Effects of antithrombin III and antivenom on procoagulant activity of Russell's viper venom in a whole blood model.

The procoagulant activities of Russell's viper venom were assessed in an in vitro whole blood model. Sequential samplings showed that the generation of fibrinopeptide A (FPA), a marker of thrombin activity, and platelet factor 4 (PF4), a marker of platelet activity, exhibited bi-phasic kinetics with an initial slow phase followed by a rapid phase of secretion. In the presence of Russell's viper venom, the generation of both FPA and PF4 was accelerated with the bi-phasic kinetics of PF4 being maintained while that of FPA completely disappeared. Administration of either antivenom (1,600 ng) or 10 IU antithrombin III (AT-III) had no antagonistic effect against the venom but combination of both resulted in a significant prolongation of both FPA and PF4 release (p < 0.05). High dose AT-III (20 IU) resulted in normalization of both FPA and PF4 kinetics and serial levels of both parameters were lower than those treated with the combined regimen, although these were not statistically significant. Unlike the untreated venom activated whole blood, there was no clot formation following treatment with either the combined regimen or high dose AT-III. The results of this study suggested that the effect of Russell's viper venom on the clotting cascade is more potent and direct than that on platelet activity. There were complementary effects between antivenom and AT-III is controlling of both FPA and PF4 release induced by the venom. Furthermore, in this in vitro experiment, AT-III alone when administered in a sufficient dose, abolished the procoagulant effects of Russell's viper venom.

Levels of plasma fibrinopeptide-A during surgery and the severity of the operation.

There is evidence to suggest that the rise of fibrinopeptide A (FPA) during surgery is influenced by tissue thromboplastin released during tissue damage. To investigate whether FPA correlates with the severity of the damage of the operation, 39 patients were recruited and venous blood samples were taken pre-operatively, during skin incision, during bowel manipulation and post-operatively for the assay of FPA. The operations are grouped as minor (A), moderate (B), major (C) and very major (D). The peak FPA levels occurred during bowel manipulation in every degree of operations, and ranged between 6.0 to 22.2 pmol/ml. There was a tendency that peak FPA values rose according to the severity of the surgery, however only very major operations (D) are significantly higher when compared with minor operations (A) (p < 0.01). There was no good correlation between peak FPA levels and length of skin incision (p = 0.83, r = 0.04) as well as peak FPA levels and duration of operation (p = 0.90, r = 0.03). Significantly higher levels of FPA in very major operation (D) was due to more excessive tissue damage during surgery, while due to relatively minimal tissue injury, size of skin incision correlated poorly with FPA.