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)

Hemostatic abnormalities are present in a majority of patients with metastatic cancer. These abnormalities can be categorized as 1) increased platelet aggregation and activation, 2) abnormal activation of coagulation cascade, 3) release of plasminogen activator, and 4) decreased hepatic synthesis of anticoagulant proteins like Protein C and antithrombin III. The abnormal activation of coagulation cascade is mediated through release of Tissue Factor, Factor X activators, and other miscellaneous procoagulants from the plasma membrane vesicles of tumor cells. Macrophages of a tumor-bearing host also produce increased amounts of Tissue Factor. Production of Factor X activators and macrophage Tissue Factor is decreased by warfarin. The ability of the tumor cells to produce platelet-aggregating activity and plasminogen activator parallels their metastatic potential in animal and experimental systems. These studies also show that antiplatelet agents and antibodies against plasminogen activator can suppress the metastatic process. One or more laboratory abnormalities of hemostasis can be shown in up to 95% of patients with metastatic cancer. These abnormalities, however, are unable to predict subsequent development of thromboembolic or hemorrhagic complications. Clinical complications occur in 9-15% of the patients in the form of thrombotic or hemorrhagic disorders. The therapy of tumor-related coagulopathy should be guided by its clinical expression. Subclinical DIC should not be treated. Coumadin is generally ineffective for therapy of thrombosis in cancer patients. There is no consensus regarding the use of heparin in acute promyelocytic leukemia (APL). The defibrination in APL may be from disseminated intravascular coagulation as well as systemic fibrinolysis, as shown by decreased alpha 2 antiplasmin levels. In such cases, epsilon aminocaproic acid plus heparin therapy may be of benefit.
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PMID:Hemostasis in malignancy. 174 46

Coagulation studies were performed in a patient who had been bitten by a snake of the species Bothrops neuwiedi. The patient presented with hemorrhagic necrosis at the envenomization site and considerable bleeding from venous puncture sites. He developed a severe defibrination syndrome with a clottable fibrinogen level of approximately 0.1 g/l. Fibrinogen was not measurable by clotting time assay. Fibrin degradation products were greatly elevated. Treatment with antivenom caused an anaphylactic reaction within ten minutes and serum sickness after three days. In vitro experiments revealed that B. neuwiedi venom directly activates Factors II and X, but does not activate Factor XIII. In vivo consumption of Factor XIII after B. neuwiedi envenomization is ascribed to the action of Factor IIa. At low venom concentrations clotting is initiated by activation of prothrombin by the venom either directly or via Factor X activation. Treatment with heparin might be beneficial in coagulopathy secondary to snake bite by reducing circulating active thrombin. The venom contains thrombin-like proteases which cause slow clotting of fibrinogen, and plasmin-like components causing further proteolysis of fibrinogen and fibrin. Antivenom has no effect on the proteolytic action of the snake venom. The in vivo effects of antivenom are presumably caused by acceleration of the elimination of venom components from the circulation. Intravenous administration of antivenom caused normalization of blood coagulation parameters within 48 h.
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PMID:Coagulopathy after snake bite by Bothrops neuwiedi: case report and results of in vitro experiments. 229 86

Twenty-seven attacks of acute human pancreatitis of different severity were analysed concerning clinical outcome and activation of the coagulation and fibrinolytic systems. Consumptive coagulopathy was suggested by decreased platelet counts, decreased prothrombin values and consumption of fibrinogen during the first days in severe attacks. Factor X was slightly decreased the first 5 days in all attacks. Increased fibrinolysis was suggested by decreased plasminogen values in severe attacks. Fibrinogen degradation products were seen in 40% of the patients in blood and in 100% of the patients in the peritoneal fluid. The four main protease inhibitors of the two systems all showed protease-antiprotease complexation and lower functional than quantitative values. Plasma levels of antithrombin III and alpha 2-macroglobulin were low, while the levels of C1-inhibitor and alpha 2-antiplasmin were high. Functional levels of all the four protease inhibitors were almost zero in the peritoneal fluid in severe attacks. It is concluded that severe acute pancreatitis results in both consumptive coagulopathy and in increased fibrinolysis. A local antiprotease deficiency is seen in the peritoneal cavity and high levels of protease-antiprotease complexes are also seen in plasma. All these changes are closely correlated to the severity of the disease and may probably determine the clinical outcome of the acute attack.
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PMID:Consumptive coagulopathy, fibrinolysis and protease-antiprotease interactions during acute human pancreatitis. 351 16

