Intraoperative Off-Label Reversal of Apixaban by Andexanet Alfa while on VA-ECMO Immediately After Emergent Surgery for Acute Type A Aortic Dissection.

The authors report a case of intraoperative reversal of apixaban with andexanet alfa in a patient supported with venoarterial extracorporeal membrane oxygenation due to low- cardiac-output immediately after surgery for acute type A aortic dissection and massive intraoperative transfusion with administration of procoagulants. In this patient, andexanet alfa's off-label use was not associated with acute thrombotic complications despite being given during extracorporeal life support and after previous administration of prothrombin complex concentrates.

Anticoagulation Monitoring Under ECMO Support: A Comparative Study Between the Activated Coagulation Time and the Anti-Xa Activity Assay.

PURPOSE: Extra Corporeal Membrane Oxygenation (ECMO) is used in cases of severe respiratory and/or circulatory failure over periods of several days to several weeks. Its circuitry requires a closely monitored anticoagulation therapy that is empirically supported by activated clotting time (ACT)-a method often associated with large inter- and intraindividual variability. We aimed to compare the measurement of heparin activity with ACT and the direct measurement of the heparin activity (anti-Xa) in a large ECMO population. METHODS: All patients treated by venoarterial or venovenous ECMO in our intensive care unit between January 2014 and December 2015 were prospectively included. A concomitant measurement of the anti-Xa activity and ACT was performed on the same sample collected twice a day (morning-evening) for unfractionated heparin adaptation with an ACT target range of 180 to 220 seconds. RESULTS: One hundred and nine patients (men 69.7%, median age 54 years) treated with ECMO (70.6% venoarterial) were included. Spearman analysis found no correlation between anti-Xa and ACT (ρ < 0.4) from day 1 and worsened over time. Kappa analysis showed no agreement between the respective target ranges of ACT and anti-Xa. CONCLUSIONS: We demonstrate that concomitant measurement of ACT and anti-Xa activity is irrelevant in ECMO patients. Since ACT is poorly correlated with heparin dosage, anti-Xa activity appears to be a more suitable assay for anticoagulation monitoring.

Does proton pump inhibition change the on-treatment anti-Xa activity in xabans-treated patients with atrial fibrillation? A pilot study.

Proton pump inhibition (PPI) reduces gastrointestinal bleeding on direct oral anticoagulants. However, PPI may affect dabigatran on-treatment levels; and there is no information regarding the effect of PPI on xabans on-treatment activity. Thus, the aim of this study was to determine the impact of PPI on therapeutic anti-Xa activity in rivaroxaban- and apixaban-treated patients with atrial fibrillation (AF). This single-centre pilot prospective study enrolled 77 consecutive xabans-treated patients (42 rivaroxaban-treated and 35 apixaban-treated patients) with AF. PPI was administrated in 44 patients. Trough and peak anti-Xa activity was assessed with factor Xa-calibrated anti-Xa chromogenic analysis. There were no significant differences in trough anti-Xa activity comparing PPI-treated patients and patients without PPI (80.5 ± 66.5 ng/mL in PPI group vs. 71.6 ± 64.1 ng/mL in non-PPI group, p = 0.57, Table 2). Similarly, there were no significant differences in peak anti-Xa activity between compared groups (175.2 ± 102.5 ng/mL in PPI group vs. 202.9 ± 84.1 ng/mL in non-PPI group, p = 0.21). This pilot study did not reveal significant changes in xabans on-treatment anti-Xa activity according the PPI status.

Carbamazepine interaction with direct oral anticoagulants: help from the laboratory for the personalized management of oral anticoagulant therapy.

Current guidelines recommend caution in prescribing concomitant use of direct-acting oral anticoagulants (DOACs) and antiepileptic drugs due to drug-drug interactions leading to potential risk of DOACs subtherapeutic concentration and treatment failure. Herein we report a significant interaction between carbamazepine (CZP) and apixaban, causing subtherapeutic concentration of the drug in a patient with atrial fibrillation who had a transient ischemic attack (TIA) episode. Another anti-Xa DOAC, edoxaban, administered to the patient after TIA occurrence did not show significant interaction with CZP. In addition to confirm that cautions should be used when antiepileptic and DOACs are concomitantly prescribed, the present case also demonstrates that, in the management of certain subsets of patients who need anticoagulant treatment, measurement of DOAC plasma concentration can help guide a personalized management and avoid adverse clinical outcomes.

