Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0002878 (hemolytic anemia)
 7,530 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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.
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PMID:Autosomal recessive inheritance of von Willebrand factor-cleaving protease deficiency. 1095 22

Infantile or congenital cases of thrombotic microangiopathy have been reported that were familial and characterized by ongoing microangiopathic hemolysis and thrombocytopenia in the absence of regular fresh-frozen plasma transfusions. The authors describe a child with congenital microangiopathic hemolytic anemia and thrombocytopenia (CMHAT) who has received regular fresh-frozen plasma transfusions since infancy and has never had thrombotic complications. von Willebrand factor (vWF)-cleaving protease activity was studied in the patient's pretransfusion and posttransfusion plasma samples as well as in her parents' plasma. The effects of the patient's and a control subject's plasma on human microvascular endothelial cells were also investigated. Unusually large vWF multimers were present in the patient's plasma both before transfusion (thrombocytopenic) and after transfusion. Unlike cases of chronic relapsing thrombotic thrombocytopenic purpura, vWF-cleaving protease activity was present and treatment of cultured human endothelial cells with the patient's plasma did not induce apoptosis. These findings suggest that the patient with CMHAT may represent a different group in the broad spectrum of thrombotic microangiopathies.
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PMID:Congenital microangiopathic hemolytic anemia and thrombocytopenia with unusually large von Willebrand factor multimers and von Willebrand factor-cleaving protease. 1156 71

Thrombotic microangiopathies (TMA) encompass various severe diseases characterized by microangiopathic hemolytic anemia and peripheral thrombocytopenia, associated with fever, neurological signs and renal involvement. Microvascular thrombosis is the typical lesion, and results in tissue ischemia. Thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS) are the two most classical forms. These two entities are clinically and histopathologically closely related. There is a body of evidence suggesting that endothelial cell injury is the initial event in TTP and HUS, and that it may be related to a large number of triggering factors, such as infection, connective tissue disease, drugs, cancer and chemotherapy, transplantation, and pregnancy. Endothelial cell injury enhances the release of ultra large forms of von Willebrand factor (ULvWF) multimers and other prothrombotic agents, such as plasminogen activator inhibitor and platelet activating factor, whereas it decreases the release of prostaglandin-I2, a strong inhibitor of platelet aggregation. Recently however, it has been shown that TTP and HUS were pathophysiologically distinct. Actually, TTP is associated with a deficiency in von Willebrand factor-cleaving protease, an enzyme involved in cleavage of ULvWF into circulating 200 kDa and 350 kDa fragments. This deficiency may be either congenital or acquired, and then related to an IgG inhibitory autoantibody. This protease deficiency may account for the high amounts of plasmatic ULvWF in TTP patients. In HUS, vWF-cleaving protease activity is found normal. HUS encompasses two distinct entities. Epidemic, or diarrhea-associated HUS, is associated with verotoxin or Shiga toxin-associated enterobacteriaceae. These toxins are directly responsible for endothelial cell injury. Sporadic HUS (also termed atypical HUS in children) is closely related to TTP, and shares the same triggering factors. Familial HUS has been associated in some cases with hypocomplementemia and factor H dysfunction, the pathophysiological role of which remains unclear. The study of the different triggering factors and predisposing factors may be useful to define different subsets of TMA, that may be characterized by their course and prognosis.
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PMID:[Pathophysiology of thrombotic microangiopathies: current understanding]. 1221 98

Thrombotic thrombocytopenic purpura(TTP) is a multisystem disorders characterized by thrombocytopenia, microangiopathic hemolytic anemia associated with red cell fragmentation, and neurological and renal symptoms. Plasma of patients with TTP has been shown to contain unusually large von Willebrand factor(vWF) multimers that may cause platelet agglutination in vivo. Recently, a metalloprotease responsible for cleavage of vWF multimers has been isolated from normal human plasma and was found to be deficient in some patients with TTP. We examined the activity of the vWF-cleaving protease(vWF-CP), by modified Furlan's method, in plasma from patients with a familial TTP, 3 acquired TTP, 4 thrombotic microangiopathy(TMA) and 2 veno-occlusive disease(VOD) associated after allo-BMT. Diluted plasma samples of patients were incubated with protease-free vWF purified from normal human plasma, in the presence of urea and barium ions. The extent of vWF degradation was assayed by electrophoresis in SDS-agarose gels and immunoblotting. Activity of vWF-CP from 12 normal plasma have been shown as 77-180%(average 115%), whereas, no vWF-CP(below 5%) was observed in plasma from familial TTP, before and after plasma exchange, although FFP infusion therapy has been effective for this patient to recover thrombocytopenia. In 3 acquired TTP, 2 patients showed lack of vWF-CP activity in plasma, and inhibitors against vWF-CP have been elucidated by plasma cross-mixing test. After extensive plasma exchange and FFP infusion followed by corticosteroid therapy, normal vWF-CP was recovered in plasma from 2 acquired TTP patients. Among BMT patients, plasma from 4 BMT-TMA showed normal vWF-CP activities as 55-111%, whereas plasma from 2 BMT-VOD revealed low vWF-CP activity, as 24% and 37%, respectively. Thus, measurement of vWF-CP is crucial to predict differentiation of primary forms of TMA to establish the pathogenesis in varied endothelial dysfunction.
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PMID:[Measurement of plasma von Willebrand factor cleaving protease in patients with varied thrombotic microangiopathy]. 1288 37

