Heparin-induced thrombocytopenia (HIT)

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Shruti Chaturvedi, MBBS, MSCI
Baltimore, MD

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Benjamin Tillman, MD
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Guidelines

ASH

All lines of therapy

Argatroban monotherapy

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Regimen

Study Evidence Comparator Efficacy
Lewis et al. 2001 (ARG-911) Prospective, historical control Multiple Reduced all-cause death, all-cause amputation, and new thrombosis
Lewis et al. 2003 (ARG-915) Prospective, historical control Multiple Reduced all-cause death, all-cause amputation, or new thrombosis
Treschan et al. 2014 (ALicia) Randomized, double-blind Lepirudin Suggests less bleeding in surgical patients with argatroban.
Kang et al. 2015 Retrospective, propensity score-matched Fondaparinux Similar efficacy and safety to fondaparinux

Note: In ALicia, only 15 patients (23%) in the study had confirmed HIT.

Anticoagulation

  • ARG-911, ARG-915: Argatroban (Acova) 2 mcg/kg/min IV adjusted to maintain activated partial thromboplastin time 1.5 to 3.0 times baseline value.
  • ALicia: Argatroban (Acova) without liver dysfunction: 0.5 mcg/kg/min IV adjusted to maintain activated partial thromboplastin time 1.5 to 2.0 times baseline value.
  • ALicia: Argatroban (Acova) with severe liver dysfunction (bilirubin >4 mg/dL): 0.25 mcg/kg/min IV adjusted to maintain activated partial thromboplastin time 1.5 to 2.0 times baseline value.

References

  1. ARG-911: Lewis BE, Wallis DE, Berkowitz SD, Matthai WH, Fareed J, Walenga JM, Bartholomew J, Sham R, Lerner RG, Zeigler ZR, Rustagi PK, Jang IK, Rifkin SD, Moran J, Hursting MJ, Kelton JG; ARG-911 Study Investigators. Argatroban anticoagulant therapy in patients with heparin-induced thrombocytopenia. Circulation. 2001 Apr 10;103(14):1838-43. link to original article PubMed
  2. ARG-915: Lewis BE, Wallis DE, Leya F, Hursting MJ, Kelton JG; ARG-915 Study Investigators. Argatroban anticoagulation in patients with heparin-induced thrombocytopenia. Arch Intern Med. 2003;164:1849-1856. link to original article PubMed
  3. ALicia: Treschan TA, Schaefer MS, Geib J, Bahlmann A, Brezina, T, Werner P, Golla, E, Greinacher A, Pannen B, Kindgen-Milles D, Kienbaum P, Beiderlinden M. Argatroban versus lepirudin in critically ill patients (ALicia): a randomized controlled trial. Critical Care. 2014 Oct 25;18(5):588. link to original article link to PMC article PubMed
  4. Kang M, Alahmadi M, Sawh S, Kovacs MJ, Lazo-Langner A. Fondaparinux for the treatment of suspected heparin-induced thrombocytopenia: a propensity score-matched study. Blood. 2015 Feb 5;125(6):924-9. link to original article PubMed

Danaparoid monotherapy

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Regimen

Study Evidence Comparator Efficacy
Chong et al. 2001 Phase III Dextran 70 Improved complete clinical recovery with danaparoid
Kang et al. 2015 Retrospective, propensity score-matched Fondaparinux Similar efficacy and safety to fondaparinux

Anticoagulation

  • Danaparoid (Orgaran) 2400 anti-Xa units IV bolus once, then 400 units per hour for 2h, 300 units per hour for 2h, and then 200 units per hour for five days.

References

  1. Chong BH, Gallus AS, Cade JF, Magnani H, Manoharan A, Oldmeadow M, Arthur C, Rickard K, Gallo J, Lloyd J, Seshadri P, Chesterman CN; Australian HIT Study Group. Prospective randomised open-label comparison of danaparoid with dextran 70 in the treatment of heparin-induced thrombocytopaenia with thrombosis: a clinical outcome study. Thromb Haemost. 2001 Nov;86(5):1170-5. link to original article PubMed
  2. Kang M, Alahmadi M, Sawh S, Kovacs MJ, Lazo-Langner A. Fondaparinux for the treatment of suspected heparin-induced thrombocytopenia: a propensity score-matched study. Blood. 2015 Feb 5;125(6):924-9. link to original article PubMed

Fondaprinux monotherapy

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Regimen

Study Evidence Comparator Efficacy
Kang et al. 2015 Retrospective, propensity score-matched 1. Argatroban
2. Danaparoid
Similar efficacy and safety to argatroban, danaparoid

To be completed

Anticoagulation

References

  1. Kang M, Alahmadi M, Sawh S, Kovacs MJ, Lazo-Langner A. Fondaparinux for the treatment of suspected heparin-induced thrombocytopenia: a propensity score-matched study. Blood. 2015 Feb 5;125(6):924-9. link to original article PubMed

Lepirudin monotherapy

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Regimen

Study Evidence Comparator Efficacy
Treschan et al. 2014 (ALicia) Randomized, double-blind Argatroban Suggests less bleeding in surgical patients with argatroban.

Note: Only 15 patients (23%) in the study had confirmed HIT.

Anticoagulation

  • Lepirudin (Refludan) as follows:
    • Patients with continuous renal replacement therapy: 5 mcg/kg/hr IV adjusted to maintain activated partial thromboplastin time 1.5 to 2.0 times baseline value.
    • Patients with moderate renal impairment (creatinine 1.3 mg/dl or more): 10 mcg/kg/hr IV adjusted to maintain activated partial thromboplastin time 1.5 to 2.0 times baseline value.
    • Patients with without renal impairment (creatinine less than 1.3 mg/dl): 50 mcg/kg/hr IV adjusted to maintain activated partial thromboplastin time 1.5 to 2.0 times baseline value.

References

  1. ALicia: Treschan TA, Schaefer MS, Geib J, Bahlmann A, Brezina, T, Werner P, Golla, E, Greinacher A, Pannen B, Kindgen-Milles D, Kienbaum P, Beiderlinden M. Argatroban versus Lepirudin in critically ill patients (ALicia): a randomized controlled trial. Critical Care. 2014 Oct 25;18(5):588. link to original article link to PMC article PubMed

Rivaroxaban monotherapy

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Regimen

Study Evidence Comparator Efficacy
Linkins et al. 2016 Prospective cohort None New thrombosis in one patient (4.5%)

Anticoagulation

  • Rivaroxaban (Xarelto): 15 mg PO BID until platelet recovery (or until day 21 if acute thrombosis present at study entry), then 20mg daily until day 30

References

  1. 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 Jun;14(6):1206-10. link to original article PubMed