Extracorporeal membrane oxygenation (ECMO) has been used for >40 years to support lung and heart failure; however, bleeding and thrombosis remain serious complications. The known etiologies of bleeding include heparin effect or overdose, coagulopathy, thrombocytopenia, platelet dysfunction, acquired von Willebrand syndrome, and hyperfibrinolysis. Bleeding sites may include cannula insertion sites, recent surgical incisions, vascular access sites, lung, gastrointestinal tract, mouth, nose, thoracic cavity, abdominal cavity, and brain. Massive bleeding in the brain, the most feared bleeding complication, can be rapidly fatal because it occurs in a rigid closed space, is difficult to drain, and cannot be stopped with direct pressure to the bleeding site. Pulmonary hemorrhage may cause irreversible lung damage. Management should be swift and precise to prevent fatal bleeding. In contrast, etiologies of thrombosis include high fibrinogen and factor VIII levels, heparin resistance, and platelet activation. Achieving the optimal anticoagulation balance to prevent bleeding and thrombosis in ECMO patients is extremely complex. Experts in hemostasis should be a part of an institutional ECMO team and continuously available for immediate management.

Context.-Elevated free hemoglobin (Hb) and bilirubinemia complicate extracorporeal membrane oxygenation and could affect unfractionated heparin (UH) therapy monitoring by anti-Xa assay and activated partial thromboplastin time (aPTT).Objectives.-To compare in vitro response of anti-Xa and aPTT assays to UH in samples with artificial hyperbilirubinemia and hyperhemoglobinemia and to estimate if this interference is also observed in vivo in pediatric extracorporeal membrane oxygenation.Design.-Measurement of aPTT and anti-Xa activity in plasma spiked with UH and increased concentration of free Hb and/or conjugated bilirubin. All samples with antiXa activity, antithrombin, free Hb, and bilirubin determination and infused dose of UH from inpatients on extracorporeal membrane oxygenation were extracted from the clinical patient database and analyzed.Results.-Each increment of free Hb by 100 mg/dL significantly shortened aPTT, whereas an increment of bilirubin by 6 mg/dL caused significant prolongation of aPTT and stepwise increase of free Hb and/or bilirubin in plasma decreased anti-Xa activity by 0.03 to 0.05 IU/mL. Extracorporeal membrane oxygenation samples with free Hb 50 mg/dL or greater had significantly lower anti-Xa activity compared with normal ones: 0.33 (0.25-0.42) versus 0.4 (0.31-0.48) IU/mL (P ¼ .01), despite the identical UH infusion and similar antithrombin activity. Moderate increase of free Hb by 59 mg/dL was associated with absolute decrease of anti-Xa activity by 0.07 IU/mL.Conclusions.-Activated partial thromboplastin time and anti-Xa assay are affected by elevated level of free Hb and/or bilirubin in the presence of UH, and lower antiXa activity is noted in extracorporeal membrane oxygenation patients with elevated free Hb. Severe hemolysis and/or hyperbilirubinemia could compromise UH monitoring based on these assays.

Introduction In an effort to administer life-saving transfusions quickly, some trauma centers maintain thawed plasma (TP). According to AABB, TP is approved for transfusion for up to five days when stored at 1 – 6 °C. However, the alterations in microparticles (MP) contained in the plasma, which are an integral component of plasma’s hemostatic capacity, are not well characterized. We report on MP changes in TP between its initial thaw (FFP-0) and five days (FFP-5) of storage. Materials and Methods FFP units (n=30) were thawed at 37 °C and kept refrigerated for five days. Phenotypes of residual cells, which include platelets, erythrocytes, leukocytes, monocytes, endothelial cells, and MP counterparts of each cell type, were analyzed by flow cytometry. Functional assays were used for MP procoagulant activity, plasma thrombin generation, and clotting properties (thromboelastography). Results In FFP-0 the majority (94%) of residual cells were platelets, along with significant levels of platelet MPs (4408×103/L). FFP-5 showed a decline in MP count by 50% (p<0.0001), and procoagulant activity by 29% (p<0.0001). FFP-5 exhibited only 54% (p<0.0001) of the potential for thrombin generation as FFP-0, while thromboelastography indicated a slower clotting response (p<0.0001) and a longer delay in reaching maximum clot (p<0.01). Removal of MP by filtration resulted in reduced thrombin generation, while the MP replacement restored it. Conclusions Decline in MP with storage contributes to FFP-5’s reduced ability to provide the hemostatic potential exhibited by FFP-0, suggesting the presence of platelet MPs in freshly TP may be beneficial and protective in the initial treatment of hemorrhage.