Apixaban: a novel agent to treat heparin induced thrombocytopenia and to prevent embolism in patient with atrial fibrillation after multiple valve replacement?

Very limited but promising experiences with the use of direct factor Xa inhibitors for the treatment of heparin-induced thrombocytopenia (HIT) have been reported. This contribution features our first experience with the use of apixaban (without a pre-treatment with parenteral anticoagulant) to treat a case of HIT which developed in a patient after multiple heart replacement surgery. Apixaban was effective, well tolerated and safe. An apixaban-calibrated chromogenic anti-Xa activity assessment was used to monitor apixaban activity throughout the therapy. Patient continued on apixaban for the prevention of thrombosis in the settings of atrial fibrillation. No ischemic or bleeding events occurred during the clinical follow up and the platelet count was stable. Our experience suggests that apixaban might be effectively used for the treatment of HIT and for the long-term prevention of embolism in patients after multiple valve replacement with biological prostheses and atrial fibrillation.

[Effectiveness and safety of selective and non - selective factor Xa inhibitors in antiphospholipid syndrome and systemic lupus erythematosus: anti - Xa - activity range].

The aim of the study was to evaluate the anti - Xa - activity (aXa) of selective and non - selective factor Xa inhibitors in patients with systemic lupus erythematosus (SLE) and antiphospholipid syndrome (APS) patients according to clinical implications and laboratory parameters. MATERIALS AND METHODS: Clinical and laboratory data were analyzed retrospectively in SLE and APS patients who protractedly received low weight molecular heparins (LWMH) and selective factor Xa inhibitors fondaparinux and rivaroxaban. The study included 70 patients in the middle age 39 [31; 43] years: 15/70 (21%) - with SLE, 10/70 (14%) - with APS and 45/70 (65%) - with SLE and APS (SLE+APS). All the patients received anticoagulants: 29 patients - nadroparin (98.3 [67.8; 129.5] IU/kg/day), 29 patients - fondaparinux (5 [5; 7.5] mg/day), 3 patients - enoxaparin (1.2 [0.8; 1.5] mg/day) and 9 patients - rivaroxaban (20 mg/day). All the patients signed informed consents. RESULTS: aXa therapeutic range of 0.1-1.5 IU/ml was found in 43/70 (61%) patients, low aXa - in 14/70 (20%) and high aXa - in 13/70 (19%) patients. Patients with low aXa underwent anticoagulant dose correction. There were not any major bleedings and thrombosis relapses in the study. Increased aXa was more common in patients, who took fondaparinux (31%), than in those, who took nadroparin (7%) and rivaroxaban (23%), p=0.02. Patients with enoxaparin had normal aXa range. In the absence of bleeding in SLE and APS patients, received anticoagulants in standardized therapeutic dose, the next factors influenced the aXa range excess: valvular heart disease (VHD) with the 3rd stage of mitral valve insufficiency as a result of aseptic Libman-Sacks endocarditis (odds ratio - OR 9.02, 95% confidential interval - CI [1.53; 53.12], p=0.015), peripheral artery disease in analogy with arteritis obliterans (AO) (OR 6.86, 95% CI [1.25; 37.71], p=0.027), and also triple - positivity of all types of antiphospholipid antibodies (OR 4.93, 95% CI [1.11; 21.99], p=0.036). According to found logistic regression model, aXa range excess risk can be prognosticated by the next formula: Z = -3.98 + 2.2 × VHD (yes-1/no-0) + 1.9 × AO (yes-1/no-0) + 1.6 × Triple - positivity (yes-1/no-0). Classified function value Z=0.39 defines the patients group with aXa range excess. Thus the value Z>0.39 indicates aXa range excess in the absence of bleeding, herewith sensibility is of 77% and specificity is 86%, positive prognostic value is 84.3%. CONCLUSION: In SLE and APS patients the next clinical and immunologic manifestations influenced the aXa therapeutic range excess: peripheral artery disease in analogy with AO, earlier aseptic Libman-Sacks endocarditis with the 3rd stage of mitral valve insufficiency and triple - positivity of all types of antiphospholipid antibodies, that does not need LWMH and fondaparinux dose correction. In contrast, anticoagulant dose reduction can cause clinical symptoms progression. Therapeutic aXa range in such patients should be extended.

