Antibodies to Platelet Factor 4–Heparin After Cardiopulmonary Bypass in Patients Anticoagulated With Unfractionated Heparin or a Low-Molecular-Weight Heparin

Abstract

Background —Cardiopulmonary bypass (CPB) induces platelet activation with release of platelet factor 4 (PF4), and patients are exposed to high doses of heparin (H). We investigated whether this contributes to the development of antibodies to H-PF4 and heparin-induced thrombocytopenia (HIT). Methods and Results —CPB was performed with unfractionated heparin (UFH) in 328 patients. After surgery, patients received UFH (calcium heparin, 200 IU · kg −1 · d −1 ) (group 1, n=157) or low-molecular-weight heparin (LMWH, Dalteparin, 5000 IU once daily) (group 2, n=171). Eight days after surgery, antibodies to H-PF4 were present in 83 patients (25.3%), 46 in group 1 and 37 in group 2 ( P =0.12). Most patients (61%) had IgG1 to H-PF4, but only 8 samples with antibodies induced platelet activation with positive results on serotonin release assay. HIT occurred in 6 patients in group 1, but no thrombocytopenia was observed in subjects receiving LMWH, although 2 had high levels of antibodies with positive serotonin release assay results. When antibodies to H-PF4 were present, mean platelet counts were lower only in patients with FcγRIIA R/R 131 platelets. Conclusions —These results provide evidence that the development of antibodies to H-PF4 after CPB performed with UFH is not influenced by the postoperative heparin treatment. The antibodies associated with high risk of HIT are mainly IgG1, which is present at high titers in the plasma of patients continuously treated with UFH.

Incidence of Venous Thromboembolism and Benefits and Risks of Thromboprophylaxis After Cardiac Surgery: A Systematic Review and Meta‐Analysis

“…The majority of the studies were observational studies (n=49), 16 studies were RCTs, and 3 were meta‐analyses (Tables 1 and 2). 15, 16, 17, 18, 19, 20, 21, 22, 23, 24, 25, 26, 27, 28, 29, 30, 31, 32, 33, 34, 35, 36, 37, 38, 39, 40, 41, 42, 43, 44, 45, 46, 47, 48, 49, 50, 51, 52, 53, 54, 55, 56, 57, 58, 59, 60, 61, 62, 63, 64, 65, 66, 67, 68, 69, 70, 71, 72, 73, 74, 75, 76, 77, 78, 79, 80, 81, 82, 83, 84 Of the 16 RCTs identified,1...…”

Heparin‐induced thrombocytopenia and thrombosis

“…In that respect, it is both highly sensitive [37] and specific, because positive reactions are extremely rare in patients not exposed to heparin [30]. In various studies, 2-13% of patients thought to have HIT on clinical grounds were antibody-negative [40][41][42][43], but it is impossible to know how many of them may have had some other cause for their thrombocytopenia. In our experience, it is extremely rare for patients with ''typical'' HIT, especially those with associated thromboses, not to test positive in the ELISA.…”

“…Yet, antibodies with this specificity are produced by 10-50% of patients treated with heparin [12,41,44,45]. Most of these antibodies are weak and may not be clinically significant.…”

Early‐onset and persisting thrombocytopenia in post‐cardiac surgery patients is rarely due to heparin‐induced thrombocytopenia, even when antibody tests are positive

“…First, a major decrease in platelet count of approximately 40-50% occurs universally during the first 72 h after cardiac surgery [3]. Second, as many as 25-70% of patients develop anti-platelet factor 4 (PF4)-heparin antibodies detectable by immunoassays, and 4-20% test positive by platelet activation assay, during the first 10 days post-cardiac surgery [4][5][6][7][8]. However, only a minority of these patients develop clinically evident HIT, characterized by a second episode of thrombocytopenia beginning within a narrow ÔwindowÕ between postoperative days 5 and 10 (the ÔP1 patternÕ reported by Pouplard et al [9]).…”