Severe deficiency of von Willebrand factor (VWF)-cleaving protease (ADAMTS-13) activity (<5% of normal) is a specific finding for acute idiopathic thrombotic thrombocytopenic purpura (TTP), a disorder that presents as thrombocytopenia, microangiopathic hemolytic anemia, and often organ dysfunction such as neurological disturbances or renal failure, and fever. Between January 2001 and July 2003, ADAMTS-13 activity was determined in plasma samples of 396 consecutive patients referred to our laboratory for diagnostic purposes. Plasma samples with ADAMTS-13 activity less than 5% were in addition tested for the presence of inhibitory antibodies. Patients were assigned to 10 predefined clinical categories according to information provided by the referring clinician: thrombotic microangiopathy (TMA) not further specified; neoplasia- or chemotherapy-associated TMA; TMA following hematopoietic stem cell transplantation; TMA with additional/alternative disorder; idiopathic TTP; hemolytic-uremic syndrome (HUS) not specified; HUS with diarrhea prodrome (D+HUS); atypical HUS; other hematological disorder; and no clinical information available. Severe ADAMTS-13 deficiency was found in 69 (17%) patients, including 42 with acquired idiopathic TTP, either at initial presentation or at relapse, 14 with confirmed or suspected hereditary TTP, 10 with TMA not further specified, two with neoplasia- or chemotherapy-associated TMA, and one in continued clinical remission 3.4 years after splenectomy for plasma-refractory TTP. Forty-three (62%) patients with ADAMTS-13 activity less than 5% displayed inhibitory antibodies. Severe ADAMTS-13 deficiency was found in 60% of patients diagnosed with acute idiopathic TTP, but in none of 130 patients diagnosed with HUS or in any of the 14 patients with hematopoietic stem cell transplantation-associated TMA. Thus, plasma ADAMTS-13 activity less than 5% does not identify all patients clinically diagnosed with TTP, and severe ADAMTS-13 deficiency is not invariably associated with clinical manifestations of microvascular platelet clumping.
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PMID:von Willebrand factor-cleaving protease (ADAMTS-13) activity determination in the diagnosis of thrombotic microangiopathies: the Swiss experience. 1472 62

Thrombotic thrombocytopenic purpura (TTP) is a syndrome of severe thrombocytopenia and microangiopathic hemolytic anemia without an alternative explanation. Although some patients also have a combination of fever and neurologic and/or renal manifestations, these are not required for the diagnosis. Thus, plasmapheresis should start as soon as TTP is placed high in the differential diagnosis to prevent significant mortality. Histopathologically, TTP is characterized by widespread platelet thrombi in the microcirculation. Ultralarge von Willebrand factor (vWf) multimers found in the patient's plasma are the basis for the platelet thrombi. Recent evidence has linked the abnormal fragments of vWf with deficiency of a plasma enzyme named vWf-cleaving protease, or ADAMTS-13. While a small percentage of patients with TTP have a constitutional defect in this enzyme, many with the acute idiopathic form have an antibody to ADAMTS-13, affecting its ability to cleave vWf. The determination of the enzyme activity and the presence of its inhibitor have emerged as a potential tool in the diagnosis and prognosis of TTP. Furthermore, it helps to differentiate TTP from the hemolytic uremic syndrome, in which the level of ADAMTS-13 is expected to be normal or only slightly decreased.
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PMID:Thrombotic thrombocytopenic purpura: from platelet aggregates to plasma. 1529 54

