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Heparin-Induced Thrombocytopenia Medication

  • Author: Sancar Eke, MD, FASN; Chief Editor: Srikanth Nagalla, MBBS, MS, FACP  more...
Updated: Oct 17, 2015

Medication Summary

The goals of pharmacotherapy in patients with heparin-induced thrombocytopenia (HIT) are to reduce morbidity and prevent complications. Anticoagulants used for prophylaxis and treatment of thrombosis in patients with HIT are the direct thrombin inhibitors (DTIs) argatroban (Acova) and bivalirudin. Bivalirudin is used in cardiac surgery and procedures in HIT patients[60, 62] .The indirect factor Xa inhibitor fondaparinux (Arixtra) is sometimes used off-label for HIT. After recovery of the platelet count, patients who require continuing anticoagulation can be transitioned to warfarin.


Anticoagulants, Hematologic

Class Summary

Anticoagulants inhibit factors responsible for thromboembolic disorders. DTIs are the principal anticoagulants used for prophylaxis and treatment of thromboembolism in patients with HIT.

Argatroban (Acova)


Argatroban is a DTI; it inhibits fibrin formation, platelet aggregation, and activation of coagulation factors V, VIII, XIII, and protein C. The dose is 2 mcg/kg/min, adjusted by the activated partial thromboplastin time (aPTT) with a target of 1.5-3 times the baseline.

Argatroban is the ideal alternative to heparin for patients receiving dialysis, because it is not excreted by the kidneys and does not require dose adjustment in those patients.[51] However, because argatroban is processed by the liver, the initial dose should be reduced by 75% in patients with liver dysfunction.

Bivalirudin (Angiomax, Angiox)


Bivalirudin is a competitive, direct inhibitor of thrombin that inhibits both free and clot-bound thrombin and thrombin-induced platelet aggregation. This agent is approved for use in patients who are undergoing percutaneous coronary intervention (PCI) and have, or are at risk for, HIT or HIT with thrombosis (HITT).

Fondaparinux (Arixtra)


Fondaparinux is a synthetic anticoagulant that works by inhibiting factor Xa, a key component involved in blood clotting. It provides a highly predictable response. Bioavailability is 100%, has a rapid onset of action, and a half-life of 14-16 h, allowing for sustained antithrombotic activity over 24-h period. Fondaparinux does not affect prothrombin time or aPTT, nor does it affect platelet function or aggregation.

Warfarin (Coumadin, Jantoven)


Warfarin interferes with hepatic synthesis of vitamin K–dependent coagulation factors. It is used for prophylaxis and treatment of venous thrombosis, pulmonary embolism, and thromboembolic disorders. To avoid warfarin-induced venous limb gangrene in patients with HIT and deep venous thrombosis, warfarin should not be started until the platelet count has risen above 150 x 109/L.[1, 49] Tailor the dose of warfarin to maintain an International Normalized Ratio (INR) in the range of 2 to 3.

Contributor Information and Disclosures

Sancar Eke, MD, FASN Physician in Nephrology and Hypertension, Washington

Sancar Eke, MD, FASN is a member of the following medical societies: American College of Physicians, American Society of Nephrology, American Society of Transplantation, American Society of Diagnostic and Interventional Nephrology

Disclosure: Nothing to disclose.


Sarah K May, MD Consulting Staff, Department of Hematology-Oncology, Caritas Carney Hospital, Commonwealth Hematology-Oncology PC

Disclosure: Nothing to disclose.

Specialty Editor Board

Francisco Talavera, PharmD, PhD Adjunct Assistant Professor, University of Nebraska Medical Center College of Pharmacy; Editor-in-Chief, Medscape Drug Reference

Disclosure: Received salary from Medscape for employment. for: Medscape.

Chief Editor

Srikanth Nagalla, MBBS, MS, FACP Director, Clinical Hematology, Cardeza Foundation for Hematologic Research; Assistant Professor of Medicine, Division of Hematology, Associate Program Director, Hematology/Medical Oncology Fellowship, Assistant Program Director, Internal Medicine Residency, Jefferson Medical College of Thomas Jefferson University

Srikanth Nagalla, MBBS, MS, FACP is a member of the following medical societies: American Society of Hematology, Association of Specialty Professors

Disclosure: Nothing to disclose.

