platelet counts exceeded 50,000/μL. Five patients had prolonged isolated thrombocytopenia (PIT) and 7 patients had secondary failure of platelet recovery (SFPR). The cumulative incidence rate of successful platelet recovery to ≥50,000/μL without transfusion support was 60% in PIT patients and 71% in SFPR patients. No patients discontinued the drug because of adverse events or intolerability. Notably, the rate of platelet recovery was higher (100% versus 58%; P = .0017) and recovery was faster (median, 33 days versus 137 days; P = .0078) in patients with normal numbers of bone marrow megakaryocytes before starting eltrombopag than in those with decreased numbers of megakaryocytes. Eltrombopag is a promising treatment for both PIT and SFPR after allogeneic HCT. The number of megakaryocytes in bone marrow before eltrombopag treatment may predict the response to eltrombopag. PMID:26785333

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

    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

  10. Linkage between the mechanisms of thrombocytopenia and thrombopoiesis.

    Eto, Koji; Kunishima, Shinji

    2016-03-10

    Thrombocytopenia is defined as a status in which platelet numbers are reduced. Imbalance between the homeostatic regulation of platelet generation and destruction is 1 potential cause of thrombocytopenia. In adults, platelet generation is a 2-stage process entailing the differentiation of hematopoietic stem cells into mature megakaryocytes (MKs; known as megakaryopoiesis) and release of platelets from MKs (known as thrombopoiesis or platelet biogenesis). Until recently, information about the genetic defects responsible for congenital thrombocytopenia was only available for a few forms of the disease. However, investigations over the past 15 years have identified mutations in genes encoding >20 different proteins that are responsible for these disorders, which has advanced our understanding of megakaryopoiesis and thrombopoiesis. The underlying pathogenic mechanisms can be categorized as (1) defects in MK lineage commitment and differentiation, (2) defects in MK maturation, and (3) defect in platelet release. Using these developmental stage categories, we here update recently described mechanisms underlying megakaryopoiesis and thrombopoiesis and discuss the association between platelet generation systems and thrombocytopenia. PMID:26787737

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

    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

  12. The gut microbiome as a target for regulatory T cell-based immunotherapy: induction of regulatory lymphocytes by oral administration of anti-LPS enriched colostrum alleviates immune mediated colitis

    Yaʼacov, Ami Ben; Lichtenstein, Yoav; Zolotarov, Lidya; Ilan, Yaron

    2015-01-01

    Background Gut-derived bacterial endotoxin is an important cofactor in the pathogenesis of IBD. Regulatory T cells (Tregs) are essential for maintenance of peripheral tolerance and can prevent and alleviate IBD. To determine the immune modulatory effect of anti-LPS enriched hyperimmune colostrum, its ability to induce Tregs and alleviate immune mediated colitis. Methods Immune-mediated colitis was induced in mice by intra-colonic instillation of Trinitrobenzene Sulfonate (TNBS). Four groups o...

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

    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

  14. High syndecan-1 levels in acute myeloid leukemia are associated with bleeding, thrombocytopathy, endothelial cell damage, and leukocytosis

    Larsen, Anne Mette Vestskov; Leinøe, Eva Birgitte; Johansson, Pär I;

    2013-01-01

    The risk of hemorrhage is influenced by multiple factors in acute myeloid leukemia (AML). We investigated whether hemorrhage in AML patients was associated with endothelial perturbation, potentially caused by thrombocytopenia, platelet dysfunction and leukocytosis. Biomarkers of endothelial pertu...

  15. [Consensus report on the management of immune thrombocytopenia in pregnancy].

    Miyakawa, Yoshitaka

    2015-10-01

    Primary immune thrombocytopenia (ITP) is a benign hematological disorder characterized by platelet counts under 100×10(9)/l. We updated the consensus report for the management of ITP in pregnancy after a 20-year lag. For this update, not only hematologists, but also obstetricians, pediatricians, and anesthesiologists joined our committee. We recommend that physicians maintain platelet counts above 20×10(6)/l in the first and second trimesters. We also agree that counts should be at least 50×10(9)/l and 80×10(9)/l for vaginal and C-section deliveries, respectively. There might be no obvious reasons to forbid lactation in ITP patients receiving treatment with corticosteroids. In this educational session, I will discuss the differential diagnosis of thrombocytopenia and the management of ITP in pregnant women and their neonates based on international and updated domestic guidelines. PMID:26458448

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

    Avital F. Barak

    2011-12-01

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

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

    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.

  18. Thrombocytopenia with absent radius in a boy and his uncle.

    Schnur, R E; Eunpu, D L; Zackai, E H

    1987-09-01

    We report a boy and his maternal uncle who have Thrombocytopenia-Absent Radius (TAR) syndrome. The mother of the propositus is normal. A maternal aunt has mild radial hypoplasia, possibly representing partial expression of the syndrome. A review of the literature shows several pedigrees in which relatives other than sibs were affected with TAR. Thus, autosomal recessive inheritance may not account for all cases and alternate modes of transmission should be considered. PMID:3314504

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

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

    2016-01-01

    Background Immune thrombocytopenia (ITP) is a hematological disorder with an isolated decrease in number of circulating platelets. Bee venom therapy (BVT) is a form of alternative medicine. It is still being practiced in the Middle East and other parts of Asia. In BVT, acupuncture points are used to inject diluted bee venom into the body. The pharmacological basis behind BVT is not fully understood. However, it has been used to treat various medical conditions such as arthritis and low back p...

  20. The pathophysiology of thrombocytopenia in chronic liver disease

    Sigal, Samuel

    2016-01-01

    Oscar Mitchell,1 David M Feldman,1,2 Marla Diakow,1 Samuel H Sigal3 1Department of Medicine, 2Division of Gastroenterology and Liver Diseases, New York University School of Medicine, Langone Medical Center, New York, 3Division of Gastroenterology and Liver Diseases, Department of Medicine, Montefiore Medical Center, Albert Einstein College of Medicine, Bronx, NY, USA Abstract: Thrombocytopenia is the most common hematological abnormality encountered in patients with chronic liver disease (CL...

  1. Clinical spectrum of thrombocytopenia in adult population of karachi

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

  2. Effect of recombinant human thrombopoietin on exsanguine thrombocytopenia mice

    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.

  3. A Rare Case of Myelodysplastic Syndrome with Refractory Thrombocytopenia.

    Jehangir, Waqas; Webb, John; Singh, Shilpi; Arshed, Sabrina; Sen, Shuvendu; Yousif, Abdalla

    2015-09-23

    Myelodysplastic syndromes (MDS) represent a variety of clonal abnormalities, possibly preleukemic and display numerous phenotypic manifestations. Specific mutations carry high morbidity and mortality rates due to cell line dysplasia. MDS commonly presents with symptoms related to anemia, and approximately two-thirds will develop thrombocytopenia, a rare, but potentially lethal complication that increases complexity in treatment and morbidity, and may be due to unique genetic mutations leading to refractory thrombocytopenia, ultimately leading to an overall reduction in survival. Careful identification and monitoring of this patient subdivision can significantly reduce morbidity and mortality, and potential identification of specific gene mutations and advances in treatment options will hopefully provide guidance on detecting at-risk patients in the future. We present a case of a man with MDS-U (karyotype 46, XY, del (20) (q11.2q13.3) (20) with no detected JAK2 V617F mutation), who in despite of appropriate evidenced based treatment, continued to exhibit refractory thrombocytopenia. PMID:26487931

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

    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...

  5. Cytokine expression during early and late phase of acute Puumala hantavirus infection

    Sadeghi Mahmoud; Eckerle Isabella; Daniel Volker; Burkhardt Ulrich; Opelz Gerhard; Schnitzler Paul

    2011-01-01

    Abstract Background Hantaviruses of the family Bunyaviridae are emerging zoonotic pathogens which cause hemorrhagic fever with renal syndrome (HFRS) in the Old World and hantavirus pulmonary syndrome (HPS) in the New World. An immune-mediated pathogenesis is discussed for both syndromes. The aim of our study was to investigate cytokine expression during the course of acute Puumala hantavirus infection. Results We retrospectively studied 64 patients hospitalised with acute Puumala hantavirus i...

  6. Comparative study of mild versus moderate to severe thrombocytopenia in third trimester of pregnancy in a tertiary care hospital

    Rupa Vyas

    2014-01-01

    Full Text Available Aims & objectives To determine etiology, maternal complications and fetomaternal outcome in third trimester of pregnancies complicated by moderate to severe thrombocytopenia and compare it with mild thrombocytopenia. Materials & methods It was a case control cross sectional study of third trimester pregnancy with thrombocytopenia. Platelet count of 1,00,000 to 1,50,000/μL, 50,000 to 1,00,000/μL & <50,000/μL were classified as mild, moderate and severe thrombocytopenia respectively. Etiology and fetomaternal outcome of thrombocytopenia in third trimester of pregnancy were evaluated and compared. Results Among 4818 deliveries, 378 women (7.67% had thrombocytopenia. Out of them 112 (2.3% women had moderate to severe thrombocytopenia (study group and 266 had mild thrombocytopenia (control group. Major causes were gestational thrombocytopenia (GT, idiopathic thrombocytopenic purpura (ITP, preeclampsia, HELLP syndrome, malaria, dengue and other etiologies of viremia. Maternal complications due to bleeding tendencies like placental abruption, postpartum hemorrhage were evident in the study population (p< 0.001. Fetal complications were significantly higher in study group. Early neonatal thrombocytopenia depended on etiology rather than severity of maternal thrombocytopenia. Conclusions Outcome of pregnancy with moderate to severe thrombocytopenia depends mainly on the primary disease causing thrombocytopenia. Adverse outcomes are especially seen with pregnancy complicated by preeclampsia and HELLP syndrome. Fetomaternal outcome is favorable in ITP and gestational thrombocytopenia. Early detection and intervention play a key role in decreasing fetomaternal morbidities.

  7. Moving towards a new era in the management of chronic immune thrombocytopenia

    Wadenvik, Hans; Olsson, Bob

    2010-01-01

    Abstract Immune thrombocytopenia (ITP) is an organ-specific autoimmune disease in which a low concentration of plasma thrombopoietin (TPO) contributes to the thrombocytopenia. Functional thrombopoietin deficiency in response to thrombocytopenia is central to the pathophysiology of chronic ITP. Decreased platelet production in ITP patients has been described only in recent years, however. Following the development of TPO-mimetics, it has become clear that the augmentation of thrombo...

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

    Ayadi, Imene Dahmane; Hamida, Emira Ben; 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 109/L. Within the sec...

  9. [Severe thrombocytopenia associated with simultaneous cytomegalovirus and Epstein-barr virus infection in an immunocompetence patient].

    Bober, Grazyna; Krawczyk-Kuliś, Małgorzata; Kopera, Małgorzata; Hołowiecki, Jerzy

    2003-06-01

    A 22 year old woman, without preceeding immunological and hematological disorders was hospitalized because of severe thrombocytopenia. The results of extended workup revealed simultaneous cytomegalovirus and Epstein-Barr virus infection as the most probable causative factor. Both, thrombocytopenia and the symptoms of viral infections resolved after consequent treatment with acyclovir, corticosteroids and intravenous immunoglobulines. Based on this original case report authors suggest the need of virological tests in newly diagnosed idiopatic thrombocytopenia. PMID:14567095

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

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

    2001-01-01

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

  11. Interferon-β therapy and risk of thrombocytopenia in multiple sclerosis patients.

    Koudriavtseva, Tatiana; Plantone, Domenico; Renna, Rosaria; Mandoj, Chiara; Giannarelli, Diana; Mainero, Caterina

    2015-12-01

    Thrombocytopenia is a well-described adverse event of several disease-modifying therapies (DMT) in multiple sclerosis (MS). On the other hand, an increased prevalence of MS has been reported in patients with immune thrombocytopenia. In this retrospective, cross-sectional, case-control study we evaluated in a heterogeneous MS cohort: (1) the prevalence of thrombocytopenia in comparison with sex- and age-matched controls; (2) the relationship between thrombocytopenia and patients' demographic, clinical characteristics; (3) the risk for thrombocytopenia in relation to DMT. 187 consecutive MS patients [51 males, mean age (±SD) 44.5 ± 10.7 years] and 200 controls (56 males, mean age 45.5 ± 12 years) were included. Thrombocytopenia was defined as platelet count lower than normal laboratory values (130-400 × 10(9)/L). The prevalence of thrombocytopenia was significantly higher in MS patients than in controls (7 vs. 2.5 %, p = 0.04). Thrombocytopenia was present only in relapsing-remitting MS cases, and significantly associated with lower EDSS (p = 0.002) and with a trend for shorter disease duration (p = 0.06). It was more frequent in patients on high-dose interferon-β therapy compared with those on low-dose interferon-β therapy, other therapies or untreated patients (p = 0.02). High-dose interferon-β therapy was associated with more than eightfold increase in the risk for thrombocytopenia (odds ratio 8.60, 95 % confidence interval: 1.01-74.48 adjusted for EDSS, disease duration and type of disease). The prevalence of thrombocytopenia was increased in MS patients treated with DMT. High-dose interferon-β therapy is the variable most strongly associated with thrombocytopenia. PMID:26209931

  12. Effect of vitamin E on thrombocytopenia in dengue fever

    Arvind Vaish

    2012-01-01

    Full Text Available Context: Dengue fever frequently causes thrombocytopenia for which there is no satisfactory treatment. Aim: To evaluate the effect of vitamin E on thrombocytopenia in dengue fever. Settings and Design: A tertiary teaching hospital during a recent outbreak of dengue fever in the area. Materials and Methods: Patients of dengue fever (as per WHO criteria with thrombocytopenia and platelet counts between 10 × 10 3 /mm 3 and 100 × 10 3 /mm 3 seen during September 1, 2010 to November 30, 2010 were enrolled. After detailed history and clinical evaluation, the patients were randomized to two groups - group I which received vitamin E 400 mg (Evion, Merck once daily along with standard treatment and group II which received standard treatment only. The platelet counts, bleeding manifestations, requirement for platelet transfusion were serially monitored for up to 1 week in these cases. Statistical Analysis Used: Percentage, mean, standard error of mean, Mann-Whitney U test, and Chi-square test. Results: We enrolled 66 cases (group I - 33 and group II - 33. Mean platelet count at baseline in both the groups was similar (group I - 28.39 ± 1.61 × 10 3 /mm 3 and group II - 27.64 ± 1.65 × 10 3 /mm 3 (P > 0.05. We observed that the mean platelet count on day 4 in group I (vitamin E was significantly higher (Mean - 122.19 ± 9.98 × 10 3 /mm 3 ; CI 95% -102.63 × 10 3 /mm 3 - 141.76 × 10 3 /mm 3 than in group II (Mean - 92.57 ± 7.93 × 10 3 /mm 3 ; CI 95% - 77.03 × 10 3 /mm 3 - 108.11 × 10 3 /mm 3 (P = 0.0436. Similar findings were also observed on day 7 in the two groups. Platelet transfusion was required in less cases in group I [2 out of 33 (6.06%] as compared to group II [5 out of 33 (15.15%]. Conclusion: We conclude that vitamin E is beneficial in thrombocytopenia in dengue fever and results in faster increase in the platelet counts.

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

    Deepak sharma; Srinivas Murki; Tejo Pratap

    2015-01-01

    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, 4...

  14. Microangiopathic hemolytic anemia and severe thrombocytopenia in Brucella infection.

    Di Mario, A; Sica, S; Zini, G; Salutari, P; Leone, G

    1995-01-01

    A case of Brucella septicemia presenting at the onset as a severe microangiopathic hemolytic anemia with coexisting dramatic hemorrhagic syndrome (severe epistaxis, gross hematuria, and skin purpura) is reported. A hemogram showed severe thrombocytopenia, anemia, and leukopenia. Bone marrow morphology showed the typical features associated with Brucella infection: numerous histiocytes with signs of activation, multiple granulomata, giant cells, and hemophagocytosis. After appropriate antimicrobial therapy, the clinical and hematological status of the patient improved, and he is alive and well 1 year later with disappearance of all hematological abnormalities. PMID:7827209

  15. Ranitidine-induced thrombocytopenia: A rare drug reaction

    Amit V Bangia

    2011-01-01

    Full Text Available H 2 antagonist ranitidine causing thrombocytopenia is a rare drug phenomenon. Here we present a case of 55 year old female of pustular psoriasis who presented with fever and vomiting. Patient. was started on roxithromycin, iv ondensetron, paracetamol and iv ranitidine. Complete blood count revealed neutrophilia with normal blood picture. However repeat investigations showed falling WBC and platelet count. After excluding other causes of pancytopenia we concluded that ranitidine was the cause for this atypical drug reaction, more so when the blood picture improved within 72 hrs of ranitidine withdrawal.

  16. Profound thrombocytopenia induced by clopidogrel with a prior history of long-term safe administration

    Guo, Yuan-Lin; Li, Jian-Jun; Yuan, Jin-qing; Qin, Xue-Wen; Zheng, Xin; Mu, Chao-Wei; Hua, Yi-Hong

    2010-01-01

    Clopidogrel has shown an excellent safety, tolerability and efficacy ever since its marketing. However, here we report a rare case with profound thrombocytopenia following clopidogrel administration previously safely exposed to this same drug. This reminds us that thrombocytopenia might be induced by clopidogrel even with a prior, safe history of long-term administration.

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

    HU, Bao-Yu; Li, Wen-Jun; Zhang Xiang-Yan; Jiang Xu-Cheng; Yang Hong-Liang; Zhao Guo-Ping; Guo Xiao-Kui

    2006-01-01

    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 o...

  18. Pentosan-induced thrombocytopenia: support for an immune complex mechanism.

    Goad, K E; Horne, M K; Gralnick, H R

    1994-12-01

    Pentosan polysulphate is a low molecular weight heparinoid that is used as an anticoagulant. Because the drug also has antineoplastic properties, it has been used experimentally at the National Institutes of Health to treat metastatic malignancies. We present the case of a patient who developed thrombocytopenia resembling Type II heparin-induced thrombocytopenia (HIT) during the course of pentosan therapy. The patient's plasma demonstrated platelet reactivity both by aggregometry and 14C-serotonin release in the presence of pentosan. Heparin and other polyanions could substitute for pentosan in aggregation studies. The aggregating activity co-purified with the patient's IgG and was inhibited by pre-incubation with monoclonal antibody (MoAb) to the platelet Fc receptor. To elucidate the relationship between the platelet, the polyanion and the antibody, we measured the binding of 3H-heparin to platelets in the presence of the patient's IgG and found that it was increased 6-fold over binding in the presence of control IgG. Heparin binding was not reduced by MoAb against the Fc receptor. Taken together, these data support a model in which polyanion-antibody complexes attach to the platelet surface by the polyanion and secondarily stimulate the platelet via their Fc termini. PMID:7529541

  19. Newly diagnosed immune thrombocytopenia: update on diagnosis and management.

    Bansal, Deepak; Rajendran, Aruna; Singhi, Sunit

    2014-10-01

    Immune thrombocytopenia (ITP) continues to intrigue pediatricians and hematologists alike. Patients can have a dramatic presentation with wide-spread bleeds over a few days. There is an aura and fear of intra-cranial hemorrhage that drives the physician to recommend and the patient's family to accept drug treatment. Difference of opinion among physicians in the recommendations for treatment is not uncommon, even though recent evidence-based guidelines recommend a conservative, observation-based approach for the majority of patients with newly diagnosed childhood ITP. It is important to note that a specific 'platelet cut-off count', is no longer suggested as an indication by itself to recommend drug therapy. The manuscript is an update on newly diagnosed ITP in children. Recent changes in definitions and recommendations for treatment are highlighted. Pros and cons of 1st line drugs, including corticosteroids, intravenous immunoglobulin and anti-D are listed. Adjunctive therapies for the management of epistaxis and menorrhagia are described. Role of splenic artery embolization and emergency splenectomy in the backdrop of severe thrombocytopenia is discussed. Realistic case scenarios, common errors and frequently asked questions are included for a practical and easy reading. PMID:24091868

  20. Heparin-Induced Thrombocytopenia Associated with a Heparin-Bonded Stent Graft.

    Blas, Joseph-Vincent V; Carsten, Christopher G; Gray, Bruce H

    2016-05-01

    We describe a case of heparin-induced thrombocytopenia (HIT) in association with heparin-bonded stent grafts. A 61-year-old man with claudication secondary to a left superficial femoral artery (SFA) occlusion was treated with 2 heparin-bonded polytetrafluorethylene (hep-PTFE) grafts. Despite the use of antiplatelet medication, he presented with thrombosed hep-PTFE grafts 1 week after initial treatment. An additional hep-PTFE graft was placed at the SFA origin because of migration of the first graft. He was discharged on anticoagulation; however, he presented again 2 weeks later with recurrent SFA thrombosis and a platelet count of 60,000, raising suspicion for HIT. All exogenous forms of heparin were discontinued, and he was started on an alternative anticoagulant. The patient returned again 5 days after being discharged with recurrent symptoms of acute limb ischemia. He underwent a left femoropopliteal artery bypass with autogenous conduit and removal of the grafts. He has since had an uneventful recovery. We believe HIT should be considered as a potential cause of hep-PTFE graft thrombosis. Diagnosis and management of these patients is complex and may require explantation of the graft. PMID:26902939

  1. RhIG for the treatment of immune thrombocytopenia: consensus and controversy

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

    2012-01-01

    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. PMID:21981825

  2. Association of the Serum Angiotensin II Level with Disease Severity in Severe Fever with Thrombocytopenia Syndrome Patients.

    Cheng, Jiamei; Li, Huiyu; Jie, Shenghua

    2016-01-01

    Objective Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease caused by a novel Bunyavirus. Recent data suggest that the physiological balance of multiple proinflammatory cytokines is substantially changed in cases of severe fever with thrombocytopenia syndrome virus (SFTSV) infection, and the inflammatory response probably plays an important role in disease progression. Angiotensin II is an important active substance of the renin-angiotensin system, and studies have demonstrated that angiotensin II is involved in key events in the inflammatory process and can regulate inflammatory cell responses. Methods In order to elucidate the role of angiotensin II in the pathogenesis of SFTS, we collected serum samples from SFTS patients in the acute or convalescent phase and tested the angiotensin II levels using an enzyme-linked immunosorbent assay as well as SFTSV viral RNA with real-time reverse-transcriptase polymerase chain reaction. Furthermore, we explored possible correlations between the angiotensin II levels and clinical parameters in SFTS patients. Results Our data showed that the serum level of angiotensin II was significantly increased in the acute phase compared with that seen in the convalescent phase and the healthy controls, while there were no significant differences between the convalescent cases and healthy controls (p>0.05). A correlation analysis demonstrated that the level of angiotensin II positively correlated with the SFTS viral RNA load. The angiotensin II levels were also found to be correlated with clinical parameters indicating impairments in organ functions. Moreover, we also found that the angiotensin II levels were significantly increased in the severe cases versus the non-severe cases (p<0.001). Conclusion The serum angiotensin II levels in SFTS patients may be used to stratify the disease severity and are possibly predictive of disease outcomes. PMID:27086801

  3. Advances in Diagnosis and Treatments for Immune Thrombocytopenia

    Nomura, Shosaku

    2016-01-01

    Immune thrombocytopenia (ITP) is an acquired hemorrhagic condition characterized by the accelerated clearance of platelets caused by antiplatelet autoantibodies. A platelet count in peripheral blood number of bleeding events. TRAs are usually considered safe, effective treatments for patients with chronic ITP at risk of bleeding after failure of first-line therapies. Due to the high costs of TRAs, however, it is unclear if patients prefer these agents. In addition, some new agents are under development now. This manuscript summarizes the pathophysiology, diagnosis, and treatment of ITP. The goal of all treatment strategies for ITP is to achieve a platelet count that is associated with adequate hemostasis, rather than a normal platelet count. The decision to treat should be based on the bleeding severity, bleeding risk, activity level, likely side effects of treatment, and patient preferences.

  4. Management of Pregnancy-Associated Thrombotic Thrombocytopenia Purpura

    Ashley Fyfe-Brown

    2013-05-01

    Full Text Available Thrombotic thrombocytopenia purpura (TTP is an infrequent but serious disease. Pregnancy is a known risk factor for presentation or relapse of TTP. Difficulties in differentiating TTP from preeclampsia/HELLP (hemolysis, elevated liver enzymes and low platelets syndrome, and current treatment recommendations are discussed in this case report. A woman with previously treated and stable TTP had a relapse at 36 weeks' gestation. Careful surveillance led to an early diagnosis. Severe disease in the peripartum period was treated successfully with cryosupernatant plasma-based plasmapheresis and platelet transfusion, with good maternal and neonatal outcomes. Cryosupernatant plasma is a viable alternative to fresh frozen plasma for plasmapheresis for TTP and may offer some therapeutic and logistical advantages. Platelet transfusion can be undertaken safely if needed to prevent or treat significant hemorrhage.

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

    Francesca Palandri

    2012-06-01

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

  6. Early-Onset Thrombocytopenia in Small-For-Gestational-Age Neonates: A Retrospective Cohort Study

    Vlug, R. D.; Smits-Wintjens, V. E. H. J.; Heckman, E. J.; te Pas, A. B.; Fijnvandraat, K.; Lopriore, E.

    2016-01-01

    Thrombocytopenia is a common finding in small for gestational age (SGA) neonates and is thought to result from a unique pathophysiologic mechanism related to chronic intrauterine hypoxia. Our objective was to estimate the incidence and severity of early-onset thrombocytopenia in SGA neonates, and to identify risk factors for thrombocytopenia. We performed a retrospective cohort study of all consecutive SGA neonates admitted to our ward and a control group of appropriate for gestational age (AGA) neonates matched for gestational age at birth. Main outcome measures were incidence and severity of thrombocytopenia, hematological and clinical risk factors for thrombocytopenia, and bleeding. A total of 330 SGA and 330 AGA neonates were included, with a mean gestational age at birth of 32.9 ± 4 weeks. Thrombocytopenia (<150x109/L) was found in 53% (176/329) of SGA neonates and 20% (66/330) of AGA neonates (relative risk (RR) 2.7, 95% confidence interval (CI) [2.1, 3.4]). Severe thrombocytopenia (21-50x109/L) occurred in 25 neonates (8%) in the SGA and 2 neonates (1%) in the AGA group (RR 12.5, 95% CI [3.0, 52.5]). Platelet counts <20x109/L were not recorded. Within the SGA group, lower gestational age at birth (p = <0.01) and erythroblastosis (p<0.01) were independently associated with a decrease in platelet count. Platelet count was positively correlated with birth weight centiles. In conclusion, early-onset thrombocytopenia is present in over 50% of SGA neonates and occurs 2.7 times as often as in AGA neonates. Thrombocytopenia is seldom severe and is independently associated with lower gestational age at birth and erythroblastosis. PMID:27177157

  7. Over-testing for heparin induced thrombocytopenia in hospitalized patients.

    Chaturvedi, Shruti; Kohli, Ruhail; McCrae, Keith

    2015-07-01

    Heparin induced thrombocytopenia (HIT) is a pro-thrombotic and potentially fatal complication of heparin therapy. Its diagnosis rests on high clinical probability and the laboratory demonstration of anti-PF4/heparin antibodies. The high prevalence of thrombocytopenia in hospitalized patients and the high sensitivity but low specificity of immunoassays for HIT antibodies can lead to over-testing and over-diagnosis. We conducted a study to review HIT screening practices in a tertiary care setting. We reviewed 63 consecutive patients undergoing testing for anti-PF4/heparin antibodies over 3 months. Pre-test probability for HIT was calculated using the 4T score. Sixty three patients underwent testing for anti-PF4/heparin antibodies. Twenty one had been admitted for cardiovascular surgery, 5 for other surgery and 35 for non-surgical indications. Twenty nine patients (46 %) had low pre- test probability, twenty three (36.5 %) had intermediate probability, and eleven (17.4 %) had high pre-test probability of having HIT. Anti-PF4/heparin ELISA was positive in 8 of 63 patients. SRA was ordered for 16 patients and was positive in 5. Only five patients were diagnosed and treated for HIT. Over-testing for HIT is highly prevalent in a tertiary care setting. This increases cost and exposes patients to expensive anti-coagulation with its attendant risk of hemorrhage. The 4Ts score has been shown to have high sensitivity and may be used to rule out HIT in most situations, although its utility depends on subjective analysis. Consistently applying this in practice could minimize over-testing and facilitate safer, cost-effective care. PMID:25127902

  8. Giant Asian honeybee stings induced acute myocarditis: a case report

    NP Dinamithra

    2013-10-01

    Full Text Available Hymenopterid stings and subsequent allergic reactions including fatal anaphylaxis are a common indication for emergency department visits worldwide. Less commonly, multiple wasp stings can result in multi-system involvement ranging from intravascular hemolysis, rhabdomyolysis, acute renal failure, cardiac involvement, hepatic dysfunction and occasionally thrombocytopenia and coagulopathy. Here we report one case of multiple Giant Asian honey bee stings induced myocarditis.

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

    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.

  10. Genetic or Pharmacologic Amplification of Nrf2 Signaling Inhibits Acute Inflammatory Liver Injury in Mice

    Osburn, William O.; YATES, Melinda S.; Dolan, Patrick D.; Liby, Karen T.; Sporn, Michael B.; Taguchi, Keiko; Yamamoto, Masayuki; Kensler, Thomas W.

    2008-01-01

    Oxidative stress-mediated destruction of normal parenchymal cells during hepatic inflammatory responses contributes to the pathogenesis of immune-mediated hepatitis and is implicated in the progression of acute inflammatory liver injury to chronic inflammatory liver disease. The transcription factor NF-E2-related factor 2 (Nrf2) regulates the expression of a battery of antioxidative enzymes and Nrf2 signaling can be activated by small-molecule drugs that disrupt Keap1-mediated repression of N...

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

    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.

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

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

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

    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

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

    Shiny Varghese; Gagandeep Kour; Tapasya Dhar

    2016-01-01

    Background: To investigate the etiology, obstetrical risk factors, complications and outcomes of pregnancies affected by thrombocytopenia. Methods: A retrospective surveillance study was conducted on the basis of hospital records of 1532 women who delivered during a period of one year, in Christian Medical College and Hospital, Ludhiana, India. Clinical data including basic history, physical examination and investigations of those women who had thrombocytopenia, was evaluated and compiled ...

  15. [Syncumar-induced necrosis following heparin-induced thrombocytopenia and thrombosis].

    Pósán, E; Adi, S; Szücs, G; Rigó, J; Boda, Z

    1995-04-30

    The authors describe the combined occurrence of heparin-induced thrombocytopenia and cumarin-induced skin necrosis, a rare condition that has not yet been reported in Hungary. The 69-year-old woman had received prophylactic heparin treatment prior to total hip arthroplasty. The first complication that the anticoagulant therapy brought about was serious thrombocytopenia paradoxically associated not with bleeding but with deep vein thrombosis. The latter necessitated coumarin therapy which resulted in severe skin necrosis. PMID:7739854

  16. Thrombocytopenia model with minimal manipulation of blood cells allowing whole blood assessment of platelet function.

    Tiedemann Skipper, Mette; Rubak, Peter; Halfdan Larsen, Ole; Hvas, Anne-Mette

    2016-06-01

    In vitro models of thrombocytopenia are useful research tools. Previously published models have shortcomings altering properties of platelets and other blood components. The aim of the present study was to develop a whole blood method to induce thrombocytopenia with minimal manipulation, and to describe platelet function in induced thrombocytopenia in individuals with healthy platelets. Hirudin anticoagulated blood was obtained from 20 healthy volunteers. One part of the blood was gently centrifuged at 130g for 15 minutes. The platelet-rich plasma was replaced with phosphate-buffered saline to establish thrombocytopenia. Various levels of thrombocytopenia were achieved by combining different volumes of baseline whole blood and thrombocytopenic blood. Platelet counts were measured by flow cytometry (Navios, Beckman Coulter) and routine haematological analyser (Sysmex XE-5000). Platelet function was analysed by impedance aggregometry (Multiplate® Analyzer, Roche) and by flow cytometry (Navios, Beckman Coulter) using collagen, adenosine diphosphate, thrombin receptor activating peptide-6 and ristocetin as agonists. Median baseline platelet count was 227×10(9)/l. The in vitro model yielded median platelet counts at 51×10(9)/l (range 26-93×10(9)/l). We observed minor, yet significant, changes in platelet size and maturity from baseline to modelled thrombocytopenia. In the thrombocytopenic samples, significant and positive linear associations were found between platelet count and platelet aggregation across all agonists (all p-valuesblood-based model of thrombocytopenia was established and validated. This new model serves as a useful future tool, particularly to explore platelet function in patients with thrombocytopenia. PMID:26555800

  17. Serum Thrombopoietin and cMpl Expression in Thrombocytopenia of Different Etiologies

    Fabrizio Vianello; Silvia Vettore; Fabiana Tezza; Luca De Toni; Raffaella Scandellari; Luisa Sambado; Martina Treleani; Fabrizio Fabris

    2014-01-01

    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 ...

  18. Immune thrombocytopenia: clinical manifestation and therapy response. The interim analysis of Russian register of patients with primary immune thrombocytopenia and literature review

    I. A. Lisukov

    2013-01-01

    Full Text Available Primary immune thrombocytopenia (ITP is a rare (orphan blood disease. Most frequent manifestations of ITP are purpura, petechiae and bleedings with many patients have either no symptoms or minimal bleedings manifestation. The management of ITP varies widely and must be based on current international recommendations and individual assessment of clinical course. The paper presents the results of interim analysis of clinical course and therapeutic approaches in the Russian register of ITP patients with immune thrombocytopenia and literature review about ITP treatment approaches.

