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)

An unusual case of a 67-year-old man is reported with fulminant pneumococcal sepsis. He had been healthy before, and the identified predisposing factors were only that he was a chronic alcohol drinker and was a HCV carrier. He presented signs of acute renal failure, liver dysfunction, adult respiratory distress syndrome and disseminated intravascular coagulation. Subsequently purpura fulminans (symmetrical peripheral gangrene) with major extremity involvement developed. He finally survived with amputation of both legs, right forearm and two fingers of left hand. Purpura fulminans is a rare catastrophic disease, with initial hemorrhagic skin lesions that progress to gangrene. It usually follows an infectious illness, and although it most commonly occurs in children, it can occur in adults with predisposing factors such as alcoholic, asplenia, AIDS and so on. In adults, pneumococcus and meningococcus are microorganisms that have been reported most frequently as caused agents in Europe and America. But in Japan the previously reported adult case was the only one complicating Xanthomonas maltophilia sepsis, and none accompanying pneumococcal sepsis. Congenital protein C deficiency is recognized to be able to cause purpura fulminans especially in patients with risk factors. In our case, protein C antigen was decreased in the acute stage but gradually increased later toward normal, so this decrease was thought to be concomitant with the initial disseminated intravascular coagulation rather than compatible with protein C deficiency.
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PMID:[Purpura fulminans complicating pneumococcal sepsis: a case report]. 796 3

Thrombomodulin is an endothelial cell surface glycoprotein that forms a 1:1 complex with thrombin. In this form, thrombin can activate approximately 1,000-fold more protein C than thrombin alone and does not activate coagulation factors, V and VIII, and platelets. Activated protein C inactivates factors Va and VIIIa. Thus thrombomodulin converts thrombin from a procoagulant protease to an anticoagulant. The soluble thrombomodulin present in human urine and plasma appears to represent a truncated form that lacks the transmembrane and cytoplasmic domains of tissue thrombomodulin. The plasma level of thrombomodulin has been used as a marker for endothelial injury in vivo. Elevated levels of soluble thrombomodulin were reported in the plasma from the patients with disseminated intravascular coagulation, adult respiratory distress syndrome (ARDS), and diabetes mellitus retinopathy.
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PMID:[Soluble thrombomodulin: as a marker of endothelial injury]. 805 97

Snake venoms contain a rich variety of factors affecting the haemostatic mechanism which can be broadly classified as possessing coagulatant, anticoagulant and haemorrhagic activity. Coagulant enzymes include activators of blood coagulation factors II (prothrombin), V and X; anticoagulants include protein C activators, inhibitors of prothrombin complex formation and fibrinogenases which can be further classified according to their specificity for the alpha-, beta- and gamma-chains of fibrinogen. Intermediate between true coagulants and true anticoagulants are the thrombin-like enzymes which bring about clotting in vitro but defibrination (anticoagulation) in vivo. Snake venoms also affect platelets either by inducing or inhibiting platelet aggregation and cause haemorrhage via an action on platelets or via proteolysis of the blood vessel wall. Haemorrhagins also include inter alia, the alpha-fibrinogenases. This rich diversity of snake venom components affecting haemostasis has enabled a range of practical applications to be established including therapeutic anticogulation with thrombin-like enzymes (Ancrod and Defibrase) and laboratory tests for individual haemostatic factors (protein C, prothrombin, factor X and lupus anticoagulant). This broad spectrum of materials in snake venoms suggests some evolutionary advantage to the venom producer, not only for dispatching prey but as agents which 'spread' the venom toxins throughout the body and initiate digestion.
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PMID:Snake venoms affecting the haemostatic mechanism--a consideration of their mechanisms, practical applications and biological significance. 807 11

