Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0022116 (ischemia)
 91,303 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thrombotic thrombocytopenic purpura (TTP) is a severe, occlusive, thrombotic microangiopathy characterized by a systemic platelet aggregation, organ ischemia, profound thrombocytopenia and erythrocyte fragmentation. Recent observations have documented that a deficiency of a von Willebrand factor (VWF)-cleaving protease, termed ADAMTS13, that normally cleaves hyper-reactive unusually large VWF multimers into smaller and less adhesive VWF forms, may be responsible for many cases of TTP. Multiple mutations of the ADAMTS13 gene can result in ADAMTS13 deficiency and cause congenital TTP, while autoantibodies neutralizing ADAMTS13 protease activity have been associated with acquired TTP. However, in spite of the recent progresses in the pathophysiology of TTP, many aspects of this disease remain still controversial. In this study, basing on the laboratory results of a group of eight patients with an acquired form of TTP, an alternative pathogenic mechanism for TTP involving Helicobacter pylori infection is proposed. In fact, Helicobacter pylori, which has been recently implied in the pathogenesis of idiopathic thrombocytopenic purpura (ITP), could function as a triggering factor in TTP by inducing platelet aggregation through an interaction with VWF.
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PMID:Thrombotic thrombocytopenic purpura: proposal of a new pathogenic mechanism involving Helicobacter pylori infection. 1608 70

Thrombotic thrombocytopenic purpura (TTP) is a life-threatening disorder characterized by microangiopathic hemolytic anemia and thrombocytopenia often accompanied by microvascular ischemia, which may manifest as sensorimotor signs, visual changes, renal impairment, cardiac ischemia, and abdominal pain, depending on the organs affected. Until a few decades ago, TTP remained an almost universally fatal disorder. The introduction of plasma exchange therapy (PE) with replacement of fresh frozen plasma has improved the survival of patients with acute TTP dramatically from less than 10% to approximately 80 to 90% and is now considered the therapy of choice. During the last decade, the understanding of the pathophysiology of thrombotic microangiopathies, especially TTP, has increased considerably. The clinical features of thrombotic sequelae in TTP are diverse and usually secondary to microvascular thrombosis. Clinical and laboratory evidence for disruption of primary and secondary hemostasis, the role of endothelial integrity and fibrinolysis, the relevance of large vessel thrombosis, and the prevalence of thrombophilic states in TTP are discussed in this review. In summary, although the syndrome of TTP can sometimes be confused with other thrombotic diatheses, it is clear that the phenomenon of thrombosis in TTP appears to be distinctly different, both biologically and clinically, from other causes of microangiopathy and/or antibody-mediated thrombosis. Traditional anticoagulant and antiplatelet strategies are generally not effective in patients with TTP, despite the predominance of thrombotic manifestations, and common prothrombotic polymorphisms detected in patients with venous thromboembolism are seldom present.
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PMID:Thrombophilia and thrombosis in thrombotic thrombocytopenic purpura. 1638 16

Coronary artery bypass graft surgery in patients with immune thrombocytopenic purpura (ITP) refractory to preoperative medical therapy accompanies an increased risk of bleeding perioperatively. In the ITP patient without responding to intravenous immunoglobulin and corticosteroids, we performed combined off-pump coronary artery bypass grafting with splenectomy to minimize the risk of intraoperative bleeding and cardiac ischemia. Using platelets infusion, we successfully managed the patient without major bleeding and ischemic events.
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PMID:[Combined surgery of off-pump coronary bypass graft with splenectomy in a patient with refractory immune thrombocytopenic purpura]. 1731 40

Thrombotic thrombocytopenic purpura (TTP) is a disorder of blood coagulation that presents classically with the pentad of fever, thrombocytopenia, microangiopathic hemolytic anemia, renal dysfunction and mental status changes. However, the clinical presentation can be quite variable making the diagnosis difficult in many cases. "Hyaline" microthrombi composed primarily of platelets and Von Willebrand Factor (VWF) are found in the small vessels of affected organs and represent the pathological hallmark of the disease. The accompanying tissue ischemia is thought to explain the clinical TTP signs and symptoms. Pathogenesis of TTP has been linked to dysfunction of ADAMTS13, a metalloprotease whose only known substrate is VWF. Interestingly, further investigation into the natural history of TTP has demonstrated that ADAMTS13 deficiency likely is necessary, but not sufficient for the development of this disease, suggesting that additional genetic and/or environmental factors are required for TTP pathogenesis. Recently, a mouse model of TTP was established that recapitulates many of the key clinical features of this disease, including the requirement for further genetic and environmental factors in addition to ADAMTS13 deficiency. Therefore, in addition to being useful for the direct study of disease pathophysiology in vivo, this mouse model may also play a key role in elucidating some of the important environmental and genetic contributors to disease pathogenesis. Here we will review TTP in humans, and then discuss recent information gained from the analysis of ADAMTS13-deficient mice.
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PMID:Thrombotic thrombocytopenic purpura in humans and mice. 1752 62

