Functional characterization of antibodies against heparin-platelet factor 4 complex in heparin-induced thrombocytopenia patients in Asian-Indians: relevance to inflammatory markers

Occurrence of heparin-induced thrombocytopenia (HIT) was investigated for 33 Indian patients undergoing cardiovascular surgery who received unfractionated heparin (UFH). Platelet counts were performed prior to the initiation of UFH therapy and 5-16 days post therapy. Heparin-induced platelet aggregation, C-14-serotonin release assay, and enzyme-linked immunosorbent assay (ELISA) tests were performed in all the patients to detect the antibodies formed against the complex of heparin and platelet factor 4 (HPF4). Levels of inflammatory markers/mediators such as CD40 ligand (CD40L) and C-reactive protein (CRP) were also measured in the patient plasmas utilizing ELISA tests. Based on clinical observations and laboratory diagnoses, five patients (15%) were considered to have confirmed HIT. Despite wide variations in the titers of inflammatory markers, patients who tested ELISA-positive for HPF4 antibodies showed markedly elevated levels of both soluble CD40L and C-reactive protein. Most strikingly, the 14 C-serotonin release assay-positive patients showed up to a 10-fold increase in the level of CD40L. It is concluded that approximately 15% Asian-Indian patients receiving UFH during cardiovascular surgery develop functional HPF4 antibodies, which are associated with the increased levels of inflammatory markers/mediators in this catastrophic HIT syndrome.