THE EXPERIMENTAL PRODUCTION OF A HEMOPHILIA-LIKE CONDITION IN HEPARINIZED MICE

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Abstract
The method of Doettl and Ripke to determine bleeding time in mice was found reliable. 310 venous bleeding time detns. in 118 normal mice ranging between 15.4 to 220 secs. had an avg. bleeding time of 54 secs. Unlike Doettl and Ripke, values agreeing within [plus or minus] 30 secs. on consecutive days were found normal. The observation that variations in temp. influence the bleeding time was verified. Heparin (Connaught Laboratories, 110 units per mg.) in large doses (1000 units per 20 gs. wt., injected subcut.) had no toxic effect. There is a definite relationship between the units of heparin injected and the prolongation of clotting time. Such a relation to bleeding time does not exist in smaller doses (5 to 100 units per 20 gs. wt.), whereas in excessive doses (200 to 1000 units per 20 gs. wt.), and then only in some instances, there was an increase of both the bleeding time and coagulation time. Repeated prickings in some excessively heparinized mice produced a prolonged bleeding time after one or several normal values. This never occurred in normal mice. It is believed that an unindentified factor exists in the skin (or tissue fluid) which may be exhausted by the inj. of heparin, resulting in a prolongation of the bleeding time. A correlation between the bleeding time and coagulation time was found in heparinized mice. It is believed that these mice are similar to hemophiliacs because both show a prolonged coagulation time and a bleeding tendency. Essential similarities of the blood, pathological anatomy and clinical behavior of hemophiliacs and heparinized animals are discussed. An equilibrium between coagulant and anticoagulant substances is believed to be present in normal circulating blood. This is greatly disturbed in hemophilia, resulting in a relative increase of anti-coagulant substances.

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