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

This study has examined membrane lipid peroxidative damage, phospholipid (PL) organization, and coagulability of red blood cells (RBC) of newborns (N) and adults (A). Peroxidative lipid damage was assessed by quantitating malonyldialdehyde (MDA) by thiobarbituric acid-reactivity and by lipid extract fluorescence. Membrane PL organization was detected by Bee venom phospholipase-A2 (Plase) treatment, which specifically hydrolyzes outer bilayer phosphatidylserine (PS), phosphatidylethanolamine (PE), and phosphatidylcholine (PC). Coagulability was measured by Russell's viper venom clotting time. Results show MDA level of 7.47 +/- 0.72 in N-RBC and 3.86 +/- 0.23 nmoles/ml PCV in A-RBC, with relative lipid extract fluorescence of 12 +/- 1 and 9 +/- 1 U respectively. PLase hydrolyzed 63 PC, 9 PE, and 0% PS in A-RBC and 56 PC, 16 PE, and 8% PS in N-RBC, suggesting that a portion of PS is also present in outer bilayer in N-RBC. N-RBC took 16% less time than A-RBC to form a firm fibrin clot on recalcification. This study suggests significantly greater membrane lipid peroxidative damage in the neonatal RBC. Hypercoagulability due to the PS externalization in N-RBC may have a role in the disseminated intravascular coagulation of newborn infants.
 ...
PMID:Elevated malonyldialdehyde levels, altered membrane lipid asymmetry, and hypercoagulability of erythrocytes from newborn infants. 359

Patients affected with the hemorrhagic syndrome caused by contact with caterpillars of the Lonomia genus show digestive, pulmonary and intraperitoneal bleeding in combination with hematomas and echymosis. Hematuria is also frequently seen. Blood coagulation tests show prolongation of PT, aPTT and ThT. There is a decrease of Fg, FV, FXIII, Pg and alpha 2AP. Factor VIII and FvW are increased while the platelet count is unaffected. FDP's are increased and D-dimers are present in most cases. Treatment with whole blood or fresh frozen plasma worsens the clinical picture causing a severe drop in the platelet count often leading to renal failure and death. However, if antifibrinolytics, either alone or in combination with cryoprecipitate or purified fibrinogen, are administered, no change in the platelet count can be detected and the patients recover rapidly. It is concluded that this syndrome is caused by a mild disseminated intravascular coagulation (DIC) in combination with a hyperfibrinolytic state; the former being partially obscured by the latter, that manifests on administration of whole blood or fresh frozen plasma. Activators of FII, FV and Pg, and compounds showing FXa, plasmin and kallikrein-like activities have been identified in the Lonomia achelous venom. Proteases capable of degrading FXIII and extracellular matrix protein and an inhibitor of FV have also been isolated from these species. In Lonomia oblique, activators of FII and FX and an enzyme with phospholipase-like activity have been identified. In rabbits, subcutaneous injection of crude extract and one of the chromatographically purified fractions of Lonomia achelous venom causes a decrease of Fg, Pg and FXIII. Intravenous administration of the same fraction causes lysis of preformed thrombus with decrease of Fg, Pg and FXIII in combination with inhibition of thrombus growth. It should be noted that, under the same conditions, injection of Lonomia obliqua prothrombin activator causes a DIC.
 ...
PMID:[Hemorrhagic syndrome induced by caterpillars. Clinical and experimental studies. Review]. 1281 46

