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]. Heparin-induced thrombocytopenia is a clinicopatho- logic diagnosis [52]. The spectrum ranges from formation of anti PF4-heparin antibodies to increasing degrees of thrombocytopenia due to platelet activation, and in its most severe form, diffuse deposition of platelet-related thrombi into microcirculation and extreme depletion of circulating platelets. In a single-center observational study of 1,722 patients undergoing cardiac surgery, HIT was suspected in 63 (3.6%) and con rmed in 24 (1.4%) [53]. Validated clinical scoring systems can guide initial decision-making and laboratory testing [37, 53 57]. These scoring methods take into consideration the characteristic temporal relationship of the onset of thrombocytopenia (with or without thrombotic event) to heparin exposure (5 to 14 days) [58], the percent decrease in platelet count (greater than 30% to 50%), and absolute level of platelets (20 to 100,000/uL), in addition to duration of CPB and other potential contributory causes of thrombocytopenia [55, 57]. The negative predictive value (for HIT) for pa- tients with a low clinical scores is 98% (range, 97% to 100%) [56, 57]. Therefore, additional serologic testing and delays in heparin anticoagulation or complications asso- ciated with heparin alternatives in these patients can be avoided. The positive predictive value of the anti PF4-heparin assay (ELISA) for HIT is very low (2% to 15%) [59, 60]. As such, this assay should be limited to patients with higher pretest probabilities (for HIT) found in those with intermediate (positive predictive value 10% to 20%) or high (positive predictive value 40% to 80%) clinical scores. 