Heparin-induced thrombocytopenia

Section editors
	Shruti Chaturvedi, MBBS, MSCI Baltimore, MD LinkedIn		Benjamin Tillman, MD Nashville, TN

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Guidelines

To be completed

All lines of therapy

Argatroban monotherapy

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

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) Bolus injection of 2400 anti-Xa units followed by 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. Thromb Haemost. 2001 Nov;86(5):1170-5. 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

Regimen

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

To be completed

Anticoagulation

• Fondaparinux (Arixtra)

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

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

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