In Vitro Apixaban Removal By CytoSorb Whole Blood Adsorber: An Experimental Study

Røed-Undlien, Henriette; Schultz, Nina Haagenrud; Lunnan, Asbjørn; Husebråten, Inger M; Wollmann, Birgit M; Molden, Espen; Bjørnstad, Johannes L.

doi:10.1053/j.jvca.2022.01.038

Cited by 17 publications

(17 citation statements)

References 34 publications

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“…This could be also verified by our group in the acute setting of aortic dissections where intraoperative hemoadsorption was capable of attenuating bleeding risk in patients pretreated with ticagrelor or rivaroxaban [ 8 ]. Just recently, a group from Oslo demonstrated the in vitro removal of apixaban from whole blood using CytoSorb ® : within 30 min of adsorption, the mean apixaban concentration was reduced from 414.3 (±69.1) ng/mL down to 33 (±11.4) ng/mL and reversal of the anticoagulant effect with normalized hemostasis [ 4 ]. Systematic, benchtop testing using a “life-size” recirculation model designed to mimic conditions encountered in clinical, intraoperative use also demonstrated efficient removal of apixaban, rivaroxaban and ticagrelor from whole blood with the DrugSorbTM-AntiThrombotic Removal (ATR) hemoadsorption device (CytoSorbents Inc., Princeton, NJ, USA) [ 3 ].…”

Section: Discussionmentioning

confidence: 99%

“…Therefore, alternate strategies are urgently needed to improve the safety of patients on anticoagulants undergoing non-deferrable surgery with high perioperative bleeding risk. Recently, apixaban removal by hemoadsorption has been demonstrated in vitro [ 3 , 4 ] and in a single case report [ 5 ]. As a result, intraoperative hemoadsorption may be a novel approach to reduce the risk of perioperative bleeding in patients undergoing emergent or urgent cardiac surgery.…”

Section: Introductionmentioning

confidence: 99%

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Removal of Apixaban during Emergency Cardiac Surgery Using Hemoadsorption with a Porous Polymer Bead Sorbent

Hassan

Thielmann

Easo³

et al. 2022

JCM

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Background: Patients on direct oral anticoagulants are at high risk of perioperative bleeding complications. We analyzed the results of intraoperative hemoadsorption (HA) in patients undergoing cardiac surgery who were also on concurrent therapy with apixaban. Methods: we included 25 consecutive patients on apixaban who underwent cardiac surgery with the use of cardio-pulmonary bypass (CPB) at three sites. The first 12 patients underwent surgery without hemoadsorption (controls), while the next 13 consecutive patients were operated with the Cytosorb® (Princeton, NJ, USA) device integrated into the CPB circuit (HA group). The primary outcome was perioperative bleeding assessed by the Bleeding Academic Research Consortium (BARC) definition and secondary outcomes included 24 h chest-tube-drainage (CTD) and need for 1-deamino-8-d-arginine-vasopressin (desmopressin (DDAVP)) administration to achieve hemostasis. Results: Preoperative mean daily dose of apixaban was higher in the HA group (8.5 ± 2.4 vs. 5.6 ± 2.2 mg, p = 0.005), while time since last apixaban dose was longer in the controls (1.3 ± 0.9 vs. 0.6 ± 1.2 days, p < 0.001). No BARC-4 bleeding events and no repeat-thoracotomies occurred in the HA group compared with 3 and 1, respectively, in the controls. Postoperative 24 h CTD volume was significantly lower in the HA group (510 ± 152 vs. 893 ± 579 mL, p = 0.03) and there was no need for DDAVP compared to controls, who received an average of 10 ± 13.6 mg (p = 0.01). Conclusions: In patients on apixaban undergoing emergent cardiac surgery, the intraoperative use of hemoadsorption was feasible and safe. Compared to patients operated on without hemoadsorption, BARC-4 bleeding complications did not occur and the need for 24 h CTD and DDAVP was significantly lower.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Removal of Apixaban during Emergency Cardiac Surgery Using Hemoadsorption with a Porous Polymer Bead Sorbent

Hassan

Thielmann

Easo³

et al. 2022

JCM

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“…To the best of our knowledge, this is the first clinical case that directly proves the efficacy of CytoSorb haemoadsorption therapy for apixaban removal in a patient undergoing emergency open‐heart surgery with direct measurements of the plasma levels of the drug. The in vitro efficacy of the adsorber in reducing apixaban concentration on whole blood samples, has been recently proved in an experimental study, 6 but no direct evidence of the efficacy of this device has been described in a real clinical setting up to now.…”

