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)

ADAMTS13 is a plasma metalloproteinase that regulates platelet adhesion and aggregation through cleavage of von Willebrand factor (VWF) multimers. In humans, genetic or acquired deficiency in ADAMTS13 causes thrombotic thrombocytopenic purpura (TTP), a condition characterized by thrombocytopenia and hemolytic anemia with microvascular platelet thrombi. In this study, we report characterization of mice bearing a targeted disruption of the Adamts13 gene. ADAMTS13-deficient mice were born in the expected mendelian distribution; homozygous mice were viable and fertile. Hematologic and histologic analyses failed to detect any evidence of thrombocytopenia, hemolytic anemia, or microvascular thrombosis. However, unusually large VWF multimers were observed in plasma of homozygotes. Thrombus formation on immobilized collagen under flow was significantly elevated in homozygotes in comparison with wild-type mice. Thrombocytopenia was more severely induced in homozygotes than in wild-type mice after intravenous injection of a mixture of collagen and epinephrine. Thus, a complete lack of ADAMTS13 in mice was a prothrombotic state, but it alone was not sufficient to cause TTP-like symptoms. The phenotypic differences of ADAMTS13 deficiencies between humans and mice may reflect differences in hemostatic system functioning in these species. Alternatively, factors in addition to ADAMTS13 deficiency may be necessary for development of TTP.
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PMID:Complete deficiency in ADAMTS13 is prothrombotic, but it alone is not sufficient to cause thrombotic thrombocytopenic purpura. 1636 88

Thrombotic microangiopathic hemolytic anemias include thrombotic thrombocytopenic purpura (TTP), hemolytic uremic syndrome (HUS) and pregnancy associated thrombotic microangiopathy (TMA). Eight adult patients (four males and four females) with TMA who were treated between 2003 and 2004 at the Hospital Italiano de Buenos Aires were reviewed. The average age was 40. Clinical diagnosis of TMA was made on admission in four patients. During their stay in hospital, 4 patients developed HUS characteristics, three as TTP and one presented pregnancy associated TMA. All of them revealed thrombocytopenia and microangiophatic hemolytic anemia. Renal impairment was the third most frequent characteristic at presentation. The patients with TTP revealed the most severe condition. All patients received daily plasma exchange. Immunosuppressants were also used. Four patients recovered completely, 2 passed away, one remains with renal impairment and requires hemodialysis, and a colectomy was performed on one of them. The TMA syndromes are occlusive disorders associated to platelet microvascular thrombi. Systemic and renal circulations are primarily affected. TTP/HUS might represent an overlapping spectrum of idiopathic or secondary disease. Prompt recognition and treatment are vital, because high mortality occurs due to these disorders. Among the differential diagnosis of TMA we can refer to sepsis, neoplasms, systemic vasculitis, eclampsia and others. The mainstay treatments are daily plasma exchange and infusion with fresh frozen plasma. Improving the management of these diseases is required considering their high morbidity and mortality.
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PMID:[Thrombotic microangiopathy in adults]. 1697 62

Thrombotic microangiopathies (TMA) are microvascular occlusive disorders characterized by hemolytic anemia caused by fragmentation of erythrocytes and thrombocytopenia due to increased platelet aggregation and thrombus formation, eventually leading to disturbed microcirculation with reduced organ perfusion. Although several disease states may manifest as TMA, the two most relevant conditions associated with TMA are thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS), characterized by prominent brain or renal lesions, respectively. However, occasionally the clinical distinction between these two conditions can be difficult. In this review, we focus on the epidemiologic and diagnostic criteria as well as on the most recent insights into the pathophysiology and treatment of these two conditions.
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PMID:Thrombotic microangiopathies: an update. 1732 53

