(1008) Predictors of Heparin Resistance in the ICU

Introduction: Critically ill patients are predisposed to parenteral unfractionated heparin (UFH) resistance due to increased acute phase reactants and extracorporeal circuit use. Most published studies that evaluate risk factors for heparin resistance include cardiac surgery or non-critically ill populations. Identification of risk factors for this high-risk patient population could lead to early diagnosis and adverse event avoidance.

Methods: A retrospective analysis of critically ill patients admitted to a single health-system over five years was performed. Adult patients admitted to any ICU that received continuous infusion UFH for at least 48 contiguous hours were included. Exclusion criteria included incarceration, pregnancy, or prophylactic UFH therapy use for renal replacement therapy. The primary outcome was to identify risk factors for heparin resistance, defined as subtherapeutic coagulation for 48 hours and >35,000 units/day of UFH. Secondary outcomes included incidence of venous thromboembolic (VTE) and bleeding events between heparin responders (HR) and non-responders (HNR). Other secondary outcomes described time until UFH therapeutic, alternate anticoagulant choice, and median daily heparin dose between groups.

Results: Of the 567 patients screened, 52 HR and 47 HNR were included. Most patients were admitted to the medical (37%) and cardiovascular (29%) ICU with VTE (37%) and atrial fibrillation (29%) as the most common indications for UFH. The HNR group had higher weight, infection diagnoses, and extracorporeal circuit use compared to HR. The median UFH dose was higher in HNR vs. HR (37,440 vs. 25,891 units/day, p< 0.001). Increased weight was as an independent predictor for heparin resistance (OR 1.05[95% CI 1.02-1.08]). New VTE (2[4.3%] vs. 0[0%], p< 0.001) and bleeding (17[36.2%] vs. 12[23.1%], p>0.001) were higher in the HNR group. Lower age and albumin were associated with an increased risk of bleeding. UFH protocol deviations were more common in the HNR group (15[31.9%] vs 11[21.2%], p< 0.001) and had the greatest predictive value for bleeding events (OR 4.35[95% CI 1.14-16.55]).

Conclusions: Increased weight was an independent predictor of heparin resistance in critically ill patients. Heparin resistance in the ICU was associated with more risk of VTE and bleeding.