Pathologic disseminated intravascular coagulation (PDIC) is a serious complication in sepsis. In an in-vitro system consisting of incubation of fresh citrated blood with lipopolysaccharides (LPS) or glucans and subsequent plasma recalcification plasmatic thrombin was quantified. Five hundred microliters of freshly drawn citrated blood of healthy donors were incubated with up to 800 ng/mL LPS (Escherichia coli) or up to 80 microg/mL Zymosan A (ZyA; Candida albicans) for 30 minutes at room temperature (RT). The samples were centrifuged, and 30 microL plasma were recalcified with 1 volume or less of CaCl(2) (25 micromoles Ca(2+)/mL plasma). After 0 to 12 minutes (37 degrees C), 20 microL 2.5 M arginine, pH 8.6, were added. Thirty microliters 0.9 mM HD-CHG-Ala-Arg-pNA in 2.3 M arginine were added, and the absorbance increase at 405 nm was determined. Fifty microliters plasma were also incubated with 5 microL 250 mM CaCl2 for 5, 10, or 15 minutes (37 degrees C). Fifty microliters 2.5 M arginine stops coagulation, and 50 microL 0.77 mM HD-CHG-Ala-Arg-pNA in 2.3 M arginine starts the thrombin detection. The standard was 1 IU/mL thrombin in 7% human albumin instead of plasma. Arginine was also added in the endotoxin exposure time (EET) or in the plasma coagulation reaction time (CRT). Tissue factor (TF)-antigen and soluble CD14 were determined. LPS at blood concentrations greater than 10 ng/mL or ZyA at greater than 1 microg/mL severalfold enhance thrombin generation, when the respective plasmas are recalcified. After 30 minutes EET at RT, the thrombin activity at 12 minutes CRT generated by the addition of 200 ng/mL LPS or 20 microg/mL ZyA is approximately 200 mIU/mL compared to approximately 20 mIU/mL without addition of endotoxin, or compared to about 7 mIU/mL thrombin at 0 minutes CRT. Arginine added to blood or to plasma inhibits thrombin generation; the inhibitory concentration 50% (IC 50) is approximately 15 mM plasma concentration. Endotoxin incubation of blood increases neither TF nor sCD14. This assay allows the study of the hemostasis alteration in PDIC, particularly in PDIC by sepsis. The thrombin generated by blood plus endotoxin incubation and plasma recalcification suggests that the contact phase of coagulation; e.g., triggered by cell components of (phospholipase-) lysed cells such as monocyte or endothelium DNA or phospholipid-vesicles (microparticles), is of primary pathologic importance in sepsis-PDIC. Arginine at plasma concentrations of 10 to 50 mM might be a new therapeutic for sepsis-PDIC.
 ...
PMID:Thrombin generation by exposure of blood to endotoxin: a simple model to study disseminated intravascular coagulation. 1670 16

Brown spiders have world-wide distribution and are the cause of health problems known as loxoscelism. Necrotic cutaneous lesions surrounding the bites and less intense systemic signs like renal failure, DIC, and hemolysis were observed. We studied molecular mechanism by which recombinant toxin, biochemically characterized as phospholipase-D, causes direct hemolysis (complement independent). Human erythrocytes treated with toxin showed direct hemolysis in a dose-dependent and time-dependent manner, as well as morphological changes in cell size and shape. Erythrocytes from human, rabbit, and sheep were more susceptible than those from horse. Hemolysis was not dependent on ABO group or Rhesus system. Confocal and FACS analyses using antibodies or GFP-phospholipase-D protein showed direct toxin binding to erythrocytes membrane. Moreover, toxin-treated erythrocytes reacted with annexin-V and showed alterations in their lipid raft profile. Divalent ion chelators significantly inhibited hemolysis evoked by phospholipase-D, which has magnesium at the catalytic domain. Chelators were more effective than PMSF (serine-protease inhibitor) that had no effect on hemolysis. By site-directed mutation at catalytic domain (histidine 12 by alanine), hemolysis and morphologic changes of erythrocytes (but not the toxin's ability of membrane binding) were inhibited, supporting that catalytic activity is involved in hemolysis and cellular alterations but not toxin cell binding. The results provide evidence that L. intermedia venom phospholipase-D triggers direct human blood cell hemolysis in a catalytic-dependent manner.
 ...
PMID:Identification of a direct hemolytic effect dependent on the catalytic activity induced by phospholipase-D (dermonecrotic toxin) from brown spider venom. 1945 8