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)

Thirty-six patients with chronic myeloproliferative disorders (CMPD) were studied as regards blood coagulation and fibrinolysis. These studies revealed various mild abnormalities: activated thromboplastin time (APTT) tended to prolong and the level of factor V decreased significantly. In several cases, the levels of D-dimer, thrombin-antithrombin III complex and plasmin-alpha 2-plasmin inhibitor complex were elevated compared to normal. These results suggest that abnormal coagulation system in the patients with CMPD is related to low grade disseminated intravascular coagulation. Many coagulation factors did not correlate with peripheral blood cell counts. Two patients with polycythemia vera were evaluated for several abnormalities of the coagulation system before and during treatment. Coagulation abnormalities persisted after hematologic control had been achieved. Our results suggest that patients with CMPD have a chronic state of abnormal blood coagulation system even after normalization of blood cell counts.
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PMID:[Abnormal blood coagulation and fibrinolysis in chronic myeloproliferative disorders]. 187 Feb 70

Effects of low molecular weight heparin (FR-860) on experimental disseminated intravascular coagulation (DIC) models in rats were compared with those of conventional unfractionated heparin (UF-heparin) and other anticoagulants. In the endotoxin-induced DIC model, FR-860 (12.5-200 U/kg/hr) and UF-heparin (25-200 U/kg/hr) inhibited dose-dependently the decreases in platelet counts, fibrinogen, antithrombin III activity and alpha 2-plasmin inhibitor activity, and they also inhibited the increases in fibrin de-products and thrombus formation in the glomerular capillary bed. Neither gabexate mesilate (FOY, 10 mg/kg/hr) nor nafamostat mesilate (FUT, 0.1 mg/kg/hr) improved endotoxin-induced DIC. FR-860 showed comparable potency to UF-heparin in plasma anti-factor Xa (F.Xa) activity. However, FR-860 was weaker than UF-heparin in prolongation of activated partial thromboplastin time. In the thrombin-induced DIC model, both FR-860 and UF-heparin significantly improved, as seen in the endotoxin-induced DIC model, the changes in coagulation and fibrinolytic parameters and suppressed the production of pulmonary thrombus. On the other hand, both FOY and FUT showed significant but weak improvement in this model. In addition, FR-860 inhibited the enhancement of fibrinolysis and the production of pulmonary thrombus in the lactic acid-induced DIC model. These results suggest that the efficacy of FR-860 on DIC in rats is comparable to that of UF-heparin and that the efficacy can be attributed to its anti-F.Xa activity. FR-860 can be expected to be a useful therapeutic drug for DIC.
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PMID:[Effects of low molecular weight heparin (FR-860) on the experimental disseminated intravascular coagulation models]. 188 62

Increased pulmonary vascular resistance (PVR) and microvascular hyperpermeability resulting in lung edema and arterial hypoxemia are mainstays in the development of adult respiratory distress syndrome (ARDS). The proposed pathophysiologic mechanisms include activation of complement and polymorphonuclear leukocytes secreting lysosomal enzymes, toxic oxygen metabolites (TOM) and eicosanoids. Platelets and coagulation factors are also involved, and in the most severe cases even monocytes are activated as reflected in release of thromboplastin. The latter may elicit disseminated intravascular coagulation (DIC). Under physiologic conditions lung blood flow is diverted from poorly to better oxygenated areas by way of hypoxic pulmonary vasoconstriction (HPV), thereby counteracting a decrease in arterial oxygenation. Many vasoactive substances have been proposed and again refuted as possible mediators of HPV. In this study we have focused on the following: histamine, catecholamines, arachidonates, calcium, phosphoinositides and TOM as well as endothelium-derived relaxing and constricting factors. Whether HPV is present in ARDS and whether it is advantageous or not seems to depend on the stage and extent of disease. We discuss possible interactions between HPV and ARDS mediators and between HPV and various vasoactive agents tested for therapeutic effects. Out of the abundance of mediators released, prostacyclin, prostaglandin E1, activated complement and platelet activating factor have been shown explicitly to inhibit HPV whereas others are suspected of doing so. In therapeutical use, prostacyclin has proved to reduce PVR and at the same time enhance cardiac output and oxygen delivery. In mild to moderate ARDS, improvement of arterial oxygenation has also been obtained employing almitrine bismesylate, a potentiator of HPV. Experimentally, adenosine effectively reduces increments in PVR and microvascular permeability with modest effects on systemic circulation. However, further investigations are warranted to decide whether adenosine or more specific blockers as, for instance, monoclonal antibodies against tumor necrosis factor should be integrated in ARDS therapy in the future.
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PMID:Hypoxic pulmonary vasoconstriction in the adult respiratory distress syndrome. 192 27