A normally functioning hemostasis system is closely related to liver function. The liver parenchymal cells produce most of the factors and inhibitors of the clotting and fibrinolytic systems, and the RES of the liver greatly aids in the clearance of activation products. Hemostasis defects thus depend on the extent of liver damage. A wide spectrum of defects is found in patients with liver cirrhosis. Owing to impaired protein synthesis, most factors and inhibitors of the clotting and the fibrinolytic systems are markedly reduced. Additionally, abnormal vitamin K-dependent factor and fibrinogen molecules have been encountered. Most patients have hyperfibrinolysis that could be DIC in nature. Thrombocytopenia and thrombocytopathy are also found. Acute or chronic hepatocellular disease may display decreased vitamin K-dependent factor levels, especially factor VII and protein C, with other factors still being normal. If patients go into hepatic failure, the abnormalities resemble those found in liver cirrhosis. Vitamin K deficiency is associated with the production of poorly functioning vitamin K-dependent factors. All other hemostasis parameters are normal. Disturbances associated with liver surgeries again depend on the underlying liver problem. Peritoneovenous shunts (LeVeen) may lead to DIC; bleeding from partially resected liver surfaces is usually a mechanical problem. Severe bleeding is encountered with orthotopic liver transplantation. It is greatly influenced by the activation of the fibrinolytic system. This occurs during the anhepatic phase and during the reperfusion phase. The hyperfibrinolysis is mediated by an intense release of t-PA. Antifibrinolytic drugs, if used cautiously, have markedly reduced bleeding and thus reduced need for blood and blood product substitution.
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PMID:Coagulation defects in liver disease. 817 Feb 58

Purpura fulminans is a rare syndrome of progressive hemorrhagic necrosis of the skin that may present as a dermatologic emergency. It most commonly affects children during the convalescent phase of a streptococcal infection or a viral exanthem. In adults, it may be associated with sepsis or acquired causes. Its pathogenesis has challenged physicians for decades. It has been discovered that purpura fulminans is almost always associated with disseminated intravascular coagulation and can occur in subjects with inherited or acquired deficiencies of the protein C anticoagulant pathway. Patients with liver compromise may also be potential candidates for coagulopathies secondary to hepatic dysfunction and impaired protein synthesis. It is widely recognized that individuals who consume alcohol on a long-term basis may develop severe hepatotoxicity from ingestion of therapeutic doses of acetaminophen (500 to 1000 mg every 4 to 6 hours). We have observed a patient with chronic alcoholism in whom hepatotoxicity and purpura fulminans developed secondary to the ingestion of acetaminophen.
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PMID:Acquired purpura fulminans induced by alcohol and acetaminophen. Successful treatment with heparin and vitamin K. 821 90

The pathophysiology of sepsis and septic shock is extremely complex and ultimately involves every physiological pathway. The initiating event is the entrance of endotoxin or similar substances into the blood which initiates the release of multiple mediators. These are designed to react locally and to protect the organism. Their constant release, however, sets in motion up- and down regulations, ultimately resulting in "metabolic anarchy". Tumor necrosis factor alpha and other cytokines trigger several systems, especially coagulation to yield DIC, and the complement system. Many treatment modalities have been developed, most recently those which substitute inhibitors of various systems. Antithrombin III concentrates and potentially protein C concentrates are designed to arrest DIC. C1-esterase inhibitor concentrates should intercept the activation of the complement system and the contact phase of coagulation and its relationship to kinin generation. Even newer approaches entail antibodies to tumor necrosis factor alpha or endotoxin itself. The complex process of sepsis will undoubtedly require a multifaceted therapeutic approach.
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PMID:Perspectives for the future. 822 36

Thrombomodulin (TM) is an endothelial cell membrane glycoprotein which neutralizes thrombin procoagulant activity and accelerates the thrombin-catalyzed activation of protein C. We expressed recombinant human soluble TM (rhs-TM) in Chinese hamster ovary cells and compared the effects of rhs-TM and heparin on endotoxin-induced experimental disseminated intravascular coagulation (DIC) in rats. Experimental DIC was induced by a continuous intravenous infusion of endotoxin for four hours. rhs-TM or heparin was infused simultaneously with endotoxin. Treatment with rhs-TM significantly reversed the endotoxin-induced changes in significantly reversed the endotoxin-induced changes in following parameters: platelet count, fibrinogen level and fibrinogen and fibrin degradation products. Furthermore, glomerular fibrin deposits elevated by endotoxin treatment were reduced by the rhs-TM administration. Heparin showed the similar effects to rhs-TM. Activated partial thromboplastin time (APTT) in rats receiving rhs-TM were slightly longer than APTT in endotoxin-treated rats, but rats receiving heparin had much more prolonged APTT. From these results, we concluded that rhs-TM may be useful for the clinical treatment of DIC while having only minor adverse effects on APTT.
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PMID:Antithrombotic effect of recombinant human soluble thrombomodulin on endotoxin-induced disseminated intravascular coagulation in rats. 823 61

