Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.4.21.6 (thromboplastin)
 13,278 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Ten clinically healthy subjects (5 men and 5 women), 31 +/- 11 yrs of age, were studied at six timepoints (0800, 1200, 1600, 2000, 0000, 0400) distributed over a 1-week span. Circadian rhythms in platelet aggregation in response to adenosine diphosphate (ADP) and adrenalin (A), platelet adhesiveness measured as retention in a glass bead column, prothrombin time (PT), activated partial thromboplastin time (APTT), thrombin time (TT), fibrinogen, Factor VIII activity and alpha-1-antitrypsin antigen showed circadian rhythms. The plasma concentrations of plasminogen, alpha-2-macroglobulin, and antithrombin III (AT III) antigen, Factor V and fibrinogen degradation products showed no circadian rhythm by ANOVA or cosinor analysis. The phase relations of the rhythms of different coagulation parameters are of interest in the physiology and pathobiology of the coagulation-fibrinolytic system. The extent of the circadian rhythm (range of change) described is not of a magnitude to lead to diagnostic problems in the clinical laboratory. The timing of these rhythms, however, may determine transient risk states for thromboembolic phenomena, including myocardial infarction and stroke. Several but not all coagulation parameters suggest a transient state of hypercoagulability during the morning hours. The recognition of these rhythmic, and thus in the time of the occurrence predictable temporary risk states for thromboembolic phenomena, may lead to timed treatment and/or effective prevention.
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PMID:Circadian variations in blood coagulation parameters, alpha-antitrypsin antigen and platelet aggregation and retention in clinically healthy subjects. 212 46

Thrombelastography, although proven as a useful research tool has not been evaluated for its clinical utility against common coagulation laboratory tests. In this study we compare the thrombelastographic measurements with six common tests (the hematocrit, platelet count, fibrinogen, prothrombin time, activated thromboplastin time and fibrin split products). For such comparisons, two samples of subjects were selected, 141 normal volunteers and 121 patients with cancer. The data was subjected to various statistical techniques such as correlation, ANOVA, canonical and discriminant analysis to measure the extent of the correlations between the two sets of variables and their relative strength to detect blood clotting abnormalities. The results indicate that, although there is a strong relationship between the thrombelastographic variables and these common laboratory tests, the thrombelastographic variables contain additional information on the hemostatic process.
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PMID:Comparison of thrombelastography with common coagulation tests. 733 Aug 29

Twenty-four horses were randomly allocated to 3 groups. All horses underwent a ventral midline celiotomy, and the large colon was exteriorized and instrumented. Group-1 horses served as sham-operated controls, group-2 horses underwent 6 hours of colonic ischemia, and group-3 horses were subjected to 3 hours of ischemia and 3 hours of reperfusion. Baseline blood samples were collected, then low-flow colonic ischemia was induced in horses of groups 2 and 3 by reducing colonic arterial blood flow to 20% of baseline. All horses were monitored for 6 hours. Citrated systemic venous (SV) blood samples were collected from the main pulmonary artery, and colonic venous (CV) samples were collected from the colonic vein draining the ventral colon. Samples were collected at 0, and 2, 3, 3.25, 4, and 6 hours for determination of one-stage prothrombin time, activated partial thromboplastin time, antithrombin III activity, and fibrinogen concentration. Data were analyzed statistically, using two-way ANOVA for repeated measures, and post-hoc comparisons were made by use of Student Newman Keul's test. Statistical significance was set at P < 0.05. There were significant decreases in all hemostatic variables by 2 hours in SV and CV samples from horses of all 3 groups, but there were no differences among the 3 groups for any of these variables. These hemostatic alterations could have been secondary to a hypercoagulable state or to fluid therapy-induced hemodilution. Colonic ischemia-reperfusion was not the cause of these alterations because these alterations also were observed in the sham-operated control horses. Significant temporal alterations existed even after accounting for the hemodilution.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Systemic and colonic venous hemostatic alterations in horses during low-flow ischemia and reperfusion of the large colon. 766 64

