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Argatroban for heparin-induced thrombocytopenia therapy in ICU patients with sepsis or multiple organ dysfunction syndrome

Introduction

Heparin-induced thrombocytopenia (HIT) is a serious, prothrombotic, immune-mediated adverse reaction triggered by heparin therapy. When HIT is diagnosed or suspected, heparins should be discontinued and an alternative, fast-acting, parenteral, nonheparin anticoagulation such as argatroban should be initiated. The recommended initial dose of argatroban in HIT is 2 μg/kg/minute with following adjustment to the activated partial thromboplastin times (aPTTs). There are limited and inconsistent data about dosing of argatroban therapy in ICU patients with multiple organ dysfunction syndrome [1, 2].

Methods

Evaluation of 11 patients with sepsis or multiorgan dysfunction syndrome treated with argatroban to demonstrate dosing adjustment difficulties of argatroban in critically ill ICU patients.

Results

Eleven ICU patients with sepsis or multiple organ dysfunction syndrome were treated with argatroban for suspected HIT (n = 11; mean thrombocyte count 44,727) using a mean argatroban starting dose of 0.46 μg/kg/minute (min 0.04; max 0.56) to achieve aPTTs >60 seconds or aPTTs of 1.5 to three times the baseline aPTT. In 10 patients (91%), desired levels of anticoagulation were achieved. Adjustment to aPTT required dose reduction in five patients (45%). Patients were treated for a mean of 4 days. The final mean dose in these critically ill ICU patients was 0.33, about one-sixth of the usually recommended dose, probably reflecting the degree of illness and that there was a tendency to target the lower end of the therapeutic aPTT range.

Conclusion

Patients with multiple organ dysfunction syndrome and HIT can be effectively treated using argatroban. In critically ill patients, the dosing of argatroban has to be adjusted. In all patients with multiorgan failure syndrome a decrease in the initial dosage is mandatory. Further studies are needed to fully elucidate argatroban elimination and dosage adjustments for intensive care patients.

References

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    Gray A, Wallis DE, Hursting MJ, Katz E, Lewis BE: Argatroban therapy for heparin-induced thrombocytopenia in acutely ill patients. Clin Appl Thromb Hemost 2007, 13: 353-361. 10.1177/1076029607303617

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    Williamson DR, Boulanger I, Tardif M, Albert M, Gregoire G: Argatroban dosing in intensive care patients with acute renal failure and liver dysfunction. Pharmacotherapy 2004, 24: 409-414. 10.1592/phco.24.4.409.33168

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Saugel, B., Huber, W. & Schmid, R. Argatroban for heparin-induced thrombocytopenia therapy in ICU patients with sepsis or multiple organ dysfunction syndrome. Crit Care 13, P442 (2009). https://doi.org/10.1186/cc7606

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Keywords

  • Multiple Organ Dysfunction Syndrome
  • Argatroban
  • Intensive Care Patient
  • Require Dose Reduction
  • Thrombocyte Count