Lean body weight is the best scale for venous thromboprophylaxis algorithm in severely obese patients undergoing bariatric surgery.

Severely obese patients undergoing bariatric surgery (BS) are at increased risk for venous thromboembolism (VTE). How standard low molecular weight heparin (LMWH) regimen should be adapted to provide both sufficient efficacy and safety in this setting is unclear. We aimed to compare the influence of four body size descriptors (BSD) on peak anti-Xa levels in BS obese patients receiving LMWH fixed doses to identify which one had the greatest impact. One hundred and thirteen BS obese patients [median body mass index (BMI), 43.3 kg/m2 (IQR, 40.6-48.7 kg/m2)] receiving subcutaneous dalteparin 5000 IU twice daily were included in this prospective monocenter study. Peak steady-state anti-Xa levels were measured peri-operatively following thromboprophylaxis initiation. Only 48% of patients achieved target anti-Xa levels (0.2-0.5 IU/ml). In univariate analysis, age, gender, total body-weight (TBW), lean body-weight (LBW), ideal body-weight (IBW), BMI and estimated glomerural filtration rate (eGFR) were associated with anti-Xa levels. The strongest negative association was observed with LBW (r = -0.56, p < .0001). Receiver operating characteristic curves indicated that among BSD, LBW (cut-off >55.8 kg) had the highest sensitivity (73%) and specificity (69%) to predict sub-prophylactic anti-Xa levels. In multivariate analysis, LBW and eGFR remained associated with anti-Xa levels (ß = -0.47 ±â€¯0.08, p < .0001 and ß = -0.19 ±â€¯0.08; p = .02, respectively). In BS morbidly obese patients receiving LMWH for thromboprophylaxis after BS, LBW and eGFR are the main determinants of anti-Xa level, and could be proposed in LMWH-based thromboprophylaxis dosing algorithms. The efficacy of a LBW-scale based dosing algorithm for optimal VTE prevention deserves further prospective randomized trials.

Anti-Xa Activity and Event Risk in Patients With Direct Factor Xa Inhibitors Initiated Early After Stroke.

BACKGROUND: Measuring anti-Xa activity (AXA) has been reported as useful for predicting future risk of hemorrhagic and ischemic events in stroke patients taking direct factor Xa inhibitors. We evaluated AXA levels of rivaroxaban or apixaban in acute stroke patients with non-valvular atrial fibrillation. Methods and Results: This was a single-center, prospective, observational study. Consecutive patients with acute ischemic stroke or transient ischemic attack who were admitted within 7 days of onset and started taking rivaroxaban or apixaban for NVAF between January 2012 and April 2017 were enrolled. AXA was measured at 2 time points: just before (AXAtrough) and 4 h after (AXApeak) taking rivaroxaban or apixaban on the 2nd day or later of administration. Of 156 patients taking rivaroxaban, hemorrhagic events occurred in 13. Patients with hemorrhagic events had higher AXApeak than those without [median (interquartile range): 1.93 (1.11-3.75) vs. 1.35 (0.80-2.00) IU/mL; P<0.01]. Multivariable-adjusted Cox models showed that AXApeak was independently related to the incidence of hemorrhagic events. Of 169 patients taking apixaban, hemorrhagic events occurred in 11. Patients with hemorrhagic events had higher AXAtrough [2.78 (1.90-3.53) vs. 1.42 (0.93-2.08) IU/mL, P<0.01] and AXApeak [4.05 (3.44-4.72) vs. 2.43 (1.79-3.35) IU/mL, P<0.01] than those without. Both AXAtrough and AXApeak were independently related to the incidence of hemorrhagic events. CONCLUSIONS: In these patients who started rivaroxaban or apixaban early after stroke, AXA levels in the early period were related to future hemorrhagic events.

