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 ... -  《-》

Blood and Anticoagulation Management in Extracorporeal Membrane Oxygenation for Surgical and Nonsurgical Patients: A Single-Center Retrospective Review.

To describe blood management and anticoagulation practice for cardiac and respiratory extracorporeal membrane oxygenation (ECMO) with consideration of major surgery at the time of its initiation. A single-center retrospective review over 18 months of blood product usage and anticoagulation in patients treated with veno-venous (VV) ECMO versus veno-arterial (VA) ECMO and after major surgery (Sx) versus no surgery (Nsx). Tertiary metropolitan hospital and state ECMO referral and heart and lung transplantation center. The study comprised 42 patients representing 48 consecutive ECMO runs (16 VV, 32 VA, 26 Sx, 22 Nsx). None. Thirty-three percent of the total run time of 362 days was with no continuous infusion of heparin. The mean (standard deviation) daily dose of heparin was lower for Sx versus Nsx patients (11,397 [9,297] v 17,324 [10,387] U, p = 0.047). Sx patients also received more fresh frozen plasma (1.1 [1.93] v 0.2 [0.59] U per day, p = 0.049) and platelets (0.5 [0.51] v 0.1 [0.25] U per day, p = 0.003). VV patients received fewer packed red cells (0.7 [0.45] v 2.0 [2.04] U per day, p = 0.016) and platelets (0.1 [0.18] v 0.4 [0.49] U per day, p = 0.008) compared with VA patients. Survival to hospital discharge was 69%. Heparin doses were low, with frequent interruption of anticoagulation. This was more pronounced in patients with a high bleeding risk recovering from major surgery. The overall usage of blood products was low in VV and Nsx patients, with an overall excellent survival rate.

Buscher H ，Vukomanovic A ，Benzimra M ，Okada K ，Nair P ... -  《-》

The Impact and Statistical Analysis of a Multifaceted Anticoagulation Strategy in Children Supported on ECMO: Performance and Pitfalls.

We sought to determine whether the introduction of a new anticoagulation protocol improved the frequency with which target anticoagulation parameters were met in children supported with extracorporeal membrane oxygenation (ECMO). Additionally, we sought to correlate the results of various tests of anticoagulation with the heparin infusion dose (HID) for patients on ECMO and to evaluate the utility of these anticoagulation monitoring tests for the titration of the HID. A retrospective chart review of 18 patients who received ECMO at an academic tertiary care children's hospital. Nine patients who were managed using a new anticoagulation protocol were matched by age and diagnosis with 9 patients managed with the old protocol. We collected data relating to patient demographics, type of extracorporeal support, disease process, and incidence of bleeding or thrombosis. Anticoagulation parameters collected include the activated clotting time (ACT), activated partial thromboplastin time (aPTT), prothrombin time/international normalized ratio, anti-factor Xa level, and antithrombin 3 level along with the HID at each time point. Patient groups were compared using a Generalized Linear Mixed Model, a mixed model analysis of variance, and correlational studies. The percentage of in-range ACT values was not different between the 2 protocols, whereas the percentage of in-range aPTT values was higher in the new anticoagulation protocol (ACT: 37.7% vs 39.5%; aPTT: 25.1% vs 39.8%). After accounting for repeated and variable measures within patients, the probability of obtaining an in-range ACT and aPTT did not differ significantly between the 2 protocols (ACT: P = .3488; aPTT: P = .16). The mean HID did not differ between the 2 groups (35.0 unit/kg/h vs 37.6 unit/kg/h, P = .56). Correlation coefficients demonstrated a significant inverse correlation between the ACT and the HID in both the groups (old: r = -.22, P < .0001; new: r = -.26, P < .0001). We observed a significant positive correlation between the aPTT and the HID in the historical group (r = .25, P < .0001), but no correlation between the aPTT and the HID in the current group (r = -.02, P = .71). The anti-factor Xa level showed a significantly positive correlation with the HID in the current group (r = .62, P < .0001). A multipronged monitoring regimen slightly increased the amount of time that anticoagulation parameters were within range. Correlations between the HID and the aPTT differed based on anticoagulation protocol, with a positive correlation in the older protocol and no correlation in the new protocol. This may highlight a problem in study design and analysis that requires further examination. Further trials are needed to assess the most useful markers with which anticoagulation protocols for ECMO can be created, adjusted, and evaluated.

Kessel AD ，Kline M ，Zinger M ，McLaughlin D ，Silver P ，Sweberg TM ... -  《-》

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 ... -  《-》

Evaluation of a pharmacy managed heparin protocol for extracorporeal membrane oxygenation patients.

Fitousis K ，Klasek R ，Mason PE ，Masud F ... -  《-》