Thrombotic microangiopathies (TMAs) are characterized by thrombocytopenia, microangiopathic hemolytic anemia, and organ failure (mostly renal dysfunction). TMA includes thrombotic thrombocytopenic purpura (TTP) with predominant neurological signs and hemolytic uremic syndrome (HUS) with predominant renal dysfunction, but they are often indistinguishable each other with the clinical signs alone. Recent availability of von Willebrand factor-cleaving protease or ADAMTS13 activity has defined that TTP is a syndrome frequently associated with a deficient ADAMTS13 activity with or without its inhibitors (autoantibodies), whereas HUS has almost the normal activity. Here, we present two cases of TMA, who were initially diagnosed as "multiple sclerosis" because of the fluctuated neurological signs. Case 1 was a 54-year-old male and case 2 was a 30-year-old female. During their clinical course, they accompanied thrombocytopenia, to which the etiology left undetermined in case 1, but case 2 was suspected DIC because she had such past history. Prophylactic infusion of platelet concentrates to both cases dramatically aggravated their clinical signs. Case 1 was diagnosed to be intravascular lymphoma complicated with acquired TTP, after showing a deficient ADAMTS13 activity. Case 2 was unable to assay ADAMTS13 activity, but later the autopsy revealed the presence of multiple hyaline membrane thrombosis in many organs, together with a lack of demyelinating lesions, solely confirming a diagnosis of TMA.
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PMID:[Thrombotic microangiopathy]. 1743 15

Thrombotic microangiopathies are life-threatening disorders characterized by vascular microthromboses, schistocytic hemolytic anemia, and thrombocytopenia. Although recent research has partially explained the pathogenesis of these rare entities, the determinants contributing to the onset and modulating the severity of thrombotic microangiopathies are largely unknown. The present study assessed the putative role of prothrombotic platelet receptor polymorphisms in thrombotic microangiopathies that have been found to be associated with premature onset of myocardial infarction in predisposed individuals. Thirty-four consecutive patients admitted with the diagnosis of thrombotic microangiopathy and 759 healthy subjects were enrolled. Genotyping of the human platelet antigen (HPA) 2 an the Kozak sequence polymorphism of GP Ibalpha of the platelets' von Willebrand factor receptor glycoprotein (GP) Ib-V-IX, the HPA-1 and the HPA-3 polymorphism of the fibrinogen receptor GP IIb-IIIa (integrin alpha(IIb)beta( 3)) and the HPA-5 and GP Ia 807 C/T polymorphism of the collagen receptor GP Ia-IIa (integrin alpha(2)beta(1)) were determined according to standard procedures. As a result, no significant differences in the prevalence of prothrombotic variants of platelet-receptor polymorphisms between patients and healthy control subjects were observed. However, although not significant, the prothrombotic bb genotype of the HPA-1 polymorphism was more prevalent in the patients. The findings do not provide evidence that platelet receptor polymorphisms are determinants for the onset of thrombotic microangiopathies or predispose to a more severe course. Along with this observation, screening for respective platelet-receptor polymorphisms does not appear to contribute to risk stratification of affected patients.
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PMID:Are prothrombotic variants of platelet glycoprotein receptor polymorphisms involved in the pathogenesis of thrombotic microangiopathies? 1850 78

Thrombotic microangiopathies are characterized by microvascular thrombosis associated with hemolytic anemia, thrombocytopenia, and red blood cell fragmentation. They represent a heterogeneous group of diseases of different etiologies and the entire group shares the same morphological features. Hemolytic uremic syndrome and thrombotic thrombocytopenic purpura are classically associated with thrombotic microangiopathy and the differential diagnosis between these diseases has been very difficult being based more often on the convictions of various specialists than on precisely defined criteria. Recent studies in the field of biology of the von Willebrand factor and also in the field of alternative complement pathway help us to better understand the pathogenesis of these diseases.
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PMID:[Thrombotic microangiopathies: thrombotic thrombocytopenic purpura (TTP) and hemolytic uremic syndrome (HUS). Morphological features, differential diagnosis, and pathogenesis]. 1878 34

Thrombotic microangiopathies are disorders of microvascular occlusion and are characterized by thrombocytopenia and microangiopathic haemolytic anaemia. Varying additional signs and symptoms of organ ischaemia may be present. Thrombotic microangiopathies are pathophysiologically heterogenous disorders and include primarily thrombotic thrombocytopenic purpura and haemolytic uraemic syndrome. Besides this, they may occur in association with certain diseases or drugs, or after allogeneic haematopoietic stem cell transplantation.
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PMID:[Thrombotic microangiopathies]. 1913 66

