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-hemolytic uremic syndrome occurs more commonly in women and among women is commonly associated with pregnancy. Case series of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome from 1964 to 2002 were reviewed (1) to document the reports of occurrence of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome during pregnancy and (2) to search for reports of women with congenital or familial thrombotic thrombocytopenic purpura-hemolytic uremic syndrome who were initially diagnosed during their first pregnancy. The time during pregnancy with greatest risk for development of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome is near term and during the postpartum period. This is also the time of greatest risk for thrombotic events and for the occurrence of other pregnancy-related syndromes: preeclampsia, eclampsia, and hemolysis, elevated liver enzymes, low platelets (HELLP) syndrome. These other syndromes may also be associated with thrombocytopenia, microangiopathic hemolytic anemia, neurologic symptoms, and renal insufficiency, making their distinction from thrombotic thrombocytopenic purpura-hemolytic uremic syndrome difficult or impossible. The occurrence of preeclampsia and related syndromes, the hypercoaguable state that occurs in late pregnancy and postpartum, and the progressively decreasing concentration of ADAMTS13 that occurs during late pregnancy may combine to increase the risk for occurrence of thrombotic thrombocytopenic purpura-hemolytic uremic syndrome.
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PMID:The association of pregnancy with thrombotic thrombocytopenic purpura-hemolytic uremic syndrome. 1291 87

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

Thrombotic thrombocytopenic purpura (TTP) is characterised by haemolytic anaemia with fragmented erythrocytes and thrombocytopenia, accompanied by other symptoms such as renal dysfunction, neurological signs and fever. Proteolysis of the Von Willebrand blood-clotting factor (VWF) by a VWF cleaving protease or ADAMTS13 is decreased in patients with TTP, leading to ultra-large Von Willebrand multimers in the circulation. A lack of ADAMTS13 activity can be caused by autoimmune inhibitors or may be due to a constitutional deficiency of this protein. Recently, the ADAMTS13 gene that encodes for the ADAMTS13 protein was found. It was mapped to chromosome 9q34 and consists of 29 exons. Several mutations have been identified in the ADAMTS13 gene in patients with the congenital form of TTP. Symptomatic episodes in congenital TTP can be prevented by prophylactic plasma infusions every 2-3 weeks, hereby preventing further organ damage due to thrombotic microangiopathy.
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PMID:[From gene to disease; congenital thrombotic thrombocytopenic purpura due to mutations in the ADAMTS13 gene]. 1469 51

The diagnosis of thrombotic thrombocytopenic purpura (TTP) rests on evidence of microangiopathic hemolytic anemia and thrombocytopenia in the absence of disseminated intravascular coagulation and other known causes of thrombotic microangiopathy. Highly specific diagnostic tools such as serum levels of ADAMTS13 are not routinely available for immediate clinical diagnosis. The presence of schistocytes on a blood smear is the morphologic hallmark of the disease, but no guidelines exist as to the number of schistocytes required to differentiate TTP from other thrombotic microangiopathies. We studied 6 patients with TTP and compared their schistocyte counts with those of 40 normal subjects, 28 patients with chronic renal disease, 5 with preeclampsia, and 5 with normal functioning mechanical heart valves. The mean schistocyte count for the TTP patients was 8.35% versus 0.05% for normal subjects, 0.2% for renal patients, 0.25% for preeclamptic patients, and 0.18% for patients with mechanical valves (P < 0.001). Schistocytes were found on 100% of blood films of TTP patients and ranged from 1.0% to 18.4% of red cells. Schistocytes are found on the smears of 58% of normal individuals and on 80-100% of the other patient groups studied, but always comprise less than 0.5% of the red cell population. An initial schistocyte count of greater than 1% strongly suggests a diagnosis of TTP in the absence of other known causes of thrombotic microangiopathy.
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PMID:Morphologic diagnosis of thrombotic thrombocytopenic purpura. 1469 28

