Values of three coagulation screening tests of precolostral calves.
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Prothrombin times, partial thromboplastin times and platelet counts were performed to determine normal values and to screen for coagulation defects of precolostral calves. The precolostral calves were in two groups: one group of a few calves was tested two years before the second larger group. The results for both groups were similar. The tests were performed on postcolostral calves and on mature cows to compare their values with those of precolostral calves. The mean values of prothrombin times and partial thromboplastin times of precolostral calves in the first group were 18.8 seconds and 54.8 seconds respectively. The mean values of prothrombin times and partial thromboplastin times of precolostral calves in the second group were 18.8 seconds and 50.8 seconds respectively. The mean platelet count was 422,400/cmm for the first group and 482,800/cmm for the second group. (+info)
Factor VII as a marker of hepatocellular synthetic function in liver disease.
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Factor VII levels have been measured in 100 patients with liver disease following parenteral vitamin K1 therapy. There was good agreement between specific factor VII measurements and the one-stage prothrombin time apart from six patients with compensated cirrhosis in whom the prothrombin time was prolonged despite the presence of normal factor VII levels. A mean activity of 58% was found in patients with cirrhosis. Cirrhotic patients with features of hepatic decompensation had a significantly lower mean level of activity (40%) than the "contrast" patients with surgical obstruction of the major bile ducts (93%). Patients with chronic active liver disease had moderate depression of factor VII levels and those with non-cirrhotic liver damage had mean activities similar to the contrast group. Factor VII levels could not be correlated with BSP retention but there was a correlation with serum albumin concentration. It is concluded that the prothrombin time using Quick test with a standardized thromboplastin showing good sensitivity to factor VII, eg, the Manchester reagent (BCT), provides a reliable index of coagulability in chronic liver disease, and specific factor VII assays are not indicated. (+info)
Medical liability risk avoidance: a case for adopting the International Normalized Ratio (INR) system.
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Since bleeding is a common adverse effect associated with the oral anticoagulant warfarin, maximizing the therapeutic potential of this drug requires close laboratory monitoring. The International Normalized Ratio (INR) is a system that has been developed to improve and standardize the assessment of the intensity of oral anticoagulation therapy. Clinical information and medicolegal arguments supporting the adoption of this system are reviewed. The potential for improvement in patient outcomes and minimization of medical liability favors the adoption of the INR system. (+info)
Effect of liver disease and transplantation on urea synthesis in humans: relationship to acid-base status.
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It has been suggested that hepatic urea synthesis, which consumes HCO-3, plays an important role in acid-base homeostasis. This study measured urea synthesis rate (Ra urea) directly to assess its role in determining the acid-base status in patients with end-stage cirrhosis and after orthotopic liver transplantation (OLT). Cirrhotic patients were studied before surgery (n = 7) and on the second postoperative day (n = 11), using a 5-h primed-constant infusion of [15N2]urea. Six healthy volunteers served as controls. Ra urea was 5.05 +/- 0.40 (SE) and 3.11 +/- 0.51 micromol. kg-1. min-1, respectively, in controls and patients with cirrhosis (P < 0. 05). Arterial base excess was 0.6 +/- 0.3 meq/l in controls and -1.1 +/- 1.3 meq/l in cirrhotic patients (not different). After OLT, Ra urea was 15.05 +/- 1.73 micromol. kg-1. min-1, which accompanied an arterial base excess of 7.0 +/- 0.3 meq/l (P < 0.001). We conclude that impaired Ra urea in cirrhotic patients does not produce metabolic alkalosis. Concurrent postoperative metabolic alkalosis and increased Ra urea indicate that the alkalosis is not caused by impaired Ra urea. It is consistent with, but does not prove, the concept that the graft liver responds to metabolic alkalosis by augmenting Ra urea, thus increasing HCO-3 consumption and moderating the severity of metabolic alkalosis produced elsewhere. (+info)
Adenovirus-mediated local expression of human tissue factor pathway inhibitor eliminates shear stress-induced recurrent thrombosis in the injured carotid artery of the rabbit.
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The main cause of acute coronary syndrome may be recurrent thrombosis, which is initiated by the activation of the extrinsic coagulation pathway. Tissue factor (TF) pathway inhibitor (TFPI) efficiently inhibits an early step in this pathway by the formation of a complex with factor VIIa, TF, and factor Xa. We determined whether local TFPI gene transfer can inhibit thrombosis in an injured artery without inducing systemic side effects. Balloon-injured rabbit carotid arteries were infected with an adenoviral vector that expressed either human TFPI (AdCATFPI) or bacterial beta-galactosidase (AdCALacZ). Two to 6 days after gene transfer, thrombosis was induced by the production of constant stenosis of the artery, and blood flow was measured continuously with an electromagnetic flow probe. A cyclic flow variation, which is thought to reflect the recurrent formation and dislodgment of mural thrombi, was observed in all AdCALacZ-infected arteries as well as in saline-infused arteries. In contrast, no cyclic flow variation was detectable in AdCATFPI-transfected arteries, even in the presence of epinephrine (1 microg. kg-1. min-1 infusion). Prothrombin time, activated partial thromboplastin time, and the ex vivo platelet aggregation induced by either adenosine diphosphate or collagen were unaltered in AdCATFPI-infected rabbits. We found that in vivo TFPI gene transfer into an injured artery completely inhibits the recurrent thrombosis induced by shear stress even in the presence of catecholamine, without affecting systemic coagulation status. Adenovirus-mediated local expression of TFPI may have the potential for the treatment of human thrombosis. (+info)
Antithrombotic efficacy of a novel murine antihuman factor IX antibody in rats.