Additional Contributors

Paul Schick, MD Emeritus Professor, Department of Internal Medicine, Jefferson Medical College of Thomas Jefferson University; Research Professor, Department of Internal Medicine, Drexel University College of Medicine; Adjunct Professor of Medicine, Lankenau Hospital

Paul Schick, MD is a member of the following medical societies: American College of Physicians, American Society of Hematology

Disclosure: Nothing to disclose.

  1. [Guideline] Warkentin TE, Greinacher A. Heparin-induced thrombocytopenia: recognition, treatment, and prevention: the Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy. Chest. 2004 Sep. 126(3 suppl):311S-337S. [Medline]. [Full Text].

  2. Warkentin TE, Roberts RS, Hirsh J, Kelton JG. An improved definition of immune heparin-induced thrombocytopenia in postoperative orthopedic patients. Arch Intern Med. 2003 Nov 10. 163(20):2518-24. [Medline]. [Full Text].

  3. Visentin GP, Ford SE, Scott JP, Aster RH. Antibodies from patients with heparin-induced thrombocytopenia/thrombosis are specific for platelet factor 4 complexed with heparin or bound to endothelial cells. J Clin Invest. 1994 Jan. 93(1):81-8. [Medline]. [Full Text].

  4. Rauova L, Poncz M, McKenzie SE, et al. Ultralarge complexes of PF4 and heparin are central to the pathogenesis of heparin-induced thrombocytopenia. Blood. 2005 Jan 1. 105(1):131-8. [Medline]. [Full Text].

  5. Chong BH, Fawaz I, Chesterman CN, Berndt MC. Heparin-induced thrombocytopenia: mechanism of interaction of the heparin-dependent antibody with platelets. Br J Haematol. 1989 Oct. 73(2):235-40. [Medline].

  6. Kelton JG, Sheridan D, Santos A, et al. Heparin-induced thrombocytopenia: laboratory studies. Blood. 1988 Sep. 72(3):925-30. [Medline]. [Full Text].

  7. Anderson GP. Insights into heparin-induced thrombocytopenia. Br J Haematol. 1992 Apr. 80(4):504-8. [Medline].

  8. Newman PM, Chong BH. Heparin-induced thrombocytopenia: new evidence for the dynamic binding of purified anti-PF4-heparin antibodies to platelets and the resultant platelet activation. Blood. 2000 Jul 1. 96(1):182-7. [Medline].

  9. Warkentin TE, Sheppard JA, Heels-Ansdell D, Marshall JC, McIntyre L, Rocha MG, et al. Heparin-induced thrombocytopenia in medical surgical critical illness. Chest. 2013 Sep. 144(3):848-58. [Medline].

  10. Kadidal VV, Mayo DJ, Horne MK. Heparin-induced thrombocytopenia (HIT) due to heparin flushes: a report of three cases. J Intern Med. 1999 Sep. 246(3):325-9. [Medline]. [Full Text].

  11. Heeger PS, Backstrom JT. Heparin flushes and thrombocytopenia. Ann Intern Med. 1986 Jul. 105(1):143. [Medline].

  12. Doty JR, Alving BM, McDonnell DE, Ondra SL. Heparin-associated thrombocytopenia in the neurosurgical patient. Neurosurgery. 1986 Jul. 19(1):69-72. [Medline].

  13. Rizzoni WE, Miller K, Rick M, Lotze MT. Heparin-induced thrombocytopenia and thromboembolism in the postoperative period. Surgery. 1988 Apr. 103(4):470-6. [Medline].

  14. Ling E, Warkentin TE. Intraoperative heparin flushes and subsequent acute heparin-induced thrombocytopenia. Anesthesiology. 1998 Dec. 89(6):1567-9. [Medline].

  15. Warkentin TE, Cook RJ, Marder VJ, Sheppard JA, Moore JC, Eriksson BI, et al. Anti-platelet factor 4/heparin antibodies in orthopedic surgery patients receiving antithrombotic prophylaxis with fondaparinux or enoxaparin. Blood. 2005 Dec 1. 106(12):3791-6. [Medline]. [Full Text].

  16. Smythe MA, Koerber JM, Mattson JC. The incidence of recognized heparin-induced thrombocytopenia in a large, tertiary care teaching hospital. Chest. 2007 Jun. 131(6):1644-9. [Medline]. [Full Text].

  17. Schmitt BP, Adelman B. Heparin-associated thrombocytopenia: a critical review and pooled analysis. Am J Med Sci. 1993 Apr. 305(4):208-15. [Medline].

