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

Heparin-induced thrombocytopenia pathophysiology is now known to be a compl ex process that involves platelets, vascular endothelium, and leukocytes/ly mphocytes. The activation products from these sites also contribute to the activation of coagulation and fibrinolytic deficit. While many of the marke rs of hemostatic activation processes have been found to be increased durin g the acute phase of heparin-induced thrombocytopenia syndromes, the circul ating levels of soluble adhesion molecules such as the P, E, and L selectin s, and intracellular and vascular cell adhesion molecules have not been rep orted. Since the pathophysiology of heparin-induced thrombocytopenia involv es 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 i n circulating blood. These alterations may also provide an index of the pat hophysiologic process. With the availability of highly sensitive enzyme-lin ked immunosorbent assays for soluble P, E, and L selectins, intracellular a nd vascular cell adhesion molecules: it is now possible to measure these ad hesion molecules in biological fluids. This study reports on the circulatin g levels of various adhesion molecules in patients with heparin-induced thr ombocytopenia and their modulation after therapeutic interventions by the u se of direct thrombin inhibitors. With the availability of recombinant hiru din, it is now possible to treat these patients with alternate antithrombin agents. However, the immunoactivation of platelets and other cells as show n here indicates the possible need for additional adjunct therapeutic appro aches to suppress their participation in the thrombotic process. The report ed increase in the circulating levels of the soluble adhesion molecules dur ing the heparin-induced thrombocytopenia and heparin-induced thrombocytopen ia 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 synd rome warrants further investigation.