Thrombotic microangiopathies (TMA) encompass various diseases characterized by a microangiopathic hemolytic anemia, platelet clumping, and organ failure of variable severity. Thrombotic thrombocytopenic purpura (TTP) is a particularly severe form of TMA characterized by systemic organ failure which results from a severe defect in ADAMTS13, a plasma enzyme specifically involved in the cleavage of highly hemostatic unusually large (UL) von Willebrand factor (VWF) multimers into smaller and less adhesive VWF forms. Failure to degrade these UL-VWF multimers leads to excessive platelet aggregates and capillary occlusion. ADAMTS13 deficiency results from bi-allelic mutations in hereditary TTP, whereas in acquired forms it results from autoantibodies that alter the protein function. Patients with acquired idiopathic TTP have a trend to develop autoimmunity, since a clinical context of autoimmunity may be found in 30 p. cent of cases. Moreover, the remarkable efficiency of monoclonal antibodies directed against CD20 antigen of B lymphocytes in refractory or chronic relapsing forms provides an additional indirect argument to consider acquired TTP as an autoimmune disease. Hemolytic uremic syndrome (HUS) is characterized prominently by a renal failure. In most cases, HUS is caused by entero-hemorrhagic Escherichia coli (diarrhea-positive HUS). Diarrhea-negative HUS, termed atypical HUS, was associated with a dysfunction in complement pathway involving mutations in factor H, factor I, CD46/MCP, factor B and C3 components. The major improvement in our understanding of TMA pathophysiology allows now a more accurate molecular classification of TMA syndromes, which opens fascinating perspectives of targeted therapies in the forthcoming years.
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PMID:Thrombotic microangiopathies: towards a pathophysiology-based classification. 1927 76

Thrombotic microangiopathies are rare conditions characterized by microangiopathic hemolytic anemia, microthrombi, and multiorgan insult. The disorders, which include hemolytic uremic syndrome and thrombotic thrombocytopenic purpura, are often acute and life threatening. We report a retrospective analysis of 65 patients presenting to our institution from 1997 to 2008 with all forms of thrombotic microangiopathy. Therapeutic plasma exchange was a requirement for analysis and 65 patients were referred to our institution; 66% of patients were female and median age at presentation was 52 years. Bacterial infection was the most commonly identified etiologic factor and in the multivariate model was the only significant variable associated with survival outcome (odds ratio 5.1, 95% confidence interval, 1.2-21.7). As infection can be considered a common trigger event for thrombotic microangiopathy, patients with hepatobiliary sepsis may benefit from elective cholecystectomy. We conclude that bacterial infection frequently triggers TTP and other thrombotic microangiopathies in patients with preexisting risk factors and propose a model for the development of these syndromes.
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PMID:Infection frequently triggers thrombotic microangiopathy in patients with preexisting risk factors: a single-institution experience. 2010 77

Thrombotic thrombocytopenia purpura (TTP) is a severe multisystem disorder characterized by fever, microangiopathic hemolytic anemia, thrombocytopenia, neurologic symptoms, and impaired renal function. Platelet counts are usually diminished, whereas the bone marrow shows a large number of megakaryocytes indicating peripheral destruction and consumption of platelets. Coagulation studies in patients with TTP are normal or slightly elevated, which helps differentiate this entity from disseminated intravascular coagulation. The peripheral smear shows an abundance of schistocytes, reticulocytes, and, at times, nucleated red blood cells. Serum lactate dehydrogenase and indirect bilirubin are elevated as a result of mechanical destruction of red blood cells. Legionella pneumophila has been identified as a relatively common cause of both community-acquired and hospital-acquired pneumonia. An association between Legionella and TTP has only been cited once in the literature. Here we present a case of severe TTP with concurrent Legionella infection. Our patient presented with the classic clinical findings of TTP and an ADAMTS13 level of less than 5% associated with an inhibitor. After a 3-week treatment course with plasma exchange, steroids, and antibiotics, he had complete clinical recovery and his ADAMTS13 level increased to greater than 75%.
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PMID:A case of severe thrombotic thrombocytopenic purpura with concomitant Legionella pneumonia: review of pathogenesis and treatment. 2021 82


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