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)

Thrombotic thrombocytopenic purpura and hemolytic uremic syndrome appear as the same expression of thrombotic microangiopathy (TMA), which is a single pathological entity affecting small blood vessels leading to hemolytic anemia, circulatory changes with renal (hemolytic uremic syndrome, HUS) or nervous (thrombotic thrombocytopenic purpura, TTP) involvement. Because of his low incidence, prospective randomized clinical trials are difficult to conduct and apart from plasma exchanges (PE) which appear superior to plasma infusions (PI), other therapeutic recommendations are based on retrospective studies or on anecdotal reports with limited number of patients. In the absence of appropriate therapy, mortality rate was initially above 90% in adults with TTP. Plasma infusions and plasma exchanges have dramatically improved prognosis of the disease, since more than 80% of patients respond to therapy with a survival greater than 80 to 90%. Analysis of data of medical literature shows that plasma exchanges can cure 82% of TMA with 15% of refractory TMA and a mortality rate of 14%. In two randomized trials, PE are more effective than PI with a response rate benefit of 25% and an overall survival increase of 15%. Although severe thrombocytopenia is frequently observed, it is important to avoid platelet transfusions. Platelets infusions induce deleterious effects since they add to the severity and the extend of microvascular thrombi formation. Use of glucocorticoids, heparin, antiplatelet therapy, intravenous immunoglobulin and vincristine are associated with variable results and no controlled study supports their use. Splenectomy is still under discussion but could be of interest in case of relapsing thrombotic microangiopathies as an attempt to reduce the rate of TMA recurrence.
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PMID:[Treatment of thrombotic microangiopathies]. 1054 47

Red cell hemolysis is classically diagnosed by a combination of nonspecific laboratory tests, including serum bilirubin, LDH, and the reticulocyte count. None of these tests alone or in combination has the specificity to reliably ascertain the presence of hemolysis. We have previously demonstrated that erythrocyte adenylate kinase (EAK) is a red cell specific enzyme released from damaged red cells. Its activity can be measured in serum by rapid electrophoresis or immunological methods and correlates linearly with the degree of hemolysis in vitro. We now report on a clinical study comparing EAK levels in patients with and without hemolysis. The clinical diagnosis of hemolysis was established in hospitalized patients with anemia by the combined elevation of the bilirubin, LDH, and reticulocyte count in the absence of liver disease and demonstrable blood loss. The normal range of serum EAK was determined in 30 healthy nonanemic voluntary blood donors and was 0-3.5 Units (mean = 0.5). In 25 patients with hemolytic anemia due to sickle cell disease, hemolytic transfusion reactions, or TTP, the mean EAK level was 62.4 with a range 0-298 Units (P < 0.001 compared to normals). Levels of EAK exceeded the normal range in 24 of 25 patients (96%). In a control group of 44 hospitalized patients with liver disease or myocardial infarction and no clinical evidence of hemolysis, the mean EAK level was 0.12 with a range of 0-3.2 (P = 0.1, NS compared to normals and P < 0.001 compared to patients with hemolysis). None of the control patients had EAK levels that exceeded the normal range. The diagnostic sensitivity of the EAK assay for hemolysis, as calculated according to Baye's algorithm, was 96%, with a specificity and accuracy of 97%. Measurement of serum EAK represents a highly sensitive and specific test for the diagnosis of hemolytic anemia.
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PMID:Diagnosis of the hemolytic state using serum levels of erythrocyte adenylate kinase. 1086 13

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

Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS) is an inclusive term describing diverse syndromes of multiple etiologies with the common features of thrombocytopenia and microangiopathic hemolytic anemia. Other organ involvement, including renal failure, neurologic abnormalities, and gastrointestinal symptoms, is common. Adverse reactions to drugs increasingly are reported as a potential cause of TTP-HUS. More than 50 drugs and other substances have been associated with the development of TTP-HUS, but many case reports are difficult to interpret because there is uncertainty regarding the diagnosis of TTP-HUS and because there is uncertainty regarding the relation of drug exposure to the onset of TTP-HUS. A systematic analysis of reports of drug-associated TTP-HUS will be required to better understand the strength of clinical evidence linking drugs to the etiology of TTP-HUS. In this review, five drugs that have been the subject of the most and the most recent reports of drug-associated TTP-HUS are discussed: mitomycin C, cyclosporine, quinine, ticlopidine, and clopidogrel. The clinical features of TTP-HUS associated with these drugs are different, suggesting two principal mechanisms by which drugs may cause TTP-HUS: dose-related toxicity (mitomycin C, cyclosporine), and immune-mediated reaction (quinine, ticlopidine, clopidogrel). The role of plasma exchange is uncertain, but this treatment is appropriate because of the high mortality and morbidity of drug-associated TTP-HUS. Recognition of a drug-associated etiology in a patient with TTP-HUS is critical to avoid re-exposure and recurrent illness.
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PMID:Drug-associated thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. 1160 63

