Thermal titration: application of calorimetry to the study of plasma coagulation

Abstract

The authors studied the coagulation of plasma by thrombin with a titration calorimeter at 20° C. When thrombin is added to plasma, 3 distinct alterations in the thermal pattern are seen. The precoagulation region is generally exothermic, although occasionally, with some plasmas, cooling is observed. The coagulation region is defined by a sharp exotherm, a plateau, and then a sharp endotherm. Postcoagulation is generally a long exothermic region, which is partially the result of frictional heat produced from the coagulum. Plasmas from 5 normal patients were assayed. The thrombin clotting times ranged from 33 to 48 sec (SD, 3 sec). After storage at -20° C for 10 days, the plasma showed a decrease of about 8 sec in the clotting time. Coagulation times were found to depend on both the fibrinogen concentration and the thrombin concentration in addition to other unknown factors. Fibrinogen content correlated roughly with the heat rise during coagulation. Heparin (final concentration, 0.25 units/ml) prevented coagulation for more than 15 min after the addition of 12.5 units of thrombin. Under normal conditions, 25 milliunits of heparin per ml doubled the clotting time. Coagulation of fibrinogen alone gave a different thermogram in that the coagulation region was prolonged and there was very little or no heat generated after the clot had formed.