1/73. Cryosupernatant plasma exchange in the treatment of antiphospholipid antibody syndrome with lupus nephritis.We report a case of a 22-year-old female with antiphospholipid antibody syndrome (APS) associated with systemic lupus erythematosus in whom cryosupernatant plasma exchange was effective and improved both the refractory venous thrombosis in her legs and relapsing thrombocytopenia. A renal biopsy specimen showed not only features of active lupus nephritis but also renal arteriolar thrombosis which is considered to be a type of thrombotic microangiopathy (TMA). Because a pathological role of unusually large von willebrand factor (vWF) multimers has been reported in patients with TMA including thrombotic thrombocytopenic purpura, plasma exchange using replacement with cryosupernatant, which is free of unusually large vWF multimers, is likely to be an option of treatment modality for patients with refractory and chronic relapsing APS manifesting TMA.- - - - - - - - - - ranking = 1keywords = von (Clic here for more details about this article) |
2/73. 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 = 2keywords = von (Clic here for more details about this article) |
3/73. Thrombotic thrombocytopenic purpura in a patient with rheumatoid arthritis treated by plasmapheresis.Thrombotic thrombocytopenic purpura (TTP) is a multisystem disorder characterized by consumptive thrombocytopenia, microangiopathic hemolytic anemia, and neurologic symptoms. TTP is associated with many diseases and several therapeutic drugs. We report the rare case of a patient with rheumatoid arthritis who developed TTP that was not associated with drug therapy, 18 months after the onset of rheumatoid arthritis. She recovered from the TTP following daily sessions of therapeutic plasma exchange (TPE) with fresh frozen plasma replacement and glucocorticoid therapy. Recent pathogenic mechanisms are reviewed as they relate to von willebrand factor. In this report of the rare association of TTP with rheumatoid arthritis, an immediate relationship is likely because both are of an immune nature. awareness of the possible development of TTP in rheumatoid arthritis is important for early diagnosis and treatment.- - - - - - - - - - ranking = 1keywords = von (Clic here for more details about this article) |
4/73. Effects of intravenous immunoglobulin in a patient with intermittent thrombotic thrombocytopenic purpura.We describe a patient with a 9-year history of thrombotic thrombocytopenic purpura (TTP) who exhibited four relapses. Intravenous immunoglobulin (IVIg) was effective for these four episodes. The patient was well and the laboratory findings were within normal ranges between each episode, although unusually large von willebrand factor multimers were observed during remission. Our results suggest the usefulness of IVIg at the time of relapse in the treatment of patients with TTP who have multiple relapses over a long period.- - - - - - - - - - ranking = 1keywords = von (Clic here for more details about this article) |
5/73. Mycoplasma-pneumoniae-induced thrombotic thrombocytopenic purpura.Thrombotic thrombocytopenic purpura (TTP) is a fatal disease characterized by widespread platelet aggregation, hemolytic anemia and fever with renal and neurological involvement. Different factors have been associated with the development of TTP, e.g. infections, pregnancy, chemotherapy, drug therapy and bone marrow transplantation. Recent data imply that all these different causes may induce the disease by decreasing the activity of the plasma von willebrand factor-cleaving protease resulting in unusually large von willebrand factor multimers that later on initiate the cascade of TTP. In this communication, we present a unique association between infection with mycoplasma pneumoniae and TTP. We believe that the emergence of antibodies that cross-react with Mycoplasma and the protease might elucidate in this case the pathogenesis of TTP.- - - - - - - - - - ranking = 2keywords = von (Clic here for more details about this article) |
6/73. Autosomal recessive inheritance of von willebrand factor-cleaving protease deficiency.A child with chronic relapsing thrombotic thrombocytopenic purpura (TTP/HUS) had recurrent thrombocytopenia, microangiopathic hemolytic anemia with fragmented erythrocytes, microthrombi in the lung vessels, and renal dysfunction. Assay of von willebrand factor (vWF)-cleaving protease showed a complete protease deficiency in the patient and subnormal activities in the mother and in two asymptomatic siblings. No inhibitor of vWF-cleaving protease was detected in the patient's plasma. Periodic transfusions of fresh-frozen plasma prevented further acute episodes of TTP/HUS. Specific diagnosis of the constitutional deficiency of vWF-cleaving protease helps to provide successful prophylactic therapy.- - - - - - - - - - ranking = 5keywords = von (Clic here for more details about this article) |
