1/17. New strategies in diagnosis and treatment of thrombotic thrombocytopenic purpura: case report and review.The pentad of thrombocytopenia, haemolytic anaemia, mild renal dysfunction, neurological signs and fever, classically characterizes the syndrome of thrombotic thrombocytopenic purpura (TTP). TTP usually occurs in adults but also children have been described with this condition. The disorder may take a relapsing course, termed chronic relapsing TTP (CRTTP), which although very rare, may also begin in childhood. Deficiency of a recently identified enzyme, the von Willebrand factor (vWF)-cleaving protease, seems to play a major role in the development of TTP. We report on a 3-year-old boy with a dramatic but typical clinical course of CRTTP. At the time of diagnosis, neurological deficits and multiple cerebral infarctions had already occurred. In plasma, vWF-cleaving protease was completely absent, both during acute TTP and in remission. There was no protease inhibitor detected. Regular infusions of fresh frozen plasma were successfully given for replacement on a prophylactic basis. CONCLUSION: Assay of von willebrand factor-cleaving protease helps to diagnose a form of thrombotic thrombocytopenic purpura which may be managed by prophylactic treatment with fresh frozen plasma.- - - - - - - - - - ranking = 1keywords = anaemia (Clic here for more details about this article) |
2/17. von willebrand factor--cleaving protease activity in congenital thrombotic thrombocytopenic purpura.Thrombotic thrombocytopenic purpura (TTP) is characterized by microangiopathic haemolytic anaemia (MAHA), thrombocytopenia, fluctuating neurological impairment, renal dysfunction and fever. Both acquired and congenital forms are recognized. Recurrent episodes, which may be predictable (occurring every 21-28 d), are seen in congenital disease and may be treated by infusion with fresh-frozen plasma (FFP). Congenital TTP has recently been associated with deficiency of a novel von willebrand factor (VWF)-cleaving protease. To investigate whether residual protease activity dictates clinical manifestations, we determined protease activity in three patients with congenital TTP of varying severity. Intrinsic VWF-cleaving protease activity of a range of plasma-derived products was also assessed as one patient had been successfully maintained for many years, initially using an intermediate-purity factor viii concentrate (Kryobulin) and then cryoprecipitate. All three patients had a severe absolute deficiency of VWF-cleaving protease activity (< 3%) up to 5 months after clinical symptoms. Three relatives were also found to have a mild reduction in protease activity (25-50%). Nevertheless, the intrinsic VWF-cleaving protease activity of plasma-derived products correlated with their clinical efficacy: significant (100%) protease activity was found in FFP, cryosupernatant, solvent-detergent-treated plasma, cryoprecipitate and Kryobulin. Two clinically ineffective factor viii products (Fahndi and Haemate P) possessed only low protease activity (6.25% and 12.5% respectively). Although this suggests that VWF-cleaving protease activity is central to the pathogenesis of congenital TTP, either small differences in protease activity below 3% or hitherto unknown factors have a profound influence on clinical phenotype. The possible use of factor viii concentrates in the treatment of this condition also warrants further investigation.- - - - - - - - - - ranking = 1keywords = anaemia (Clic here for more details about this article) |
3/17. von willebrand factor-cleaving protease inhibitor in a patient with human immunodeficiency syndrome-associated thrombotic thrombocytopenic purpura.antibodies that inhibit von willebrand factor (VWF)-cleaving protease activity occur in patients with acute thrombotic thrombocytopenic purpura (TTP) and often persist in the chronic phase. A deficiency of this protease is likely to be responsible for the generation of ultrahigh VWF multimers and influence the formation of intra-arterial platelet aggregates that result in microangiopathic haemolytic anaemia, thrombocytopenia and end in organ failure. This report demonstrates complete deficiency of VWF-cleaving protease and the presence of a concentration-dependent IgG1 inhibitor in the plasma of a patient with acquired immunodeficiency syndrome (AIDS). These data may contribute to understanding the pathophysiology of human immunodeficiency syndrome (hiv)-related TTP.- - - - - - - - - - ranking = 1keywords = anaemia (Clic here for more details about this article) |
