INHIBITION OF RED-CELL AGGREGATION PREVENTS SPONTANEOUS ECHOCARDIOGRAPHIC CONTRAST FORMATION IN HUMAN BLOOD

Background Spontaneous echocardiographic contrast (SEC) is a pattern o f blood echogenicity that has been attributed to ultrasonic backscatte r from blood cell aggregates that form under low shear conditions. Pat ients with left atrial SEC have an increased thromboembolic risk. This study examined the role of red cell and platelet aggregates in the pa thogenesis of SEC in human blood and the effects on SEC of antithrombo tic therapy and red cell disaggregatory agents. Methods and Results Bl ood echogenicity was examined with the use of quantitative videodensit ometry over a controlled range of flow velocities in an in vitro model characterized by nonlaminar flow conditions. One hundred ninety study samples were prepared from single fresh blood donations (40 to 120 mt ) from 24 healthy volunteers and 11 patients. Whole blood echogenicity was unaltered by depletion of platelets, stimulation of platelet aggr egation with adenosine diphosphate, or inhibition of platelet aggregat ion with aspirin. Low flow-related echogenicity increased with increas ing hematocrit (P<.001) but was abolished when red cells were lysed se lectively with saponin (P<.001). In the presence of red cells, low flo w-related echogenicity increased with increasing fibrinogen concentrat ion (P<.001) and with plasma paraproteins. Low how-related echogenicit y in whole blood was unaltered by heparin and warfarin but was reduced in a dose-dependent manner by dextran 40 (40 mg/mL, 70% reduction, P< .001) and poloxamer 188 (8 mg/mL, 47% reduction, P<.001), which inhibi ted red cell aggregation. Conclusions These results support protein-me diated red cell aggregation as the mechanism of SEC in human blood. In hibition of red cell aggregation, indexed by resolution of SEC, may pr ovide an alternative to anticoagulant and antiplatelet therapy to redu ce cardiac thromboembolic risk.