Phenylhydrazine (PHZ) is a hemolytic agent which has been used in the treatment of
polycythemia vera. Recent studies performed in our laboratory have indicated that the PHZ-induced
anemia is immuno-hemolytic in etiology, and a prolonged bleeding time was present in some of the rats chronically treated with PHZ. The nature of this
bleeding tendency was explored in the present experiment. PHZ was administered to rats once a week for a six week period. During this time, the animals were monitored for prothrombin time (PT), activated partial thromboplastin time (APTT),
fibrinogen concentration, and individual
coagulation factor levels as well as routine plasma chemistries and blood cell counts. In addition, radioimmunoassays (RIA) for
prostacyclin, a
platelet aggregation inhibitor, and
prostaglandin (PG) E2 were performed. PHZ-treated animals displayed a significant elevation in both PT and APTT when compared with saline injected controls, although plasma
fibrinogen levels were not appreciably altered. Further tests revealed a PHZ-induced decrease in
prothrombin and
factor V levels. In addition, a significant increase in plasma serum
glutamate oxaloacetate transaminase (
SGOT),
lactate dehydrogenase (LDH), and
alkaline phosphatase levels was observed as well as a diminution in
cholesterol and
triglycerides following PHZ administration. PHZ treatment also induced an elevation in
prostacyclin levels and transient
thrombocytopenia. These findings indicate that several factors may contribute to the prolonged bleeding time in PHZ-treated rats including a
drug induced
thrombocytopenia possibly associated with enhanced synthesis of autologous
immunoglobulin G (
IgG) against the senescent red cell
antigen, and diminished synthesis of
vitamin K-dependent
coagulation factors which may be mediated by
reduced vitamin K uptake by the hypo-cholesterolemic subjects.