Pharmacokinetic and Tissue Distribution of Fucoidan from Fucus vesiculosus after Oral Administration to Rats.

Fucus vesiculosus L., known as bladderwrack, belongs to the brown seaweeds, which are widely distributed throughout northern Russia, Atlantic shores of Europe, the Baltic Sea, Greenland, the Azores, the Canary Islands, and shores of the Pacific Ocean. Fucoidan is a major fucose-rich sulfated polysaccharide found in Fucus (F.) vesiculosus. The pharmacokinetic profiling of active compounds is essential for drug development and approval. The aim of the study was to evaluate the pharmacokinetics and tissue distribution of fucoidan in rats after a single-dose oral administration. Fucoidan was isolated from F. vesiculosus. The method of measuring anti-activated factor X (anti-Xa) activity by amidolytic assay was used to analyze the plasma and tissue concentrations of fucoidan. The tissue distribution of fucoidan after intragastric administration to the rats was characterized, and it exhibited considerable heterogeneity. Fucoidan preferentially accumulates in the kidneys (AUC0–t = 10.74 µg·h/g; Cmax = 1.23 µg/g after 5 h), spleen (AUC0–t = 6.89 µg·h/g; Cmax = 0.78 µg/g after 3 h), and liver (AUC0–t = 3.26 µg·h/g; Cmax = 0.53 µg/g after 2 h) and shows a relatively long absorption time and extended circulation in the blood, with a mean residence time (MRT) = 6.79 h. The outcome of this study provides additional scientific data for traditional use of fucoidan-containing plants and offers tangible support for the continued development of new effective pharmaceuticals using fucoidan.

Comparison of three different anti-Xa assays in major orthopedic surgery patients treated with direct oral anticoagulant.

BACKGROUND: Measurement of edoxaban plasma concentration has been gathering attention in major orthopedic surgery patients receiving edoxaban for the prevention of venous thromboembolism (VTE). METHODS: The anti-Xa activity was measured one hour after edoxaban intake using 3 different assays in 200 patients after major orthopedic surgery. RESULTS: The anti-Xa activities on Day 8 were significantly higher than those on Day 4 and those on Day 4 were significantly higher than those on Day 1. The anti-Xa activities in two assays closely correlated with each other, but the other anti-Xa assay did not correlated with other two assays. The anti-Xa activities as detected in the three Xa assays were significantly higher in the patients without deep vein thrombosis (DVT) than in those with DVT on Day 4. Additionally, there were no significant differences in the anti-Xa activities of assays A, B and C between patients with and without massive bleeding (MB) on Days 1, 4, 8 and 15. CONCLUSION: The results of this study suggest that anti-Xa level could be predictive of the risk of VTE, but not of the risk of massive bleeding.

Correlation between activated partial thromboplastin time and anti-Xa activity in patients who received low-molecular weight heparin as anticoagulation for haemodialysis.

Plasma anti-Xa activity, the recommended test to monitor low-molecular weight heparin (LMWH) therapy, is not readily available in many laboratories. In our clinical trials on the use of LMWH as anticoagulation for haemodialysis, a consistent prolongation of APTT in addition to the elevated anti-Xa activity was observed in the patients after LMWH administration. Hence, the paired anti-Xa activity and APTT data were re-analyzed. The APTT ratio, which was the proportional change in APTT from the baseline value after LMWH administration, was found to have a strong correlation with anti-Xa activity (coefficient of determination, R 2 = 0.72, P < 0.001). In the receiver operating characteristic analysis, the APTT ratio was also found to be an excellent predictor of therapeutic anti-Xa activity ≧0.5 IU/mL (area under curve = 0.93, P < 0.001). The sensitivity was 88% and the specificity was 83.3% when an APTT ratio ≧1.4 was used as the cut point to predict the achievement of therapeutic anti-Xa activity. Our results illustrated that APTT is a potentially useful screening test to assess the degree of anticoagulation achieved by LMWH during haemodialysis, if the testing for plasma anti-Xa activity is not available.

The effect of immunoadsorption with the Immusorba TR-350 column on coagulation compared to plasma exchange.

