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)

Homozygous protein C (PC) deficiency is a rare genetic defect that usually results in fatal thrombotic complications (purpura fulminans and DIC), but it can be successfully managed with oral anticoagulants or PC replacement. The successful use of PC replacement for two individuals is described. The activity and antigen levels of PC in fresh frozen plasma (FFP) and prothrombin complex concentrate (PCC) are also reported. The concentration of PC in FFP is 87 +/- 15 units/dl. PC is present in all PCC analyzed; however, a ten-fold difference between the various brands and/or lots is noted. The PC activity and antigen correlates well with no significant levels of APC. Upon infusion of FFP into two homozygous PC-deficient children, the PC levels obtained were less than or equal to 30 units/dl post-infusion and undetectable after 12-18 hr. With infusions of PCC, plasma levels of PC obtained were 100-145 units/dl and less than 10 units/dl after 48 hr. The percent recovery and half-lives of PC from FFP and PCC were 49.8% and 7.8 hr, and 84% and 7.4 hr, respectively. One infant was treated every 48 hr for 2 years without significant purpura fulminans or DIC complications. The levels of the other PC system components did not change during the infusion of the PC-rich material. Based on this information, a specific replacement protocol has been developed using a PC-rich concentrate. However, several problems may arise with the "less pure" PC-rich concentrates: catheter-tip thrombosis, related large vessel thrombosis and blood-transmitted diseases. With a specific PC concentrate, replacement therapy is a viable alternative for the long-term management/treatment of homozygous PC deficiency.
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PMID:Protein C survival during replacement therapy in homozygous protein C deficiency. 150 96

Activation and inactivation of protein C during the clinical course of disseminated intravascular coagulation (DIC) was studied in three patients by qualitative (Western blotting) and quantitative (ELISA) analysis and the intensity of procoagulant activity monitored by the measurement of thrombin and factor Xa antithrombin III complexes. In one patient, inhibitor complexes of APC with protein C inhibitor (PCI) and alpha 1-antitrypsin (alpha 1-AT) were observed and the latter predominated at presentation. Both disappeared during the development of remission but the loss of alpha 1-AT complexes preceded PCI complexes which on Western blotting appeared to increase in intensity prior to disappearance. The two other patients bled to death from uncontrollable haemorrhage. In both cases, APC/inhibitor complexes with alpha 2-macroglobulin (alpha 2-M) in addition to PCI and alpha 1-AT were detected and persisted until death. Although PCI appeared to be the primary inhibitor in all three cases, alpha 1-antitrypsin and particularly alpha 2-macroglobulin appeared to assume greater roles in the two fatal cases. These data are similar to previous findings in an experimental animal model of DIC that suggested that alpha 2-macroglobulin and alpha 1-antitrypsin become more important inhibitors of APC as the primary inhibitor PCI is consumed in the face of a sustained procoagulant challenge.
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PMID:Activation of protein C and its distribution between its inhibitors, protein C inhibitor, alpha 1-antitrypsin and alpha 2-macroglobulin, in patients with disseminated intravascular coagulation. 768 92

Protein C (PC) is the zymogen of an anticoagulant serine protease and is converted to its active form (activated protein C: APC) by thrombin in the presence of thrombomodulin. APC plays an important role in regulating thrombosis and fibrinolysis by inhibiting not only blood coagulation factors Va and VIIIa but also type-1 plasminogen activator inhibitor (PAI-1). In the present study we examined the effects of human APC on tissue thromboplastin-induced disseminated intravascular coagulation (DIC) in rabbits and compared them with those of heparin. Both APC (300-3000 U/kg) and heparin (100-300 IU/kg) inhibited the decreases in platelet count and fibrinogen level equally. APC improved the prolonged bleeding time, but heparin aggravated bleeding with potent prolongation of activated partial thromboplastin time (APTT). Furthermore, in APC-treated animals, fibrin deposition in glomeruli was less than in heparin-treated animals. This result that APC accelerated local fibrinolysis by neutralizing PAI-1. From our findings, we concluded that APC can improve both coagulation and fibrinolysis in a DIC model and should be useful for the clinical remedy of DIC without having an adverse side effect like a bleeding tendency.
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PMID:Characteristic effects of activated human protein C on tissue thromboplastin-induced disseminated intravascular coagulation in rabbits. 787 94

Coagulation factor V (FV) and factor VIII (FVIII) are usually decreased in septicemic DIC. Low doses of endotoxin administered to healthy volunteers stimulate activation of the fibrinolytic, contact and coagulation systems, but not clinical DIC. Following the administration of endotoxin (4 ng/kg) to normal volunteers (n = 15), we applied new assays for FV antigens using monoclonal antibodies to the activation peptide (C1) and to the light chain of FV. At 5 hours, FV coagulant activity was significantly decreased (64 +/- 9%), as was the FV light chain antigen (74 +/- 6%), without a change in factor V C1 antigen or total protein C. In contrast, FVIII coagulant activity was greater than preinfusion levels at 2-5 hours. The decrease in FV activity may be due to APC cleavage of FV heavy chain, but the loss of light chain antigen suggests that plasmin and/or calpain also contribute. APC may not be the only enzyme responsible for cofactor inactivation. FV is one of the most sensitive markers, even reflecting subclinical activation of coagulation.
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PMID:Cofactors V and VIII after endotoxin administration to human volunteers. 858 99