Thrombotic thrombocytopenic purpura (TTP) is a dramatic intravascular platelet-clumping disorder characterized by microangiopathic hemolytic anemia, thrombocytopenia, neurologic abnormalities, renal insufficiency and fever. TTP is a rare disease but is almost always fatal if untreated. More than 80% of patients survive with plasma therapy. In healthy individuals, the proteolytic cleavage of ultralarge von Willebrand factor (vWF) multimers prevents spontaneous clumping of platelets in the microcirculation. Patients with TIP have either severe congenital deficiency of von Willebrand factor-cleaving protease (vWF-cp), or have autoantibodies that inhibit the protease. Determination of vWF-cp levels in patient plasma helps to distinguish between TTP and other thrombotic microangiopathies with similar clinical signs and symptoms. vWF-cp is a member of the ADAMTS family of metalloproteases and has been designated ADAMTS13.
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PMID:Deficient activity of von Willebrand factor-cleaving protease in thrombotic thrombocytopenic purpura. 1503 Feb 84

Thrombotic thrombocytopenic purpura (TTP) is an uncommon but severe disorder that classically presents with microangiopathic hemolytic anemia (MAHA), thrombocytopenia, and fluctuating neurological changes. Previously, it was impossible to make a diagnosis of TTP in the absence of thrombocytopenia or microangiopathic hemolysis (MAHA). We describe two cases of relapsing TTP that presented with acute cerebrovascular accident (CVA) without concurrent thrombocytopenia or MAHA after initial classical presentation of TTP. In both cases, the diagnosis of TTP as the cause of the CVA was attributed to severe deficiency of the von Willebrand factor cleaving protease, ADAMTS13 in plasma (11 and 12%, normal 79-127%). Each patient had a dramatic clinical improvement in response to therapeutic plasma exchange. The experience in these two cases suggests that TTP should be considered as a potential cause among patients presenting with a CVA, particularly if the patients have a history of TTP.
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PMID:Relapsed thrombotic thrombocytopenic purpura presenting as an acute cerebrovascular accident. 1527 97

Congenital thrombotic thrombocytopenic purpura (TTP) is an inherited form of TTP due to the deficiency of von Willebrand factor (vWF) cleaving protease ADAMTS13. The authors describe two children with congenital TTP who presented with thrombocytopenia, hemolytic anemia, elevated LDH levels, and schistocytes on peripheral blood smear. In both children, the diagnosis of the disease was delayed despite neonatal histories significant for thrombocytopenia, anemia, and severe hyperbilirubinemia. Severely decreased ADAMTS13 activity (<0.1 U/mL), the absence of an inhibitor to the protease, and partial deficiency found in the parents confirmed the diagnosis of congenital TTP. The authors suggest that congenital TTP should be considered in the differential diagnosis for newborns presenting with severe hyperbilirubinemia, anemia, and thrombocytopenia.
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PMID:Thrombocytopenia and severe hyperbilirubinemia in the neonatal period secondary to congenital thrombotic thrombocytopenic purpura and ADAMTS13 deficiency. 1528 96

