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Background: Life-long vitamin K antagonist (VKA) therapy is recommended as a standard of care in antiphospholipid syndrome (APS) patients with thrombosis. Concerns have been raised about the validity of international normalized ratio (INR) measurements in lupus anticoagulant (LA)-positive APS patients because LA may interfere with phospholipid-dependent coagulation tests and could elevate INR measurements. Objectives: Here, we aimed to determine the interference of antigen-specific monoclonal and isolated patient antibodies with LA activity on INR measurements. Methods: Pooled normal plasma and control plasma from patients on VKA (without LA) were incubated with monoclonal and isolated patient immunoglobulin G antiprothrombin and anti–beta-2-glycoprotein I antibodies that express LA activity. INR was determined before and after addition using 3 laboratory assays (Owren STA-Hepato Prest, Quick STA-NeoPTimal, and Quick STA-Neoplastine R) and 1 point-of-care test device (CoaguChek Pro II). Results: Antiprothrombin and anti–beta-2-glycoprotein I antibodies with LA activity interfered with recombinant human thromboplastin reagents (Quick STA-Neoplastine R and CoaguChek Pro II), particularly when added to plasma of VKA-treated controls. This effect was most evident on point-of-care test INR measurements, while the recombinant Quick reagent exhibited a lesser degree of interference. In contrast, tissue-derived thromboplastin reagents (Owren STA-Hepato Prest and Quick STA-NeoPTimal) remained largely unaffected by these antibodies, both in pooled normal plasma and VKA anticoagulated control plasma. Among these reagents, the Owren INR reagent exhibited the lowest sensitivity to the influence of LA antibodies. This observed difference in sensitivity is independent of the plasma dilution factor or the presence of factor V or fibrinogen in Owren reagent. Conclusion: INR reagents that utilize recombinant human thromboplastin are more sensitive to the presence of monoclonal and patient-derived antibodies with LA activity. Consequently, APS patients positive for LA should be monitored using tissue-derived thromboplastin reagents, given its reduced susceptibility to interference by LA-causing antibodies.

Background: The risk of adults with a congenital heart defect (ACHD) developing heart failure, stroke, arrhythmias, and the need for valve replacement is increased compared to healthy peers. Evidence for the use of novel oral anticoagulants (NOAC) in this patient group is still lacking and vitamin K antagonists (VKA) are the primary choice for patients with a mechanical valve. The present aim was to determine the rate of thromboembolic and major bleeding events in ACHD patients on VKA therapy. Methods: This was a retrospective study on ACHD patients on VKA treatment registered in the National Quality Registry for Congenital Heart Disease, SWEDCON, and Atrial fibrillation and Anticoagulation, AuriculA, from Southern Sweden. Results: 213 patients were included with a mean age of 50 years (±18) years and a mean follow-up of 6.6 years (±3.3 years), 16% had complex defects and 41% had valvular VKA therapy indication. In total, 34 complications were registered, of which 14 were thromboembolic events and 20 were major bleeding events. The rate of thromboembolism and major bleeding events was 1.0 (95% CI: 0.6–1.6) and 1.4 (95% CI: 0.9–2.2) per 100 patient-years, respectively. Forty-three patients died during the study period. The mortality rate was 3.1 per 100 patient-years (95% CI: 2.2–4.1). Conclusion: We found a low rate of thromboembolic events and major bleeding events for low-moderate risk ACHD patients with good quality of VKA anticoagulation. The target of TTR>65% for ACHD patients is recommended.

Background: Vitamin K (VK) deficiency (VKD) impairs γ-carboxylation of VK-dependent factors (VKDFs), resulting in higher factor (F)II levels measured by Ecarin (FIIE) reagents (that convert des-γ-carboxylated FII to meizothrombin) than by prothrombin time (FII) reagents., Objectives: To evaluate FII/FIIE abnormalities among patients assessed for coagulopathies and identify findings predictive of coagulopathy improvement after VK., Methods: We retrospectively assessed consecutive cases from 2002 to 2021 with FII/FIIE tests and the sensitivity and specificity of FII/FIIE ratios and FIIE-FII differences for VKD defined as international normalized ratio correction/improvement of ≥0.5 after VK., Results: Two hundred ninety-two patients (males, 58.2%; adults, 85.6%; median age, 73 years) were evaluated (84.2% hospitalized, 48.3% in intensive care, 71.6% with active liver disease, and 28% deceased at discharge) and 25% to 38% had FII/FIIE findings suggestive of VKD. Among 170 patients assessed for response to VK, FII/FIIE ratios of ≤0.84 to 0.91 and FIIE-FII differences of >0.04 U/mL had similar modest sensitivity (47.7%-69.3%) and modest to good specificity (67.1%-91.5%) for VKD. FII/FIIE ratios of <0.86, suggestive of VKD (sensitivity, 47.7%; specificity, 90.2%), were more common in patients deficient in only VKDF (P = .0001), but were detected in 16% with non-VKDF deficiencies. Low FIIE was commonly associated with active liver disease (P = .0002). Patients with and without probable VKD (based on FII/FIIE ratios of <0.86) had similar mortality, bleeding, and rates of prothrombin complex concentrate and red cell transfusions (P ≥ .78), but fewer with probable VKD received plasma and fibrinogen replacement (P ≤ .024)., Conclusion: FII/FIIE comparison aids the diagnosis of VKD and predicts clinical responses to VK treatment among patients with coagulopathies., Competing Interests: Declaration of competing interests There are no competing interests to disclose., (Copyright © 2024 The Author(s). Published by Elsevier Inc. All rights reserved.)

