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Open Access 01-12-2017 | Case report

Apixaban for treatment of confirmed heparin-induced thrombocytopenia: a case report and review of literature

Authors: Daniel E. Ezekwudo, Rebecca Chacko, Bolanle Gbadamosi, Syeda Batool, Sussana Gaikazian, Theodore E. Warkentin, Jo-Ann I. Sheppard, Ishmael Jaiyesimi

Published in: Experimental Hematology & Oncology | Issue 1/2017

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Abstract

Background

Heparin-induced thrombocytopenia (HIT) is a life and limb-threatening condition caused by the binding of platelet-activating antibodies (IgG) to multimolecular platelet factor 4 (PF4)/heparin complexes because of heparin exposure. The by-product of this interaction is thrombin formation which substantially increases the risk of venous and/or arterial thromboembolism. Currently, only one anticoagulant, argatroban, is United States Food and Drug Administration-approved for management of HIT; however, this agent is expensive and can only be given by intravenous infusion. Recently, several retrospective case-series, case reports, and one prospective study suggest that direct oral anticoagulants (DOACs) are also efficacious for treating HIT. We further review the literature regarding current diagnosis and clinical management of HIT.

Case presentation

A 66-year-old male patient developed HIT beginning on day 5 post-cardiovascular surgery; the platelet count nadir on day 10 measured 16 × 109/L. Both the PF4-dependent ELISA and Serotonin-release assay were strongly positive. Despite initial anticoagulation with argatroban (day 6), the patient developed symptomatic Doppler ultrasound-documented bilateral lower extremity deep vein thrombosis on day 14 post-surgery. The patient was transitioned to the DOAC, apixaban, while still thrombocytopenic (platelet count 108) and discharged to home, with platelet count recovery and no further thrombosis at 3-month follow-up.

