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

TY - JOUR

T1 - Argatroban therapy for heparin-induced thrombocytopenia in ICU patients with multiple organ dysfunction syndrome

T2 - a retrospective study

AU - Saugel, Bernd

AU - Phillip, Veit

AU - Moessmer, Georg

AU - Schmid, Roland M

AU - Huber, Wolfgang

PY - 2010/1/1

Y1 - 2010/1/1

N2 - 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. Limited and inconsistent data exist about dosing of argatroban in intensive care unit (ICU) patients with critical illnesses.METHODS: Retrospective analysis of 12 ICU patients with multiple organ dysfunction syndrome (MODS) treated with argatroban for suspected or diagnosed HIT.RESULTS: The 12 ICU patients with a mean platelet count of 46,000 +/- 30,310 had a mean APACHE II score of 26.7 +/- 7.8 on ICU admission and a mean SAPS II score of 61.5 +/- 16.3 on the first day of argatroban administration. A mean argatroban starting dose of 0.32 +/- 0.25 microg/kg/min (min, 0.04; max, 0.83) was used to achieve activated partial thromboplastin times (aPTTs) >60 sec or aPTTs of 1.5 to 3 times the baseline aPTT. Adjustment to aPTT required dose reduction in six (50%) patients. Patients were treated for a mean of 5.5 +/- 3.3 days. The final mean dose in these critically ill patients was 0.24 +/- 0.16 microg/kg/min, which is about one eighth of the usually recommended dose and even markedly lower than the previously suggested dose for critically ill ICU patients. In all patients, desired levels of anticoagulation were achieved. The mean argatroban dose was significantly lower in patients with hepatic insufficiency compared with patients without hepatic impairment (0.10 +/- 0.06 microg/kg/min versus 0.31 +/- 0.14 microg/kg/min; P = 0.026). The mean argatroban dose was significantly correlated with serum bilirubin (r = -0.739; P = 0.006).CONCLUSIONS: ICU Patients with MODS and HIT can be effectively treated with argatroban. A decrease in the initial dosage is mandatory in this patient population. Further studies are needed to investigate argatroban elimination and dosage adjustments for critically ill patients.

AB - 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. Limited and inconsistent data exist about dosing of argatroban in intensive care unit (ICU) patients with critical illnesses.METHODS: Retrospective analysis of 12 ICU patients with multiple organ dysfunction syndrome (MODS) treated with argatroban for suspected or diagnosed HIT.RESULTS: The 12 ICU patients with a mean platelet count of 46,000 +/- 30,310 had a mean APACHE II score of 26.7 +/- 7.8 on ICU admission and a mean SAPS II score of 61.5 +/- 16.3 on the first day of argatroban administration. A mean argatroban starting dose of 0.32 +/- 0.25 microg/kg/min (min, 0.04; max, 0.83) was used to achieve activated partial thromboplastin times (aPTTs) >60 sec or aPTTs of 1.5 to 3 times the baseline aPTT. Adjustment to aPTT required dose reduction in six (50%) patients. Patients were treated for a mean of 5.5 +/- 3.3 days. The final mean dose in these critically ill patients was 0.24 +/- 0.16 microg/kg/min, which is about one eighth of the usually recommended dose and even markedly lower than the previously suggested dose for critically ill ICU patients. In all patients, desired levels of anticoagulation were achieved. The mean argatroban dose was significantly lower in patients with hepatic insufficiency compared with patients without hepatic impairment (0.10 +/- 0.06 microg/kg/min versus 0.31 +/- 0.14 microg/kg/min; P = 0.026). The mean argatroban dose was significantly correlated with serum bilirubin (r = -0.739; P = 0.006).CONCLUSIONS: ICU Patients with MODS and HIT can be effectively treated with argatroban. A decrease in the initial dosage is mandatory in this patient population. Further studies are needed to investigate argatroban elimination and dosage adjustments for critically ill patients.

KW - Aged

KW - Aged, 80 and over

KW - Anticoagulants

KW - Antithrombins

KW - Critical Care

KW - Dose-Response Relationship, Drug

KW - Female

KW - Heparin

KW - Humans

KW - Intensive Care Units

KW - Male

KW - Middle Aged

KW - Multiple Organ Failure

KW - Pipecolic Acids

KW - Retrospective Studies

KW - Survival Analysis

KW - Thrombocytopenia

U2 - 10.1186/cc9024

DO - 10.1186/cc9024

M3 - SCORING: Journal article

C2 - 20487559

VL - 14

SP - R90

JO - CRIT CARE

JF - CRIT CARE

SN - 1364-8535

IS - 3

ER -