OBJECTIVE The combined use of coumarin and low-dose aspirin appears to reduce the risk of systemic embolism at a low risk of bleeding. The remaining incidence of embolism of approximately 2%/y is still high. Methods for real-time detection of embolic events have not been used thus far to monitor the efficacy of therapeutic strategies. They might permit individually tailored, effective treatments. METHODS The frequency of embolic signals in both middle cerebral arteries was monitored using a two-channel 2-MHz transcranial Doppler system. We examined five patients with mechanical prosthetic heart valves suffering from recurrent cerebral ischemic symptoms despite adequate anticoagulant therapy (international normalized ratio, 3.0 to 4.3). Measurements were performed on coumarin alone (four baseline values) and subsequent to the addition of intravenous (500 mg bolus) and oral (100 mg/d for 10 days) aspirin or intravenous (5000 IU bolus) heparin. The prothrombotic markers thrombin-antithrombin III complex, fibrinopeptide A, D-dimer, and platelet beta-thromboglobulin were measured simultaneously. RESULTS None of the combined drug regimens led to a significant reduction of the emboli count. The values of thrombin-antithrombin III complex, fibrinopeptide A, and D-dimer were already within normal limits with coumarin alone. The beta-thromboglobulin levels, however, were increased, and additional aspirin or heparin did not reduce them. There was no correlation between the emboli count and the prothrombotic markers or between the prothrombotic markers and the different drug regimens. CONCLUSIONS The rate of cerebral emboli measured with transcranial Doppler in the group of high-risk patients studied was not influenced by additional antiplatelet therapy. The emboli are likely to be composed at least in part of platelets, and their generation seems not dependent on thrombin or cyclooxygenase. There is an apparent discrepancy between the unchanged rate of emboli during Doppler monitoring found in this and other studies and the partial efficacy of combined treatment with coumarin and aspirin in clinical long-term studies. This may be explained by differences in the composition or size of the emboli.