Effects of Thorium Dioxide upon Blood Clotting and Platelets. II. In Vivo Studies in Rabbits^[*]

Summary

An intravenous injection of the usual “blocking” dose of thorium dioxide (3 ml/kg) into rabbits damaged platelets, granulocytes and clotting factors :

1. Platelets immediately decreased and took more than 24 hrs to return to normal. Abnormalities of platelet morphology were noted.

2. Granulocytes also decreased immediately but returned to normal or higher than normal levels in 1 hr.

3. The thrombin time immediately increased. Its return to normal paralleled the clearance of thorium dioxide from the blood. Fibrinogen decreased slightly but the fall was not statistically significant.

4. Factors II, V, VII, VIII, IX, and X dropped progressively over 8 hrs to levels between 5 and 40%. Low levels of these factors persisted for several hours after the thorium dioxide had disappeared from the blood. Modest decreases were also noted in factors XI and XII.

The clotting factor abnormalities were more marked with unfiltered (TDS) than with filtered (Thorotrast) suspensions of thorium dioxide, and cardiac tamponade after heart puncture occurred more frequently in the TDS-animals. It became evident from these studies that a rabbit prepared for the generalized Shwartzman reaction with thorium dioxide has a severe hemostatic defect when it receives the triggering injection of endotoxin 8 hrs later.

^* Supported by research grant H-6128-04 from the National Heart Institute, USPH, by The Norwegian Research Council for Science and the Humanities, and by The Norwegian Council on Cardiovascular Diseases.

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