Twenty-eight peritoneovenous shunts were placed to relieve ascites in 26 patients with a variety of underlying malignancies. Nine of the patients had documented liver metastases and hyperbilirubinemia. Severe thrombocytopenia with laboratory evidence of disseminated intravascular coagulation (DIC) occurred in four of these nine patients following shunt placement. Relative or absolute thrombocytopenia was also commonly observed in this series. Other complications included pulmonary edema, ventricular tachycardia, culture-negative fever, pneumonia, and late shunt occlusion. Good palliation, with relief of abdominal pain or respiratory compromise, was achieved in 57% of these patients. Our experience suggests that DIC following peritoneovenous shunts in patients with malignancy may be more common than previously reported, although not as frequent as the incidence of DIC associated with shunt placement for cirrhotic ascites. Platelet aggregation or Factor X activation by ascitic fluid and failure of the liver to inactivate activated clotting factors may play a role in this coagulopathy. Because of the risk of potentially fatal DIC, palliative peritoneovenous shunts should be considered with caution in patients with liver metastases and hyperbilirubinemia.
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PMID:Thrombocytopenia and laboratory evidence of disseminated intravascular coagulation after shunts for ascites in malignant disease. 399 80

An experimental animal model of disseminated intravascular coagulation (DIC) induced by the co-infusion of coagulant-active phospholipid and activated Factor X (Factor Xa) is described. The infusion of Factor Xa at a dose of 6.6 X 10(-12) mol/kg with phosphatidylcholine/phosphatidylserine (PCPS) lipid vesicles at a dose of 4.0 X 10(-8) mol/kg was associated with significant falls in the levels of fibrinogen and Factors V and VIII, and a bleeding diathesis developed. Assays of Factors V and VIII were performed by a one-stage prothrombin time and activated partial thrombin time system, respectively. In additional experiments, the effect of the same dose combination of Factor Xa/PCPS on Factor V kinetics was studied by preinfusing 125I-labeled Factor V. After Factor Xa/PCPS infusion, Factors VIII and V were reduced at 2 min by 90 and 50% of the preinfusion levels, respectively, and at 1 h by 80 and 75%, respectively. During the same period, there was little change in the total circulating radioactivity. Autoradiography indicated small but detectable levels of circulating proteolytic products of Factor V that comigrated with peptides obtained by the incubation of Factor V with Factor Xa and activated protein C. The majority of radioactivity remained associated with the intact single-chain precursor Factor V. These observations suggested maintenance of the precursor pool after the onset of DIC. This was confirmed by performing two-stage assays of Factors V and VIII, whereby each was completely converted to the active cofactor, i.e., Va and VIII:Ca, by preincubation of the test sample with thrombin before assaying in a one-stage system as before. The Factor V levels assayed by the two-stage procedure did not change appreciably over 1 h. The Factor VIII levels fell but corrected within 1 h at a time when the level measured by a one-stage assay remained depressed. These results indicate that in the dog, infusion of Factor Xa/PCPS induces changes characteristic of DIC, and this is associated with the appearance of Factor V peptides characteristic of the expression of Factor Xa and activated protein C-like activities. The differences noted between the one-stage and two-stage assays suggest that the one-stage assay is measuring the activated fraction of each cofactor and not the total level of the available precursor for each activated species. The results suggest a close correlation between the activated fraction of both cofactors and the hemostatic abnormality that occurs in DIC.
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PMID:Studies of Factors V and VIII:C in an animal model of disseminated intravascular coagulation. 643 44

Two patients diagnosed as having acute promyelocytic leukemia (APL) and disseminated intravascular coagulation (DIC) were closely followed from the day of admission until completion of the first course of chemotherapy with serial coagulation studies including plasma levels of functional antithrombin III activity (AT III) by fluorometric analysis and anti-activated Factor X activity (anti-Xa) by coagulation assay. Both patients were treated with intravenous heparin and the presence of heparin in plasma was followed by the thrombin time. Consistently normal levels of AT III (greater than 80%) were found despite evidence of intravascular coagulation. However, plasma levels of anti-Xa were often low (less than 70%) and increased only in the presence of heparin. The significance of these results in relationship to heparin therapy for disseminated intravascular coagulation of APL is discussed.
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PMID:Antithrombin III and anti-activated factor X activity in patients with acute promyelocytic leukemia and disseminated intravascular coagulation treated with heparin. 657