The HELLP syndrome (HS) belongs to the list of obstetric complications believed to be associated with coagulation disorders. It was formerly thought that chronic intravascular clotting (DIC) in the placental vessels was the main cause. A hypercoagulable state has been reported in cases of severe HS associated with microvascular abnormalities that may involve cerebral, placental, hepatic and renal vessels. A case of acute pancreatitis and DVT of inferior cava in a pregnant woman, presenting with HS at 29 weeks, who was found to have a R506Q mutation, is reported. Preeclampsia-associated pancreatitis and DVT have rarely been reported. It is hypothesized that APC-R and Factor V Leiden mutation may prove to be new and more important markers capable of predicting a more significant maternal morbidity associated with HS. Thrombosis prophylaxis may be considered during pregnancy in order to reduce hazardous multiorgan failure (MOF) in women who are heterozygous for Factor V Leiden mutation.
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PMID:Acute pancreatitis and deep vein thrombosis associated with HELLP syndrome. 1023 Feb 42

Protein C is the zymogen of an anticoagulant serine protease and is converted to its active form (activated protein C: APC) by thrombin in the presence of thrombomodulin. APC plays an important role in regulating coagulation and fibrinolysis by inactivating not only blood coagulation factors Va and VIIIa but also type-1 plasminogen activator inhibitor (PAI-1). The aim of the present study was to examine the effect of a human APC product (designated as CTC-111), compared with that of heparin, on the disseminated intravascular coagulation (DIC) induced by lipopolysaccharide (LPS) in rats. LPS (1 mg/kg/h) infusion was performed through a femoral vein for 4 h. One-fifth amount of the total dosage of CTC-111 or heparin was injected into the other femoral vein, followed by a 4-h infusion of the remainder. Both CTC-111 (10,000-100,000 U/kg) and heparin (400-800 IU/kg) inhibited the decrease in platelet count and fibrinogen level equally. The prolonged activated partial thromboplastin time and prothrombin time observed in DIC rats were further elongated in both CTC-111- and heparin-treated rats. But, this prolongation was less in CTC-111-treated rats than in the heparin-treated ones. Heparin inhibited the increase in fibrin and fibrinogen degradation products more prominently than CTC-111. On the other hand, CTC-111 strongly inhibited the increase in PAI-1 activity but heparin did not. These results suggest that CTC-111 may enhance fibrinolysis through its direct inhibitory effect on PAI-1. The parameters for liver or renal damage, i.e., plasma glutamic-oxaloacetic transaminase (GOT), glutamic-pyruvic transaminase (GPT), creatinine (Cre) and blood urea nitrogen (BUN), were significantly increased by LPS infusion. Both CTC-111 (100,000 U/kg) and heparin (800 IU/kg) decreased the increase in GOT and GPT levels significantly, whereas neither affected the increase in Cre or BUN. From these results, the activation of the blood coagulation system might partially contribute to the progression of liver damage caused by LPS, and might be less involved in the progression of renal damage in this model. In conclusion, CTC-111 showed both anticoagulant and profibrinolytic activity in the LPS-induced DIC model without excessive prolongation of coagulation time. From these results, CTC-111 is expected to be a useful remedy for DIC without the risk of bleeding.
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PMID:Effect of activated human protein C on disseminated intravascular coagulation induced by lipopolysaccharide in rats. 1105 Jun 97

Placental abruption is due to the rupture of the uterine spiral artery. The placenta separates totally or partially from the uterine wall during pregnancy. This serious syndrome has a great risk for the mother (shock and disseminated intravascular coagulation) and her child (mortality or morbidity). To the known risk factors like hypertension, the use of cocaine and smoking, homocysteine is recognized as an independent risk factor for vascular disease and endothelial dysfunction. In contrast to normal pregnancy where the spiral artery endothelium is replaced by trophoblast, the endothelium persists in case of placental abruption. In 165 women with placental vasculopathy and 139 matched controls hyperhomocysteinemia resulted in an odds ratio of 4.7 (95% CI: 1.6-14.0). The C677T mutation gave a risk of 2.5 (95% CI: 1.0-6.0). Even up to 2 or 3 years post-partum evidence could be found of endothelial dysfunction. The combination of hyperhomocysteinemia and thrombotic factors like APC resistance, Protein-C, Protein-S, antithrombin and factor V Leiden increases the risk of placental abruption 3-7 times. The common denominator of the effect of homocysteine on blood vessels could be sited in the process of proliferation of cells that need proper methyl groups for proper function (DNA synthesis and expression). These methyl groups are delivered by D-adenosylmethionine formed from methionine after remethylation of homocysteine. The coagulation factors and plasma homocysteine values can be modulated by vitamins, folic acid and folates in particular. To prove the clinical value of folate supplementation placebo-randomized trials are urgently needed: for placebo to be started after the period of neural tube closure.
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PMID:Clotting disorders and placental abruption: homocysteine--a new risk factor. 1130 Nov 73

The aim of this work was to assess the prevalence of the blood plasma resistance to activated protein C as a risk factor of disseminated intravascular coagulation (DIC) in acute-poisoned patients. The number of examined people was 231, including 140 acute-poisoned patients (of whom 83 showed DIC's finding) and 91 clinically healthy controls. The resistance of examined plasma to the anticoagulating properties of activated protein C was assessed by Chromogenix APC-Resistance V assay (APC-R-V). Abnormal results of APC-R-V were found to be 6-fold more frequent in acute-poisoned patients with DIC syndrome: 20 of 83 (24.1%), vs 3 of 91 (3.3%) for the control. The differences were statistically significant at p=0.0001 Mean values of coefficient R were statistically significantly lower in the acute-poisoned patients with DIC syndrome than the control, p<0.001. Genetic tests preformed in 37 patients confirmed V Leiden mutation to be present people whose R index value was below 2.0. Detection of APC-R in acute-poisoned patients could facilitate implementation of suitable preventive procedure before the DIC symptoms become manifest.
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PMID:[Blood plasma resistance to activated protein C as a risk factor of disseminated intravascular coagulation in acute-poisoned patients]. 1569 Jul 1