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Background: Heparin induced thrombocytopenia (HIT) is reported at a variable rate in extracorporeal membrane oxygenation (ECMO) patients. A critical factor impacting platelet factor-4 (PF4)-heparin antibody formation is plasma PF4 concentration. We hypothesized that PF4 concentration would be increased during veno-arterial (VA) ECMO. Methods: Plasma PF4 concentration was measured during the first 5 ECMO days in 20 VA ECMO patients and 10 control plasma samples. PF4-heparin ratios were estimated using an assumed heparin concentration of 0.4 IU/mL. This correlates with an activated partial thromboplastin time of 60 to 80 seconds, which is the anticoagulation target in our center. Results: Twenty VA ECMO patients were enrolled, 10 of which had pulmonary embolism. Median PF4 concentration was 0.03 µg/mL [0.01, 0.13] in control plasma. Median PF4 concentration was 0.21 µg/mL [0.12, 0.34] on ECMO day 1 or 2, 0.16 µg/mL [0.09, 0.25] on ECMO day 3, and 0.12 µg/mL [0.09, 0.22] on ECMO day 5. Estimated median PF4-heparin ratios were 0.04, 0.03, and 0.02 respectively. Two patients (10%) developed HIT that was confirmed by serotonin release assay. PF4 concentration did not differ significantly in these patients compared to non-HIT patients (p = 0.37). No patient had an estimated PF4-heparin ratio between 0.7 and 1.4, which is the reported optimal range for PF4-heparin antibody formation. Conclusion: Our data suggest that PF4 concentration is mildly elevated during VA ECMO compared to control plasma. Estimated PF4-heparin ratios were not optimal for HIT antibody formation. These data support epidemiologic studies where HIT incidence is low during VA ECMO. [ABSTRACT FROM AUTHOR]

Objective: There is no universally accepted algorithm for anticoagulation in patients on veno-venous extracorporeal membrane oxygenation. The purpose of this pilot study was to compare a non-titrating weight-based heparin infusion to that of a standard titration algorithm. Methods: We performed a prospective randomized non-blinded study of patients: Arm 1—standard practice of titrating heparin to activated partial thromboplastin times goal of 45-55 seconds, and Arm 2—a non-titrating weight-based (10 units/kg/h) infusion. Primary outcome was need for oxygenator/circuit changes. Secondary outcomes included differences in hemolysis and bleeding episodes. Descriptive statistics were performed for the continuous data, and primary and secondary outcomes were compared using Fisher's exact test as appropriate. Results: Six patients were randomized to Arm 1 and four to Arm 2. There was no difference in age, pH, PaO2/FiO2 ratio, peak inspiratory pressure, positive end expiratory pressure, mean airway pressure at time of cannulation, time on extracorporeal membrane oxygenation, or survival to hospital discharge in the two arms. Arm 1 had a statistically higher median activated partial thromboplastin times (48 (43, 52) vs 38 (35, 42), p < 0.008) and lower LDH (808 units/L (727, 1112) vs 940 units/L (809, 1137), p = 0.02) than Arm 2. There was no difference in plasma hemoglobin (4.3 (2.5, 8.7) vs 4.3 (3.0, 7.3), p = 0.65) between the two arms. There was no difference in mean oxygenator/circuit change, transfused packed red blood cell, or documented bleeding complications per patient in each arm (p = 0.56, 0.43, 0.77, respectively). Conclusion: In this pilot study, a non-titrating, weight-based heparin infusion appears safe and as effective in preventing veno-venous extracorporeal membrane oxygenation circuit thrombotic complications as compared to a titration algorithm. Larger studies are needed to confirm these preliminary findings. [ABSTRACT FROM AUTHOR]