Prothrombin Deficiency and the Bleeding Tendency in Liver Injury (chloroform

Chloroform has been used extensively in experimental work for the production of liver injury. In pronounced intoxication there is extensive necrosis of the liver, and the animal shows marked disturbance of blood coagulation. Clots which form are flabby and are ineffectual in controlling hemorrhage from minor incisions. The work of Doyon (1) suggested that there is a decrease in the plasma fibrinogen. Whipple and Hurwitz (2) and Foster and Whipple (3) in careful quantitative studies confirmed this. Recently we have developed a method for the quantitative determination of prothrombin (4). With large chloroform doses we found not only a decrease in fibrinogen, but also a very marked fall in plasma prothrombin. The bleeding tendency in this condition is dearly due to a deficiency in both of these factors. In the present paper we shall demonstrate that the prothrombin is more labile than the fibrinogen. When the chloroform dosage is small the prothrombin falls much more markedly than the fibrinogen. It is even possible by giving small repeated doses of chloroform to completely dissociate these two clotting factors. In such experiments, the fibrinogen level remains unaffected, but the prothrombin falls markedly, often with the development of a hemorrhagic tendency.