Effect of Initial Anticoagulation Targets on Bleeding and Thrombotic Complications for Patients With Acute Respiratory Distress Syndrome Receiving Extracorporeal Membrane Oxygenation.

To evaluate the effect of anticoagulation targets and intensity on bleeding events, thrombotic events, and transfusion requirements in patients with acute respiratory distress syndrome (ARDS) receiving venovenous extracorporeal membrane oxygenation (ECMO) and continuous-infusion heparin. A retrospective cohort study. At a single-center, large academic medical center. One hundred thirty-six critically ill patients. The following three therapeutic targets were implemented over time and evaluated: (1) no protocol (September 2013-August 2016): no standardized anticoagulation protocol or transfusion thresholds; (2) <50 seconds (September 2016-January 2018): standardized activated partial thromboplastin time (aPTT) goal of <50 seconds, maximum heparin infusion rate of 1,200 units/h, transfusion threshold of hemoglobin (Hgb) <8 g/dL; and (3) 40-to-50 seconds (February 2018-December 2019): aPTT goal of 40-to-50 sec, no maximum heparin infusion rate, transfusion threshold of Hgb <7 g/dL. Continuous variables were compared using the Kruskal-Wallis test, and categorical variables were compared using Fisher exact tests. The primary endpoint, an incidence of at least 1 bleeding event, was highest in the no-protocol group though not statistically different among groups (39.3% v 26.7% v 34%, p = 0.5). Thrombotic complications were similar. The median units of packed red blood cells transfused were highest in the no-protocol group (3 v 2 v 0.5, p < 0.001). Anticoagulation protocols standardizing aPTT goals to <50 or 40-to-50 seconds may be a reasonable strategy for patients receiving venovenous ECMO for ARDS. More restrictive hemoglobin transfusion thresholds, in combination with lower aPTT targets, may be associated with a reduction in transfusion requirements.

Cercone JL ，Kram SJ ，Trammel MA ，Rackley CR ，Lee HJ ，Merchant J Jr ，Kram BL ... -  《-》

Anticoagulation Practices during Venovenous Extracorporeal Membrane Oxygenation for Respiratory Failure. A Systematic Review.

Sklar MC ，Sy E ，Lequier L ，Fan E ，Kanji HD ... -  《-》

Venovenous Extracorporeal Membrane Oxygenation With Prophylactic Subcutaneous Anticoagulation Only: An Observational Study in More Than 60 Patients.

Extracorporeal lung support and therapeutic anticoagulation are dogmatically linked for most clinicians in fear of clotting of the extracorporeal circuit. In the last decade, however, we have learned that bleeding complications in the course of extracorporeal membrane oxygenation (ECMO) therapy are common and not occasionally limiting or fatal. Even though international guidelines lowered the PTT-target values, ECMO therapy without anticoagulation has only been reported sporadically in case reports heretofore. This monocentric, observational study was designed to evaluate a protocol for venovenous ECMO therapy without additional anticoagulation. Patients without former thrombotic events solely received thrombosis prophylaxis with 40 mg subcutaneous enoxaparin per day like every critical care patient. After approval by the local ethics committee (Albert-Ludwigs-University Freiburg ethics committee, EK 513/14) all consecutive patients treated with venovenous ECMO therapy since introduction of the protocol have been identified. Digital charts of the patients have been evaluated with special regard to bleeding and thrombotic or embolic events or breakdown of the extracorporeal circuit. Sixty-one patients received venovenous ECMO therapy with prophylactic subcutaneous enoxaparin only. Median duration of ECMO therapy was 7 days (2-32). Overall 560 ECMO days have been observed. No system exchange because of thrombotic occlusion was necessary within the permitted 5 days run time of the centrifugal pump. Overall we identified thrombotic complications in four patients. In three of them centrifugal pump after a runtime of more than 5 days unexpectedly stopped completely because of thrombotic occlusion. In all cases pump exchange was performed promptly and patients did not incur hypoxic deficit. One other patient received substitution of blood products and coagulation factor concentrates because of severe bleeding and sustained myocardial infarction the day after. Only 18% of patients presented with essential clinical bleeding after 7 days of therapy. No fatal bleeding event and no intracranial hemorrhage was observed. Patients required only a third of blood product transfusion compared to published data. Venovenous ECMO therapy with prophylactic anticoagulation only was feasible in this study. It was not associated with an increased rate of system exchanges compared to regimes with therapeutic anticoagulation in registry data. It provides the potential to relevantly decrease the incidence of severe bleeding events and blood transfusion requirements. The apodictic adherence to anticoagulation in therapeutic dosage should be critically scrutinized in every patient.

