Skip to main content
Erschienen in: Journal of Thrombosis and Thrombolysis 2/2016

21.04.2016

Novel oral anticoagulants for heparin-induced thrombocytopenia

verfasst von: Jessica W. Skelley, Jeffrey A. Kyle, Rachel A. Roberts

Erschienen in: Journal of Thrombosis and Thrombolysis | Ausgabe 2/2016

Einloggen, um Zugang zu erhalten

Abstract

To review the use of the novel oral anticoagulant (NOAC) agents for the treatment of heparin-induced thrombocytopenia (HIT) from relevant clinical trial data. A MEDLINE, International Pharmaceutical Abstracts, ClinicalTrials.gov, and Google-Scholar searches (1966–March 2016) were conducted using the keywords: thrombocytopenia, NOACs, dabigatran, apixaban, rivaroxaban, edoxaban, Xa inhibitor, direct thrombin inhibitor. Articles evaluating the new oral anticoagulants for thrombocytopenia published in English and using human subjects were selected. Eight clinical trials were identified. References cited in identified articles were used for additional citations. Approximately 12 million hospitalized patients each year are exposed to heparin for thromboprophylaxis. HIT, an immune-mediated, prothrombotic adverse reaction is a potential complication of heparin therapy. As a result, heparin products must be immediately withdrawn and replaced by alternative anticoagulants to compensate for the thrombotic risk associated with HIT. Limitations exist with the only currently FDA approved heparin alternative, argatroban. NOACs have been considered as potential alternatives to traditional agents based on their pharmacologic activity. Case reports have indicated positive results in patients, with clinical outcomes and tolerability supporting the use of the NOACs as alternative agents in the treatment of HIT. Positive results have been reported for the use of NOACs in the treatment of HIT. Further robust studies are needed for definitive decision making by clinicians.
Literatur
1.
Zurück zum Zitat Campbell KR, Mahaffey KW, Lewis BE et al (2000) Bivalirudin in patients with heparin-induced thrombocytopenia undergoing percutaneous coronary intervention. J Invasive Cardiol. 12(Suppl F):14F-9PubMed Campbell KR, Mahaffey KW, Lewis BE et al (2000) Bivalirudin in patients with heparin-induced thrombocytopenia undergoing percutaneous coronary intervention. J Invasive Cardiol. 12(Suppl F):14F-9PubMed
2.
Zurück zum Zitat Martel N, Lee J, Wells PS (2005) Risk for heparin-induced thrombocytopenia with unfractionated and low-molecular-weight heparin thromboprophylaxis: a meta-analysis. Blood 106:2710–2715CrossRefPubMed Martel N, Lee J, Wells PS (2005) Risk for heparin-induced thrombocytopenia with unfractionated and low-molecular-weight heparin thromboprophylaxis: a meta-analysis. Blood 106:2710–2715CrossRefPubMed
3.
Zurück zum Zitat Lubenow N, Hinz P, Thomaschewski S et al (2010) The severity of trauma determines the immune response to PF4/heparin and the frequency of heparin-induced thrombocytopenia. Blood 115:1797–1803CrossRefPubMed Lubenow N, Hinz P, Thomaschewski S et al (2010) The severity of trauma determines the immune response to PF4/heparin and the frequency of heparin-induced thrombocytopenia. Blood 115:1797–1803CrossRefPubMed
4.
