What is Heparin-Induced Thrombocytopenia (HIT)?

From the Guidelines

Heparin-induced thrombocytopenia (HIT) is a serious immune-mediated complication of heparin therapy that requires immediate discontinuation of all forms of heparin and initiation of a non-heparin anticoagulant, such as argatroban or bivalirudin, as recommended by the American Society of Hematology guidelines 1. If HIT is suspected, the first step is to estimate the probability of HIT using the 4Ts score, which includes assessment of thrombocytopenia, timing of platelet count fall, thrombosis, and absence of other causes of thrombocytopenia 1. Some key points to consider in the management of HIT include:

• Discontinuation of heparin therapy and switching to a non-heparin anticoagulant is the critical step in the management of HIT, as recommended by the International Society on Thrombosis and Haemostasis (ISTH) Scientific and Standardization Committee (SSC) Subcommittee on Platelet Immunology 1.
• Approved alternative anticoagulants include direct thrombin inhibitors such as argatroban and bivalirudin or heparinoids such as danaparoid, with dosing regimens and monitoring requirements as specified in the guidelines 1.
• Direct oral anticoagulants (DOACs) are not currently licensed for patients with HIT, although some case series have shown they may be a safe and effective alternative in select cases, and the American Society of Hematology guidelines provide weak conditional support for their use in these cases 1.
• The management of HIT should prioritize the prevention of thrombosis and the recovery of platelet counts, with treatment continuing for at least 4-6 weeks if thrombosis is present, or until platelet count recovers and alternative anticoagulation can be established 1. Some of the key considerations in the diagnosis and management of HIT include:
• The use of immunoassays and functional assays to confirm the diagnosis of HIT, with a low threshold preferred for enzyme-linked immunoassay (ELISA) and a functional assay not always necessary for patients with a high-probability 4Ts score and very strongly positive immunoassay 1.
• The importance of avoiding heparin and continuing administration of a non-heparin anticoagulant at therapeutic intensity in patients with a high-probability 4Ts score and a positive immunoassay, as recommended by the American Society of Hematology guidelines 1.
• The need for frequent reassessment of patients with suspected HIT and recalculation of the 4Ts score if there is a change in the clinical picture, with every effort made to obtain accurate and complete information necessary to calculate the 4Ts score 1.

From the FDA Drug Label

Heparin-induced thrombocytopenia (HIT) is a serious antibody-mediated reaction. HIT occurs in patients treated with heparin and is due to the development of antibodies to a platelet Factor 4-heparin complex that induce in vivo platelet aggregation HIT may progress to the development of venous and arterial thromboses, a condition referred to as heparin-induced thrombocytopenia with thrombosis (HITT). If the platelet count falls below 100,000/mm3 or if recurrent thrombosis develops, promptly discontinue heparin, evaluate for HIT and HITT, and, if necessary, administer an alternative anticoagulant.

Heparin-Induced Thrombocytopenia (HIT) is a serious reaction that can occur in patients treated with heparin. It is caused by the development of antibodies to a platelet Factor 4-heparin complex, leading to in vivo platelet aggregation.

• Key characteristics of HIT:
  • Serious antibody-mediated reaction
  • Occurs in patients treated with heparin
  • Caused by antibodies to a platelet Factor 4-heparin complex
  • May progress to venous and arterial thromboses (HITT)
• Management of HIT:
  • Discontinue heparin if platelet count falls below 100,000/mm3 or if recurrent thrombosis develops
  • Evaluate for HIT and HITT
  • Administer an alternative anticoagulant if necessary 2

From the Research

Definition and Diagnosis of Heparin-Induced Thrombocytopenia (HIT)

• Heparin-induced thrombocytopenia (HIT) is a prothrombotic disorder that occurs following the administration of heparin and is caused by antibodies to platelet factor 4 and heparin 3.
• Diagnosis of HIT is essential to guide treatment strategies using non-heparin anticoagulants and to avoid unwanted and potential fatal thromboembolic complications 3.
• A 4Ts score is recommended for all patients with suspected HIT prior to laboratory testing 3.
• Further laboratory testing with a screening immunoassay or confirmatory functional assay is not recommended in individuals with a low 4Ts score, but should be performed if there are missing or unreliable clinical data 3.

Treatment and Management of HIT

• For patients receiving heparin in whom the clinician considers the risk of HIT to be > 1.0%, platelet count monitoring is recommended over no platelet count monitoring (Grade 1C) 4.
• For patients with strongly suspected (or confirmed) HIT, whether or not complicated by thrombosis, use of an alternative, nonheparin anticoagulant (danaparoid, lepirudin, argatroban, fondaparinux, or bivalirudin) is recommended over the further use of unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) therapy or initiation/continuation of vitamin K antagonists (VKAs) 4.
• Non-heparin anticoagulants (danaparoid, argatroban, fondaparinux, and bivalirudin) used to treat HIT should be given in therapeutic rather than prophylactic doses 3.
• Direct oral anticoagulants may be used in place of warfarin after patients with HIT have responded to alternative parenteral anticoagulants with platelet count recovery 3.

Anticoagulant Therapy in Patients with HIT

• For patients with heparin-induced thrombocytopenia (HIT), reexposure to heparin is generally not recommended 5.
• In patients with subacute HIT, when platelets have recovered but HIT antibodies are still present, therapy with heparin should be avoided 5.
• In patients with a remote history of HIT, when HIT antibodies have cleared, heparin reexposure may be safe, although recurrent HIT has been described in some patients 5.
• The use of alternate anticoagulant agents, including direct thrombin inhibitors and anti-Xa agents, is preferable for patients with a history of HIT 5.