To assess the potential for interference of Hb with the normal coagulation mechanism, we performed in-vitro hemodilution tests. Platelet rich plasma (PRP) was prepared from citrated blood samples of 5 normal volunteers diluted 3:1, 1:1, and 1:3 volume ratio with human stroma-free hemoglobin solution (SFH) or human albumin (HSA). Coagulation kinetics and clot strength were assessed with a thrombelastograph (TEG). Extrinsic and intrinsic coagulation factors were assessed measuring prothrombin time (PT) and activated partial thromboplastin time (aPTT) with an optical coagulation timer. Statistical significance was assessed using ANOVA and Neuman-Keuls tests at p < 0.05. At all dilutions, SFH diluted plasma showed significantly prolonged initial rate of clot formation compared to undiluted control or HSA (p < 0.05). However, there was no difference in formed clot strength between SFH and HSA. At high Hb concentrations Hb seems to interfere with the optical measurements of coagulation times (particularly aPTT). SFH appears to interfere with the initial phase coagulation mechanism in human plasma in-vitro; further study is needed to clarify the cause. In measuring coagulation times of plasma containing Hb a non-optical instrument should be considered.
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PMID:Coagulation responses of human plasma after hemodilution with hemoglobin solution in-vitro. 799 81

Protamine reversal of unfractionated and low-molecular-weight heparin (LMWH) causes hypotension, bradycardia, pulmonary artery hypertension, and declines in oxygen consumption. Furthermore, protamine incompletely reverses the anti-Xa activity of LMWH. The present study assesses the efficacy and toxicity of three protamine variants having +16 and +18 charges in reversal of LMWH (Logiparin, LHN-1): [+16] P(AK2A2K2)4, [+18] PK(K2A2K2A)3K2AK3, and [+18B] acetyl-PA(K2A2K2A)4K2-amide. The [+18B] compound was made by acetylating and amidating the [+18] to decrease in vivo degradation and to increase the alpha-helix forming propensity. Variants were examined in a canine model (n = 7, each variant) and compared to controls (n = 7, each variant) and compared to controls (n = 7) reversed with standard protamine with a +21 charge. Animals were anesthetized, anticoagulated with LMWH (150 IU factor Xa activity/kg), and reversed with protamine variants (1.5 mg/kg with 100 IU/mg). Blood pressure (BP), heart rate (HR), cardiac output (CO), pulmonary artery pressures, oxygen saturations, and oxygen consumption (VO2) were continuously monitored. Comparisons were undertaken at baseline, after heparin, before variant administration, and for 30 min thereafter. A total toxicity score (TTS) was calculated for each variant, accounting for maximal declines in BP, HR, CO, and VO2 during the first 5 min after reversal. Protamine [+21] was most toxic, TTS -7.6, with the variants being less toxic (P < 0.01, ANOVA): TTS = [+16] -2.8, [+18] -1.3, and [+18B] -4.1.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:Reversal of low-molecular-weight heparin anticoagulation by synthetic protamine analogues. 801 15

