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)

Human protein C is the central protein of an important regulatory mechanism, as shown by the high incidence of thromboembolic complications in congenital deficiencies of protein C. Both abnormal molecules and half-normal levels of protein C antigen and activity have been found in patients with familial thrombotic complications. Newborn infants with congenital homozygous protein C deficiency develop catastrophic thrombosis (purpura fulminans) and will not survive beyond the neonatal period without protein C replacement. Individuals with systemic thrombosis have significantly decreased levels of protein C concomitant with the severity of the DIC. These studies suggest that protein C is important not only in the congenital deficiencies, but also in acquired deficiencies, such as during DIC or possibly the postsurgical hypercoagulable state.
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PMID:Protein C in thromboembolic disease. 384 Sep 18

Protein C was measured by means of enzyme-linked immunosorbent assay (ELISA) in plasmas from 58 normal subjects, 39 patients with disseminated intravascular coagulation (DIC) and 5 patients with thrombotic thrombocytopenic purpura (TTP). Protein C levels ranged from 69.7 to 163.6% (95% confidence limits) in normal subjects. In patients with DIC, protein C concentrations were significantly decreased, with a geometric mean value of 42.1%. Protein C concentration was positively correlated with plasma prothrombin, antithrombin III and serum pseudocholinesterase, and was negatively correlated with von Willebrand factor antigen (vWF:Ag) and vWF:Ag/factor VIII ratio. These findings suggest that low protein C concentrations in DIC mean a consumption of protein C probably due to its activation by thrombin and/or impaired liver synthetic function. In patients with TTP, protein C levels were normal with a geometric mean value of 116.7%, indicating that the pathophysiology of TTP is quite different from that of DIC.
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PMID:Protein C levels in disseminated intravascular coagulation and thrombotic thrombocytopenic purpura: its correlation with other coagulation parameters. 384 Dec 32

An enzyme-linked immunosorbent assay (ELISA) for measuring human protein C by using two monoclonal antibodies directed toward the heavy chain of protein C is reported. This assay enabled the determination of protein C in concentrations of 10 to 400 ng/ml in less than 3 hours with a single antigen-antibody reaction. Within-run and between-run coefficients of variation were less than 8%. The mean concentrations of protein C in plasma of 42 normal subjects, 24 patients with liver disease, 27 with DIC, 48 with warfarin therapy and 15 with congenital protein C deficiency, were 4.2, 3.0, 2.3, 2.1 and 1.9 micrograms/ml, respectively. The results obtained with the present ELISA correlated well with those of radioimmunoassay (r = 0.935, n = 81) as well as those of Laurell's Rocket method (r = 0.910, n = 81) by using rabbit anti-human protein C serum. The present method was sensitive and specific for measurement of protein C and also PIVKA-protein C in plasma.
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PMID:Enzyme immunoassay of human protein C by using monoclonal antibodies. 389 62

This study was undertaken to determine the levels of protein C antigen and activity and protein C inhibitor in sequential plasma samples of disseminated intravascular coagulation (DIC) patients. Our normal range for both protein C antigen and activity is 70 to 130 U/dL, and protein C inhibitor is 65 to 135 U/dL. A decreased level of protein C activity was found in 96% of the plasma samples from individuals with DIC; the protein C antigen was decreased in 73%. The inhibitor of protein C was decreased in all samples. Analysis of serial samples from patients with DIC reveals that protein C activity and antigen and protein C inhibitor decrease progressively during the initial stages of DIC and remain at a low level for 24 to 48 hours before gradually returning toward normal in nonfatal cases. The protein C activity decreases in parallel with protein C inhibitor and is lower than protein C antigen. In a fatal case of DIC, protein C activity and protein C inhibitor rapidly decreased to undetectable levels; however, protein C antigen was gradually decreasing but still detectable at time of death. In DIC, a discrepancy initially occurs between the activity and antigen of protein C, suggesting a complex with the inhibitor or other inactive forms of protein C. Protein C appears to play a major role in the control of DIC.
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PMID:Serial studies of protein C and its plasma inhibitor in patients with disseminated intravascular coagulation. 392 42

Protein C is a vitamin-K-dependent plasma glycoprotein that when activated inhibits coagulation by selectively inactivating the active forms of factor V and factor VIII. A specific antiserum to protein C has been raised, and plasma protein C levels have been measured by means of an electroimmunoassay in several physiological and pathological conditions. In 60 healthy adults there were no differences in protein C related to age or sex; protein C levels ranged from 72 to 139% of values in a normal plasma pool. Low levels were found in 12 healthy full-term newborn infants; the levels in 20 women in the last trimester of normal pregnancy were no different from those in healthy non-pregnant women. In 58 patients with chronic liver diseases protein C levels were lower than those in healthy subjects, in degrees roughly proportional to the severity of the disease. Protein C levels were very low in 21 patients with the disseminated intravascular coagulation syndrome, particularly in those who had evidence of consumption coagulopathy. Very low levels were also found, however, in 20 patients with adult respiratory distress syndrome without consumption coagulopathy. Acquired defects of protein C developed after surgery in the patients operated on for malignancies, after major abdominal operations for benign conditions, and also after relatively minor procedures such as appendicectomy and hernia repair. These findings indicate that protein C deficiencies occur in several conditions associated with increased tendency to thrombosis.
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PMID:Deficiencies of protein C, an inhibitor of blood coagulation. 612 39

