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Anticoagulation during extracorporeal membrane oxygenation (ECMO) for Coronovirus Disease 2019 (COVID-19) can be performed by direct or indirect thrombin inhibitors but differences in outcomes with these agents are uncertain. A retrospective, multicenter study was conducted. All consecutive adult patients with COVID-19 placed on ECMO between March 1, 2020 and April 30, 2021 in participating centers, were included. Patients were divided in groups receiving either a direct thrombin inhibitor (DTI) or an indirect thrombin inhibitor such as unfractionated heparin (UFH). Overall, 455 patients with COVID-19 from 17 centers were placed on ECMO during the study period. Forty-four patients did not receive anticoagulation. Of the remaining 411 patients, DTI was used in 160 (39%) whereas 251 (61%) received UFH. At 90-days, in-hospital mortality was 50% (DTI) and 61% (UFH), adjusted hazard ratio: 0.81, 95% confidence interval (CI): 0.49-1.32. Deep vein thrombosis [adjusted odds ratio (aOR): 2.60, 95% CI: 0.90-6.65], ischemic (aOR: 1.58, 95% CI: 0.18-14.0), and hemorrhagic (aOR:1.22, 95% CI: 0.39-3.87) stroke were similar with DTI in comparison to UFH. Bleeding requiring transfusion was lower in patients receiving DTI (aOR: 0.40, 95% CI: 0.18-0.87). Anticoagulants that directly inhibit thrombin are associated with similar in-hospital mortality, stroke, and venous thrombosis and do not confer a higher risk of clinical bleeding in comparison to conventional heparin during ECMO for COVID-19., Competing Interests: Disclosure: The authors have no conflicts of interest to report., (Copyright © ASAIO 2022.)

Background: Hemolysis, even at low levels, activates platelets to create a prothrombotic state and is common during mechanical circulatory support. We examined the association of low-level hemolysis (LLH) and nonhemorrhagic stroke during venoarterial extracorporeal membrane oxygenation (VA ECMO) support., Methods: A single-center retrospective review of all adult patients placed on VA ECMO from January 2012 to September 2017 was conducted. To determine the association between LLH and nonhemorrhagic stroke, patients were categorized as those with and without LLH. LLH was defined by 48-hour plasma free hemoglobin (PFHb) of 11 to 50 mg/dL after VA ECMO implantation., Results: Of 201 patients who underwent VA ECMO placement, 150 (75%) met inclusion criteria and comprised the study population. They were 55 ± 14 years of age and 50 (33%) were women. Sixty-two (41%) patients had LLH. Patients with LLH had a higher likelihood of incident nonhemorrhagic stroke during VA ECMO support (20 [32%] versus 4 [5%]; adjusted hazard ratio [HR], 7.6; 95% confidence interval [CI], 2.2 to 25.9; p = 0.001). The severity of LLH was associated with an incrementally higher likelihood of a nonhemorrhagic stroke (PFHb 26 to 50 mg/dL: HR, 11.3; 95% CI, 3.6 to 35.1; p = 0.001; PFHb 11 to 25 mg/dL: HR, 4.4; 95% CI, 1.36 to 14.85; p = 0.014) in comparison with no LLH. Those with LLH had a 2-fold greater increase in mean platelet volume after VA ECMO placement (0.98 ± 1.1 fL versus 0.49 ± 0.96 fL; p = 0.03). Patients with a nonhemorrhagic stroke had a higher operative mortality (20 [83%] versus 57 [45%]; adjusted HR, 3.1; 95% CI, 1.8 to 5.3; p < 0.001)., Conclusions: Hemolysis at low levels during VA ECMO support is associated with subsequent nonhemorrhagic stroke., (Copyright © 2019 The Society of Thoracic Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: Persistent low-level hemolysis (LLH) during continuous-flow mechanical circulatory support is associated with subsequent thrombosis. Free hemoglobin from ongoing hemolysis scavenges nitric oxide (NO) to create an NO deficiency which can augment platelet function leading to a prothrombotic state. The phosphodiesterase-5 inhibitor, sildenafil, potentiates NO signaling to inhibit platelet function. Accordingly, we investigated the association of sildenafil administration and thrombotic events in patients with LLH during Heart Mate II support., Methods and Results: A single-center review of all patients implanted with a Heart Mate II who survived to discharge (n=144). LLH was defined by a discharge lactate dehydrogenase level of 400 to 700 U/L. Patients were categorized as (1) LLH not on sildenafil, (2) LLH on sildenafil, (3) no LLH not on sildenafil, and (4) no LLH on sildenafil. Age, sex, platelet count, and mean platelet volume were similar between groups. Seventeen patients had either device thrombosis or ischemic stroke. Presence of LLH was associated with a greater risk of thrombosis (adjusted hazard ratio, 15; 95% confidence interval, 4.5-50; P <0.001 versus no LLH, not on sildenafil). This risk was reduced in patients with LLH on sildenafil (adjusted hazard ratio, 1.7; 95% confidence interval, 0.2-16.1; P =0.61). Device thrombosis and ischemic stroke were associated with an increase in mean platelet volume (9.6±0.5 to 10.9±0.8 fL, P <0.001). Patients with LLH not on sildenafil had a greater increase in mean platelet volume in comparison to those with LLH on sildenafil ( P <0.001)., Conclusions: Sildenafil is associated with reduced device thrombosis and ischemic stroke during ongoing LLH on Heart Mate II support., (© 2017 American Heart Association, Inc.)

Background and Purpose: This study evaluated the use of an artificial intelligence platform on mobile devices in measuring and increasing medication adherence in stroke patients on anticoagulation therapy. The introduction of direct oral anticoagulants, while reducing the need for monitoring, have also placed pressure on patients to self-manage. Suboptimal adherence goes undetected as routine laboratory tests are not reliable indicators of adherence, placing patients at increased risk of stroke and bleeding., Methods: A randomized, parallel-group, 12-week study was conducted in adults (n=28) with recently diagnosed ischemic stroke receiving any anticoagulation. Patients were randomized to daily monitoring by the artificial intelligence platform (intervention) or to no daily monitoring (control). The artificial intelligence application visually identified the patient, the medication, and the confirmed ingestion. Adherence was measured by pill counts and plasma sampling in both groups., Results: For all patients (n=28), mean (SD) age was 57 years (13.2 years) and 53.6% were women. Mean (SD) cumulative adherence based on the artificial intelligence platform was 90.5% (7.5%). Plasma drug concentration levels indicated that adherence was 100% (15 of 15) and 50% (6 of 12) in the intervention and control groups, respectively., Conclusions: Patients, some with little experience using a smartphone, successfully used the technology and demonstrated a 50% improvement in adherence based on plasma drug concentration levels. For patients receiving direct oral anticoagulants, absolute improvement increased to 67%. Real-time monitoring has the potential to increase adherence and change behavior, particularly in patients on direct oral anticoagulant therapy., Clinical Trial Registration: URL: http://www.clinicaltrials.gov. Unique identifier: NCT02599259., (© 2017 American Heart Association, Inc.)