Introduction of the International Normalized Ratio (INR) has improved the standardization of laboratory control of oral anticoagulant therapy (OAT). However, it has been reported that misleading INR results can be obtained from OAT patients with lupus anticoagulant (LA). To investigate this claim, we studied 35 OAT patients, 14 of whom had anti-phospholipid syndrome (APS) with a documented LA. Attainment of anticoagulation was confirmed by chromogenic assay of factor VII and factor X. Prothrombin times were performed using eight thromboplastins (five derived from rabbit brain, two recombinant human tissue factor and one made from human placenta) with an International Sensitivity Index (ISI) of <1.40. When using the thromboplastin manufacturers' ISI there was a significant difference (ANOVA, P<0.0001) between INR results obtained with the eight reagents for both APS (average CV = 12.4%) and non-APS (average CV = 12.5%) patient groups. Variation using the eight thromboplastins was assessed by calculating the CV for each sample; these values were then pooled for each patient group to give the average CV for all samples with all reagents for the two patient groups. Results for both patient groups exhibited markedly reduced variation (APS group average CV = 6.5%, non-APS group average CV = 5.8%) when locally assigned ISI values were employed in the calculation of INRs. Our data does not support the suggestion that the INR may not reflect the true level of anticoagulation in the long-term warfarin-treated patient, in whom lupus anticoagulant was detected. However, there was strong evidence that thromboplastin use should be restricted to those clot detection systems for which the reagent's manufacturer has assigned an ISI, or local ISI assignment must be undertaken. The inappropriate use of a generic (i.e. optical or mechanical clot detection system without regard to specific analyser type) ISI value can lead to ambiguous results.
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PMID:Monitoring of oral anticoagulant therapy in lupus anticoagulant positive patients with the anti-phospholipid syndrome. 960 41

Besides its central role in coagulatory pathways, thrombin is known to be a key mediator of macrophage and granulocyte activation in vitro. During recent years the concept of thrombin inhibition by the specific thrombin inhibitor, hirudin, has been established to treat septic disorders. Since basic mechanisms of sepsis include leukocyte/endothelial cell interaction and deterioration of capillary perfusion, we hypothesized that hirudin modulates leukocyte activation and microvascular injury. Severe endotoxemia was induced in Syrian hamsters by intravenous administration of endotoxin (lipopolysaccharide [LPS], E. coli, 2mg/kg) at 0 h. Hirudin (0.25 mg/kg/h) was substituted intravenously during the 4 h after the induction of endotoxemia (n = 7, hirudin). In control animals (n = 6, control) LPS was given without hirudin substitution. In skinfold chamber preparations leukocyte/endothelial cell interaction and functional capillary density (FCD, measure of capillary perfusion) were analyzed during a 24-h period after LPS injection using intravital fluorescence microscopy. Hirudin effectively normalized thromboplastin time and antithrombin activity when compared to controls (P < 0.05, ANOVA). However, hirudin did not attenuate LPS-induced arteriolar and venular leukocyte adherence, and even tended to increase leukocyte adherence after 24 h (P > 0.05, MANOVA). In parallel, addition of hirudin led to a significant deterioration of FCD over time when compared to controls (hirudin: baseline = 171 +/- 19 cm(-1) versus 16 +/- 9 at 24 h; control: baseline = 150 +/- 20 cm(-1) versus 62 +/- 18 at 24 h; P < 0.05). The fall in FCD in hirudin animals was associated with a significant increase of wet-to-dry weight ratios in lung, kidney, muscle, and small intestine (P < 0.05 versus control, ANOVA). Thus our study does not indicate a protective effect of hirudin on microcirculation during endotoxemia, despite an improvement of coagulatory parameters. This result may at least in part explain the lack of efficacy of hirudin on lethality during endotoxemia and sepsis.
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PMID:The thrombin antagonist hirudin fails to inhibit endotoxin-induced leukocyte/endothelial cell interaction and microvascular perfusion failure. 1109 85

Conventional unfractionated heparin substantially enhances spontaneous platelet aggregation in pregnancy in vitro, and may cause platelet activation in healthy volunteers in vivo. It is unknown, however, whether therapeutically administered heparin affects platelet behavior during pregnancy. In a parallel group ex vivo study, 8 third trimester pregnant patients requiring anticoagulation with heparin exhibited a trend to a greater spontaneous platelet aggregation, in comparison to 11 age-matched healthy third trimester pregnant controls. This is consistent with heparin-induced platelet activation in vivo during therapeutic anticoagulation. Peak aggregation in the heparin-treated group was 48 +/- 4% compared to 37 +/- 5% in the healthy controls, (P = 0.086 ANOVA): and significant time treatment interaction (P = 0.03 ANOVA). There was also a weak positive correlation (r = 0.54) between the peak % spontaneous platelet aggregation and the activated partial thromboplastin time ratio during heparin administration.
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PMID:Evidence of in vivo platelet activation during heparin anticoagulation in pregnancy for prophlaxis or treatment of thromboembolism. 1295 99