Zurück zum Zitat Greinacher A, Warkentin TE (2008) Risk of heparin-induced thrombocytopenia in patients receiving thromboprophylaxis. Expert Rev Hematol 1:75–85CrossRefPubMed Greinacher A, Warkentin TE (2008) Risk of heparin-induced thrombocytopenia in patients receiving thromboprophylaxis. Expert Rev Hematol 1:75–85CrossRefPubMed
5.
Zurück zum Zitat Warkentin TE, Sheppard JA, Sigouin CS et al (2006) Gender imbalance and risk factor interactions in heparin-induced thrombocytopenia. Blood 108(9):2937–2941CrossRefPubMed Warkentin TE, Sheppard JA, Sigouin CS et al (2006) Gender imbalance and risk factor interactions in heparin-induced thrombocytopenia. Blood 108(9):2937–2941CrossRefPubMed
6.
Zurück zum Zitat Greinacher A, Lubenow N (2003) Heparin-induced thrombocytopenia. In: Arnout J, de Gaetano G, Hoylaerts M et al (eds) Thrombosis: fundamental and clinical aspects. Leuven University Press, Leuven Greinacher A, Lubenow N (2003) Heparin-induced thrombocytopenia. In: Arnout J, de Gaetano G, Hoylaerts M et al (eds) Thrombosis: fundamental and clinical aspects. Leuven University Press, Leuven
8.
Zurück zum Zitat Bakchoul T, Greinacher A (2012) Recent advances in the diagnosis and treatment of heparin-induced thrombocytopenia. Ther Adv Hematol 3(4):237–251CrossRefPubMedPubMedCentral Bakchoul T, Greinacher A (2012) Recent advances in the diagnosis and treatment of heparin-induced thrombocytopenia. Ther Adv Hematol 3(4):237–251CrossRefPubMedPubMedCentral
9.
Zurück zum Zitat Cosmi B (2015) Current management of heparin-induced thrombocytopenia. Expert Rev Hematol 8(6):837–849CrossRefPubMed Cosmi B (2015) Current management of heparin-induced thrombocytopenia. Expert Rev Hematol 8(6):837–849CrossRefPubMed
10.
Zurück zum Zitat Prechel M, Walenga J (2008) The laboratory diagnosis and clinical management of patients with heparin-induced thrombocytopenia: an update. Semin Thromb Hemost 34:86–96CrossRefPubMed Prechel M, Walenga J (2008) The laboratory diagnosis and clinical management of patients with heparin-induced thrombocytopenia: an update. Semin Thromb Hemost 34:86–96CrossRefPubMed
11.
Zurück zum Zitat Warkentin TE, Roberts RS, Hirsh J et al (2003) An improved definition of immune heparin-induced thrombocytopenia in postoperative orthopedic patients. Arch Intern Med 163(20):2518–2524CrossRefPubMed Warkentin TE, Roberts RS, Hirsh J et al (2003) An improved definition of immune heparin-induced thrombocytopenia in postoperative orthopedic patients. Arch Intern Med 163(20):2518–2524CrossRefPubMed
12.
Zurück zum Zitat Singla A, Amini MR, Alpert MA et al (2013) Fatal anaphylactoid reaction associated with heparin-induced thrombocytopenia. Vasc Med 18(3):136–138CrossRefPubMed Singla A, Amini MR, Alpert MA et al (2013) Fatal anaphylactoid reaction associated with heparin-induced thrombocytopenia. Vasc Med 18(3):136–138CrossRefPubMed
13.
Zurück zum Zitat Lo GK, Juhl D, Warkentin TE et al (2006) Evaluation of pretest clinical score (4 T’s) for the diagnosis of heparin-induced thrombocytopenia in two clinical settings. J Thromb Haemost 4(4):759–765CrossRefPubMed Lo GK, Juhl D, Warkentin TE et al (2006) Evaluation of pretest clinical score (4 T’s) for the diagnosis of heparin-induced thrombocytopenia in two clinical settings. J Thromb Haemost 4(4):759–765CrossRefPubMed
14.
Zurück zum Zitat Greinacher A (2015) Clinical practice. Heparin-induced thrombocytopenia. N Engl J Med 373:252–261CrossRefPubMed Greinacher A (2015) Clinical practice. Heparin-induced thrombocytopenia. N Engl J Med 373:252–261CrossRefPubMed