Two patients diagnosed as having acute promyelocytic leukemia (APL) and disseminated intravascular coagulation (DIC) were closely followed from the day of admission until completion of the first course of chemotherapy with serial coagulation studies including plasma levels of functional antithrombin III activity (AT III) by fluorometric analysis and anti-activated Factor X activity (anti-Xa) by coagulation assay. Both patients were treated with intravenous heparin and the presence of heparin in plasma was followed by the thrombin time. Consistently normal levels of AT III (greater than 80%) were found despite evidence of intravascular coagulation. However, plasma levels of anti-Xa were often low (less than 70%) and increased only in the presence of heparin. The significance of these results in relationship to heparin therapy for disseminated intravascular coagulation of APL is discussed.
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PMID:Antithrombin III and anti-activated factor X activity in patients with acute promyelocytic leukemia and disseminated intravascular coagulation treated with heparin. 695 57

Disseminated intravascular coagulation (DIC) is a common occurrence during clinical sepsis and can be induced in the experimental host by LPS. Fibrin deposition in the hepatic microcirculation has been observed within 30 min of i.v. injection of LPS. Because mononuclear phagocytes have been shown to produce a PCA after exposure to LPS, we have examined the ability of a homogeneous population of explanted hepatic macrophages to express PCA. Addition of as little as 10 ng/ml of LPS stimulated a 15- to 20-fold increase in PCA over control culture levels within 7 1/2 hr post-treatment. The PCA was found to be membrane-associated, with approximately 90 to 95% of the total PCA present in the cellular lysates, and more than 85% was inhibited by pretreatment of the cells with the diazonium salt of sulfanilic acid, an inhibitor of ecto-enzymes. In contrast to tissue thromboplastin produced by other M phi populations, the H-M phi PCA was found to be markedly sensitive both to heat inactivation at 56 degrees C and to inhibition by 1 mM DFP. Additionally, assays involving both a 1-stage coagulation test as well as an enzyme assay with a Factor Xa-specific substrate (using normal and deficient human plasmas) demonstrated that the H-M phi PCA appears to activate Factor X directly. Unlike tissue thromboplastin, the H-M phi PCA is non-dependent of Factor VII activation. These studies: 1) demonstrate the LPS induces a unique PCA in the H-M phi, and 2) support a role for the H-M phi in the initiation of DIC in endotoxemic shock.
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PMID:The induction of a unique procoagulant activity in rabbit hepatic macrophages by bacterial lipopolysaccharides. 702 10

Among 379 patients with AML with FAB type M1, 2 and M4-7 diagnosed between 1978 and 1997 in our institution, 19 (5%) had hypofibrinogenemia (HF), ie a fibrinogen level <180 mg/dl. Compared to patients with normal fibrinogen (n = 360) patients with HF had significantly elevated markers of activation of coagulation (TAT, F1.2, FPA) and fibrinolysis (D-dimer, FDP) indicating that disseminated intravascular coagulation/hyperfibrinolysis was the cause of hypofibrinogenemia. Patients with HF had significantly longer prothrombin times, thrombin clotting and reptilase times. Factor X and VIII were significantly lower than in patients without HF. With the exception of M7, HF occurred in all FAB subtypes, but was most common in M5 (12.1%). Patients with HF did not differ from those with normal fibrinogen with regard to age, sex, leukocyte count and other hematological parameters. During induction chemotherapy fibrinogen normalized rapidly (median 5 days) and there was no increased incidence of early hemorrhagic death. The overall and disease-free survival was similar to that of patients without HF.
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PMID:Hypofibrinogenemia in non-M3 acute myeloid leukemia. Incidence, clinical and laboratory characteristics and prognosis. 969 71

We examined tissue factor expression on lipopolysaccharide-stimulated endothelial cells and their small vesicles by using specific antibodies and flow cytometry. Tissue factor functional activity was also assessed by activation of factor X. Endothelial cells were stimulated with 10 microg/ml of lipopolysaccharide in M-199/bovine serum albumin. Flow cytometry showed that expression of tissue factor on endothelial cells reached a maximum at 6 hours after stimulation, whereas that on small vesicles reached a maximum after 12 hours. Factor X activation mediated by factor VIIa and tissue factor was observed over a similar time course and was inhibited by the addition of antitissue factor antibody. Immunoelectron microscopy suggested that small vesicles with expression of some tissue factor were produced from the surface of endothelial cells. Our findings thus showed that tissue factor on endothelial cells produced by lipopolysaccharide stimulation was partly released to small vesicles. This may cause disseminated intravascular coagulation and related coagulation disorders.
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PMID:Expression of functional tissue factor on small vesicles of lipopolysaccharide-stimulated human vascular endothelial cells. 977 11


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