A 26-year-old pregnant woman was diagnosed as having both lupus anticoagulant (LA) and anticardiolipin antibody (ACA). Her previous pregnancy ended in intrauterine fetal death at 27 weeks' gestation. During the present pregnancy she was treated with aspirin, dipiridamole, predonisolone, and heparin. At 24 weeks, fetal growth became retarded, accompanied by markedly decreased activities of AT-III, protein C, plasminogen and alpha 2-plasmin inhibitor. Supplement of human AT-III led both to prolongation of the gestational period and improvement of fetal growth. The pregnancy ended in cesarean section because of signs of fetal distress at 30 weeks. The infant was a 1025-g male with Apgar scores of 5 and 9 at one and five minutes, respectively, and is healthy. The mother developed DIC after surgery, but recovered after therapy. In this case, TAT, alpha 2PI-plasmin complex, FDP Ddimer, FPB beta 15-42, L-FDP showed little correlation with the clinical course.
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PMID:[Administration of human AT-III in a case of lupus anticoagulant positive pregnancy]. 831 36

Thrombomodulin-protein C system plays a very important role for the blood fluidity converting thrombin from a procoagulant protease to an anticoagulant and degrading activated factors Va and V III a. By their properties, both thrombomodulin and protein C may be expected for therapeutic medicines in DIC and some thromboembolic disorders. We reviewed and evaluated the probability of activated protein C and thrombomodulin for DIC treatment. Both appeared to be a very expectant for DIC medicine based on the preliminary clinical or experimental trials. Activated protein C is now under clinical trial in DIC. Recombinant thrombomodulin is also going to start its clinical trial in very near future.
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PMID:[Therapeutic strategy of newly developing medicines for disseminated intravascular coagulation--activated protein C and thrombomodulin]. 838 87

The bleeding diathesis in patients with acute promyelocytic leukemia (APL) is generally attributed to disseminated intravascular coagulation (DIC), initiated by the release of procoagulant activity from leukemic cells. Primary fibrinogenolysis, mediated by the release of leukocyte proteases, may also contribute to this disorder. We analyzed coagulation parameters in 15 non-septic APL patients. Before treatment, there was evidence of thrombin activation with DIC: increased levels of circulating thrombin-antithrombin III complexes, prothrombin fragments 1 + 2 and D-Dimer complexes. This DIC syndrome was probably limited, since no prothrombin time decrease, no significant factor V consumption, and normal levels of coagulation inhibitors (antithrombin III and protein C) were observed in APL patients when compared to normal controls. In this context, marked hypofibrinogenemia suggested primary fibrinogenolysis as the predominant etiology. Despite normal or high tissue plasminogen activator (tPA) and plasminogen activator inhibitor (PAI-1) antigen levels, the plasma PAI-1 activity and the formation of tPA/PAI-1 complexes were lower in APL patients than in normal controls, suggesting a proteolytic degradation of PAI-1, not able to complex tPA. Two other fibrinolytic inhibitor molecules (alpha-2 plasmin inhibitor antigen and histidine-rich glycoprotein antigen) were also significantly reduced, as well as the two subunits of fibrin stability factor XIII, although only subunit A is known to be susceptible to thrombin action. Evidence of degraded forms of von Willebrand factor in the plasma suggested an extended proteolytic activity. Four patients treated with all-trans-retinoic acid (ATRA) as a single differentiating agent were studied serially. A dissociation between these two syndromes--DIC and fibrinogenolysis/proteolysis--was observed. The rapid correction of the lysis markers contrasted with a more prolonged persistence of the procoagulant activity. We observed persistently high elastase/alpha 1-proteinase inhibitor complex levels during ATRA therapy, despite progressive correction of all lysis markers. Thus, the release of elastase from promyelocytic leukemic cells is probably not the only determinant of the fibrinogenolytic/proteolytic syndrome. In summary, the present findings provide new arguments for the association of DIC and proteolysis syndromes in APL-associated coagulation disorders. Further prospective studies are needed in order to confirm the persistence of thrombin activation in course of ATRA therapy.
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PMID:Coagulation disorders associated with acute promyelocytic leukemia: corrective effect of all-trans retinoic acid treatment. 841 75


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