G. P. McNicol

Studies on Blood Coagulation, Fibrinolysis and Platelet Function Following Exercise in Normal and Splenectomized People

The effect of a short period of strenuous exercise on the haemostatic mechanism has been studied. Following exercise there was an increase of factor VIII which was not affected by prior splenectomy or by aminocaproic acid, an inhibitor of plasminogen activator. Although exercise produced increased plasminogen activator concentrations, as measured by the euglobulin lysis time, there was no alteration in the FR‐antigen (fibrinolytic degradation product) concentration. Platelet adhesiveness, and ADP‐induced aggregation were significantly increased after exercise and in the latter test the phase of platelet disaggregation was impaired.

Effects on blood coagulation, fibrinolysis, and platelet aggregation of normal and atheromatous aortic tissue

A comparison was made between the effects of atheromatous and normal areas of the same aorta on coagulation, fibrinolytic, and platelet aggregating systems. In the thromboplastin generation test it was found that atheromatous aorta possessed significantly greater ability to generate intrinsic prothrombin activator than did normal aortic tissue. But, by the one-stage prothrombin time technique, the content of extrinsic thromboplastin in both types of aorta was similar. Aortic preparations, consisting of intimal and medial layers only, were not found to possess fibrinolytic ability and did not contain inhibitors of the fibrinolytic system. The adhesion of platelets to ulcerated atheromatous areas of aorta was significantly greater than to normal or non-ulcerated atheromatous areas. However, homogenates of atheromatous and normal aorta did not differ in their ability to accelerate platelet aggregation and fibrin clot formation when tested by a modified Chandlers tube technique. The significance of the findings is discussed and the suggestion made that the mechanisms by which atheromatous aortic tissue might predispose towards intravascular thrombosis in vivo are the ability of such tissue to enhance intrinsic prothrombin activator formation and platelet aggregation.

Effect of RA233 on platelet function in vitro.

RA233, a new pyrimido-pyrimidine compound, is a powerful inhibitor of platelet function tested in vitro; it inhibits calcium and adenosine diphosphate (A.D.P.)-induced platelet aggregation, inhibits the retention of platelets by glass beads, decreases the release of platelet factor 3 by kaolin, and inhibits clot retraction. In some in-vitro systems RA233 is significantly more potent that its analogue RA433 in inhibiting platelet function.

In-Vitro Studies with Ancrod (‘Arvin’)

Summary. The effect of ancrod on the fibrinolytic enzyme system in vitro and on artificial thrombi in the Chandler tube system has been studied. Ancrod has no direct lytic activity and does not influence the rate of lysis of artificial thrombi in the Chandler tube. Clots formed by the action of ancrod are more susceptible to the lytic action of urokinase compared to those formed by thrombin but are equally as susceptible to spontaneous lysis as comparable thrombin clots. The rapidity with which the fibrin formed in vivo by ancrod is removed must be attributed to some process other than the generalized activity of the plasminogen–plasmin system.

Effect of gaboon viper (Bitis gabonica) venom on blood coagulation, platelets, and the fibrinolytic enzyme system

The action of the venom of the gaboon viper (Bitis gabonica) on blood coagulation, platelets, and the fibrinolytic enzyme system was studied. The results confirm that the venom of Bitis gabonica has a marked anticoagulant action in vitro. The venom appears to impair clot formation by a direct proteolytic action on fibrinogen, releasing soluble breakdown products.

Aggregation of human platelets by commercial preparations of bovine and porcine antihaemophilic globulin

Infusion of commercial preparations of porcine and bovine antihaemophilic globulin into three haemophilic patients produced transient thrombocytopenia. This platelet-aggregating activity has been shown to be present in a wide range of animal plasmas and is related to the fibrinogen fraction. The mechanism of platelet aggregation by animal fibrinogen is discussed and some inhibitors of the reaction are described.

Urokinase therapy: dosage schedules and coagulant side effects.

The effect of a new preparation of urokinase (Roche) has been studied, in the laboratory and in 10 patients and three volunteers. It is a non‐toxic and active fibrinolytic agent if given in adequate dosage, but it was found that a small initial infusion gave rise to a paradoxical coagulant effect in the recipient. This effect was associated with the formation of‘cryofibrinogen’ and an increase in factor‐VIII activity. The coagulant effect was probably mediated by a low‐grade process of plasminogen activation rather than due to the preparation of urokinase itself. The preparation did have minor intrinsic thromboplastic activity similar to that described in other preparations of urokinase, but it is unlikely that this would produce a significant effect in vivo. The coagulant effect could be overcome by increasing the initial dose of urokinase to produce rapidly the haemostatic defect normally associated with fibrinolytic therapy.

Relationships between platelet function tests in normal and uraemic subjects

In tests of platelet function in normal subjects, the following relationships were found: the greater the platelet adhesiveness the less the ability to disaggregate after challenge with adenosine diphosphate (ADP), and the greater the disaggregation after ADP, the longer the clotting time in the test for platelet factor 3 availability. Such correlations were disturbed in uraemic patients.

Action of a Pyrimido-pyrimidine Compound on Platelet Behaviour in Vitro

A pyrimido-pyrimidine compound (RA433) was found in vitro to be a significantly more potent inhibitor of platelet behaviour than the previously available pyrimido-pyrimidine compound RA8—dipyridamole. In a turbidimetric system RA433 inhibits platelet aggregation induced by adenosine diphosphate, collagen, and noradrenaline; further, in a glass-bead-column technique it is a powerful inhiitor of platelet adhesiveness.

Experimental warfarin poisoning in the dog: Platelet function, coagulation and fibrinolysis

Abstract Experimental warfarin poisoning in dogs produced a profound haemostatic defect with depression in the levels of factors II, VII, IX and X and gross prolongation of the bleeding time. Surprisingly platelet function was unaltered suggesting that in the dog the intrinsic coagulation pathway plays an important part in the normal bleeding time. There was slight shortening of the euglobulin lysis time, but no other changes in the components of the fibrinolytic enzyme system. Rapid reversal of the clotting abnormality was produced by the intravenous injection of vitamin K1.