Heparin Induced Thrombocytopenia – Pathophysiology, Diagnosis and Treatment: A Narrative Review

Abstract

Heparin-induced thrombocytopenia (HIT) is a life-threatening, immune-mediated complication following heparin exposure and is considered to be the most severe adverse reaction to heparin treatment that is not associated with bleeding. Development of autoantibodies against platelet factor 4 (PF4) – heparin complex constitutes the basis of the pathophysiological changes in patients suffering from HIT, which then binds to the surface of platelets and monocytes, thus provoking their activation and subsequent aggregation, ultimately leading to the formation of thrombosis. Formation of arterial and venous thrombosis is aggravated by the simultaneous activation of platelets and monocytes with a substantial mortality rate. The incidence of HIT is reported to be significantly lower in pediatric patients compared with adults. Diagnosis of HIT in pediatric population remains a clinical entity supplemented by laboratory evaluation. The positive predictive value of laboratory evaluation is further elevated by the use of scoring systems and predictive models used for hastening the diagnosis of HIT. Use of alternative anticoagulants like direct thrombin inhibitors and factor Xa inhibitors form the mainstay of treatment in cases of HIT, however, more prospective studies would be required in the pediatric population to delineate definitive guidelines for proper management of patients in this age-group. This article delivers diagnostic and treatment approach in case of patients with HIT, wherein the pathophysiology, clinical manifestations, diagnostic approach and the management of patients with HIT has been described.

A Rare Case of Argatroban-Induced Anaphylaxis in a Patient With Intermediate-High Risk Pulmonary Embolism

“…Due to our patient’s marked drop in platelets, intermediate 4T score, and positive PF4 IgG antibodies, there was clinical suspicion for type II HIT and the decision was made to switch from unfractionated heparin to argatroban. Argatroban and bivalirudin are approved intravenous anticoagulants in suspected and confirmed HIT [ 3 , 4 ]. Alternatives to these therapies, including fondaparinux and direct oral anticoagulants, have also been studied and shown to have similar rates of platelet recovery, safety profiles (i.e., major bleeding), and risk of new or worsening thromboembolism [ 4 , 9 ].…”

“…A rare, life-threatening complication of heparin therapy is type II heparin-induced thrombocytopenia (HIT), described as an acute drop in platelets after heparin exposure due to the development of platelet factor 4 (PF4) autoantibodies. Type II HIT can be seen in patients with prior heparin exposure and can cause a hypercoagulable state resulting in venous and arterial thromboses [ 3 ]. The workup of HIT includes laboratory evaluation for PF4 IgG antibodies (highly sensitive) and the serotonin release assay (highly specific) [ 3 ].…”

“…Type II HIT can be seen in patients with prior heparin exposure and can cause a hypercoagulable state resulting in venous and arterial thromboses [ 3 ]. The workup of HIT includes laboratory evaluation for PF4 IgG antibodies (highly sensitive) and the serotonin release assay (highly specific) [ 3 ]. Once HIT is suspected, heparin should be discontinued, and patients should be transitioned to an alternative intravenous anticoagulant, such as argatroban or bivalirudin (direct thrombin inhibitors) [ 3 , 4 ].…”