Ine Reyers

Failure of aspirin at different doses to modify experimental thrombosis in rats

Aspirin inhibits the synthesis of both platelet and vascular arachidonic acid metabolites which have opposite effects on platelet function. The rationale for its clinical use as an antithrombotic drug has therefore been questioned. Previous studies in rats indicated that platelets are more sensitive to aspirin than arterial tissues and are almost as sensitive as venous tissues. We have now assessed the effects of aspirin at various doses on an arterial and a venous model of experimentally-induced thrombosis. Aspirin at high doses (50–200 mg/kg b.w.) neither reduced nor potentiated the thrombosis tendency in either model. Lower doses (2.5–10 mg/kg b.w.) — which preferentially inhibited platelet prostaglandin formation — did not protect the animals against thrombosis. It is possible, on one hand, that the metabolic pathways of arachidonic acid which are blocked by aspirin do not play a crucial role in the models used. One the other hand, the difficulty to completely dissociate the inhibitory effects of aspirin on platelet and vascular prostaglandins could be crucial for the antithrombotic activity of this drug. The concept that, when administered in large doses, aspirin — by inhibiting vascular prostacyclin activity — potentiates experimental thrombosis, is not supported by the present study.

Delayed hypercoagulability after a single dose of adriamycin to normal rats

Abstract Single doses of Adriamycin to normal rats, at levels active as an anticancer agent in this animal species, did not induce any acute changes in haemostatic parameters such as blood platelets, fibrinogen level or spontaneous fibrinolytic activity, as long as plasma drug levels were measurable. Starting from 2 weeks after a single dose, however, a hypercoagulable state developed, characterized by increased fibrinogen and factor VIII levels, short activated partial thromboplastin time, low antithrombin levels and depressed fibrinolytic activity. These changes were dose-related and lasted at least 5 weeks after treatment. An increased tendency to occlusive arterial thrombosis was also observed in treated rats. The pathogenesis of this disorder could be related to tissue damage induced by the drug, possibly nephrotoxicity.

Moderate anticoagulation by salicylate prevents thrombosis without bleeding complications: An experimental study in rats

It has previously been shown that salicylate (S) acts as a vitamin K (vit K)-antagonist inducing a decrease in plasma levels of vit K-dependent clotting factors and inhibiting the vit K-dependent carboxylation reaction in the liver. In this study we evaluated whether this biochemical effect had a possible functional role. Indeed, we tested in rats the antithrombotic potency of S (175 mg/kg/i.p. twice a day for 3 days) on experimentally induced venous thrombosis. Its possible haemorrhagic effect was evaluated by measuring the bleeding time. Low-dose warfarin (W) (0.2, 0.1, 0.1 mg/kg/i.v. for 3 days) was utilized as control drug. To check for a possible potentiation between S and W, we tested the effects of their combination (S + W). Thrombotest was used to monitor the anticoagulant effect of each treatment. The incidence of thrombus formation, after venous stasis, was not significantly affected by any of the treatments used, but a significant reduction in thrombus weight was observed after either S or W treatment. Both drugs partially prolonged the Thrombotest without affecting either the bleeding time or the peri-operative mortality (mainly due to internal bleeding). When the combination S + W was used, no significant benefit was observed on the prevention of thrombus incidence or weight, although a marked Thrombotest prolongation was recorded. On the other hand this combination resulted in a pronounced bleeding tendency, as expressed in a significant prolongation of bleeding time and increased total mortality. Thus S, at doses inducing moderate anticoagulation may prevent venous thrombosis without relevant bleeding complications.

Effect of acetylsalicylate on surgical bleeding, postoperative mortality and allograft survival in rats undergoing heart transplantation

18 rats were treated with L-ASA before heart transplantation and daily thereafter until death or rejection. 22 animals acted as controls. A significantly higher post-operative mortality rate, without any significant modification of the transplant survival time, was found in L-ASA-treated group.

Prolongation by warfarin of templatë bleeding time in rats: a vitamin K-dependent effect

Abstract Administration of warfarin to rats induced not only the well-known anticoagulant effect, but also an impairment of primary hemostasis as reflected by a significant prolongation of the “template” bleeding time. This effect was very closely associated with lowering of the prothrombin complex level and was reversed by administration of vitamin K. It is suggested that some of the clotting factors known to be vitamin K-dependent also play a role in primary hemostasis; alternatively, a putative vascular “bleeding factor” could be modulated by vitamin K availability.

Plasmatic and vascular factors of the hemostatic system in rats receiving an estrogen-progestogen combination

Treatment of rats for 10 estral cycles with an estrogen-progestogen combination giving 100% infertility triggered a vascular response characterized by increased prostacyclin activity in arterial walls and increased systolic blood pressure. In contrast, plasma fibrinolytic activity and physiological coagulation inhibitors as well as vascular fibrinolytic activity were not changed by this treatment. The same rats tended to have shorter occlusion times of an aortic prosthesis, and could represent a useful model to study the blood-vessel-wall interplay during oral contraceptive treatment.

Effect of pretreatment with acetylsalicylate on surgical bleeding and peroperative mortality in rats undergoing kidney transplantation.

42 rats were pretreated with L-ASA before kidney transplantation, 43 rats acted as controls. 9 rats with L-ASA. but no control rats, died with i.p. haemorrhage. However, in animals surviving the operation, the intraoperative blood loss did not differ significantly between the 2 groups.