Anti‐platelet factor 4/heparin antibodies in patients with Hantaan virus infection

BACKGROUND: Hemorrhagic fever with renal syndrome (HFRS) induced by Hantaan virus infection and heparin‐induced thrombocytopenia (HIT) are associated with symptoms such as thrombocytopenia and thrombosis. However, related molecules, such as anti–platelet factor 4 (PF4)/heparin antibodies, in patients with HFRS have not been evaluated. OBJECTIVES: To test plasma levels of anti‐PF4/heparin antibodies and study the possible role of these antibodies in HFRS pathogenesis. METHODS: Indirect ELISA was used to determine plasma levels of anti‐PF4/heparin antibodies in 75 patients with HFRS and 20 normal controls. The 4Ts (thrombocytopenia, timing of platelet count fall, thrombosis or other sequelae, and other causes of thrombocytopenia) scoring system was used to determine the probability of HIT occurrence. A PF4‐enhanced platelet activation assay was used to detect the pathological effects of anti‐PF4/heparin antibodies. The laboratory/clinical features and viral load of all the patients were also assessed. RESULTS: Of the 75 patients with HFRS enrolled in this study, 69 had thrombocytopenia. Platelet count was negatively correlated with Hantaan viral load. Moreover, the optical density (OD) values of plasma antibodies against PF4/heparin in normal controls were less than 0.65, 4 patients tested strongly positive for anti‐PF4/heparin antibodies (OD values, 1.51–3.87), 21 patients were weakly positive (OD values, 0.66–0.74), and 50 patients were negative (OD values, 0.16–0.65). Moreover, all 4 patients who tested strongly positive for anti‐PF4/heparin antibodies showed a low probability of HIT (4Ts score of 3 or less) and had negative results in the PF4‐enhanced platelet activation assay. CONCLUSIONS: Hantaan virus infection produces nonpathogenic antibodies against PF4/heparin; however, the generation mechanism of these antibodies requires further study.