Our previous studies demonstrated that orally administered heparins prevent thrombosis in a rat jugular vein thrombosis model, where bovine unfractionated heparin (UFH) and the low molecular weight heparin tinzaparin reduced thrombotic incidence by 50% at 7.5 and 0.1 mg/kg, respectively. Our objectives were to determine if similar antithrombotic effects of oral heparin could be observed in an arterial thrombosis model. In this model, filter paper soaked in 30% ferric chloride was applied to the exposed rat carotid artery. A flowmeter recorded blood flow over a 60 min period determining time when the thrombus began forming (TTB) and time till occlusion (TTO). Immediately following, the thrombus was removed, dried and weighed 24 h later. Bovine UFH (7.5 mg/kg), tinzaparin (0.1 mg/kg) or saline was administered by stomach tube at 2, 5 and 25 h prior to thrombus initiation. TTB was significantly increased when UFH was given at 5 and 25 h but not 2 h prior, and when tinzaparin was given at 5 but not 2 or 25 h prior compared to rats given oral saline. TTO was significantly increased for both UFH and tinzaparin when given 5 and 25 h but not 2 h prior (one-way ANOVA). There was no difference in TTO and TTB between UFH and tinzaparin treated groups. A trend in reduction in thrombus weight was observed for UFH at 5 and 25 h prior and tinzaparin at 5 h prior to thrombus initiation (one-way ANOVA). Although no significant changes were observed in activated partial thromboplastin times, Heptest or anti-Xa activity from plasma of heparin treated rats, endothelial heparin concentrations were significantly greater than controls for UFH at 5 h and for tinzaparin at 2, 5, and 24 h. Thus, heparins administered by the oral route are effective antithrombotic agents in arterial as well as venous models.
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PMID:Orally administered heparins prevent arterial thrombosis in a rat model. 1511 52

We recently demonstrated that patients with increased blood loss due to intraoperative coagulopathy show a persistent pre-, intra- and postoperative increase in fibrin monomer concentration. We thus tested the hypothesis that preoperative fibrin monomer concentrations can be used as a risk indicator for intraoperative blood loss in a study designed for diagnostic test evaluation in 168 patients admitted to the surgical service of our hospital. Intraoperative blood loss increased with preoperative fibrin monomer concentration (median blood loss of 50, 100, 200 and 400 ml in preoperative fibrin monomer quartile groups 1 to 4, p<0.001, ANOVA on ranks; interquartile comparisons p < 0.05 (4/6), Mann Whitney Rank Sum test). In contrast, intraoperative blood loss was unrelated to preoperative values of prothrombin time, activated partial thromboplastin time and platelet count. By multivariate (logistic regression) analysis, only fibrin monomer remained a significant predictor of intraoperative blood loss > 500 ml when age, gender, BMI, fibrin monomer and the different types of surgical procedures (tumor surgery, vascular surgery, cholecystectomy, gastric banding, varicous vein surgery and hernia repair) were included as independent variables. Most importantly, accuracy evaluation showed that preoperative fibrin monomer concentration < 3 microg/l excluded intraoperative blood loss > 500 ml with 92% sensitivity and 95% negative predictive value. These results support our hypothesis that preoperative fibrin monomer concentrations are related to intraoperative blood loss in elective surgery. Fibrin monomer should be further investigated for it's potential to serve as a routine tool for preoperative risk stratification of intraoperative bleeding.
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PMID:Preoperative fibrin monomer measurement allows risk stratification for high intraoperative blood loss in elective surgery. 1611 6


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