Russell's viper venom: effects on coagulating whole blood in vitro.
Russell's viper venom (RVV) leads to a strong activation of the coagulation system with consumptive coagulopathy and thrombopenia. For better comprehension of the pathophysiologic process, the effect of RVV was examined in an in vitro model of hemostasis. The stimulation of the coagulation system and of platelet activity can be discriminated by sequential measuring of fibrinopeptide A (FPA) generation and platelet factor 4 (PF 4) release, respectively. In coagulating whole blood both parameters show a parallel response curve in the control series (n = 6) with an initial slow phase followed by a rapid phase after 4.7 +/- 0.8 min (FPA) and 6.0 +/- 0.9 min (PF 4) of the incubation period. Varying concentrations of RVV (15, 50, 100 and 1,000 ng/ml; n = 6 each) cause a dose-dependent stimulation of FPA generation as well as of PF 4 secretion. Clot formation time shows a decrease from 9 min (controls) to 6.3 +/- 2.0 min (100 ng/ml RVV) and 2.7 +/- 0.5 min (1,000 ng/ml), respectively. The concomitant addition of antithrombin III (AT III, 20 U/ml) and RVV (100 ng/ml) leads to a nearly complete normalization of hemostasis in vitro. The beginning of the rapid activation phase is comparable to that of the control group, clot formation does not occur during the 10-min incubation period. Heparin (1 IU/ml) acts as an antagonist not only of the venom-induced FPA generation, but also of the PF 4 release. Prostaglandin E1 (PGE1) (150 ng/ml) does not inhibit the RVV-stimulated FPA generation, but causes a moderate inhibition of PF 4 secretion, especially during the rapid phase.(ABSTRACT TRUNCATED AT 250 WORDS)
Lorenz
R
R
Department of Internal Medicine II, Technical University of Munich, Klinikum rechts der Isar, FRG.
Vlizou
M
M
Clemens
R
R
Tornieporth
N
N
Pukrittayakammee
S
S
D004305:Dose-Response Relationship, Drug; D010450:Endopeptidases / Q000494:pharmacology / Q000633:toxicity*; D005344:Fibrinopeptide A / Q000032:analysis; D006487:Hemostasis / Q000187:drug effects*; D006493:Heparin / Q000494:pharmacology; D006801:Humans; D008666:Metalloendopeptidases; D010978:Platelet Factor 4 / Q000378:metabolism; D014757:Viper Venoms / Q000037:antagonists & inhibitors / Q000494:pharmacology / Q000633:toxicity*
D014757:Viper Venoms; D005344:Fibrinopeptide A; D010978:Platelet Factor 4; D006493:Heparin; D010450:Endopeptidases; D008666:Metalloendopeptidases; C033858:russellysin