EFFECTS OF HEPARIN AND COUMARIN ON DEPOSITION OF FIBRIN, PLATELETS AND PLATELET THROMBI ON RABBIT AORTA SUBENDOTHELIUM EXPOSED TO FLOWING HUMAN BLOOD

The effect of heparin and phenprocoumon on thrombogenesis induced by rabbit aorta subendothelium (SE) was investigated in 20 volunteers using an ex vivo perfusion system. Blood was drawn directly from an antecubital vein through an annular chamber with exposed SE at lOml/min flow rate (650sec⁻¹ shear rate) for 5min. Following buffer perfusion for 15sec, the middle portion of SE was removed for plasmin digestion and adjacent segments were fixed and embedded for morphometric analysis. Perfusions were performed 20 min after i.v. injection of heparin 1000, 2500 and 5000 IU, respectively; and during the decline and steady-state of prothrombin activity during a 2 weeks treatment with phenprocoumon to target INR of 5.0.

The amount of fibrin attached to SE, as measured by fragment E RIA in plasmin digests, correlated negatively with the dose of heparin (r=−0.83, P<0.001, n=48) and with INR during coumarin intake (r=−0.58, P<0.01, n=40). After high doses of either heparin or coumarin fibrin deposition on SE was virtually abolished (table). Platelet adhesion was increased. Platelet thrombus volumes and heights were reduced by heparin and coumarin.

We conclude that both heparin and coumarin dose-dependently inhibit fibrin formation induced by SE. In addition, both drugs impair platelet thrombus growth and/or stability indicating that these processes may also depend on the coagulation mechanism.