Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0012739 (disseminated intravascular coagulation)
 8,673 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Gabexate mesylate is a non-antigenic synthetic inhibitor of trypsin-like serine proteinases that is therapeutically used in the treatment of pancreatitis and disseminated intravascular coagulation and as a regional anticoagulant for hemodialysis. Considering the structural similarity between gabexate mesylate and arginine-based inhibitors of trypsin-like serine proteinases, the effect of gabexate mesylate on human and bovine mast cell tryptase action was investigated. Values of the inhibition constant (K(i)) for gabexate mesylate binding to human and bovine tryptase were 3.4 x 10(-9) M and 1.8 x 10(-7) M (at pH 7.4 and 37.0 degrees ), respectively. Furthermore, gabexate mesylate inhibited the fibrinogenolytic activity of human tryptase. On the basis of the available x-ray crystal structure of human tryptase, the possible binding mode of gabexate mesylate to human and bovine tryptase was analyzed. Human tryptase inhibition by gabexate mesylate may account for the reported prevention of inflammation, erosion, and ulceration of skin and mucosae.
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PMID:Selective inhibition of human mast cell tryptase by gabexate mesylate, an antiproteinase drug. 1117 30

A 28-year-old woman, G3P3, who was otherwise healthy and had taken no medication and had no known allergy, was admitted to our hospital for delivery after a normal pregnancy. An epidural catheter was inserted for analgesia and labour was induced with oxytocin. Two hours later, she suffered a sudden cardiac arrest. She was immediately treated and, since a normal cardiac rhythm and a blood pressure of 90 mmHg has been obtained 30 minutes later, a 3750 g child was delivered by caesarean section. Soon after delivery, a life-threatening uterine haemorrhage appeared, due to DIC. Evolution was favourable, after bilateral uterine arteries embolization had been performed. The diagnosis of amniotic fluid embolism was established by the clinical course, the absence of local cause and the presence of a large number of amniotic cells in the mother's peripheral blood. Tryptase blood concentration was normal in the mother's blood.
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PMID:[Amniotic fluid embolism: successful evolution course after uterine arteries embolization]. 1207 39

We report on a patient with coagulation abnormalities induced by a wasp sting anaphylaxis. First, we observed an unclottable activated partial thromboplastin time and a significant anti-Xa activity (equivalent to a therapeutic heparin range), whereas the patient had received no heparin. This phenomenon is probably due to activated mast cells that release mediators such as heparin and tryptase. Heparin can then act as an anticoagulant by binding to antithrombin. This "heparinization" explains the anti-Xa activity contributing to the unclottable activated partial thromboplastin time detected in our patient. Second, we noted an extremely low fibrinogen level in the presence of normal platelet count and only a slight increase of D-dimers (absence of important disseminated intravascular coagulation). This is probably due to serum tryptase released during massive mast cell activation. Tryptase cleaves the alpha and beta chains of fibrinogen. This results in the removal of the thrombin cleavage site and of the critical polymerization site from the fibrinogen beta chain. Thrombin- initiated clot formation is therefore inhibited. Tryptase also acts directly on the fibrinolytic pathway by activating the single-chain urinary-type plasminogen activator, resulting in conversion of plasminogen into plasmin and therefore degradation of fibrinogen and other coagulation factors. This hyperfibrinogenolysis explains both the prolonged clotting times and the low fibrinogen level observed. Although our patient did not bleed, in other settings (trauma, during surgery) patients with anaphylaxis may present bleeding disorders. Although the mechanisms underlying these abnormalities have been described in vitro and in vivo animal trials, this is the first time they are described in a human clinical setting.
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PMID:"Heparinization" and hyperfibrinogenolysis by wasp sting. 2207 26

Amniotic fluid embolism (AFE) is a rare, high-risk obstetric complication primarily found in the lungs and potentially related to anaphylaxis. Tryptase release from the mast cell reflects anaphylaxis. Case report and findings: A female, aged over 40 years, presented with uterine atony and lethal hemorrhage after induced vaginal labor. Cervical laceration was accompanied by severe hemorrhage. Stromal edema and myometrial swelling were consistent with uterine atony. Alcian blue staining and zinc coproporphyrin immunostaining disclosed AFE, which was more prominent in the uterus than in the lungs. Tryptase immunostaining was diffuse and prominent around the activated mast cells (halos) in the uterus, including the cervix. Similar distribution of findings on the AFE markers, tryptase halos, complement receptor C5aR, and atony in the uterus suggested the causality of AFE to anaphylaxis, complement activation and atony. It is probable that disseminated intravascular coagulation (DIC), induced by AFE, uterine atony and cervical laceration, caused the lethal hemorrhage. It is likely that AFE, in association with cervical laceration, induces uterine anaphylaxis, complement activation, atony, DIC and lethal hemorrhage.
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PMID:Amniotic fluid embolism induces uterine anaphylaxis and atony following cervical laceration. 2492 37