PLATELETS The Platelet That Came in From the Cold

Hoffmeister et al. discovered that clearance of chilled platelets from the blood depended upon enhanced phagocytosis by liver macrophages. Platelets, anucleate blood cells that adhere to sites of vascular injury and promote formation of blood clots, disappear from the circulation if they have been chilled, a property that limits long-term storage of platelets for transfusions. This "clearance" of prechilled platelets has been attributed to shape changes leading to entrapment in the microcirculation. Hoffmeister et al., however, showed that chilled mouse platelets treated to maintain their shape, which appeared functionally normal, still disappeared. The authors used labeled platelets injected into mice to show that chilled platelets disappeared more rapidly than platelets stored at room temperature and that they accumulated in the liver. Chilled platelets adhered to Kupfer cells (liver macrophages); both rapid clearance and adherence to macrophages depended on mouse expression of complement receptor-3 (CR3, _Mß₂ integrin). Chilled platelets injected into mice lacking CR3 showed normal hemostatic function. Removal of the extracellular domain of GPIB, part of the receptor for von Willebrandt factor (vWf) that also binds CR3, abolished rapid clearance and reduced phagocytosis of chilled human platelets. Chilling caused clustering of immunogold-labeled GPIB but did not affect binding of activated vWf. Platelet counts in mice with CR3 receptors dropped when they were exposed to cold temperatures, whereas platelet counts in mice lacking CR3 did not. Mild chilling primes platelets for activation, which the authors previously proposed limits bleeding at exposed surfaces; in this paradigm, rapid clearance prevents thrombosis in critical core regions by these primed platelets.

K. M. Hoffmeister, T. M. Felbinger, H. Falet, C. V. Denis, W. Bergmeier, T. N. Mayadas, U. H. von Andrian, D. D. Wagner, T. P. Stossel, J. H. Hartwig, The clearance mechanism of chilled blood platelets. Cell 112, 87-97 (2003). [Online Journal]