Plasma levels of beta-thromboglobulin and platelet factor 4 as indices of platelet activation in vivo

Measurement of plasma levels of two secreted platelet proteins (beta-thromboglobulin and platelet factor 4) has been suggested as a means for detecting increased platelet activation in vivo. A crucial question in the measurement is the distinction between in vivo and in vitro secretion of the proteins. One approach to this distinction is the measurement of both proteins in each sample. These proteins are present in platelets in similar amounts and are released in similar quantities, but the plasma levels of beta-thromboglobulin exceed the plasma levels of platelet factor 4. This difference in plasma level is presumably due to more rapid removal of platelet factor 4 from the plasma level, and there is suggestive evidence that the rapid removal of released platelet factor 4 is due to its binding to endothelial cells. It appears that when there is increased release of beta-thromboglobulin and platelet factor 4 in vivo, there is an increase in the ratio of plasma beta-thromboglobulin to plasma platelet factor 4 compared to that found in normal individuals, whereas when in vitro release is responsible for elevated levels, the ratio decreases. Thus measurements of both proteins in each blood sample will allow distinction between in vivo release and artefactual in vitro release.