  19. Severity of thrombocytopenia in patients with plasmodium vivax malaria; a single center study

    Thrombocytopenia has been frequently observed in plasmodium vivax malaria in different studies. Finding out the severity of thrombocytopenia is perhaps equally important, as it has practical as well as prognostic implications. The objective of the study was to assess the severity of thrombocytopenia in patients suffering from malaria caused by plasmodium vivax. Methods: This cross-sectional study was carried out at Combined Military Hospital (CMH) Malir, Karachi, which is a tertiary care Hospital for all military personnel and their families in the province of Sindh. All patients of smear positive Vivax malaria during the study period were included, and those having hrombocytopenia from any other reason were excluded. They were treated with anti-malarial drugs and their platelet counts were monitored till they normalized and discharged from the hospital. Thrombocytopenia was defined as platelets count of <150,000/cu mm. Results were analysed by SPSS 11. Results: Out of 150 cases, 133 (88%) had thrombocytopenia. Their ages ranged from 15 to 55; mean age was 35 with SD ± 20. Low platelet count observed was between 11000 and 146000/cu mm with SD ± 27404. Mean value was 79 832/cu mm. None of the patient had any bleeding episode requiring a blood transfusion. Conclusion: Plasmodium vivax associated thrombocytopenia has a benign outcome irrespective of severity of the platelet counts. (author)

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

    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.

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

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

    2016-01-01

    The introduction of targeted biological therapies has revolutionised the management of immune-mediated inflammatory diseases (IMIDs) such as rheumatoid arthritis, ankylosing spondylitis, psoriasis and inflammatory bowel disease. Following treatment with these therapies, many patients experience significant improvements in different aspects of their disease, including symptoms, work productivity and other outcomes relevant for individuals and society. However, due to the complexity of biological drug development and manufacturing processes, the costs of these therapies are relatively high. Indeed, the financial burden on healthcare systems due to biological therapies is considerable and lack of patient access to effective treatment remains a concern in many parts of the world. As many reference biological therapies have now reached or are near to patent expiry, a number of 'biosimilar' drugs have been developed for use in various clinical settings, and some of these drugs are already in use in several countries. While the potential pharmacoeconomic benefits of cost-effective biosimilars seem clear, several issues have been raised regarding, for example, the definition of biosimilarity and the validity of indication extrapolation, as well as the 'switchability' and relative immunogenicity of biosimilars and their reference drugs. In this review, these issues will be discussed with reference to CT-P13, a biosimilar of the anti-tumour necrosis factor monoclonal antibody infliximab, which is approved in Europe and elsewhere for the treatment of various IMIDs. Other important issues, including those related to data collection during nonclinical and clinical development of biosimilars, are also discussed. PMID:26403380

  2. Paradoxical reactions under TNF-α blocking agents and other biological agents given for chronic immune-mediated diseases: an analytical and comprehensive overview

    Toussirot, Éric; Aubin, François

    2016-01-01

    Paradoxical adverse events (PAEs) have been reported during biological treatment for chronic immune-mediated diseases. PAEs are defined as the occurrence during biological agent therapy of a pathological condition that usually responds to this class of drug. A wide range of PAEs have been reported including dermatological, intestinal and ophthalmic conditions, mainly with antitumour necrosis factor α (TNF-α) agents. True PAEs include psoriasis, Crohn's disease and hidradenitis suppurativa. Other PAEs may be qualified as borderline and include uveitis, scleritis, sarcoidosis and other granulomatous diseases (granuloma annulare, interstitial granulomatous dermatitis), vasculitis, vitiligo and alopecia areata. Proposed hypotheses to explain these PAEs include an imbalance in cytokine production, the differential immunological properties between the monoclonal antibodies and TNF-α soluble receptor, an unopposed type I interferon production and a shift towards a Th1/Th2 profile. Data from registries suggest that the risk for paradoxical psoriasis is low and non-significant. We discuss management of these PAEs, which depends on the type and severity of the adverse events, pre-existing treated conditions and the possibility of alternative therapeutic options for the underlying disease. Paradoxical adverse events are not restricted to anti-TNF-α agents and close surveillance of new available biological drugs (anti-interleukin-17/23, anti-integrin) is warranted in order to detect the occurrence of new or as yet undescribed events. PMID:27493788

  3. Integration of disease association and eQTL data using a Bayesian colocalisation approach highlights six candidate causal genes in immune-mediated diseases.

    Guo, Hui; Fortune, Mary D; Burren, Oliver S; Schofield, Ellen; Todd, John A; Wallace, Chris

    2015-06-15

    The genes and cells that mediate genetic associations identified through genome-wide association studies (GWAS) are only partially understood. Several studies that have investigated the genetic regulation of gene expression have shown that disease-associated variants are over-represented amongst expression quantitative trait loci (eQTL) variants. Evidence for colocalisation of eQTL and disease causal variants can suggest causal genes and cells for these genetic associations. Here, we used colocalisation analysis to investigate whether 595 genetic associations to ten immune-mediated diseases are consistent with a causal variant that regulates, in cis, gene expression in resting B cells, and in resting and stimulated monocytes. Previously published candidate causal genes were over-represented amongst genes exhibiting colocalisation (odds ratio > 1.5), and we identified evidence for colocalisation (posterior odds > 5) between cis eQTLs in at least one cell type and at least one disease for six genes: ADAM15, RGS1, CARD9, LTBR, CTSH and SYNGR1. We identified cell-specific effects, such as for CTSH, the expression of which in monocytes, but not in B cells, may mediate type 1 diabetes and narcolepsy associations in the chromosome 15q25.1 region. Our results demonstrate the utility of integrating genetic studies of disease and gene expression for highlighting causal genes and cell types. PMID:25743184

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

    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.

  5. Epidemiological and clinical characteristics of severe fever with thrombocytopenia syndrome (SFTS) in China: an integrated data analysis.

    Guo, C-T; Lu, Q-B; Ding, S-J; Hu, C-Y; Hu, J-G; Wo, Y; Fan, Y-D; Wang, X-J; Qin, S-L; Cui, N; Yang, Z-D; Zhang, X-A; Liu, W; Cao, W-C

    2016-04-01

    Severe fever with thrombocytopenia syndrome (SFTS) is an emerging infectious disease that was caused by a novel bunyavirus, SFTSV. The study aimed to disclose the epidemiological and clinical characteristics of SFTSV infection in China so far. An integrated clinical database comprising 1920 SFTS patients was constructed by combining first-hand clinical information collected from SFTS sentinel hospitals (n = 1159) and extracted data (n = 761) from published literature. The considered variables comprised clinical manifestations, routine laboratory tests of acute infection, hospitalization duration and disease outcome. SFTSV-IgG data from 19 119 healthy subjects were extracted from the published papers. The key clinical variables, case-fatality rate (CFR) and seroprevalence were estimated by meta-analysis. The most commonly seen clinical manifestations of SFTSV infection were fever, anorexia, myalgia, chill and lymphadenopathy. The major laboratory findings were elevated lactate dehydrogenase, aminotransferase, followed by thrombocytopenia, lymphocytopenia, elevated alanine transaminase and creatine kinase. A CFR of 12·2% was estimated, significantly higher than that obtained from national reporting data, but showing no geographical difference. In our paper, the mortality rate was about 1·9 parts per million. Older age and longer delay to hospitalization were significantly associated with fatal outcome. A pooled seroprevalence of 3·0% was obtained, which increased with age, while comparable for gender. This study represents a clinical characterization on the largest group of SFTS patients up to now. A higher than expected CFR was obtained. A wider spectrum of clinical index was suggested to be used to identify SFTSV infection, while the useful predictor for fatal outcome was found to be restricted. PMID:26542444

  6. Transfusion-Related Acute Lung Injured (TRALI): Current Concepts.

    Álvarez, P; Carrasco, R; Romero-Dapueto, C; Castillo, R L

    2015-01-01

    Transfusion-related acute lung injury (TRALI) is a life-threatening intervention that develops within 6 hours of transfusion of one or more units of blood, and is an important cause of morbidity and mortality resulting from transfusion. It is necessary to dismiss other causes of acute lung injury (ALI), like sepsis, acute cardiogenic edema, acute respiratory distress syndrome (ARDS) or bacterial infection. There are two mechanisms that lead to the development of this syndrome: immune-mediated and no immune- mediated TRALI. A common theme among the experimental TRALI models is the central importance of neutrophils in mediating the early immune response, and lung vascular injury. Central clinical symptoms are dyspnea, tachypnea, tachycardia, cyanosis and pulmonary secretions, altogether with other hemodynamic alterations, such as hypotension and fever. Complementary to these clinical findings, long-term validated animal models for TRALI should allow the determination of the cellular targets for TRALI-inducing alloantibodies as well as delineation of the underlying pathogenic molecular mechanisms, and key molecular mediators of the pathology. Diagnostic criteria have been established and preventive measures have been implemented. These actions have contributed to the reduction in the overallnumber of fatalities. However, TRALI still remains a clinical problem. Any complication suspected of TRALI should immediately be reported. PMID:26312100

  7. Severe Fever with Thrombocytopenia Syndrome Virus Antigen Detection Using Monoclonal Antibodies to the Nucleocapsid Protein

    Fukuma, Aiko; Fukushi, Shuetsu; Yoshikawa, Tomoki; Tani, Hideki; Taniguchi, Satoshi; Kurosu, Takeshi; Egawa, Kazutaka; Suda, Yuto; Singh, Harpal; Nomachi, Taro; Gokuden, Mutsuyo; Ando, Katsuyuki; Kida, Kouji; Kan, Miki; Kato, Nobuyuki; Yoshikawa, Akira; Kitamoto, Hiroaki; Sato, Yuko; Suzuki, Tadaki; Hasegawa, Hideki; Morikawa, Shigeru; Shimojima, Masayuki; Saijo, Masayuki

    2016-01-01

    Background Severe fever with thrombocytopenia syndrome (SFTS) is a tick-borne infectious disease with a high case fatality rate, and is caused by the SFTS virus (SFTSV). SFTS is endemic to China, South Korea, and Japan. The viral RNA level in sera of patients with SFTS is known to be strongly associated with outcomes. Virological SFTS diagnosis with high sensitivity and specificity are required in disease endemic areas. Methodology/Principal Findings We generated novel monoclonal antibodies (MAbs) against the SFTSV nucleocapsid (N) protein and developed a sandwich antigen (Ag)-capture enzyme-linked immunosorbent assay (ELISA) for the detection of N protein of SFTSV using MAb and polyclonal antibody as capture and detection antibodies, respectively. The Ag-capture system was capable of detecting at least 350–1220 TCID50/100 μl/well from the culture supernatants of various SFTSV strains. The efficacy of the Ag-capture ELISA in SFTS diagnosis was evaluated using serum samples collected from patients suspected of having SFTS in Japan. All 24 serum samples (100%) containing high copy numbers of viral RNA (>105 copies/ml) showed a positive reaction in the Ag-capture ELISA, whereas 12 out of 15 serum samples (80%) containing low copy numbers of viral RNA (<105 copies/ml) showed a negative reaction in the Ag-capture ELISA. Among these Ag-capture ELISA-negative 12 samples, 9 (75%) were positive for IgG antibodies against SFTSV. Conclusions The newly developed Ag-capture ELISA is useful for SFTS diagnosis in acute phase patients with high levels of viremia. PMID:27045364

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

    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. PMID:26564154

  9. Evaluation of reticulated platelets in dogs with breed-related thrombocytopenia.

    Zmigrodzka, M; Guzera, M; Winnicka, A

    2014-01-01

    The aim of this study was to evaluate the percentage of reticulated platelets in healthy dogs with breed-related thrombocytopenia. Seventy two dogs, clinically healthy, were enrolled in the study. Blood was collected from the patients and anticoagulated with tripotassium ethylenediaminetetraacetic acid (K3-EDTA) and sodium citrate. Platelet count was obtained by an impedance haematology analyser and platelet morphology was evaluated by examination of blood smears. Patients were allocated into two groups. Group 1 consisted of 30 dogs with normal platelet count, whereas group 2 was composed of 42 dogs with thrombocytopenia. Thrombocytopenia was present in both K3-EDTA and citrate blood samples. Patients with thrombocytopenia were divided into two subgroups: the first subgroup included dogs with platelet count in K3-EDTA anticoagulated blood from 100 to 200 x10(9)/L, patients in the second subgroup had a platelet count of less than 100 x10(9)/L. The percentage of young reticulated platelets (RPs) labelled with thiazole orange, and the percentage of platelets coated with platelet surface-associated IgG, were determined in platelet-rich plasma (PRP) by a flow cytometer. The mean percentage of RPs in K3-EDTA and citrate PRP was significantly higher in dogs with thrombocytopenia than in dogs with normal platelet count. The mean percentage of RPs was significantly higher in citrate PRP than in K3-EDTA PRP in all groups. The results suggest that idiopathic, asymptomatic thrombocytopenia is not caused by platelet surface-associated IgG. Dogs with breed-related thrombocytopenia have a competent bone marrow. PMID:24724481

  10. Acute Myeloid Leukemia Presenting as Acute Appendicitis

    Sherri Rauenzahn

    2013-01-01

    Full Text Available Appendicitis in leukemic patients is uncommon but associated with increased mortality. Additionally, leukemic cell infiltration of the appendix is extremely rare. While appendectomy is the treatment of choice for these patients, diagnosis and management of leukemia have a greater impact on remission and survival. A 59-year-old Caucasian female was admitted to the surgical service with acute right lower quadrant pain, nausea, and anorexia. She was noted to have leukocytosis, anemia, and thrombocytopenia. Abdominal imaging demonstrated appendicitis with retroperitoneal and mesenteric lymphadenopathy for which she underwent laparoscopic appendectomy. Peripheral smear, bone marrow biopsy, and surgical pathology of the appendix demonstrated acute myeloid leukemia (AML with nonsuppurative appendicitis. In the setting of AML, prior cases described the development of appendicitis with active chemotherapy. Of these cases, less than ten patients had leukemic infiltration of the appendix, leading to leukostasis and nonsuppurative appendicitis. Acute appendicitis with leukemic infiltration as the initial manifestation of AML has only been described in two other cases in the literature with an average associated morbidity of 32.6 days. The prompt management in this case of appendicitis and AML resulted in an overall survival of 185 days.

  11. Candidate Soluble Immune Mediators in Young Women with High-Risk Human Papillomavirus Infection: High Expression of Chemokines Promoting Angiogenesis and Cell Proliferation

    Zanotta, Nunzia; Tornesello, Maria Lina; Annunziata, Clorinda; Stellato, Giovanni; Buonaguro, Franco Maria; Comar, Manola

    2016-01-01

    Background The causal interpretation of cervical immune response to Human Papillomavirus (HPV) infection is complex and poorly characterized mainly due to the delicate balance that exists between viral infection, increase of inflammatory cytokines and host risk factors. This study aims to explore the significance of cervical immune mediators associated to cell survival, angiogenesis and interaction with immune response, in predicting the risk to develop HPV-related intraepithelial lesions. Methods A panel of 48 cytokines and growth factors were explored in a selected cohort of 168 immunocompetent women including 88 diagnosed with low (LSIL) or high (HSIL) squamous intraepithelial lesions of the cervix and 80 with normal cervical cytology (NIL). HPV genotyping was performed by Linear Array HPV test and the soluble concentration of 48 immune molecules was analyzed using the Bio-Plex platform. Results The prevalence of single HR-HPV infection was 30% in NIL and 100% in LSIL and HSIL women. The expression of 13 cytokines, including interleukins IL-6, IL-3, IL-12p40, IL-12p70, IL-16, IL-18, LIF, of chemokines CCL7 (MCP-3), CXCL9 (MIG), CXCL12 (SDF-1α) and of the tropic factors VEGF, G-CSF, M-CSF were significantly associated with the presence of infection, with levels being higher in women with precancerous lesions compared to NIL HPV negative women. Only the growth factor GM-CSF was positively associated with the cytological abnormalities. Conclusions The ability of HR-HPV to escape from innate immune recognition and to orchestrate the production of specific inflammatory and growth factors, involved in early inflammatory response and in the cell-proliferating phase of intraepithelial damage, was documented in women before the development of cervical lesions. PMID:26990868

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

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

    2016-01-01

    Summary Enteropathogenic Escherichia coli (EPEC), enterohaemorrhagic E. coli (EHEC) and Citrobacter rodentium colonize their respective hosts while forming attaching and effacing lesions. Their infection strategy relies on translocation of a battery of type III secretion system effectors, including Map, EspM and EspT, which belong to the WxxxE/SopE family of guanine nucleotide exchange factors. Using the C. rodentium mouse model we found that EspT triggers expression of KC and TNFα in vivo. Indeed, a growing body of evidence suggests that, in addition to subversion of actin dynamics, the SopE and the WxxxE effectors activate signalling pathways involved in immune responses. In this study we found that EspT induces expression of the pro-inflammatory mediators cyclooxygenase-2 (COX-2) an enzyme involved in production of prostaglandin E(2) (PGE2), interleukin (Il)-8 and Il-1β in U937 human macrophages by activating the nuclear factor kappa-B (NF-κB), the extracellular signal-regulated kinases 1 and 2 (Erk1/2) and c-Jun N-terminal kinase (JNK) pathways. Since EspT modulates the activation of Cdc42 and Rac1, which mediates bacterial invasion into epithelial cells, we investigated the involvement of these Rho GTPases and bacterial invasion on pro-inflammatory responses and found that (i) Rac1, but not Cdc42, is involved in EspT-induced Il-8 and Il-1β secretion and (ii) cytochalasin D inhibits EspT-induced EPEC invasion into U937 but not Il-8 or Il-1β secretion. These results suggest that while EPEC translocates a number of effectors (i.e. NleC, NleD, NleE, NleH) that inhibit inflammation, a subset of strains, which encode EspT, employ an infection strategy that also involves upregulation of immune mediators. PMID:21848814

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

    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.

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

    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.

  15. Elevated expression of NLRP3 in patients with immune thrombocytopenia.

    Qiao, Jianlin; Liu, Yun; Li, Xiaoqian; Xia, Yuan; Wu, Yulu; Li, Depeng; Li, Hongchun; Ma, Ping; Zhu, Feng; Li, Zhenyu; Xu, Kailin; Zeng, Lingyu

    2016-04-01

    Immune thrombocytopenia (ITP) is a heterogeneous autoimmune disease, which is characterized by dysregulation of T cell-mediated autoimmunity. NLRP3, a largest and mostly well-studied inflammasome, has been shown to be important in the regulation of adaptive immune response, especially in T cell response. Given the closely association of imbalance of T cell response with ITP, whether NLRP3 is involved in the pathogenesis of ITP remains poorly understood. In this study, 69 active ITP patients, 21 ITP in remission and 24 age- and gender-matched healthy controls were included. Peripheral blood mononuclear cells (PBMCs) were isolated from ITP and control for isolation of RNA and plasma, which were used to measure mRNA level of NLRP3 and adaptor protein ASC by quantitative real-time PCR and IL-18 plasma level by ELISA. Meanwhile, protein was also extracted from PBMCs for Western blot analysis of NLRP3 expression. Our results showed a significantly higher expression of NLRP3, ASC and plasma IL-18 level in patients with active ITP when compared to control. The expression of NLRP3, ASC and plasma IL-18 level was significantly lower in patients in remission than that in active ITP, and no difference was observed when compared to control. Furthermore, a significantly positive correlation of NLRP3 with ASC was observed in patients with active ITP. In conclusion, increased expression of NLRP3 was associated with the pathogenesis of ITP and therapeutically targeting it might be a new strategy in the treatment of ITP. PMID:26306997

  16. Does the Microbiome Cause B27-related Acute Anterior Uveitis?

    Rosenbaum, James T; Lin, Phoebe; Asquith, Mark

    2016-08-01

    The microbiome is strongly implicated in a broad spectrum of immune-mediated diseases. Data support the concept that HLA molecules shape the microbiome. We provide hypotheses to reconcile how HLA-B27 might affect the microbiome and in turn predispose to acute anterior uveitis. These theories include bacterial translocation, antigenic mimicry, and dysbiosis leading to alterations in regulatory and effector T-cell subsets. Received 31 October 2015; revised 7 January 2016; accepted 8 January 2016; published online 22 March 2016. PMID:27002532

  17. Re-evaluation of Need for Bone Marrow Examination in Patients with Isolated Thrombocytopenia Contributors.

    Purohit, Abhishek; Aggarwal, Mukul; Singh, Pawan Kumar; Mahapatra, Manoranjan; Seth, Tulika; Tyagi, Seema; Saxena, Renu; Pati, Hara P; Mishra, Pravas

    2016-06-01

    Diagnosis of immune thrombocytopenia (ITP) is based on clinical suspicion and normal peripheral smear except for thrombocytopenia. Bone marrow examination is carried out to rule out leukemia, myelodysplastic syndrome or aplastic anemia. However, in most cases, clinical diagnosis is not altered after the bone marrow reports. Hence, this present study was carried out to evaluate the justification for bone marrow examination in the setting of isolated thrombocytopenia. All patients presenting to the hematology OPD with isolated thrombocytopenia and suspected diagnosis of ITP, between October 2011 and April 2013, were included in the study. Data was collected from bone marrow reports and outpatient records. A total of 353 cases were found. 319 cases had features of typical ITP and the rest had some form of organomegaly and/or lymphadenopathy. Bone marrow examination in all cases revealed normal hematopoietic elements and prominence of megakaryocytes including juvenile forms with no novel diagnosis in any patient. Routine use of bone marrow examination in the diagnostic workup of isolated thrombocytopenia is not required in our center even if steroids are planned as a first line therapy. However, a detailed history, thorough examination with complete hemogram and peripheral smear examination are essential. PMID:27065582

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

    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

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

    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.

  20. Corticosteroid in the Treatment of Moderate to Severe Thrombocytopenia Due to Leptospirosis

    Alian, Shahriar; Asghari, Hasan; Najafi, Narges; Davoudi, Alireza; Yazdani, Jamshid

    2014-01-01

    Background: Thrombocytopenia is associated with a bad prognosis in Leptospirosis. Objectives: We investigated the effect of corticosteroids to improve thrombocytopenia due to leptospirosis. Patients and Methods: In a clinical trial, all patients admitted with leptospirosis in Razi Hospital of Ghaemshahr, north of Iran were enrolled in a 2-year study. Totally, 56 patients with moderate to severe thrombocytopenia were randomized to control and treatment groups. The treatment group received corticosteroid (prednisolone 1 mg/kg/day for maximum one week) in addition to the standard antibiotic therapy. Results: There was no significant difference regarding age and gender between the two groups (P = 0.254, P = 0.789, respectively). The mean duration to improve thrombocytopenia was 4.41 ± 0.197 days in the treatment group and 5.72 ± 0.318 days in the control group, which was significantly different (P = 0.003). Duration of hospitalization in the treatment group was 5.24 ± 0.244 days and 6.23 ± 0.329 days in the control group, which was significantly different (P = 0.028). The two groups had no significant difference regarding mortality, intubation, level of platelet, duration of ICU admission and pulmonary, renal or hepatic involvement. Conclusions: Corticosteroid therapy decreased the length of hospitalization only in severe subgroup thrombocytopenia, but not in the moderate subgroup. PMID:25763200

  1. A case of familial X-linked thrombocytopenia with a novel WAS gene mutation

    Eu Kyoung Lee

    2013-06-01

    Full Text Available Wiskott-Aldrich syndrome (WAS is an inherited X-linked disorder. The WAS gene is located on the X chromosome and undergoes mutations, which affect various domains of the WAS protein, resulting in recurrent infection, eczema, and thrombocytopenia. However, the clinical features and severity of the disease vary according to the type of mutations in the WAS gene. Here, we describe the case of a 4-year-old boy with a history of marked thrombocytopenia since birth, who presented with recurrent herpes simplex infection and late onset of eczema. Examination of his family history revealed that older brother, who died from intracranial hemorrhage, had chronic idiopathic thrombocytopenia. Therefore, we proceeded with genetic analysis and found a new deletion mutation in the WAS gene: c.858delC (p.ser287Leufs*21 as a hemizygous form.

  2. [A Case of Drug-Induced Thrombocytopenia Resulting from Sensitivity to Oxaliplatin].

    Masuda, Taiki; Nagai, Kagami; Sanada, Katsuya

    2015-11-01

    A 67-year-old man was diagnosed with pulmonary metastasis from advanced transverse colon cancer. Thus, a local resection was performed. Adjuvant chemotherapy with mFOLFOX6 was started. Sixteen courses were carried out without problems. However, he complained of chills and chest discomfort 2 hours after beginning the 17th course of chemotherapy. Laboratory data showed remarkable thrombocytopenia, and platelet-associated IgG level was high. After administration of steroids and platelet transfusions, the platelet count improved. Therefore, we diagnosed drug-induced thrombocytopenia resulting from sensitivity to oxaliplatin (L-OHP). Since then, sLV5FU2 therapy was started, and the patient received the whole adjuvant chemotherapy without problems. Thrombocytopenia resulting from sensitivity to L-OHP is a relatively rare side effect. We herein report this case with a review of the relevant literature. PMID:26805296

  3. Bone Marrow Suppression and Hemophagocytic Histiocytes Are Common Findings in Korean Severe Fever with Thrombocytopenia Syndrome Patients.

    Shin, Sang Yong; Cho, Oh Hyun; Bae, In Gyu

    2016-09-01

    The causes of cytopenia in patients with severe fever with thrombocytopenia syndrome (SFTS) are not fully understood until now. We reviewed the bone marrow (BM) findings of patients with SFTS to unravel the cause of the cytopenia. Three Korean SFTS were enrolled in this study. Thrombocytopenia, neutropenia, and anemia were detected in all three patients. Severe hypocellular marrow (overall cellularity Korean SFTS. PMID:27401664

  4. Pharmacodynamic model for chemoradiotherapy-induced thrombocytopenia in mice.

    Krzyzanski, Wojciech; Perez-Ruixo, Juan Jose; Harrold, John

    2015-12-01

    A mechanistic model describing the effects of chemotherapy and radiation on platelet counts and endogenous thrombopoietin (eTPO) in mice was developed. Thrombocytopenia was induced in mice by injection of carboplatin followed by the whole body irradiation on days 0, 28, and 56, with platelet and eTPO samples collected over 84 days. The pharmacodynamic model consisted of a series of aging compartments representing proliferating megakaryocyte precursors, megakaryocytes, and platelets with possible eTPO clearance through internalization. The cytotoxic effects of treatment were described by the kinetics of the effect (K-PD) model, and stimulation of platelet production by eTPO was considered to be driven by receptor occupancy. The proposed PD model adequately described the platelet counts and eTPO concentrations in mice by accounting for nadirs and peaks of platelet count, and rebounds in eTPO time course profiles. The estimates of model parameters were in good agreement with their physiological values reported in literature for mice with platelet lifespan of 4.3 days and 185 cMpl receptors per platelet. The predicted duration of the treatment effect was 0.82 h (approximately 5 carboplatin half-lives in mice). The data was not informative about the eTPO stimulatory effect as the nominal precursor production rate was sufficient to account for platelet response to treatment. The model quantified the inverse relationship between eTPO levels and platelet counts and offered an explanation of the tolerance effect observed in the eTPO data. The simulated rebound in free receptors levels correlated with rebounds in eTPO levels. The model suggests that the duration of the toxic effects is determined by the turnover of the proliferating cells in the bone marrow. This indicates that the lifespan of the target cells (megakaryocyte precursors, megakaryocytes and platelets) is a key determinant in the duration of both drug exposure and toxicity due to treatment. The model can be

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

    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

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

  7. Alcohol-induced severe acute pancreatitis followed by hemolytic uremic syndrome managed with continuous renal replacement therapy

    Fu, Peng; Yuan, Ai-hong; Wang, Chun-Hua; LI, XIN; Wu, Hai-yang

    2014-01-01

    Background Acute kidney injury in patients with acute pancreatitis carries a poor prognosis. Hemolytic uremic syndrome (HUS) is characterized by non-immune hemolytic anemia, thrombocytopenia, and renal failure caused by platelet thrombi in the microcirculation of the kidney, and though rare in adults it is associated with high mortality and a high rate of chronic renal failure. Case presentation Herein, we report a case of alcohol-induced acute pancreatitis in a 38-year-old Chinese female com...

  8. Comparison between IV immune globulin (IVIG) and anti-D globulin for treatment of immune thrombocytopenia: a randomized open-label study.

    Eghbali, Aziz; Azadmanesh, Peyman; Bagheri, Bahador; Taherahmadi, Hasan; Sadeghi Sedeh, Bahman

    2016-08-01

    To compare the effect of IV immune globulin (IVIG) and anti-D globulin (anti-D) for treatment of immune thrombocytopenia (ITP) in children. A randomized, open-label, single-center clinical trial was carried out in Amir-Kabir Hospital (Arak, Iran). The study was performed on 60 children with acute and chronic ITP, aged from 1 to 15 years. Patients were randomly assigned (1:1) to 50 μg/kg anti-D or 1 g/kg IVIG. Platelet counting was performed at baseline and at 3, 7, and 14 days after treatment termination. Safety assessment was performed in all patients. Anti-D caused a quicker response on the 3rd day of treatment (P anti-D had lower rate of side effects including fever (P anti-D was associated with rapid rise of platelets compared to IVIG. In addition, anti-D treatment had acceptable safety profile. PMID:26991138

  9. Haemolytic Uraemic Syndrome Following Acute Pancreatitis

    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.

  10. Heparin induced thrombocytopenia thrombosis (HIT/T) syndrome: diagnosis and treatment

    T. Baglin

    2001-01-01

    Heparin induced thrombocytopenia thrombosis (HIT/T) is associated with a high morbidity and mortality. Diagnosis is essentially clinical and negative results of laboratory assays do not exclude the diagnosis. Treatment involves stopping all heparin immediately and giving an alternative thrombin inhibitor. The adoption of low molecular weight heparins is one reason for the reduced incidence of this disease in recent years.

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

    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.

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

    Kuzmanović Miloš; Kunishima Shinji; Putnik Jovana; Stajić Nataša; Paripović Aleksandra; Bogdanović Radovan

    2014-01-01

    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 dia...

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

    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

  14. Severe Fever with Thrombocytopenia Syndrome Virus in Ticks Collected from Humans, South Korea, 2013

    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

    2014-01-01

    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.

  15. Saddle Pulmonary Embolism in a Cancer Patient with Thrombocytopenia: A Treatment Dilemma

    Ali Zalpour; Katy Hanzelka; John T. Patlan; Marc A. Rozner; Syed Wamique Yusuf

    2011-01-01

    The association between cancer and venous thromboembolism (VTE) is well established. Saddle pulmonary embolism is not uncommon in hospitalized cancer patients and confers a higher mortality. We report a case of saddle pulmonary embolism in a cancer patient with thrombocytopenia, discuss the bleeding risks, complexity of managing such patients and review current guidelines.

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

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

    2008-09-15

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

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

    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

  18. Immune Thrombocytopenic Purpura During Maintenance Phase of Acute Lymphoblastic Leukemia: A Rare Coexistence Requiring a High Degree of Suspicion, a Case Report and Review of the Literature.

    Bayhan, Turan; Ünal, Şule; Gümrük, Fatma; Çetin, Mualla

    2015-12-01

    Thrombocytopenia may develop in patients with acute lymphoblastic leukemia (ALL) due to myelosuppression of chemotherapy or relapse. Here we report a pediatric patient with ALL whose platelet counts decreased at the 102nd week of maintenance treatment. Thrombocytopenia was refractory to platelet infusions and bone marrow aspiration revealed remission status for ALL along with increased megakaryocytes. The cessation of chemotherapy for 2 weeks caused no increase in thrombocyte counts. The viral serology was unrevealing. A diagnosis of immune thrombocytopenic purpura (ITP) was established. After administration of intravenous immunoglobulin, the thrombocytopenia resolved. When thrombocytopenia occurs in patients with ALL in remission, ITP should be kept in mind after exclusion of the more common etiologies. PMID:25913619

  19. Immune Thrombocytopenic Purpura During Maintenance Phase of Acute Lymphoblastic Leukemia: A Rare Coexistence Requiring a High Degree of Suspicion, a Case Report and Review of the Literature

    Turan Bayhan

    2015-12-01

    Full Text Available Thrombocytopenia may develop in patients with acute lymphoblastic leukemia (ALL due to myelosuppression of chemotherapy or relapse. Here we report a pediatric patient with ALL whose platelet counts decreased at the 102nd week of maintenance treatment. Thrombocytopenia was refractory to platelet infusions and bone marrow aspiration revealed remission status for ALL along with increased megakaryocytes. The cessation of chemotherapy for 2 weeks caused no increase in thrombocyte counts. The viral serology was unrevealing. A diagnosis of immune thrombocytopenic purpura (ITP was established. After administration of intravenous immunoglobulin, the thrombocytopenia resolved. When thrombocytopenia occurs in patients with ALL in remission, ITP should be kept in mind after exclusion of the more common etiologies.

  20. Acute gingival bleeding as a complication of dengue hemorrhagic fever

    Saif Khan; Gupta, N. D.; Sandhya Maheshwari

    2013-01-01

    Dengue fever is mosquito borne disease caused by dengue virus (DENV) of Flaviviridae family. The clinical manifestations range from fever to severe hemorrhage, shock and death. Here, we report a case of 20-year-old male patient undergoing orthodontic treatment presenting with acute gingival bleeding with a history of fever, weakness, backache, retro orbital pain and ecchymosis over his right arm. The hematological investigations revealed anemia, thrombocytopenia and positive dengue non-struct...

  1. Severe Acute Respiratory Syndrome: Clinical and Laboratory Manifestations

    Lam, Christopher W.K.; Chan, Michael H M; Wong, Chun K.

