Covert anticoagulant ingestion: study of 25 patients and review of world literature.

Twenty-five patients with covert ingestion of oral anticoagulant drugs were studied. Most of the patients were women who were either connected with the medical profession or were previously treated with antigoagulants. The most common findings were ecchymoses, hematuria, and a markedly prolonged prothrombin time. The anticoagulant drug was identified in the plasma of all 25 patients. Most patients responded promptly to administration of vitamin K1. The most common motives were malingering and suicide. The world literature was reviewed for covert ingestion of oral anticoagulant drugs and 48 other cases were found. The correct diagnosis is important to focus the physician's attention on the psychiatric rather than the somatic aspects of the disorder.

Hageman factor (factor XII) deficiency in marine mammals.

Hematologic and coagulation studies were conducted on Atlantic bottlenose dolphins and killer whales. Hematologic values were similar to those in man. These animals differed from other mammals in that the Hageman factor (factor XII) was absent and this absence caused marked prolongation of coagulation. Levels of factors VIII and V were high and those of VII and X were low compared with levels in man.

Studies on coumarin anticoagulant drugs. Initiation of warfarin therapy without a loading dose.

Thirty normal subjects were given a single loading dose of warfarin sodium, 1.5 mg/kg of body weight. The drug was metabolized slowly (mean biological half-life, 47 hr) and showed a prolonged biological effect (over 6 days). In two separate experiments no loading dose was given; instead, daily doses of 15 mg and 10 mg were administered to 15 of the subjects. The prothrombin complex responses were compared with those obtained in the same subjects after the large loading dose. The mean time in days to reach the therapeutic range (prothrombin complex activity < 35% of normal) was 1.1 days with the dose of 1.5 mg/kg of body weight, 2.7 days with the dose of 15 mg/day, and 5.2 days with 10 mg/day. With all three methods the therapeutic range was reached soon after a level of warfarin of 2 mg/L plasma was attained. The rates of fall of the four vitamin K-dependent clotting factors (II, VII, IX, and X) with the large loading dose and with the daily dosage of 15 mg were compared in six of the subjects. With the loading dose, factor VII activity was less during the first 48 hr, but there was no other significant difference between the two methods of drug administration in the amount of reduction of any of the four factors. Since the role of factor VII in thrombogenesis is questioned, these results provide a rational basis for the induction of prophylactic anticoagulant therapy without large loading doses of warfarin. Avoidance of the customary loading dose should reduce the danger of hemorrhage, particularly in patients who are sensitive to the drug because of advanced age, sepsis, liver disease, congestive heart failure, or recent surgery or trauma.