Conclusions

We report a patient with serologically confirmed HIT who developed symptomatic bilateral lower limb deep vein thrombosis despite anticoagulation with argatroban. The patient was switched to oral apixaban and made a complete recovery. Our patient case adds to the emerging literature suggesting that DOAC therapy is safe and efficacious for management of proven HIT.
Literature
1.
go back to reference Warkentin TE, Kelton JG. A 14-year study of heparin-induced thrombocytopenia. Am J Med. 1996;101(5):502–7.CrossRefPubMed Warkentin TE, Kelton JG. A 14-year study of heparin-induced thrombocytopenia. Am J Med. 1996;101(5):502–7.CrossRefPubMed
2.
go back to reference Nand S, Wong W, Yuen B, Yetter A, Schmulbach E, Gross Fisher S. 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;56(1):12–6.CrossRefPubMed Nand S, Wong W, Yuen B, Yetter A, Schmulbach E, Gross Fisher S. 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;56(1):12–6.CrossRefPubMed
3.
go back to reference Aljabri A, Huckleberry Y, Karnes JH, Gharaibeh M, Kutbi HI, Raz Y, Yun S, Abraham I, Erstad B. Cost-effectiveness of anticoagulants for suspected heparin-induced thrombocytopenia in the United States. Blood. 2016;128(26):3043–51.PubMed Aljabri A, Huckleberry Y, Karnes JH, Gharaibeh M, Kutbi HI, Raz Y, Yun S, Abraham I, Erstad B. Cost-effectiveness of anticoagulants for suspected heparin-induced thrombocytopenia in the United States. Blood. 2016;128(26):3043–51.PubMed
4.
go back to reference Linkins LA, Warkentin TE, Pai M, Shivakumar S, Manji RA, Wells PS, Wu C, Nazi I, Crowther MA. Rivaroxaban for treatment of suspected or confirmed heparin-induced thrombocytopenia study. J Thromb Haemost. 2016;14(6):1206–10.CrossRefPubMed Linkins LA, Warkentin TE, Pai M, Shivakumar S, Manji RA, Wells PS, Wu C, Nazi I, Crowther MA. Rivaroxaban for treatment of suspected or confirmed heparin-induced thrombocytopenia study. J Thromb Haemost. 2016;14(6):1206–10.CrossRefPubMed
5.
go back to reference Walenga JM, Prechel M, Jeske WP, Hoppensteadt D, Maddineni J, Iqbal O, Messmore HL, Bakhos M. Rivaroxaban—an oral, direct Factor Xa inhibitor—has potential for the management of patients with heparin-induced thrombocytopenia. Br J Haematol. 2008;143(1):92–9.CrossRefPubMed Walenga JM, Prechel M, Jeske WP, Hoppensteadt D, Maddineni J, Iqbal O, Messmore HL, Bakhos M. Rivaroxaban—an oral, direct Factor Xa inhibitor—has potential for the management of patients with heparin-induced thrombocytopenia. Br J Haematol. 2008;143(1):92–9.CrossRefPubMed
6.
go back to reference Shatzel JJ, Crapster-Pregont M, Deloughery TG. Non-vitamin K antagonist oral anticoagulants for heparin-induced thrombocytopenia. a systematic review of 54 reported cases. Thromb haemost. 2016;116(2):397.CrossRefPubMed Shatzel JJ, Crapster-Pregont M, Deloughery TG. Non-vitamin K antagonist oral anticoagulants for heparin-induced thrombocytopenia. a systematic review of 54 reported cases. Thromb haemost. 2016;116(2):397.CrossRefPubMed
7.
go back to reference Linkins LA, Warkentin TE, Pai M, Shivakumar S, Manji RA, Wells PS, Crowther MA. Design of the rivaroxaban for heparin-induced thrombocytopenia study. J Thromb Thrombolysis. 2014;38(4):485–92.CrossRefPubMed Linkins LA, Warkentin TE, Pai M, Shivakumar S, Manji RA, Wells PS, Crowther MA. Design of the rivaroxaban for heparin-induced thrombocytopenia study. J Thromb Thrombolysis. 2014;38(4):485–92.CrossRefPubMed
8.
go back to reference Warkentin TE, Greinacher A. Management of heparin-induced thrombocytopenia. Curr Opin Hematol. 2016;23(5):462–70.CrossRefPubMed Warkentin TE, Greinacher A. Management of heparin-induced thrombocytopenia. Curr Opin Hematol. 2016;23(5):462–70.CrossRefPubMed
9.
go back to reference Warkentin TE, Levine MN, Hirsh J, Horsewood P, Roberts RS, Gent M, Kelton JG. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med. 1995;332(20):1330–6.CrossRefPubMed Warkentin TE, Levine MN, Hirsh J, Horsewood P, Roberts RS, Gent M, Kelton JG. Heparin-induced thrombocytopenia in patients treated with low-molecular-weight heparin or unfractionated heparin. N Engl J Med. 1995;332(20):1330–6.CrossRefPubMed
10.
go back to reference Warkentin TE, Greinacher A, Koster A, Lincoff AM. Treatment and prevention of heparin-induced thrombocytopenia: American college of chest physicians evidence-based clinical practice guidelines. Chest J. 2008;133:340S–80S.CrossRef Warkentin TE, Greinacher A, Koster A, Lincoff AM. Treatment and prevention of heparin-induced thrombocytopenia: American college of chest physicians evidence-based clinical practice guidelines. Chest J. 2008;133:340S–80S.CrossRef
12.
