There is, therefore, a very decided difference between venoms of divers origins as regards their effects upon the coagulation of the blood.
Noc has determined more especially the coagulant action of the venom of Lachesis lanceolatus (Fer-de-lance of Martinique) upon 1 per cent. citrate-plasmas, 1 per cent. oxalate-plasmas, 4 per cent. chloridate-plasmas, and upon blood rendered non-coagulable by extract of leeches’ heads. He found that, while weak doses of venom (1 milligramme per cubic centimetre of horse- or rabbit-plasma) produce coagulation in a few minutes in the citrate-plasmas, chloridate-plasmas, or those treated with extract of leeches, the doses of the same venom greater than 4 milligrammes on the contrary suppress the coagulability of these plasmas, even when there be added to them doses of chloride of calcium (for the citrate- and oxalate-plasmas), or of distilled water (for the chloridate-plasma), or of fibrin-ferment (for the plasma treated with leech-extract) sufficient to cause rapid coagulation in the control tubes that do not contain venom.
Noc also observed that the venom of the same species of snake (Lachesis lanceolatus), when heated to 75° C., entirely loses its coagulant properties; and that, with a temperature of 58° C., its coagulant power already commences to diminish. When heated for thirty minutes at a temperature of 65° C., a dose of 1 milligramme does not coagulate more than 1 c.c. of citrate-plasma in one hour. G. Lamb has likewise found that the venom of Vipera russellii loses its coagulant power when heated to 75° C.
The coagulant substance in these venoms is precipitable by alcohol at the same time as the neurotoxin and other active substances. The precipitate, when dissolved again in physiological water, preserves all the properties of the original solution.
Antivenomous anticolubrine serum, that is to say, that furnished by horses vaccinated against the venoms of the Cobra and the Krait, does not prevent coagulation by coagulant venoms. This need not surprise us, since the coagulant substances in venoms are destroyed by heating, and the animals vaccinated in order to obtain antitoxic serum are usually inoculated exclusively with heated venoms.
It is easy, however, to obtain active serums specific against the coagulant venoms; it is sufficient to treat these animals by inoculation with progressively increasing doses of the same venoms unheated. I have had no difficulty in achieving this result with small laboratory animals (guinea-pigs and rabbits) and also with the horse, but I have never had at my disposal a sufficient amount of the venoms of Lachesis or Vipera russellii to undertake with them the regular acquisition of large quantities of horse-serum, at once antineurotoxic and anticoagulant. The preparation of such a serum, nevertheless, presents much interest for certain countries, such as Burma, where the Daboia (Vipera russellii) is almost as common as the Cobra, and Brazil, where nearly all the casualties due to venomous snakes are produced by Lachesis.[38]
II.—Anticoagulant Venoms.
Contrary to what is observed with the venoms of Viperidæ in general, all the venoms of Colubridæ and, as exceptions to the rule, the venoms of some North American Crotalinæ (Ancistrodon contortrix and A. piscivorus) suppress the coagulability of the blood in vivo and in vitro. It is, however, important to observe that, in vivo, the blood remains fluid after death only if the dose of venom absorbed has been sufficient. In vitro this phenomenon is easier to study, and has been the subject of several important memoirs.
Halford,[39] Sir Joseph Fayrer,[40] C. J. Martin,[41] Delezenne,[42] Phisalix,[43] and lastly Noc,[44] have shown that the venoms of Colubridæ exert a manifestly anticoagulant action upon citrate-, chloridate-, or oxalate-plasmas, and also upon blood mixed with venom on issuing from the vessels.
On adding 1 milligramme of Cobra-, Bungarus-, Australian Pseudechis-, or Ancistrodon-venom to 1 c.c. of citrate-, oxalate-, or chloridate-plasma, and supplementing the mixture, after varying periods of contact, with a quantity of chloride of calcium (for the citrate- or oxalate-plasmas), or distilled water (for the saline plasma) sufficient to produce coagulation in a few minutes in the control tubes without venom, we find that coagulation no longer takes place after one hour in the tubes containing Cobra- or Bungarus-venom, and after ten minutes in those that contain the venom of Ancistrodon.