The last 10 years witnessed the publication of many studies on the pathophysiology of thrombotic thrombocytopenic purpura (TTP), a life-threatening disease characterized by microangiopathic hemolytic anemia, thrombocytopenia and multiorgan failure. The most important finding was the identification of a novel metalloprotease, named ADAMTS13 (a disintegrin and metalloproteinase with thrombospondin type 1 motives), that is involved in the regulation of the size of von Willebrand factor (VWF), a major modulator of platelet adhesion and aggregation in the microcirculation. Inherited or acquired deficiencies of ADAMTS13 impair VWF cleavage, leading in turn to the disseminated formation of platelet-rich thrombi in the micro-circulation and to symptoms of end-organ ischemia. By measuring ADAMTS13 in plasma, it has been clearly shown that patients with inherited TTP have severe ADAMTS13 deficiency. However, patients with acquired TTP present with clinical and laboratory heterogeneity, and there are unequivocal cases of acquired TTP with measurable plasma levels of ADAMTS13. This heterogeneity poses a challenge for understanding the pathogenesis of TTP and selecting appropriate therapies.
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PMID:TTP and ADAMTS13: When Is Testing Appropriate? 1802 19

Thrombotic thrombocytopenic purpura (TTP) related to a severely deficient activity of the von Willebrand factor cleaving protease, ADAMTS (A Disintegrin And Metalloprotease with ThromboSpondin type 1 repeats) 13, is a life-threatening event, the onset of which may occur as early as childhood. TTP is either inherited (Upshaw-Schulman syndrome) via ADAMTS13 gene mutations (neonatal onset) or acquired via anti-ADAMTS13 autoantibodies (childhood onset). TTP is due to platelet- and von-Willebrand-factor-rich thrombi of the microvasculature, inducing mechanical hemolytic anemia, consumption thrombocytopenia, and multivisceral ischemia. Clinical course consists of relapsing acute events triggered mostly by infections, associated icterus and hyperbilirubinemia, severe hemolytic anemia with schistocytosis and a negative Coombs test, severe thrombocytopenia, and sometimes symptoms related to visceral ischemia (renal failure, central nervous system vascular events, other organ failure). The recently available ADAMTS13 laboratory investigation combining measurement of ADAMTS13 activity in plasma, search for an ADAMTS13 circulating inhibitor, and anti-ADAMTS13 IgG and ADAMTS13 gene sequencing is a crucial addition to TTP diagnosis. Plasma exchanges are first-line treatment of acquired TTP, combined with steroids and immunosuppressive drugs. Curative treatment of acute events in Upshaw-Schulman syndrome relies on plasma infusions (provider of active ADAMTS13). Guidelines for preventive treatment of relapses are not clearly established but should associate plasmatherapy and caution to triggers of relapses. Therapeutic perspectives are focused on the development of concentrated plasma-derived ADAMTS13 or recombinant ADAMTS13.
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PMID:Thrombotic thrombocytopenic purpura related to severe ADAMTS13 deficiency in children. 1857 2

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. About 10-20% of TTP cases are associated with the pregnancy. Preterm delivery and intrauterine fetal death are frequent pregnancy complications of TTP. The following paper presents the case of a 32-year-old woman with TTP relapse at 10 weeks of her second pregnancy. Despite regular fresh frozen plasma transfusions, intrauterine fetal death occurred at 21 weeks of gestation. Current views on TTP management during pregnancy have been presented in the article as well.
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PMID:[Thrombotic thrombocytopenic purpura in pregnancy. A case report]. 1881 60

Thrombotic thrombocytopenic purpura (TTP) is a severe multisystemic microvascular disease defined by the association of hemolytic anemia, thrombocytopenia, acute renal failure, fever, and neurological disorders. The pathophysiology has recently been elucidated by the discovery of a von Willebrand factor-cleaving protease (ADAMTS13) deficiency involved in platelet aggregation and ischemia. The association between TTP and acute pancreatitis (AP) has rarely been reported, described either as a cause or a consequence. The role of ADAMTS13 during AP is still unknown. We describe the case of a 41-year-old woman who developed a TTP, with decreased ADAMTS13 activity, associated with severe AP. Published cases of thrombotic microangiopathy associated with AP are reviewed. The pathophysiology, management, prognostic factors, and rationale for treatment are discussed. AP should be sought in patients with TTP presenting with abdominal pain. On the other hand, TTP should be considered in patients with AP and thrombocytopenia.
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PMID:Thrombotic thrombocytopenic purpura associated with severe acute pancreatitis in a context of decreased ADAMTS13 activity: a case report. 1898 46

Spontaneous hemothorax in the left pleural space occurred suddenly in a patient with thrombotic thrombocytopenic purpura (TTP). In spite of massive blood transfusion, the hemorrhage could not be stopped. The patient suffered shock due to tension hemothorax and hypovolemia, resulting in cardiac arrest. After successful cardiopulmonary resuscitation, surgical hemostasis was performed. The main cause of the bleeding was rupture of the left intercostal vein. TTP is a severe microvascular occlusive thrombotic microangiopathy that can induce congestion, vasculitis, and ischemia. This mechanism is thought to have been involved in the rupture of the intercostal vein in the present patient.
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PMID:Life-threatening spontaneous hemothorax in a patient with thrombotic thrombocytopenic purpura. 1923 38

ADAMTS-13, the thirteenth member of the ADAMTS (A Disintegrin And Metalloprotease with Thrombo-Spondin 1 repeats) family, is the plasma metalloprotease responsible for regulating the multimeric structure of VWF. In congenital or acquired deficiency it is actively involved in the pathophysiology of thrombotic thrombocytopenic purpura (TTP), a rare but life threatening disease characterized by microangiopathic haemolytic anaemia and consumptive thrombocytopenia leading to disseminated microvascular thrombosis and variable signs and symptoms of organ ischemia and damage. In the last few years, a number of in house and commercial laboratory assays for ADAMTS-13 and its autoantibodies have been developed. The features and clinical utility of ADAMTS-13 assays are summarized in this review.
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PMID:ADAMTS-13 assays in thrombotic thrombocytopenic purpura. 2008 24


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