Heparin-induced thrombocytopenia

Overview 
Theory 
Diagnosis 
Management 
Follow up 
Resources 

Last reviewed: 11 Sep 2025

Last updated: 20 Jun 2023

Heparin-induced thrombocytopenia (HIT) is a severe drug reaction to heparin that can lead to life- and limb-threatening venous and/or arterial thromboembolism.

Diagnosis requires the combination of a compatible clinical picture and laboratory confirmation of the presence of heparin-dependent platelet-activating HIT antibodies.

The 4Ts score is commonly used to determine the clinical probability of HIT.

Neither discontinuation of heparin alone nor initiation of a vitamin K antagonist alone (e.g., warfarin) is sufficient to stop the development of thrombosis in a patient with acute HIT.

If a patient has suspected HIT and at least an intermediate-probability 4Ts score, all sources of heparin (including low molecular weight heparin) must be discontinued and a nonheparin anticoagulant should be initiated.

Definition

Heparin-induced thrombocytopenia (HIT) is a clinicopathologic syndrome that occurs when heparin-dependent, IgG antibodies bind to heparin/platelet factor 4 (PF4) complexes to activate platelets and produce a hypercoagulable state. This results in thrombocytopenia and/or thrombosis in temporal relationship to a preceding immunizing exposure to heparin.[1] HIT typically develops 5 to 10 days after exposure to heparin (range of 4-15 days) and can occur with unfractionated heparin, low molecular weight heparin, or, more rarely, fondaparinux. The presence of heparin-dependent antibodies alone, without any clinical manifestations, is insufficient for a diagnosis of HIT.

Fondaparinux, a pentasaccharide anticoagulant, does not usually promote antibody binding to PF4, despite its structural similarity to heparin, owing to absent/weak cross-reactivity. Therefore, it has a very low risk of inducing HIT. Despite rare reports of fondaparinux-induced HIT, observational studies report the successful use of fondaparinux to treat HIT, and it is considered to be a nonheparin anticoagulant.[2][3]

History and exam

Key diagnostic factors

history of recent heparin exposure
history of HIT
absence of conditions and medications that cause thrombocytopenia
history of recent surgery or trauma
features consistent with recent venous or arterial thromboembolic event (e.g., PE, DVT, stroke, MI)
necrosis at heparin injection site(s)

Full details

Other diagnostic factors

absence of bleeding
signs of adrenal hemorrhagic necrosis
acute systemic reaction
signs of venous limb gangrene

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Risk factors

recent heparin exposure (within past 100 days)
recent orthopedic or cardiovascular surgery
female sex

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Diagnostic investigations

1st investigations to order

Full details

Investigations to consider

4Ts score
HIT antigen assay
HIT functional assay
coagulation studies
venous Doppler ultrasound
computed tomography pulmonary angiogram (CTPA)
ventilation-perfusion scan (V/Q scan)
cerebral computed tomography venogram
magnetic resonance venography (head)

Full details

Treatment algorithm

ACUTE

suspected HIT with 4Ts score ≥4, or confirmed acute HIT

suspected HIT with 4Ts score ≤3

ONGOING

platelet recovery (subacute HIT A)

remote HIT

Contributors

Authors

Lori-Ann Linkins, MD, MSc(Clin Epi), FRCPC

Associate Professor

Department of Medicine

McMaster University

Thrombosis Consultant

Juravinski Hospital and Cancer Centre

Hamilton

Ontario

Canada

Disclosures

LL is an author of several references cited in this topic.

Peer reviewers

Jeffrey S. Wasser, MD

Assistant Clinical Professor of Medicine

Acting Associate Chair of the Division of Hematology and Medical Oncology

University of Connecticut School of Medicine

Farmington

Disclosures

JSW declares that he has no competing interests.

Henry Watson, MD, FRCP, FRCPath

Consultant Haematologist

Aberdeen Royal Infirmary

Foresterhill Health Campus

Aberdeen

Disclosures

HW declares that he has no competing interests.

Simon Davidson, MPhil

Clinical Scientist

Royal Brompton Hospital

Honorary Clinical Lecturer

Imperial College London

London

Declarações

SD is a consultant for Mitsubishi Pharma, the manufacturer of argatroban.

Peer reviewer acknowledgements

BMJ Best Practice topics are updated on a rolling basis in line with developments in evidence and guidance. The peer reviewers listed here have reviewed the content at least once during the history of the topic.

Disclosures

Peer reviewer affiliations and disclosures pertain to the time of the review.

Referências

Nossas equipes internas de editoria e de evidências trabalham em conjunto com colaboradores internacionais especializados e pares revisores para garantir que forneçamos acesso às informações o mais clinicamente relevantes possível.

Principais artigos

Warkentin T, Kelton J. Temporal aspects of heparin-induced thrombocytopenia. N Engl J Med. 2001;344:1286-1292.Texto completo Resumo

Cuker A, Arepally GM, Chong BH, et al. American Society of Hematology 2018 guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia. Blood Adv. 2018 Nov 27;2(22):3360-92.Texto completo Resumo

Linkins LA, Dans AL, Moores LK, et al. Treatment and prevention of heparin-induced thrombocytopenia: antithrombotic therapy and prevention of thrombosis (9th ed). American College of Chest Physicians evidence-based clinical practice guidelines. Chest. 2012 Feb;141(2 Suppl):e495S-e530S.Texto completo Resumo

Watson H, Davidson S, Keeling D, et al. Guidelines on the diagnosis and management of heparin-induced thrombocytopenia: second edition. Br J Haematol. 2012 Dec;159(5):528-40.Texto completo Resumo

Artigos de referência

Uma lista completa das fontes referenciadas neste tópico está disponível para os usuários com acesso total ao BMJ Best Practice.

Diagnósticos diferenciais
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- Guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia
- Treatment and prevention of heparin-induced thrombocytopenia
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Heparin-induced thrombocytopenia

Summary

Definition

History and exam

Key diagnostic factors

Other diagnostic factors

Risk factors

Diagnostic investigations

1st investigations to order

Investigations to consider

Treatment algorithm

suspected HIT with 4Ts score ≥4, or confirmed acute HIT

suspected HIT with 4Ts score ≤3

platelet recovery (subacute HIT A)

remote HIT

Contributors

Authors

Lori-Ann Linkins, MD, MSc(Clin Epi), FRCPC

Disclosures

Peer reviewers

Jeffrey S. Wasser, MD

Disclosures

Henry Watson, MD, FRCP, FRCPath

Disclosures

Simon Davidson, MPhil

Declarações

Peer reviewer acknowledgements

Disclosures

Referências

Principais artigos

Artigos de referência

Uma lista completa das fontes referenciadas neste tópico está disponível para os usuários com acesso total ao BMJ Best Practice.

Diagnósticos diferenciais

Diretrizes

Conectar-se ou assinar para acessar todo o BMJ Best Practice

Conectar-se ou assinar para acessar todo o BMJ Best Practice

Conectar-se para acessar todo o BMJ Best Practice