Pathogenic mechanisms of renal injury by thrombotic microangiopathies present a challenge to the multidisciplinary team caring for a patient with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome (TTP-HUS). First recognized 77 years ago as a rare disorder characterized by reversible platelet aggregation in the microcirculation causing ischemia in various organs, the prognosis was always fatal. In the past 20 years, due to effective treatment with plasma exchange therapy, there has been a decline in the mortality rate to 10-20%. The classic pentad of symptoms of TPP-HUS include thrombocytopenia, microangiopathic hemolytic anemia, neurologic abnormalities, fever, and renal impairment. Frequency of TTP-HUS appears to be increasing. Due to the urgent need for a diagnosis, sufficient diagnostic criteria for TTP-HUS are currently thrombocytopenia and microangiopathic hemolytic anemia in the absence of another apparent cause. It is imperative to have a solid understanding of the pathophysiology and current standards of practice of TTP-HUS in order to facilitate positive patient outcomes in this unique group of patients.
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PMID:Thrombotic thrombocytopenic purpura-hemolytic uremic syndrome: pathophysiology and management. 1199 52

We report the first known case of chronic relapsing thrombotic thrombocytopenic purpura associated with adult-onset Still's disease. The patient presented with diffuse arthralgias, sore throat, and a maculopapular rash involving the trunk and extremities; she was hospitalized with fever and confusion. Thrombocytopenia, renal failure, and microangiopathic hemolytic anemia developed within several days. After a diagnosis of thrombotic thrombocytopenic purpura was made, she responded well to a series of plasma exchanges. Evaluation for infection, autoimmune disorders, and malignancy was negative. She was discharged to home in good condition, with normal renal function and normal platelet count. Two more episodes of TTP developed 7 and 9 months after the first hospitalization. The diagnosis of adult-onset Still's disease was then determined on the basis of clinical and laboratory criteria. She was successfully treated with plasma exchange, prednisone, and azathioprine. She later had splenectomy and has subsequently been without recurrence of thrombotic thrombocytopenic purpura for 2 years.
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PMID:Chronic relapsing thrombotic thrombocytopenic purpura in adult onset Still's disease. 1260 13

Thrombotic thrombocytopenic purpura is a multisystem disease characterized by thrombocytopenia, hemolytic anemia, renal failure, fever, and neurologic abnormalities. Plasma exchange has revolutionized the outcome of this entity from a once fatal disease to a disease that potentially is cured or has prolonged remission. The understanding of the pathophysiology of TTP continues to evolve. Recently, investigators showed that a deficiency in a specific plasma protease responsible for cleaving vWf plays a crucial role in the familial form of TTP. This explains in part why patients usually respond to plasma exchange therapy. The identification of a mutation in a specific gene that belongs to the metalloproteinase family located at chromosome 9q34 could have important therapeutic implications. TTP can be induced by certain drugs, especially immunosuppressants, in the setting of bone marrow and solid organ transplantation. This disease also has been described in association with HIV, pregnancy, cancer, and chemotherapy. TTP remains an ideal example of how knowledge about the etiology of a disease can improve therapeutic interventions.
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PMID:Current concepts in the diagnosis and management of thrombotic thrombocytopenic purpura. 1262 68

Our understanding of the pathophysiology of thrombotic thrombocytopenic purpura, TTP, has increased dramatically in the past few years with the identification of the role of ADAMTS13. Nonetheless, risk factors for the development of acute TTP are few. Informally, obesity was felt to be common in patients with TTP and so a formal study was undertaken to further define this association. We report our data in 105 patients with classical TTP as defined by thrombocytopenia and microangiopathic hemolytic anemia. We found that marked obesity is a previously unrecognized risk factor with an associated odds ratio of 7.6. Interestingly, despite this increased risk, obesity might well be associated with lower mortality, although this did not reach statistical significance.
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PMID:Overweight individuals are at increased risk for thrombotic thrombocytopenic purpura. 1458 43

TTP is a rare but potentially fatal disease unless plasmapheresis is initiated promptly. Although most hospitals will only treat such patients sporadically, unless the possibility of TTP is explored, the diagnosis may be missed. In patients with unexplained severe thrombocytopenia (usually less than 10,000 platelets/microL) and hemolytic anemia with schistocytes, TTP must be ruled out. The presence of other clinical and laboratory features as described in Table 1 may aid in the differential diagnosis. Often, however, TTP remains a possibility and the patient should be transferred to a facility where plasmapheresis is available. Further, a sample of citrated plasma should be collected prior to any plasma transfusion, and sent frozen to a reference laboratory for determinations of the vWF-CP activity and the presence of an inhibitor to the enzyme. The clinical laboratory should be aware of this test to help ensure that the sample is correctly collected and shipped. Although the patient should be treated as if having TTP until the result of the tests is available, the assays may help determine the specific diagnosis, as well as the potential need for further therapy as discussed above. We anticipate that continued accumulation of vWF-CP data with clinical correlation will further define the role of this enzyme in the diagnosis and management of patients with TMAs.
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PMID:Von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura. 1462 38

A 6-year-old boy presented with microangiopathic hemolytic anemia, thrombo-cytopenia, altered sensorium and intractable bleeding. A diagnosis of thrombotic thrombocytopenic purpura was made and the child recovered dramatically after plasmapheresis. Recent developments in the understanding of TTP are reviewed, including the importance of a metaloprotease required to cleave multimers of von Willibrand factor.
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PMID:Thrombotic thrombocytopenic purpura. 1506 18


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