Eighty-two women whose pregnancy was complicated by anemias of varying severity and twelve healthy pregnant women were examined. Blood plasma immunoglobulins A, G, and M were measured by immunochemical methods, as were the immune complexes of various levels and some parameters of the homeostasis system. The findings evidence a noticeable elevation of the concentrations of all immunoglobulins, of low-disperse immune aggregates in severe anemia of pregnancy, as well as intensive synthesis of immunoglobulin M in the fetus, low level of large immune complexes, and stimulation of some homeostasis components that results in consumption coagulopathy and chronic DIC syndrome. Correlations between some parameters of the blood coagulation and fibrinolysis systems, on the one hand, and humoral immunity characteristics, on the other, may be traced, among these correlations being reverse correlations between IgG level, activated recalcification time, fibrinogen concentration, and activated partial thromboplastin time.
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PMID:[Various factors of nonspecific resistance in pregnant women with anemia]. 195 69

High-dose interleukin-2 (IL-2) immunotherapy can cause hypotension, respiratory distress, interstitial edema, and thrombocytopenia, similar to endotoxic shock. We have observed that IL-2 has no direct effect on coagulation factors in vitro, but it has been observed to alter the coagulant properties of vascular endothelium. Accordingly, we investigated the possibility that IL-2 infusions initiate plasma fibrinolysis and disseminated intravascular coagulation (DIC). We studied the clinical course, platelet count, and coagulation profile in response to IL-2 infusion in seven patients, two with metastatic melanoma and five with metastatic renal cell carcinoma. Every patient experienced hemodynamic instability and thrombocytopenia, and one patient suffered an unusual complication, mesenteric thrombosis. No patient had appreciable changes in the prothrombin time or the partial thromboplastin time, nor did factors V or VIII decline in the two patients observed. In four patients examined, we found decreased titers of Hageman factor (factor XII), high molecular weight kininogen, prekallikrein, and plasma thromboplastin antecedent, as if these had been consumed by reactions of the intrinsic pathway of thrombin formation. Circulating D-dimer fragments were found in the plasma of every patient at some point during each infusion cycle, and we observed decreased titers of plasminogen in the four patients just mentioned, suggesting that IL-2 infusions initiated fibrinolysis. Taken together, the clotting factor derangements and related toxicity phenomena cannot be ascribed firmly to DIC. Activation of the intrinsic (contact) system of coagulation, however, may provide one link between the vascular endothelial surface alterations caused by IL-2 infusions and the development of the systemic toxicity that resembles septic shock.
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PMID:Fibrinolysis, thrombocytopenia, and coagulation abnormalities complicating high-dose interleukin-2 immunotherapy. 198 12

Antistasin (ATS) is a selective, tight-binding inhibitor of blood coagulation Factor Xa originally isolated from the salivary glands of the Mexican leech Haementeria officinalis. In order to provide sufficient quantities of ATS to further investigate the role of Factor Xa in blood coagulation, a recombinant version of ATS has been produced in an insect baculovirus host-vector system. In this study, we describe the purification and in vitro and in vivo characterization of a single recombinant antistasin (rATS) isoform. The purified protein constitutes a minor isoform relative to the more abundant ATS isoforms present in leech salivary gland extracts. In vitro, rATS inhibits purified human Factor Xa stoichiometrically, prolongs plasma-based clotting assays at nanomolar concentrations, and like native ATS, is cleaved at a single position by Factor Xa during the course of inhibition. An initial evaluation of the in vivo efficacy of rATS was addressed utilizing a rhesus monkey model of mild disseminated intravascular coagulation. rATS was shown to fully suppress thromboplastin-induced fibrinopeptide A generation in a dose-dependent fashion. The availability of rATS should provide a valuable tool for the critical evaluation of the specific role played by Factor Xa in coagulation.
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PMID:Purification and characterization of recombinant antistasin: a leech-derived inhibitor of coagulation factor Xa. 199 Sep 79

The hemostasis profiles of 24 dogs with histologically confirmed hemangiosarcoma were prospectively evaluated. Microangiopathic hemolysis was defined as the presence of schistocytes; disseminated intravascular coagulation was defined as 1) thrombocytopenia, 2) fibrin(ogen) degradation products greater than 10 micrograms/mL, 3) prolongation of one or more coagulation times (activated partial thromboplastin time or one-stage prothrombin time) by greater than 25% of the control, 4) fragmented red blood cells (greater than or equal to 1+ based on a semiquantitative grading scale), and 5) fibrinogen less than or equal to 80 mg/dL. Three of the five criteria listed above had to be met for disseminated intravascular coagulation to be diagnosed. Fifty percent of the dogs were considered to have disseminated intravascular coagulation at presentation. Thrombocytopenia was present in 75% of the dogs and was the most common abnormality. The mean platelet count was 137,800/microL. Twenty-five percent of the dogs died as a result of the hemostatic abnormalities. Only 12% of the dogs had microangiopathic hemolysis without other evidence of disseminated intravascular coagulation. Hemostatic abnormalities are present in many dogs with hemangiosarcoma at the initial clinical presentation and represent an important clinical finding.
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PMID:Hemostatic abnormalities in dogs with hemangiosarcoma. 202 11

