What is Heparin-Induced Thrombocytopenia (HIT)?

From the Guidelines

Heparin-Induced Thrombocytopenia (HIT) is a rare but potentially lethal side effect of heparin administration, characterized by the formation of antibodies against heparin-PF4 complexes, leading to platelet activation and thrombosis.

Definition and Pathophysiology

• HIT occurs when heparin binds to endogenous platelet factor 4 (PF4), triggering the development of heparin-PF4 antibodies, which activate platelets, leukocytes, and endothelial cells, resulting in thrombocytopenia and thrombosis 1.
• There are two types of thrombocytopenia associated with heparin use: a benign, non-immune type (type I) and a more severe, immune-mediated type (type II), which is the true HIT syndrome 1.

Diagnosis

• The diagnosis of HIT is challenging and requires a combination of clinical and laboratory findings, including the detection of anti-PF4 antibodies and evidence of platelet activation 1.
• Biological confirmation of the diagnosis is necessary, but should not delay the discontinuation of heparin and the initiation of alternative anticoagulation therapy 1.

Subtypes and Variants

• Several subtypes and variants of HIT have been described, including autoimmune HIT (aHIT), delayed-onset HIT, and fondaparinux-associated HIT 1.
• aHIT is characterized by the presence of anti-PF4 antibodies in the absence of heparin exposure, and can be further divided into spontaneous and persistent subtypes 1.

Treatment

• The management of HIT involves the immediate discontinuation of heparin therapy and the initiation of alternative anticoagulation with a non-heparin anticoagulant, such as a direct thrombin inhibitor or a heparinoid 1.
• Direct oral anticoagulants (DOACs) may be a safe and effective alternative in select cases, but are not currently licensed for the treatment of HIT 1.

From the Research

Definition and Pathophysiology of Heparin-Induced Thrombocytopenia (HIT)

• Heparin-induced thrombocytopenia (HIT) is an immune-mediated disorder caused by the development of antibodies to platelet factor 4 (PF4) and heparin 2, 3, 4, 5, 6.
• The formation of an immunocomplex consisting of an auto-antibody against PF4-heparin complex leads to the activation of platelets and monocytes, resulting in catastrophic arterial and venous thrombosis 5.
• HIT is characterized by an increased risk for thromboembolic complications, primarily venous thromboembolism 2.

Clinical Manifestations and Diagnosis of HIT

• The thrombocytopenia in HIT is typically moderate, with a median platelet count nadir of approximately 50 to 60 x 10(9) platelets/L 2.
• The timing of the thrombocytopenia in relation to the initiation of heparin therapy is critically important, with the platelet count beginning to drop within 5 to 10 days of starting heparin 2, 6.
• A more rapid drop in the platelet count can occur in patients who have been recently exposed to heparin (within the preceding 3 months), due to preformed anti-heparin/PF4 antibodies 2.
• The 4Ts Score is recommended to identify patients at increased likelihood of HIT and direct further evaluation 4.

Management of HIT

• Heparin and all heparin-containing products should be discontinued and an alternative, non-heparin anticoagulant initiated 2, 6.
• Alternative agents that have been used effectively in patients with HIT include lepirudin, argatroban, bivalirudin, and danaparoid 2.
• Warfarin therapy should not be initiated until the platelet count has recovered and the patient is systemically anticoagulated, and vitamin K should be administered to patients receiving warfarin at the time of diagnosis of HIT 2.