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

We studied the coagulation of plasma by thrombinwith a titration calorimeter at 20 #{176}C. When thrombin is added to plasma, three 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 five normal patients were assayed. The thrombin clotting times ranged from 33 to 48 S (SD, 3 s). After storage at -20 #{176}C for 10 days, the plasma showed a decrease of about 8 s 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/mI) prevented coagulation for more than 15 mm after the addition of 12.5 units of thrombin. Under normal conditions, 25 milliunits of heparm per milliliter 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.