  18. Arepally G, Cines DB. Heparin-induced thrombocytopenia and thrombosis. Clin Rev Allergy Immunol. 1998 Fall. 16(3):237-47. [Medline].

  19. Warkentin TE. Heparin-induced thrombocytopenia: a ten-year retrospective. Annu Rev Med. 1999. 50:129-47. [Medline].

  20. Warkentin TE, Eikelboom JW. Who is (still) getting HIT?. Chest. 2007 Jun. 131(6):1620-2. [Medline].

  21. Warkentin TE, Kelton JG. A 14-year study of heparin-induced thrombocytopenia. Am J Med. 1996 Nov. 101(5):502-7. [Medline].

  22. Nand S, Wong W, Yuen B, et al. Heparin-induced thrombocytopenia with thrombosis: incidence, analysis of risk factors, and clinical outcomes in 108 consecutive patients treated at a single institution. Am J Hematol. 1997 Sep. 56(1):12-6. [Medline]. [Full Text].

  23. Boshkov LK, Warkentin TE, Hayward CP, Andrew M, Kelton JG. Heparin-induced thrombocytopenia and thrombosis: clinical and laboratory studies. Br J Haematol. 1993 Jun. 84(2):322-8. [Medline].

  24. King DJ, Kelton JG. Heparin-associated thrombocytopenia. Ann Intern Med. 1984 Apr. 100(4):535-40. [Medline].

  25. Lewis BE, Wallis DE, Hursting MJ, Levine RL, Leya F. Effects of argatroban therapy, demographic variables, and platelet count on thrombotic risks in heparin-induced thrombocytopenia. Chest. 2006 Jun. 129(6):1407-16. [Medline]. [Full Text].

  26. Warkentin TE, Sheppard JA, Sigouin CS, Kohlmann T, Eichler P, Greinacher A. Gender imbalance and risk factor interactions in heparin-induced thrombocytopenia. Blood. 2006 Nov 1. 108(9):2937-41. [Medline]. [Full Text].

  27. Greinacher A, Farner B, Kroll H, Kohlmann T, Warkentin TE, Eichler P. Clinical features of heparin-induced thrombocytopenia including risk factors for thrombosis. A retrospective analysis of 408 patients. Thromb Haemost. 2005 Jul. 94(1):132-5. [Medline].

  28. Greinacher A, Lubenow N. Heparin-induced thrombocytopenia. Arnout J, de Gaetano G, Hoylaerts M, et al, eds. Thrombosis: Fundamental and Clinical Aspects. Leuven, Belgium: Leuven University Press; 2003.

  29. Warkentin TE. Clinical presentation of heparin-induced thrombocytopenia. Semin Hematol. 1998 Oct. 35(4 suppl 5):9-16; discussion 35-6. [Medline].

  30. Warkentin TE, Kelton JG. Delayed-onset heparin-induced thrombocytopenia and thrombosis. Ann Intern Med. 2001 Oct 2. 135(7):502-6. [Medline].

  31. Greinacher A, Warkentin TE. Recognition, treatment, and prevention of heparin-induced thrombocytopenia: review and update. Thromb Res. 2006. 118(2):165-76. [Medline].

  32. Warkentin TE. An overview of the heparin-induced thrombocytopenia syndrome. Semin Thromb Hemost. 2004 Jun. 30(3):273-83. [Medline].

  33. Cuker A, Gimotty PA, Crowther MA, Warkentin TE. Predictive value of the 4Ts scoring system for heparin-induced thrombocytopenia: a systematic review and meta-analysis. Blood. 2012 Nov 15. 120(20):4160-7. [Medline]. [Full Text].

  34. Lo GK, Juhl D, Warkentin TE, Sigouin CS, Eichler P, Greinacher A. Evaluation of pretest clinical score (4 T's) for the diagnosis of heparin-induced thrombocytopenia in two clinical settings. J Thromb Haemost. 2006 Apr. 4(4):759-65. [Medline].

  35. Cuker A, Arepally G, Crowther MA, Rice L, Datko F, Hook K, et al. The HIT Expert Probability (HEP) Score: a novel pre-test probability model for heparin-induced thrombocytopenia based on broad expert opinion. J Thromb Haemost. 2010 Dec. 8(12):2642-50. [Medline].

  36. Berry C, Tcherniantchouk O, Ley EJ, et al. Overdiagnosis of heparin-induced thrombocytopenia in surgical ICU patients. J Am Coll Surg. 2011 Jul. 213(1):10-7; discussion 17-8. [Medline].

