Bleeding can occur unexpectedly during antithrombotic therapy. Impaired haemostasis is commonly measured by the bleeding time. We measured it by 3 methods in controls and in anticoagulated animals and related it to their antithrombotic status. In 42 control rats template, tail-tip transection and needle occlusion bleeding times correlated poorly (r = 0.05-0.34). The template method had the best range (mean 126.97 +/- SEM secs) and consistency. In 10 control animals it correlated mildly (r = 0.55) with venous thrombus in the same animal. Thrombus was measured by its weight deposited on platinum wires (2 cm long, 0.4 mm diameter) set in vein and in artery for 1 h. In respective groups of 10 rats, a decrease of mean thrombogenesis was obtained using aspirin, heparin and low molecular weight heparin in 2 dosages and hirudin in 1 dosage. The drugs reduced mean venous thrombus by 13-86 per cent of the mean control thrombus, and prolonged the mean template bleeding time by 29-199 per cent. The ranking of the drugs according to their increase of template bleeding time was virtually the same as the ranking given by their reduction of thrombus weight (Spearman rank coefficient 0.81, sig 0.007). The transection test produced a similar ranking and similar correlation with thrombus (0.71, sig 0.049). Low molecular weight heparin induced the greatest thrombus reduction (39 per cent) for least prolongation of bleeding time (24 per cent). Arterial thrombus was more variable. The bleeding times and thrombus weight were measured in each animal of 2 groups given aspirin, the template method correlating mildly with venous thrombus reduction (r = 0.23, 0.58 respectively), the transection method with arterial (0.74, 0.45) and the occlusion test poorly with either (0.13, 0.22). Bleeding time lengthens with increasing antithrombotic effect of drugs, but not in direct proportion, nor similarly with each drug.
SummaryThrombus weight was used as a measure of the thrombus enhancing effect of drugs in 135 rats. The weight of thrombus formed in one hour, on a 20 × 0.5 mm platinum wire, inserted in the vena cava was taken as a measure of thrombosis. The change in thrombus weight which followed the injection of ellagic acid to activate the coagulation system, adenosine diphosphate to activate the platelets, and epsilon-aminocaproic acid to inhibit the fibrinolytic system, was measured. Pilot studies showed that the drug doses used brought about the appropriate changes in the factors named. The mean thrombus weight in 45 control animals was 1.93 mg. Ellagic acid increased it about five-fold, and epsilon- aminocaproic acid almost two-fold, while adenosine diphosphate reduced it by almost a half. Concurrent controls were used in each case. Clotting tests (whole blood clotting time, kaolin-activated whole blood clotting time, thrombin time, and partial thromboplastin time), performed at the end of the hour, showed no significant correlation with thrombus weight.
The amount of thrombus formed in one hour, on standard platinum wire in aorta and vena cava of 48 control and 96 warfarin treated rats of both sexes, was measured. Warfarin was given in varying doses (0.1-0.18 mg/kg) for ten consecutive days before operation to enable the coagulation factors to stabilize. Factors II, VII and X levels as well as prothrombin time (PT) values were obtained for each animal. Factor levels and PT ratio were related to reduction in arterial and venous thrombus weight. The relation between reduction in thrombus weight and depletion in coagulation factor levels was best for factor II and fairly good for factor X at all levels of anticoagulation. All animals which were haemorrhagic had factor II levels of below 15%, with a mean of 8%. At low warfarin dosage a significant reduction of thrombus (> 30%) went undetected by any test, but was least frequently undetected by factor II and most frequently undetected by PT. All rats with diminished thrombus had at least one factor depleted. Haemorrhagic animals were found with any PT ratio in excess of unity. Factor II reflected antithrombotic and haemorrhagic effects of warfarin much better than factors X, VII, or PT.
Groups of rats were injected with warfarin in dosage necessary to reduce factor II to the selected range. They were then injected with dipyridamole (14 mgm/kg) and aspirin (14 mgm/kg). One group received no warfarin.At 2 hours and 6 hours afterwards a pair and an untreated control were anaesthetised and a sterile platinum wire (0.5 × 20 min.) was inserted in the inferior vena cava for 30 minutes. The thrombus adherent to the wire was fixed with gluteraldehyde and weighed, after a blood sample had been taken for assay of factor II.Dipyridamole and aspirin reduced thrombus weight by 40%. This effect was enhanced by factor II levels of less than 50% induced by wafarin.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
Copyright © 2024 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.