BACKGROUND AND OBJECTIVES: Plasma exchange (PE) and immunoadsorption with the Immusorba TR-350 column (IA) are used to remove autoantibodies from plasma in acute neurological autoimmune disorders. The impact of IA on coagulation and on low molecular weight heparin (LMWH) levels in comparison with PE was investigated. PATIENTS AND METHODS: In five patients with neurological autoimmune disorders, coagulation parameters (global tests, coagulation factors) were measured before and after PE or IA (Part A). In five other patients under anticoagulation with LMWH, anti-Xa activity and global tests were measured before and after the treatments (Part B). RESULTS: After PE, coagulation factors were significantly reduced by 50-70%. After IA, a distinct reduction was observed for fibrinogen, but not for antithrombin and most of the other coagulation factors. Anti-Xa activity was reduced after PE (from 0.57 ± 0·10 to 0.13 ± 0.05 IU/ml) and almost unchanged after IA. CONCLUSION: It is advisable to discontinue or to reduce LMWH doses and to monitor coagulation parameters and anti-Xa activity after PE or IA to decide about further LMWH dosing.

Bedside monitoring of anticoagulation in chronic haemodialysis patients treated with tinzaparin.

BACKGROUND: During haemodialysis, anticoagulants are required to prevent clotting in the extracorporeal circuit. Low-molecular weight heparins (LMWH) are frequently used because of the ease of a single injection at the start of dialysis. Disadvantages of LMWH include the lack of a reliable bedside assay for measuring their anticoagulant effect. METHODS: We investigated a bedside test for LMWH activity. The relationship between anti-Xa (chromogenic assay) and Hemonox point-of-care assay was evaluated in 21 dialysis patients (12 men and 9 women) with a median age of 71 years, receiving tinzaparin at the start of a haemodiafiltration session. RESULTS: At the start, before tinzaparin administration, median (interquartile ranges) of Hemonox values were 74 (67-82) s. Thirty minutes after tinzaparin administration, Hemonox values were increased to 496 (360-736) s, followed by a decrease to 149 (135-301) s after 120 min, 102 (97-144) s after 180 min and 92 (83-100) s after 240 min. Corresponding anti-Xa activities were 0 (0-0), 1.12 (0.9-1.29), 0.74 (0.57-0.96), 0.47 (0.31-0.7) and 0.31(0.16-0.49) IU/mL. Hemonox values showed an exponential relation to anti-Xa levels. Interchangeability of tests was shown by Bland-Altman plot. CONCLUSION: Point-of-care Hemonox test is a valuable bedside method for monitoring anti-Xa activity in dialysis patients anticoagulated with tinzaparin.

Development and evaluation of PEGylated Enoxaparin: a novel approach for enhanced anti-Xa activity.

Enoxaparin (ENX) is one of the most widely prescribed low molecular weight heparin inprophylaxis and treatment of venous thromboembolism. In this study, Enoxaparin-PEG conjugate (P-ENX) was synthesized from Enoxaparin and polyethylene glycol (PEG) and evaluated for its potential for extended duration of action. The esterification of the carboxyl groups of the drug moiety with the hydroxyl groups of mPEG-2000 was done by employing carbodiimide coupling chemistry. P-ENX conjugate was purified by dialysis and characterized by Fourier transform infrared spectroscopy (FTIR), Proton-Nuclear magnetic resonance ((1)H NMR) and matrix-assisted laser desorption/ionization (MALDI) mass analysis techniques. FTIR analysis revealed frequency of the carbonyl group in accord with ester linkage formation between the drug and the PEG moiety. (1)H NMR of the conjugate showed significant change in the chemical shift further indicative of ENX and PEG chemical interaction. In MALDI spectra, small peaks at 12,907 and 16,137 m/z confirmed the probability of conjugation of ENX and PEG. P-ENX exhibited considerable enhancement in anti-Xa activity (by three-folds) in comparison to free ENX. Further, an increase in AUC (over four-folds) was observed in P-ENX. Thus, PEGylation of ENX is a novel approach for extended and enhanced activity of ENX with a potential for decreased dosing frequency.