4/17. Thrombotic thrombocytopenic purpura as an initial presentation of primary sjogren's syndrome.A healthy woman presented with ecchymoses due to thrombocytopenia, with numerous bone marrow megakaryocytes, microangiopathic haemolytic anaemia, disorientation, irritability, and normal renal function. Thrombotic thrombocytopenic purpura (TTP) was diagnosed and treated successfully by plasma exchange therapy, both on presentation and during a further three relapses. The TTP was considered idiopathic until, 4 months later, definite primary sjogren's syndrome (1 degree SS) was diagnosed following the appearance of sicca symptoms. Only four similar cases have been cited in the literature. TTP should be added to the varied haematological manifestations that may occur in patients with 1 degree SS. The possible presentation of 1 degree SS not with classic sicca symptoms but rather with haematological abnormalities, including TTP, should be recognised.- - - - - - - - - - ranking = 1keywords = anaemia (Clic here for more details about this article) |
5/17. Remission of thrombotic thrombocytopenic purpura in a patient with compound heterozygous deficiency of von willebrand factor-cleaving protease by infusion of solvent/detergent plasma.plasma exchange or plasma infusion is considered to be the therapy of choice in patients with thrombotic thrombocytopenic purpura (TTP) who are deficient in von Willebrand factor-cleaving protease (VWF-CP). Recently, mutations in the ADAMTS 13 gene were identified as being responsible for VWF-CP deficiency in patients with familial TTP (VWF-CP deficiency in the absence of an inhibitor). Here we report on a girl who presented with recurrent thrombocytopenia and anaemia since birth, developing the full pentad of characteristic TTP at the age of 16 y. Congenital TTP was confirmed on the basis of severe VWF-CP deficiency in the absence of an acquired inhibitor. The patient was found to be compound heterozygous for two hitherto undescribed mutations in the ADAMTS 13 gene: a truncating frame shift mutation, 4143insA in exon 29, and the nonsense mutation 3100A >T in exon 24 (R1034X). After infusion of solvent/detergent plasma, the patient went into remission and remained asymptomatic under regular plasma therapy at 2-wk intervals for over two years. Conclusion: TTP in childhood may be mild and oligosymptomatic. Determination of VWF-CP activity is helpful in the differential diagnosis of thrombocytopenia.- - - - - - - - - - ranking = 1keywords = anaemia (Clic here for more details about this article) |
6/17. Double relapse of incomplete form of thrombotic thrombocytopenic purpura.BACKGROUND: Although several etiologies can be identified in thrombotic thrompocytopenic purpura (TTP), idiopathic cases are still frequent. Incomplete forms are rare and the diagnosis should be suspected in case of thrombocytopenia and microangiopathic haemolytic anaemia. Relapses are frequent in the complete classic form but rarely reported in incomplete forms. According to the literature, mortality and morbidity are significantly improved with plasma exchange (PE). Nevertheless, the management and treatment of relapses remain problematic. CASE REPORT: A 35-year-old woman presented with a double relapse of an incomplete TTP form in the second (24 months) and the fourth year (40 months) after the initial episode. The patient underwent plasma infusion, PE, and was then started on corticosteroids. She also received antiplatelet agents. The main biological indicators were platelet count, haematocrit, lactate dehydrogenase level and schistocytes. Following this treatment, the patient's condition rapidly improved. CONCLUSION: In this incomplete form of TTP, two relapses occurred, with the same presentation. Standard therapy was effective in this case.- - - - - - - - - - ranking = 1keywords = anaemia (Clic here for more details about this article) |