Plasma exchange is the standard treatment for thrombotic thrombocytopenic purpura (TTP). For patients refractory to plasma exchange, treatment options are limited and often unsuccessful. The platelet thrombi that form in acquired TTP are believed to result from the presence of procoagulant ultralarge multimers of von Willebrand factor (VWF) in the circulation due to autoantibody inhibition of VWF cleaving protease (ADAMTS-13), the enzyme that normally cleaves the ultralarge multimers. Rituximab, a chimeric monoclonal antibody against CD20, has been recognized as a useful therapy for antibody-mediated autoimmune disease. We therefore treated four patients with recurrent TTP with 2 or 4 weekly doses of rituximab in addition to corticosteroids, vincristine, plasma, or continuing plasma exchange. Three patients responded with prompt improvement in microangiopathic hemolytic anemia and thrombocytopenia, which allowed plasma exchange to be discontinued or avoided and prednisone to be rapidly discontinued. Two of the 3 responders have remained in unmaintained complete remission for 13+ months. The third patient relapsed at 13 months; a second course of rituximab and prednisone resulted in an unmaintained remission for 6+ months. All four patients were tested for ADAMTS-13 activity and its inhibitor at a point in their course when samples were available. Low ADAMTS-13 activity was noted in 3 patients tested at relapse, and the inhibitor activity was detectable in 2 patients. ADAMTS-13 activity increased during remission in one of these 2 patients although the patient had a persistence of the inhibitor. One patient tested only during remission had a normal ADAMTS-13 level. We conclude that rituximab may have a role and deserves further study in the treatment of patients with relapsing TTP.
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PMID:Rituximab for treatment of refractory/relapsing thrombotic thrombocytopenic purpura (TTP). 1613 32

Arterial thrombotic events, thrombocytopenia, and hemolytic anemia with schistocytes may be encountered in the setting of both thrombotic thrombocytopenic purpura (TTP) and primary antiphospholipid syndrome (APS). We report 2 cases of TTP occurring in patients with definite primary APS. We also describe the results of tests for ADAMTS-13 activity in 20 consecutive patients with primary APS, as well as tests for antiphospholipid antibodies in 26 patients who had TTP, severe ADAMTS-13 deficiency, and ADAMTS-13-inhibiting antibodies. In both of the patients with primary APS and TTP, ADAMTS-13 activity was undetectable, and ADAMTS-13-inhibiting antibodies were present. None of the 26 patients with TTP and severe ADAMTS-13 deficiency was positive for the lupus anticoagulant. One of these patients had a low level of anticardiolipin antibodies (22 IgG phospholipid units). In the 20 patients with primary APS, mean ADAMTS-13 activity was 116% (range 44-250%), and no severe deficiency (< 5%) was observed. Our findings suggest that primary APS must be added to the list of autoimmune disorders that can be complicated by TTP.
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PMID:Thrombotic thrombocytopenic purpura with severe ADAMTS-13 deficiency in two patients with primary antiphospholipid syndrome. 1547 41

The congenital or acquired deficiency of the von Willebrand factor (VWF) cleaving protease, ADAMTS-13 has been specifically associated with a diagnosis of thrombotic thrombocytopenic purpura (TTP), a microangiopathy characterized by the formation of occlusive platelet thrombi. The mechanisms of TTP were investigated in 100 patients diagnosed on the basis of the presence of at least three of the following: thrombocytopenia, haemolytic anaemia, elevated serum levels of lactate dehydrogenase and neurological symptoms. Plasma levels of ADAMTS-13 were severely reduced (<10% of normal) in 48%, moderately reduced (between 10% and 46%) in 24% and normal (>46%) in 28%. A neutralizing antibody was the cause of the deficiency in 38% of the cases, with a higher prevalence of this mechanism (87%) in the 48 patients with severely reduced ADAMTS-13. Double heterozygosity for a 29 base pair (bp) deletion and a nucleotide insertion and homozygosity for a 6 bp deletion in the ADAMTS13 gene were identified only in two patients born from consanguineous marriages. In conclusion, this study indicated that ADAMTS-13 was normal in nearly one-third of patients with TTP and that ADAMTS-13 deficiency was not associated with the presence of neutralizing antibodies in more than half of the patients.
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PMID:von Willebrand factor cleaving protease (ADAMTS-13) and ADAMTS-13 neutralizing autoantibodies in 100 patients with thrombotic thrombocytopenic purpura. 1552 21

A 41-year-old woman with known systemic lupus erythematosus (SLE) was diagnosed with thrombotic thrombocytopaenic purpura (TTP). At the time of admission she was suffering from petechia, purpura and had neurological symptoms. At first a relapse of the SLE was suspected. Additional laboratory findings demonstrated haemolytic anaemia, thrombocytopaenia and high levels of fragmentocytes. After multiple plasmapheresis treatments and immunosuppressive therapy she recovered. TTP can be differentiated from other thrombotic microangiopathic syndromes by its normal levels of prothrombin time, partially activated thromboplastin time (APTT), fibrinogen and direct Coombs-test. Further investigation is needed to confirm the diagnosis by determination of the activity of Von Willebrand factor cleaving protease ADAMTS-13. In this patient, the ADAMTS-13 activity returned after plasmapheresis. This case demonstrates the importance of fast and appropriate laboratory testing in order to diagnose TTP quickly.
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PMID:[A woman suffering from systemic lupus erythematosus and acquired thrombotic thrombocytopenic purpura]. 1552 34


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