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Treatment options

Drugs approved for the treatment of HIT include argatroban, lepirudin and danaparoid(1).  There are no prospective studies comparing these agents so definitive conclusions about efficacy and safety cannot be made. However, there are several pharmacologic and pharmacokinetic considerations that could be considered when determining which drug may be preferred in an individual patient. The following table describes the characteristics of each agent.

For example, an agent with a short half life may be preferred in a patient who might need urgent surgical intervention. Argatroban may be well suited for patients with renal insufficiency and requires no dose adjustment(2), while lepirudin may be preferred in patients with liver impairment.


Table : Characteristics of the approved drugs for the treatment of HIT


Argatroban
Lepirudin
Danaparoid

Mode of action

Direct thrombin inhibitor
Reversible inhibitor

Direct thrombin inhibitor
Irreversible inhibitor

Indirect factor Xa inhibitor
Requires antithrombin

Therapeutic dosing

Dose as given in the SPC

Initial infusion rate:
2 mcg/kg/min. adjust  to achieve aPTT 1.5-3.0 times baseline value*

0.5 mcg/kg/min in hepatic impairment, 
critically ill patients with (multiple) organ failure, after cardiac surgery

Bolus: 0.4 mg/kg
Initial infusion rate : 0.15 mg/kg/hour, adjust to achieve aPTT 1.5-2.5 normal value*

Reduce dose in renal impairment

IV Bolus 1250-3750 U adjust for bodyweight, infusion 400 U/hour for 4 hours, then 300 U/h for 4 hours, then maintenance 150-200 U/h

Dose reduction in renal impairment (2)

Primary route of Elimination

Hepatic

Renal 

Renal

Elimination Half-Life

52 min

1.3 h

25 h (anti-Xa activity)

Monitoring

aPTT

aPTT

Plasma Xa activity, amidolytic assay

Undesirable effects

Bleeding complications

Bleeding complications
Allergic reactions (anaphylaxis)

Bleeding complications
Cross-reactivity to HIT antibodies  

* Reports from clinical practice suggest lower initial doses may be appropriate in certain patients. Alternatives to SPC recommendations are given in the ACCP guidelines (1).

ArgatraŽ SPC , RefludanŽ SPC, OrgaranŽ SPC 

1. Warkentin TE, Greinacher A, Koster A, Lincoff AM. Treatment and prevention of heparin-induced thrombocytopenia: ACCP evidence based clinical practice guidelines (8th Edition). Chest 2008; 133:340-380

2.Selleng K et al. Heparin-induced thrombocytopenia in intensive care patients. Crit Care Med 2007; 35(4):1165-76

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