Heparin-induced Thrombocytopenia

Overview

Journal Blood

Publisher Elsevier

Specialty Hematology

Date 2017 Apr 19

PMID 28416511

Citations 165

Authors

Gowthami M Arepally

Affiliations

Soon will be listed here.

Abstract

Heparin-induced thrombocytopenia (HIT) is an immune complication of heparin therapy caused by antibodies to complexes of platelet factor 4 (PF4) and heparin. Pathogenic antibodies to PF4/heparin bind and activate cellular FcγRIIA on platelets and monocytes to propagate a hypercoagulable state culminating in life-threatening thrombosis. It is now recognized that anti-PF4/heparin antibodies develop commonly after heparin exposure, but only a subset of sensitized patients progress to life-threatening complications of thrombocytopenia and thrombosis. Recent scientific developments have clarified mechanisms underlying PF4/heparin immunogenicity, disease susceptibility, and clinical manifestations of disease. Insights from clinical and laboratory findings have also been recently harnessed for disease prevention. This review will summarize our current understanding of HIT by reviewing pathogenesis, essential clinical and laboratory features, and management.

Citing Articles

A Comprehensive Review of Fc Gamma Receptors and Their Role in Systemic Lupus Erythematosus.

Sepulveda-Delgado J, Llorente L, Hernandez-Dono S Int J Mol Sci. 2025; 26(5).

PMID: 40076476 PMC: 11899777. DOI: 10.3390/ijms26051851.

Secondary prevention of preeclampsia.

Akbar M, Rosaudyn R, Gumilar K, Shanmugalingam R, Dekker G Front Cell Dev Biol. 2025; 13:1520218.

PMID: 39989985 PMC: 11842342. DOI: 10.3389/fcell.2025.1520218.

Imaging flow cytometry as a novel approach for the diagnosis of heparin-induced thrombocytopenia.

Carre J, Demont Y, Mouton C, Vayne C, Guery E, Voyer A Br J Haematol. 2024; 206(2):666-674.

PMID: 39658032 PMC: 11829136. DOI: 10.1111/bjh.19945.

Heparin-induced thrombocytopenia: a rare presentation with skin necrosis.

David F, Trigo A, Ribeiro J, Cancela J Dermatol Reports. 2024; 16(3):9855.

PMID: 39635571 PMC: 11616585. DOI: 10.4081/dr.2023.9855.

Prothrombotic Antibodies Targeting the Spike Protein's Receptor-Binding Domain in Severe COVID-19.

Zhu W, Zheng Y, Yu M, Witman N, Zhou L, Wei J Blood. 2024; .

PMID: 39576992 PMC: 11811936. DOI: 10.1182/blood.2024025010.

References

Sharifi M, Bay C, Vajo Z, Freeman W, Sharifi M, Schwartz F . New oral anticoagulants in the treatment of heparin-induced thrombocytopenia. Thromb Res. 2015; 135(4):607-9. DOI: 10.1016/j.thromres.2015.01.009. View

Pouplard C, Iochmann S, Renard B, Herault O, Colombat P, Amiral J . Induction of monocyte tissue factor expression by antibodies to heparin-platelet factor 4 complexes developed in heparin-induced thrombocytopenia. Blood. 2001; 97(10):3300-2. DOI: 10.1182/blood.v97.10.3300. View

Lewis B, Wallis D, Leya F, Hursting M, Kelton J . Argatroban anticoagulation in patients with heparin-induced thrombocytopenia. Arch Intern Med. 2003; 163(15):1849-56. DOI: 10.1001/archinte.163.15.1849. View

WEISMANN R, TOBIN R . Arterial embolism occurring during systemic heparin therapy. AMA Arch Surg. 1958; 76(2):219-25. DOI: 10.1001/archsurg.1958.01280200041005. View

Fausett M, Vogtlander M, Lee R, Esplin M, Branch D, Rodgers G . Heparin-induced thrombocytopenia is rare in pregnancy. Am J Obstet Gynecol. 2001; 185(1):148-52. DOI: 10.1067/mob.2001.114690. View