    2004-01-01

    Severe acute respiratory syndrome (SARS) is a recently emerged infectious disease with significant morbidity and mortality. An epidemic in 2003 affected 8,098 patients in 29 countries with 774 deaths. The aetiological agent is a new coronavirus spread by droplet transmission. Clinical and general laboratory manifestations included fever, chills, rigor, myalgia, malaise, diarrhoea, cough, dyspnoea, pneumonia, lymphopenia, neutrophilia, thrombocytopenia, and elevated serum lactate dehydrogenase...

  2. Factors linked to severe thrombocytopenia during antiviral therapy in patients with chronic hepatitis c and pretreatment low platelet counts

    Lin Kung-Hung

    2012-01-01

    Full Text Available Abstract Background Baseline low platelet count ( Methods Medical records were reviewed for 125 patients with CHC treated with antiviral therapy according to the standard of care, with regular follow-up examinations. Early platelet decline was defined as platelet decrease during the first 2 weeks of therapy. Results Severe thrombocytopenia developed in 12.8% of patients with baseline thrombocytopenia, and predicted a higher therapeutic dropout rate. Multivariate analysis revealed baseline platelet count 30% decline in the first 2 weeks were significantly associated with severe thrombocytopenia (P Conclusions For patients with CHC on antiviral therapy, baseline platelet counts

  3. Frank hematuria as the presentation feature of acute leukemia

    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.

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

    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

  5. Mercaptopurine metabolite levels are predictors of bone marrow toxicity following high-dose methotrexate therapy of childhood acute lymphoblastic leukaemia

    Vang, Sophia Ingeborg; Schmiegelow, Kjeld; Frandsen, Thomas;

    2015-01-01

    High-dose methotrexate (HD-MTX) courses with concurrent oral low-dose MTX/6-mercaptopurine (6MP) for childhood acute lymphoblastic leukaemia (ALL) are often followed by neutro- and thrombocytopenia necessitating treatment interruptions. Plasma MTX during HD-MTX therapy guides folinic acid rescue ...

  6. Experimental and Natural Infections of Goats with Severe Fever with Thrombocytopenia Syndrome Virus: Evidence for Ticks as Viral Vector

    Jiao, Yongjun; Qi, Xian; Liu, Dapeng; ZENG, XIAOYAN; Han, Yewu; Guo, Xiling; Shi, Zhiyang; Hua WANG; Zhou, Minghao

    2015-01-01

    Background Severe fever with thrombocytopenia syndrome virus (SFTSV), the causative agent for the fatal life-threatening infectious disease, severe fever with thrombocytopenia syndrome (SFTS), was first identified in the central and eastern regions of China. Although the viral RNA was detected in free-living and parasitic ticks, the vector for SFTSV remains unsettled. Methodology/Principal Findings Firstly, an experimental infection study in goats was conducted in a bio-safety level-2 (BSL-2)...

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

    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.

  8. [Effect of the evaluation parameter on sensitivity of resonance thrombography of thrombocytopenia in dogs].

    Adamik, A; Mischke, R

    1998-11-01

    Based on 109 blood samples taken from 36 dogs suffering from thrombocytopenia resonance thrombography with the resonance thrombograph RTG 801 (von Hoerner und Sulger Electronic GmbH, Schwetzingen; manufacturer: Fresenius AG, Bad Homburg) was distinctly more sensitive and more closely correlated to the platelet count using an optimized parameter of the resonance thrombogramm (RTG) in comparison to usual parameters. Nevertheless, clinical requirements regarding samples with platelet counts > 25,000/microliter were not fulfilled. Out of 13 samples with reduced platelet count and simultanous extended capillary bleeding time, depending on the used parameter a maximum of 9 samples could be detected as pathological by the RTG. The normal RTG in part of the cases with clearly altered primary haemostasis contrasts to the exclusive use of RTG in the screening of thrombocytopenia in dogs. PMID:9857562

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

    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.

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

    Sartaj Bhat; Suhail Naik; Wasim Rafiq; Syed Tariq A

    2015-01-01

    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...

  11. Resolution of Dialyzer Membrane-Associated Thrombocytopenia with Use of Cellulose Triacetate Membrane: A Case Report

    Feyisayo Olafiranye; Win Kyaw; Oladipupo Olafiranye

    2011-01-01

    Blood and dialyzer membrane interaction can cause significant thrombocytopenia through the activation of complement system. The extent of this interaction determines the biocompatibility of the membrane. Although the newer synthetic membranes have been shown to have better biocompatibility profile than the cellulose-based membranes, little is known about the difference in biocompatibility between synthetic membrane and modified cellulose membrane. Herein, we report a case of a patient on hemo...

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

    Marković-Sovtić Gordana; Janković Borisav; Rakonjac Zorica; Martić Jelena; Pejić Katarina

    2013-01-01

    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 intr...

  13. Comparison of dexamethasone and Anti-D Immune globulin for immune thrombocytopenia purpura in children

    Abdollah Banihashem; Hamid Farhangi; Mojtaba Mousavi Bazaz; Zahra Badiee; Ali Ghasemi; Sara Hesari

    2014-01-01

    Different therapeutic options in children with immune thrombocytopenic purpura include observation alone, periodic treatment with corticosteroids, intravenous immunoglobulin (IVIG) or anti-D, chronic administration of immunosuppressive agents, and splenectomy. Preference of the type of therapy depends on the degree of thrombocytopenia and clinical bleeding manifestations. Dexamethasone is safe but its side effects are the main disadvantages for its usage. Anti-D is more expensive than dexamet...

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

    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, ...

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

    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

  16. Rapid Diagnosis of Vivax Malaria by the SD Bioline Malaria Antigen Test When Thrombocytopenia Is Present▿

    Lee, Sei Won; Jeon, Kyeongman; Jeon, Byung Ryul; Park, Inho

    2007-01-01

    An easy and reliable diagnostic method for malaria is highly desirable. We examined the recently introduced SD Bioline Malaria Antigen test, which detects Plasmodium lactate dehydrogenase, with the additional aid of the presence or absence of thrombocytopenia to diagnose vivax malaria. We enrolled 732 patients with clinically suspected malaria in an area where vivax malaria is endemic. We performed microscopic examination of thin film, applied the SD Bioline Malaria Antigen test, and checked ...

  17. CD32a antibodies induce thrombocytopenia and type II hypersensitivity reactions in FCGR2A mice.

    Meyer, Todd; Robles-Carrillo, Liza; Davila, Monica; Brodie, Meghan; Desai, Hina; Rivera-Amaya, Mildred; Francis, John L; Amirkhosravi, Ali

    2015-11-01

    The CD32a immunoglobulin G (IgG) receptor (Fcγ receptor IIa) is a potential therapeutic target for diseases in which IgG immune complexes (ICs) mediate inflammation, such as heparin-induced thrombocytopenia, rheumatoid arthritis, and systemic lupus erythematosus. Monoclonal antibodies (mAbs) are a promising strategy for treating such diseases. However, IV.3, perhaps the best characterized CD32a-blocking mAb, was recently shown to induce anaphylaxis in immunocompromised "3KO" mice. This anaphylactic reaction required a human CD32a transgene because mice lack an equivalent of this gene. The finding that IV.3 induces anaphylaxis in CD32a-transgenic mice was surprising because IV.3 had long been thought to lack the intrinsic capacity to trigger cellular activation via CD32a. Such an anaphylactic reaction would also limit potential therapeutic applications of IV.3. In the present study, we examine the molecular mechanisms by which IV.3 induces anaphylaxis. We now report that IV.3 induces anaphylaxis in immunocompetent CD32a-transgenic "FCGR2A" mice, along with the novel finding that IV.3 and 2 other well-characterized CD32a-blocking mAbs, AT-10 and MDE-8, also induce severe thrombocytopenia in FCGR2A mice. Using recombinant variants of these same mAbs, we show that IgG "Fc" effector function is necessary for the induction of anaphylaxis and thrombocytopenia in FCGR2A mice. Variants of these mAbs lacking the capacity to activate mouse IgG receptors not only failed to induce anaphylaxis or thrombocytopenia, but also very potently protected FCGR2A mice from near lethal doses of IgG ICs. Our findings show that effector-deficient IV.3, AT-10, and MDE-8 are promising candidates for developing therapeutic mAbs to treat CD32a-mediated diseases. PMID:26396093

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

    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.

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

    Borges, Alvaro Humberto Diniz; Lundgren, Jens D; Ridolfo, Annalisa; Katlama, Christine; Antunes, Francisco; Grzeszczuk, Anna; Blaxhult, Anders; Mitsura, Viktar M; Doroana, Manuela; Battegay, Manuel; Gargalianos, Panagiotis; Mocroft, Amanda

    2014-01-01

    OBJECTIVE: To assess the relationship between platelet counts and risk of AIDS and non-AIDS-defining events.DESIGN: Prospective cohort.METHODS: EuroSIDA patients with at least one platelet count were followed from baseline (first platelet ≥ 1 January 2005) until last visit or death. Multivariate...... patients, including 1168 non-AIDS-defining events [crude incidence 18.6/1000 PYFU, 95% confidence interval (CI) 17.5-19.6] and 735 AIDS-defining events (crude incidence 11.7/1000 PYFU, 95% CI 10.8-12.5). Patients with thrombocytopenia (platelet count ≤100 × 10/l) had a slightly increased incidence of AIDS...... (aIRR 2.20, 95% CI 1.61-3.01), but not cardiovascular disease (aIRR 0.66, 95% CI 0.32-1.34), was significantly higher in patients with thrombocytopenia. The association between thrombocytopenia and cancer remained unaltered in sensitivity analyses requiring repeated platelet counts to confirm...

  20. Gestational Thrombocytopenia: Does It Cause Any Maternal and /or Perinatal Morbidity?

    Carlo Pafumi

    2013-06-01

    Full Text Available Purpose: The iam of this study was retrospectively evaluate maternal platelet count fluctuation during pregnancy and puerperium and its correlation with the newborn’s platelet levels. Method: A group of 36 patients who have been referred to a haematology-clinic for gestational thrombocytopenia (GT and who delivered at the same hospital during a period of 4 years, from January 2006 to December2009 were included in the study. Mothers and their related foetuses- newborns were evaluated retrospectively for symptoms and/or signs of external and internal haemorrhage throughout pregnancy and early puerperium, even in relationship with mode of delivery (caesarean section versus spontaneous vaginal delivery. Results: All observed cases of GT have an uncomplicated course with no related perinatal and maternal morbidity even in patients with initial platelet count < 75.000/ml independently from the route of delivery. Conclusion: In case of gestational thrombocytopenia a complete normalization of maternal platelet count should be expected during the postpartum period, even if a diagnosis of a concomitant incidental neonatal thrombocytopenia cannot be excluded.No intervention, such as a foetal platelet count or caesarean section, is necessary. [Cukurova Med J 2013; 38(3.000: 349-357

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

    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

  2. Dose escalation study of an anti-thrombocytopenic agent in patients with chemotherapy induced thrombocytopenia

    Preclinical studies demonstrated that small chain RNA fragments accelerate the recovery of platelets numbers in animals exposed to high doses of chemotherapeutic drugs. There is anecdotal data supporting the same application in humans. The Phase I clinical trial described here was designed to investigate the relationship between the administration of small chain RNA fragments and the recovery in platelets following Chemotherapy-Induced Thrombocytopenia (CIT). Cancer patients with solid tumors that experienced post chemotherapy thrombocytopenia with a nadir of < = 80,000 platelets/ml were eligible for this clinical trial. There were no exclusions based on ECOG status, tumor type, tumor burden or chemotherapeutic agents. Patients received a unique preparation of RNA derived from either E. coli or yeast. Ten patients per group received 20, 40, or 60 mg as a starting dose. Subjects self-administered RNA fragments sublingually on an every other day schedule while undergoing chemotherapy. The dose was escalated in 20 mg increments to a maximum dose of 80 mg if the nadir was < 80,000 platelets/ml at the start of the next cycle. Subjects were treated for three cycles of chemotherapy with the maximum effective dose of RNA fragments. Subjects continued on planned chemotherapy as indicated by tumor burden without RNA fragment support after the third cycle. Subjects kept a diary indicating RNA fragment and magnesium administration, and any experienced side effects. Patients receiving E. coli RNA fragments demonstrated a more rapid recovery in platelet count and higher nadir platelet count. None of the patients receiving the E. coli RNA fragments required a chemotherapy dose reduction due to thrombocytopenia. The optimal dose for minimizing CIT was 80 mg. Conversely, subjects receiving yeast RNA fragments with dose escalation to 80 mg required a chemotherapy dose reduction per American Society of Clinical Oncology guidelines for grade 3 and 4 thrombocytopenia. Patients

  3. The use of biosimilars in immune-mediated disease: A joint Italian Society of Rheumatology (SIR), Italian Society of Dermatology (SIDeMaST), and Italian Group of Inflammatory Bowel Disease (IG-IBD) position paper.

    Fiorino, Gionata; Girolomoni, Giampiero; Lapadula, Giovanni; Orlando, Ambrogio; Danese, Silvio; Olivieri, Ignazio

    2014-07-01

    Biological agents are widely used in rheumatology, dermatology and inflammatory bowel disease. Evidence about their efficacy and safety has been strengthened for all those therapeutic indications over the last decade. Biosimilar agents are monoclonal antibodies similar to previously approved biologics. In the European Union, they have been approved for all the indications in the management of immune-mediated inflammatory diseases (IMIDs), although data only in rheumatoid arthritis and ankylosing spondylitis are currently available. Direct evidence on efficacy, safety, and immunogenicity of biosimilars is mandatory in psoriasis, psoriatic arthritis, and inflammatory bowel disease, as well as in children. Based on the current evidence in the literature, we present the joint official position of the Italian Societies of Rheumatology, Dermatology and Inflammatory Bowel Disease on the use of biosimilars in IMIDs. PMID:24657898

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

    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.

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

    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.

  6. Immunhämolytische Anämie und immunbedingte Thrombozytopenie beim Hund, eine prospektive Studie (1997 - 1999)

    Engelbrecht, Rolf

    2010-01-01

    VII. Summary: Immune-mediated hemolytic anemia and immune-mediated thrombo-cytopenia in dogs, a prospective study (1997 ý1999) In this prospective study all patients with immune-mediated thrombocytopenia (ITP) and immune-hemolytic anemia (IHA), which were presented within two years (January 1997 - January 1999) at the Clinic for Small Animals, Free University of Berlin, were studied and clinical findings, diagnostics and treatment results were evaluated. Immune-mediated thrombo...

  7. Thrombocytopenia in Patients with Gastric Varices and the Effect of Balloon-occluded Retrograde Transvenous Obliteration on the Platelet Count

    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.

  8. Management of an acute outbreak of diarrhoea-associated haemolytic uraemic syndrome with early plasma exchange in adults from southern Denmark: an observational study

    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....

  9. The Role of Platelet Factor 4 in Radiation-Induced Thrombocytopenia

    Purpose: Factors affecting the severity of radiation-induced thrombocytopenia (RIT) are not well described. We address whether platelet factor 4 (PF4; a negative paracrine for megakaryopoiesis) affects platelet recovery postradiation. Methods and Materials: Using conditioned media from irradiated bone marrow (BM) cells from transgenic mice overexpressing human (h) PF4 (hPF4+), megakaryocyte colony formation was assessed in the presence of this conditioned media and PF4 blocking agents. In a model of radiation-induced thrombocytopenia, irradiated mice with varying PF4 expression levels were treated with anti-hPF4 and/or thrombopoietin (TPO), and platelet count recovery and survival were examined. Results: Conditioned media from irradiated BM from hPF4+ mice inhibited megakaryocyte colony formation, suggesting that PF4 is a negative paracrine released in RIT. Blocking with an anti-hPF4 antibody restored colony formation of BM grown in the presence of hPF4+ irradiated media, as did antibodies that block the megakaryocyte receptor for PF4, low-density lipoprotein receptor-related protein 1 (LRP1). Irradiated PF4 knockout mice had higher nadir platelet counts than irradiated hPF4+/knockout litter mates (651 vs. 328 x 106/mcL, p = 0.02) and recovered earlier (15 days vs. 22 days, respectively, p <0.02). When irradiated hPF4+ mice were treated with anti-hPF4 antibody and/or TPO, they showed less severe thrombocytopenia than untreated mice, with improved survival and time to platelet recovery, but no additive effect was seen. Conclusions: Our studies show that in RIT, damaged megakaryocytes release PF4 locally, inhibiting platelet recovery. Blocking PF4 enhances recovery while released PF4 from megakaryocytes limits TPO efficacy, potentially because of increased release of PF4 stimulated by TPO. The clinical value of blocking this negative paracrine pathway post-RIT remains to be determined.

  10. Thrombocytopenia in malaria: can platelet counts differentiate malaria from other infections

    To determine the accuracy of thrombocytopenia as a diagnostic marker for malaria. Study Design: Cross-sectional study. Place and Duration of Study: Department of Medicine, 1 Mountain Medical Battalion (Bagh, Azad Kashmir) from July to September 2013. Methodology: Adult patients presenting with a short history of fever without any localizing symptoms or signs were included. Exclusion criteria included patients with fever of > 7 days duration, those in whom an underlying diagnosis could be easily confirmed on the basis of history and physical examination, those on antibiotics/ antimalarials or antiplatelet agents and patients with Dengue fever. Platelet counts in venous whole blood samples were analysed with Sysmex KX-21 Haematology analyzer. Thick and thin peripheral blood smears were then prepared and examined for malarial parasites. Diagnosis of malaria was established on the basis of smear findings. Results: There were 245 patients in total. Out of the 109 patients with thrombocytopenia, 61 had vivax malaria. Platelets count was normal in 136 patients, including 4 with vivax malaria. Falciparum malaria was not seen in any patient. All cases with malaria were uncomplicated. Various measures of accuracy thus calculated were sensitivity 93.85%, specificity 73.33%, positive predictive value 55.96%, negative predictive value 97.06%, positive likelihood ratio of 3.52, negative likelihood ratio of 0.08, diagnostic odds ratio 41.94 and diagnostic accuracy of 78.78%. Conclusion: Thrombocytopenia has an excellent sensitivity and a very good specificity for vivax malaria. Normal platelet counts provide very strong evidence against malaria as the etiology of fever without a focus. (author)

  11. Interleukin-11-induced capillary leak syndrome in primary hepatic carcinoma patients with thrombocytopenia

    Li-Rong Shen

    2011-05-01

    Full Text Available Abstract Background Capillary leak syndrome (CLS is a rare condition characterized by recurrent episodes of generalized edema and severe hypotension associated with hypoproteinemia. Interleukin-11 (IL-11 is a promising therapeutic agent for thrombocytopenia. A direct correlation between IL-11 and CLS has never been reported previously, particularly in patients with hepatic carcinoma. Case presentation We describe two cases of CLS after IL-11 administration in two males with thrombocytopenia. Case 1 was a 46-year-old man with recurrence of hepatic carcinoma who was treated with IL-11 (3 mg per day. After four days of therapy, hypotension and hypoproteinemia were detected. The chest X-ray and B ultrasound of the abdomen showed pleural effusion and ascites. IL-11 was then discontinued, fluid resuscitation was performed, and fresh frozen plasma and packed red blood cells were transfused into this patient. The patient had recovered after 19 days of treatment. Case 2 was a 66-year-old man who had undergone radiofrequency ablation (RFA for hepatic carcinoma. He was treated with IL-11 (3 mg per day for thrombocytopenia. After two days of therapy, this patient complained of dyspnea with bilateral edema of the hands. Laboratory values showed hypoproteinemia. IL-11 was stopped and human albumin was transfused at a rate of 10 g per day. On the 4th day, fluid resuscitation was performed. The patient had recovered after treatment for two weeks. Conclusions The detection of IL-11-induced CLS supports the hypothesis that CLS could be a severe side effect of IL-11 treatment in some patients. These two case reports also demonstrate that patients with hepatic carcinoma who experience this rare form of CLS after treatment with IL-11 seem to respond to a therapeutic regimen that involves hydroxyethyl starch, albumin, and diuretic therapy. Liver cancer patients might be more susceptible to CLS because of poor liver function and hypersplenia. In addition, bleeding

  12. Thrombosis during off pump LVAD placement in a patient with heparin induced thrombocytopenia using bivalirudin

    Awad, Hamdy; Bryant, Richard; Malik, Obaid; Dimitrova, Galina; Sai-Sudhakar, Chittoor Bhaskar

    2013-01-01

    Here we present our attempt at off pump HeartMate II left ventricular assist device (LVAD) implantation using the anticoagulant bivalirudin in a patient with heparin induced thrombocytopenia, which resulted in thrombosis within the LVAD device. This required that our procedure be converted to on pump, and a new HeartMate II LVAD device to be implanted. In our view, this thrombotic event may have been caused by a number of factors that include bivalirudin’s (1) short half-life of about 20 minu...

  13. Urothelial Carcinoma of the Bladder Metastatic to Bone Marrow Presenting as Isolated Thrombocytopenia

    Robert C. Chan

    2007-01-01

    Full Text Available The skeletal system is a frequent site for metastases of urothelial carcinoma (UC of the bladder (22–37%. Of those cases involving bone, the marrow is infiltrated in 27% of patients. Imaging modalities, such as X-ray and CT, will detect gross skeletal lesions in the vast majority of these patients with bone marrow involvement, however, most patients with bone involvement are symptomatic at presentation. Additionally, there have been few reports in the literature of bone marrow metastases from UC presenting with isolated thrombocytopenia.

  14. Platelet production and platelet destruction: assessing mechanisms of treatment effect in immune thrombocytopenia

    Barsam, Sarah J.; Psaila, Bethan; Forestier, Marc; Page, Lemke K.; Sloane, Peter A.; Geyer, Julia T.; Villarica, Glynis O.; Ruisi, Mary M.; Gernsheimer, Terry B.; Beer, Juerg H.; Bussel, James B.

    2011-01-01

    This study investigated the immature platelet fraction (IPF) in assessing treatment effects in immune thrombocytopenia (ITP). IPF was measured on the Sysmex XE2100 autoanalyzer. The mean absolute-IPF (A-IPF) was lower for ITP patients than for healthy controls (3.2 vs 7.8 × 109/L, P < .01), whereas IPF percentage was greater (29.2% vs 3.2%, P < .01). All 5 patients with a platelet response to Eltrombopag, a thrombopoietic agent, but none responding to an anti-FcγRIII antibody, had correspondi...

  15. Correlation of thrombocytopenia with grading of esophageal varices in chronic liver disease patients

    To determine the severity of thrombocytopenia in different grades of esophageal varices. Study Design: Cross-sectional analytical study. Place and Duration of Study: Jinnah Postgraduate Medical Centre, Karachi, Medical Unit-III, Ward-7 from January to December 2008. Methodology: Subjects were eligible if they had a diagnosis of cirrhosis. Patient with advanced cirrhosis (Child-Pugh class C), human immunodeficiency virus (HIV) infection, hepatocellular carcinoma, portal vein thrombosis, parenteral drug addiction, current alcohol abuse and previous or current treatment with b-blockers, diuretics and other vasoactive drugs were excluded from the study. All patients under went upper gastrointestinal endoscopy after consent. On the basis of platelet count patients were divided into four groups. Group I with platelets greater or equal to 20000/mm/sup 3/, Group II with values of 21000- 50000/mm/sup 3/, Group III with count of 51000-99000/mm/sup 3/ and Group IV with count of 100000-150000/mm/sup 3/. Correlation of severity of thrombocytopenia with the grading of esophageal varices was assessed using Spearman's correlation with r-values of 0.01 considered significant. Results: One hundred and two patients with thrombocytopenia and esophageal varices were included in the study. There were 62 (60.8%) males and 40 (39.2%) females. The mean age of onset of the disease in these patients was 49.49 +- 14.3 years with range of 11-85 years. Major causes of cirrhosis were hepatitis C (n=79, 77.5%), hepatitis B (n=12, 11.8%), mixed hepatitis B and C infection (n=8, 7.8%) and Wilson's disease (n=3,2.9%). Seven patients had esophageal grade I, 24 had grade II, 35 had grade III, and 36 had grade IV. Gastric varices were detected in 2 patients. Portal hypertensive gastropathy were detected in 87 patients. There was an inverse correlation of platelet count with grading of esophageal varices (r=-0.321, p < 0.001). Conclusion: The severity of thrombocytopenia increased as the grading of

  16. Development of myelofibrosis during eltrombopag treatment in a patient with immune thrombocytopenia.

    Horikoshi, Akira; Tsukuda, Jumpei; Abe, Ryouhei; Fujiwara, Naoki; Ito, Eisaku; Takaku, Tomoo

    2016-05-01

    Eltrombopag, a thrombopoietin (TPO) receptor agonist, is effective for treating refractory immune thrombocytopenia (ITP). However, the development of bone marrow fibrosis is a concern. A 78-year-old man was diagnosed with ITP in 2004. His platelet count did not increase after eltrombopag treatment initiation in 2014. However, anemia progressed, along with the presence of immature myelocytes, erythroblasts, and tear drop cells. At 8 months after initiating eltrombopag treatment, the patient underwent a bone marrow biopsy that showed grade 2 myelofibrosis. Hence, eltrombopag was discontinued. In our experience with this case indicates that careful observation is required while using TPO receptor agonists. PMID:27263792

  17. Platelet depletion and aspirin treatment protect mice in a two-event model of transfusion-related acute lung injury

    Looney, Mark R.; Nguyen, John X.; Hu, Yongmei; Van Ziffle, Jessica A.; Lowell, Clifford A.; Matthay, Michael A

    2009-01-01

    Transfusion-related acute lung injury (TRALI) is the leading cause of transfusion-associated mortality in the US. Previously, we established an immune-mediated TRALI mouse model, wherein mice with cognate antigen were challenged with MHC class I mAb. In this study, when mice housed in a rodent, specific pathogen–free barrier room were challenged with MHC I mAb, there was significant protection from TRALI compared with nonbarrier mice. Priming mice with LPS restored lung injury with mAb challe...

  18. Estudo epidemiológico das doenças dermatológicas imunologicamente mediadas na cavidade oral An epidemiological study of immune-mediated skin diseases affecting the oral cavity

    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

  19. Acute liver failure caused by drug-induced hypersensitivity syndrome associated with hyperferritinemia

    Masayuki Miyazaki

    2011-01-01

    Full Text Available Drug-induced hypersensitivity syndrome (DIHS is a severe 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.

  20. Use of peptide thrombopoietin receptor agonist romiplostim (Nplate) in a case of primary HIV-associated thrombocytopenia.

    Aslam, M Imran; Cardile, Anthony P; Crawford, George E

    2014-01-01

    Thrombocytopenia is frequently encountered in HIV-infected patients, and the predominant cause is primary HIV-associated thrombocytopenia (PHAT). Standard treatment regimens include optimization of antiretroviral therapy, intravenous immunoglobulin, anti-D, and corticosteroids. Retreatment due to the inability to sustain remission or inferior responses is common, and investigation into the safety and efficacy of alternative therapies is warranted. We describe novel and effective treatment of PHAT with the peptide thrombopoietin receptor agonist romiplostim in a patient with a minimal response to conventional therapy. PMID:24036490

  1. Gene expression profiling of mammary gland development reveals putative roles for death receptors and immune mediators in post-lactational regression

    In order to gain a better understanding of the molecular processes that underlie apoptosis and tissue regression in mammary gland, we undertook a large-scale analysis of transcriptional changes during the mouse mammary pregnancy cycle, with emphasis on the transition from lactation to involution. Affymetrix microarrays, representing 8618 genes, were used to compare mammary tissue from 12 time points (one virgin, three gestation, three lactation and five involution stages). Six animals were used for each time point. Common patterns of gene expression across all time points were identified and related to biological function. The majority of significantly induced genes in involution were also differentially regulated at earlier stages in the pregnancy cycle. This included a marked increase in inflammatory mediators during involution and at parturition, which correlated with leukaemia inhibitory factor–Stat3 (signal transducer and activator of signalling-3) signalling. Before involution, expected increases in cell proliferation, biosynthesis and metabolism-related genes were observed. During involution, the first 24 hours after weaning was characterized by a transient increase in expression of components of the death receptor pathways of apoptosis, inflammatory cytokines and acute phase response genes. After 24 hours, regulators of intrinsic apoptosis were induced in conjunction with markers of phagocyte activity, matrix proteases, suppressors of neutrophils and soluble components of specific and innate immunity. We provide a resource of mouse mammary gene expression data for download or online analysis. Here we highlight the sequential induction of distinct apoptosis pathways in involution and the stimulation of immunomodulatory signals, which probably suppress the potentially damaging effects of a cellular inflammatory response while maintaining an appropriate antimicrobial and phagocytic environment

  2. Mutations in MECOM, Encoding Oncoprotein EVI1, Cause Radioulnar Synostosis with Amegakaryocytic Thrombocytopenia.

    Niihori, Tetsuya; Ouchi-Uchiyama, Meri; Sasahara, Yoji; Kaneko, Takashi; Hashii, Yoshiko; Irie, Masahiro; Sato, Atsushi; Saito-Nanjo, Yuka; Funayama, Ryo; Nagashima, Takeshi; Inoue, Shin-Ichi; Nakayama, Keiko; Ozono, Keiichi; Kure, Shigeo; Matsubara, Yoichi; Imaizumi, Masue; Aoki, Yoko

    2015-12-01

    Radioulnar synostosis with amegakaryocytic thrombocytopenia (RUSAT) is an inherited bone marrow failure syndrome, characterized by thrombocytopenia and congenital fusion of the radius and ulna. A heterozygous HOXA11 mutation has been identified in two unrelated families as a cause of RUSAT. However, HOXA11 mutations are absent in a number of individuals with RUSAT, which suggests that other genetic loci contribute to RUSAT. In the current study, we performed whole exome sequencing in an individual with RUSAT and her healthy parents and identified a de novo missense mutation in MECOM, encoding EVI1, in the individual with RUSAT. Subsequent analysis of MECOM in two other individuals with RUSAT revealed two additional missense mutations. These three mutations were clustered within the 8(th) zinc finger motif of the C-terminal zinc finger domain of EVI1. Chromatin immunoprecipitation and qPCR assays of the regions harboring the ETS-like motif that is known as an EVI1 binding site showed a reduction in immunoprecipitated DNA for two EVI1 mutants compared with wild-type EVI1. Furthermore, reporter assays showed that MECOM mutations led to alterations in both AP-1- and TGF-β-mediated transcriptional responses. These functional assays suggest that transcriptional dysregulation by mutant EVI1 could be associated with the development of RUSAT. We report missense mutations in MECOM resulting in a Mendelian disorder that provide compelling evidence for the critical role of EVI1 in normal hematopoiesis and in the development of forelimbs and fingers in humans. PMID:26581901

  3. Randomized clinical trial of human interleukin-11 in dengue fever-associated thrombocytopenia

    Objective: To assess the effectiveness of recombinant human (rh) IL-11 to increase platelets count in patients suffering from Dengue fever (DF). Study Design: Randomized double blind placebo control study. Place and Duration of Study: Farooq Hospital, Lahore, from July to October 2011. Methodology: Forty hospitalized patients suffering from Dengue fever having platelets count A 30000 per micro liter were randomly categorized into two groups, rhIL-11 (test) and distilled water (placebo) groups. The efficacy outcomes (as indicated by step up in platelets count at 48 hours) for the treatment group were compared with the outcomes for the placebo group. Results: The data revealed that the increase in platelet response with recombinant human interleukin 11, 1.5 mg subcutaneously is significantly more brisk than the placebo group. The platelets response in patients with severe thrombocytopenia was greater in the treatment group (50%) at 48 hours as compared to the placebo group (20%) (p=0.047). Response rate was slightly greater among males (6/10, 60%) than females (8/16, 50%); moreover, three-fourth (75%) female responders were in the placebo group, compared to half (50%) male responders in the treatment group. Conclusion: Results of the study suggest that treatment of severe thrombocytopenia accompanying DF with recombinant human interleukin 11 may be a useful therapeutic option. (author)

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

    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.

  5. Serum thrombopoietin and cMpl expression in thrombocytopenia of different etiologies

    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.

  6. Acute Bronchitis

    ... of bronchitis: acute and chronic. Most cases of acute bronchitis get better within several days. But your cough ... that cause colds and the flu often cause acute bronchitis. These viruses spread through the air when people ...

  7. Acute Autonomic, Sensory and Motor Neuropathy Associated with Meningoencephalitis

    Satoko Kinoshita

    2009-01-01

    Full Text Available 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.

  8. Immune Thrombocytopenia

    ... severe forms of chronic ITP can live for decades. Most people who have chronic ITP can stop treatment at some point and maintain a safe platelet count. Rate This Content: NEXT >> Updated: March 14, 2012 Twitter Facebook YouTube Google+ SITE INDEX ACCESSIBILITY PRIVACY STATEMENT FOIA ...

  9. Disseminated Intravascular Coagulation (DIC) Accompanied by Acute Rejection in a Post Renal Transplant Recipient

    Dohi, Kiyohiko; Eto, Takaaki; Ono, Eiji; Fukuda, Yasuhiko; Takenaka, Masaharu; Yahata, Hiroshi; Asahara, Toshimasa; Tabe, Yasuji; Marubayashi, Seiji; Ezaki, Haruo

    1984-01-01

    A kidney transplant recipient with disseminated intravascular coagulation (DIC) accompanied by acute rejection was described. The principal symptome of the patient was massive gross hematuria. She showed thrombocytopenia, marked decrease of fibrinogen and elevation of fibrinogen degradation products (FDP) level. The patient was treated by continuous intravenous heparin infusion (total dose was 85, 800 units), and it was very effective. The symtoms due to DIC were improved on the 9th day after...