  37. [Guideline] Linkins LA, Dans AL, Moores LK, Bona R, Davidson BL, Schulman S, 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-530S. [Medline]. [Full Text].

  38. [Guideline] Cuker, A; Crowther, M. 2013 Clinical Practice Guideline on the Evaluation and Management of Adults with Suspected Heparin-Induced Thrombocytopenia (HIT). American Society of Hematology Quick Reference Guides. Available at Accessed: October 2015.

  39. Hein PA, Lembcke A, Rogalla P. Images in cardiovascular medicine. Multiple thrombosis with aortic occlusion after heparin-induced thrombocytopenia demonstrated by multislice computed tomography. Circulation. 2006 Feb 14. 113(6):e80-3. [Medline]. [Full Text].

  40. Lee GM, Arepally GM. Heparin-induced thrombocytopenia. Hematology Am Soc Hematol Educ Program. 2013. 2013:668-74. [Medline].

  41. Meyer O, Salama A, Pittet N, Schwind P. Rapid detection of heparin-induced platelet antibodies with particle gel immunoassay (ID-HPF4). Lancet. 1999 Oct 30. 354(9189):1525-6. [Medline].

  42. Baroletti S, Hurwitz S, Conti NA, et al. Thrombosis in suspected heparin-induced thrombocytopenia occurs more often with high antibody levels. Am J Med. 2012 Jan. 125(1):44-9. [Medline].

  43. Whitlatch NL, Kong DF, Metjian AD, Arepally GM, Ortel TL. Validation of the high-dose heparin confirmatory step for the diagnosis of heparin-induced thrombocytopenia. Blood. 2010 Sep 9. 116(10):1761-6. [Medline].

  44. Sheridan D, Carter C, Kelton JG. A diagnostic test for heparin-induced thrombocytopenia. Blood. 1986 Jan. 67(1):27-30. [Medline]. [Full Text].

  45. Eichler P, Raschke R, Lubenow N, et al. The new ID-heparin/PF4 antibody test for rapid detection of heparin-induced antibodies in comparison with functional and antigenic assays. Br J Haematol. 2002 Mar. 116(4):887-91. [Medline].

  46. Arepally G, Reynolds C, Tomaski A, et al. Comparison of PF4/heparin ELISA assay with the 14C-serotonin release assay in the diagnosis of heparin-induced thrombocytopenia. Am J Clin Pathol. 1995 Dec. 104(6):648-54. [Medline].

  47. Chong BH, Burgess J, Ismail F. The clinical usefulness of the platelet aggregation test for the diagnosis of heparin-induced thrombocytopenia. Thromb Haemost. 1993 Apr 1. 69(4):344-50. [Medline].

  48. Look KA, Sahud M, Flaherty S, Zehnder JL. Heparin-induced platelet aggregation vs platelet factor 4 enzyme-linked immunosorbent assay in the diagnosis of heparin-induced thrombocytopenia-thrombosis. Am J Clin Pathol. 1997 Jul. 108(1):78-82. [Medline].

  49. Warkentin TE. Heparin-induced thrombocytopenia: diagnosis and management. Circulation. 2004 Nov 2. 110(18):e454-8. [Medline]. [Full Text].

  50. Cuker A, Cines DB. How I treat heparin-induced thrombocytopenia. Blood. 2012 Mar 8. 119(10):2209-18. [Medline].

  51. Swan SK, Hursting MJ. The pharmacokinetics and pharmacodynamics of argatroban: effects of age, gender, and hepatic or renal dysfunction. Pharmacotherapy. 2000 Mar. 20(3):318-29. [Medline].

  52. Junqueira DR, Perini E, Penholati RR, Carvalho MG. Unfractionated heparin versus low molecular weight heparin for avoiding heparin-induced thrombocytopenia in postoperative patients. Cochrane Database Syst Rev. 2012 Sep 12. 9:CD007557. [Medline].

  53. Levine RL, McCollum D, Hursting MJ. How frequently is venous thromboembolism in heparin-treated patients associated with heparin-induced thrombocytopenia?. Chest. 2006 Sep. 130(3):681-7. [Medline]. [Full Text].

  54. Mallik A, Carlson KB, DeSancho MT. A patient with 'spontaneous' heparin-induced thrombocytopenia and thrombosis after undergoing knee replacement. Blood Coagul Fibrinolysis. January 2011. (22) 1:73-5. [Medline].

