The HIT pyramid. Most patients with thrombocytopenia after initiation of heparin therapy will reflect a non-immune and transient platelet drop; these patients will be negative for anti-PF4 antibodies using immunological assays and functional platelet activation assays. However, some patients with thrombocytopenia after initiation of heparin therapy will reflect an immune-mediated platelet drop due to the production of anti-PF4 antibodies and the clearance of platelets (‘HIT’). These patients will be positive for anti-PF4 antibodies using immunological assays but negative by functional platelet activation assays. Only a small proportion of patients (at the ‘top’ of the pyramid) will have HITT, being HIT patients with resultant thrombosis, due to platelet activation, aggregation, and thrombotic vessel occlusion. These patients will be positive for anti-PF4 antibodies using immunological assays, as well as by functional platelet activation assays.