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
Treschan et al. 2014 (ALicia)	Randomized, double-blind	Lepirudin	Suggests less bleeding in surgical patients with argatroban.
Kang M et al. 2015	Retrospective, propensity score-matched	Fondaparinux	Similar efficacy and safety to fondaparinux

Anticoagulation

• ARG-911: 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.anja A Treschan[author],
2. 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. PubMed.
   • Only 15 patients (23%) in the study had confirmed HIT.
3. 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
Kang M et al. 2015	Retrospective, propensity score-matched	Fondaparinux	Similar efficacy and safety to fondaparinux

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.

Fondaprinux monotherapy

Regimen

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

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.

Anticoagulation

• ALicia: Lepirudin paitents 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.
• ALicia: Lepirudin paitents with moderate renal impairment (creatinine >=1.3 mg/dl): 10 mcg/kg/hr IV adjusted to maintain activated partial thromboplastin time 1.5 to 2.0 times baseline value.
• ALicia: Lepirudin paitents with without renal impairment (creatinine <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. PubMed.
   • Only 15 patients (23%) in the study had confirmed HIT.

Rivaroxaban monotherapy

Regimen

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

Anticoagulation

• Rivaroxaban: 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.