7/73. High titers of inhibitors of von willebrand factor-cleaving metalloproteinase in a fatal case of acute thrombotic thrombocytopenic purpura.Acute thrombotic thrombocytopenic purpura is a disease with diffuse platelet thrombi in the microcirculation. Despite plasma exchange therapy, approximately 20 percent of the patients succumb to the disease. A significant number of the survivors suffer one or more relapses. This study investigated the activity of von willebrand factor-cleaving metalloproteinase and the titers of IgG inhibitors to the proteinase in serial plasma samples from a patient who died during a relapse of the disease despite continued plasma exchanges. A deficiency in the von willebrand factor-cleaving metalloproteinase activity, due to inhibitory IgG, was detected at presentation. After initiation of plasma exchange, a transient increase in proteinase activity coincided with clinical remission. When thrombocytopenia relapsed, the activity of the proteinase also declined to undetectable levels. Toward the end of her course, proteinase levels raised by plasma exchange were not sustained because the proteinase activity was quickly neutralized by rising titers of inhibitors. High titers of inhibitors of von willebrand factor-cleaving metalloproteinase cause refractoriness to standard plasma therapy. These findings suggest that intensive plasma exchanges and measures that suppress antibody titers may prevent death and promote remission in refractory cases.- - - - - - - - - - ranking = 7keywords = von (Clic here for more details about this article) |
8/73. 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 = von (Clic here for more details about this article) |
9/73. Ten years of prophylactic treatment with fresh-frozen plasma in a child with chronic relapsing thrombotic thrombocytopenic purpura as a result of a congenital deficiency of von willebrand factor-cleaving protease.We report the results of 10 years of prophylactic fresh-frozen plasma (FFP) infusion therapy in a 14-year-old girl with chronic relapsing thrombotic thrombocytopenic purpura (TTP), in whom a severe congenital von willebrand factor (VWF)-cleaving protease deficiency has been documented. Severe haemolytic crises triggered by infections were prevented and her present renal and neurological functions have been preserved. Sequential measurements of protease activity and platelet count after FFP infusion led us to conclude tentatively that 5% may be sufficient to degrade very large and adhesive VWF multimers.- - - - - - - - - - ranking = 5keywords = von (Clic here for more details about this article) |
10/73. Frequently relapsing thrombotic thrombocytopenic purpura treated with cytotoxic immunosuppressive therapy.BACKGROUND AND OBJECTIVES: Treatment of thrombotic thrombocytopenic purpura (TTP) with plasma exchange has reduced mortality rates from 90% in untreated cases to less than 20%. Despite plasma exchange, relapses may occur in as many as 40% of cases. Multiple relapses occur in a minority but pose a significant therapeutic challenge. Recent evidence supports the presence of an autoantibody which inhibits proteolysis of von willebrand factor (vWF) in active TTP, allowing large multimers of vWF to form and promote platelet aggregation. Additional evidence suggests autoantibodies activate capillary endothelium and promote platelet aggregation in the microcirculation. immunosuppression, thus, has a biologically plausible role in TTP. We describe three consecutive cases of relapsing TTP treated with cytotoxic therapy to highlight the potential role of immunosuppression. DESIGN AND methods: Cytotoxic immunosuppressive therapy with either cyclophosphamide or azathioprine was used in three consecutive patients with frequently relapsing TTP. RESULTS: All three patients have maintained remissions of 8 to 10 months without recurrence. INTERPRETATION AND CONCLUSIONS: Cytotoxic immunosuppressive therapy may have a role in inducing long-term remissions in recurrent TTP.- - - - - - - - - - ranking = 1keywords = von (Clic here for more details about this article) |
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