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)

The mechanism of the early stage of metastasis formation by sticky blood-born cancer cells is discussed. Abnormal platelet aggregation to circulating and lodged cancer cells, as well as alterations of blood coagulation and fibrinolysis play an important role. The reducing effect of several platelet aggregation inhibitors on cancer cell stickiness and tumor embolism mortality has been investigated in rats after intravenous transplantation of 1 X 10(6) Walker-256 carcinosarcoma cells. The tested substances diminished platelet aggregation to circulating cancer cells, leading to a dose-dependent inhibition of cancer cell lodgment to the endothelium. Furthermore, some of the substances prevented lethal pulmonary tumor cell embolism which was observed in 60% of the controls. These results are interpreted by assuming an inhibition of disseminated intravascular coagulation which occured after intravenous transplantation of Walker-256 carcinosarcoma. On this basis a clinical long-term study for metastasis prophylaxis was started more than 4 years ago with one of the tested substances, the dipyridamole derivative RA 233, in 40 patients with sarcoma or malignant lymphoma of the head and neck region. The provisional results obtained in matched pairs are discussed.
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PMID:Platelet-cancer cell interaction in metastasis formation: a possible therapeutic approcach to metastasis prophylaxis. 26 96

Employing the test model which we developed for the investigation of platelet adhesiveness and aggregation in vivo, experiments demonstrated that the sulfonyl urea derivatives, glibenclamide, gliclazide, and HB 180, as well as the carboxylic acid derivative, meglitinide, are able to inhibit, in a dose-dependent relationship, the adherence of i.v. injected Walker-256-carcinosarcoma cells to the vascular endothelium of the rat mesentery, as well as to reduce significantly the rate of instantly occurring terminal tumor cell embolism of the lung. Since venous blood platelet count in surviving animals is inversely proportional to the number of the tumor cells which adhere to the vascular endothelium, one can deduce that tumor cell embolism is an immediate result of a massively occurring disseminated intravascular coagulation (DIC) which may be induced by i.v. injection of thromboplastic active carcinosarcoma cells and leads primarily to a drastic platelet count reduction. All four substances inhibit this platelet count reduction as well as the directly correlated tumor cell embolism mortality rate in a linear dose-dependent fashion. Their action can therefore be explained as being mediated via an inhibition of platelet adhesion and aggregation to the circulating tumor cells. Our proof of platelet aggregation in vivo correlates with the results obtained by Klaff et al. (1979), as far as a normalization of the pathologically increased platelet aggregation tendency in vitro in diabetics following 4-6 weeks of therapy with the sulfonyl urea derivatives glibenclamide and gliclazide.
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PMID:The inhibition of cancer cell stickiness, a model for investigation of platelet aggregation inhibitors in vivo. Effect of the sulfonyl urea derivatives, glibenclamide, gliclazide, and HB180, as well as the carboxylic acid derivative, meglitinide. 680 52

In rats bearing the solid Walker 256 carcinosarcoma microangiopathic haemolytic anaemia (MHA) developed during the course of tumour growth. A phase of hypercoagulability was followed by a significant decrease in plasma fibrinogen, platelet count and antithrombin III. A diminished haematocrit and a rise in plasma haemoglobin and schistocyte count were accompanied by fibrin deposits in the tumour vessels. When the rats were treated with heparin during the growth of the Walker tumour, both DIC and MHA were prevented except of the last period of the experiment. The tumour sizes, however, did not differ in the controls and the heparinized animals. There is a fair amount of evidence to suggest that the MHA was induced by a tumour-dependent DIC which was blocked by heparin over a certain time period. In contrast, the tumour growth was not modified by effective suppression of DIC and MHA.
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PMID:Heparin treatment of microangiopathic haemolytic anaemia associated with an experimental tumour. 716 29

In southern Brazil, envenomation by larvae of the moth Lonomia obliqua (Walker) may result in blood clotting factor depletion, leading to disseminated intravascular coagulation with subsequent haemorrhage and acute renal failure which may prove fatal. We have examined the effect of a crude extract of spicules from these caterpillars on in vitro hemostasis. The extract alone did not aggregate platelets and had no detectable effect on purified fibrinogen, suggesting that extract induces clot formation by triggering activation of the clotting cascade. In agreement with the presence of thrombin-mediated activity, hirudin prevented clot formation. The extract was found to activate both prothrombin and factor X, suggesting that the depletion of blood clotting factors results from the steady activation of factor X and prothrombin. Heating and diisopropylfluorophosphate abolished the procoagulant activity of the extract, indicating that the active component involved is a protein that may belong to the serine protease family of enzymes. The ability of hirudin to inhibit this coagulant activity suggests that this inhibitor could be beneficial in the treatment of patients envenomed by L. obliqua caterpillars.
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PMID:Lonomia obliqua caterpillar spicules trigger human blood coagulation via activation of factor X and prothrombin. 953 Oct 36

In southern Brazil, since 1989, several cases of accidents produced by unwilling contact with the body of poisonous caterpillars of the moth species Lonomia obliqua Walker, 1855 (Lepidoptera: Saturniidae), were described. L. obliqua caterpillars have gregarious behavior and feed on leaves of host trees during the night, staying grouped in the trunk during the day, which favors the occurrence of accidents with the species. This caterpillar has the body covered with bristles that on contact with the skin of individuals, breaks and release their contents, inoculating the venom into the victim. The basic constitution of the venom is protein and its components produce physiological changes in the victim, which include disturbances in hemostasis. Hemorrhagic syndrome associated with consumption coagulopathy, intravascular hemolysis and acute renal failure are some of the possible clinical manifestations related to poisoning by L. obliqua. Specific laboratory tests for diagnosis of poisoning have not been described previously. The diagnosis of poisoning is made based on the patient's medical history, clinical manifestations, erythrocyte levels, and, primarily, parameters that evaluate blood coagulation. Treatment is performed with the use of supportive care and the administration of specific hyperimmune antivenom. Poisoning can be serious and even fatal.
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PMID:Lonomia obliqua Walker (Lepidoptera: Saturniidae): hemostasis implications. 2624 50