Padmanabhan A, Jones C, Curtis B, Bougie D, Sullivan M, Peswani N . A Novel PF4-Dependent Platelet Activation Assay Identifies Patients Likely to Have Heparin-Induced Thrombocytopenia/Thrombosis. Chest. 2016; 150(3):506-15. PMC: 5028397. DOI: 10.1016/j.chest.2016.02.641. View

Morris T, Castrejon S, Devendra G, Gamst A . No difference in risk for thrombocytopenia during treatment of pulmonary embolism and deep venous thrombosis with either low-molecular-weight heparin or unfractionated heparin: a metaanalysis. Chest. 2007; 132(4):1131-9. DOI: 10.1378/chest.06-2518. View

Bock P, LUSCOMBE M, Marshall S, Pepper D, HOLBROOK J . The multiple complexes formed by the interaction of platelet factor 4 with heparin. Biochem J. 1980; 191(3):769-76. PMC: 1162276. DOI: 10.1042/bj1910769. View

Warkentin T, Kelton J . Temporal aspects of heparin-induced thrombocytopenia. N Engl J Med. 2001; 344(17):1286-92. DOI: 10.1056/NEJM200104263441704. View

10.

Sun L, Gimotty P, Lakshmanan S, Cuker A . Diagnostic accuracy of rapid immunoassays for heparin-induced thrombocytopenia. A systematic review and meta-analysis. Thromb Haemost. 2016; 115(5):1044-55. DOI: 10.1160/TH15-06-0523. View

11.

Rauova L, Poncz M, McKenzie S, Reilly M, Arepally G, Weisel J . Ultralarge complexes of PF4 and heparin are central to the pathogenesis of heparin-induced thrombocytopenia. Blood. 2004; 105(1):131-8. DOI: 10.1182/blood-2004-04-1544. View

12.

Cai Z, Yarovoi S, Zhu Z, Rauova L, Hayes V, Lebedeva T . Atomic description of the immune complex involved in heparin-induced thrombocytopenia. Nat Commun. 2015; 6:8277. PMC: 4580983. DOI: 10.1038/ncomms9277. View

13.

Trikalinos T, Karassa F, Ioannidis J . Meta-analysis of the association between low-affinity Fcgamma receptor gene polymorphisms and hematologic and autoimmune disease. Blood. 2001; 98(5):1634-5. DOI: 10.1182/blood.v98.5.1634. View

14.

Handin R, Cohen H . Purification and binding properties of human platelet factor four. J Biol Chem. 1976; 251(14):4273-82. View

15.

Hursting M, Pai P, McCracken J, Hwang F, Suvarna S, Lokhnygina Y . Platelet factor 4/heparin antibodies in blood bank donors. Am J Clin Pathol. 2010; 134(5):774-80. PMC: 3766530. DOI: 10.1309/AJCPG0MNR5NGKNFX. View

16.

Greinacher A, Alban S, Omer-Adam M, Weitschies W, Warkentin T . Heparin-induced thrombocytopenia: a stoichiometry-based model to explain the differing immunogenicities of unfractionated heparin, low-molecular-weight heparin, and fondaparinux in different clinical settings. Thromb Res. 2008; 122(2):211-20. DOI: 10.1016/j.thromres.2007.11.007. View

17.

Khandelwal S, Lee G, Hester C, Poncz M, McKenzie S, Sachais B . The antigenic complex in HIT binds to B cells via complement and complement receptor 2 (CD21). Blood. 2016; 128(14):1789-1799. PMC: 5054694. DOI: 10.1182/blood-2016-04-709634. View

18.

Watson H, Davidson S, Keeling D . Guidelines on the diagnosis and management of heparin-induced thrombocytopenia: second edition. Br J Haematol. 2012; 159(5):528-40. DOI: 10.1111/bjh.12059. View

19.

Tomer A . A sensitive and specific functional flow cytometric assay for the diagnosis of heparin-induced thrombocytopenia. Br J Haematol. 1997; 98(3):648-56. DOI: 10.1046/j.1365-2141.1997.2613077.x. View

20.

Amiral J, Bridey F, Dreyfus M, Vissoc A, Fressinaud E, Wolf M . Platelet factor 4 complexed to heparin is the target for antibodies generated in heparin-induced thrombocytopenia. Thromb Haemost. 1992; 68(1):95-6. View