ABSTRACT
Introduction Edoxaban is a non-vitamin K dependent oral anticoagulant (NOAC) licensed for venous thromboembolism (VTE) treatment or stroke prevention in atrial fibrillation (SPAF). Major surgical procedures are not uncommon in anticoagulated patients but data on perioperative edoxaban management are scarce. Method Using data from the prospective DRESDEN NOAC REGISTRY we extracted data on major surgical procedures in patients who took edoxaban within the preceding 7 days. Periinterventional edoxaban management patterns and rates of outcome events were evaluated until day 30 after procedure. Results Between 2011 and 2021, 3448 procedures were identified in edoxaban patients, including 287 (8.3 %) major procedures. Overall, patient characteristics were comparable for major and non-major procedures, but significant differences existed with regard to gender, concomitant antiplatelet therapies and the proportion of patients with a CHA2DS2-VASc score >= 2 (Table 1). Major procedures consisted of orthopaedic/trauma surgery (44.3 %);open pelvic, abdominal or thoracic surgery (30.4 %), central nervous system surgery and procedures (13.9 %), vascular surgery (9.1 %) and extensive wound revision surgery (2.4 %). A scheduled interruption of edoxaban was observed in 284/287 major procedures (99 %) with a total median edoxaban interruption time of 11.0 days (25- 75th percentile 5.0-18.0 days). Heparin bridging was documented in 183 procedures (46 prophylactic dosages, 111 intermediate and 26 therapeutic dosages). Overall, 7 (2.4 %;95 %-CI 1.2 %-4.9 %) major cardiovascular events (5 VTE, 2 arterial thromboembolic events) occurred and 63 bleeding events were observed in 287 major procedures (22.0 %;95 %-CI 17.6 %-2.71 %), comprising of 38 ISTH major bleeding events (13.2 %;95 %-CI 9.8 %-17.7 %) and 25 ISTH CRNM bleedings (8.7 %;95 %-CI 6.0 %-12.5 %). Rates of major cardiovascular events with or without heparin bridging were comparable (6/183;3.3 %;95 %-CI 1.5 %-7.0 % vs. 1/36;2.8 %;95 %-CI 0.5 %-14.2 %;p = 0.7173). ISTH major bleeding occurred numerically more frequent in patients receiving heparin bridging (30/183;16.4 %;95 %-CI 11.7 %-22.4 %) versus procedures without heparin bridging (2/36;5.6 %;95 %-CI 1.5 %-18.1 %;p = 0.1542) (Fig. 1). Within 30 days of follow up, 6 patients died (2.1 %;95 %-CI 1.0 %-4.5 %) with causes of death being a ruptured truncus coeliacus following palliative angioplasty for an infiltrating pancreas cancer (ruled as fatal bleeding), septic organ failure, pneumocystis jirovecii pneumonia, COVID-19-pneumonia, septic complications following clipping of a ruptured cerebrovascular aneurism or terminal malignant disease. No fatal cardiovascular event occurred. Conclusion Within the limitations of our study design, periprocedural edoxaban management seems effective and safe in routine care. Use of heparin bridging seems to have limited effects on reducing vascular events but may increase bleeding risk. (Table Presented).
ABSTRACT
Introduction Argatroban is indicated for treatment of heparin-induced thrombocytopenia, but is also used in critical ill COVID-19 patients presenting with extensive thrombin overload. Direct drug monitoring is not available and argatroban dosing is mainly based on activated partial plasmin time (aPTT), which has limitations in hypercoagulable patients with increased FVIII [1, 2]. The aim of this study was to compare correlation of routine clotting tests (aPTT, ecarin clotting time [ECA-CT] and diluted thrombin time [dTT]) [3] to argatroban plasma levels measured by gold standard mass spectrometry (LC/MS/MS). Method From 06/2021 to 03/2022, 205 samples from 22 COVID-19 ICU patients were analyzed: aPTT and dTT on STA R Max3-Analyzer (Stago Deutschland GmbH, Germany) using the BIOPHEN DTI Kit with Argatroban-calibration (CoaChrom Diagnostica GmbH, Austria);ECA-CT was measured using ClotPro ecarin assay. LC/MS/MS was performed using an RP column, a solvent gradient and an API4000 mass spectrometer with electrospray. Correlation was analyzed using Pearson correlation coefficient r in R version 3.2.4. This study was approved by the Ethics Committee of the Technical University of Dresden, Germany (BO-EK-64022022) and registered with German Clinical Trials Register DRKS00028689. Results From 205 samples with LC/MS/MS analysis, 195 were compared to aPTT, 153 to ECA-CT and 105 to dTT. In 40 samples, dTT was not measureable due high bilirubin values. Compared to LC/MS/MS, correlation of dTT was highest (r = 0.924), followed by ECA-CT (r 0.609) and aPTT (r 0.367;p < 0.001;Fig. 1). When recommended cut-offs for argatroban plasma levels (500-1000 ng/ml according to SmPC) were applied, dTT (when measurable) and ECA-CT better identified critical values of argatroban plasma values > 1000ng/ml than aPTT (Fig. 2). Conclusion Argatroban in critical ill COVID-19 patients should be monitored using dTT. If dTT is not possible or measurements are highly time-sensitive, point-of-care ClotPro ECA-test should be preferably used instead of aPTT. (Table Presented).
