Historical perspective
Heparin-induced thrombocytopenia (HIT) and heparin-induced thrombocytopenia and thrombosis syndrome (HITTS) are well-described phenomena, particularly in the adult population. These conditions were first described several decades ago [1,2]. At first, these syndromes were under-recognized, leading to limb and life-threatening thrombosis. Recently, due to increased recognition, testing, availability of novel anticoagulants and high concern for missing a case, the trend has shifted to over-diagnosis.
Pathophysiology
The HIT/HITTS condition requires the interaction between heparin, platelet factor 4 (PF4), immunoglobulin G (IgG) and an Fc receptor on the platelet. This interaction results in procoagulant activity of the platelets and a prothrombotic state. These complexes are most likely to be formed under proinflammatory conditions such as surgery, described by Warkentin as “point immunization” [3]. There is a high rate of thrombosis even once heparin is discontinued. This is because the HIT antibody can bind to heparin-PF4 complexes on the surface of endothelial cells, monocytes and polymorphonuclear (PMN) cells, and lead to vessel injury and inflammation, PMN activation and exposure of tissue factor on monocytes.
Special considerations in children
The pathophysiology of HIT/HITTS likely differs between adults and children. This may be related to differences in PF4 levels and immune response, which contribute to immune complex formation as well as platelet reactivity and underlying prothrombotic risk, which contribute to the incidence of thrombosis in the presence of HIT antibodies [4].
Diagnosis
Clinical symptoms
The primary manifestation of HITTS is thrombosis. Venous thrombosis occurs more often than arterial thrombosis. Thrombosis most often occurs within 5–10 days of initial heparin exposure, and if heparin has been given within the past 100 days, within 24 hours of repeat heparin exposure (rapid HITTS). Thrombosis may also occur weeks after heparin exposure (delayed HITTS). Other manifestations include heparin-induced skin necrosis and acute systemic reaction coincident with heparin infusion. Even in the presence of significant thrombocytopenia, bleeding is rare. In fact, bleeding with thrombocytopenia should decrease the suspicion of HIT.