134 VENOMOUS SNAKES AND THE PHENOMENA OF THEIR VENOMS 



remains fluid. A very remarkable fact was found by Martin, namely, that if 

 the fluidity of the blood be once produced by injecting a small quantity of the 

 venom no increase of coagulability can again be obtained by giving a second 

 large dose, which would otherwise culminate in an extensive thrombosis. It 

 is very interesting, again, to notice that the plasmas which exhibit only a 

 weak negative phase can be induced to clot by the addition of (i) solution 

 of nucleo-albumin (Wooldridge's tissue fibrinogen); (2) calcium chloride; 

 (3) dilution; (4) passage of C0 2 ; (5) Alexander Schmidt's fibrin ferment. 

 These are most active in the order indicated. 



The plasms which have lost all spontaneous coagulability may, however, 

 be made to clot by the following means : (1) addition of a saturated solution 

 of NaCl up to an equal volume; (2) addition of an equal volume of a satu- 

 rated MgS0 4 solution; (3) addition of acetic acid, until the plasma is just 

 faintly acidulous; (4) similar addition of weak sulphuric, hydrochloric, 

 or phosphoric acids (oxalic acid is ineffectual). 



In studying the effect of calcium chloride upon the plasmas of varying 

 stages or degrees of non-coagulability through the effect of the venom, Martin 

 divides the plasmas into three classes: 



(1) The cases where only a very moderate negative phase has been pro- 

 duced and the clotting of the shed blood is delayed from 30 minutes to 2 or 

 3 hours. The addition of a few drops of calcium chloride to a sample of blood 

 drawn from this class causes almost immediate solidification, and if a few 

 cubic centimeters of a 1 per cent solution of this salt in 0.9 per cent NaCl be 

 injected into a vein, the coagulability of the blood is raised above the normal, 

 and very frequently the animal dies in a few minutes from extensive 

 thrombosis. 



(2) Cases in which the negative phase is more pronounced and the blood 

 which is shed clots only after some hours or days. With this class calcium 

 chloride is without influence upon the extravascular plasma, but raises the 

 coagulability towards the normal. 



(3) A very pronounced negative phase in which the blood never clots 

 spontaneously, and in which the addition of saturated solution of sodium 

 chloride, etc., only occasions a very small amount of coagulum. With this 

 class CaC^ has no effect either when it is injected or added to the plasma 

 in vitro. 



In this early investigation Martin drew a parallelism existing between the 

 phenomena produced by venom and those produced by the tissue fibrinogen 

 of Wooldridge, but in 1905 this analogy was abandoned by him, when he 

 made a further inquiry into the nature of the clotting principle of various 

 venoms in general. 



In 1901 Lamb 1 made a remarkable discovery, which has since become 

 quite important in its bearing on the nature of the coagulating property of 

 certain snake venoms on the blood plasma — that the fluid plasma or blood 

 containing 1 to 2 per cent sodium citrate can be coagulated by adding a small 



1 Lamb. Indian Med. Gazette, 1901, XXXVI, 443. 



