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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 sick neonate may develop spontaneous or catheter-related thromboses, which must in part reflect poor regulation of the formation and activities of the coagulation enzyme, thrombin. We hypothesized that the balance between the generation and inhibition of thrombin may differ in sick neonates compared with healthy neonates. Fifty neonates with respiratory failure requiring mechanical ventilation and 40 healthy neonates were studied on d 1 of life. All neonates had normal coagulation screening tests and a platelet count greater than 150 x 10(9)/L. Plasma pools from neonates with similar gestational age (GA), birth weight, and health status were prepared. Eight plasma pools from 40 healthy neonates of GA 30-38 wk were compared with six plasma pools from 30 sick neonates of GA 30-38 wk. An additional four plasma pools prepared from 20 sick neonates of GA less than 30 wk were studied. Thrombin generation was measured by amidolysis of a chromogenic substrate, S2238, after defibrination, contact activation, and recalcification of the test plasmas. The contributions of antithrombin III, heparin cofactor II, and alpha 2-macroglobulin as inhibitors of 125I-thrombin were quantitated by SDS-PAGE followed by autoradiography and densitometry. Thrombin generation was similar for both healthy and sick neonates of GA 30-38 wk. However, the inhibition of thrombin was impaired in plasma from sick neonates of GA 30-38 wk compared with plasma from healthy neonates of GA 30-38 wk (4.37 +/- 0.22 versus 5.21 +/- 0.21 nmol; p less than 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Thrombin inhibition is impaired in plasma of sick neonates. 137 86

We measured plasma heparin cofactor II (HC II) activity in patients with disseminated intravascular coagulation (DIC) due to various underlying diseases together with the levels of antithrombin III (AT III), pseudocholinesterase (a marker of hepatic synthesis), and various haemostatic molecular markers. Both HC II and AT III were decreased in DIC secondary to all the underlying diseases studied, except acute promyelocytic leukemia (APL), when compared with healthy subjects. The lowest HC II and AT III levels was observed in coagulopathy secondary to liver disease, the HC II level in sepsis was the second lowest. In DIC due to APL, the decrease in HC II was not accompanied by a decrease in AT III. Thus, we divided all 124 samples tested into APL and non-APL groups. The HC II level correlated positively with fibrinogen and plasminogen in both the APL and non-APL groups. In the APL group, the HC II level had a significant negative correlation with the thrombin-AT III complex (TAT), fibrinogen/fibrin degradation products, and D-dimer levels as well as the prothrombin time, while AT III showed no correlations with any of the haemostatic parameters. These results suggest that HC II may be consumed preferentially by thrombin in APL patients with DIC, and thus may spare the consumption of AT III. Accordingly, HC II seems to be a superior indicator of DIC than AT III in APL patients. Moreover, replacement therapy with HC II instead of AT III may be useful to treat DIC associated with APL. In the non-APL group, the HC II levels were positively correlated with the levels of AT III and pseudocholinesterase activity. This indicates that plasma HC II levels are closely related not only to consumption coagulopathy but also to hepatic synthetic activity, as is the case for plasma AT III.
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PMID:Preferential consumption of heparin cofactor II in disseminated intravascular coagulation associated with acute promyelocytic leukemia. 141 8

An ELISA assay for quantitation of the thrombin-heparin cofactor II complex (T-HC II) in plasma was developed. Plasma was incubated with immobilized, specific antibodies to human thrombin. The second, biotinylated antibody was directed against human HC II. The assay was insensitive to thrombin-antithrombin complex (TAT) and to uncomplexed HC II. In plasma samples from 31 normal individuals (aged 21-68, mean 43.3 years), the T-HC II ranged 0.3-6.1 ng/ml; median 1.5, mean 2.0, and SD 1.6 ng/ml. In plasma samples from 13 patients with disseminated intravascular coagulation (DIC), T-HC II ranged 0.4-30.0 (median 13.5) ng/ml. In plasma samples from 6 patients in which the clinical suspicion of DIC was not verified, T-HC II complex ranged 1.4-14.3 (median 3.6) ng/ml. In plasma samples with elevated T-HC II levels, TAT was usually elevated, and on the average more than was T-HC II. These results indicate that HC II contributes significantly to the inactivation of in vivo generated thrombin.
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PMID:Elevated levels of thrombin-heparin cofactor II complex in plasma from patients with disseminated intravascular coagulation. 152 13

