Anti-Heparin/PF4 Complexes by ELISA in Patients with Disseminated Intravascular Coagulation

Abstract

Heparin-induced thrombocytopenia (HIT) is known to complicate disseminated intravascular coagulation (DIC), but rarely to be complicated by DIC. We measured the titers of anti-PF4/hepatin complex antibodies by ELISA (HIT-Elisa) and examined 4 parameters of coagulation and fibrinolysis [D-dimer, thrombin/antithrombin complex (TAT), plasmin/α2-plasmin inhibitor complex (PIC), and antithrombin levels] in 80 patients with DIC diagnosed by a DIC scoring system. Fourteen patients were HIT-Elisa-positive, 11 of whom received heparin. In 3 of these 11 patients, platelet counts were ≤10 × 10⁹/l and/or reduced by more than 50% for 5–10 days after the heparin (2 patients treated with renal replacement therapy for chronic uremia and postoperative renal failure, and 1 with DIC from a solid tumor). The 3 patients had an optical density reading of >1.0 and a high level of IgG for HIT antibodies, and were thus considered to have DIC complicated with HIT (DIC-HIT). The other 8 patients had optical density readings of 0.4–1.0, and it was unclear whether their thrombocytopenia was caused by HIT alone or by sustained DIC. There were no significant differences in platelet counts and the 4 parameters of coagulation and fibrinolysis between the patients with DIC-HIT and DIC patients with a weakly positive result (0.4–1.0). No differences were observed in platelet counts, or levels of D-dimer and antithrombin between HIT-Elisa-positive and -negative DIC patients. However, the HIT-Elisa-negative patients showed significantly higher levels of TAT and PIC, presumably reflecting DIC-related hypercoagulability. In conclusion, DIC patients treated with heparin occasionally showed HIT antibody seroconversion and developed HIT. HIT-Elisa could assist in the diagnosis of HIT.