EFFECTS OF SNAKE VENOM ON COAGULABILITY OF THE BLOOD 141 



blood vessels, and, if only a small fraction of such clotting dose be given, a 

 total or partial loss of coagulability ensues. 



The anticoagulating effect of cobra venom upon the whole blood and blood 

 plasma has been demonstrated by Lamb in a quite ingenious manner. The 

 whole blood was made incoagulable by means of i per cent sodium citrate or 

 0.2 per cent potassium oxalate. Then the quantity of solution of calcium 

 chloride which, when added, brings about coagulation of the citrate or oxa- 

 late blood in a few minutes was determined. Now varying amounts of cobra 

 venom were mixed with these incoagulable bloods before adding the lime 

 solution. It was found that even 0.02 to 0.03 gm. cobra venom did not pro- 

 duce coagulation when added to 1 ex. of the citrate blood. On the con- 

 trary, 0.0004 g m - °f this venom kept 1 c.c. of the citrate blood unclotted, when 

 the amount of calcium chloride solution sufficient to produce coagulation in 

 1 to 3 minutes in the venom-free control citrate blood was added. Distinct 

 inhibiting effect was exerted even by as minute a quantity as 0.00001 gm. of 

 the venom. Lamb mentions that heating cobra venom to 75 C. for half an 

 hour diminishes its anticoagulating power, but does not destroy it. 



With the citrate and oxalate blood plasmas the results obtained were 

 practically the same as with the whole blood. In the case of the citrate 

 plasma 0.001 gm. of cobra venom prevented coagulation of 2 c.c. of the 

 plasma. 



The experiment with hydrocele fluid seems to be of much significance in 

 interpreting the action of cobra venom in bringing about incoagulability of 

 the blood and plasma. As is well known, the hydrocele fluid requires fibrin 

 ferment or at least protothrombin, but not calcium chloride, to become 

 clotted. Lamb found that 0.1 gm. of the citrate donkey plasma (1 per cent) 

 was sufficient to clot 2 c.c. of the hydrocele fluid in 20 minutes. But, when 

 the venom was allowed to act for 10 minutes upon the plasma before the addi- 

 tion of the hydrocele fluid, no coagulation took place. The addition of a 

 small quantity of lime solution did not affect this result in any way. 



Now, returning to the action of daboia venom as an anticoagulating agent, 

 Lamb could not observe any inhibitory effect upon the whole blood or blood 

 plasma in vitro. The venom of Daboia, like that of Pseudechis, Notechis, and 

 Echis, is a powerful anticoagulating agent when allowed to act in vivo, but not 

 at all in vitro. Every varying subclotting dose, even as small as 0.000000009 

 gm. has been tried, but on every trial the coagulability increased more or 

 less, without, however, any diminishing effect. Thus the negative phase of 

 coagulability in vivo produced by daboia venom is of an entirely different 

 process from that observed with a large dose of cobra venom both in vivo 

 and in vitro. 



Finally an interesting observation was made to ascertain whether the 

 previous addition of a large dose of cobra venom to the citrate plasma would 

 prevent coagulation by a later addition of daboia venom to such mixture. 

 It was found that the presence of a large quantity of cobra venom does not 

 inhibit in the slightest degree the clotting action of daboia venom. In this 