15.
Zurück zum Zitat Watson H, Davidson S, Keeling D (2012) Guidelines on the diagnosis and management of heparin induced thrombocytopenia: second edition. Br J Haematol 159:528–540PubMed Watson H, Davidson S, Keeling D (2012) Guidelines on the diagnosis and management of heparin induced thrombocytopenia: second edition. Br J Haematol 159:528–540PubMed
16.
Zurück zum Zitat Linkins LA, Dans AL, Moores LK et al (2012) 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 141(2 Suppl):e495S–e530SCrossRefPubMedPubMedCentral Linkins LA, Dans AL, Moores LK et al (2012) 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 141(2 Suppl):e495S–e530SCrossRefPubMedPubMedCentral
17.
Zurück zum Zitat Bhatt VR, Aryal MR, Armitage JO (2013) Nonheparin anticoagulants for heparin-induced thrombocytopenia. N Engl J Med 368:2334CrossRef Bhatt VR, Aryal MR, Armitage JO (2013) Nonheparin anticoagulants for heparin-induced thrombocytopenia. N Engl J Med 368:2334CrossRef
18.
Zurück zum Zitat Mavrakanas T, Bounameaux H (2011) The potential role of new oral anticoagulants in the prevention and treatment of thromboembolism. Pharmacol Ther 130(1):46–58CrossRefPubMed Mavrakanas T, Bounameaux H (2011) The potential role of new oral anticoagulants in the prevention and treatment of thromboembolism. Pharmacol Ther 130(1):46–58CrossRefPubMed
19.
Zurück zum Zitat Chan NC, Bhagirath V, Eikelboom JW (2015) Profile of betrixaban and its potential in the prevention and treatment of venous thromboembolism. Vasc Health Risk Manag 11:343–351PubMedPubMedCentral Chan NC, Bhagirath V, Eikelboom JW (2015) Profile of betrixaban and its potential in the prevention and treatment of venous thromboembolism. Vasc Health Risk Manag 11:343–351PubMedPubMedCentral
20.
Zurück zum Zitat Walenga JM, Prechel M, Jeske WP et al (2008) Rivaroxaban—an oral, direct factor Xa inhibitor—has potential for the management of patients with heparin-induced thrombocytopenia. Br J Haematol 143(1):92–99CrossRefPubMed Walenga JM, Prechel M, Jeske WP et al (2008) Rivaroxaban—an oral, direct factor Xa inhibitor—has potential for the management of patients with heparin-induced thrombocytopenia. Br J Haematol 143(1):92–99CrossRefPubMed
21.
Zurück zum Zitat Krauel K, Hackbarth C, Furll B, Greinacher A (2012) 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 119(5):1248–1255CrossRefPubMed Krauel K, Hackbarth C, Furll B, Greinacher A (2012) 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 119(5):1248–1255CrossRefPubMed
22.
Zurück zum Zitat Walenga JM, Prechel M, Hoppensteadt D et al (2013) Apixaban as an alternate oral anticoagulant for the management of patients with heparin-induced thrombocytopenia. Clin Appl Thromb Hemost 19:482–487CrossRefPubMed Walenga JM, Prechel M, Hoppensteadt D et al (2013) Apixaban as an alternate oral anticoagulant for the management of patients with heparin-induced thrombocytopenia. Clin Appl Thromb Hemost 19:482–487CrossRefPubMed
23.
Zurück zum Zitat Sanidas EA, Viniou NA, Diamantopoulos P, Barbetseas J (2015) Heparin induced thrombocytopenia: contemporary therapeutic approaches in light of the new oral anticoagulants. Hamostaseologie 35:372–375CrossRefPubMed Sanidas EA, Viniou NA, Diamantopoulos P, Barbetseas J (2015) Heparin induced thrombocytopenia: contemporary therapeutic approaches in light of the new oral anticoagulants. Hamostaseologie 35:372–375CrossRefPubMed