To investigate the physio-pathological functions of HC-II, assays for HC-II and AT-III were performed simultaneously on the samples from patients with DIC, liver dysfunction or renal disease from the three view points of consumption, production and loss of AT-III and HC-II. For the AT-III activity, two kinds of assays were applied: the automatic chromogenic substrate method and a newly developed clotting method which receives no effects from HC-II activity. The activity of HC-II was significantly lower than that of AT-III in patients with either DIC or liver dysfunction. However, no significant difference between HC-II and AT-III activities in patients with either thrombosis or renal disease. There were high correlations between HC-II and AT-III activities were found in the patients with liver dysfunction, suggesting that low activity was due to decreased production of HC-II and AT-III in the liver. It will be necessary that elucidation of the significant functions of HC-II not only in coagulation and hemostasis but also in regulation of local inflammation and invasion of neoplasm is necessary.
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PMID:[Activities of antithrombin III and heparin cofactor II in patients with pathologic blood coagulation conditions]. 157 30

A simple method for biological assay of dermatan sulfate (DS) in plasma is described. DS accelerates thrombin inhibition by heparin cofactor II (HC II). The principle of the assay is to measure the residual amidolytic thrombin activity after a short period of incubation with HC II in defibrinated plasma at low ionic strength. For this method we take advantage of two observations. Firstly, at fixed concentrations of DS and of HC II, the rate of thrombin inhibition increases when the ionic strength of the medium decreases. Secondly, defibrination by bentonite absorption also removes antithrombin III, HC II and for a large part alpha-2 macroglobulin from the plasma, so that no other thrombin inhibitor competes with HC II added as a reagent in a second step. In the conditions described, there is a linear relationship between DS concentrations in plasma from 0 to 2 micrograms/ml and the log of residual thrombin activity. The limit of sensitivity is 0.1 micrograms/ml. The assay displays an acceptable reproducibility in intra-assay, inter-assay and inter-individual experiments. It can be used to measure DS in human, rabbit and rat plasmas. The assay is also sensitive to other HC II activators such as heparin and pentosan polysulfate. DS is effective in experimental thrombosis without any detectable anticoagulant effect ex vivo. Pharmacological concentrations of DS in plasma fall into the range of sensitivity of this assay, which would be helpful in experimental or clinical studies of DS and related glycosaminoglycans.
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PMID:A simple method to measure dermatan sulfate at sub-microgram concentrations in plasma. 321 19

A simple assay method of heparin cofactor II (HC II) activity is described. The procedure is based on the following principle: Antithrombin III (AT III) in plasma is inactivated by addition of an IgG fraction of goat serum after immunization of the animals against human AT III. Complete inactivation of AT III could be shown by absence of an anti Xa-effect of heparinized plasma treated with this antibody. Thrombin was only partially inhibited after inactivation of AT III. The characteristics of this inhibition were typical for the action of HC II. This method was applied for an assay of HC II activity. After optimizing of the method practical application in clinical routine screening was carried out. A diminution of HC II was observed in liver cirrhosis and in DIC but not in AT III deficiency. In 15 out of 269 cases of recurrent DVT there were HC II activities below 70% of normal. In 4 out of these patients activities of HC II were repeatedly between 44% and 52%. In arterial obstructive disease there was an HC II activity of less than 60% in 18 out of 583 patients and in 11 of them the HC II levels were repeatedly between 45% and 54%.
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PMID:Heparin cofactor II: a simple assay method and results of its clinical application. 342 87

Reversible acute disseminated intravascular coagulation (DIC) has been induced in dogs by intravenous injection of homologous tissue thromboplastin. There was no measurable consumption of antithrombin III and heparin cofactor II even if fibrinogen was reduced during DIC by more than 80% of its baseline. The prothrombin level remained practically constant. These data correspond to the generation of a few nanomoles of thrombin in vivo with subsequent pseudo-first order inactivation by the major thrombin inhibitors. An ex vivo measure of the pseudo-first order rate constant (dynamic thrombin inhibitory capacity, DTIC) was a sensitive probe of circulating heparin. There was no change of DTIC during DIC in the absence of exogenous heparin suggesting that heparin-like endogenous glycosaminoglycans were not released in substantial amounts. Pretreatment with heparin efficiently inhibited the development of tissue thromboplastin induced DIC. This animal model may serve as a tool for the study of glycosaminoglycan anticoagulants in vivo.
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PMID:Tissue thromboplastin induced reversible DIC and heparin-enhanced inhibitors in dogs. 351 33

