Extracorporeal membrane oxygenation (ECMO) causes both thrombosis and bleeding. Major society guidelines recommend continuous, systemic anticoagulation to prevent thrombosis of the ECMO circuit, though this may be undesirable in those with active, or high risk of, bleeding. We aimed to systematically review thrombosis and bleeding outcomes in published cases of adults treated with ECMO without continuous systemic anticoagulation. Ovid MEDLINE, Cochrane CENTRAL and CDSR, and hand search via SCOPUS were queried. Eligible studies were independently reviewed by two blinded authors if they reported adults (≥18 years) treated with either VV- or VA-ECMO without continuous systemic anticoagulation for ≥24 hours. Patient demographics, clinical data, and specifics of ECMO technology and treatment parameters were collected. Primary outcomes of interest included incidence of bleeding, thrombosis of the ECMO circuit requiring equipment exchange, patient venous or arterial thrombosis, ability to wean off of ECMO, and mortality. Of the 443 total publications identified, 34 describing 201 patients met our inclusion criteria. Most patients were treated for either acute respiratory distress syndrome or cardiogenic shock. The median duration of anticoagulant-free ECMO was 4.75 days. ECMO circuity thrombosis and patient thrombosis occurred in 27 (13.4%) and 19 (9.5%) patients, respectively. Any bleeding and major or “severe” bleeding was reported in 66 (32.8%) and 56 (27.9%) patients, respectively. Forty patients (19%) died. While limited by primarily retrospective data and inconsistent reporting of outcomes, our systematic review of anticoagulant-free ECMO reveals an incidence of circuity and patient thrombosis comparable to patients receiving continuous systemic anticoagulation while on ECMO.

BACKGROUND Up to 40% of combat casualties with a truncal injury die of massive hemorrhage before reaching a surgeon. This hemorrhage can be prevented with damage control resuscitation (DCR) methods, which are focused on replacing shed whole blood by empirically transfusing blood components in a 1:1:1:1 ratio of platelets:fresh frozen plasma:erythrocytes:cryoprecipitate (PLT:FFP:RBC:CRYO). Measurement of hemostatic function with rotational thromboelastometry (ROTEM) may allow optimization of the type and quantity of blood products transfused. Our hypothesis was that incorporating ROTEM measurements into DCR methods at the US Role 3 hospital at Bagram Airfield, Afghanistan would change the standard transfusion ratios of 1:1:1:1 to a product mix tailored specifically for the combat causality. METHODS This retrospective study collected data from the Department of Defense Trauma Registry to compare transfusion practices and outcomes before and after ROTEM deployment to Bagram Airfield. Over the course of six months, 134 trauma patients received a transfusion (pre-ROTEM) and 85 received a transfusion and underwent ROTEM testing (post-ROTEM). Trauma teams received instruction on ROTEM use and interpretation, with no provision of a specific transfusion protocol, to supplement their clinical judgment and practice. RESULTS The pre and post groups were not significantly different in terms of mortality, massive transfusion protocol activation, mean injury severity score, or coagulation measurements. Despite the difference in size, each group received an equal total number of transfusions. However, the post-ROTEM group received a significant increase in PLT and CRYO transfusions ratios, 4× and 2×, respectively. CONCLUSION The introduction of ROTEM significantly improved adherence to DCR practices. The transfusion differences suggest that aggressive DCR without thromboelastometry data may result in reduced hemostatic support and underestimate the need for PLT and CRYO. Thus, future controlled trials should include ROTEM-guided coagulation management in trauma resuscitation. LEVEL OF EVIDENCE Therapeutic, level IV.