go back to reference Pathak R, Bhatt VR, Karmacharya P, Aryal MR, Donato AA. Medical and economic burden of heparin-induced thrombocytopenia: a retrospective nationwide inpatient sample (nis) study. J Hospital Med. 2017;12(2):94–7.CrossRef Pathak R, Bhatt VR, Karmacharya P, Aryal MR, Donato AA. Medical and economic burden of heparin-induced thrombocytopenia: a retrospective nationwide inpatient sample (nis) study. J Hospital Med. 2017;12(2):94–7.CrossRef
13.
go back to reference 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;4(4):759–65.CrossRefPubMed 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;4(4):759–65.CrossRefPubMed
14.
go back to reference Cuker A, Arepally G, Crowther MA, Rice L, Datko F, Hook K, Propert KJ, Kuter DJ, Ortel TL, Konkle BA, Cines DB. 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;8(12):2642–50.CrossRefPubMed Cuker A, Arepally G, Crowther MA, Rice L, Datko F, Hook K, Propert KJ, Kuter DJ, Ortel TL, Konkle BA, Cines DB. 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;8(12):2642–50.CrossRefPubMed
15.
go back to reference Warkentin TE. Heparin-induced thrombocytopenia: pathogenesis and management. Br J Haematol. 2003;121(4):535–55.CrossRefPubMed Warkentin TE. Heparin-induced thrombocytopenia: pathogenesis and management. Br J Haematol. 2003;121(4):535–55.CrossRefPubMed
16.
go back to reference Amiral J, Wolf M, Fischer A, Boyer-Neumann C, Vissac A, Meyer D. Pathogenicity of IgA and/or IgM antibodies to heparin–PF4 complexes in patients with heparin-induced thrombocytopenia. Br J Hematol. 1996;92(4):954–9.CrossRef Amiral J, Wolf M, Fischer A, Boyer-Neumann C, Vissac A, Meyer D. Pathogenicity of IgA and/or IgM antibodies to heparin–PF4 complexes in patients with heparin-induced thrombocytopenia. Br J Hematol. 1996;92(4):954–9.CrossRef
17.
go back to reference Rice L. Heparin-induced thrombocytopenia: myths and misconceptions (that will cause trouble for you and your patient). Arch Intern Med. 2004;164(18):1961–4.CrossRefPubMed Rice L. Heparin-induced thrombocytopenia: myths and misconceptions (that will cause trouble for you and your patient). Arch Intern Med. 2004;164(18):1961–4.CrossRefPubMed
18.
19.
go back to reference Raschke RA, Curry SC, Warkentin TE, Gerkin RD. Improving clinical interpretation of the anti-platelet factor 4/heparin enzyme-linked immunosorbent assay for the diagnosis of heparin-induced thrombocytopenia through the use of receiver operating characteristic analysis, stratum-specific likelihood ratios, and Bayes theorem. Chest J. 2013;144(4):1269–75.CrossRef Raschke RA, Curry SC, Warkentin TE, Gerkin RD. Improving clinical interpretation of the anti-platelet factor 4/heparin enzyme-linked immunosorbent assay for the diagnosis of heparin-induced thrombocytopenia through the use of receiver operating characteristic analysis, stratum-specific likelihood ratios, and Bayes theorem. Chest J. 2013;144(4):1269–75.CrossRef
20.
go back to reference Cuker A, Crowther M. Clinical practice guideline on the evaluation and management of adults with suspected heparin-induced thrombocytopenia (HIT). Am Soc Hematol. 2013;1:1–4. Cuker A, Crowther M. Clinical practice guideline on the evaluation and management of adults with suspected heparin-induced thrombocytopenia (HIT). Am Soc Hematol. 2013;1:1–4.
21.
go back to reference Kleinschmidt S, Stephan B, Pindur G, Bauer C. Argatroban: pharmacological properties and anaesthesiological aspects. Der Anaesth. 2006;55(4):443–50.CrossRef Kleinschmidt S, Stephan B, Pindur G, Bauer C. Argatroban: pharmacological properties and anaesthesiological aspects. Der Anaesth. 2006;55(4):443–50.CrossRef
23.
go back to reference Krauel K, Hackbarth C, Fürll B, Greinacher A. Heparin-induced thrombocytopenia: in vitro studies on the interaction of dabigatran, rivaroxaban, and low-sulfated heparin, with platelet factor 4 and anti-PF4/heparin antibodies. Blood. 2012;119(5):1248–55.CrossRefPubMed Krauel K, Hackbarth C, Fürll B, Greinacher A. Heparin-induced thrombocytopenia: in vitro studies on the interaction of dabigatran, rivaroxaban, and low-sulfated heparin, with platelet factor 4 and anti-PF4/heparin antibodies. Blood. 2012;119(5):1248–55.CrossRefPubMed
Metadata
Title
Apixaban for treatment of confirmed heparin-induced thrombocytopenia: a case report and review of literature
Authors
Daniel E. Ezekwudo
Rebecca Chacko
Bolanle Gbadamosi
Syeda Batool
Sussana Gaikazian
Theodore E. Warkentin
Jo-Ann I. Sheppard
Ishmael Jaiyesimi
Publication date
01-12-2017
Publisher
BioMed Central
Published in
Experimental Hematology & Oncology / Issue 1/2017
Electronic ISSN: 2162-3619
DOI
https://doi.org/10.1186/s40164-017-0080-7

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