Introduction: Warfarin is the core component in the management of various thromboembolic disorders, which requires specialized expertise to optimize outcomes. There is limited data comparing a pharmacist vs. a haematologist-managed anticoagulation clinic in our setting, and in the Middle East. We aimed to evaluate the effectiveness and safety of a pharmacist vs. a haematologist-managed anticoagulation clinic in the Ambulatory Care Center at King Abdulaziz Medical City, Jeddah, Saudi Arabia. Methods: A retrospective cohort study was conducted from 2016 to 2018, which included adult patients who have been followed-up for at least six months and who received warfarin for an extended period. The primary outcome was the proportion of time the patients in the two arms were in the therapeutic range. The secondary outcomes were the differences in expanded time in the therapeutic range, as well as the frequency of bleeding and thromboembolic events between the two arms. Results: We enrolled 104 and 124 patients in the pharmacist and haematologist arms respectively. The median time in the therapeutic range for the pharmacist arm was 71.4%, IQR (60.8–83.8) vs. 65%, IQR (43.5–79.1), in the haematologist arm (p = 0.0049). The median expanded time in the therapeutic range was 86.4%, IQR (77.5–95.3) vs. 81.21%, IQR (67.1–93.3) in the pharmacist vs. haematologist arm (p = 0.015) respectively. Major bleeding events occurred in 5.7 % vs. 3.2 %, and thromboembolic events in 5.7% vs. 4%, in the pharmacist vs. haematologist arm respectively. Conclusions: Our results demonstrated that the time in the therapeutic range was significantly higher in the pharmacist arm, with no significant difference in bleeding and thromboembolic events compared to the haematologist arm.

Abstract Background The optimal prophylactic preprocedural management of patients with coagulopathy due to liver disease is not known. Objectives Our objective was to compare the efficacy and safety of fresh frozen plasma (FFP) with prothrombin complex concentrate (PCC) in the preprocedural management of patients with coagulopathy of liver disease. Methods We conducted a systematic review to examine published evidence regarding treatment with FFP or PCC in adults with coagulopathy of liver disease undergoing an invasive procedure. Direct comparisons and single‐arm studies were eligible. Efficacy outcomes included major bleeding, mortality, and correction of prothrombin time (PT) and/or international normalized ratio (INR). Safety outcomes included thrombosis and transfusion‐related complications. Results A total of 95 articles were identified for full‐text review. Nine studies were eligible and included in the review. No randomized trials comparing FFP versus PCC were identified. Only two studies directly compared FFP versus PCC. In these studies, PCC appeared to result in higher rates of correction of PT/INR, but bleeding outcomes were not different. In the single‐arm studies, bleeding events appeared low overall. Volume overload was the most common recorded adverse event in patients receiving FFP. Thromboembolic events occurred rarely, but exclusively in the PCC group. Due to heterogeneity in study definitions and bias, meta‐analysis was not possible. Our study found no evidence to favor a specific product over another. Conclusions Insufficient data exist on the effects of FFP versus PCC administration before invasive procedures in patients with coagulopathy of liver disease to make conclusions with respect to relative efficacy or safety.

Abstract Recognizing the complexity of coagulation tests and currently used anticoagulants, we developed this illustrated review on bleeding assessment tools and common coagulation screening tests. Quantitative bleeding assessment tools (BATs) are available to standardize the bleeding history and improve the pretest probability prior to coagulation testing. We describe use of BATs and the principles, indications, and limitations of the prothrombin time (PT)/International Normalized Ratio, activated partial thromboplastin time (APTT), and 50:50 mix. Use of these tests to identify coagulation factor deficiencies, specific and nonspecific inhibitors, coagulopathy of liver disease, disseminated intravascular coagulation, and commonly used anticoagulant medications are reviewed. Current literature suggests that unnecessary coagulation testing is rampant. The PT and APTT have astoundingly low sensitivity (1.0%‐2.1%) for detection of clinically significant bleeding disorders. Thus, current guidelines recommend against the use of screening PT and APTT in preoperative patients undergoing noncardiac/vascular surgery.