  10. A pilot study to assess the hemostatic function of pathogen-reduced platelets in patients with thrombocytopenia

    Johansson, Pär I; Simonsen, Anne Catrine; Brown, Peter de Nully;

    2013-01-01

    Platelet (PLT) support is critical to the care of patients with thrombocytopenia, but allogeneic transfusions carry risk. Pathogen reduction mitigates some transfusion risks, but effects on PLT function remain a concern. This clinical pilot study assessed the effect of pathogen reduction technolo...... with riboflavin plus ultraviolet light using thrombelastography (TEG)....

  11. Thrombocytopenia associated with dengue hemorrhagic fever responds to intravenous administration of anti-D (Rh(0)-D) immune globulin.

    de Castro, Reynaldo Angelo C; de Castro, Jo-Anne A; Barez, Marie Yvette C; Frias, Melchor V; Dixit, Jitendra; Genereux, Maurice

    2007-04-01

    Severe thrombocytopenia and increased vascular permeability are two major characteristics of dengue hemorrhagic fever (DHF). An immune mechanism of thrombocytopenia due to increased platelet destruction appears to be operative in patients with DHF (see Saito et al., 2004, Clin Exp Immunol 138: 299-303; Mitrakul, 1979, Am J Trop Med Hyg 26: 975-984; and Boonpucknavig, 1979, Am J Trop Med Hyg 28: 881-884). The interim data of two randomized placebo controlled trials in patients (N = 47) meeting WHO criteria for dengue hemorrhagic fever (DHF) with severe thrombocytopenia (platelets WinRho SDF), 50 microg/kg (250 IU/kg) intravenously is more brisk than the placebo group. The mean maximum platelet count of the anti-D-treated group at 48 hours was 91,500/mm(3) compared with 69,333/mm(3) in the placebo group. 75% of the anti-D-treated group demonstrated an increase of platelet counts > or = 20,000 compared with only 58% in the placebo group. These data suggest that treatment of severe thrombocytopenia accompanying DHF with anti-D may be a useful and safe therapeutic option. PMID:17426181

  12. Extreme Elevation of Alkaline Phosphatase in a Pregnancy Complicated by Gestational Diabetes and Infant with Neonatal Alloimmune Thrombocytopenia.

    Lozo, Svjetlana; Atabeygi, Amir; Healey, Michael

    2016-01-01

    There have been few case reports of isolated elevation of alkaline phosphatase beyond the normal physiologic amount with subsequent return to baseline after delivery. Here we present a similar case of extreme elevation of alkaline phosphatase in a pregnancy complicated by gestational diabetes and subsequently by neonatal alloimmune thrombocytopenia (NAIT). PMID:27610256

  13. Association of beta2-glycoprotein I IgG and IgM antibodies with thrombosis and thrombocytopenia

    Voss, Anne-Sofie Boertmann; Jacobsen, Søren; Heegaard, Niels Henrik Helweg

    2001-01-01

    Antiphospholipid antibodies (APA) have been known for decades. Their relation to clinical manifestations, primarily thromboses and thrombocytopenia, was recognised in the 1980s. In this clinical study two cohorts of patients, a population-based (84 patients with systemic lupus erythematosus (SLE)...

  14. Impact of Helicobacter pylori eradication on refractory thrombocytopenia in patients with chronic HCV awaiting antiviral therapy.

    Hanafy, A S; El Hawary, A T; Hamed, E F; Hassaneen, A M

    2016-07-01

    The possibility of delaying treatment of HCV due to severe thrombocytopenia is challenging. This study aimed to detect the prevalence of active helicobacter infection as a claimed cause of thrombocytopenia in a cohort of Egyptian patients with chronic active HCV awaiting combined anti-viral therapy. The study included 400 chronic HCV patients with thrombocytopenia. Laboratory investigations included liver function tests, real time quantitative PCR, reticulocytic count, ESR, ANA, bone marrow aspiration, measurement of anti-helicobacter antibodies, and helicobacter stool antigen. Positive cases for active H. pylori were given the standard triple therapy for 2 weeks. Helicobacter stool antigen was detected 4 weeks after termination of therapy and the change in platelet count was detected 1 month after eradication. A total of 248 out of 281 seropositive patients for H. pylori (88.3 %) showed positive stool antigen (p = 0.01). Eradication was achieved in 169 (68.1 %) patients with platelet mean count 114.9 ± 18.8 × 10(3)/μl with highly significant statistical difference from pretreatment value (49.7 ± 9.2 × 10(3)/μl, p = 0.000). Seventy-nine patients were resistant to conventional triple therapy and given a 7-day course of moxifloxacin-based therapy; 61 patients responded (77.1 %) with mean platelet improvement from 76.4 ± 17.4 × 10(3)/μl to 104.2 ± 15.2 × 10(3)/μl (p = 0.000). The non-responders showed no improvement in their platelet count (74.6 ± 20.5 vs. 73.6 ± 15.3 × 10(3)/ul, P = 0.5). Eradication of active H. pylori in HCV augments platelet count and enhances the early start of antiviral therapy. PMID:27180243

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

    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.

  16. Role of romiplostim in splenectomized and nonsplenectomized patients with immune thrombocytopenia.

    Perdomo, Jose

    2016-01-01

    Romiplostim is a thrombopoietin receptor agonist (TPO-RA) used for the treatment of adult primary immune thrombocytopenia (ITP). ITP is an autoimmune condition characterized by low platelet counts due to increased destruction and reduced platelet production. First-line interventions include corticosteroids, anti-D, and intravenous immunoglobulins, while second-line therapies comprise splenectomy, rituximab, cyclosporine A, and TPO-RAs. The recognition that compromised platelet production is a critical part of the pathogenesis of ITP prompted the development of therapeutic strategies based on the stimulation of the TPO receptor. TPO-RAs enhance megakaryocyte proliferation, increase platelet production, and lead to a reduction in bleeding episodes in ITP patients. This review will summarize current data on the TPO-RA romiplostim, with a particular focus on its relation to splenectomy. PMID:27529057

  17. Targeting autophagy as a potential therapeutic approach for immune thrombocytopenia therapy.

    Shan, Ning-Ning; Dong, Li-Li; Zhang, Xiao-Mei; Liu, Xin; Li, Ying

    2016-04-01

    Autophagy involves the sequestration and lysosomal degradation of various cytoplasmic structures, including damaged organelles and invading microorganisms. Autophagy is not only an essential cell-intrinsic mechanism for protecting against internal and external stress conditions but is also key in the cellular response against microbes, in antigen processing for major histocompatibility complex (MHC) presentation, and in lymphocyte development, survival, and proliferation. In recent years, perturbations in autophagy have been implicated in a number of diseases, including autoimmune diseases, such as systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and multiple sclerosis (MS). Immune thrombocytopenia (ITP) is a multifactorial disease characterized by autoimmune responses to self-platelet membrane proteins. Recently, our unpublished original data demonstrated aberrant expression of molecules in the autophagy pathway in ITP patients compared with controls, and we found a close correlation between the pathogenesis of ITP and the autophagy pathway. The potential of targeting the autophagy pathway in ITP as a novel therapeutic approach has been discussed. PMID:26830007

  18. Her-2 Positive Gastric Cancer Presented with Thrombocytopenia and Skin Involvement: A Case Report

    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.

  19. Her-2 Positive Gastric Cancer Presented with Thrombocytopenia and Skin Involvement: A Case Report

    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

  20. Cytokine expression during early and late phase of acute Puumala hantavirus infection

    Sadeghi Mahmoud

    2011-11-01

    Full Text Available Abstract Background Hantaviruses of the family Bunyaviridae are emerging zoonotic pathogens which cause hemorrhagic fever with renal syndrome (HFRS in the Old World and hantavirus pulmonary syndrome (HPS in the New World. An immune-mediated pathogenesis is discussed for both syndromes. The aim of our study was to investigate cytokine expression during the course of acute Puumala hantavirus infection. Results We retrospectively studied 64 patients hospitalised with acute Puumala hantavirus infection in 2010 during a hantavirus epidemic in Germany. Hantavirus infection was confirmed by positive anti-hantavirus IgG/IgM. Cytokine expression of IL-2, IL-5, IL-6, IL-8, IL-10, IFN-γ, TNF-α and TGF-β1 was analysed by ELISA during the early and late phase of acute hantavirus infection (average 6 and 12 days after onset of symptoms, respectively. A detailed description of the demographic and clinical presentation of severe hantavirus infection requiring hospitalization during the 2010 hantavirus epidemic in Germany is given. Acute hantavirus infection was characterized by significantly elevated levels of IL-2, IL-6, IL-8, TGF-β1 and TNF-α in both early and late phase compared to healthy controls. From early to late phase of disease, IL-6, IL-10 and TNF-α significantly decreased whereas TGF-β1 levels increased. Disease severity characterized by elevated creatinine and low platelet counts was correlated with high pro-inflammatory IL-6 and TNF-α but low immunosuppressive TGF-β1 levels and vice versa . Conclusion High expression of cytokines activating T-lymphocytes, monocytes and macrophages in the early phase of disease supports the hypothesis of an immune-mediated pathogenesis. In the late phase of disease, immunosuppressive TGF-β1 level increase significantly. We suggest that delayed induction of a protective immune mechanism to downregulate a massive early pro-inflammatory immune response might contribute to the pathologies characteristic of

  1. Acute Pancreatitis and Pregnancy

    ... Acute Pancreatitis > Acute Pancreatitis and Pregnancy test Acute Pancreatitis and Pregnancy Timothy Gardner, MD Acute pancreatitis is ... of acute pancreatitis in pregnancy. Reasons for Acute Pancreatitis and Pregnancy While acute pancreatitis is responsible for ...

  2. Acute Pancreatitis-Induced Thrombotic Thrombocytopenic Purpura

    Mohan Gurjar

    2012-01-01

    Full Text Available Context Acute pancreatitis due to thrombotic thrombocytopenic purpura is a well recognized condition. Here, we are reporting a rare converse phenomenon, in which thrombocytopenic purpura occurred secondary to acute pancreatitis. Case report A 19-year-old male referred to our intensive care unit with diagnosis of acute pancreatitis with multi-organ dysfunction. He had history of severe abdominal pain and recurrent vomiting about one month ago, requiring hospital admission. There, on diagnostic work-up at admission, abdominal ultrasonography was suggestive of pancreatitis. His serum amylase and lipase were 1,900 and 1,582 U/L, respectively. Other laboratory parameters were within normal limits. He was managed conservatively with intravenous fluids, antibiotics and analgesics; and discharged after about 2 weeks One week after discharge he was readmitted in same hospital with abdominal pain, multiple episodes of bilious vomiting and abdominal distention. Later on he was referred to our intensive care unit; having classical pentad of thrombocytopenic purpura, i.e., thrombocytopenia, micro-angiopathic hemolytic anemia, renal failure, encephalopathy, and fever. His condition improved with plasma exchange therapy and transferred out from our ICU to ward after 10 days of stay. Conclusion Thrombocytopenic purpura may be precipitate by acute pancreatitis due to multiple mechanisms. A high clinical suspicion is required to make an early diagnosis and allow early initiation of plasma exchange therapy, resulting in a goodprognosis.

  3. Bronchitis - acute

    ... sharing features on this page, please enable JavaScript. Acute bronchitis is swelling and inflammation in the main passages ... present only for a short time. Causes When acute bronchitis occurs, it almost always comes after having a ...

  4. Bronchitis - acute

    Acute bronchitis is swelling and inflammation in the main passages that carry air to the lungs. The swelling narrows ... makes it harder to breathe. Another symptom of bronchitis is a cough. Acute means the symptoms have ...

  5. Acute Bronchitis

    Bronchitis is an inflammation of the bronchial tubes, the airways that carry air to your lungs. It ... chest tightness. There are two main types of bronchitis: acute and chronic. Most cases of acute bronchitis ...

  6. Acute pancreatitis

    Bo-Guang Fan; Åke Andrén-Sandberg

    2010-01-01

    Background : Acute pancreatitis continues to be a serious illness, and the patients with acute pancreatitis are at risk to develop different complications from ongoing pancreatic inflammation. Aims : The present review is to highlight the classification, treatment and prognosis of acute pancreatitis. Material & Methods : We reviewed the English-language literature (Medline) addressing pancreatitis. Results : Acute pancreatitis is frequently caused by gallstone disease or excess alcohol ingest...

  7. Acute pancreatitis

    Bo-Guang Fan; Åke Andrén-Sandberg

    2010-01-01

    Background: Acute pancreatitis continues to be a serious illness, and the patients with acute pancreatitis are at risk to develop different complications from ongoing pancreatic inflammation. Aims: The present review is to highlight the classification, treatment and prognosis of acute pancreatitis. Material & Methods: We reviewed the English-language literature (Medline) addressing pancreatitis. Results: Acute pancreatitis is frequently caused by gallstone disease or excess alcohol ingestion....

  8. Immune mediators of chronic pelvic pain syndrome.

    Murphy, Stephen F; Schaeffer, Anthony J; Thumbikat, Praveen

    2014-05-01

    The cause of chronic pelvic pain syndrome (CPPS) has yet to be established. Since the late 1980s, cytokine, chemokine, and immunological classification studies using human samples have focused on identifying biomarkers for CPPS, but no diagnostically beneficial biomarkers have been identified, and these studies have done little to deepen our understanding of the mechanisms underlying chronic prostatic pain. Given the large number of men thought to be affected by this condition and the ineffective nature of current treatments, there is a pressing need to elucidate these mechanisms. Prostatitis types IIIa and IIIb are classified according to the presence of pain without concurrent presence of bacteria; however, it is becoming more evident that, although levels of bacteria are not directly associated with levels of pain, the presence of bacteria might act as the initiating factor that drives primary activation of mast-cell-mediated inflammation in the prostate. Mast cell activation is also known to suppress regulatory T cell (Treg) control of self-tolerance and also activate neural sensitization. This combination of established autoimmunity coupled with peripheral and central neural sensitization can result in the development of multiple symptoms, including pelvic pain and bladder irritation. Identifying these mechanisms as central mediators in CPPS offers new insight into the prospective treatment of the disease. PMID:24686526

  9. Narcolepsy as an Immune-Mediated Disease

    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.

  10. Cancer as an immune-mediated disease

    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

  11. Hymenoptera Stings and the Acute Kidney Injury

    Yashad Dongol

    2013-07-01

    Full Text Available Hymenoptera stings are a health concern. Apidae (bees, Vespidae (hornets, yellow jackets and wasps and Formicidae (ants are medically-important stinging insects under the order Hymenoptera. Clinical features from simple skin manifestations to severe and fatal organ injury are due to the hypersensitivity reactions and/ or the toxic effects of the venom inoculated. Here we discuss on Hymenoptera stings involving apids (honey bees and vespids (wasps, hornets and yellow jackets and their effect on renal function and associated morphological changes in the kidney. Despite the differences in venom composition and quantity released per sting in two insect groups, both lead to similar medical consequences, such as localised normal allergic reactions, mild to severe anaphylaxis and shock and multiple organ and tissue injury leading to multiple organ failure. Acute kidney injury (AKI is one of the unusual complications of Hymenoptera stings and has the basis of both immune-mediated and toxic effects. Evidence has proven that supportive therapy along with the standard medication is very efficient in completely restoring the kidney function without any recurrence.

  12. A Case of Thrombotic Thrombocytopenia Purpura Associated with Systemic Lupus Erythematosus: Diagnostic Utility of ADAMTS-13 Activity

    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.

  13. Heparin: Induced thrombocytopenia: Incidence and laboratory approach to diagnosis in Indians

    Jyoti Kotwal

    2014-01-01

    Full Text Available Background and objectives: One of the most common complications of heparin administration is heparin-induced thrombocytopenia (HIT which can also lead to catastrophic thrombotic events. The problem of identifying the cause of thrombocytopenia, as due to heparin, in patients with multiple co-morbid conditions is very essential for management. Thus, the laboratory investigations for diagnosis of HIT play a pivotal role. The objective of the study was to arrive at the incidence of HIT in ethnic Indian population and provide a decision after analysis of tests used to diagnose HIT. Materials and Methods: 125 consecutive patients (Power of study being 80% undergoing open heart surgery and receiving unfractionated heparin were taken as subjects. Blood samples were collected a day before the surgery and days 1, 3, 5 and 7 after surgery. The cases were categorized into probable and unlikely groups depending on the clinical presentation and degree fall of platelet count. Anti-heparin PF4-associated antibodies were detected using rapid-ID gel microtyping system and ELISA tests. HIT was also tested using functional assays:- heparin-induced platelet aggregation test (PAT and the rapid luminographic assay of heparin-induced ATP release. Results: Of the 125 patients, 11 patients were clinically labeled as probable HIT and 29 patients were clinically labeled as unlikely HIT. There were seven confirmed cases of HIT cases that were positive for one functional and one immunological assay. Only one case of HITT was encountered. Accordingly, the incidence of HIT was found to be 5.6 % and that of HITT to be 0.8%. ELISA tests were positive in 21 cases (17% which demonstrated the presence of anti-HPF4 antibodies in non-HIT cases as well. It was found that the rapid gel test had sensitivity comparable to functional assay with better specificity than ELISA. Interpretation and conclusions: Incidence of HIT in ethnic Indian population is 5.6%. Patients with a drop of >50

  14. Clinical manifestations and predictors of thrombocytopenia in hospitalized adults with dengue fever

    Akshatha Rao Aroor

    2015-01-01

    Full Text Available Background: India is one of the seven identified Southeast Asian countries reporting frequent outbreaks of dengue fever (DF. Aims: This study was to analyze clinical and laboratory profile and predictive markers of thrombocytopenia and length of hospital stay in DF. Materials and Methods: This record-based retrospective study conducted in a coastal district of Karnataka, South India, included all dengue cases in adults aged >18 years, admitted during period of January 2011 to December 2014. Multivariate logistic regression analysis was carried out to compute odds ratio (OR and 95% confidence interval (CI to assess independent associations of variables with low platelet count and longer duration of hospital stay. Results: Among 207 dengue immunoglobulin M (IgM antibody confirmed cases (mean age of 36.94 ± 14.61 years, 143 (69.1% were males and 64 were females. The mean duration of illness and hospital stay were 4.94 ± 3.58 days and 5.98 ± 2.58 days, respectively. Abdominal symptoms included nausea and vomiting (53.6%, abdominal pain (25.1%, and diarrhea (13.5%. Bleeding manifestations were seen in 24 (11.6% cases and fluid accumulation was revealed in 18 (8.7% cases. The mean platelet count was 110,159.42 ± 68,397.32 (cells/mm 3 . Low platelet count on admission was associated with the presence of rash (OR = 0.43, 95% CI 0.23-0.81, high aspartate aminotransferase (AST levels (OR = 3.14, 95% CI 1.58-6.23, high alanine aminotransferase (ALT levels (OR = 2.91, 95% CI 1.55-5.47, and low albumin levels (OR = 4.48, 95% CI 1.02-19.75. The duration of hospital stay was associated with diarrhea (OR = 0.4, 95% CI 0.18-0.9, abdominal pain (OR = 0.52, 95% CI 0.27-1.00, ascites (OR = 0.26, 95% CI 0.09-0.69, and low hemoglobin (OR = 0.46, 95% CI 0.25-0.86 level on admission. Conclusions: Though thrombocytopenia on admission was associated with the presence of rash, high AST and ALT levels, and low albumin levels, it was not predictive of length of

  15. Srčna operacija pri bolniku s heparinom povzročeno trombocitopenijo: Heparin induced thrombocytopenia and cardiac surgery:

    Geršak, Borut; Preložnik-Zupan, Irena; Šoštarič, Maja

    2008-01-01

    Background Heparin induced thrombocytopenia (HIT) is a serious complication related to the heparin treatment and might lead to the life-threatening consequences such as arterial and venous thrombosis. The patient with HIT scheduled for cardiac surgery represents serious problem because heparin, mostcommon used anticoagulation drug during cardiac surgery, must be avoided. Conclusions From the results of the recent clinical studies it seems that direct thrombin inhibitors, especially bivalirudi...

  16. Development of a Colloidal Gold Kit for the Diagnosis of Severe Fever with Thrombocytopenia Syndrome Virus Infection

    Xianguo Wang; Quanfu Zhang; Fen Hao; Xunian Gao; Wei Wu; Minyao Liang; Zhihua Liao; Shuhong Luo; Weiwen Xu; Dexin Li; Shiwen Wang

    2014-01-01

    It is critical to develop a cost-effective detection kit for rapid diagnosis and on-site detection of severe fever with thrombocytopenia syndrome virus (SFTSV) infection. Here, an immunochromatographic assay (ICA) to detect SFTSV infection is described. The ICA uses gold nanoparticles coated with recombinant SFTSV for the simultaneous detection of IgG and IgM antibodies to SFTSV. The ICA was developed and evaluated by using positive sera samples of SFTSV infection (n = 245) collected from the...

  17. [The prognostic indicators of development of ATRA-syndrome under treatment of acute promyelocyte leucosis].

    Skol'skaia, O Iu; Tarasova, L N; Vladimirova, S G; Cherepanova, V V

    2012-10-01

    The application of all-trans-retinoic acid (ATRA) in the protocols of treatment of acute promyelocyte leucosis provided the achievement of 95% of full remissions and fast correction of coagulopathy. Besides, ATRA along with positive impact can exert the side effects, among which the most dangerous is the differentiation syndrome. On the basis of analysis of clinical signs, biochemical, hemostasiologic and morphologic blood indicators it is established that among prognostic criteria of differentiation syndrome development are presence of febrile temperature, decrease of content of thrombocytes lesser than 20-109/l (deep degree of thrombocytopenia), prolongation of index of activated partial thromboplastin time relative to norm before treatment start. Apart from this, the following factors also are among such kind of criteria: decrease of hemoglobin after ATRA prescription before differentiation syndrome development, on-going hypofibrinogenemia and deep degree of thrombocytopenia under concurrent increase of content of urea and creatinine as compared with initial values in treatment dynamics. PMID:23265056

  18. Vitamin B12 and Vitamin D Deficiencies: An Unusual Cause of Fever, Severe Hemolytic Anemia and Thrombocytopenia

    Mishra, Vikas A.; Harbada, Rishit; Sharma, Akhilesh

    2015-01-01

    The array of diagnostic workup for pyrexia of unknown origin (PUO) generally revolves in searching for infections, inflammatory/autoimmune, and endocrine etiologies. A differential diagnosis of fever, hemolytic anemia, and thrombocytopenia can have etiologies varying from infections like malaria, dengue, cytomegalovirus, Ebstein barr virus, Parvovirus, infective endocarditis, to autoimmune disorder (systemic lupus erythromatosis), vasculitis, hemolytic uremic syndrome, thrombotic thrombocytopenic purpura (TTP), autoimmune hemolytic anemia/Evan's syndrome, paroxysmal nocturnal hemoglobinuri (PNH), or drugs. Nutritional deficiencies (especially vitamin B12 deficiency) as a cause of fever, hemolytic anemia, and thrombocytopenia are very rare and therefore rarely thought of. Severe vitamin B12 deficiency may cause fever and if accompanied by concurrent hyper-homocysteinemia and hypophosphatemia can sometimes lead to severe hemolysis mimicking the above-mentioned conditions. We present a case that highlights vitamin B12 and vitamin D deficiency as an easily treatable cause of PUO, hemolytic anemia, and thrombocytopenia, which should be actively looked for and treated before proceeding with more complicated and expensive investigation or starting empiric treatments. PMID:25811010

  19. Acute pancreatitis

    Bo-Guang Fan

    2010-05-01

    Full Text Available Background: Acute pancreatitis continues to be a serious illness, and the patients with acute pancreatitis are at risk to develop different complications from ongoing pancreatic inflammation. Aims: The present review is to highlight the classification, treatment and prognosis of acute pancreatitis. Material & Methods: We reviewed the English-language literature (Medline addressing pancreatitis. Results: Acute pancreatitis is frequently caused by gallstone disease or excess alcohol ingestion. There are a number of important issues regarding clinical highlights in the classification, treatment and prognosis of acute pancreatitis, and treatment options for complications of acute pancreatitis including pancreatic pseudocysts. Conclusions: Multidisciplinary approach should be used for the management of the patient with acute pancreatitis.

  20. Acute pancreatitis

    Bo-Guang Fan

    2010-01-01

    Full Text Available Background : Acute pancreatitis continues to be a serious illness, and the patients with acute pancreatitis are at risk to develop different complications from ongoing pancreatic inflammation. Aims : The present review is to highlight the classification, treatment and prognosis of acute pancreatitis. Material & Methods : We reviewed the English-language literature (Medline addressing pancreatitis. Results : Acute pancreatitis is frequently caused by gallstone disease or excess alcohol ingestion. There are a number of important issues regarding clinical highlights in the classification, treatment and prognosis of acute pancreatitis, and treatment options for complications of acute pancreatitis including pancreatic pseudocysts. Conclusions : Multidisciplinary approach should be used for the management of the patient with acute pancreatitis.

  1. Progresses of antithrombotic therapy for heparin-induced thrombocytopenia%肝素诱导的血小板减少症抗栓治疗进展

    唐永靖; 陈颖

    2016-01-01

    肝素诱导的血小板减少症(HIT)是指应用肝素之中或之后出现血小板计数减少,且可伴有血栓形成的一种严重并发症.在给予肝素治疗患者中,HIT是一种较常见的并发症,而HIT部分患者可发展致灾难性血栓形成和血栓栓塞并发症,包括肺栓塞、缺血性肢体坏死、急性心肌梗死和脑卒中.临床判断存在HIT时,需停用所有来源的肝素,并给予替代性抗凝治疗措施,应用直接凝血酶抑制剂及类肝素等药物.本文对HIT抗栓治疗进展进行综述.%Heparin-induced thrombocytopenia (HIT) is a serious complication,which refers to decreased in platelet count during or after use of heparin with and may be associated with thrombosis.HIT is a common complication in patients treated with heparin.In some HIT paitents,catastrophic thrombosis and thromboembolism complications including pulmonary embolism,ischemic limb necrosis,acute myocardial infarction,and stroke may develop.When HIP is diagnosed in clinical,all sources of heparin must be stopped and alternative anticoagulant therapy,such as direct thrombin inhibitors and heparin,should be given instead.This article reviewed the progresses of antithrombotic therapy for HIT.

  2. Thrombocytopenia as a surrogate marker of hepatosplenic schistosomiasis in endemic areas for Schistosomiasis mansoni

    Sandra Costa Drummond

    2014-04-01

    Full Text Available Introduction This study aimed to evaluate whether a low platelet count is a good surrogate marker of hepatosplenic schistosomiasis (HSS in a rural area of Brazil. A small district in southeastern Brazil, with a population of 1,543 individuals and a 23% prevalence of schistosomiasis, was selected for this investigation. Methods In July 2012, 384 volunteers were subjected to clinical, ultrasonography (US, and laboratory examinations, including stool sample analysis. The HSS patients were classified into four groups: Group 1 consisted of patients with a spleen >13cm and liver fibrosis; Group 2 consisted of patients with a palpable spleen and spleen>13cm measured by US; Group 3 consisted of patients with a spleen >13cm measured by US; and Group 4 consisted of patients with a palpable spleen. Results Eight patients were in Group 1 (2.1%, twenty-one were in Group 2 (5.5%, eight were in Group 3 (2.1%, and eighteen were in Group 4 (4.7%. A significant difference in the mean platelet counts was observed between the patients with and without HSS (p<0.01. Based on the receiver operating characteristic (ROC curve (platelet count <143,000/mm3, the sensitivity was greater than 92% in all groups, and the specificity varied from 44.4% to 75%. Conclusions We concluded that in endemic areas, thrombocytopenia demonstrates good sensitivity for detecting HSS and may be used as a screening tool to identify patients with HSS.

  3. Anti-D treatment for pediatric immune thrombocytopenia: Is the bad reputation justified?

    Yacobovich, Joanne; Abu-Ahmed, Sabreen; Steinberg-Shemer, Orna; Goldberg, Tracie; Cohen, Miriam; Tamary, Hannah

    2016-04-01

    The purpose of this study was to assess the efficacy and side effect profile of the repeated use of anti-D for the treatment of pediatric immune thrombocytopenia (ITP) in a large pediatric hematology center. We performed a retrospective analysis of patient records for children (aged 4 months-18 years) treated for ITP at Schneider Children's Medical Center of Israel from 1995-2015. Demographic and clinical data, reported adverse events, and therapy response were extracted from written and electronic files for all patients having received anti-D. Therapy response was defined as time to platelet count >30 x 10(9)/L. Thirty-six patients received 170 treatments of anti-D at a dose of 75 μg/kg. The majority were previously treated with corticosteroids and/or intravenous immunoglobulin (IVIG). Minimal adverse events were recorded including fever (3.5%), vomiting (2.9%), and headaches (1.7%). Notably only 1/170 treatments required blood transfusion and no life-threatening events occurred. The average time to platelets >30 x 10(9)/L was 2.3 days, with a median of 1 day, range 1-12 days. Despite the reported severe adverse events in mainly elderly patients, the use of anti-D can be safe and effective in carefully chosen, low-risk pediatric patients with ITP. PMID:27312170

  4. CD8+ T cells induce platelet clearance in the liver via platelet desialylation in immune thrombocytopenia

    Qiu, Jihua; Liu, Xuena; Li, Xiaoqing; Zhang, Xu; Han, Panpan; Zhou, Hai; Shao, Linlin; Hou, Yu; Min, Yanan; Kong, Zhangyuan; Wang, Yawen; Wei, Yu; Liu, Xinguang; Ni, Heyu; Peng, Jun; Hou, Ming

    2016-01-01

    In addition to antiplatelet autoantibodies, CD8+ cytotoxic T lymphocytes (CTLs) play an important role in the increased platelet destruction in immune thrombocytopenia (ITP). Recent studies have highlighted that platelet desialylation leads to platelet clearance via hepatocyte asialoglycoprotein receptors (ASGPRs). Whether CD8+ T cells induce platelet desialylation in ITP remains unclear. Here, we investigated the cytotoxicity of CD8+ T cells towards platelets and platelet desialylation in ITP. We found that the desialylation of fresh platelets was significantly higher in ITP patients with positive cytotoxicity of CD8+ T cells than those without cytotoxicity and controls. In vitro, CD8+ T cells from ITP patients with positive cytotoxicity induced significant platelet desialylation, neuraminidase-1 expression on the platelet surface, and platelet phagocytosis by hepatocytes. To study platelet survival and clearance in vivo, CD61 knockout mice were immunized and their CD8+ splenocytes were used. Platelets co-cultured with these CD8+ splenocytes demonstrated decreased survival in the circulation and increased phagocytosis in the liver. Both neuraminidase inhibitor and ASGPRs competitor significantly improved platelet survival and abrogated platelet clearance caused by CD8+ splenocytes. These findings suggest that CD8+ T cells induce platelet desialylation and platelet clearance in the liver in ITP, which may be a novel mechanism of ITP. PMID:27321376

  5. CD8(+) T cells induce platelet clearance in the liver via platelet desialylation in immune thrombocytopenia.

    Qiu, Jihua; Liu, Xuena; Li, Xiaoqing; Zhang, Xu; Han, Panpan; Zhou, Hai; Shao, Linlin; Hou, Yu; Min, Yanan; Kong, Zhangyuan; Wang, Yawen; Wei, Yu; Liu, Xinguang; Ni, Heyu; Peng, Jun; Hou, Ming

    2016-01-01

    In addition to antiplatelet autoantibodies, CD8(+) cytotoxic T lymphocytes (CTLs) play an important role in the increased platelet destruction in immune thrombocytopenia (ITP). Recent studies have highlighted that platelet desialylation leads to platelet clearance via hepatocyte asialoglycoprotein receptors (ASGPRs). Whether CD8(+) T cells induce platelet desialylation in ITP remains unclear. Here, we investigated the cytotoxicity of CD8(+) T cells towards platelets and platelet desialylation in ITP. We found that the desialylation of fresh platelets was significantly higher in ITP patients with positive cytotoxicity of CD8(+) T cells than those without cytotoxicity and controls. In vitro, CD8(+) T cells from ITP patients with positive cytotoxicity induced significant platelet desialylation, neuraminidase-1 expression on the platelet surface, and platelet phagocytosis by hepatocytes. To study platelet survival and clearance in vivo, CD61 knockout mice were immunized and their CD8(+) splenocytes were used. Platelets co-cultured with these CD8(+) splenocytes demonstrated decreased survival in the circulation and increased phagocytosis in the liver. Both neuraminidase inhibitor and ASGPRs competitor significantly improved platelet survival and abrogated platelet clearance caused by CD8(+) splenocytes. These findings suggest that CD8(+) T cells induce platelet desialylation and platelet clearance in the liver in ITP, which may be a novel mechanism of ITP. PMID:27321376

  6. A Non-Invasive Strategy for Neonatal Alloimmune Thrombocytopenia Diagnosis: Newborn Platelet Genotyping with Buccal Swabs

    Gérald Bertrand

    2016-07-01

    Full Text Available Neonatal alloimmune thrombocytopenia results from the maternal immune response against fetal-specific antigens inherited from the father. The diagnosis is ascertained only when the maternal alloantibody and the offending antigen present in the newborn are identified. Up until now most laboratories perform DNA extraction for neonatal genotyping from newborn blood samplings. In order to avoid such an invasive procedure, two protocols of DNA extraction from buccal swabs were developed: a manual protocol using the QIAamp mini blood kit (Qiagen, and an automated procedure with the MagNA Pure Compact instrument (Roche. Both EDTA-blood and buccal swabs from thrombocytopenic newborns were genotyped manually (14 samples, automatically (15 samples or both manually and automatically (two samples. Human Platelet Antigen (HPA genotyping was performed using the BeadChip assay (BioArray, Immucor. Concordant genotypings were obtained for all samples except for one swab with the manual method. The automated DNA extraction from newborn buccal swabs with the MagNA Pure Compact instrument was chosen as the first-line strategy, with a significant gain of time in processing buccal swabs.