Intravenous injection of homologous lung or brain tissue thromboplastin in dogs under general anesthesia induced changes of conventional hemostasis variables consistent with acute DIC (prolongation of prothrombin times, thrombin times, APTT, drop of fibrinogen and a transient reduction of the platelet count). The animals reacted with accelerated respiration and pulse rates. After recovery from anesthesia they resumed their normal activity as before. Fibrinogen reached a minimum within 40 min after the DIC trigger dose had been injected. Dependent on the size of the latter up to 80% of clottable fibrinogen was consumed. No consumption of antithrombin III and heparin cofactor II could be demonstrated by functional assays based on thrombin inhibition by diluted plasma in the presence of heparin or dermatan sulfate. Prothrombin measured amidolytically by an Echis Carinatus venom assay remained practically unchanged. These findings are consistent with free thrombin concentrations in the nanomolar range sufficient to clot fibrinogen rapidly without visibly affecting the up to 1,000 fold higher concentrations of inhibitors and prothrombin. Heparin administered before tissue thromboplastin virtually suppressed the evolution of DIC but its protective effect was overcome by higher trigger doses. Heparin injected after the induction of DIC had no protective effect. The reversible DIC model in dogs may be a promising tool to study activated coagulation in vivo at practically constant inhibitor concentrations. One dog can be used for several acute experiments with homologous tissue thromboplastin, thus the number of animals and their costs may remain within reasonable limits.
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PMID:Heparin-enhanced inhibitors during reversible disseminated intravascular coagulation. 386 25

A technique is described to completely remove antithrombin III (AT) from small amounts of human plasma by immunoaffinity chromatography on antibodies against human AT linked to Sepharose 4B. The level of heparin cofactor II (HCII) was not affected by the immunoadsorption. HCII activity was then determined by measuring the rate of human thrombin inhibition by 3 ways: a) activation with heparin in AT-free plasma, b) activation with dermatan sulfate in normal plasma and c) activation with dermatan sulfate in AT-free plasma. The normal range of HCII varied between 0.7-1.5 U/ml, as compared to a normal plasma pool containing by definition 1 U/ml. Highly significant correlations between assays as obtained from 40 normal plasmas proved the suitability of the 3 assays, although the progressive thrombin inhibition by AT, when not removed, contributed about one fifth to the thrombin inhibition by HCII in the presence of dermatan sulfate. There were also highly significant correlations between HCII activity and antigen, as determined by rocket immunoelectrophoresis using specific antibodies against HCII. Levels of HCII and AT were examined in 7 patients with hereditary AT deficiency and 7 patients with disseminated intravascular coagulation (DIC). In hereditary AT deficiency, whereas the AT activity was reduced by half, levels of HCII activity and antigen were in the normal range. In DIC, a parallel decrease of HCII and AT suggests that HCII may participate in the inhibition of thrombin released during DIC and thus provides an inhibitor reserve, once the AT level becomes subnormally low.
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PMID:Heparin cofactor II determination--levels in normals and patients with hereditary antithrombin III deficiency and disseminated intravascular coagulation. 639 34

Patients infected with the human immunodeficiency virus (HIV) appear to have a high risk of ischaemic cerebral events. We observed two cases of cerebral infarction in patients with acquired immune deficiency syndrome (AIDS). In the first case, a 38-year-old homosexual with no cardiovascular risk other than smoking presented with rapidly progressive hemiparesia. Brain CT-scan visualized two infarcts in the territory of the right sylvian artery and the arteriography an occlusion of the internal carotid artery. In the second, a 37-year-old homosexual, hospitalization was required for a left-sided pure sensitive epilepsy seizure. There was no cardiovascular risk other than smoking. Magnetic resonance imaging showed parietal ischaemia and thrombus in the left atrium without atrial hypertrophy was seen at transoesophageal echocardiography. In both cases, there was no evidence of endocarditis, dissection of the neck vessels or disseminated intravascular coagulation nor of associated viral or bacterial infectious complication of AIDS. Angiographic findings eliminated cerebral vascularitis. Among the perturbed haemostasis factors previously reported in HIV+ patients, we observed free proteins S deficiency (68 and 43%) and heparin cofactor II deficiency (54 and 40%). Serum albumin was 33 and 32 g/l respectively. Outcome was favourable in both cases with anticoagulant therapy. These coagulation anomalies would not appear sufficient to explain cerebral infarction. Other mechanisms including immune complexed deposition, direct HIV toxicity for endothelial cells or the effect of cytokines on smooth muscles fibres and fibroblasts are probably more important causal factors.
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PMID:[Cerebral infarction in human immunodeficiency virus infection]. 763 44


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