Abstract Background In patients with a venous outflow obstruction following iliofemoral deep vein thrombosis stenting of the venous tract to prevent or alleviate postthrombotic syndrome is applied with increasing frequency. The impact of the quality of anticoagulant therapy with vitamin K antagonists (VKAs) on the development of in‐stent thrombosis is currently unknown. Objectives To determine the association between the quality of postinterventional VKA treatment and the occurrence of in‐stent thrombosis. Methods Seventy‐nine patients with iliofemoral and/or caval venous stent placement for obstruction of the venous outflow were included in this study. All patients received postinterventional VKA. The quality of VKA anticoagulant therapy was expressed as the time within therapeutic range (TTR) calculated using the linear interpolation method and as the proportion of International Normalized Ratio (INR) values

Background: The effect of the vitamin K antagonist acenocoumarol on coagulation needs to be reversed when patients undergo an invasive procedure with considerable bleeding risk. A strategy to achieve this is by administering oral vitamin K before a procedure while continuing acenocoumarol., Objectives: To assess the effect on periprocedural international normalized ratio (INR) values and safety using oral vitamin K as anticoagulant reversal method., Methods: In this prospective cohort study, consecutive patients using acenocoumarol undergoing elective procedures between 2019 and 2022 were included. According to standard of care in our hospital, patients took 10 mg oral vitamin K 36 to 48 hours before the procedure while continuing their normal use of acenocoumarol. Effectiveness to lower INR to <1.8 preprocedural was assessed. Bleeding and thrombotic complications within 30 days after the procedure were assessed. Periprocedural course of INR was monitored by collecting additional blood samples., Results: Seventy-four patients were included for analysis. On the day of the procedure, an adequate INR of <1.8 was achieved in 99% of patients. One clinically relevant nonmajor bleeding complication and no thrombotic complications were observed during the first 30 days after the procedure. INR gradually restored to therapeutic level during the days after the procedure., Conclusion: Using oral vitamin K while patients continue acenocoumarol intake is an effective way to adequately lower INR before an invasive procedure. Low amount of bleeding complications and absence of thromboembolic complications suggest that this is a safe strategy. The INR values returned gradually to therapeutic range after the procedure, probably contributing to the observed low bleeding rate., Competing Interests: Declaration of competing interests The authors state that they have no conflicts of interest., (Copyright © 2024 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Background: Life-long vitamin K antagonist (VKA) therapy is recommended as a standard of care in antiphospholipid syndrome (APS) patients with thrombosis. Concerns have been raised about the validity of international normalized ratio (INR) measurements in lupus anticoagulant (LA)-positive APS patients because LA may interfere with phospholipid-dependent coagulation tests and could elevate INR measurements., Objectives: Here, we aimed to determine the interference of antigen-specific monoclonal and isolated patient antibodies with LA activity on INR measurements., Methods: Pooled normal plasma and control plasma from patients on VKA (without LA) were incubated with monoclonal and isolated patient immunoglobulin G antiprothrombin and anti-beta-2-glycoprotein I antibodies that express LA activity. INR was determined before and after addition using 3 laboratory assays (Owren STA-Hepato Prest, Quick STA-NeoPTimal, and Quick STA-Neoplastine R) and 1 point-of-care test device (CoaguChek Pro II)., Results: Antiprothrombin and anti-beta-2-glycoprotein I antibodies with LA activity interfered with recombinant human thromboplastin reagents (Quick STA-Neoplastine R and CoaguChek Pro II), particularly when added to plasma of VKA-treated controls. This effect was most evident on point-of-care test INR measurements, while the recombinant Quick reagent exhibited a lesser degree of interference. In contrast, tissue-derived thromboplastin reagents (Owren STA-Hepato Prest and Quick STA-NeoPTimal) remained largely unaffected by these antibodies, both in pooled normal plasma and VKA anticoagulated control plasma. Among these reagents, the Owren INR reagent exhibited the lowest sensitivity to the influence of LA antibodies. This observed difference in sensitivity is independent of the plasma dilution factor or the presence of factor V or fibrinogen in Owren reagent., Conclusion: INR reagents that utilize recombinant human thromboplastin are more sensitive to the presence of monoclonal and patient-derived antibodies with LA activity. Consequently, APS patients positive for LA should be monitored using tissue-derived thromboplastin reagents, given its reduced susceptibility to interference by LA-causing antibodies., (© 2024 The Author(s).)