  7. Rituximab and dexamethasone vs dexamethasone monotherapy in newly diagnosed patients with primary immune thrombocytopenia

    Gudbrandsdottir, Sif; Birgens, Henrik Sverre; Frederiksen, Henrik;

    2013-01-01

    In this study, we report the results from the largest cohort to date of newly diagnosed adult immune thrombocytopenia patients randomized to treatment with dexamethasone alone or in combination with rituximab. Eligible were patients with platelet counts ≤25×10(9)/L or ≤50×10(9)/L with bleeding...... symptoms. A total of 133 patients were randomly assigned to either dexamethasone 40 mg/day for 4 days (n = 71) or in combination with rituximab 375 mg/m(2) weekly for 4 weeks (n = 62). Patients were allowed supplemental dexamethasone every 1 to 4 weeks for up to 6 cycles. Our primary end point, sustained...... response (ie, platelets ≥50×10(9)/L) at 6 months follow-up, was reached in 58% of patients in the rituximab + dexamethasone group vs 37% in the dexamethasone group (P = .02). The median follow-up time was 922 days. We found longer time to relapse (P = .03) and longer time to rescue treatment (P = .007) in...

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

    Ashok S

    2016-03-01

    Full Text Available 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 development. Other common links between with TAR seem to include heart problems, kidney problems, knee joint problems, frequently lactose intolerance and often thumb hypoplasia. The incidence is 0.5-1 per 100,000 live births. Mutations in the RBM8A gene cause TAR syndrome. It is inherited in an autosomal recessive pattern. This disorder is to be differentiated from Holt-Oram syndrome, which has similar presentation. Prevention of bleeding with physiotherapy and occupational therapy are mainstay of management. With this case report we try to discuss the complexity of the condition and its management in the neonatal period.

  9. Thromboembolism in patients with immune thrombocytopenia (ITP): a meta-analysis of observational studies.

    Langeberg, Wendy J; Schoonen, W Marieke; Eisen, Melissa; Gamelin, Laurence; Stryker, Scott

    2016-06-01

    This meta-analysis describes the incidence rate of arterial and venous thromboembolism (ATE and VTE) in patients with immune thrombocytopenia (ITP), and the relative risk of ATE and VTE in patients with ITP and comparable populations without ITP. MEDLINE and EMBASE were systematically searched for observational studies reporting incidence rates of ATE and VTE in populations with and without ITP between 1996 and 2013 [follow-up completed before thrombopoietin receptor (TPOr) agonists were commercially available]. Three large, population-based studies were identified from Denmark, the United Kingdom, and the United States. The incidence of ATE per 100 patient-years among patients with ITP ranged from 1.0 to 2.8, and among populations without ITP ranged from 0.7 to 1.8; the summary relative risk adjusted for matching factors (aRR) was 1.5 [95 % confidence interval (CI) 1.3, 1.8]. The incidence of VTE per 100 patient-years among patients with ITP ranged from 0.4 to 0.7, and among populations without ITP ranged from 0.1 to 0.4; the summary aRR (95 % CI) was 1.9 (1.4, 2.7). The risk of ATE and VTE among patients with ITP, based on evidence from three large, population-based observational studies, should be considered when evaluating the risk of thromboembolism attributed to ITP treatments, such as TPOr agonists. PMID:27084254

  10. Long-term treatment with romiplostim in patients with chronic immune thrombocytopenia: safety and efficacy

    D. J. Kuter

    2015-01-01

    Full Text Available Romiplostim was effective, safe, and well-tolerated over 6–12 months of continuous treatment in Phase 3 trials in patients with immune thrombocytopenia (ITP. This report describes up to 5 years of weekly treatment with romiplostim in 292 adult ITP patients in a long-term, single-arm, open-label study. Outcome measures included adverse events (including bleeding, thrombosis, malignancy, and reticulin / fibrosis, platelet response (platelet count >50 × 109 per litre, and the proportion of patients requiring rescue treatments. Treatment – related serious adverse events were infrequent and did not increase with longer treatment. No new classes of adverse events emerged. Thrombotic events occurred in 6.5 % of patients and were not associated with platelet count. Median platelet counts of 50–200 × 109 per litre were maintainedwith stable doses of romiplostim (mean 5–8 μg / kg; generally self-administered at home throughout the study. A platelet response was achieved at least once by 95 % of patients, with a platelet response maintained by all patients on a median 92 % of study visits. There was a low rate of bleeding and infrequent need for rescue treatments. In conclusion, this study demonstrated that romiplostim was safe and welltolerated over 614 patient-years of exposure in ITP patients, and that efficacy was maintained with stable dosing for up to 5 years of continuous treatment.

  11. Acute inflammation reduces kisspeptin immunoreactivity at the arcuate nucleus and decreases responsiveness to kisspeptin independently of its anorectic effects

    Castellano, J M; Bentsen, A H; Romero, M;

    2010-01-01

    suggested as potential target for transmitting immune-mediated repression of the gonadotropic axis during acute inflammation, and yet key facets of such a phenomenon remain ill defined. Using lipopolysaccharide S (LPS)-treated male rats as model of inflammation, we document herein the pattern of...... intake and body weight. Yet pair-fed males did not show similar alterations in LH and testosterone secretory responses to Kp-10, whose magnitude was preserved, if not augmented, during food restriction. In summary, our data document the impact of acute inflammation on kisspeptin content at the ARC as key...... center for the neuroendocrine control of reproduction. Our results also suggest that suppressed gonadotropic function following inflammatory challenges might involve a reduction in absolute responsiveness to kisspeptin that is independent of the anorectic effects of inflammation....

  12. Bortezomib-Induced Acute Pancreatitis

    Bouraoui Elouni

    2010-05-01

    Full Text Available Dear Sir, Bortezomib is the first proteasome inhibitor approved by the Food and Drug Administration (FDA and indicated for patients with multiple myeloma refractory to at least one prior therapy [1]. The most common adverse effects of bortezomib include hematological toxicities (especially transient thrombocytopenia, gastrointestinal disturbances, peripheral neuropathy, fatigue, fever, dyspnea, rash, and myalgia [2]. We herein present the first case of acute pancreatitis induced by bortezomib. A 58-year-old female was treated with vincristine, doxorubicin, and dexamethasone for a myeloma. She had no history of dyslipidemia or alcohol abuse. In relation to the relapse of the myeloma, two doses of bortezomib (1.3 mg/m2 were administered intravenously at a 4-day time interval. Concomitant medications in our patient included dexamethasone, levothyroxine for hypothyroidism, and paracetamol. Two days later, she presented because of abdominal pain of medium intensity localized in the epigastrium for which she was hospitalized. On admission, the patient had normal vital signs without fever. Abdominal examination revealed only mild epigastric tenderness. There was no rigidity or guarding. There were no palpable abdominal masses. The remainder of the examination was normal. A laboratory work-up showed a normal blood cell count and did not demonstrate hypertriglyceridemia, hypercholesterolemia or hypercalcemia. A liver test, renal function, serum electrolytes and blood sugars were all normal.

  13. Quadro seroproteico como auxílio diagnóstico na anemia hemolítica imunomediada em cães Serum proteic profile as diagnosis aids in immune-mediated hemolytic anemia in dogs

    Patrícia Mendes Pereira

    2010-04-01

    maior nestes. Tais achados analisados em conjunto agregam informações adicionais úteis à elucidação das AHIMs em cães.This assay aimed to determine the serum protein - via polyacrylamide gel electrophoresis, which contained duodecil sodium sulfate (SDS-PAGE - in 120 dogs, with different breeds and ages, seen by the Veterinary Hospital "Governor Laudo Natel." These animals were grouped into five experimental groups: Group 1 - group control with 20 dogs, group 2 - 28 dogs with regenerative anemia; group 3 - 27 dogs with arregenarative; anemia group 4 - 10 dogs with primary immune-mediated hemolytic anemia (AHIM 1.rd; group 5 - 35 dogs with secondary immune-mediated hemolytic anemia (AHIM 2.rd. The technique allowed the SDS-PAGE fractionation of 24 protein, whose molecular weights (PM ranged from 18,000 to 165,000 daltons (Da. The dogs with 1st and 2nd AHIM showed 24 protein fractions in their tracks electrophoretic, while other groups of dogs showed 23 fractions of protein, whose molecular protein weight of 68,000Da was not found. Thus, twenty-three proteins were common to proteinograms of the five experimental groups. From these, it was possible to identify eleven protein fractions nominally, and others were identified by their molecular weights. For control dogs, the anemic (groups 2, 3, 4 and 5 showed higher concentrations of serum transferrin and between them, the animals carrying the primary IMHA. All groups of dogs showed anemic levels of serum haptoglobin and phosphorylase significantly higher than the control dogs, while the serum ceruloplasmin was lower in anemic dogs. These findings provide additional information to the elucidation of the AHIMs in dogs.

  14. Acute megakaryoblastic leukemia with increased hematogones in children.

    Anton-Harisi, Marieta; Douna, Varvara; Baka, Margarita; Servitzoglou, Marina; Kosmidis, Helen V; Georgouli, Helen; Anastasiou, Theodora

    2012-11-01

    We describe 2 patients, a 4-month-old male and a 17-month-old female, with de novo acute megakaryoblastic leukemia with increased number of hematogones at diagnosis. Both children were admitted in the hospital with thrombocytopenia. The bone marrow smears in the first child revealed the presence of 60% cells with morphologic features consistent with acute megakaryoblastic leukemia. In the other, the initial bone marrow aspirate was dry tap but on the following aspirate 10% cells with lymphoblastic morphology could be seen. The bone marrow flow cytometry showed the presence of hematogones-38% in the first case and 20% in the second-with absence of blasts. Repeated bone marrow aspirates, trephines, and immunophenotypic as well as molecular studies, confirmed the diagnosis of M7. Both children were treated according to the Berlin-Frankfurt-Munster 2004 protocol. PMID:22983420

  15. Acute Splenic Sequestration Crisis in a 70-Year-Old Patient With Hemoglobin SC Disease.

    Squiers, John J; Edwards, Anthony G; Parra, Alberto; Hofmann, Sandra L

    2016-01-01

    A 70-year-old African American female with a past medical history significant for chronic bilateral shoulder pain and reported sickle cell trait presented with acute-onset bilateral thoracolumbar pain radiating to her left arm. Two days after admission, Hematology was consulted for severely worsening microcytic anemia and thrombocytopenia. Examination of the patient's peripheral blood smear from admission revealed no cell sickling, spherocytes, or schistocytes. Some targeting was noted. A Coombs test was negative. The patient was eventually transferred to the medical intensive care unit in respiratory distress. Hemoglobin electrophoresis confirmed a diagnosis of hemoglobin SC disease. A diagnosis of acute splenic sequestration crisis complicated by acute chest syndrome was crystallized, and red blood cell exchange transfusion was performed. Further research is necessary to fully elucidate the pathophysiology behind acute splenic sequestration crisis, and the role of splenectomy to treat hemoglobin SC disease patients should be better defined. PMID:27047980

  16. Thrombocytopenia in plasmodium parasitized pregnant women in the Niger Delta of Nigeria

    O Erhabor

    2010-01-01

    Full Text Available O Erhabor1, Z A Jeremiah1, T C Adias2, M L Hart11Department of Medical Laboratory Sciences, College of Health Sciences, Niger Delta University, Wilberforce Island, Bayelsa State, Nigeria; 2Department of Medical Laboratory Sciences, Rivers State University of Science and Technology, Port Harcourt, NigeriaBackground: Malaria infection during pregnancy is a major public health problem in tropical and subtropical regions of the world. Hematological changes associated with malaria in pregnancy are not well documented, and have focused predominantly on anemia. The aim of this study was to determine the impact of Plasmodium parasitaemia on the platelet count of pregnant women in the Niger Delta of Nigeria.Methods: In this observational study we reviewed the platelet counts from routine complete blood count (CBC in a cohort of healthy (pregnant and nonpregnant and malaria-infected pregnant women attending antenatal clinics. A platelet count of 100 × 109/L was the threshold at two standard deviations below the mean for healthy Nigerian pregnant women used to indicate thrombocytopenia. Differences in platelet counts were compared based on malaria species and parasitemia in matched nonpregnant and pregnant women. Blood smears from Quantitative Buffy Coat malaria-positive samples stained with Giemsa were used for determination of parasite load and specie identification by light microscopy.Study design: This case control study evaluated the effect of malaria parasitemia on the platelet count of 50 plasmodium parasitized pregnant subjects. Fifty nonmalaria parasitized pregnant women and fifty nonpregnant and nonmalaria-infected subjects served as control.Results: The mean platelet counts (×109/L were significantly lower in pregnant subjects with an episode of Plasmodium falciparum malaria 111.3 ± 9.3 × 109/L compared to nonparasitized and healthy nonpregnant controls (255.09 ± 24.10 and 270 ± 51.5 × 109/L respectively. Platelet count values were 112

  17. Thrombocytopenia, splenomegaly, and portal blood flow in patients who have undergone liver transplantation for cirrhosis.

    Eyraud, Daniel; Granger, Benjamin; Ionescu, Christian; Fratéa, Silvia; Darnat, Sabine; Vaillant, Jean-Christophe; Siksik, Jean-Michel; Hannoun, Laurent; Coriat, Pierre

    2012-03-01

    The platelet count (PC), the spleen size (SS), and the portal blood flow (PBF) have been independently studied in the perioperative period after orthotopic liver transplantation (OLT) for cirrhosis, but these parameters have not been described and analyzed in combination. We analyzed PC data and Doppler sonography measurements of SS and PBF from 125 adult patients before OLT and 1, 3, 6, 9, and 12 months after transplantation. A linear mixed model with fixed subject random intercepts was used. PCs increased significantly from 101.5 ± 68.5 × 10(9) /L before OLT to 162.4 ± 86 × 10(9) /L 1 month after OLT and remained stable for 1 year after the operation. PBF increased significantly from 619 ± 239 mL/minute before OLT to 1379 ± 491 mL/minute after OLT and remained stable during the first year. SS slowly decreased after OLT, but the decrease became significant only 9 months after the operation (13.8 ± 4.2 cm before OLT versus 11.7 ± 3.7 cm at 9 months, P < 0.05). The cirrhosis etiology did not influence the evolution of the parameters. With or without replication or interferon treatment before OLT, the hepatitis C group viruses did not influence PCs postoperatively. The evolution of SS was correlated to the evolution of PCs in the year after transplantation. In conclusion, PCs and PBF increase rapidly after OLT, whereas SS slowly decreases. The cirrhosis etiology does not influence the evolution of PCs. Thrombocytopenia and splenomegaly are 2 results of portal hypertension, but the rapid normalization of PBF does not completely or rapidly reverse these 2 phenomena. PMID:22006447

  18. A case of refractory immune thrombocytopenia in pregnancy managed with elthrombopag

    Jyothis Purushothaman

    2016-01-01

    Full Text Available Immune thrombocytopenic purpura is a common acquired autoimmune disorder defined by a low platelet count secondary to accelerated platelet destruction or impaired thrombopoesis by anti-platelet antibodies. Thrombopoietin (TPO-mimetic drugs such as eltrombopag and romiplostim have been used successfully in many nonpregnant individuals with immune thrombocytopenia (ITP but studies based on its effects in pregnancy are limited. A 27-year-old multigravida who is a known case of ITP with bad obstetric history was referred to the Department of Obstetrics and Gynecology at 26 weeks of gestation with complaints of mucosal bleeding and recurrent abortions. After 2 weeks of hospital stay, the patient did not respond to treatment with steroid and immunosuppressant. There was a rapid decline in platelet count with mucosal bleeds for which she required frequent platelet transfusions. Due to high costs, short action periods, and other potential maternal and fetal side effects of intravenous immunoglobulin (IVIgG and anti-D, it was decided that TPO-mimetic drug eltrombopag would be given. After starting treatment with eltrombopag, the patient's platelet count could be maintained between 30,000/μl and 50,000/μl. At 36 weeks of gestation following preterm-induced vaginal delivery, she delivered a male active baby weighing 1.86 kg with an Apgar score of 8/10. After delivery, her platelet count was 60,000/μl. Eltrombopag is a thrombopoietin receptor agonist. It has been assigned to pregnancy category C by the Food and Drug Administration (FDA. There are no adequate and well-controlled studies of use of eltrombopag in pregnancy. In our case, the drug was given in the last trimester of pregnancy and the mother and baby were in good health at the time of discharge from the hospital and during follow-up.

  19. PCI postoperative tirofiban cause severe thrombocytopenia three cases of clinical analysis%PCI术后应用替罗非班致重度血小板减少3例临床分析

    赵国伟

    2015-01-01

    ObjectiveDiscussion after PCI tirofiban-induced platelet reducing acute severe clinical symptoms, diagnosis and treatment strategies.MethodsOur hospital in January 2014 --2015 in three cases in May after PCI tirofiban-induced thrombocytopenia in patients with severe reduction of clinical data were retrospectively analyzed.Result 3 patients on admission were within the normal range of platelets, PCI postoperative intravenous infusion of tirofiban people, 0.5-2 hours of the onset chills, fever and other symptoms, severe thrombocytopenia Jicha confirmed, promptly disable tirofiban and other antiplatelet drugs, hormone therapy, the platelet count in 10 hours to 5 days to return to normal, fatal bleeding and thrombosis and other adverse events did not occur.ConclusionApplication should be after PCI tirofiban should be closely observed for the disease, chills, fever and other symptoms of acute thrombocytopenia taking into account the possibility of acute check platelets, disable the anti-platelet drugs, hormone and other drugs, to avoid serious adverse events occur.%目的:探讨P C I术后替罗非班致急性血小板重度减少的临床症状,诊断及处理策略。方法:收集我院2014年1月-2015年5月的3例PCI术后替罗非班致血小板重度减少患者的病例资料,进行回顾性分析。结果:3例患者入院时血小板均在正常范围,PCI术后应用替罗非班静脉泵人,0.5-2小时发生寒颤,高热等症状,急查证实血小板重度减少,及时停用替罗非班及其他抗血小板药物,应用激素等治疗,血小板计数于10小时-5天恢复正常,未发生致命性出血及血栓等不良事件。结论:PCI术后应用替罗非班时应严密观察病情,出现寒颤,高热等症状时应考虑到急性血小板减少的可能,急性查血小板,停用抗血小板药物,应用激素等药物治疗,避免严重不良事件发生。

  20. Acute Herpes Simplex Viral Esophagitis Occurring in 5 Immunocompetent Individuals With Eosinophilic Esophagitis

    Criblez, Dominique H.; Dellon, Evan S.; Bussmann, Christian; Pfeifer, David; Froh, Matthias; Straumann, Alex

    2016-01-01

    Herpes simplex esophagitis (HSE) is an acute, severe viral infection of the esophagus, rarely occurring in immunocompetent individuals. Eosinophilic esophagitis (EoE) is a rare immune-mediated esophageal disorder. We recently observed 5 severe HSE cases in diagnosed EoE patients. Four of the 5 patients had active, untreated EoE at the time of infection, so HSE is not likely a side effect of swallowed topical corticosteroids, the first-line medical treatment of EoE. However, this coincidence of these 2 rare conditions raises the question of a causal relationship between these 2 forms of esophagitis, and whether active EoE might predispose to HSE infection.

  1. [Acute tubulointerstitial nephritis following adenovirus and respiratory syncytial virus infection].

    de Suremain, A; Somrani, R; Bourdat-Michel, G; Pinel, N; Morel-Baccard, C; Payen, V

    2015-05-01

    Acute tubulointerstitial nephritis (TIN) is responsible for nearly 10% of acute renal failure (ARF) cases in children. It is mostly drug-induced, but in a few cases viruses are involved, probably by an indirect mechanism. An immune-competent 13-month-old boy was admitted to the intensive care unit for severe ARF with anuria in a context of fever, cough, and rhinorrhea lasting 1 week. The kidney biopsy performed early brought out tubulointerstitial damage with mild infiltrate of lymphocytes, without any signs of necrosis. There were no virus inclusion bodies, no interstitial hemorrhage, and no glomerular or vascular damage. Other causes of TIN were excluded: there was no biological argument for an immunological, immune, or drug-induced cause. Adenovirus (ADV) and respiratory syncytial virus (RSV) were positive in respiratory multiplex polymerase chain reaction (PCR) in nasal aspirate but not in blood, urine, and renal tissue. The patient underwent dialysis for 10 days but the response to corticosteroid therapy was quickly observed within 48 h. The mechanism of TIN associated with virus infection is unknown. However, it may be immune-mediated to be able to link severe renal dysfunction and ADV and/or RSV invasion of the respiratory tract. PMID:25842199

  2. Thrombocytopenia in early pregnancy predicting partial haemolysis, elevated liver enzyme and low platelet count syndrome: a case report and review of literature

    Kavitha Nagandla

    2016-08-01

    Full Text Available The incidence of thrombocytopenia in pregnancy is 6-10% and is classically defined as a platelet count of less than 150,000/ L. Counts less than 100,000 to 150,000/L are considered mild, 50,000 to 100,000/L as moderate, and less than 50,000/L are considered as severe thrombocytopenia. It is the second most common hematological condition in pregnancy with anaemia being the leading cause. Thrombocytopenia may be related to disorders that are intrinsic to pregnancy such as gestational thrombocytopenia that is seen in three-fourths of all cases. The second common cause is hypertensive disorders in pregnancy more commonly seen in severe pre-eclampsia in 21% and in HELLP (haemolysis, elevated liver enzyme and low platelet count that accounts for 12% of thrombocytopenia cases in pregnancy. This case report revisits the diagnosis of partial HELLP under the background of preeclampsia that warrants aggressive treatment like complete HELLP syndrome to optimize the maternal and fetal outcome. [Int J Reprod Contracept Obstet Gynecol 2016; 5(8.000: 2847-2850

  3. Maintenance treatment with azacytidine for patients with high-risk myelodysplastic syndromes (MDS) or acute myeloid leukaemia following MDS in complete remission after induction chemotherapy

    Grövdal, Michael; Karimi, Mohsen; Khan, Rasheed;

    2010-01-01

    This prospective Phase II study is the first to assess the feasibility and efficacy of maintenance 5-azacytidine for older patients with high-risk myelodysplastic syndrome (MDS), chronic myelomonocytic leukaemia and MDS-acute myeloid leukaemia syndromes in complete remission (CR) after induction ......-IV thrombocytopenia and neutropenia occurred after 9.5 and 30% of the cycles, respectively, while haemoglobin levels increased during treatment. 5-azacytidine treatment is safe, feasible and may be of benefit in a subset of patients....

  4. Recurrent gastrointestinal hemorrhage in treatment with dasatinib in a patient showing SMAD4 mutation with acute lymphoblastic leukemia Philadelphia positive and juvenile polyposis hereditary hemorrhagic telangiectasia syndrome

    Chiara Sartor

    2013-07-01

    Full Text Available We report a case of a patient affected by juvenile polyposis and hereditary hemorrhagic telangiectasia linked to a SMAD4 mutation who developed acute lymphoblastic leukemia positive for the Philadelphia chromosome translocation and with a complex karyotype. During the treatment with the tyrosine kinase inhibitor dasatinib the patient presented recurrent severe gastrointestinal hemorrhages linked to the genetic background and aggravated by thrombocytopenia.

  5. Evaluation of the effect of partial splenic embolization on platelet values for liver cirrhosis patients with thrombocytopenia

    Chi-Ming Lee; Ting-Kai Leung; Hung-Jung Wang; Wei-Hsing Lee; Li-Kuo Shen; Jean-Dean Liu; Chun-Chao Chang; Ya-Yen Chen

    2007-01-01

    AIM: To investigate the effect of partial splenic embolization (PSE) on platelet values in liver cirrhosis patients with thrombocytopenia and to determine the effective embolization area for platelet values improvement.METHODS: Blood parameters and liver function indicators were measured on 10 liver cirrhosis patients (6 in Child-Pugh grade A and 4 in grade B) with thrombocytopenia (platelet values < 80 × 103/μL) before embolization. Computed tomography scan was also needed in advance to acquire the splenic baseline. After 2 to 3 d, angiography and splenic embolization were performed. A second computed tomography scan was made to confirm the embolization area after 2 to 3 wk of embolization. The blood parameters of patients were also examined biweekly during the 1 year follow-up period.RESULTS: According to the computed tomography images after partial splenic embolization, we divided all patients into two groups: low (< 30%), and high (≥ 30%) embolization area groups. The platelet values were increased by 3 times compared to baseline levels after 2 wk of embolization in high embolization area group. In addition, there were significant differences in platelet values between low and high embolization area groups. GPT values decreased significantly in all patients after 2 wk of embolization. The improvement in platelet and GPT values still persisted until 1 year after PSE.In addition, 3 of 4 (75%) Child-Pugh grade B patients progressed to grade A after 2 mo of PSE. The complication rate in < 30% and ≥ 30% embolization area groups was 50% and 100%, respectively.CONCLUSION: Partial splenic embolization is an effective method to improve platelet values and GPT values in liver cirrhosis patients with thrombocytopenia and the ≥ 30% embolization area is meaningful for platelet values improvement. The relationship between the complication rate and embolization area needs further studies.

  6. Immune thrombocytopenia. Use of a Coombs antiglobulin test to detect IgG and C3 on platelets

    We applied a radiolabeled Coombs antiglobulin test to the diagnosis and management of immune thrombocytopenia in adults and children. This assay substantiated that the majority of patients with idiopathic thrombocytopenic purpura have increased levels of IgG on their platelets. Platelets from a patient with the post-transfusion-purpura syndrome also carried increased IgG, indicating a role for IgG antibody or IgG-containing immune complexes in the destruction of host platelets in this disease. The radiolabeled Coombs test provides a general means to help diagnose, manage, and study immune platelet disorders

  7. Trends in anti-D immune globulin for childhood immune thrombocytopenia: Usage, response rates, and adverse effects

    Long, Michelle; Kalish, Leslie A.; Neufeld, Ellis J.; Grace, Rachael F.

    2011-01-01

    In 2010, the Food and Drug Administration (FDA) added a black box warning to anti-D immune globulin (Rho(D) immune globulin, anti-D) for immune thrombocytopenia (ITP) to warn of the complications related to severe hemolysis. The objective of this retrospective medical record review was to examine recent trends in anti-D use to treat ITP and rates of adverse events in a single large pediatric hematology program. Over a 7-year period, 176 (35%) of 502 ITP patients at our center received anti-D....

  8. Thrombocytopenia-associated multiple organ failure or severe haemolysis, elevated liver enzymes, low platelet count in a postpartum case

    Manish Jagia

    2013-01-01

    Full Text Available Thrombocytopenia-associated multiple organ failure (TAMOF is a thrombotic microangiopathic syndrome that includes thrombotic thrombocytopenic purpura, secondary thrombotic microangiopathy, and disseminated intravascular coagulation. We report a case of postpartum female who presented with TAMOF or severe Haemolysis, elevated liver enzymes, low platelet count (HELLP which was managed with plasma exchange. This case report is to make clinicians aware that TAMOF, severe HELLP, and other differential diagnosis in a postpartum case have a thin differentiating line and plasma exchange can be considered as one of the management options.

  9. Increased number of Tc17 and correlation with Th17 cells in patients with immune thrombocytopenia.

    Yu Hu

    Full Text Available BACKGROUND: IL-17-secreting CD8+ T cells (Tc17 subset have recently been defined as a subpopulation of effector T cells implicated in the pathogenesis of autoimmune diseases. The role of Tc17 and correlation with Th17 cells in the pathophysiology of immune thrombocytopenia (ITP remain unsettled. DESIGN AND METHODS: We studied 47 ITP patients (20 newly-diagnosed and 27 with complete response and 34 healthy controls. IL-17-producing CD3+CD8+ cells (Tc17 and IL-17-producing CD3+CD8- cells (Th17 were evaluated by flow cytometry and expressed as a percentage of the total number of CD3+ cells. Specific anti-platelet glycoprotein (GP GPIIb/IIIa and/or GPIb/IX autoantibodies were measured by modified monoclonal antibody specific immobilization of platelet antigens. Peripheral blood mononuclear cells of ITP patients were isolated, incubated in the presence of 0, 0.25, 0.5, or 1 µmol/L of dexamethasone for 72 h, and collected to detect Tc17 and Th17 cells by flow cytometric analysis. RESULTS: IL-17 was expressed on CD3+CD8- and CD3+CD8+ T cells. The percentages of Tc17 and Th17 cells in newly-diagnosed patients were significantly elevated compared to controls, and Tc17 was decreased after clinical treatment. The Th17∶Tc17 ratio was significantly lower in newly-diagnosed patients compared with controls, and was increased in patients who had complete response. There was a significantly positive correlation between Tc17 and Th17 cells in the control group, but not in the ITP patients. A positive correlation existed between Tc17 and the CD8∶CD4 ratio, as well as CD8+ cells in patients with ITP. The frequencies of Tc17 were marginally higher in autoantibody-negative patients than autoantibody-positive patients. Moreover, both Tc17 and Th17 cell percentages decreased as the concentration of dexamethasone in the culture media increased in ITP patients. CONCLUSIONS: Tc17 and the Th17 subset are involved in the immunopathology of ITP. Blocking the abnormally

  10. Treatment of patients with refractory immune thrombocytopenia: literature review and case report

    V. V. Ptushkin

    2014-07-01

    with severe bleeding. Patient received 1 mg/kg of romiplostim and a week later platelet count was 250  10 9/l. Successfully tumor resection was done. No romiplostim side effects or thrombotic complications during postoperative period were found. The obtained data together with similar case reports of successful surgery after TPO-agonists administration allow considering romiplostim as an effective method of thrombocytopenia therapy before surgery in ITP patients.

  11. Acute pancreatitis

    ... page: //medlineplus.gov/ency/article/000287.htm Acute pancreatitis To use the sharing features on this page, ... fatty foods after the attack has improved. Outlook (Prognosis) Most cases go away in a week. However, ...

  12. Acute Pericarditis

    ... Sugar Control Helps Fight Diabetic Eye Disease Are 'Workaholics' Prone to OCD, Anxiety? ALL NEWS > Resources First ... cancer, or heart surgery, the fluid is blood. Causes Acute pericarditis usually results from infection or other ...

  13. Acute dyspnea

    Radiodiagnosis is applied to determine the causes of acute dyspnea. Acute dyspnea is shown to aggravate the course of pulmonary diseases (bronchial asthma, obstructive bronchitis, pulmonary edema, throboembolism of pulmonary arteries etc) and cardiovascular diseases (desiseas of myocardium). The main tasks of radiodiagnosis are to determine volume and state of the lungs, localization and type of pulmonary injuries, to verify heart disease and to reveal concomitant complications

  14. Bronchitis (acute)

    Wark, Peter

    2008-01-01

    Acute bronchitis, with transient inflammation of the trachea and major bronchi, affects over 40/1000 adults a year in the UK. The causes are usually considered to be infective, but only around half of people have identifiable pathogens.The role of smoking or environmental tobacco smoke inhalation in predisposing to acute bronchitis is unclear.A third of people may have longer-term symptoms or recurrence.

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

    Baidya; Chakraborty; Ray; MR Pradhan

    2015-01-01

    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...

  16. Health-related quality of life in nonsplenectomized immune thrombocytopenia patients receiving romiplostim or medical standard of care.