ABSTRACT
Introduction Anticoagulation is indicated for the prevention or therapy of thromboembolic events, but remains highly challenging considering the high risk of bleeding events in critically ill patients.Unfractionated heparin (UFH) is widely used as preferred anticoagulation for patients on intensive care units (ICU) due to its beneficial short half time and fast elimination. For monitoring of UFH, activated partial thromboplastin time (aPTT) is mainly used, but aPTT can be misleading in both directions [1]. While high factor VIII plasma values may decrease aPTT, a reduced factor XII under extracorporal circulation may prolong aPTT that no longer correlates to anticoagulation intensity [2]. Anticoagulation monitoring using specific UFH calibrated anti-Xa levels is an established alternative to overcome aPTT limitations but is rarely available 24/7 [3, 4]. Using point-of-care (POC) viscoelastic testing (VET) [5] with a specific ratio between clotting time (CT) in intrinsic test (IN-test) compared to heparinase test (HI-test) - which includes the inactivation of heparin in the probe - might help to determine the UFH effect in critically ill patients [6]. Method From 09/2020 to 07/2022, 467 samples from 120 adult ICU patients receiving UFH therapy were prospectively collected. Samples for aPTT, anti-Xa measurement and POC VET using ClotPro (Haemonetics, Boston, Massachusetts, USA) were simultaneously collected. Measurement for aPTT (C.K. Prest) and anti-Xa (Liquid AntiXa) were performed using STA R Max 3 device (Stago Deutschland GmbH, Dusseldorf). Correlation was analyzed using Kruskal-Wallis test in SPSS version 27 and R version 3.2.4. This study was approved by the local Ethics Committee at the Technische Universitat Dresden, Germany (BOEK- 374072021) and registered with the German Clinical Trials Register DRKS00028689. Results 467 samples under UFH treatment were included in this analysis, the majority of these patients were treated for COVID-19 associated acute distress syndrome. According to our institutional guidelines, anti-Xa target levels for UFH were set at 0.3-0.5 IE/ml for standard high-risk prophylaxis and 0.5-0.7 IE/ ml for therapeutic anticoagulation therapy with values < 0.3 and > 0.7 being defined as under- or over-treatment. Table 1 presents the median aPTT and CT IN/HI ratio values for patients within these anti-Xa categories. CT IN/HI ratio correlation to anti-Xa levels was considerably better than aPTT correlation (Tab. 1). Notably, aPTT could not exactly discriminate between patients receiving UFH dosages correlating to high-risk prophylaxis or therapeutic anticoagulation. Conclusion Whole blood POC VET using a specific heparinase-approach (IN/ HI ratio) is superior to aPTT in detecting patients in or out of targeted anti-Xa levels. POC VET should be made available for ICUs as bedside test and might help to guide anticoagulation management in critical ill patients, being faster and potentially more widely available than lab-based anti-Xa testing (Fig. 1). (Table Presented).
ABSTRACT
Preliminary data and clinical experience have suggested an increased risk of abnormal uterine bleeding (AUB) in women of reproductive age treated with anticoagulants, but solid data are lacking. The TEAM-VTE study was an international multicenter prospective cohort study in women aged 18 to 50 years diagnosed with acute venous thromboembolism (VTE). Menstrual blood loss was measured by pictorial blood loss assessment charts at baseline for the last menstrual cycle before VTE diagnosis and prospectively for each cycle during 3 to 6 months of follow-up. AUB was defined as an increased score on the pictorial blood loss assessment chart (>100 or >150) or self-reported AUB. AUB-related quality of life (QoL) was assessed at baseline and the end of follow-up using the Menstrual Bleeding Questionnaire. The study was terminated early because of slow recruitment attributable to the COVID-19 pandemic. Of the 98 women, 65 (66%) met at least one of the 3 definitions of AUB during follow-up (95% confidence interval [CI], 57%-75%). AUB occurred in 60% of women (36 of 60) without AUB before VTE diagnosis (new-onset AUB; 95% CI, 47%-71%). Overall, QoL decreased over time, with a mean Menstrual Bleeding Questionnaire score increase of 5.1 points (95% CI, 2.2-7.9), but this decrease in QoL was observed only among women with new-onset AUB. To conclude, 2 of every 3 women who start anticoagulation for acute VTE experience AUB, with a considerable negative impact on QoL. These findings should be a call to action to increase awareness and provide evidence-based strategies to prevent and treat AUB in this setting. This was an academic study registered at www.clinicaltrials.gov as #NCT04748393; no funding was received.