24.
Zurück zum Zitat Sharifi M, Bay C, Vajo Z, Freeman W, Sharifi M, Schwartz F (2015) New oral anticoagulants in the treatment of heparin-induced thrombocytopenia. Thromb Res 135:607–609CrossRefPubMed Sharifi M, Bay C, Vajo Z, Freeman W, Sharifi M, Schwartz F (2015) New oral anticoagulants in the treatment of heparin-induced thrombocytopenia. Thromb Res 135:607–609CrossRefPubMed
25.
Zurück zum Zitat Mirdamadi A (2013) Dabigatran, a direct thrombin inhibitor, can be a life-saving treatment in heparin-induced thrombocytopenia. ARYA Artherscler 9:112–114 Mirdamadi A (2013) Dabigatran, a direct thrombin inhibitor, can be a life-saving treatment in heparin-induced thrombocytopenia. ARYA Artherscler 9:112–114
26.
Zurück zum Zitat Fieland D, Taylor M (2012) Dabigatran use in a postoperative coronary artery bypass surgery patient with nonvalvular atrial fibrillation and heparin-PF4 antibodies. Ann Pharmacother 46(1):46e3CrossRef Fieland D, Taylor M (2012) Dabigatran use in a postoperative coronary artery bypass surgery patient with nonvalvular atrial fibrillation and heparin-PF4 antibodies. Ann Pharmacother 46(1):46e3CrossRef
27.
Zurück zum Zitat Lo GK, Juhl D, Warkentin TE, Sigouin CS, Eichler P, Greinacher A (2006) Evaluation of pretest clinical score (4 T’s) for the diagnosis of heparin-induced thrombocytopenia in two clinical settings. J Thromb Haemost 4:759–765CrossRefPubMed Lo GK, Juhl D, Warkentin TE, Sigouin CS, Eichler P, Greinacher A (2006) Evaluation of pretest clinical score (4 T’s) for the diagnosis of heparin-induced thrombocytopenia in two clinical settings. J Thromb Haemost 4:759–765CrossRefPubMed
28.
Zurück zum Zitat Hantson P, Lambert C, Hermans C (2014) Rivaroxaban for arterial thrombosis related to heparin-induced thrombocytopenia. Blood Coagul Fibrinolysis 38:485–492 Hantson P, Lambert C, Hermans C (2014) Rivaroxaban for arterial thrombosis related to heparin-induced thrombocytopenia. Blood Coagul Fibrinolysis 38:485–492
29.
Zurück zum Zitat Ng H, Than H, Teo E (2015) First experiences with the use of rivaroxaban in the treatment of heparin-induced thrombocytopenia. Thromb Res 135:205–207CrossRefPubMed Ng H, Than H, Teo E (2015) First experiences with the use of rivaroxaban in the treatment of heparin-induced thrombocytopenia. Thromb Res 135:205–207CrossRefPubMed
30.
Zurück zum Zitat Tardy-Poncet B, Piot M, Montmartin A, Burdier A, Chalayer E, Tardy B (2015) Delayed-onset heparin-induced thrombocytopenia without thrombosis in a patient receiving postoperative thromboprophylaxis with rivaroxaban. Thromb Haemost 114:652–654CrossRefPubMed Tardy-Poncet B, Piot M, Montmartin A, Burdier A, Chalayer E, Tardy B (2015) Delayed-onset heparin-induced thrombocytopenia without thrombosis in a patient receiving postoperative thromboprophylaxis with rivaroxaban. Thromb Haemost 114:652–654CrossRefPubMed
31.
Zurück zum Zitat Sharifi M, Freeman W, Bay C, Sharifi M, Breed C, Schwartz F (2014) Treatment of heparin-induced thrombocytopenia with new oral anticoagulants. J Am Coll Cardiol 63:A2096CrossRef Sharifi M, Freeman W, Bay C, Sharifi M, Breed C, Schwartz F (2014) Treatment of heparin-induced thrombocytopenia with new oral anticoagulants. J Am Coll Cardiol 63:A2096CrossRef
