These are used to prevent thrombus formation or the extension of an existing thrombus. Heparin combines with antithrombin and is an immediate acting inhibitor of the thrombin/fibrinogen reac-tion. Heparin can be given s.c. (prophylaxis), i.m. (not recommended) or i.v.

Effects are short lived and therefore continuous i.v. infusion seems to be associated with better results and fewer complica-tions, under carefully controlled conditions, e.g. in an Intensive Care Unit or with an infusion pump. Hemorrhage can be treated with protamine sulphate. One mg neutralizes 100 units of heparin.

Oral anticoagulants act by inhibiting the hepatic synthesis of the vitamin K dependent clotting factors. It makes 36 - 48 hours for the anticoagulant effect to develop and so if immediate effect is required then heparin must be started simultaneously and given 2 - 5 days.

Laboratory control of prothrombin time is essential. Drugs such as phenyl-butazone, indomethacin, sali-cylates and clofibrate increase the effect of oral anti-coagulants while barbiturates diminish its effect. Hemorrhage should be treated by omission of the drug (if mild) or with i.m. or i.v. vitamin K. Sensitivity is rare with warfarin but more common with phenindione.

Dose Range Loading doses are no longer recommended.

Start patient on expected daily dose or as a compromise give four (4) times expected daily dose on day one and the daily dose on each subsequent day (the latter regime takes into account the half-time of warfarin). The daily dose varies depending on body weight, sex, age, diseases and other drugs. Thus a 90 kg six foot tall man of fifty may require 12.5 mg per day while a five foot, 50 kg elderly lady may require only 2 mg.