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

Thrombotic thrombocytopenic purpura (TTP) is characterized by microangiopathic hemolytic anemia and thrombocytopenia, accompanied by microvascular thrombosis that causes variable degrees of tissue ischemia and infarction. Intravascular coagulation is not a prominent feature of the disorder. Plasma exchange can induce remissions in approximately 80% of patients with idiopathic TTP, but patients have a much worse prognosis when thrombotic microangiopathy is associated with cancer, certain drugs, infections, or tissue transplantation. Recently, acquired autoimmune deficiency of a plasma metalloprotease named ADAMTS13 was shown to cause many cases of idiopathic TTP. This review describes our current understanding of how to use this knowledge clinically. In Section I, Dr. Joel Moake describes the presentation of thrombotic microangiopathy, emphasizing the pathophysiology of idiopathic TTP. Platelets adhere to ultra-large (or "unusually large") von Willebrand factor (ULVWF) multimers that are immobilized in exposed subendothelial connective tissue and secreted into the circulation in long "strings" from stimulated endothelial cells. ADAMTS13 cleaves ULVWF multimers within growing platelet aggregates under flowing conditions, and this normally limits platelet thrombus formation. If ADAMTS13 is absent, either congenitally or due to acquired autoantibodies, platelet-rich microvascular thrombosis proceeds unchecked and TTP ensues. Plasma exchange is effective therapy for idiopathic TTP, probably because it replenishes the deficient ADAMTS13 and removes some of the pathogenic autoantibodies and endothelial-stimulating cytokines. Some patients have a type of thrombotic microangiopathy after transplantation/chemotherapy but do not have severe ADAMTS13 deficiency. The pathogenesis of their disease must differ but remains poorly understood. In Section II, Dr. Toshiyuki Miyata describes recent advances in assay methods that should facilitate routine laboratory testing of ADAMTS13 for patients with thrombotic microangiopathy. ADAMTS13 cleaves a single Tyr-Met bond in domain A2 of the VWF subunit. ADAMTS13 assays based on the cleavage of plasma VWF multimers have been used extensively but require considerable time and expertise to perform. A recombinant substrate containing 73 amino acid residues of VWF domain A2 has been devised that allows short incubation times and rapid product detection by gel electrophoresis or immunoassay. These results should encourage the development of even simpler assays that can be performed in most clinical laboratories. In Section III, Dr. James George provides an update on the long-term prospective study of thrombotic microangiopathy in the Oklahoma TTP-HUS Registry. At presentation, the clinical distinction between idiopathic TTP, various forms of secondary thrombotic microangiopathy, and even Shiga toxin-associated hemolytic uremic syndrome (HUS) can be problematic because the symptoms and laboratory findings often overlap. Consequently, plasma exchange usually is administered to any patient with thrombotic microangiopathy if there is doubt about the cause. The role of ADAMTS13 testing in choosing therapy remains uncertain, but the results do appear to have prognostic significance. Severe ADAMTS13 deficiency is specific for idiopathic TTP and identifies a subgroup with a high likelihood of response to plasma exchange, and high-titer ADAMTS13 inhibitors correlate strongly with a high risk of relapsing disease. Patients with normal ADAMTS13 activity have a much worse prognosis, although many factors probably contribute to this difference. Longitudinal study of these patients will continue to clarify the relationship of ADAMTS13 deficiency to the clinical course of thrombotic microangiopathy.
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PMID:Recent advances in thrombotic thrombocytopenic purpura. 1556 95

Patients with malignant hypertension sometimes exhibit microangiopathic hemolytic anemia/thrombocytopenia known as thrombotic microangiopathy (TMA). On the other hand, severe hypertension is sometimes associated with hemolytic uremic syndrome (HUS)/thrombotic thrombocytopenic purpura (TTP). Because the clinical features of the two entities overlap significantly, it is sometimes difficult to distinguish one from the other. However, such differentiation is indispensable, since early performance of plasmapheresis is critical in HUS/TTP. It has been suggested that severe thrombocytopenia is one of the most useful differential points in diagnosing HUS/TTP from malignant hypertension caused by other etiologies. Early performance of plasmapheresis can be justified in the presence of both TMA and thrombocytopenia. However, thrombocytopenia can be seen in the cases with malignant hypertension from etiologies other than HUS/TTP, and in these particular cases, plasmapheresis is useless and can be harmful. Recently, the plasma level of ADAMTS13 (a disintegrin and metalloprotease domain, with thrombospondin type 1 motif 13), which is a von Willebrand Factor cleaving protease, has been shown to be very low in familial or some of the sporadic cases of TTP, and a low level of ADAMTS13 is very specific to TTP. Some reports have shown that patients with a very low plasma level of ADAMTS13 respond very well to plasmapheresis. We recently experienced two cases with TMA. Although both of our patients had severe hypertension with TMA, different therapeutic strategies ameliorated their illness: symptomatic treatment was effective in case 1, which showed normal ADAMTS13 activity, whereas plasma infusion was necessary to save case 2, which showed low ADAMTS13 activity. Thus, patients with a low level of ADAMTS13 activity might respond well to plasmapheresis or plasma infusion. When presented with patients with severe hypertension and thrombotic microangiopathy, ADAMTS13 activity may prove to be a promising adjunctive tool in differentiating TTP from TMA due to other etiologies, but in the meantime, we should make the choice of whether or not to perform plasmapheresis based on the degree of thrombocytopenia.
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PMID:Thrombotic microangiopathy in malignant hypertension and hemolytic uremic syndrome (HUS)/ thrombotic thrombocytopenic purpura (TTP): can we differentiate one from the other? 1596 59


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