    Kuter, David J; Mathias, Susan D; Rummel, Mathias; Mandanas, Romeo; Giagounidis, Aristoteles A; Wang, Xuena; Deuson, Robert R

    2012-05-01

    Immune thrombocytopenia (ITP) is an autoimmune disorder characterized by platelet destruction and insufficient platelet production. The resulting thrombocytopenia reduces patient health-related quality of life (HRQOL). In a randomized, open-label, 52-week study of non-splenectomized ITP patients treated with romiplostim or medical standard of care (SOC), patients completed the 10-scale ITP-patient assessment questionnaire (PAQ) at the start of the study and after 12, 24, 36, 48,and 52 weeks of treatment. HRQOL changes were examined for all patients in both treatment groups and by responder status, splenectomy status, and after the use of rituximab. Patients in both groups showed marked increases in all HRQOL scales over 52 weeks of treatment.These change scores exceeded the minimally important difference values (a measure of clinical relevance) for most of these scales,especially in responders to treatment. Compared with baseline,patients receiving romiplostim showed statistically significant improvements compared to SOC over 52 weeks for the ITP-PAQ scales of Symptoms, Bother, Activity, Psychological Health, Fear, Overall QOL,and Social QOL. Overall, treatment of ITP was associated with improvement in HRQOL. Patients receiving romiplostim had greater HRQOL improvements than those receiving SOC, but the magnitude ofthe difference is of uncertain clinical benefit. PMID:22460421

  17. Partial response to sorafenib treatment associated with transient grade 3 thrombocytopenia in a patient with locally advanced thyroid cancer

    Pitoia Fabian; Abelleira, Erika; Jerkovich, Fernando; Urciuoli, Carolina; Cross, Graciela, E-mail: fpitoia@intramed.net [Division de Endocrinologia, Hospital de Clinicas, Universidad de Buenos Aires Buenos Aires (Argentina)

    2015-08-15

    Advanced radioactive refractory and progressive or symptomatic differentiated thyroid carcinoma (DTC) is a rare condition. Sorafenib was recently approved for the treatment of these patients. We present the case of a 67 year old woman diagnosed with DTC who underwent a total thyroidectomy with central, lateral-compartment neck dissection and shaving of the trachea and esophagus due to tumor infiltration. A local recurrence was detected 14 months later requiring, additionally, two tracheal rings resection. The patient received a cumulative {sup 131}I dose of 650 mCi and developed dysphagia and dyspnea 63 months after initial surgery. A {sup 18}FGD-PET/CT showed progression of the local mass associated to hypermetabolic pulmonary nodules. Sorafenib 800 mg/day was then prescribed. A dose reduction to 400 mg/day was necessary due to grade 3 thrombocytopenia that appeared four months after drug prescription. Platelet count went to normal after this dose reduction. Five months after initiation of sorafenib, a partial response of the local mass with significant intra-tumoral necrosis was observed. We conclude that sorafenib is a valid option for locally advanced DTC and that the platelet count should be evaluated regularly because it seems that thrombocytopenia might be more frequently observed in DTC than in other types of tumors. (author)

  18. Trombocitopenia fetal/neonatal aloinmune: Revisión a propósito de un caso Foetal/neonatal alloimmune thrombocytopenia: A review and case report

    P. Rodríguez Wilhelmi

    2008-12-01

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

  19. False positivity of monospot test in an immunocompetent elderly woman with acute cytomegalovirus infection.

    Thamcharoen, Natanong; Sornprom, Suthanya; Permpalung, Nitipong; Hyman, Charles L

    2015-10-01

    A 75-year-old woman presented with altered mental status, septic picture, and influenza-like symptoms. Initial investigations revealed atypical lymphocytosis, thrombocytopenia, elevated liver enzymes, and a positive monospot test result. Further investigation showed the Epstein-Barr virus viral capsid antibody IgM/IgG and Epstein-Barr virus DNA by polymerase chain reaction to be negative; however, interestingly her cytomegalovirus (CMV) IgM and IgG were positive, suggesting that her mononucleosis-like syndrome was due to acute CMV infection. Herein, we report the first case of a heterophile-positive mononucleosis syndrome caused by acute CMV infection in an elderly immunocompetent woman. This case conveys that monospot test can yield false-positive result in the setting of acute CMV infection. PMID:26275628

  20. Controversies in the diagnosis and management of childhood acute immune thrombocytopenic purpura.

    Segel, George B; Feig, Stephen A

    2009-09-01

    Acute immune thrombocytopenic purpura (ITP) occurs most commonly in young children who present with severe isolated thrombocytopenia and purpura. A marrow examination is not required unless glucocorticoids are used, lest treatment mask incipient acute lymphoblastic leukemia, but controversy exists here. The recommendations for evaluation and management remain controversial, since prospective controlled trials have not been done. There is some consensus based on experience and empiric data. Almost all children with acute ITP will recover completely without therapy. Although the various treatments may increase the platelet count, they do not influence the outcome of the illness, may increase cost, and cause significant side effects. Therefore, careful observation may be the best management option for the patient with ITP, in the absence of severe bleeding. The data available relevant to these issues are discussed. PMID:19165890

  1. Acute myelogenous leukemia (AML) - children

    Acute myelogenous leukemia - children; AML; Acute myeloid leukemia - children; Acute granulocytic leukemia - children; Acute myeloblastic leukemia - children; Acute non-lymphocytic leukemia (ANLL) - children

  2. Heparin-induced anaphylactoid reaction associated with heparin-induced thrombocytopenia in the ED.

    Foreman, Juron S; Daniels, Lauren M; Stettner, Edward A

    2014-12-01

    Although rare, heparin-induced anaphylactic and anaphylactoid reactions have been previously described in the literature. We present a case of a patient who presented to the emergency department with dyspnea and was subsequently diagnosed with an acute pulmonary venous thromboembolism. Shortly after being started on intravenous unfractionated heparin, she developed sudden cardiovascular collapse leading to a cardiopulmonary arrest. She was successfully resuscitated and, after further diagnostic evaluation, was found to have developed a heparin-induced anaphylactoid reaction. PMID:25097093

  3. In vitro effects of mesenchymal stem cells on secreting function of T lymphocytes and CD4~+CD25~+T cells from patients with immune thrombo-cytopenia

    赵霞

    2014-01-01

    Objective To analyze in vitro the effect of mesenchymal stem cells(MSCs)on secreting cytokines by T lymphocytes and ratio of CD4+CD25+T cells from patients with immune thrombocytopenia(ITP).Methods Human bone marrow-derived MSCs were isolated by Ficoll Hypaque and cultured for proliferating to passage cells.Allogeneic T lymphocytes

  4. Helicobacter pylori infection influences the severity of thrombocytopenia and its treatment response in chronic hepatitis B patients with compensatory cirrhosis: A multicenter, observational study.

    Zhang, Xiao-Hui; He, Yun; Feng, Ru; Xu, Lan-Ping; Jiang, Qian; Jiang, Hao; Lu, Jin; Fu, Hai-Xia; Liu, Hui; Wang, Jing-Wen; Wang, Qian-Ming; Feng, Fei-Er; Zhu, Xiao-Lu; Xu, Lin-Lin; Xie, Yang-Di; Ma, Hui; Wang, Hao; Liu, Kai-Yan; Huang, Xiao-Jun

    2016-05-01

    The role of Helicobacter pylori (H. pylori) infection on thrombocytopenia in chronic hepatitis B (CHB) related compensatory cirrhotic patients is unknown. We conducted an observational study to determine whether H. pylori plays a role in these patients. A total of 255 patients from three centers in China were enrolled in the study. All patients received nucleoside analogs (NA) therapy and were screened for H. pylori infection. Patients were divided into three groups based on their H. pylori infection status and the therapy administered: patients without H. pylori infection who received NA therapy alone (N = 146); patients with H. pylori infection who received NA therapy alone (n = 48); and patients with H. pylori infection who received H. pylori eradication combined with NA therapy (N = 61). We observed that in CHB compensatory cirrhotic patients with H. pylori infection, the platelets count was significantly lower relative to uninfected patients (31 versus 60 × 10(9)/L, p pylori co-infected patients who received the NA and H. pylori eradication treatment compared to the other two groups (p pylori infection and eradication treatment combined with NA were independent risk factors associated with platelets response during treatment of thrombocytopenia in CHB compensatory cirrhosis (p pylori infection may associate with thrombocytopenia in CHB compensatory cirrhosis. H. pylori eradication combined with NA treatment may prove to be beneficial to CHB compensatory cirrhotic patients with thrombocytopenia who are infected with H. pylori. PMID:26338255

  5. Recent Research Progress of Pregnancy with Thrombocytopenia%妊娠合并血小板减少的研究新进展

    肖慧英

    2013-01-01

    Pregnancy with thrombocytopenia is a common disease during perinatal period, the incidence of which is about 10% . The platelet count in pregnancy less than 100 × 109/L by 2 checks( excluding the coagulation dysfunction ) is the diagnosis of thrombocytopenia. It can be caused by a variety of reasons,such as pregnancy associated thrombocytopenia, idiopathic thrombocytopenic purpura, hypertensive disorders in pregnancy, aplastic anemia, hypersplenism , and systemic lupus erythematosus. Pregnant women with thrombocytopenia should be given strict prenatal care. The focus of treatment is to actively prevent bleeding due to thrombocytopenia, and strive to give appropriate treatment, and active treatment to the comorbidities and complications during the prenatal stage.%妊娠合并血小板减少(PT)是围生期一种常见疾病,其发病率约为10%.孕期2次检测血小板计数<100×109/L(排除有凝血功能障碍者)即诊断为血小板减少.它可由多种原因引起,如妊娠相关性血小板减少、特发性血小板减少性紫癜、妊娠期高血压疾病、再生障碍性贫血、脾功能亢进、系统性红斑狼疮等.PT患者在孕期应进行严格的产前检查.处理的重点是积极预防由于血小板减少所致的出血,争取在产前给予相应的治疗,积极治疗合并症和并发症.

  6. Acute gingival bleeding as a complication of dengue hemorrhagic fever

    Saif Khan

    2013-01-01

    Full Text Available Dengue fever is mosquito borne disease caused by dengue virus (DENV of Flaviviridae family. The clinical manifestations range from fever to severe hemorrhage, shock and death. Here, we report a case of 20-year-old male patient undergoing orthodontic treatment presenting with acute gingival bleeding with a history of fever, weakness, backache, retro orbital pain and ecchymosis over his right arm. The hematological investigations revealed anemia, thrombocytopenia and positive dengue non-structural protein-1 antigen and also positive immunoglobulin M and immunoglobulin G antibodies for DENV. Patient was diagnosed as a case of dengue hemorrhagic fever and was immediately referred for appropriate management. This case report emphasizes the importance of taking correct and thorough medical history.

  7. Acute gingival bleeding as a complication of dengue hemorrhagic fever.

    Khan, Saif; Gupta, N D; Maheshwari, Sandhya

    2013-07-01

    Dengue fever is mosquito borne disease caused by dengue virus (DENV) of Flaviviridae family. The clinical manifestations range from fever to severe hemorrhage, shock and death. Here, we report a case of 20-year-old male patient undergoing orthodontic treatment presenting with acute gingival bleeding with a history of fever, weakness, backache, retro orbital pain and ecchymosis over his right arm. The hematological investigations revealed anemia, thrombocytopenia and positive dengue non-structural protein-1 antigen and also positive immunoglobulin M and immunoglobulin G antibodies for DENV. Patient was diagnosed as a case of dengue hemorrhagic fever and was immediately referred for appropriate management. This case report emphasizes the importance of taking correct and thorough medical history. PMID:24174736

  8. UNUSUAL CLINICAL CASES THAT MIMIC ACUTE DISSEMINATED ENCEPHALOMYELITIS.

    Duman, Özgür; Yürekli, Vedat Ali; Gencpinar, Pinar; Karaali, Kamil; Gümüş, Hakan; Okuyaz, Çetin; Hazar, Volkan; Haspolat, Şenay

    2015-09-01

    Acute disseminated encephalomyelitis (ADEM) is an immune-mediated monophasic inflammatory demyelinating disorder of the central nervous system which poses a diagnostic challenge. We report on six cases of different etiologies that mimicked the clinical and radiologic findings of ADEM. The cases were collected from four different reference hospitals in Turkey. The same radiologist from the Akdeniz University Faculty of Medicine examined the magnetic resonance images of all patients. Three (50%) patients had antecedent infections. Initial symptoms of the patients were as follows: fever in 50%, altered consciousness in 33.3% and convulsions in 16.7% of patients. Neurologic examination showed long tract signs in 83.3%, ataxia in 50% and altered consciousness in 50% of patients. Cerebrospinal fluid examination revealed lymphocytic pleocytosis only in case 6. Four patients received steroid pulse therapy and one of these initially underwent intravenous immunoglobulin therapy. The patients' definitive diagnoses were as follows: paraspinal neuroblastoma-associated paraneoplastic syndrome; histiocytic sarcoma; mitochondrial myopathy, encephalopathy, lactic acidosis and stroke-like episodes; and cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy in one patient each, while two patients had hemophagocytic syndrome. The present case series demonstrated difficulties in diagnosing ADEM while revealing extremely rare disorders that mimic ADEM radiologically and clinically. PMID:26666111

  9. Coronary artery bypass grafting (CABG) in patients with immune thrombocytopenia (ITP): a community hospital experience and review of the literature.

    Jubelirer, Steven J; Mousa, Luay; Reddy, Usha; Mir, Mohsin; Welch, Christine A

    2011-01-01

    We reviewed the records of 51 patients with Immune Thrombocytopenia (ITP) who underwent Coronary Artery Bypass Grafting (CABG) at Charleston Area Medical Center between June 1992 and September 2005. There were 41 males and 10 females with a median age of 68 years (range 49-87). Four patients had a previous splenectomy, one of whom had it performed concomitantly with the CABG. Three patients were on chronic corticosteroids on admission. The median pump time was 114 minutes (range: 42-244 minutes). The median cross-clamp time was 62 minutes (range 22-192 minutes). The median total chest tube drainage postoperatively was 1,346 cc (range: 265-9875cc). The mean preoperative and 24 hour postoperative platelet count was 126,000 (range 58,000-323,000) and 99,000/mm3 (range: 27,000-194,000), respectively. Twenty-one (40%) patients received platelet transfusions. Platelets were given intraoperatively or postoperatively in all but two of those patients. The median number of units of platelets given was 10 (range: 6-52). Twenty-seven (53%) received packed red cells intraoperatively or postoperatively. The median number of red cells given was 2 (range: 1-34). Other hemostatic agents given intraoperatively/ postoperatively included aprotinin (8 patients), aminocaproic acid (10 patients), DDAVP (5 patients), and intravenous gammaglobulin (IgG) in 3 patients. Thirteen patients were given corticosteroids preoperatively with little improvement in platelet count. CABG may be successfully performed in ITP patients with moderate thrombocytopenia (> or = 50,000/mm3) using conventional therapies (e.g., transfusions, IV IgG, hematinics) without the need for preoperative splenectomy or prolongation of hospital stay. However, a prospective study on the ideal management of ITP patients undergoing CABG would be beneficial. PMID:22235705

  10. Experimental and Natural Infections of Goats with Severe Fever with Thrombocytopenia Syndrome Virus: Evidence for Ticks as Viral Vector.

    Yongjun Jiao

    Full Text Available Severe fever with thrombocytopenia syndrome virus (SFTSV, the causative agent for the fatal life-threatening infectious disease, severe fever with thrombocytopenia syndrome (SFTS, was first identified in the central and eastern regions of China. Although the viral RNA was detected in free-living and parasitic ticks, the vector for SFTSV remains unsettled.Firstly, an experimental infection study in goats was conducted in a bio-safety level-2 (BSL-2 facility to investigate virus transmission between animals. The results showed that infected animals did not shed virus to the outside through respiratory or digestive tract route, and the control animals did not get infected. Then, a natural infection study was carried out in the SFTSV endemic region. A cohort of naïve goats was used as sentinel animals in the study site. A variety of daily samples including goat sera, ticks and mosquitoes were collected for viral RNA and antibody (from serum only detection, and virus isolation. We detected viral RNA from free-living and parasitic ticks rather than mosquitoes, and from goats after ticks' infestation. We also observed sero-conversion in all members of the animal cohort subsequently. The S segment sequences of the two recovered viral isolates from one infected goat and its parasitic ticks showed a 100% homology at the nucleic acid level.In our natural infection study, close contact between goats does not appear to transmit SFTSV, however, the naïve animals were infected after ticks' infestation and two viral isolates derived from an infected goat and its parasitic ticks shared 100% of sequence identity. These data demonstrate that the etiologic agent for goat cohort's natural infection comes from environmental factors. Of these, ticks, especially the predominant species Haemaphysalis longicornis, probably act as vector for this pathogen. The findings in this study may help local health authorities formulate and focus preventive measures to contain

  11. Acute pancreatitis

    Al Mofleh Ibrahim

    1997-01-01

    Full Text Available The past few years have witnessed a tremendous progress in our knowledge regarding the pathogenesis, diagnosis, prognostic evaluation and classification of acute pancreatitis. The role of ischemia, lysosomal enzymes, oxygen free radicals, polymorphnuclear cells-byproducts and inflammatory mediators in the pathogenesis of pancreatic necrosis and multiple organ failure has been emphasized. Furthermore, the recent knowledge about agents infecting pancreatic necrosis, routes of infection, bacteriological examination of fine needle aspirate and appropriate antibiotics have changed the concept of acute pancreatitis. New diagnostic tests such as rapid urinary trypsinogen-2 test and inflammatory mediators including polymorphnuclear elastase, C-reactive protein and interleukin-6 contribute to early diagnosis, prognostic evaluation and initiation of an appropriate therapy.

  12. [The condition of endothelium and hemostasis in patients with primary diagnosed acute lymphoblast leucosis].

    Vladimorova, S G; Skol'skaia, O Iu; Tarasova, L N; Dokshina, I A

    2012-08-01

    The evaluation of state of endothelium and plasma hemostasis, thrombocytopenia degree, rate of thrombo-hemorrhagic complications in adult patients with acute lymphoblastic leucosis in the period of disease manifestation was made. The thrombosis developed in 1 out of 24 (4.2%) examined patients, hemorrhagic syndrome in 11 out of 24 (45.8%) examined patients. The last case is closely linked with severity of thrombocytopenia occurred in patients with number of thrombocytes less than 50 x 109/l. At the same time, high correlation between number of leukemic cells and level of B-dimers (rs = 0.703) testifies that the leucosis process activates intravascular thrombus formation. The higher content of B-dimers in 100% of patients validates this assumption. The high levels of soluble thrombo-modulin and von Willebrand factor indicate the loss of thromboresistance by vessel endothelium and the activation of prothrombin mechanisms. The statistically valid coefficients of correlation between concentrations of thrombomodulin and D-dimers (rs = 0.598) and the level of von Willebrand factor and severity of hemorrhagic syndrome prove that disorders of blood coagulation under acute lymphoblast leucosis occur with active involvement of endothelium. PMID:23097989

  13. Lassa fever presenting as acute abdomen: a case series.

    Dongo, Andrew E; Kesieme, Emeka B; Iyamu, Christopher E; Okokhere, Peter O; Akhuemokhan, Odigie C; Akpede, George O

    2013-01-01

    Lassa fever, an endemic zoonotic viral infection in West Africa, presents with varied symptoms including fever, vomiting, retrosternal pain, abdominal pain, sore-throat, mucosal bleeding, seizures and coma. When fever and abdominal pain are the main presenting symptoms, and a diagnosis of acute abdomen is entertained, Lassa fever is rarely considered in the differential diagnosis, even in endemic areas. Rather the diagnosis of Lassa fever is suspected only after surgical intervention. Therefore, such patients often undergo unnecessary surgery with resultant delay in the commencement of ribavirin therapy. This increases morbidity and mortality and the risk of nosocomial transmission to hospital staff. We report 7 patients aged between 17 months and 40 years who had operative intervention for suspected appendicitis, perforated typhoid ileitis, intussuception and ruptured ectopic pregnancy after routine investigations. All seven were post-operatively confirmed as Lassa fever cases. Four patients died postoperatively, most before commencement of ribavirin, while the other three patients eventually recovered with appropriate antibiotic treatment including intravenous ribavirin. Surgeons working in West Africa should include Lassa fever in the differential diagnosis of acute abdomen, especially appendicitis. The presence of high grade fever, proteinuria and thrombocytopenia in patients with acute abdomen should heighten the suspicion of Lassa fever. Prolonged intra-operative bleeding should not only raise suspicion of the disease but also serve to initiate precautions to prevent nosocomial transmission. PMID:23597024

  14. Lassa fever presenting as acute abdomen: a case series

    2013-01-01

    Lassa fever, an endemic zoonotic viral infection in West Africa, presents with varied symptoms including fever, vomiting, retrosternal pain, abdominal pain, sore-throat, mucosal bleeding, seizures and coma. When fever and abdominal pain are the main presenting symptoms, and a diagnosis of acute abdomen is entertained, Lassa fever is rarely considered in the differential diagnosis, even in endemic areas. Rather the diagnosis of Lassa fever is suspected only after surgical intervention. Therefore, such patients often undergo unnecessary surgery with resultant delay in the commencement of ribavirin therapy. This increases morbidity and mortality and the risk of nosocomial transmission to hospital staff. We report 7 patients aged between 17 months and 40 years who had operative intervention for suspected appendicitis, perforated typhoid ileitis, intussuception and ruptured ectopic pregnancy after routine investigations. All seven were post-operatively confirmed as Lassa fever cases. Four patients died postoperatively, most before commencement of ribavirin, while the other three patients eventually recovered with appropriate antibiotic treatment including intravenous ribavirin. Surgeons working in West Africa should include Lassa fever in the differential diagnosis of acute abdomen, especially appendicitis. The presence of high grade fever, proteinuria and thrombocytopenia in patients with acute abdomen should heighten the suspicion of Lassa fever. Prolonged intra-operative bleeding should not only raise suspicion of the disease but also serve to initiate precautions to prevent nosocomial transmission. PMID:23597024

  15. Paroxysmal nocturnal hemoglobinuria: rare cause of acute renal failure

    Vilma Takayasu

    2012-12-01

    Full Text Available Paroxysmal nocturnal hemoglobinuria is a rare acquired disease, characterized by hemolytic anemia, recurrent infections, cytopenias, and vascular thrombosis. It occurs by non-malignant clonal expansion of one or more hematopoietic stem cells that acquired somatic mutations in PIG-A gene linked to chromosome X. This mutation results in lower erythrocyte expression of CD55 and CD59 surface proteins and consequently increased susceptibility to the complement system. The renal involvement is generally benign, resulting in mild impairment in urinary concentration. Acute renal failure requiring hemodialytic support accompanying PNH is rarely observed. The authors report a case of a 37-year-old male who presented with bicytopenia (hemolytic anemia and thrombocytopenia associated with acute renal failure requiring dialysis. Diagnosis was challenging because of the rarity and unfamiliarity with this entity, but was confirmed by flow cytometry. In the course of the disease, acute pyelonephritis with multiple renal abscesses was diagnosed requiring prolonged antibiotic therapy. Patient outcome was favorable after the control of hemolysis and the infection treatment.

  16. A case of thrombotic thrombocytopenic purpura induced by acute pancreatitis

    Arimoto M

    2012-03-01

    Full Text Available Miyoko Arimoto1, Yutaka Komiyama2, Fumiko Okamae1, Akemi Ichibe1, Setsuko Teranishi1, Hirohiko Tokunaga1, Keiko Nakaya3, Michie Fujiwara3, Manabu Yamaoka4, Shuji Onishi4, Rie Miyamoto5, Naoto Nakamichi5, Shosaku Nomura51Blood Transfusion Unit, Kansai Medical University Takii Hospital, 2Department of Clinical Sciences and Laboratory Medicine, Kansai Medical University, 3Clinical Medical Technology Unit, Kansai Medical University Takii Hospital, 4Blood Transfusion Unit, Kansai Medical University Hirakata Hospital, 5First Department of Internal Medicine, Kansai Medical University, Moriguchi, JapanAbstract: Thrombotic thrombocytopenic purpura (TTP is a multisystemic microvascular disorder that may be caused by an imbalance between unusually large von Willebrand factor multimers and the cleaving protease ADAMTS13. In acquired TTP, especially in secondary TTP with various underlying diseases, the diagnosis is difficult because there are many cases that do not exhibit severe deficiency of ADAMTS13 or raised levels of ADAMST13 inhibitors. It is well known that collagen disease, malignancy, and hematopoietic stem cell transplantation can be underlying conditions that induce TTP. However, TTP induced by acute pancreatitis, as experienced by our patient, has rarely been reported. Our patient completely recovered with treatments using steroids and plasma exchange (PE only. In cases where patients develop acute pancreatitis with no apparent causes for hemolytic anemia and thrombocytopenia, the possibility of TTP should be considered. Treatments for TTP including PE should be evaluated as soon as a diagnosis is made.Keywords: thrombotic thrombocytopenic purpura, ADAMTS13, acute pancreatitis, plasma exchange

  17. Trombocitopenia induzida por heparina e necrose cutânea por varfarina: relato de caso Heparin-induced thrombocytopenia and warfarin-induced skin necrosis: case report

    Flávia Larissa Kaiber

    2010-12-01

    Full Text Available É relatado um caso de trombocitopenia induzida por heparina complicada, com necrose cutânea induzida por varfarina em paciente de 74 anos, sexo feminino, internada com diagnóstico de fratura do colo do fêmur, trombose venosa profunda e tromboembolismo pulmonar. A necrose cutânea induzida por varfarina é uma complicação rara da terapia anticoagulante, com alta morbidade e mortalidade, que pode estar associada à trombocitopenia induzida por heparina.This paper describes a case of heparin-induced thrombocytopenia complicated by warfarin-induced skin necrosis in a 74-year old female patient hospitalized with diagnoses of a hip fracture, deep vein thrombosis and pulmonary thromboembolism. Warfarin-induced skin necrosis is a rare complication of anticoagulant therapy, with high morbidity and mortality that may be associated with heparin-induced thrombocytopenia.

  18. Autosomal Recessive Chronic Granulomatous Disease, IgA Deficiency and Refractory Autoimmune Thrombocytopenia Responding to Anti-CD20 Monoclonal Antibody

    Shahin Shamsian Bibi

    2008-09-01

    Full Text Available Immunodeficiency and autoimmune disease may occur concomitantly in the same individual. Some of the immunodeficiency syndromes, especially humoral defects are associated with autoimmune disorders. Hematological manifestations such as thrombocytopenia and hemolytic anemia are the most common presentations. Persistent antigen stimulation due to an inherent defect in the ability of the immune system to eradicate pathogens is the primary cause leading to autoimmunity in patients with primary immunodeficiency states.We describe a 10 year old Iranian girl with chronic granulomatous disease -the autosomal recessive type with mutation of NCF1 gene P47- associated with selective IgA deficiency, refractory immune thrombocytopenia that showed an excellent response to Rituximab (Anti-CD20 monoclonal antibody.Patients with primary immunodeficiencies may have variable autoimmune manifestations. So for early detection and appropriate treatment, autoimmune diseases should always be suspected in such patients.

  19. Rates of clinically apparent heparin-induced thrombocytopenia for unfractionated heparin vs. low molecular weight heparin in non-surgical patients are low and similar

    Gerber Jonathan

    2005-04-01

    Full Text Available Abstract With the growing use of low-molecular-weight heparins (LMWH for the treatment and prevention of venous thromboembolism (VTE, it is important to provide an evidence-based comparison with unfractionated heparin (UFH concerning rates of heparin-induced thrombocytopenia (HIT. Such comparisons are essential in clinical decision-making and cost-modeling. In this paper we review data regarding non-surgical (medical patients. We conclude that the lack of uniform evaluation and standardized testing for HIT in the current literature precludes making a reliable estimate of the relative risk of HIT in UFH vs. LMWH in either the treatment or prevention of VTE in non-surgical patients. However, current data suggest that the risk of thrombocytopenia and HIT is low and similar for non-surgical patients who receive either LMWH or UFH.

  20. Acute abdomen

    Acute abdomen may be connected with the injury of one of the internal organs, injury of large blood vessels, with the spreading of pains from some other area. It may also be a manifestation of systemic disease or poisoning. The main purposes of radiodiagnosis are: determination of the cause of clinical syndrome; determination of the localization and spreading of pathological changes in abdominal organs; finding out the character of complications. If the data of the ordinary roentgenological investiagtion and isn't complete, the computer tomography of abdominal and pelvic cavities is needed

  1. Efficacy of T-705 (Favipiravir) in the Treatment of Infections with Lethal Severe Fever with Thrombocytopenia Syndrome Virus

    Tani, Hideki; Fukuma, Aiko; Fukushi, Shuetsu; Taniguchi, Satoshi; Yoshikawa, Tomoki; Iwata-Yoshikawa, Naoko; Sato, Yuko; Suzuki, Tadaki; Nagata, Noriyo; Hasegawa, Hideki; Kawai, Yasuhiro; Uda, Akihiko; Morikawa, Shigeru; Shimojima, Masayuki; Watanabe, Haruo

    2016-01-01

    ABSTRACT Severe fever with thrombocytopenia syndrome virus (SFTSV) is the causative agent of SFTS, an emerging hemorrhagic fever. This disease has a high case fatality rate and is endemic to China, South Korea, and Japan. Because there are currently no effective therapeutics for SFTS, potent and safe antivirals are needed for the treatment of SFTS. The inhibitory effect of T-705 (favipiravir) on the replication of SFTSV in Vero cells was evaluated. Mice lacking the type I interferon receptor (IFNAR−/−) were used as an in vivo lethal model for SFTSV infection. T-705, which has been licensed as an anti-influenza drug in Japan, inhibits SFTSV replication both in vitro and in vivo. T-705 inhibited replication of SFTSV in Vero cells by 5 log units, with a 50% inhibitory concentration (IC50) and IC90 of 6.0 µM and 22 µM, respectively. Intraperitoneal or oral administration of T-705 for 5 days to IFNAR−/− mice infected with lethal SFTSV significantly improved survival rates (100% survival) without causing body weight loss and reduced the viral load in the serum. Ribavirin also inhibited SFTSV replication. However, it was less effective than T-705 both in vitro and in vivo. A time-of-drug-addition study revealed that therapeutic T-705 treatment of SFTSV infection in IFNAR−/− mice was effective. These results suggest that T-705 is a promising candidate for the treatment of SFTS. IMPORTANCE Severe fever with thrombocytopenia syndrome (SFTS), caused by SFTS virus (SFTSV), is a recently identified emerging viral infectious disease. Despite the medical importance of this disease, there are currently neither vaccines nor effective therapeutics for SFTS. T-705, which is a pyrazine derivative, has shown broad antiviral activity against various RNA viruses. The present study demonstrated, for the first time to our knowledge, the efficacy of T-705 in treating SFTSV infection in a mouse lethal model. T-705 showed a high efficacy in the treatment of SFTSV infection in

  2. The mouse mutation “thrombocytopenia and cardiomyopathy” (trac) disrupts Abcg5: a spontaneous single gene model for human hereditary phytosterolemia/sitosterolemia

    Chase, Thomas H.; Bonnie L Lyons; Bronson, Roderick T.; Foreman, Oded; Donahue, Leah Rae; Lisa M Burzenski; Gott, Bruce; Lane, Priscilla; Harris, Belinda; Ceglarek, Uta; Thiery, Joachim; Wittenburg, Henning; Thon, Jonathan N.; Italiano, Joseph E.; Johnson, Kenneth R.

    2010-01-01

    The spontaneous mouse mutation “thrombocytopenia and cardiomyopathy” (trac) causes macrothrombocytopenia, prolonged bleeding times, anemia, leukopenia, infertility, cardiomyopathy, and shortened life span. Homozygotes show a 20-fold decrease in platelet numbers and a 3-fold increase in platelet size with structural alterations and functional impairments in activation and aggregation. Megakaryocytes in trac/trac mice are present in increased numbers, have poorly developed demarcation membrane ...

  3. Thymic retention of CD4+CD25+FoxP3+ T regulatory cells is associated with their peripheral deficiency and thrombocytopenia in a murine model of immune thrombocytopenia.

    Aslam, Rukhsana; Hu, Yu; Gebremeskel, Simon; Segel, George B; Speck, Edwin R; Guo, Li; Kim, Michael; Ni, Heyu; Freedman, John; Semple, John W

    2012-09-01

    Immune thrombocytopenia (ITP) is a bleeding disorder in which antibodies and/or T cells lead to enhanced peripheral platelet destruction and reduced bone marrow platelet production. Several reports have observed that ITP is associated with a peripheral deficiency of tolerance-inducing CD4+CD25+FoxP3+ T regulatory cells (Tregs). Using a murine model of ITP, we analyzed Tregs in the spleen and thymus. CD61 knockout mice were immunized against wild-type (CD61+) platelets, and their splenocytes were transferred into severe combined immunodeficient (SCID) mice. Compared with SCID mice receiving naive splenocytes, within 2 weeks after transfer, the ITP SCID mice became thrombocytopenic (< 200 × 10(9) platelets/L) and had increased serum anti-CD61 antibodies. The quantity of thymic Tregs by 2 weeks after transfer was significantly elevated, whereas Tregs in the spleens were significantly reduced. Treatment of the ITP mice with 2 g/kg intravenous immunoglobulin raised the platelet counts, reduced antibody production, and normalized the thymic and splenic Treg populations. Compared with thymocytes from ITP mice treated with intravenous immunoglobulin, thymocytes from untreated ITP mice delayed the onset of ITP when administered before engraftment with immune splenocytes. These results suggest that ITP in mice is associated with a peripheral Treg deficiency because of thymic retention and therapy normalizes the Tregs. PMID:22760780

  4. [Acute myocarditis].

    Combes, Alain

    2013-05-01

    Myocarditis is defined as inflammation of the myocardium accompanied by myocellular necrosis. Acute myocarditis must be considered in patients who present with recent onset of cardiac failure or arrhythmia. Fulminant myocarditis is a distinct entity characterized by sudden onset of severe congestive heart failure or cardiogenic shock, usually following a flu-like illness, parvovirus B19, human herpesvirus 6, coxsackievirus and adenovirus being the most frequently viruses responsible for the disease. Treatment of myocarditis remains largely supportive, since immunosuppression has not been proven to be beneficial for acute lymphocytic myocarditis. Trials of antiviral therapies, or immunostimulants such as interferons, suggest a potential therapeutic role but require further investigation. Lastly, early recognition of patients rapidly progressing to refractory cardiac failure and their immediate transfer to a medical-surgical center experienced in mechanical circulatory support is warranted. In this setting, ECMO should be the first-line mechanical assistance. For highly unstable patients, a Mobile Cardiac Assistance Unit, that rapidly travels to primary care hospitals with a portable ECMO system and hooks it up before refractory multiorgan failure takes hold, is the preferred option. PMID:23789482

  5. SNP array and phenotype correlation shows that FLI1 deletion per se is not responsible for thrombocytopenia development in Jacobsen syndrome.

