(Level of Evidence C) The chief contraindications to the use of heparin for CPB are a history of HIT and known hypersensitivity to heparin. Whereas HIT is characterized by the develop- ment of immunoglobulin G antibodies recognizing PF4- heparin complexes [33, 34], hypersensitivity reactions to heparin can be type I, II, or IV [35, 36]. Heparin-induced thrombocytopenia with or without thrombosis occurs in patients who form PF4-heparin immune complexes capable of activating platelets [37, 38]. These anti PF4- heparin antibodies form the basis for the clinical anti- genic assay (enzyme-linked immunosorbent assay [ELISA]) for HIT [37]. Although PF4-heparin complexes after heparin exposure can be quite high (greater than 30% among surgical patients), the incidence of HIT is much lower (1% to 2%) [39 43]. Patients who test positive (antigen assay) for anti PF4-heparin antibodies preoper- atively appear to have a higher overall risk for complications and increased mortality after cardiac sur- gery [44 46]. Given the 60- to 90-day amnestic period for HIT antibodies, postponing elective cardiac surgery in patients with elevated PF4-heparin antibodies could potentially mitigate this avoidable risk [47 50]. Platelet count monitoring is currently recommended for patients with heparin exposure before cardiac surgery (eg, cardiac catheterization or deep vein thrombosis prophylaxis) to determine whether further testing is indicated [43]. Detection of PF4-heparin antibodies that activate platelets and trigger serotonin release requires a highly speci c and sensitive functional test for HIT [51]. Func- tional testing with SRA or HIPA detect only those immunoglobulin G antibodies capable of activating platelets [43]. Thrombocytopenia or thrombosis are much more likely when platelet activation occurs. Speci c tests of platelet serotonin release can be particularly helpful when low levels of positivity are detected using HIT antibody (antigen) assays, which are sensitive but not speci c to platelet activation [37, 51]. 