Rapid determination of anti-heparin/platelet factor 4 antibody titers in the diagnosis of heparin-induced thrombocytopenia

Purpose Heparin-induced thrombocytopenia is mediated by antibodies directed against the heparin–platelet factor 4 (heparin/PF4) complex. Our aim was to investigate whether rapid measurement of anti-heparin/PF4 antibodies could improve the diagnostic workup of patients with suspected heparin-induced thrombocytopenia. Methods We examined 148 consecutive patients in our laboratory between January 1995 and June 2001 for suspected heparin-induced thrombocytopenia. Clinical data allowed retrospective assessment of the likelihood of heparin-induced thrombocytopenia. Antibodies against the heparin/PF4 complex were detected by a rapid particle gel immunoassay. Results Anti-heparin/PF4 antibodies were detected in 69 (47%) of the 148 patients, at dilution titers from 1 to 256. Clinically “likely” or “very likely” heparin-induced thrombocytopenia was significantly more common in patients with titers ≥4 (95% [39/41]) than in those with undetectable antibodies (13% [9/70]; P<0.0001), a titer of 1 (18% [4/22]; P<0.0001), or a titer of 2 (33% [2/6]; P = 0.001). All 19 samples with a positive platelet aggregation test had anti-heparin/PF4 antibody titers of at least 4, including 15 samples with titers ≥32. Thromboembolic complications in heparin-treated patients were significantly more prevalent in patients with titers ≥4 (63% [26/41]) than in those with undetectable antibodies (8% [6/79]; P<0.0001) or a titer of 1 (9% [2/22]; P<0.0001). Of the 11 patients with a titer of 1 who were maintained on heparin, none developed worse thrombocytopenia or thromboembolic complications. Conclusion Anti-heparin/PF4 antibody titers, which can be measured rapidly and reproducibly using a particle gel immunoassay, can be used as a confirmatory test to complement a clinical likelihood score among patients with suspected heparin-induced thrombocytopenia.