Clinical Management and Outcomes of Patients with Heparin/Platelet Factor 4 Antibodies: Retrospective Review at a Single Center.
Authors: Perry Stephanie L. , Whitlatch Nicole L. , Ortel Thomas L. 
Published: April 2020

Abstract
Depending on the clinical setting, anti-platelet factor 4 (PF4)/heparin antibodies may be present in the absence of manifestations of heparin-induced thrombocytopenia (HIT), such as after bypass surgery. In addition, some patients have heparin-independent antibodies (ie, no inhibition of antibody binding in the ELISA with added heparin), but the clinical significance of a negative confirmatory result is unknown. Current recommendations for patients with HIT include treatment with a direct thrombin inhibitor (DTI) for up to 4 weeks. To assess current practice at a tertiary care center, we performed a retrospective analysis of patients with anti-PF4/heparin antibodies at Duke University Medical Center from January to July 2005, investigating diagnostic criteria, co-morbid conditions, therapeutic interventions, and outcomes. Anti-PF4/heparin antibody titers were determined by ELISA using a confirmatory step with excess heparin. A positive confirmatory result was defined as &gt;50% decrease in antibody binding in the presence of heparin. Of 59 patients with PF4/heparin antibodies, 50 had positive confirmatory results. For the confirm-positive patients, median platelet count nadir was 51,000±51,776/μL and % decrease from baseline was 71%±25%. Median peak PF4/heparin antibody titer was 0.9±0.8 AU. Seven patients were on the cardiology service, 15 were post-cardiac bypass surgery, 18 were on general medicine, and 4 were on general surgery. Sixteen patients (32%) had other potential causes for thrombocytopenia. Fifteen patients had thromboembolic events (TE); 12 had TE prior to the diagnosis of HIT (24%) and 3 patients sustained TE within 2 days of the positive test result. Twenty-six patients (52%) were treated with a DTI. Seven (of 21 evaluated) sustained bleeding complications requiring discontinuation of therapy. Six patients treated with a DTI died, 4 of whom had TE. Twenty-four patients were not treated with a DTI: 10 did not meet clinical criteria for HIT and 3 had bleeding complications that precluded DTI therapy. Of the remaining 11 patients not treated with a DTI, two died; one with sepsis, one with sepsis and stroke. One sustained DVT, but was therapeutic on warfarin at home when the positive ELISA result returned. Eight had no TE. Nine of the 59 patients had anti-PF4/heparin antibodies with a negative confirmatory test. Median platelet count nadir was 57,000±24,947/μL and % decrease from baseline was 62%±16%. Median peak PF4/heparin titer was 0.93±0.89 AU. Three patients were on the cardiology service, 1 was post-cardiac bypass surgery, 1 was on general surgery, and 4 were on general medicine. Eight patients had other causes for thrombocytopenia. Five patients sustained TE: one with lung cancer, one with clot on a central catheter, one with DIC and sepsis, and two with acute coronary syndromes at presentation. Only 1 patient with a negative confirmatory test was felt to have HIT, and that patient was treated with a DTI. One patient died with sepsis. In conclusion, anti-PF4/heparin antibodies are detected in diverse patient populations who frequently have additional risk factors for thrombocytopenia and thrombosis. Negative confirmatory results in the PF4/heparin ELISA were more frequently obtained in patients who did not meet clinical criteria for HIT. The decision to use a DTI in patients with anti-heparin PF4 antibodies must be individualized, since bleeding complications are frequent. Some patients with anti-heparin PF4 antibodies and no TE may not require treatment with a DTI, but this observation needs to be confirmed prospectively.