32.
Zurück zum Zitat Linkins LA, Warkentin TE, Pai M et al (2014) Design of the rivaroxaban for heparin-induced thrombocytopenia study. J Thromb Thromolysis 38:485–492CrossRef Linkins LA, Warkentin TE, Pai M et al (2014) Design of the rivaroxaban for heparin-induced thrombocytopenia study. J Thromb Thromolysis 38:485–492CrossRef
33.
Zurück zum Zitat Larsen PB, Jorgensen M, Fris-Hansen L et al (2015) Apixaban used for the management of heparin-induced thrombocytopenia in a 72-year-old woman with lung cancer. Clin Case Rep 3:987–989CrossRefPubMedPubMedCentral Larsen PB, Jorgensen M, Fris-Hansen L et al (2015) Apixaban used for the management of heparin-induced thrombocytopenia in a 72-year-old woman with lung cancer. Clin Case Rep 3:987–989CrossRefPubMedPubMedCentral
34.
Zurück zum Zitat Linkins LA, Warkentin TE (2011) Heparin-induced thrombocytopenia: real-world issues. Semin Thromb Hemost 37:653–663CrossRefPubMed Linkins LA, Warkentin TE (2011) Heparin-induced thrombocytopenia: real-world issues. Semin Thromb Hemost 37:653–663CrossRefPubMed
35.
Zurück zum Zitat Warkentin TE (2014) Anticoagulant failure in coagulopathic patients: PTT confounding and other pitfalls. Expert Opin Drug Saf 13:25–43CrossRefPubMed Warkentin TE (2014) Anticoagulant failure in coagulopathic patients: PTT confounding and other pitfalls. Expert Opin Drug Saf 13:25–43CrossRefPubMed
36.
Zurück zum Zitat Jeske WP, Walenga JM (2002) Antithrombotic drugs for the treatment of heparin-induced thrombocytopenia. Curr Opin Investig Drugs 3:1171–1180PubMed Jeske WP, Walenga JM (2002) Antithrombotic drugs for the treatment of heparin-induced thrombocytopenia. Curr Opin Investig Drugs 3:1171–1180PubMed
37.
Zurück zum Zitat Messmore H, Jeske WP, Wehrmacher W, Walenga JM (2003) Benefit–risk assessment of treatments for heparin-induced thrombocytopenia. Drug Saf 26:625–641CrossRefPubMed Messmore H, Jeske WP, Wehrmacher W, Walenga JM (2003) Benefit–risk assessment of treatments for heparin-induced thrombocytopenia. Drug Saf 26:625–641CrossRefPubMed
42.
Zurück zum Zitat Perzborn E, Heitmeier S, Buetehorn U, Laux V (2014) Direct thrombin inhibitors, but not the direct factor Xa inhibitor rivaroxaban, increase tissue factor-induced hypercoagulability in vitro and in vivo. J Thromb Haemost 12:1054–1065CrossRefPubMedPubMedCentral Perzborn E, Heitmeier S, Buetehorn U, Laux V (2014) Direct thrombin inhibitors, but not the direct factor Xa inhibitor rivaroxaban, increase tissue factor-induced hypercoagulability in vitro and in vivo. J Thromb Haemost 12:1054–1065CrossRefPubMedPubMedCentral
Metadaten
Titel
Novel oral anticoagulants for heparin-induced thrombocytopenia
verfasst von
Jessica W. Skelley
Jeffrey A. Kyle
Rachel A. Roberts
Publikationsdatum
21.04.2016
Verlag
Springer US
Erschienen in
Journal of Thrombosis and Thrombolysis / Ausgabe 2/2016
Print ISSN: 0929-5305
Elektronische ISSN: 1573-742X
DOI
https://doi.org/10.1007/s11239-016-1365-0

Weitere Artikel der Ausgabe 2/2016

Journal of Thrombosis and Thrombolysis 2/2016 Zur Ausgabe

Leitlinien kompakt für die Innere Medizin

Mit medbee Pocketcards sicher entscheiden.

Seit 2022 gehört die medbee GmbH zum Springer Medizin Verlag

Update Innere Medizin

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.