[Interference of oral anti-Xa anticoagulants during monitoring of unfractionated heparin treatments: practical and future attitudes]. / Interférence des anticoagulants oraux directs anti-Xa lors de la surveillance des traitements par héparine non-fractionnée : attitudes pratiques et à venir.

Contrary to direct oral anticoagulants (DOAC), unfractionated heparin (UFH) requires daily monitoring when administered at therapeutic dose. At present, UFH monitoring is preferably carried out by measuring plasma anti-Xa activity, however, in patients previously treated with an anti-Xa DOAC and switched to UFH, there is a high risk of DOAC interfering with the measurement of UFH anti-Xa activity. Residual anti-Xa DOAC in the sample can lead to an overestimation of the anticoagulant activity attributed to heparin and thus to incorrect anticoagulation. This risk of interference should not be overlooked because interference may occur even at concentration of DOAC below the hemostatic safety threshold and can last several days. To overcome this issue, several alternatives are being studied. This note provides an update on anti-Xa DOAC interference and different strategies available in current practice. It also underlines the importance of communication between biologists and clinicians on anticoagulant treatments received by patients.

DOAC-Remove to counteract the interference of anti-Xa oral anticoagulants on the monitoring of heparin.

INTRODUCTION: The monitoring of unfractionated heparin (UFH) by anti-factor Xa activity (AXA) is commonly used to ensure effective anticoagulation and prevent bleeding risk. However, in patients previously treated with an anti-Xa direct oral anticoagulant (DOAC) switching to UFH therapy, there is a risk of interference that may lead to inappropriate anticoagulation. The first objective of this study was to validate DOAC-Remove to remove DOAC for measuring UFH specific AXA. The second objective was to assess the length of DOAC interference on UFH monitoring and to identify potential predictive factors. MATERIALS AND METHODS: This monocentric retrospective study included all patients admitted from April 2019 to April 2021 previously treated with anti-Xa DOAC, and for whom an interference on UFH monitoring was suspected. Interference was defined as a difference in the AXA measured before and after using DOAC-Remove >2.8-fold standard deviation of the method. RESULTS: Removal with DOAC-Remove was specific of DOAC (apixaban n = 42, rivaroxaban n = 41, UFH n = 20) and sufficient to avoid interference on UFH AXA measurement. The exact interference length was 6.0 days [IQR 3.0-11.0] for apixaban (n = 26) and 4.5 days [IQR 2.0-5.8] for rivaroxaban (n = 20). Among the 89 patients sorted based on an interference length ≤ or >3 days, 74 (83.1%) presented an interference greater than 3 days. Correlations were observed with age for apixaban and creatinine for rivaroxaban. CONCLUSIONS: Our results suggest that DOAC-Remove could be of high interest in patients receiving UFH previously treated with an anti-Xa DOAC even if DOAC was stopped for more than 3 days.

Anti-Xa Activity Monitoring for Optimizing Rivaroxaban Dosage in Chinese Patients with Cerebral Venous Thrombosis.

BACKGROUND: Rivaroxaban, a direct Factor Xa inhibitor, is commonly used for cerebral venous thrombosis (CVT) correction. However, pharmacokinetic differences in Chinese may vary in sensitivity and tolerance, resulting in either insufficient or excessive anticoagulation. Herein, the optimizing dosages of rivaroxaban in Chinese patients with CVT were analyzed based on monitoring anti-Xa activity dynamically, to maintain therapeutic efficacy and reduce rivaroxaban-related bleeding. METHODS: A real-world cohort study was conducted involving 112 CVT patients in Xuanwu Hospital, from August 2021 through January 2024. Patients were grouped according to their doses of rivaroxaban use (5, 10, 15, and 20 mg daily) based on dynamic plasma anti-Xa activity monitored using the chromogenic anti-Xa assay. Plasma levels of anti-Xa activity reached the therapeutic range, bleeding events and the dosage of rivaroxaban among these groups were analyzed. RESULTS: The ratios of the patients whose plasma anti-Xa levels reached the standard therapeutic level (0.3-0.7 IU/mL) between the cohorts less than 20 mg/d and 20 mg/d showed no statistical difference, and no significant disparities were observed among 5, 10, 15, and 20 mg/d dose groups. There was a discernible increase in the proportion of patients with bleeding events in the 20 mg/d group, even though the results did not reach a statistical difference. Meanwhile, in patients with bleeding events, their plasma anti-Xa levels could exceed 0.7 IU/mL. CONCLUSION: Sensitivity and tolerance to rivaroxaban in Chinese may vary. Individualized therapy dosage under the guidance of anti-Xa activity monitoring may not only guarantee anticoagulation effect, but also reduce rivaroxaban-related bleeding events.