  55. Pongas G, Dasgupta SK, Thiagarajan P. Antiplatelet factor 4/heparin antibodies in patients with gram negative bacteremia. Thromb Res. August 2013. 132(2):217-20. [Medline].

  56. Smythe MA, Warkentin TE, Stephens JL, Zakalik D, Mattson JC. Venous limb gangrene during overlapping therapy with warfarin and a direct thrombin inhibitor for immune heparin-induced thrombocytopenia. Am J Hematol. 2002 Sep. 71(1):50-2. [Medline]. [Full Text].

  57. [Guideline] Theodore E. Warkentin, Andreas Greinacher, Andreas Koster and A. Michael Lincoff. Treatment and Prevention of Heparin-Induced Thrombocytopenia: American College of Chest Physicians Evidence-Based Clinical Practice Guidelines (8th Edition). Chest. 2008. 133:340-380. [Full Text].

  58. Wrkentin TE, Makris M, Jay RM, Kelton JG. A spontaneous prothrombotic disorder resembling heparin-induced thrombocytopenia. AM J Med. 2008. 121(7):632. [Medline].

  59. Zheng Y, Wang AW, Yu M, Padmanabhan A, Tourdot BE, Newman DK, et al. B-cell tolerance regulates production of antibodies causing heparin-induced thrombocytopenia. Blood. 2014 Feb 6. 123(6):931-4. [Medline]. [Full Text].

  60. Cosmi B. Current management of heparin-induced thrombocytopenia. Expert Rev Hematol. 2015 Sep 14. 1-13. [Medline].

  61. Greinacher A. CLINICAL PRACTICE. Heparin-Induced Thrombocytopenia. N Engl J Med. 2015 Jul 16. 373 (3):252-61. [Medline].

  62. Audette MD, Glymph DC. Bivalirudin in off-pump coronary artery bypass graft in a patient with heparin-induced thrombocytopenia: a case report of its use. AANA J. 2015 Apr. 83 (2):116-22. [Medline].

  63. Miyares MA, Davis KA. Direct-acting oral anticoagulants as emerging treatment options for heparin-induced thrombocytopenia. Ann Pharmacother. 2015 Jun. 49 (6):735-9. [Medline].

  64. Obeng EA, Harney KM, Moniz T, Arnold A, Neufeld EJ, Trenor CC 3rd. Pediatric heparin-induced thrombocytopenia: prevalence, thrombotic risk, and application of the 4Ts scoring system. J Pediatr. 2015 Jan. 166 (1):144-50. [Medline].

Ultrasonographic image of a deep vein thrombosis (DVT).
Sequential images demonstrate treatment of iliofemoral deep venous thrombosis due to May-Thurner (Cockett) syndrome. Far left: View of the entire pelvis demonstrates iliac occlusion. Middle left: After 12 hours of catheter-directed thrombolysis, an obstruction at the left common iliac vein is evident. Middle right: After 24 hours of thrombolysis, a bandlike obstruction is seen; this is the impression made by the overlying right common iliac artery. Far left: After stent placement, image shows wide patency and rapid flow through the previously obstructed region. Note that the patient is in the prone position in all views. (Right and left are reversed.)
Ventilation-perfusion scan. Left image: Posterior view of normal findings on ventilation-perfusion scan. Right image: Posterior view of a perfusion scan that reveals a perfusion defect in the left upper quadrant. The defect in the middle of the image is due to the position of the heart.
Helical computed tomography scan of the pulmonary arteries. A filling defect in the right pulmonary artery is present, consistent with a pulmonary embolism.
Table. 4Ts score [31, 34]
Feature Score
2 points 1 point 0 points
Thrombocytopenia >50% fall


platelet nadir 20-100 × 109/L

30%-50% fall


platelet nadir 10-19× 109/L

>30% fall


platelet nadir < 10× 109/L

Timing of platelet count fall Clear onset on day 5-10, or =1 d if heparin exposure within past 30 d Consistent with day 5-10 fall, but not clear (eg, missing platelet counts); onset after day 10; or fall = 1 day if heparin exposure 30-100 days ago Platelet count fall =4 d without recent heparin exposure
Thrombosis or other sequelae New thrombosis (confirmed); skin necrosis; acute systemic reaction after IV UHF bolus Progressive or recurrent thrombosis; erythematous skin lesions; thrombosis suspected but not proven None
Other causes of thrombocytopenia None apparent Possible Definite
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