Objective: A state-of-the-art centrifugal pump combined with hollow-fiber oxygenator for extracorporeal membrane oxygenation has potential advantages such as smaller priming volumes and decreased potential to cause tubing rupture as compared with the traditional roller head/silicone membrane systems. Adoption of these state-of-the-art systems has been slow in neonates as a result of past evidence of severe hemolysis that may lead to renal failure and increased mortality. Extracorporeal systems have also been linked to platelet dysfunction, a contributing factor toward intracranial hemorrhage, a leading cause of infant morbidity. Little data exist comparing the centrifugal systems with the roller systems in terms of hemolysis and platelet aggregation at low flow rates commonly used in neonatal extracorporeal membrane oxygenation. Design: Prospective, comparative laboratory study. Setting: University research laboratory. Subjects: Centrifugal pump, roller pump, hollow-fiber oxygenator, and silicone membrane oxygenator. Interventions: Comparative study using two pumps, the centrifugal Jostra Rotaflow (Maquet, Wayne, NJ) and the roller-head (Jostra, Maquet, Wayne, NJ), and two oxygenators, polymethlypentene Quadrox-D (Maquet) and silicone membrane (Medtronic, Minneapolis, MN). Five test runs of four circuit combinations were examined for hemolysis and platelet aggregation during 6 hrs of continuous use in a simulated in vitro extracorporeal membrane oxygenation circuit circulating whole swine blood at 300 mL/min. Measurements and Main Results: Hemolysis was assessed by spectrophometric measurement of plasma-free hemoglobin. Platelet aggregation was evaluated using monoclonal CD61 antibody fluorescent flow cytometry profiles. All of the extracorporeal membrane oxygenation systems created plasma-free hemoglobin at a similar rate compared with static blood control. There was no difference in the mean normalized index of hemolysis of the centrifugal/hollow-fiber oxygenator system as compared with the roller-head/silicone membrane systems (0.0032 g/100 L vs. 0.0058 g/100 L, p ≥ .7). None of the extracorporeal membrane oxygenation systems had a significant increase in platelet aggregation above baseline. Conclusions: In a low-flow neonatal environment, a state-of-the-art centrifugal pump combined with new fiber-type oxygenators appear to be safe in regard to hemolysis and platelet aggregation.

Current anticoagulation strategies do not eliminate thromboembolic stroke or limb loss during neonatal extracorporeal membrane oxygenation (ECMO), a form of cardiopulmonary bypass (CPB). In adults, CPB surgery generates prothrombotic platelet-derived microparticles (PMPs), submicron membrane vesicles released from activated platelets. However, information on PMP generation in neonatal ECMO systems is lacking. The objective of this study was to compare PMP generation in five different neonatal ECMO systems, using a simulated circuit with swine blood at 300 ml/min for 4 hours. Systems were composed of both newer components (centrifugal pump and hollow-fiber oxygenator) and traditional components (roller-head pump and silicone membrane oxygenator). Free plasma hemoglobin levels were measured as an indicator of hemolysis and flow cytometry-measured PMP. Hemolysis generated in all ECMO systems was similar to that observed in noncirculated static blood (p = 0.48). There was no difference in net PMP levels between different oxygenators with a given pump. In contrast, net PMP generation in ECMO systems with a centrifugal pump was at least 2.5 times greater than in roller-head pump systems. This was significant when using either a hollow-fiber (p < 0.005) or a silicone membrane (p < 0.05) oxygenator. Future studies are needed to define the relationship between pump-generated PMP and thrombosis.

We evaluated the extent (luminal coverage) of the endothelial cell (EC) lining/neointimal development and the thromboresistance of electrostatically EC seeded small diameter Chrono Flex-polyurethane vascular grafts. The evaluation consisted of harvesting autologous, canine jugular vein ECs, electrostatically seeding the polyurethane grafts (4-mm I.D., length = 6 cm) with the harvested ECs, implanting the grafts in a canine femoral artery model for four to six weeks, and excising the grafts for histological and scanning electron microscopy evaluations. Results of the histological evaluation (mid-graft region only) indicated that electrostatic EC seeding led to neointimal development and to minimal to no thrombus formation within the EC seeded grafts. The unseeded control grafts resulted in no neointimal development and substantial thrombus formation on the graft luminal surfaces. Scanning electron microscopy examination demonstrated a mature, confluent endothelium with a ‘‘cobblestone’’ appearance on the EC seeded graft luminal surface after six weeks. We conclude that electrostatic EC seeding enhanced the development of a neointima and reduced the incidence of thrombosis in polyurethane grafts implanted in a canine femoral artery model.