Spontaneous Hemorrhagic Diathesis in Inbred Mice Due to Single or Multiple "Prothrombin-Complex" Deficiencies

Spontaneous hemorrhagic diathesis had been observed in certain inbred strains of mice. Characteristically, bilateral hemothorax with or without multiple bleedings occurred elsewhere in the body; the mice were anemic and jaundiced.

The major histopathologic findings were myocarditis and various degrees of hepatomegaly. Associated with myocarditis was elevation of lactic dehydrogenase; anemia and icterus were thought to be consequent to extensive hemorrhage rather than to hepatic dysfunction since serum phosphatase and transaminase were, except for lowered serum glutamic pyruvic transaminase, within normal range or only slightly altered.

The mice were found to suffer from single and multiple prothrombin-complex deficiencies, specifically affecting Stuart-Prower factor (X), PTC (IX), SPCA (VII), and prothrombin. Activities of the first three factors were less than three per cent of normal and the last was less than 10; Ac-G (V), Hageman factor and fibrinogen were normal. Details of component assays and substitution analyses were given. The disease was acquired, but affected various strains differentially, and involved only males. No explanation was offered for this peculiar strain and sex susceptibility. Evidence was presented for implicating ethylene glycol and higher polymers produced by ethylene oxide sterilization of mouse cage bedding.