WorldWideScience

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. 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 )

  14. 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

  15. 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...

  16. 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...

  17. 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...

  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. 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.

  7. 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,...

  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. 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...

  9. 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

  10. 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...

  11. 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.

  12. 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.

  13. 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...

  14. 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...

  15. 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...

  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. 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.

  9. 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.

  10. 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

  11. 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

  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. 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

  17. 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

  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. 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

  1. 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

  2. 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...

  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. 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

  9. 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

  10. 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)

  11. 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

  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. 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

  19. 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.

  20. 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

  1. 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

  2. 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

  3. 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.

  4. 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

  5. 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

  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. 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

  2. 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

  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. 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.

  8. 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%.

  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

    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

  11. 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

  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. 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.

  15. 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...

  16. 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

  17. 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

  18. 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

  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. 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

  1. 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

  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. 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

  9. 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

  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. 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

  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. 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...

  18. 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....

  19. 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.

  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. 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

  8. 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

  9. 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

  10. 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.

  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. 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...

  18. 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.

  19. 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

  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. 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

  3. 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.

  4. 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...

  5. 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...

  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. [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

  9. 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...

  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. 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...

  13. 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.

  14. 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.

  15. 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

  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. 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

  19. 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

  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...