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A murine antihuman factor IX monoclonal antibody (BC2) has been generated and evaluated for its capacity to prolong the activated partial thromboplastin time (aPTT) in vitro and ex vivo and to prevent arterial thrombosis in a rat model in vivo. BC2 extended aPTT to a maximum of 60 to 80 seconds at 100 to 1000 nmol/L in vitro (rat and human plasma, respectively) and ex vivo (rat) after dosing of rats up to 6 mg/kg in vivo. BC2, administered as bolus (1 to 6 mg/kg) followed by infusion (0.3 to 2 mg x kg(-1) x h(-1)), dose-dependently prevented thrombosis of an injured rat carotid artery (FeCl(3)-patch model), increased time to artery occlusion, and reduced incidence of vessel occlusion. BC2 efficacy in preventing arterial thrombosis exceeded that of heparin (bolus 15 to 120 U/kg followed by infusion 0.5 to 4.0 U x kg(-1) x min(-1)), whereas the latter rendered the blood incoagulable (aPTT>1000 seconds). BC2 demonstrated complete antithrombotic efficacy also as a single bolus given either as prevessel or postvessel injury as evidenced by reduction of thrombus mass (from 4.18+/-0.49 to 1.80 +/-0.3 mg, P<0.001), increasing vessel patency time (from 14.9+/-0.9 minutes to 58.3+/-1.7 minutes, P<0.001) and decreasing incidence of vessel occlusion from 100% to 0% in vehicle- versus BC2-treated rats, respectively. BC2 (3 mg/kg, IV) administered in a single bolus resulted in 50% reduction in thrombus mass (P<0.01), extended vessel patency time (P<0.001), extended aPTT only 4-fold, and had no effect on blood loss via a tail surgical wound; heparin, at doses that reduced thrombus mass to a similar extent, extended aPTT beyond 1000 seconds (over 500-fold) and increased blood loss from 1.8+/-0.7 to 3.3 +/-0.6 mL (P<0.001). These data suggest that BC2 may provide enhanced therapeutic efficacy in humans at lesser interference with blood hemostasis than heparin. (+info)
An IgG antiprothrombin antibody enhances prothrombin binding to damaged endothelial cells and shortens plasma coagulation times.
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OBJECTIVE: To test the hypothesis that some lupus anticoagulants are antiprothrombin antibodies, and that such antibodies enhance prothrombin binding to endothelial cells (EC) and thus promote clotting on the cell surface. METHODS: We generated a monoclonal antiprothrombin antibody (designated IS6) from a patient with primary antiphospholipid syndrome (APS). The antibody was analyzed for its binding properties, lupus anticoagulant activity, and pathophysiologic activity, using an EC-based plasma coagulation assay. RESULTS: IS6 is the first patient-derived monoclonal IgG antiprothrombin antibody. It bound to prothrombin with low affinity, reacted with 3 phospholipids (cardiolipin, phosphatidylethanolamine, and phosphatidylserine), and showed lupus anticoagulant activity. Moreover, IS6 enhanced the binding of prothrombin to damaged EC and shortened the EC-based plasma coagulation times. CONCLUSION: These findings suggest that IS6 may promote coagulation in areas of damaged EC in the host, and thus contribute to thrombosis in patients with APS. (+info)
Effect of maternal anticonvulsant treatment on neonatal blood coagulation.
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AIMS: To investigate the impact of maternal anticonvulsant use on the ability of cord blood to coagulate. METHODS: Cord blood prothrombin times were measured, over 15 years in a consecutive series of 137 term babies born to women taking phenobarbitone, phenytoin, and/or carbamazepine while pregnant. The response to parenteral vitamin K was measured in 83 neonates. RESULTS: Only 14 of the 105 babies born to the mothers who had therapeutic anticonvulsant blood concentrations at birth had a prolonged prothrombin time (outside the 95% reference range). None had an overt bleeding tendency. The abnormality was corrected within 2 hours by 1 mg of parenteral vitamin K, but rapid intravenous prophylaxis produced complications in three infants. CONCLUSIONS: A policy of giving vitamin K throughout the last third of pregnancy to all women being treated with anticonvulsants, as recently recommended, is not justified by the available evidence. The belief that there is a distinct, early form of neonatal vitamin K deficiency that is different from, and more dangerous than, the classic form of the disease, is not supported by a review of the published evidence. (+info)