A coumarin-responsive chronic relapsing purpura fulminans syndrome is described in a protein-C-deficient newborn infant. Episodes of acute disseminated intravascular coagulation (DIC) and cutaneous gangrene, which first appeared at age 11 h, were effectively controlled for 28 months with transfusions of fresh-frozen plasma. Cryoprecipitate and cryoprecipitate-poor plasma induced remissions as long as those induced by fresh-frozen plasma (less than or equal to 72 h). Coumarins sustained a cryoprecipitate-induced remission for 19 days: they were then electively discontinued and 17 h later the patient had an acute exacerbation of DIC with haemorrhaging. Family studies showed protein C levels of 31-40% in the subject's symptom-free mother and full and half brothers. DIC, the coumarin effect, and the inherited protein C abnormality appear to have contributed to the extremely low plasma levels (less than or equal to 6%) of protein C in the patient. This experience suggests that protein C deficiency may greatly compromise the ability of newborn infants to control consumptive disorders.
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PMID:Inherited protein C deficiency and coumarin-responsive chronic relapsing purpura fulminans in a newborn infant. 613 28

A relapsing clinical syndrome of skin lesions and disseminated intravascular coagulation (DIC) that showed remission with the infusion of fresh frozen plasma is described in a newborn infant with homozygous deficiency of protein C antigen. This patient presented since birth a recurrent clinical picture of DIC and ecchymotic skin lesions that resembled typical ecchymosis except for the fact that they showed immediate improvement with the administration of fresh frozen plasma. Using an enzyme linked immunosorbent assay method, the determination of protein C antigen levels in the patient, without ingestion of coumarin drugs, showed very low values (less than 1%). No other deficiencies in the vitamin-K-dependent factors or in antithrombin III, antiplasmin, and plasminogen were found. Seven relatives of the infant had heterozygous deficiency in protein C antigen (values between 40-55%), without clinical history of venous thrombosis. The pedigree analysis of this family suggests an autosomal recessive pattern of inheritance for the clinical phenotype, although an autosomal dominant pattern has been postulated until now in other reported families. We conclude that our patient has a homozygous deficiency in protein C and this homozygous state may be compatible with survival beyond the neonatal period.
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PMID:Severe inherited "homozygous" protein C deficiency in a newborn infant. 654 87

We measured levels of protein C inhibitor in patients with disseminated intravascular coagulation (DIC) and liver disease using a functional assay. Levels in 24 normal subjects averaged 93% of the amount in normal pooled plasma, giving a normal range of 65 to 121%. Levels were below normal in 8 of 17 patients with DIC, in 4 of 19 patients with liver cirrhosis, and in 3 patients with acute hepatic necrosis. Levels were normal or elevated in 9 of 10 patients with cirrhosis and accelerated fibrinolysis, and in 6 patients receiving warfarin. We conclude that protein C inhibitor may be involved in regulation of protein C activity during pathologic activation of the hemostatic system (DIC). Decreased protein C inhibitor does not appear to contribute to the pathogenesis of accelerated fibrinolysis in liver disease. The liver may be the site of synthesis of protein C inhibitor.
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PMID:Behaviour of protein C inhibitor in intravascular coagulation and liver disease. 654 88

We have developed a radioimmunoassay (RIA) for the dodecapeptide that is liberated from protein C when this zymogen is activated by thrombin bound to thrombomodulin present on the vascular endothelium. The protein C activation peptide (PCP) was synthesized using the solid-phase method of Merrifield. Antisera were raised in rabbits to the synthetic analogue coupled to bovine serum albumin with glutaraldehyde. The antibody population obtained was used together with a 125I-labeled tyrosinated ligand and various concentrations of unlabeled PCP to construct a double antibody RIA capable of measuring as little as 10 pM of this component. We have established that the synthetic dodecapeptide has the same immunoreactivity as the native peptide and that the reactivity of protein C is less than 1/2,000 that of PCP on a molar basis. The extremely low levels of peptide in normal individuals as well as the nonspecific contributions of plasma constituents to the immunoreactive signal, necessitated the development of a procedure by which the PCP could be reproducibly extracted from plasma and concentrated approximately 20-fold. This methodology permitted us to demonstrate that the plasma PCP levels in 17 normal donors averaged 6.47 pM, and that elevations up to 180 pM were observed in individuals with evidence of disseminated intravascular coagulation. The validity of these measurements of protein C activation is supported by the fact that, in both of these situations, the RIA signal migrates on reverse-phase high pressure liquid chromatography in a manner identical to that of the native dodecapeptide. We have also noted that the mean PCP concentration in seven patients fully anticoagulated with warfarin averaged 2.61 pM. Our studies also show that PCP is cleared from the plasma of primates with a t1/2 of approximately 5 min. Given that the t1/2 of activated protein C is estimated to be 10-15 min, the latter enzyme appears to exert its effects on the activated cofactors of the coagulation system at concentrations considerably less than 1.0 nM.
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PMID:Detection of protein C activation in humans. 654 15

Protein C, a newly identified inhibitor of blood coagulation, was measured immunologically in 58 patients with untreated acute leukemias and compared with that of normal subjects. On the average, slightly lower values were found. However, the 17 patients with overt laboratory pictures of decompensated disseminated intravascular coagulation (DIC), including 11 cases with acute promyelocytic leukemia, had protein C concentrations no lower than those of the remaining 41 patients without DIC. Antithrombin III activity and antigen were normal and, like protein C, not lowered in DIC. The concentrations of both proteins were closely correlated with changes in the indexes for liver synthetic function. A subgroup of 13 patients with hyperleukocytic leukemias had lower protein C and antithrombin III, in line with the more compromised synthetic function of their livers. Our findings indicate that liver impairment rather than DIC is the main cause of the changes in the two naturally occurring inhibitors of blood coagulation.
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PMID:Liver dysfunction rather than intravascular coagulation as the main cause of low protein C and antithrombin III in acute leukemia. 658 88


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