Blood coagulation tests in toxicological studies--review of methods and their significance for drug safety assessment.
In general toxicological studies, prothrombin time and activated partial thromboplastin time are routinely measured to assess blood coagulation. Special (problem-driven) tests for blood coagulation are of significance to detect abnormalities and investigate the mechanism of toxicity in detail. In this review, we compiled widely scattered information on blood coagulation testing from different fields in the biological area, and reviewed the methods available and their significance in toxicological studies. The relevant literature cited here reports large species differences in platelet aggregation, coagulation factors or fibrinolysis, and technical limitations. However, the following tests are basically applicable to laboratory animals; (1) assays for individual coagulation factors and protein induced by vitamin K absence or antagonists (PIVKA) to investigate coagulation factor abnormalities; (2) platelet aggregation-, platelet adhesion-, platelet release-tests and von Willebrand factor assay to screen and/or investigate platelet dysfunction; (3) fibrin/fibrinogen degradation products (FDP), D-dimer and thromboelastogram to detect fibrinolitic abnormalities, and assays for plasminogen, plasmin and their activator/inhibitor to investigate fibrinolysis in detail; and (4) bleeding-time to grossly evaluate blood coagulation capability in vivo. An appropriate battery of these tests provides significant information for risk assessment of drugs.
Kurata
Masaaki
M
Worldwide Safety Sciences, Pfizer Global Research and Development, Nagoya Laboratories, Pfizer Inc., 5-2 Taketoyo, Aichi 470-2393, Japan.
Horii
Ikuo
I
D000818:Animals; D000830:Animals, Laboratory; D001780:Blood Coagulation Tests / Q000379:methods*; D004353:Drug Evaluation, Preclinical; D018570:Risk Assessment; D018675:Toxicity Tests / Q000379:methods*