||Heparin-induced thrombocytopenia (HIT) is a clinical diagnosis, supported by confirmatory laboratory testing. The traditional clinical definition of HIT is an acquired platelet count of <150K or a 50 % fall from baseline occurring 5-10 days after initiation of heparin therapy in the absence of another etiology. This means that some patients with HIT have platelet counts that are still within the normal range, but always lower than the pre-heparin exposure baseline. Isolated HIT refers to heparin-induced thrombocytopenia in the absence of thrombosis. Individuals with isolated HIT are at high risk for thrombotic events, as discussed below. A thrombotic event occurring in an individual on heparin therapy within this temporal window should always trigger consideration of HIT. Variant presentations of HIT have been described recently, including delayed HIT (e.g., a patient presenting to the emergency room with pulmonary embolism a week after being discharged from a hospitalization with heparin exposure). One of the challenges in HIT diagnosis is that these patients are often critically ill or post-surgery, and often have alternative explanations for thrombocytopenia (e.g., infection, other drugs). To assist in the evaluation of such patients, useful scoring systems based on clinical criteria have been developed to aid in the assessment of likelihood of HIT (See Warkentin, ASH 2003). The most commonly used (and only FDA-approved) tests for HIT are ELISA kits measuring the presence of anti-heparin-PF4 antibodies. These tests are reported as positive if the ELISA result exceeds a threshold value. The sensitivity of this test is high (>90%, depending on the cutoff used). The most common clinical problem with this test is the high incidence of false positive results (i.e., positive tests in the absence of HIT or even thrombocytopenia), which varies from 1% – 3% in dialysis patients, to 10-15 % of medical patients and >20 % of patients receiving heparin for peripheral vascular surgery. This is most troublesome in intensive care units, where there is ubiquitous heparin exposure and often multiple potential etiologies for thrombocytopenia. In certain populations, such as that undergoing cardiopulmonary bypass, the seroconversion rate approaches 50 %. While all antibody subclasses have been reported in HIT, important antibody responses appear to be high titer IgG, thus specificity may be improved by an IgG-subclass specific ELISA method. The Sanford laboratory performs IgG specific ELISA to aid in clinical decision making. There may be utility in performing both ELISA screen and a platelet activation assay (Heparin Induced Thrombocytopenia Functional Assay or HITIA) in borderline and positive cases. If both are positive the likelihood of HIT is high.