    Trkova, Marie; Becvarova, Vera; Hynek, Martin; Hnykova, Lenka; Hlavova, Eva; Kreckova, Gabriela; Kulovany, Eduard; Cutka, David; Zatloukalova, Jitka; Markova, Kristyna; Sukova, Martina; Horacek, Jiri; Stejskal, David

    2012-10-01

    Jacobsen syndrome (JBS) is a rare chromosomal disorder caused by terminal deletion of the long arm of chromosome 11. We report on four prenatally diagnosed patients with JBS with variable prenatal and postnatal phenotypes and 11q deletions of varying sizes. Precise characterization of the deleted region in three patients was performed by SNP arrays. The severity of both the prenatal and postnatal phenotypes did not correlate with the size of the haploinsufficient region. Despite the large difference in the deletion size (nearly 6 Mb), both of the live-born patients had similar phenotypes corresponding to JBS. However, one of the most prominent features of JBS, thrombocytopenia, was only present in the live-born boy. The girl, who had a significantly longer deletion spanning all four genes suspected of being causative of JBS-related thrombocytopenia (FLI1, ETS1, NFRKB, and JAM3), did not manifest a platelet phenotype. Therefore, our findings do not support the traditional view of deletion size correlation in JBS or the causative role of FLI1, ETS1, NFRKB, and JAM3 deletion per se for the development of disease-related thrombocytopenia. PMID:22887642

  6. Acute neuromuscular weakness associated with dengue infection

    Harmanjit Singh Hira

    2012-01-01

    Full Text Available Background: Dengue infections may present with neurological complications. Whether these are due to neuromuscular disease or electrolyte imbalance is unclear. Materials and Methods: Eighty-eight patients of dengue fever required hospitalization during epidemic in year 2010. Twelve of them presented with acute neuromuscular weakness. We enrolled them for study. Diagnosis of dengue infection based on clinical profile of patients, positive serum IgM ELISA, NS1 antigen, and sero-typing. Complete hemogram, kidney and liver functions, serum electrolytes, and creatine phosphokinase (CPK were tested. In addition, two patients underwent nerve conduction velocity (NCV test and electromyography. Results: Twelve patients were included in the present study. Their age was between 18 and 34 years. Fever, myalgia, and motor weakness of limbs were most common presenting symptoms. Motor weakness developed on 2 nd to 4 th day of illness in 11 of 12 patients. In one patient, it developed on 10 th day of illness. Ten of 12 showed hypokalemia. One was of Guillain-Barré syndrome and other suffered from myositis; they underwent NCV and electromyography. Serum CPK and SGOT raised in 8 out of 12 patients. CPK of patient of myositis was 5098 IU. All of 12 patients had thrombocytopenia. WBC was in normal range. Dengue virus was isolated in three patients, and it was of serotype 1. CSF was normal in all. Within 24 hours, those with hypokalemia recovered by potassium correction. Conclusions: It was concluded that the dengue virus infection led to acute neuromuscular weakness because of hypokalemia, myositis, and Guillain-Barré syndrome. It was suggested to look for presence of hypokalemia in such patients.

  7. RECURRENT SEASONAL ACUTE PSYCHOSIS

    Agarwal, Vivek

    1999-01-01

    Acute psychoses have been reported to occur more frequently in summer. This is a report of seasonal recurrence of acute psychosis in a patient. This case report emphasizes towards the biological etiology of acute psychoses.

  8. Acute cerebellar ataxia

    Cerebellar ataxia; Ataxia - acute cerebellar; Cerebellitis; Post-varicella acute cerebellar ataxia; PVACA ... Acute cerebellar ataxia in children, especially younger than age 3, may occur several weeks after an illness caused by a virus. ...

  9. Autoimmune autonomic ganglionopathy in a pediatric patient presenting with acute encephalitis.

    Kuki, Ichiro; Kawawaki, Hisashi; Okazaki, Shin; Hattori, Yuka; Horino, Asako; Higuchi, Osamu; Nakane, Shunya

    2016-06-01

    Autoimmune autonomic ganglionopathy (AAG) is an acquired immune-mediated disorder that leads to systemic autonomic failure. Autoantibodies to the ganglionic nicotinic acetylcholine receptor (gAChR) are detected in 50% of AAG patients. We report the first pediatric case of AAG presenting with acute encephalitis. The patient was a 13-year-old boy who presented with orthostatic hypotension, followed by rapidly progressing disturbance of consciousness. Cerebrospinal fluid analysis revealed significant pleocytosis and increased neopterin concentration. Head MRI showed hyperintensities in bilateral caudate nuclei, putamen, hippocampus, and insula cortex. Severe autonomic dysfunctions such as severe orthostatic hypotension, bradycardia, dysuria, prolonged constipation and vomiting appeared. These symptoms were successfully controlled by repeated immunomodulating therapy with intravenous methylprednisolone pulse therapy and intravenous immunoglobulin. Autoantibodies to the α3 subunit of gAChR were detected at neurological onset, but were undetectable five months later. This observation indicates that AAG should be suspected in patients manifesting acute encephalitis characterized by preceding and prolonged autonomic symptoms, and immunomodulating therapy from an early stage can be effective. PMID:26740077

  10. Diversity and severity of adverse reactions to quinine: A systematic review.

    Liles, Nathan W; Page, Evaren E; Liles, Amber L; Vesely, Sara K; Raskob, Gary E; George, James N

    2016-05-01

    Quinine is a common cause of drug-induced thrombocytopenia and the most common cause of drug-induced thrombotic microangiopathy. Other quinine-induced systemic disorders have been described. To understand the complete clinical spectrum of adverse reactions to quinine we searched 11 databases for articles that provided sufficient data to allow evaluation of levels of evidence supporting a causal association with quinine. Three reviewers independently determined the levels of evidence, including both immune-mediated and toxic adverse reactions. The principal focus of this review was on acute, immune-mediated reactions. The source of quinine exposure, the involved organ systems, the severity of the adverse reactions, and patient outcomes were documented. One hundred-fourteen articles described 142 patients with definite or probable evidence for a causal association of quinine with acute, immune-mediated reactions. These reactions included chills, fever, hypotension, painful acral cyanosis, disseminated intravascular coagulation, hemolytic anemia, thrombocytopenia, neutropenia, acute kidney injury, rhabdomyolysis, liver toxicity, cardiac ischemia, respiratory failure, hypoglycemia, blindness, and toxic epidermal necrolysis. One hundred-two (72%) reactions were caused by quinine pills; 28 (20%) by quinine-containing beverages; 12 (8%) by five other types of exposures. Excluding 41 patients who had only dermatologic reactions, 92 (91%) of 101 patients had required hospitalization for severe illness; 30 required renal replacement therapy; three died. Quinine, even with only minute exposure from common beverages, can cause severe adverse reactions involving multiple organ systems. In patients with acute, multi-system disorders of unknown origin, an adverse reaction to quinine should be considered. PMID:26822544

  11. Antigenic Complementarity in the Origins of Autoimmunity: A General Theory Illustrated With a Case Study of Idiopathic Thrombocytopenia Purpura

    Jacob Couturier

    2006-01-01

    Full Text Available We describe a novel, testable theory of autoimmunity, outline novel predictions made by the theory, and illustrate its application to unravelling the possible causes of idiopathic thrombocytopenia purpura (ITP. Pairs of stereochemically complementary antigens induce complementary immune responses (antibody or T-cell that create loss of regulation and civil war within the immune system itself. Antibodies attack antibodies creating circulating immune complexes; T-cells attack T-cells creating perivascular cuffing. This immunological civil war abrogates the self-nonself distinction. If at least one of the complementary antigens mimics a self antigen, then this unregulated immune response will target host tissues as well. Data demonstrating that complementary antigens are found in some animal models of autoimmunity and may be present in various human diseases, especially ITP, are reviewed. Specific mechanisms for preventing autoimmunity or suppressing existing autoimmunity are derived from the theory, and critical tests proposed. Finally, we argue that Koch's postulates are inadequate for establishing disease causation for multiple-antigen diseases and discuss the possibility that current research has failed to elucidate the causes of human autoimmune diseases because we are using the wrong criteria.

  12. Budd-Chiari syndrome and heparin-induced thrombocytopenia in polycythemia vera: Successful treatment with repeated TIPS and interferon alpha

    Akoum Riad

    2009-01-01

    Full Text Available Polycythemia vera (PV is a common cause of Budd-Chiari syndrome (BCS and portal vein thrombosis (PVT. The postpartum period is a precipitating cofactor. An additional heparin-induced thrombocytopenia/thrombosis (HIT/T leads to a life-threatening condition in which transjugular intrahepatic portosystemic shunting (TIPS seems to be the only life-saving procedure. We describe the case of a subacute BCS and PVT in the late postpartum period. The diagnosis was established using CT scan, MRI, and Doppler ultrasonography of abdominal vessels and the laboratory findings were compatible with PV. After a successful creation of TIPS, a HIT/T worsened the hemorrhagic and thrombotic picture. TIPS procedure was successfully repeated and heparin was replaced with Fondaparinux and then vitamin K antagonist. The treatment with interferon alpha-2A, started after the normalization of liver functions, resulted in a complete remission within 6 months. The JAK2 V617F mutation clone remained undetectable after 2 years′ follow-up.

  13. Development of a Colloidal Gold Kit for the Diagnosis of Severe Fever with Thrombocytopenia Syndrome Virus Infection

    Xianguo Wang

    2014-01-01

    Full Text Available It is critical to develop a cost-effective detection kit for rapid diagnosis and on-site detection of severe fever with thrombocytopenia syndrome virus (SFTSV infection. Here, an immunochromatographic assay (ICA to detect SFTSV infection is described. The ICA uses gold nanoparticles coated with recombinant SFTSV for the simultaneous detection of IgG and IgM antibodies to SFTSV. The ICA was developed and evaluated by using positive sera samples of SFTSV infection (n=245 collected from the CDC of China. The reference laboratory diagnosis of SFTSV infection was based on the “gold standard”. The results demonstrated that the positive coincidence rate and negative coincidence rate were determined to be 98.4% and 100% for IgM and 96.7% and 98.6% for IgG, respectively. The kit showed good selectivity for detection of SFTSV-specific IgG and IgM with no interference from positive sera samples of Japanese encephalitis virus infection, Dengue virus infection, Hantavirus infection, HIV infection, HBV surface antigen, HCV antibody, Mycobacterium tuberculosis antibody, or RF. Based on these results, the ICS test developed may be a suitable tool for rapid on-site testing for SFTSV infections.

  14. Mechanistic properties of intravenous immunoglobulin in murine immune thrombocytopenia: support for FcγRIIB falls by the wayside.

    Crow, Andrew R; Lazarus, Alan H

    2016-04-01

    Immune thrombocytopenia (ITP) is an autoimmune disorder characterised by platelet clearance resulting from the production of platelet-reactive autoantibodies. Platelet clearance appears to occur mainly via phagocytosis in the mononuclear phagocytic system, although T-cell-mediated platelet destruction, platelet apoptosis and dysregulation of platelet production can also play a role in disease pathogenesis. One of the most successful treatments for ITP is intravenous immunoglobulin (IVIg), and while it has been used in ITP for over 30 years, its mechanism(s) of action still remain unclear. Animal models of ITP have proven useful in understanding IVIg's immunomodulatory properties, providing a valuable tool to test new mechanistic theories as well as further explore the soundness of older ones. This model has also provided the key evidence that IVIg exerts its effects via activating receptors for IgG Fc, specifically FcγRIII, via formation of IgG dimers or immune complexes. Here, we discuss the validity of one prominent theory of IVIg function, anti-inflammatory activity mediated through the inhibitory Fcγ receptor FcγRIIB, and review evidence to suggest that this theory is not likely valid in the practical sense. PMID:27312158

  15. The ratio of Treg/Th17 cells correlates with the disease activity of primary immune thrombocytopenia.

    Lili Ji

    Full Text Available BACKGROUND: Primary immune thrombocytopenia (ITP is an autoimmune heterogeneous disorder that is characterized by decreased platelet count. Regulatory T (Treg cells and T helper type 17 (Th17 cells are two subtypes of CD4(+ T helper (Th cells. They play opposite roles in immune tolerance and autoimmune diseases, while they share a common differentiation pathway. The imbalance of Treg/Th17 has been demonstrated in several autoimmune diseases. In this study, we aimed to investigate the ratio of the number of Treg cells to the number of Th17 cells in ITP patients and evaluate the clinical implications of the alterations in this ratio. METHODS: Thirty adult patients with newly diagnosed ITP enrolled in this study. Twelve patients had been clinically followed up for 12 months. The percentages of CD4(+CD25(hiFoxp3(+ Treg cells and CD3(+CD4(+IL-17-producing Th17 cells in these patients and healthy controls (n = 17 were longitudinally analyzed by flow cytometry. RESULTS: The percentage of Treg cells in ITP patients was significantly lower than that of healthy controls, and the percentage of Th17 cells increased significantly at disease onset. The ratio of Treg/Th17 correlated with the disease activity. CONCLUSION: The ratio of Treg/Th17 might be relevant to the clinical diversity of ITP patients, and this Treg/Th17 ratio might have prognostic role in ITP patients.

  16. Acute Myopericarditis Mimicking Acute Myocardial Infarction

    Seval İzdeş; Neriman Defne Altıntaş; Gülin Karaaslan; Recep Uygun; Abdulkadir But

    2011-01-01

    Acute coronary syndromes among young adults are relatively low when compared with older population in the intensive care unit. Electrocardiographic abnormalities mimicking acute coronary syndromes may be caused by non-coronary syndromes and the differential diagnosis requires a detailed evaluation. We are reporting a case of myopericarditis presenting with acute ST elevation and elevated cardiac enzymes simulating acute coronary syndrome. In this case report, the literature is reviewed to dis...

  17. 妊娠合并血小板减少89例临床分析%Clinical analysis of 89 thrombocytopenia in pregnancy

    王洪英; 齐小雪; 王跃莲

    2009-01-01

    目的 探讨妊娠合并血小板减少的病因、治疗及分娩方式.方法 回顾性分析我院2006年1月~2009年3月收治的89例妊娠合并血小板减少患者的临床资料.结果 妊娠期血小板减少的主要病因有妊娠相关性血小板减少症(PAT)65例(73.03%),妊娠期高血压疾病(HDCP)11例(12.36%),特发性血小板减少性紫癜(ITP)6例(6.74%),妊娠合并肝脏疾病5例(5.61%),系统性红宽狼疮合并妊娠2例(2.24%).PAT孕期不需特殊处理,妊娠结局良好,对血小板<50×109/L的12例患者分娩前给予地塞米松10~20mg/d,5例无效者分娩时输注血小板.结论 妊娠期血小板减少以PAT多见,孕期不需特殊处理.其次为妊娠期高血压疾病(HDCP).当血小板≤50×109/L分娩前给予地塞米松治疗,静脉点滴3~5d,无效者分娩时输注血小板,分娩方式以剖宫产为宜,产后出血发生率12.35%.%Objective To explore the causes,therapy and the way of delive of pregnant women with thromboeytopenia. Methods The data of 89 cases with thrombocytopenia during pregnancy were reviewed from Jan. 2006 to Mar. 2009. Results The main cause of thrombocytopenia during pregnancy were pregnancy associated thrombocytopenia (PAT) has 65 cases (73.03%), Hypertensive disorder complicating pregnancy(HDCP) has 11 cases(12.36%). Idiopathic thromboeytopenia(ITP) has 6 cases(6.74%). Hepatic disease in pregnancy has 5 cases (5.61% ,Systemic lupus erythematosus in pregnancy has 2cases (2.24%). Pregnancy associated thrombocytopenia need not to be specially treated during pregnancy, To the 12 patients whose platelet <50×109/L given dexamethasone 10~20mg/d treatment before delivery ,But five patients who has no effect intravenous platelet treatment during delivery. Conclusion Pregnancy associated thrombocytopenia is the common reason in thrombocytope-nia during pregnancy, Pregnancy associated thrombocytopenia need not to be specially treated during pregnancy. The second rea-son is hypertensive

  18. Acute idiopathic pericarditis: current immunological theories

    Caforio AL

    2012-09-01

    Full Text Available Alida LP Caforio,1 Renzo Marcolongo,2 Antonio Brucato,3 Luca Cantarini,4 Massimo Imazio,5 Sabino Iliceto11Division of Cardiology, Department of Cardiology, Thoracic and Vascular Sciences, University of Padua, Padua; 2Haematology and Clinical Immunology, Department of Medicine, University of Padua, Padua, 3Internal Medicine, Ospedali Riuniti, Bergamo, 4Rheumatology Unit, Policlinico Le Scotte, University of Siena, Siena, 5Department of Cardiology, Maria Vittoria Hospital, Torino, ItalyAbstract: Idiopathic recurrent acute pericarditis (IRAP is a rare disease of suspected immune-mediated pathogenesis. It represents a diagnosis of exclusion. It is necessary to rule out infectious and noninfectious causes of pericardial inflammation, including systemic autoimmune and immune-related disorders, eg, Sjögren’s disease, systemic lupus erythematosus. Since pericarditis may precede diagnosis of these disorders, IRAP diagnosis is often made after a long follow-up. According to the two main pathogenetic theories IRAP may represent an organ-specific autoimmune disease or an autoinflammatory disease (AInfD. The main evidence for autoimmunity in IRAP is provided by the detection of serum antiheart and antiintercalated-disk autoantibodies, and the response to anti-inflammatory or immunosuppressive therapy. The findings of familial forms and of proinflammatory cytokines in the pericardial fluid in IRAP would be in keeping with both organ-specific autoimmune disease and AInfD. In fact, AInfD are genetic disorders characterized by primary dysfunction of the innate immune system, due to mutations of genes involved in the regulation of the inflammatory response, in the absence of antigen specific T cells or autoantibodies. In AInfD there are active disease phases with raised non-cardiac specific inflammatory markers, such as C-reactive protein, as well as symptom-free intervals with possible C-reactive protein normalization. A minority of IRAP patients (6% carry a

  19. Presence of Essential Hypertension or Diabetes Mellitus Is a Predictor of Intracranial Bleeding in Elderly Patients: A Study of 108 Patients with Isolated Thrombocytopenia from a Single Reference Center

    Rajan Kapoor

    2015-06-01

    Full Text Available INTRODUCTION: Thrombocytopenia poses a significant problem in the elderly. Not only are there varied causes, but it is also associated with significant morbidity and mortality. We carried out a study to learn the causes of isolated thrombocytopenia in elderly patients and to correlate the severity of thrombocytopenia and bleeding manifestations with various etiologic factors and comorbidities. METHODS: A total of 108 patients above 50 years of age presenting with isolated thrombocytopenia (platelet counts of <100x109/L with normal hemoglobin and total leukocyte counts were enrolled in the study. Detailed history and clinical examinations were carried out for each patient. Complete blood counts were analyzed by automated cell counter. Peripheral smears were examined in all cases. HbsAg, anti-HCV, and anti-HIV testing by enzyme-linked immunosorbent assay was done in all patients. Wherever clinically indicated, bone marrow aspiration biopsy and cytogenetic studies were done. RESULTS: Out of 108 patients, 102 (94.4% presented with bleeding tendencies. Twenty-nine (26.8% presented with serious (World Health Organization grade 3/4 bleedings. Major findings were immune thrombocytopenic purpura in 79 (73.1%, myelodysplastic syndrome in 7 (6.5%, drug-induced thrombocytopenia in 7 (6.5%, and connective tissue disorder in 4 (3.7% cases. Ten patients presented with intracranial bleedings. Upon logistic regression analysis, comorbidities in the form of essential hypertension and diabetes mellitus were significantly associated with occurrence of intracranial bleeding. There was no correlation of serious bleedings with platelet counts. DISCUSSION AND CONCLUSION: Isolated thrombocytopenia in the elderly is associated with significant morbidity. Diligent clinical and laboratory evaluation is required to elucidate the cause of thrombocytopenia in the elderly. Comorbidities in this population are associated with serious bleedings and not low platelet counts as is

  20. Immune Thrombocytopenia Resolved by Eltrombopag in a Carrier of Glucose-6-Phosphate Dehydrogenase Deficiency

    Laura Scaramucci

    2016-03-01

    Full Text Available Eltrombopag, a thrombopoietin mimetic peptide, may provide excellent clinical efficacy in steroid-refractory patients with immune thrombocytopenic purpura (ITP [1,2]. Eltrombopag is generally well tolerated. However, its use in the particular setting of glucose-6-phosphate dehydrogenase (G6PD and history of acute hemolytic anemia (AHA has not been reported so far. A 51-year-old female was diagnosed as having ITP in September 2014. She was not taking any medication and her past history was negative, apart from having been diagnosed a carrier (heterozygous of G6PD deficiency (Mediterranean variant after a familial screening by molecular and biochemical methods. She presented with only slightly reduced (about 50% enzyme level, belonging to World Health Organization-defined class 3 [3,4]. In the following years, the patient experienced some episodes of AHA, which were managed at outside institutions; in particular, a severe episode of AHA, probably triggered by urinary infection and antibiotics [5], had complicated her second and last delivery. The hemolytic episodes were selflimiting and resolved without sequelae. No other causes of hemolysis were documented. When the case came to our attention, a diagnosis of ITP was made; hemolytic parameters were normal, although the G6PD enzyme concentration was not measured. Oral prednisone (1 mg/kg was given with only a transient benefit. The patient was then a candidate for elective splenectomy. However, given her extremely low platelet count, she was started in October 2014 on eltrombopag at 50 mg/day as a bridge to splenectomy. Given that, to the best of our knowledge, the use of this drug has never been reported in the particular setting of G6PD deficiency, the patient was constantly monitored. A prompt platelet increase (178x109/L was observed 1 week after the start of treatment. After she achieved the target platelet count, the dose of eltrombopag was tapered to the lowest effective dose. The patient

  1. Acute abdomen

    The book first presents the anatomy and physiology of the abdomen and continues with chapters discussing clinical and laboratory aspects and a suitable order of diagnostic examinations with reference to the acute processes, explaining the diagnostic tools: ultrasonography, radiography including angiography and CT, tapping techniques and endoscopy together with their basic principles, examination techniques, and diagnosis. One chapter presents a complete survey of the processes involving the entire abdomen - as e.g. peritonitis, ileus, abdominal trauma, intraperitoneal hemorrage. This chapter profoundly discusses the diagnostics and therapies including emergency measures and surgery. Problems requiring consultation among varous specialists, in internal medicine, gynecology, urology, or pediatrics, are discussed in great detail. Information for the anesthetist is given for cases of emergency. More than one third of the book is devoted to organ-specific information, dicussing the pathogenesis, diagnostics, and therapy of the oesophagus, stomach, large and small intestine, bile ducts, pankreas, liver, spleen, and the abdominal vessels and the abdominal wall. (orig.) With 153 figs., 90 tabs

  2. Acute pancreatitis

    A prospective study was performed on the relationship of CT findings to the clinical course of 148 patients with acute pancreatitis. The type of pancreatic inflammation seen on CT was classified into six categories based on an overall assessment of size, contour and density of the gland, and peripancreatic abnormalities. The majority (94%) of patients in whom CT showed mild pancreatic changes (grades A, B and C) had two or less positive clinical indicaters of severe pancreatitis (Ranson's signs). In contrast, 92% of patients in whom CT showed more severe changes of pancreatitis (grades D, E or F) had three or more positive signs. The nine patients who died with pancreatitis-related complications were in grades D, E or F. We wish to draw attention to a CT appearance which we have called 'fat islets' (low density intrapancreatic or peripancreatic areas, the contents of which approach fat in attenuation values); there was a strong correlation between this appearance and subsequent infection. (author). 24 refs.; 7 figs.; 4 tabs

  3. Detection of Severe Fever with Thrombocytopenia Syndrome Virus from Wild Animals and Ixodidae Ticks in the Republic of Korea.

    Oh, Sung-Suck; Chae, Jeong-Byoung; Kang, Jun-Gu; Kim, Heung-Chul; Chong, Sung-Tae; Shin, Jeong-Hwa; Hur, Moon-Suk; Suh, Jae-Hwa; Oh, Myoung-Don; Jeong, Soo-Myoung; Shin, Nam-Shik; Choi, Kyoung-Seong; Chae, Joon-Seok

    2016-06-01

    Severe fever with thrombocytopenia syndrome (SFTS) is caused by SFTS virus (SFTSV), a novel bunyavirus reported to be endemic to central-northeastern China, southern Japan, and the Republic of Korea (ROK). To investigate SFTSV infections, we collected serum samples and ticks from wild animals. Using serum samples and ticks, SFTSV-specific genes were amplified by one-step RT-PCR and nested PCR and sequenced. Indirect immunofluorescence assay (IFA) was performed to analyze virus-specific antibody levels in wild animals. Serum samples were collected from a total of 91 animals: 21 Korean water deer (KWD), 3 Siberian roe deer, 5 gorals, 7 raccoon dogs, 54 wild boars (WBs), and 1 carrion crow. The SFTSV infection rate in wild animals was 3.30% (3 of 91 animals: 1 KWD and 2 WBs). The seropositive rate was 6.59% (6 of 91 animals: 5 KWD and 1 WB). A total of 891 ticks (3 species) were collected from 65 wild animals (9 species). Of the attached tick species, Haemaphysalis longicornis (74.86%) was the most abundant, followed by Haemaphysalis flava (20.20%) and Ixodes nipponensis (4.94%). The average minimum infection rate (MIR) of SFTSV in ticks was 4.98%. The MIRs of H. longicornis, H. flava, and I. nipponensis were 4.51%, 2.22%, and 22.73%, respectively. The MIRs of larvae, nymphs, and adult ticks were 0.68%, 6.88%, and 5.53%, respectively. In addition, the MIRs of fed and unfed ticks were 4.67% and 4.96%, respectively. We detected a low SFTSV infection rate in wild animals, no differences in SFTSV infection rate with respect to bloodsucking in ticks, and SFTSV infection for all developmental stages of ticks. This is the first report describing the detection of SFTSV in wild animals in the ROK. PMID:27043361

  4. The effects of panaxadiol saponins on megakaryocytic maturation and immune function in a mouse model of immune thrombocytopenia.

    Lin, Xiaojie; Yin, Liming; Gao, Ruilan; Liu, Qinghua; Xu, Weihong; Jiang, Xingmai; Chong, Beng Hock

    2015-05-01

    We have identified a biologically active component, panaxadiol saponins component (PDS-C), from Chinese ginseng herb extract. Panaxadiol saponins component contains five ginsenoside monomers with total purity of 92.44%. In this study, the BALB/c mouse model with immune thrombocytopenia (ITP) was established by injection of antiplatelet antibody every other day for 5 total times; the peripheral blood platelet counts steadily decreased to 20%-30% of normal levels and remained decreased for about 10 days. The antiplatelet antibody was derived from the sera of guinea pigs immunized with the platelets of BALB/c mice. Mice with ITP were treated with PDS-C at a low, a moderate, or a high dose for 10 consecutive days. We observed that the peripheral blood platelet counts of ITP mice were significantly higher than that of ITP controls (untreated) after treatment of PDS-C in a dose-dependent manner. Treatment with PDS-C also increased the mature megakaryocytes in the bone marrow of treated ITP animals with a concomitant decease of immature megakaryocyte precursors. Furthermore, macrophage phagocytosis of exogenous erythrocytes in the intra-abdominal cavity of ITP mice was inhibited by PDS-C treatment, indicating that PDS-C also could modulate immune function and may possibly prevent phagocytosis of antibody-coated platelets. Altogether, our findings suggest that PDS-C may have a dual role, promoting proliferation and differentiation of megakaryocytes, as well as modulating immune function, and it may therefore be very helpful in the treatment of ITP. PMID:25578384

  5. High-dose dexamethasone corrects impaired myeloid-derived suppressor cell function via Ets1 in immune thrombocytopenia.

    Hou, Yu; Feng, Qi; Xu, Miao; Li, Guo-Sheng; Liu, Xue-Na; Sheng, Zi; Zhou, Hai; Ma, Ji; Wei, Yu; Sun, Yuan-Xin; Yu, Ying-Yi; Qiu, Ji-Hua; Shao, Lin-Lin; Liu, Xin-Guang; Hou, Ming; Peng, Jun

    2016-03-24

    Myeloid-derived suppressor cells (MDSCs) are heterogeneous immature cells and natural inhibitors of adaptive immunity. In this study, the MDSC population was evaluated in adult patients with primary immune thrombocytopenia (ITP), where cell-mediated immune mechanisms are involved in platelet destruction. Our data demonstrated that both the numbers and suppressive functions of MDSCs were impaired in the peripheral blood and spleens of patients with ITP compared with healthy control patients. High-dose dexamethasone (HD-DXM) treatment rescued MDSC numbers in patients with ITP. And DXM modulation promoted the suppressive function of MDSCs induced in vitro. Moreover, the expression of interleukin 10 and transforming growth factor β was significantly upregulated in DXM-modulated MDSCs compared with the unmodulated cultures. DXM-modulated MDSCs inhibited autologous CD4(+)T-cell proliferation and significantly attenuated cytotoxic T lymphocyte-mediated platelet lysis, further indicating enhanced control over T-cell responses. Elevated expression of the transcription factor Ets1 was identified in DXM-modulated MDSCs. Transfection of Ets-1 small interfering RNA efficiently blocked regulatory effects of MDSCs, which almost offset the augmentation of MDSC function by DXM. Meanwhile, splenocytes from CD61 knockout mice immunized with CD61(+)platelets were transferred into severe combined immunodeficient (SCID) mouse recipients (C57/B6 background) to induce a murine model of severe ITP. We passively transferred the DXM-modulated MDSCs induced from bone marrow of wild-type C57/B6 mice into the SCID mouse recipients, which significantly increased platelet counts in vivo compared with those receiving splenocyte engraftment alone. These findings suggested that impaired MDSCs are involved in the pathogenesis of ITP, and that HD-DXM corrected MDSC functions via a mechanism underlying glucocorticoid action and Ets1. PMID:26744458

  6. Platelet Apoptosis in Adult Immune Thrombocytopenia: Insights into the Mechanism of Damage Triggered by Auto-Antibodies

    Goette, Nora P.; Glembotsky, Ana C.; Lev, Paola R.; Grodzielski, Matías; Contrufo, Geraldine; Pierdominici, Marta S.; Espasandin, Yesica R.; Riveros, Dardo; García, Alejandro J.; Molinas, Felisa C.; Heller, Paula G.

    2016-01-01

    Mechanisms leading to decreased platelet count in immune thrombocytopenia (ITP) are heterogeneous. This study describes increased platelet apoptosis involving loss of mitochondrial membrane potential (ΔΨm), caspase 3 activation (aCasp3) and phosphatidylserine (PS) externalization in a cohort of adult ITP patients. Apoptosis was not related to platelet activation, as PAC-1 binding, P-selectin exposure and GPIb-IX internalization were not increased. Besides, ITP platelets were more sensitive to apoptotic stimulus in terms of aCasp3. Incubation of normal platelets with ITP plasma induced loss of ΔΨm, while PS exposure and aCasp3 remained unaltered. The increase in PS exposure observed in ITP platelets could be reproduced in normal platelets incubated with ITP plasma by adding normal CD3+ lymphocytes to the system as effector cells. Addition of leupeptin -a cathepsin B inhibitor- to this system protected platelets from apoptosis. Increased PS exposure was also observed when normal platelets and CD3+ lymphocytes were incubated with purified IgG from ITP patients and was absent when ITP plasma was depleted of auto-antibodies, pointing to the latter as responsible for platelet damage. Apoptosis was present in platelets from all patients carrying anti-GPIIb-IIIa and anti-GPIb auto-antibodies but was absent in the patient with anti-GPIa-IIa auto-antibodies. Platelet damage inversely correlated with platelet count and decreased during treatment with a thrombopoietin receptor agonist. These results point to a key role for auto-antibodies in platelet apoptosis and suggest that antibody-dependent cell cytotoxicity is the mechanism underlying this phenomenon. PMID:27494140

  7. A dominant gain-of-function mutation in universal tyrosine kinase SRC causes thrombocytopenia, myelofibrosis, bleeding, and bone pathologies.

    Turro, Ernest; Greene, Daniel; Wijgaerts, Anouck; Thys, Chantal; Lentaigne, Claire; Bariana, Tadbir K; Westbury, Sarah K; Kelly, Anne M; Selleslag, Dominik; Stephens, Jonathan C; Papadia, Sofia; Simeoni, Ilenia; Penkett, Christopher J; Ashford, Sofie; Attwood, Antony; Austin, Steve; Bakchoul, Tamam; Collins, Peter; Deevi, Sri V V; Favier, Rémi; Kostadima, Myrto; Lambert, Michele P; Mathias, Mary; Millar, Carolyn M; Peerlinck, Kathelijne; Perry, David J; Schulman, Sol; Whitehorn, Deborah; Wittevrongel, Christine; De Maeyer, Marc; Rendon, Augusto; Gomez, Keith; Erber, Wendy N; Mumford, Andrew D; Nurden, Paquita; Stirrups, Kathleen; Bradley, John R; Lucy Raymond, F; Laffan, Michael A; Van Geet, Chris; Richardson, Sylvia; Freson, Kathleen; Ouwehand, Willem H

    2016-03-01

    The Src family kinase (SFK) member SRC is a major target in drug development because it is activated in many human cancers, yet deleterious SRC germline mutations have not been reported. We used genome sequencing and Human Phenotype Ontology patient coding to identify a gain-of-function mutation in SRC causing thrombocytopenia, myelofibrosis, bleeding, and bone pathologies in nine cases. Modeling of the E527K substitution predicts loss of SRC's self-inhibitory capacity, which we confirmed with in vitro studies showing increased SRC kinase activity and enhanced Tyr(419) phosphorylation in COS-7 cells overexpressing E527K SRC. The active form of SRC predominates in patients' platelets, resulting in enhanced overall tyrosine phosphorylation. Patients with myelofibrosis have hypercellular bone marrow with trilineage dysplasia, and their stem cells grown in vitro form more myeloid and megakaryocyte (MK) colonies than control cells. These MKs generate platelets that are dysmorphic, low in number, highly variable in size, and have a paucity of α-granules. Overactive SRC in patient-derived MKs causes a reduction in proplatelet formation, which can be rescued by SRC kinase inhibition. Stem cells transduced with lentiviral E527K SRC form MKs with a similar defect and enhanced tyrosine phosphorylation levels. Patient-derived and E527K-transduced MKs show Y419 SRC-positive stained podosomes that induce altered actin organization. Expression of mutated src in zebrafish recapitulates patients' blood and bone phenotypes. Similar studies of platelets and MKs may reveal the mechanism underlying the severe bleeding frequently observed in cancer patients treated with next-generation SFK inhibitors. PMID:26936507

  8. Thrombopoietin receptor agonists for preparing adult patients with immune thrombocytopenia to splenectomy: results of a retrospective, observational GIMEMA study.

