The existence of a phenomenon of rebound hypercoagulability after cessation of oral anticoagulant therapy is controversial. The sensitive procoagulant markers for in vivo thrombin and fibrin formation are potential tools for the reassessment of the presence of each a phenomenon. We examined 19 patients anticoagulated for 6 +/- 2 months (SD, range 3-12) because of venous thromboembolism or myocardial infarction as follows: twice during stable, oral anticoagulation (INR 3.1-3.7) and then on days 1, 2, 3, 4, 5, 7, 9, 11, 13, 15, and > 30 after cessation of oral anticoagulation. Thrombin-antithrombin III complexes (TAT) and fibrinopeptide A (FPA) were measured in addition to the prothrombin times and factors II, V, VII, and X. None of the 19 patients developed clinically manifest thromboembolism within the following 9-18 months. However, the patients' TAT levels increased transiently: rising from 1.5 +/- 0.1 ng/ml (SEM) to 3.0 +/- 0.2 ng/ml on day 4 (P < 0.001), and returned to 1.7 +/- 0.1 ng/ml after day 30 (normals 1.8 +/- 0.33). 17/19 patients showed TAT peak levels above the upper limit of normal between days 3 and 11 (average: day 4), which normalized again after 30 d. 8/19 patients also had transient FPA levels above the upper normal limits ( < 1.81). We conclude that our patients increased their thrombin and fibrin formation transiently and that a subpopulation reached values consistent with a prethrombotic state.

Concentrations of thrombin-antithrombin III (TAT) complexes in plasma were previously reported to be increased after a 100-km run, while fibrinopeptide A (FPA) concentration remained unchanged. Thus, antithrombin III appears to neutralize thrombin generated during running and prevents fibrin formation. To determine the clinical relevance of these findings, we compared the effects of exhaustive running (1 h, n = 10) on the plasma concentrations of prothrombin fragments F1 and F2, TAT, FPA, and beta-thromboglobulin with the effects of recreational jogging (1 h, n = 10) and exhaustive bicycling on an ergometer (1 h, n = 8). Prothrombin fragments F1 and F2 and TAT concentrations increased significantly in each group. The most significant increase in TAT concentration was measured in the running group (from 1.72 +/- 0.49 to 3.61 +/- 1.03 ng/ml, P < 0.001). The best correlation was found between the postexercise TAT and lactate concentrations (r = 0.62, n = 28, P < 0.001). Mean FPA concentrations after exercise did not exceed normal values in any of the three groups analyzed. An increase in beta-thromboglobulin concentration was measured in the running and in the cycling group. Thus, thrombin is formed, in particular, when associated with anaerobic metabolism, and platelets are activated during high-intensity exercise.

There is evidence of enhanced thrombin formation in patients with PAD compared with an age- and sex-matched control group without clinical and sonographic evidence of arteriosclerosis. The thrombin formed, however, appears to be almost completely neutralized by antithrombin III. No direct evidence of fibrin formation was obtained, since the FPA concentrations were not different. In the patients with PAD, the higher concentrations of D-dimers are indicative of in vivo fibrinolysis. Thus, some fibrin formation must be postulated to occur in patients with arteriosclerosis.

The influence of erythrocyte shape changes on the sedimentation rate was studied in vitro and in vivo. In vitro the highest sedimentation rate was observed with a slight degree of stomatocytosis (morphological index-0.3; i.e. one red cell out of three being a stomatocyte I). With increasing degrees of stomatocytosis the sedimentation rate gradually decreased. Echinocytosis reduced the aggregation and sedimentation very drastically; the sedimentation rate was virtually zero when echinocytosis I or higher degrees were present. The influence of abnormal cell shapes occurring in vivo was studied in patients with an abnormal blood smear. It was found that a severely abnormal red cell morphology reduced the sedimentation rate in a standardized, fibrinogen-rich plasma to about half. These results indicate that the shape plays a crucial role in the aggregation and sedimentation of red cells and they may contribute to the understanding of the interaction of red cells with other cells such as endothelium.