[Use of heparin calibrated anti-Xa assay for apixaban and rivaroxaban measurement in the context of regional telestroke activity]. / Estimation de la concentration en apixaban et en rivaroxaban par l'activité anti-Xa héparine en contexte d'activité régionale de télé-AVC.

INTRODUCTION: In Bordeaux University Hospital, neurologists are required to prescribe thrombolysis using telemedicine (telethrombolysis) for anticoagulated stroke patients admitted in peripheral centers in the Nouvelle-Aquitaine region. However, due to the bleeding risk, the maximum concentration of DOAC authorizing thrombolysis is 30, 50 or 100 ng/mL (depending on the sources and the patient-specific benefit-risk ratio). Most of the time, specific assays of Direct Oral Anticoagulants (DOACs) are not available in these peripheral centers. We therefore studied an alternative test: the Unfractionated Heparin (UFH) anti-Xa activity which is available in most laboratories and could be used to estimate the DOAC concentration. METHODS: Five centers were included in our study: three centers using the Liquid Anti-Xa HemosIL® Werfen reagent and two centers using the STA-Liquid Anti-Xa® Stago reagent. For each reagent, we established correlation curves between DOAC and UFH anti-Xa activities and determinated UFH cut-offs for the thresholds of 30, 50 and 100 ng/mL respectively. RESULTS: A total of 1455 plasmas were tested. There is an excellent correlation between DOAC and UFH anti-Xa activities using a third-degree modeling curve, independently the reagent used. However, a significant inter-reagent variability is observed concerning the obtained cut-offs. CONCLUSION: Our study makes unsuitable the use of a universal cut-off. In opposition to recommendations made by other publications, the UFH cut-offs must be adapted to the reagent used locally by the laboratory, and to the considered DOAC.

Weight-adjusted dosing of tinzaparin for thromboprophylaxis in obese medical patients.

Background: The optimal dose of tinzaparin for prophylaxis in obese medical patients is not well defined. Objectives: To evaluate the anti-Xa activity in obese medical patients on tinzaparin prophylaxis adjusted for actual bodyweight. Methods: Patients with a body mass index of ≥30 kg/m2 treated with 50 IU/kg tinzaparin once daily were prospectively included. Anti-Xa and anti-IIa activity; von Willebrand factor antigen and von Willebrand activity; factor VIII activity; D-dimer, prothrombin fragments; and thrombin generation were measured 4 hours after subcutaneous injection between days 1 and 14 after the initiation of tinzaparin prophylaxis. Results: We included 121 plasma samples from 66 patients (48.5% women), with a median weight of 125 kg (range, 82-300 kg) and a median body mass index of 41.9 kg/m2 (range, 30.1-88.6 kg/m2). The target anti-Xa activity of 0.2 to 0.4 IU/mL was achieved in 80 plasma samples (66.1%); 39 samples (32.2%) were below and 2 samples (1.7%) above the target range. The median anti-Xa activity was 0.25 IU/mL (IQR, 0.19-0.31 IU/mL), 0.23 IU/mL (IQR, 0.17-0.28 IU/mL), and 0.21 IU/mL (IQR, 0.17-0.25 IU/mL) on days 1 to 3, days 4 to 6, and days 7 to 14, respectively. The anti-Xa activity did not differ among the weight groups (P = .19). Injection into the upper arm compared to the abdomen resulted in a lower endogenous thrombin potential, a lower peak thrombin, and a trend to a higher anti-Xa activity. Conclusion: Dosing of tinzaparin adjusted for actual bodyweight in obese patients achieved anti-Xa activity in the target range for most patients, without accumulation or overdosing. In addition, there is a significant difference in thrombin generation depending on the injection site.