Section: Discussion/conclusionmentioning

confidence: 99%

CytoSorb haemoadsorption for removal of apixaban—A proof‐of‐concept pilot case for a randomized controlled trial

Buonocore

Rex

Degezelle

et al. 2022

Clinical Pharmacy Therapeu

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What is known and objective Emergent cardiac surgery in patients under anticoagulant therapy is still a major point of concern. Recently approved reversal agents are often not available or not suitable in the cardiac surgery setting, and timely discontinuation of the drug is not always feasible. CytoSorb® haemoadsorption therapy has been approved in Europe for intraoperative ticagrelor and rivaroxaban removal during cardiopulmonary bypass (CPB), but thus far the efficacy of CytoSorb® haemoadsorber on other anticoagulants (apixaban, dabigatran, edoxaban) has only been tested in vitro, and some signals of clinical benefits have reported in a few case reports. Case summary We describe a case of CPB implementation with CytoSorb® in a haemodynamic unstable patient with prosthetic aortic valve endocarditis on apixaban therapy. What is new and conclusion CytoSorb® proved to be effective for removal of apixaban in emergency surgery setting by direct measurements of drug levels before and during CPB circulation.

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“…Furthermore, dabigatran plasma concentrations can be decreased by hemodialysis and plasma concentrations of xabans by hemoperfusion with Cytosorb filters during cardiopulmonary bypass. [143][144][145][146][147] SPECIFIC DRUGS FOR REVERSAL OF ANTICOAGULANTS For dabigatran reversal, a specific antidot is available. Idarucizumab, a humanized antibody fragment that specifically binds dabigatran with high affinity and reverses its effects within minutes.…”

Section: Thirdmentioning

confidence: 99%

Early Goal-Directed Hemostatic Therapy for Severe Acute Bleeding Management in the Intensive Care Unit: A Narrative Review

Crochemore,

Görlinger,

Lance

2023

Anesthesia &Amp; Analgesia

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This is a narrative review of the published evidence for bleeding management in critically ill patients in different clinical settings in the intensive care unit (ICU). We aimed to describe “The Ten Steps” approach to early goal-directed hemostatic therapy (EGDHT) using point-of-care testing (POCT), coagulation factor concentrates, and hemostatic drugs, according to the individual needs of each patient. We searched National Library of Medicine, MEDLINE for publications relevant to management of critical ill bleeding patients in different settings in the ICU. Bibliographies of included articles were also searched to identify additional relevant studies. English-language systematic reviews, meta-analyses, randomized trials, observational studies, and case reports were reviewed. Data related to study methodology, patient population, bleeding management strategy, and clinical outcomes were qualitatively evaluated. According to systematic reviews and meta-analyses, EGDHT guided by viscoelastic testing (VET) has been associated with a reduction in transfusion utilization, improved morbidity and outcome in patients with active bleeding. Furthermore, literature data showed an increased risk of severe adverse events and poor clinical outcomes with inappropriate prophylactic uses of blood components to correct altered conventional coagulation tests (CCTs). Finally, prospective, randomized, controlled trials point to the role of goal-directed fibrinogen substitution to reduce bleeding and the amount of red blood cell (RBC) transfusion with the potential to decrease mortality. In conclusion, severe acute bleeding management in the ICU is still a major challenge for intensive care physicians. The organized and sequential approach to the bleeding patient, guided by POCT allows for rapid and effective bleeding control, through the rational use of blood components and hemostatic drugs, since VET can identify specific coagulation disorders in real time, guiding hemostatic therapy with coagulation factor concentrates and hemostatic drugs with individual goals.

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In Vitro Apixaban Removal By CytoSorb Whole Blood Adsorber: An Experimental Study

Cited by 17 publications

References 34 publications

Removal of Apixaban during Emergency Cardiac Surgery Using Hemoadsorption with a Porous Polymer Bead Sorbent

Removal of Apixaban during Emergency Cardiac Surgery Using Hemoadsorption with a Porous Polymer Bead Sorbent

CytoSorb haemoadsorption for removal of apixaban—A proof‐of‐concept pilot case for a randomized controlled trial

Early Goal-Directed Hemostatic Therapy for Severe Acute Bleeding Management in the Intensive Care Unit: A Narrative Review

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