Use of direct oral anticoagulants in ICU patients. Part II – Clinical evidence

Wahab, Abdul; Patnaik, Rupali; Gurjar, Mohan

doi:10.5114/ait.2021.110608

Cited by 4 publications

(3 citation statements)

References 82 publications

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“…Critically ill patients often receive anticoagulants to prevent thrombosis, and even if they had been taking a direct oral anticoagulant (thrombin, or factor Xa inhibitor) before hospitalization, low molecular-weight heparin is the preferred anticoagulant in intensive care units ( 36 ). In addition to their anticoagulant action, heparins are known to neutralize certain histone-mediated toxic effects and might reduce mortality among septic patients ( 37 – 39 ).…”

Section: Discussionmentioning

confidence: 99%

DNA and histones impair the mechanical stability and lytic susceptibility of fibrin formed by staphylocoagulase

Komorowicz,

Farkas,

Szabó

et al. 2023

Front. Immunol.

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BackgroundStaphylocoagulase (SCG) is a virulence factor of Staphylococcus aureus, one of the most lethal pathogens of our times. The complex of SCG with prothrombin (SCG/ProT) can clot fibrinogen, and SCG/ProT-induced fibrin and plasma clots have been described to show decreased mechanical and lytic resistance, which may contribute to septic emboli from infected cardiac vegetations. At infection sites, neutrophils can release DNA and histones, as parts of neutrophil extracellular traps (NETs), which in turn favor thrombosis, inhibit fibrinolysis and strengthen clot structure.ObjectivesTo characterize the combined effects of major NET-components (DNA, histone H1 and H3) on SCG/ProT-induced clot structure, mechanical and lytic stability.MethodsRecombinant SCG was used to clot purified fibrinogen and plasma. The kinetics of formation and lysis of fibrin and plasma clots containing H1 or core histones+/-DNA were followed by turbidimetry. Fibrin structure and mechanical stability were characterized with scanning electron microscopy, pressure-driven permeation, and oscillation rheometry.ResultsHistones and DNA favored the formation of thicker fibrin fibers and a more heterogeneous clot structure including high porosity with H1 histone, whereas low porosity with core histones and DNA. As opposed to previous observations with thrombin-induced clots, SCG/ProT-induced fibrin was not mechanically stabilized by histones. Similarly to thrombin-induced clots, the DNA-histone complexes prolonged fibrinolysis with tissue-type plasminogen activator (up to 2-fold). The anti-fibrinolytic effect of the DNA and DNA-H3 complex was observed in plasma clots too. Heparin (low molecular weight) accelerated the lysis of SCG/ProT-clots from plasma, even if DNA and histones were also present.ConclusionsIn the interplay of NETs and fibrin formed by SCG, DNA and histones promote structural heterogeneity in the clots, and fail to stabilize them against mechanical stress. The DNA-histone complexes render the SCG-fibrin more resistant to lysis and thereby less prone to embolization.

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Section: Discussionmentioning

confidence: 99%

DNA and histones impair the mechanical stability and lytic susceptibility of fibrin formed by staphylocoagulase

Komorowicz,

Farkas,

Szabó

et al. 2023

Front. Immunol.

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Section: Introductionmentioning

confidence: 99%

“…12,13 Expert opinion advises against the use of DOACs in the ICU population due to the deranged and unpredictable pharmacokinetics and suggests utilizing more conventional and familiar agents such as LMWH during ICU admission. 14,15 We undertook this project to the current prescribing practices of direct oral anticoagulants (continuation of the same agent, discontinuation of the DOAC without transition to another agent, and discontinuation of the DOAC with a transition to another agent) for ICU patients with prehospital use of DOACs and the associated clinical outcomes, including the incidence of major bleeding episodes and need for intervention (endoscopic, surgical, or interventional radiology guided), hospital, and ICU length of stay (LOS), and mortality (ICU and hospital).…”

Section: Introductionmentioning

confidence: 99%

Anticoagulation Prescribing Patterns in Intensive Care Unit Patients Admitted with Prehospital Direct Oral Anticoagulant Therapy: A Single Academic Center Experience

et al. 2022

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Objective:To describe the current prescribing practices of direct oral anticoagulants (DOACs) in intensive care unit (ICU) patients and the associated clinical outcomes, including the incidence of major bleeding episodes and the need for intervention (endoscopic, surgical, or interventional radiology guided). Design:Observational, retrospective chart review. Setting and Participants:Single large academic center study. Participants included patients with critical illness who were admitted to the intensive care units (ICU) at Mayo Clinic from January 1st, 2012, until May 4th, 2018. Adult ICU patients with a DOAC (apixaban, rivaroxaban, dabigatran, or edoxaban) listed as one of the active medications at the time of hospital admission were included. Results:37 249 patients in medical and surgical intensive care units were screened for the study period. After excluding patients who did not qualify, 558 unique encounters were included. The median age was 69 (IQR 59-78) years; most patients were male, white Caucasians, and had a median SOFA score of 4. After excluding the patients who had major bleeding episodes in the first 24 hours, 188 (39%) were continued on the same DOAC therapy, 204 (42%) were discontinued without transitioning to another agent, and 95 (20%) were transitioned to another agent. Finally, 410 (84%) were dismissed on DOAC therapy at the end of hospitalization. The difference in the continuation rate of the same DOAC agent beyond 24 hours, discontinuation without transition to an alternate agent, or discontinuation of DOAC with a transition to an alternate anticoagulation agent was not statistically significant ( P = .60). A total of 52 major bleeding events were identified. Gastrointestinal bleeding was the most common bleeding complication [n (%): 34 (65)], followed by intra-abdominal and peri-procedural bleeding [7 (13.5) and 7 (13.5)]. Thirty-three (65%) patients had a major bleeding complication requiring intervention. Conclusions:Our single-center retrospective study describes the current prescribing practices and preliminary outcomes in ICU patients with prehospital use of DOACs. Up to 20% of the patients were transitioned to a different agent within 24 hours of ICU admission, whereas a significant proportion of patients (42%) had anticoagulation discontinued altogether. Most patients who suffered a major bleeding episode required either endoscopic or surgical intervention to control bleeding.

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