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An architecturally rational hemostat for rapid stopping of massive bleeding on anticoagulation therapy.

ABSTRACT: Hemostatic devices are critical for managing emergent severe bleeding. With the increased use of anticoagulant therapy, there is a need for next-generation hemostats. We rationalized that a hemostat with an architecture designed to increase contact with blood, and engineered from a material that activates a distinct and undrugged coagulation pathway can address the emerging need. Inspired by lung alveolar architecture, here, we describe the engineering of a next-generation single-phase chitosan hemostat with a tortuous spherical microporous design that enables rapid blood absorption and concentrated platelets and fibrin microthrombi in localized regions, a phenomenon less observed with other classical hemostats without structural optimization. The interaction between blood components and the porous hemostat was further amplified based on the charged surface of chitosan. Contrary to the dogma that chitosan does not directly affect physiological clotting mechanism, the hemostat induced coagulation via a direct activation of platelet Toll-like receptor 2. Our engineered porous hemostat effectively stopped the bleeding from murine liver wounds, swine liver and carotid artery injuries, and the human radial artery puncture site within a few minutes with significantly reduced blood loss, even under the anticoagulant treatment. The integration of engineering design principles with an understanding of the molecular mechanisms can lead to hemostats with improved functions to address emerging medical needs.

SUBMITTER: Lee VK

PROVIDER: S-EPMC10835033 | biostudies-literature | 2024 Jan

REPOSITORIES: biostudies-literature

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An architecturally rational hemostat for rapid stopping of massive bleeding on anticoagulation therapy.

Lee Vivian K VK Lee Taewoo T Ghosh Amrit A Saha Tanmoy T Bais Manish V MV Bharani Kala Kumar KK Chag Milan M Parikh Keyur K Bhatt Parloop P Namgung Bumseok B Venkataramanan Geethapriya G Agrawal Animesh A Sonaje Kiran K Mavely Leo L Sengupta Shiladitya S Mashelkar Raghunath Anant RA Jang Hae Lin HL

Proceedings of the National Academy of Sciences of the United States of America 20240122 5

Hemostatic devices are critical for managing emergent severe bleeding. With the increased use of anticoagulant therapy, there is a need for next-generation hemostats. We rationalized that a hemostat with an architecture designed to increase contact with blood, and engineered from a material that activates a distinct and undrugged coagulation pathway can address the emerging need. Inspired by lung alveolar architecture, here, we describe the engineering of a next-generation single-phase chitosan ...[more]

PMID: 38252814

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Project description:BackgroundAcute gastrointestinal (GI) bleeding is not an uncommon complication of oral anticoagulation (OAC) therapy that requires medication cessation. However, drug cessation may cause fatal stroke or systemic embolization in patients at high thromboembolic risk. Here we sought to find an appropriate anticoagulation cessation strategy in cases of GI bleeding during OAC therapy.MethodsThis single-center retrospective cohort analysis was performed between 2010 and 2018. Patients were enrolled if the following three consecutive conditions were met: 1) electrocardiography electrocardiography-proven atrial fibrillation; 2) OAC therapy; and 3) GI bleeding. We divided the drug cessation strategy into the continuation and discontinuation groups. During 1-year follow-up, the rates of major thromboembolic and rebleeding events were calculated.ResultsOne hundred and forty-six patients (continuation [n = 54] vs. discontinuation [n = 92] group) were enrolled. Patients in the discontinuation group were more likely to be older (69.8 ± 9.0 yrs vs. 74.9 ± 8.9 yrs, p = 0.001), while patients in the continuation group were more likely to have undergone cardiac valve surgery (51.9% vs. 20.7%, p<0.001). The presence of a mechanical mitral valve was a determinant of continuation strategy (38.9% vs. 7.5%, p<0.001). However, the mean CHA₂DS₂-VASc (3.4±1.3 vs. 4.1±1.6, p = 0.010) and Glasgow-Blatchford (8.0±2.4 vs. 8.9±2.5, p = 0.037) scores were higher in the discontinuation group. Two major embolic strokes occurred in each group (3.7% vs. 2.2%, p = 0.585). Four of 54 (7.4%) and five of 92 (5.4%) patients had rebleeding events during follow-up (p = 0.632). One embolic event in the continuation group and one rebleeding event in the discontinuation group were fatal. The Glasgow-Blatchford score was a predictor of 1-year rebleeding events (odds ratio [OR], 1.36; 95% confidence interval [CI], 0.68-2.20; p = 0.028). The high CHA₂DS₂-VASc score showed a strong trend (OR, 1.71; 95% CI, 0.92-3.20; p = 0.089) in 1-year thromboembolic events.ConclusionNo single risk factor or drug cessation strategy was attributed to adverse clinical events after GI bleeding. The risk of future thrombotic or rebleeding events should be individualized and controlled for based on a pre-existing stratification system.

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An architecturally rational hemostat for rapid stopping of massive bleeding on anticoagulation therapy.

Publications

An architecturally rational hemostat for rapid stopping of massive bleeding on anticoagulation therapy.

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