Heparin-induced thrombocytopenia

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

Last reviewed: 11 Aug 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

Full details

Risk factors

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

Full details

Diagnostic tests

1st tests to order

Full details

Tests 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

Disclosures

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.

References

Our in-house evidence and editorial teams collaborate with international expert contributors and peer reviewers to ensure that we provide access to the most clinically relevant information possible.

Key articles

Warkentin T, Kelton J. Temporal aspects of heparin-induced thrombocytopenia. N Engl J Med. 2001;344:1286-1292.Full text Abstract

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.Full text Abstract

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.Full text Abstract

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.Full text Abstract

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials
- Postoperative state
- Thrombotic thrombocytopenic purpura
- Drug-induced thrombocytopenic purpura
More Differentials
Guidelines
- Guidelines for management of venous thromboembolism: heparin-induced thrombocytopenia
- Treatment and prevention of heparin-induced thrombocytopenia
More Guidelines
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Heparin-induced thrombocytopenia

Summary

Definition

History and exam

Key diagnostic factors

Other diagnostic factors

Risk factors

Diagnostic tests

1st tests to order

Tests 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

Disclosures

Peer reviewer acknowledgements

Disclosures

References

Key articles

Reference articles

A full list of sources referenced in this topic is available to users with access to all of BMJ Best Practice.

Differentials

Guidelines

Log in or subscribe to access all of BMJ Best Practice

Log in or subscribe to access all of BMJ Best Practice

Log in to access all of BMJ Best Practice