Most infants with hemophilia have no bleeding in the neonatal period even if birth trauma occurs. The explanation for this lack of bleeding in the first few days of life in most hemophiliacs is unknown. Maternal factors VIII and IX fail to cross the placenta and cannot, therefore, protect the neonate. There have, however, been an increasing number of reports of severe neonatal bleeding in hemophiliac neonates. Herein, a case of severe neonatal bleeding responsible for hypovolemic shock and disseminated intravascular coagulation masking the hemophilia and delaying its diagnosis is reported. Transfusion of twice the total globular mass and exchange-transfusion were required. Hemorrhagic gastric necrosis occurred, requiring subtotal gastrectomy. The diagnosis of severe hemophilia A (factor VIII = 1%) was established only at 17 days of age. At the age of five months, the child developed a dumping syndrome which improved under appropriate dietary therapy and finally resolved. Outcome was favorable and at the evaluation at two years of age the child was leading a normal life. This case underlines the difficulty of the diagnosis of hemophilia at birth. When there is no family history of bleeding, the diagnosis of hemophilia is usually missed in the neonatal period and established only later or retrospectively. Factors VIII and IX should consequently be measured in male neonates with unusual bleeding and an increased activated partial thromboplastin time, even if disseminated intravascular coagulation is present. Prompt diagnosis and initiation of specific therapy may lessen acute morbidity and prevent long-term sequelae in affected infants.
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PMID:[Disseminated intravascular coagulation masking neonatal hemophilia]. 203 86

Disseminated intravascular coagulation (DIC) or renal damage associated with septicemia was induced in rats by ligating the cecum or by injecting endotoxin. In the septicemia model, the number of E. coli and Bacteroides spp in the blood increased concomitantly with an increase of endotoxin. In this model the development of hypercoagulability with mild fibrinolysis was observed. Histopathologic findings in the kidneys, including the formation of microthrombi in the glomeruli and the vacuolization and dilatation of renal tubular cells, suggest the development of mild DIC. In the endotoxin-induced DIC model, both remarkable state of hypercoagulability and fibrinolysis were observed with fibrin thrombi in glomeruli. The administration of the platelet-activating factor antagonist, CV-6209, or of human antithrombin III, ameliorated DIC significantly by limiting the increases in prothrombin time, activated partial thromboplastin time and fibrin degradation products. These agents significantly reduced the deposition of fibrin in the glomeruli and significantly prolonged the survival time of the endotoxin injected rats. These observations suggest that the PAF antagonist CV-6209 and ATIII merit clinical evaluation in the management of DIC caused by septisemia.
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PMID:Effect of a platelet activating factor antagonist and antithrombin III on septicemia and endotoxemia in rats. 206 2

To clarify whether activated platelets play an important role in the occurrence and exacerbation of disseminated intravascular coagulation (DIC), we investigated the effects of 4 anti-platelet drugs, a PGI2 analog (CS-570), a thromboxane synthetase inhibitor (dazoxiben), a thromboxane receptor antagonist (BM-13177), and ticlopidine, in an experimental DIC model in rats. Experimental DIC was induced by a continuous infusion of lipopolysaccharide (LPS derived from E. coli, 055 B5, 25 mg/kg/hr) for 4 hrs. In the time-course determination of the coagulation parameters and prostanoids, an abrupt increase in TxB2 (a stable metabolite of TxA2) and 6-keto-PGF1 alpha (a stable metabolite of PGI2) was followed by a decrease in platelet count, a prolongation of blood coagulation time, and an increase in fibrinogen/fibrin degradation products (FDP). Four hours after the start of LPS infusion, the rats were considered to be in the state of DIC. The effects of the anti-platelet drugs were investigated 4 hrs after the start of LPS infusion. CS-570 and ticlopidine ameliorated DIC in a dose-dependent manner. CS-570 (10 micrograms/kg/min) improved DIC in the platelet count, prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (Fbg), and FDP, without affecting TxB2 and 6-keto-PGF1 alpha formation. Ticlopidine (200 mg/kg, i.p.) prevented the exacerbation of DIC in such item parameters as platelet count, APTT, and FDP. Both dazoxiben and BM-13177 (30 mg/kg, i.p.) ameliorated DIC in following parameters as platelet count, APTT and FDP. Dazoxiben, but not BM-13177, significantly inhibited the increase in TxB2 concentration at 4 hr. These observations suggest that drugs which inhibit platelet activation by a TxA2-dependent route are effective in improving DIC induced by LPS, and that drugs which inhibit multiple platelet-activating routes improve DIC in more item parameters than drugs which inhibit only the TxA2-dependent activating route. Consequently, it is concluded that activated platelets might play an important role in the occurrence and exacerbation of DIC induced by LPS, and that one of the roles of TxA2 in DIC is to activate platelets.
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PMID:Role of activated platelets in endotoxin-induced DIC in rats. 208 Apr 92


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