    Zaja, Francesco; Barcellini, Wilma; Cantoni, Silvia; Carpenedo, Monica; Caparrotti, Giuseppe; Carrai, Valentina; Di Renzo, Nicola; Santoro, Cristina; Di Nicola, Massimo; Veneri, Dino; Simonetti, Federico; Liberati, Anna M; Ferla, Valeria; Paoloni, Francesca; Crea, Enrico; Volpetti, Stefano; Tuniz, Enrica; Fanin, Renato

    2016-05-01

    In patients with immune thrombocytopenia (ITP) refractory to corticosteroids and intravenous immunoglobulins (IVIG), splenectomy may result at higher risk of peri-operative complications and, for this reason, potentially contraindicated. The thrombopoietin receptor agonists (TPO-RAs) romiplostim and eltrombopag have shown high therapeutic activity in primary ITP, but data of efficacy and safety regarding their use in preparation for splenectomy are missing. Thirty-one adult patients, median age 50 years, with corticosteroids and/or IVIG refractory persistent and chronic ITP who were treated with TPO-RAs (romiplostim= 24; eltrombopag= 7) with the aim to increase platelet count and allow a safer execution of splenectomy were retrospectively evaluated. Twenty-four patients (77%) responded to the use of TPO-RAs with a median platelet count that increased from 11 × 10(9) /L before starting TPO-RAs to 114 × 10(9) /L pre-splenectomy, but a concomitant treatment with corticosteroids and/or IVIG was required in 19 patients. Twenty-nine patients underwent splenectomy while two patients who responded to TPO-RAs subsequently refused surgery. Post-splenectomy complications were characterized by two Grade 3 thrombotic events (1 portal vein thrombosis in the patient with previous history of HCV hepatitis and 1 pulmonary embolism), with a platelet count at the time of thrombosis of 260 and 167 × 10(9) /L, respectively and one Grade 3 infectious event. TPO-RAs may represent a therapeutic option to improve platelet count and reduce the risk of peri-operative complications in ITP candidates to splenectomy. An increased risk of post-splenectomy thromboembolic events cannot be ruled out and thromboprophylaxis with low-molecular weight heparin is generally recommended. Am. J. Hematol. 91:E293-E295, 2016. © 2016 Wiley Periodicals, Inc. PMID:26910388

  9. Delayed Diagnosis of Falciparum Malaria with Acute Kidney Injury.

    Choi, Iee Ho; Hwang, Pyoung Han; Choi, Sam Im; Lee, Dae Yeol; Kim, Min Sun

    2016-09-01

    Prompt malaria diagnosis is crucial so antimalarial drugs and supportive care can then be rapidly initiated. A 15-year-old boy who had traveled to Africa (South Africa, Kenya, and Nigeria between January 3 and 25, 2011) presented with fever persisting over 5 days, headache, diarrhea, and dysuria, approximately 17 days after his return from the journey. Urinalysis showed pyuria and hematuria. Blood examination showed hemolytic anemia, thrombocytopenia, disseminated intravascular coagulation, and hyperbilirubinemia. Plasmapheresis and hemodialysis were performed for 19 hospital days. Falciparum malaria was then confirmed by peripheral blood smear, and antimalarial medications were initiated. The patient's condition and laboratory results were quickly normalized. We report a case of severe acute renal failure associated with delayed diagnosis of falciparum malaria, and primary use of supportive treatment rather than antimalarial medicine. The present case suggests that early diagnosis and treatment is important because untreated tropical malaria can be associated with severe acute renal failure and fatality. Physicians must be alert for correct diagnosis and proper management of imported tropical malaria when patients have travel history of endemic areas. PMID:27510397

  10. Effect of hUC-MSCs treatment on immune function, tryptophan metabolic pathways and related gene expression of children with immune thrombocytopenia

    Zu-Bin Wang; Yi-Lin Zhu

    2016-01-01

    Objective:To study the effect of hUC-MSCs treatment on immune function, tryptophan metabolic pathways and related gene expression of children with immune thrombocytopenia. Methods: A total of 58 cases of children with immune thrombocytopenia were enrolled for study and randomly divided into hUC-MSCs group and conventional group, hUC-MSCs group received glucocorticoid + gamma globulin + hUC-MSCs treatment and conventional group received glucocorticoid + gamma globulin treatment. Then platelet content, immune function, tryptophan metabolism as well as expression of T-bet and GATA-3 of two groups were compared.Results: Platelet content of hUC-MSCs group was higher than that of conventional group; serum IFN-γ and IL-2 contents of hUC-MSCs group were lower than those of conventional group, and serum IL-4 and IL-10 contents as well as peripheral blood Treg cell ratio was higher than those of conventional group; serum Trp concentration and Trp/Kyn ratio of hUC-MSCs group were lower than those of conventional group, Kyn concentration was higher than that of conventional group, IDO expression in peripheral blood mononuclear cells was higher than that of conventional group, and TTS expression was lower than that of conventional group; mRNA content of T-bet in peripheral blood mononuclear cells of hUC-MSCs group was lower than that of conventional group, and mRNA content of GATA-3 was higher than that of conventional group.Conclusion: hUC-MSCs therapy can increase platelet content and regulate Th1/Th2 balance and tryptophan metabolism; it's an ideal method for the treatment of immune thrombocytopenia.

  11. 妊娠合并血小板减少105例临床分析%Clinical analysis of 105 patients with thrombocytopenia in pregnancy

    黄鑫; 朱艳; 黄达; 余宏男

    2012-01-01

    Objective To investigate the pregnancy with the pathogenesis of thrombocytopenia and perinatal treatment. Methods We take the clinical data of 105 pregnant women with thrombocytopenia for retrospective study. Results There were 55 cases of PAT, 19 cases of ITP, 37 cases of PIH, 3 cases of liver disease and 1 case of systemic lupus erythematosus. And there were 65 ca ses of cesarean section, accounting for 61. 9% and 40 cases of vaginal delivery, accounting for 38. 1%. Conclusion The pregnancy with thrombocytopenia generally occurs in late pregnancy, and PAT is the most common. An appropriate prenatal platelet level in crease could reduce the incidence of complications.%目的 探讨妊娠合并血小板减少症的发病机制及围生期处理方法.方法 对105例妊娠合并血小板减少患者的临床资料作回顾性研究.结果 出现妊娠相关性血小板减少症(PAT)55例,特发性血小板减少性紫癜(ITP)19例,妊娠期高血压疾病先兆子痫(PIH)37例,肝病3例,系统性红斑狼疮1例.其中剖宫产65例,占61.9%;阴道分娩40例,占38.1%.结论 PAT一般发生在妊娠晚期,以PAT最常见,产前适当提高血小板水平,可以减少并发症发生.

  12. Acute chylous peritonitis due to acute pancreatitis

    2012-01-01

    We report a case of acute chylous ascites formation presenting as peritonitis (acute chylous peritonitis) in a patient suffering from acute pancreatitis due to hypertriglyceridemia and alcohol abuse. The development of chylous ascites is usually a chronic process mostly involving malignancy, trauma or surgery, and symptoms arise as a result of progressive abdominal distention. However, when accumulation of “chyle” occurs rapidly, the patient may present with signs of peritonitis. Preoperative...

  13. 妊娠合并血小板减少与新生儿转归的分析%Thrombocytopenia in pregnancy and neonatal outcomes

    晁爽; 曾超美; 刘捷

    2011-01-01

    Objective To study the relationship between thrombocytopenia in pregnancy associated with various causes and neonatal outcomes. Methods Medical records of 140 pregnant women with thrombocytopenia in pregnancy and the neonatal outcomes from January 2009 to December 2010 were reviewed retrospectively. The pregnant women were classified into four groups according to the causes of thrombocytopenia: gestational thrombocytopenia ( GT; n =94), pregnancy with immune thrombocytopenic purpura (ITP; n =30) , pregnancy with other hematological disease (aplastic anemia or myelodysplastic syndrome; n = 12) , and other causes (n =4) : pregnancy induced hypertension syndrome, pregnancy with systemic lupus erythematosus, and pregnancy with alcoholic cirrhosis. The neonatal outcomes in the four groups were compared. Results The premature birth rates in the GT and the ITP groups were 11. 3% and 16. 7% , respectively. There was no significant difference between the two groups. The premature birth rate in the other hematological disease group was 53. 8% , which was significantly higher than that in the GT (P 0.05).妊娠合并其他血液系统疾病组早产率53.8%,明显高于GT组(P<0.01)和ITP组(P<0.05).GT组和ITP组中分别有2例(2%)和4例(13%)患新生儿先天性被动免疫性血小板减少症,其发生比率差异有统计学意义(P<0.05).ITP组中1例(3%)患ITP,1例(3%)患Evans综合征.妊娠合并其他血液系统疾病组1例(8%)患颅内出血.其他原因组中1例(25%)患新生儿狼疮综合征.结论 不同病因所致妊娠期血小板减少可致不同的围产期母婴结局.

  14. Acute arterial occlusion - kidney

    ... arterial thrombosis; Renal artery embolism; Acute renal artery occlusion; Embolism - renal artery ... often result in permanent kidney failure. Acute arterial occlusion of the renal artery can occur after injury ...

  15. Acute Pancreatitis in Children

    ... a feeding tube or an IV to prevent malnutrition and improve healing. Does my child have to ... intestines. Can my child die from acute pancreatitis? Death from acute pancreatitis is quite rare in children– ...

  16. Diagnosing and Treating Acute Bronchitis

    ... Lung Disease Lookup > Acute Bronchitis Diagnosing and Treating Acute Bronchitis It is important to get your questions about ... Symptoms that last a few weeks How Is Acute Bronchitis Diagnosed? Healthcare providers diagnose acute bronchitis by asking ...

  17. Ghrelin Therapy Improves Survival after Whole-Body Ionizing Irradiation or Combined with Burn or Wound: Amelioration of Leukocytopenia, Thrombocytopenia, Splenomegaly, and Bone Marrow Injury

    Kiang, Juliann G.; Zhai, Min; Liao, Pei-Jyun; Elliott, Thomas B.; Gorbunov, Nikolai V.

    2014-01-01

    Exposure to ionizing radiation alone (RI) or combined with traumatic tissue injury (CI) is a crucial life-threatening factor in nuclear and radiological events. In our laboratory, mice exposed to 60Co-γ-photon radiation (9.5 Gy, 0.4 Gy/min, bilateral) followed by 15% total-body-surface-area skin wounds (R-W CI) or burns (R-B CI) experienced an increment of ≥18% higher mortality over a 30-day observation period compared to RI alone. CI was accompanied by severe leukocytopenia, thrombocytopenia, erythropenia, and anemia. At the 30th day after injury, numbers of WBC and platelets still remained very low in surviving RI and CI mice. In contrast, their RBC, hemoglobin, and hematocrit were recovered towards preirradiation levels. Only RI induced splenomegaly. RI and CI resulted in bone-marrow cell depletion. In R-W CI mice, ghrelin (a hunger-stimulating peptide) therapy increased survival, mitigated body-weight loss, accelerated wound healing, and increased hematocrit. In R-B CI mice, ghrelin therapy increased survival and numbers of neutrophils, lymphocytes, and platelets and ameliorated bone-marrow cell depletion. In RI mice, this treatment increased survival, hemoglobin, and hematocrit and inhibited splenomegaly. Our novel results are the first to suggest that ghrelin therapy effectively improved survival by mitigating CI-induced leukocytopenia, thrombocytopenia, and bone-marrow injury or the RI-induced decreased hemoglobin and hematocrit. PMID:25374650

  18. Metformin induced acute pancreatitis

    Alsubaie, Sadeem; Almalki, Mussa H.

    2013-01-01

    Acute pancreatitis frequently presents with abdomen pain but may presents with various skin manifestations as rash and rarely, pancreatic panniculitis. Metformin, one of the most effective and valuable oral hypoglycemic agents in the biguanide class was linked to acute pancreatitis in few cases. Here, we report a case of metformin induce acute pancreatitis in young healthy man with normal renal function.

  19. Acute mastoiditis in children

    Anthonsen, Kristian; Høstmark, Karianne; Hansen, Søren;

    2013-01-01

    Conservative treatment of acute otitis media may lead to more complications. This study evaluates changes in incidence, the clinical and microbiological findings, the complications and the outcome of acute mastoiditis in children in a country employing conservative guidelines in treating acute ot...

  20. Recurrent acute renal failure

    Satish, S.; Rajesh, R.; Kurian, G.; Seethalekshmi, N. V.; Unni, M.; Unni, V. N.

    2010-01-01

    While acute renal failure secondary to intravascular hemolysis is well described in hemolytic anemias, recurrent acute renal failure as the presenting manifestation of a hemolytic anemia is rare. We report a patient with recurrent acute renal failure who was found to have paroxysmal nocturnal hemoglobinuria (PNH), on evaluation.

  1. [Acute renal failure after dengue virus infection: A pediatric case report].

    Nicolon, C; Broustal, E

    2016-01-01

    Dengue is an emerging, rapidly expanding disease, whose clinical and biological manifestations vary. Kidney injury is not usual but can be severe, and it is most often associated with dengue hemorrhagic fever or shock. Guadeloupe, which is located in an endemic area, experienced an epidemic from 2013 to 2014. During this outbreak, a case of renal failure during dengue was observed in a 10-year-old child. No evidence of dengue hemorrhagic fever or shock syndrome was found. The clinical and biological course improved with symptomatic treatment. The association of acute renal failure with hemolytic anemia suggested a diagnosis of hemolytic uremic syndrome. However, this could not be confirmed in the absence of thrombocytopenia and cytopathologic evidence. This case illustrates the diversity of clinical presentations of dengue, and the possibility of severe renal impairment unrelated to the usual factors encountered in dengue. PMID:26563725

  2. OSTEOPOROSIS IN A SEVENTH YEAR OLD BOY WITH ACUTE LYMPHOBLASTIC LEUKEMIA (Case Report

    H Salim

    2013-09-01

    Full Text Available Osteoporosis in children is rare and usually secondary to an underlying disease process whose diagnosis may be difficult to detect. It can be a manifestation of acute lymphoblastic leukemia (ALL. About a-quarters of children with ALL will have signs and symptoms of osteoporosis. We report the case of a seventh-year-old boy with back pain. His antero-posterior pelvic radiograph showed the osteoporotic bone. The bone age study revealed six-year-old bone. Review of peripheral blood smear showed normochromic anemia with thrombocytopenia. Immunophenotyping of peripheral blood revealed no dominant marker was seen, but the bone marrow aspiration confirms the diagnosis of ALL (L2.

  3. Refractory chronic immune thrombocytopenic purpura in a child with acute lymphoblastic leukemia.

    Horino, Satoshi; Rikiishi, Takeshi; Niizuma, Hidetaka; Abe, Hiroshi; Watanabe, Yuko; Onuma, Masaei; Hoshi, Yoshiyuki; Sasahara, Yoji; Yoshinari, Miyako; Kazama, Takuro; Hayashi, Yutaka; Kumaki, Satoru; Tsuchiya, Shigeru

    2009-11-01

    Immune thrombocytopenic purpura (ITP) has been associated with several hematologic malignancies such as Hodgkin and non-Hodgkin lymphomas and chronic lymphocytic leukemia, but it is rare in children with acute lymphoblastic leukemia (ALL). Here, we report a 7-year-old girl with chronic ITP during early intensive phase of chemotherapy for ALL. She underwent splenectomy because thrombocytopenia had persisted even after treatment with intravenous immunoglobulin (IVIG), steroids, vincristine, rituximab, and anti-D antibody. After splenectomy, her platelet count had recovered, and maintenance therapy could be resumed with a support of IVIG. To our knowledge, this is the first child case of chronic ITP during chemotherapy for ALL and splenectomy was effective in this patient. PMID:19816666

  4. Acute encephalitis and encephalopathy associated with human parvovirus B19 infection in children.

    Watanabe, Toru; Kawashima, Hideshi

    2015-11-01

    Reports of neurologic manifestations of human parvovirus B19 (B19) infection have been on the rise. Acute encephalitis and encephalopathy is the most common, accounting for 38.8% of total B19-associated neurological manifestations. To date, 34 children with B19 encephalitis and encephalopathy have been reported, which includes 21 encephalitis and 13 encephalopathy cases. Ten (29%) were immunocompromised and 17 (39%) had underlying diseases. Fever at the onset of disease and rash presented in 44.1% and 20.6% of patients, respectively. Neurological manifestations include alteration of consciousness occurred in all patients, seizures in 15 (44.1%) patients, and focal neurologic signs in 12 (35.3%) patients. Anemia and pleocytosis in cerebrospinal fluid (CSF) occurred in 56.3% and 48.1% of patients, respectively. Serum Anti-B19 IgM (82.6%) and CSF B19 DNA (90%) were positive in the majority of cases. Some patients were treated with intravenous immunoglobulins and/or steroids, although an accurate evaluation of the efficacy of these treatment modalities cannot be determined. Nineteen (57.6%) patients recovered completely, 11 (33.3%) patients had some neurological sequelae and 3 (8.8%) patients died. Although the precise pathogenesis underlying the development of B19 encephalitis and encephalopathy is unclear, direct B19 infection or NS1protein of B19 toxicity in the brain, and immune-mediated brain injuries have been proposed. PMID:26566485

  5. Living with Thrombocytopenia

    ... as using a seatbelt while riding in a car and wearing gloves when working with knives and ... NEXT >> Updated: September 25, 2012 Twitter Facebook YouTube Google+ SITE INDEX ACCESSIBILITY PRIVACY STATEMENT FOIA OIG CONTACT ...

  6. Heparin-Induced Thrombocytopenia

    ... LIBRARY Hello, Guest! My alerts Sign In Join Facebook Twitter Home About this Journal Editorial Board General Statistics Circulation Cover Doodle → Blip the Doodle Go Red For Women's Issue Information for Advertisers Author Reprints Commercial Reprints Customer Service and Ordering ...

  7. Toward an immune-mediated subtype of autism spectrum disorder.

    McDougle, Christopher J; Landino, Samantha M; Vahabzadeh, Arshya; O'Rourke, Julia; Zurcher, Nicole R; Finger, Beate C; Palumbo, Michelle L; Helt, Jessica; Mullett, Jennifer E; Hooker, Jacob M; Carlezon, William A

    2015-08-18

    A role for immunological involvement in autism spectrum disorder (ASD) has long been hypothesized. This review includes four sections describing (1) evidence for a relationship between familial autoimmune disorders and ASD; (2) results from post-mortem and neuroimaging studies that investigated aspects of neuroinflammation in ASD; (3) findings from animal model work in ASD involving inflammatory processes; and (4) outcomes from trials of anti-inflammatory/immune-modulating drugs in ASD that have appeared in the literature. Following each section, ideas are provided for future research, suggesting paths forward in the continuing effort to define the role of immune factors and inflammation in the pathophysiology of a subtype of ASD. This article is part of a Special Issue entitled SI: Neuroimmunology in Health And Disease. PMID:25445995

  8. Oligodendrocyte death results in immune-mediated CNS demyelination

    Traka, Maria; Podojil, Joseph R.; McCarthy, Derrick P.; Miller, Stephen D.; Popko, Brian

    2015-01-01

    Although multiple sclerosis is a common neurological disorder, the origin of the autoimmune response against myelin, which is the characteristic feature of the disease, remains unclear. To investigate whether oligodendrocyte death could cause this autoimmune response, we examined the oligodendrocyte ablation Plp1-CreERT;ROSA26-eGFP-DTA (DTA) mouse model. Approximately 30 weeks after recovering from oligodendrocyte loss and demyelination, DTA mice develop a fatal secondary disease characterize...

  9. Oligodendrocyte death results in immune-mediated CNS demyelination

    Traka, Maria; Podojil, Joseph R; McCarthy, Derrick P; Miller, Stephen D; Popko, Brian

    2016-01-01

    Although multiple sclerosis is a common neurological disorder, the origin of the autoimmune response against myelin, which is the characteristic feature of the disease, remains unclear. To investigate whether oligodendrocyte death could cause this autoimmune response, we examined the oligodendrocyte ablation Plp1-CreERT;ROSA26-eGFP-DTA (DTA) mouse model. Approximately 30 weeks after recovering from oligodendrocyte loss and demyelination, DTA mice develop a fatal secondary disease characterized by extensive myelin and axonal loss. Strikingly, late-onset disease was associated with increased numbers of T lymphocytes in the CNS and myelin oligodendrocyte glycoprotein (MOG)-specific T cells in lymphoid organs. Transfer of T cells derived from DTA mice to naive recipients resulted in neurological defects that correlated with CNS white matter inflammation. Furthermore, immune tolerization against MOG ameliorated symptoms. Overall, these data indicate that oligodendrocyte death is sufficient to trigger an adaptive autoimmune response against myelin, suggesting that a similar process can occur in the pathogenesis of multiple sclerosis. PMID:26656646

  10. Unmet challenges in immune-mediated hepatobiliary diseases.

    Beuers, Ulrich; Gershwin, M Eric

    2015-06-01

    It is ironic that the liver, which serves a critical function in immune tolerance, itself becomes the victim of an autoimmune attack. Indeed, liver autoimmunity and the autoimmune diseases associated with both innate and adaptive responses to hepatocytes and/or cholangiocytes are models of human autoimmunity. For example, in primary biliary cirrhosis, there exists a well-defined and characteristic autoantibody and considerable homogeneity between patients. In autoimmune hepatitis, there are clinical characteristics that allow a rigorous subset definition and well-defined inflammatory infiltrates. In both cases, there are defects in a variety of immune pathways and including regulatory cells. In primary sclerosing cholangitis, with its characteristic overlap with inflammatory bowel disease, there are unique defects in innate immunity and particular important contribution of lymphoid homing to disease pathogenesis. In these diseases, as with other human autoimmune processes, there is the critical understanding that pathogenesis requires a genetic background, but is determined by environmental features, and indeed the concordance of these diseases in identical twins highlights the stochastic nature of immunopathology. Unfortunately, despite major advances in basic immunology and in immunopathology in these diseases, there remains a major void in therapy. The newer biologics that are so widely used in rheumatology, neurology, and gastroenterology have not yet seen success in autoimmune liver disease. Future efforts will depend on more rigorous molecular biology and systems analysis in order for successful application to be made to patients. PMID:25820618

  11. Proline Rich Motifs as Drug Targets in Immune Mediated Disorders

    Mythily Srinivasan

    2012-01-01

    Full Text Available The current version of the human immunome network consists of nearly 1400 interactions involving approximately 600 proteins. Intermolecular interactions mediated by proline-rich motifs (PRMs are observed in many facets of the immune response. The proline-rich regions are known to preferentially adopt a polyproline type II helical conformation, an extended structure that facilitates transient intermolecular interactions such as signal transduction, antigen recognition, cell-cell communication and cytoskeletal organization. The propensity of both the side chain and the backbone carbonyls of the polyproline type II helix to participate in the interface interaction makes it an excellent recognition motif. An advantage of such distinct chemical features is that the interactions can be discriminatory even in the absence of high affinities. Indeed, the immune response is mediated by well-orchestrated low-affinity short-duration intermolecular interactions. The proline-rich regions are predominantly localized in the solvent-exposed regions such as the loops, intrinsically disordered regions, or between domains that constitute the intermolecular interface. Peptide mimics of the PRM have been suggested as potential antagonists of intermolecular interactions. In this paper, we discuss novel PRM-mediated interactions in the human immunome that potentially serve as attractive targets for immunomodulation and drug development for inflammatory and autoimmune pathologies.

  12. Immune-mediated mechanisms influencing the efficacy of anticancer therapies.

    Coffelt, Seth B; de Visser, Karin E

    2015-04-01

    Conventional anticancer therapies, such as chemotherapy, radiotherapy, and targeted therapy, are designed to kill cancer cells. However, the efficacy of anticancer therapies is not only determined by their direct effects on cancer cells but also by off-target effects within the host immune system. Cytotoxic treatment regimens elicit several changes in immune-related parameters including the composition, phenotype, and function of immune cells. Here we discuss the impact of innate and adaptive immune cells on the success of anticancer therapy. In this context we examine the opportunities to exploit host immune responses to boost tumor clearing, and highlight the challenges facing the treatment of advanced metastatic disease. PMID:25857662

  13. Supplemental vitamin A prevents the acute radiation-induced defect in wound healing

    Acute radiation injury leads to thymic involution, adrenal enlargement, leukopenia, thrombocytopenia, gastrointestinal ulceration, and impaired wound healing. The authors hypothesized that supplemental vitamin A would mitigate these adverse effects in rats exposed to acute whole-body radiation. To test their hypothesis, dorsal skin incisions and subcutaneous implantation of polyvinyl alcohol sponges were performed in anesthetized Sprague-Dawley rats at varying times following sham radiation or varying doses of whole-body radiation (175-850 rad). In each experiment, the control diet [which contains about 18,000 IU vit. A/kg chow (3 X the NRC RDA for normal rats)] was supplemented with 150,000 IU vit. A/kg diet beginning at, before, or after sham radiation and wounding or radiation and wounding. The supplemental vitamin A prevented the impaired wound healing and lessened the weight loss, leukopenia, thrombocytopenia, thymic involution, adrenal enlargement, decrease in splenic weight, and gastric ulceration of the radiated (750-850 rad) wounded rats. This was true whether the supplemental vitamin A was begun before (2 or 4 days) or after (1-2 hours to 4 days) radiation and wounding; the supplemental vitamin A was more effective when started before or up to 2 days after radiation and wounding. The authors believe that prevention of the impaired wound healing following radiation by supplemental vitamin A is due to its enhancing the early inflammatory reaction to wounding, including increasing the number of monocytes and macrophages at the wound site; possible effect on modulating collagenase activity; effect on epithelial cell (and possible mesenchymal cell) differentiation; stimulation of immune responsiveness; and lessening of the adverse effects of radiation

  14. Management Of Acute Migraine

    Mehndiratta M

    2002-01-01

    Full Text Available Pharmacotherapy for migraine involves treatment for the acute attack as well as using long-term prophylaxis in order to reduce the frequency and severity of the attacks. Based on severity, there are a number of drugs available to treat the acute attacks. For mild to moderate attacks, analgesics, NSAIDs and Ergotamine are effective but severe attacks may need Dihydroergotamine (DHE or a triptan. Sumatriptan and the second generation triptans have revolutionized the acute treatment of migraine. Early and appropriate treatment holds the key to successful therapy of the acute attack. This article discusses the various acute treatment options available.

  15. Acute loss of consciousness.

    Tristán, Bekinschtein; Gleichgerrcht, Ezequiel; Manes, Facundo

    2015-01-01

    Acute loss of consciousness poses a fascinating scenario for theoretical and clinical research. This chapter introduces a simple yet powerful framework to investigate altered states of consciousness. We then explore the different disorders of consciousness that result from acute brain injury, and techniques used in the acute phase to predict clinical outcome in different patient populations in light of models of acute loss of consciousness. We further delve into post-traumatic amnesia as a model for predicting cognitive sequels following acute loss of consciousness. We approach the study of acute loss of consciousness from a theoretical and clinical perspective to conclude that clinicians in acute care centers must incorporate new measurements and techniques besides the classic coma scales in order to assess their patients with loss of consciousness. PMID:25702218

  16. Therapeutic plasma exchange in acute disseminated encephalomyelitis in children.

    Borras-Novell, Cristina; García Rey, Enric; Perez Baena, Luis Francisco; Jordan Garcia, Iolanda; Catella Cahiz, Dolors; Cambra, Francisco

    2015-12-01

    Acute disseminated encephalomyelitis (ADEM) is an inflammatory demyelinating disease of the central nervous system that is probably due to an autoimmune mechanism with an acute presentation and a monophasic course. The management of patients with ADEM is based on supportive therapy, corticosteroids, and intravenous immunoglobulin, and in selected cases, with therapeutic plasma exchange (TPE). The aim of our study is to evaluate the efficacy of TPE, as adjuvant therapy in pediatric patients with ADEM. We retrospectively reviewed the medical records of children with the diagnosis of ADEM between 2009 and 2011 to which TPE was indicated and were admitted in the ICU of Hospital Sant Joan de Deu (Spain). The diagnosis of ADEM was made by clinical and laboratory criteria and by the presence of compatible lesions on cranio-spinal Magnetic Resonance Imaging (MRI). For signaling TPE, we followed the guidelines established by the American Association of Apheresis (ASFA) in 2010. Five cases were identified. The predominant neurological symptoms in our patients were: altered level of consciousness, seizures, motor deficits, cranial nerve disorders, and aphasia. Most important demyelinating lesions were located in cortical and subcortical white matter of the brain and highlighted brainstream. Patients performed between 4 and 5 sessions, with no reported side effects. Progressive clinical improvement was evident in all patients, with good neurosensory response to stimulation, cessation of seizures, and recovery of limb mobility. Nowadays, one patient's right paresis persists and another suffers epileptic seizures. None of the cases in our series presented new episodes of demyelination. Due to the suggested immune-mediated pathogenesis of ADEM, treatment is based on immunomodulatory agents, being glucocorticoids the most important ones. The treatment can be complemented with intravenous immunoglobulin and plasmapheresis. Available data suggests that plasma exchange is beneficial

  17. Acute pancreatitis in acute viral hepatitis

    2007-01-01

    AIM: To elucidate the frequency and characteristics of pancreatic involvement in the course of acute (nonfulminant) viral hepatitis.METHODS: We prospectively assessed the pancreatic involvement in patients with acute viral hepatitis who presented with severe abdomimanl pain.RESULTS: We studied 124 patients with acute viral hepatitis, of whom 24 presented with severe abdominal pain. Seven patients (5.65%) were diagnosed to have acute pancreatitis. All were young males. Five patients had pancreatitis in the first week and two in the fourth week after the onset of jaundice. The pancreatitis was mild and all had uneventful recovery from both pancreatitis and hepatitis on conservative treatment.The etiology of pancreatitis was hepatitis E virus in 4,hepatitis A virus in 2, and hepatitis B virus in 1 patient.One patient had biliary sludge along with HEV infection.The abdominal pain of remaining seventeen patients was attributed to stretching of Glisson's capsule.CONCLUSION: Acute pancreatitis occurs in 5.65% of patients with acute viral hepatitis, it is mild and recovers with conservative management.

  18. Acute chylous peritonitis due to acute pancreatitis.

    Georgiou, Georgios K; Harissis, Haralampos; Mitsis, Michalis; Batsis, Haralampos; Fatouros, Michalis

    2012-04-28

    We report a case of acute chylous ascites formation presenting as peritonitis (acute chylous peritonitis) in a patient suffering from acute pancreatitis due to hypertriglyceridemia and alcohol abuse. The development of chylous ascites is usually a chronic process mostly involving malignancy, trauma or surgery, and symptoms arise as a result of progressive abdominal distention. However, when accumulation of "chyle" occurs rapidly, the patient may present with signs of peritonitis. Preoperative diagnosis is difficult since the clinical picture usually suggests hollow organ perforation, appendicitis or visceral ischemia. Less than 100 cases of acute chylous peritonitis have been reported. Pancreatitis is a rare cause of chyloperitoneum and in almost all of the cases chylous ascites is discovered some days (or even weeks) after the onset of symptoms of pancreatitis. This is the second case in the literature where the patient presented with acute chylous peritonitis due to acute pancreatitis, and the presence of chyle within the abdominal cavity was discovered simultaneously with the establishment of the diagnosis of pancreatitis. The patient underwent an exploratory laparotomy for suspected perforated duodenal ulcer, since, due to hypertriglyceridemia, serum amylase values appeared within the normal range. Moreover, abdominal computed tomography imaging was not diagnostic for pancreatitis. Following abdominal lavage and drainage, the patient was successfully treated with total parenteral nutrition and octreotide. PMID:22563182

  19. Acute chylous peritonitis due to acute pancreatitis

    Georgios K Georgiou; Haralampos Harissis; Michalis Mitsis; Haralampos Batsis; Michalis Fatouros

    2012-01-01

    We report a case of acute chylous ascites formation presenting as peritonitis (acute chylous peritonitis) in a patient suffering from acute pancreatitis due to hypertriglyceridemia and alcohol abuse.The development of chylous ascites is usually a chronic process mostly involving malignancy,trauma or surgery,and symptoms arise as a result of progressive abdominal distention.However,when accumulation of "chyle" occurs rapidly,the patient may present with signs of peritonitis.Preoperative diagnosis is difficult since the clinical picture usually suggests hollow organ perforation,appendicitis or visceral ischemia.Less than 100 cases of acute chylous peritonitis have been reported.Pancreatitis is a rare cause of chyloperitoneum and in almost all of the cases chylous ascites is discovered some days (or even weeks) after the onset of symptoms of pancreatitis.This is the second case in the literature where the patient presented with acute chylous peritonitis due to acute pancreatitis,and the presence of chyle within the abdominal cavity was discovered simultaneously with the establishment of the diagnosis of pancreatitis.The patient underwent an exploratory laparotomy for suspected perforated duodenal ulcer,since,due to hypertriglyceridemia,serum amylase values appeared within the normal range.Moreover,abdominal computed tomography imaging was not diagnostic for pancreatitis.Following abdominal lavage and drainage,the patient was successfully treated with total parenteral nutrition and octreotide.

  20. Acute renal failure associated with nonfulminant acute viral hepatitis A

    Sarawgi, S.; Gupta, A. K.; Arora, D S; Jasuja, S.

    2008-01-01

    Hepatitis A runs a benign course in children, but may have atypical presentations in adults. Very rarely acute renal failure complicates nonfulminant hepatitis A. We report a patient with nonfulminant acute viral hepatitis A with multiorgan involvement. Patient had biopsy proven acute interstitial nephritis, acute pancreatitis, acute myocarditis and required hemodialysis for 6 weeks.