Selectins in the HIT syndrome: Pathophysiologic role and therapeutic modulation

The pathophysiology of heparin-induced thrombocytopenia (HIT) is now known to be a complex process which involves platelets, vascular endothelium, and leukocytes. The activation products from these sites also contribute to th e activation of coagulation and to the fibrinolytic deficit. While many of the markers of hemostatic activation processes have been found to be at inc reased levels during acute phases of the HIT syndromes, the circulating lev els of soluble P-, E-, and L- selectins have not been reported. Since the p athophysiology of HIT involves the activation of platelets, endothelium, an d leukocytes, it is expected that activation products related to these hemo static systems, including soluble selectins, will also be increased in circ ulating blood. These alterations mag provide an index of the pathophysiolog ic process. With the availability of highly sensitive ELISAs for soluble P- , E-, and L-selectins, it is now possible to measure these adhesion molecul es in biological fluids. This study reports on the circulating levels of P- , E-, and L-selectins in HIT patients and their modulation after therapeuti c intervention. With the availability of recombinant hirudin, it is now pos sible to provide alternate anticoagulants to HIT patients. However, the imm unoactivation of platelets and other cells may require additional adjunct t herapeutic approaches.