Krueger K ，Schmutz A ，Zieger B ，Kalbhenn J ... -  《-》

Bleeding, Thrombosis, and Transfusion With Two Heparin Anticoagulation Protocols in Venoarterial ECMO Patients.

To compare the incidence of bleeding and thrombosis between adult venoarterial (VA) extracorporeal membrane oxygenation (ECMO) patients managed with an activated clotting time (ACT)-guided heparin anticoagulation protocol and activated partial thromboplastin time (aPTT) protocol. Retrospective cohort study. Tertiary care, academic medical center. Consecutive adult VA ECMO patients during a 6-year period. None. Demographic, medical, transfusion, and ECMO data were collected for all patients. Primary study outcomes were bleeding and thrombosis. Secondary outcomes were stroke and in-hospital mortality. One hundred twenty-one patients were included in the cohort. Fifty patients had ACT monitoring, and 71 had aPTT monitoring. There was no difference in the incidence of bleeding or thrombosis between the 2 groups (78.0% v 67.6% for bleeding [p = 0.21] and 16.0% v 19.7% for thrombosis [p = 1.0]). After adjusting for age and total ECMO days, patients managed with ACT received approximately 30% more red blood cell, fresh frozen plasma, and platelet transfusion (all p < 0.05). There is no apparent difference in the incidence rate of bleeding or thrombosis between VA ECMO patients managed with an ACT- or aPTT-guided heparin anticoagulation protocol. Patients managed with an ACT-guided protocol received more blood transfusion, which could reflect greater total bleeding. Future randomized controlled trials would help to elucidate optimal anticoagulation strategies for VA ECMO patients.

Mazzeffi MA ，Tanaka K ，Roberts A ，Rector R ，Menaker J ，Kon Z ，Deatrick KB ，Kaczorowski D ，Griffith B ，Herr D ... -  《-》

Comparison of Anticoagulation Strategies in Patients Requiring Venovenous Extracorporeal Membrane Oxygenation: Heparin Versus Bivalirudin.

Extracorporeal membrane oxygenation is a life-sustaining therapy for severe respiratory failure. Extracorporeal membrane oxygenation circuits require systemic anticoagulation that creates a delicate balance between circuit-related thrombosis and bleeding-related complications. Although unfractionated heparin is most widely used anticoagulant, alternative agents such as bivalirudin have been used. We sought to compare extracorporeal membrane oxygenation circuit thrombosis and bleeding-related outcomes in respiratory failure patients receiving either unfractionated heparin or bivalirudin for anticoagulation on venovenous extracorporeal membrane oxygenation support. Retrospective cohort study. Single-center, cardiothoracic ICU. Consecutive patients requiring venovenous extracorporeal membrane oxygenation who were maintained on anticoagulation between 2013 and 2020. IV bivalirudin or IV unfractionated heparin. Primary outcomes were the presence of extracorporeal membrane oxygenation in-circuit-related thrombotic complications and volume of blood products administered during extracorporeal membrane oxygenation duration. One hundred sixty-two patients receiving unfractionated heparin were compared with 133 patients receiving bivalirudin for anticoagulation on venovenous extracorporeal membrane oxygenation. In patients receiving bivalirudin, there was an overall decrease in the number of extracorporeal membrane oxygenation circuit thrombotic complications (p < 0.005) and a significant increase in time to circuit thrombosis (p = 0.007). Multivariable Cox regression found that heparin was associated with a significant increase in risk of clots (Exp[B] = 2.31, p = 0.001). Patients who received bivalirudin received significantly less volume of packed RBCs, fresh frozen plasma, and platelet transfusion (p < 0.001 for each). There was a significant decrease in the number major bleeding events in patients receiving bivalirudin, 40.7% versus 11.7%, p < 0.001. Patients receiving bivalirudin for systemic anticoagulation on venovenous extracorporeal membrane oxygenation experienced a decrease in the number of extracorporeal membrane oxygenation circuit-related thrombotic events as well as a significant decrease in volume of blood products administered.

Rivosecchi RM ，Arakelians AR ，Ryan J ，Murray H ，Ramanan R ，Gomez H ，Phillips D ，Sciortino C ，Arlia P ，Freeman D ，Sappington PL ，Sanchez PG ... -  《-》