7/17. Schistocytic anaemia, severe thrombocytopenia, and renal dysfunction: thrombotic microangiopathy due to severe acquired ADAMTS-13 deficiency. Case 2.We present the case of a woman (age: 64 years) with acute thrombotic microangiopathy due to severe acquired ADAMTS-13 (von willebrand factor-cleaving protease) deficiency. She was successfully treated with plasma exchange therapy and glucocorticosteroids. She relapsed seven months later, and splenectomy led to lasting remission. Pathomechanisms of thrombotic thrombocytopenic purpura, especially the role of ADAMTS-13, are discussed and therapeutic measures outlined.- - - - - - - - - - ranking = 4keywords = anaemia (Clic here for more details about this article) |
8/17. Rituximab for chronic recurring thrombotic thrombocytopenic purpura: a case report and review of the literature.Deficiency of von willebrand factor (VWF) cleaving protease ADAMTS13 has been demonstrated to be the proximate cause of a subset of thrombotic microangiopathic haemolytic anaemias (MAHA) typical for thrombotic thrombocytopenic purpura (TTP). ADAMTS13 gene mutations cause the hereditary form; acquired deficiency has been attributed to presence of an autoantibody, which may represent a specific subset of MAHA best termed 'autoimmune thrombotic thrombocytopenic purpura'. We describe a patient with relapsing TTP because of ADAMTS13 inhibitors, who failed to achieve sustained remission despite therapies with plasma exchange, steroids, vincristine, staphylococcal protein a and splenectomy. The ADAMTS13 inhibitor titre remained elevated and clinical stability was only maintained by plasma exchange every 2-3 d over a period of 268 d. The patient then received rituximab therapy (eight doses of 375 mg/m2 weekly), during which she required five plasma exchanges in the first 10 d, two exchanges in the next 3 weeks, and none thereafter for 450 d and ongoing. The ADAMTS13 inhibitor titre decreased and enzyme activity increased. We compared this case with that of seven previously reported TTP cases also treated with rituximab; experience suggests that rituximab therapy deserves further investigation for patients with either refractory or relapsing TTP caused by ADAMTS13 inhibitors.- - - - - - - - - - ranking = 1keywords = anaemia (Clic here for more details about this article) |
9/17. Thrombotic microangiopathy: an atypical cause of acute renal failure in patients with acute pancreatitis.OBJECTIVE: To report on the development and treatment of thrombotic microangiopathy, an atypical cause of acute renal failure in patients with acute pancreatitis. DESIGN: case reports. SETTING: A 21-bed medical intensive care unit at an university hospital. patients: Two men with acute pancreatitis presented with acute renal failure, neurological manifestations, haemolytic anaemia and thrombocytopenia. Both patients required intensive care. MEASUREMENTS: Fragmented red cell count; levels of haptoglobin, amylase and lipase; serological testing for escherichia coli o157; computed tomography of the abdomen. MAIN RESULTS: The patients' courses were rapidly favourable after daily plasma exchange. A review of the existing medical literature was also undertaken. CONCLUSION: As thrombotic microangiopathy may be life-threatening without administration of fresh frozen plasma or plasma exchange, physicians should consider this disease as a possible cause of acute renal failure in patients with acute pancreatitis.- - - - - - - - - - ranking = 1keywords = anaemia (Clic here for more details about this article) |
10/17. Thrombotic thrombocytopenic purpura associated with statin treatment.Thrombotic thrombocytopenic purpura (TTP) is a rare condition but associated with 90% mortality if left untreated. The diagnosis is usually made when there is thrombocytopenia and microangiopathic haemolytic anaemia, although the full pentad also includes fever, renal impairment, and neurological dysfunction. A variety of underlying causes have been implicated in acquired TTP including bacterial and viral infections, bone marrow and organ transplantation, pregnancy, immune disorders, and certain drugs. To date there is just one case report of TTP associated with statin treatment. The clinical course of a patient who presented with TTP after being started on simvastatin, a HMG-CoA inhibitor, is described.- - - - - - - - - - ranking = 1keywords = anaemia (Clic here for more details about this article) |
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