Soluble adhesion molecules in the HIT syndrome: Pathophysiologic role and therapeutic modulation

Heparin-induced thrombocytopenia pathophysiology is now known to be a complex process that involves platelets, vascular endothelium, and leukocytes/lymphocytes. The activation products from these sites also contribute to the activation of coagulation and fibrinolytic deficit. While many of the markers of hemostatic activation processes have been found to be increased during the acute phase of heparin-induced thrombocytopenia syndromes, the circulating levels of soluble adhesion molecules such as the P, E, and L selectins, and intracellular and vascular cell adhesion molecules have not been reported. Since the pathophysiology of heparin-induced thrombocytopenia involves the activation of platelets, endothelium, and leukocytes, it is expected that the activation products related to these hemostatic systems including soluble selectins and cellular adhesion molecules will also be increased in circulating blood. These alterations may also provide an index of the pathophysiologic process. With the availability of highly sensitive enzyme-linked immunosorbent assays for soluble P, E, and L selectins, intracellular and vascular cell adhesion molecules: it is now possible to measure these adhesion molecules in biological fluids. This study reports on the circulating levels of various adhesion molecules in patients with heparin-induced thrombocytopenia and their modulation after therapeutic interventions by the use of direct thrombin inhibitors. With the availability of recombinant hirudin, it is now possible to treat these patients with alternate antithrombin agents. However, the immunoactivation of platelets and other cells as shown here indicates the possible need for additional adjunct therapeutic approaches to suppress their participation in the thrombotic process. The reported increase in the circulating levels of the soluble adhesion molecules during the heparin-induced thrombocytopenia and heparin-induced thrombocytopenia with thrombosis syndrome suggests that the antiheparin platelet factor 4 antibody is capable of modulating their regulation. The prognostic role of these mediators in the management of heparin-induced thrombocytopenia syndrome warrants further investigation.