Abstract Background Coagulopathy has been reported in severely ill patients with coronavirus disease 2019 (COVID‐19). It is unclear whether outpatients with COVID‐19 who are treated with vitamin K antagonists (VKAs) have unstable anticoagulation. Objective To assess the stability of VKA therapy in patients with COVID‐19 through a case‐crossover study. Methods Between February and July 2020, we included patients who tested positive for COVID‐19 from two anticoagulant clinics in the Netherlands. We collected international normalized ratios (INRs) determined between 26 weeks before infection and 12 weeks after. Time in therapeutic range (TTR) and the variance growth rate (VGR) were calculated within patients. Results Fifty‐one patients with COVID‐19 (mean age, 84 years) were included, of whom 15 (29%) were men. Mean TTR in the 26 weeks before COVID‐19 was 80% (95% confidence interval [CI], 75‐85) compared to 59% (95% CI, 51‐68) in the 6 weeks after infection. Mean TTR difference was −23% (95% CI, −32 to −14) with a time above therapeutic range of 38% (95% CI, 30‐47) in the 6 weeks after infection. The TTR rose again to 79% (95% CI, 69‐89) between 6 and 12 weeks after infection. Also, VGR increased, with a mean increase of 4.8 (95% CI, 2.1‐7.5) in the 6 weeks after infection. In the 26 weeks before infection, we registered 19 of 641 (3%) of INR ≥5.0 compared with 35 of 247 (14%) in the 6 weeks after (risk ratio, 4.4; 95% CI, 2.7‐7.3). Conclusions COVID‐19 is associated with a strong decrease in TTR and in therapeutic stability in patients taking VKAs. Additional monitoring in these patients is advised to maximize therapeutic stability.

Background: Acute bleeding requires fast and targeted therapy. Therefore, knowledge of the patient's potential to form a clot is crucial. Point-of-care testing (POCT) provides fast and reliable information on coagulation. Structural circumstances, such as person-bound sample transport, can prolong the reporting of the results. The aim of the present study was to investigate the diagnostic quality and accuracy between POCT INR diagnostics and standard laboratory analysis (SLA) as well as the time advantage between a pneumatic tube and a personal-based transport system. Methods: Two groups of haemorrhagic patients (EG: emergency department; OG: delivery room; each n = 12) were examined in the context of bleeding emergencies using POCT and SLA. Samples were transported via a pneumatic tube system or by a personal transport service. Results: INR results between POCT and SLA showed a high and significant correlation (EG: p

Background: In patients with unremarkable medical history, comprehensive preoperative hemostasis screening in elective neurosurgery remains debated. Comprehensive medical history has shown to be noninferior to coagulation profile to evaluate surgical outcomes. This study aims to evaluate the predictiveness of preoperative coagulation screening and medical history for surgical outcomes., Methods: Databases were searched until April 2023 for observational cohort studies that reported preoperative hemostasis screening and clinical history prior to elective neurosurgical procedures. Outcomes of interest included postoperative transfusion, mortality, and complications. Pooled relative risk ratios (RRs) were analyzed using random-effects models., Results: Out of 604 studies, 3 cohort studies met our inclusion criteria, adding a patient population of 83,076. Prolonged partial thromboplastin time (PTT; RR=1.42, 95% confidence interval [CI] =1.14, 1.77, P=0.002), elevated international normalized ratio (INR; RR=2.01, 95% CI=1.14, 3.55, P=0.02), low platelet count (RR=1.58, 95% CI=1.34, 1.86, P<0.00001), and positive bleeding history (RR=2.14, 95% CI=1.16, 3.93, P=0.01) were associated with postoperative transfusion risk. High PTT (RR=2.42, 95% CI=1.24, 4.73, P=0.010), High INR (RR=8.15, 95% CI=5.97, 11.13; P<0.00001), low platelet count (RR=4.89, 95% CI=3.73, 6.41, P<0.00001), and bleeding history (RR=7.59, 95% CI=5.84, 9.86, P<0.00001) were predictive of mortality. Prolonged PTT (RR=1.53, 95% CI=1.25, 1.86, P=<0.0001), a high INR (RR=3.41, 95% CI=2.63, 4.42, P=< 0.00001), low platelets (RR=1.63, 95% CI=1.40, 1.90, P=<0.00001), and medical history (RR=2.15, 95% CI=1.71, 2.71, P=<0.00001) were predictive of complications., Conclusions: Medical history was a noninferior predictor to coagulation profile for postoperative transfusion, mortality, and complications. However, our findings are mostly representative of elective spinal procedures. Cost-effective alternatives should be explored to promote affordable patient care in patients with unremarkable history., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Objective: Spontaneous intracerebral hemorrhage (ICH) poses a public health issue due to its elevated mortality rates. The International Normalized Ratio-platelet index (INR-Plt index) has recently been recognized as a predictive factor for liver disease progression. The potential of applying the INR-Plt index in forecasting ICH prognosis presents an intriguing subject. This study endeavors to examine the correlation between the INR-Plt index and hospital outcomes in patients with spontaneous supratentorial ICH., Methods: A retrospective examination of 283 adult ICH patients was undertaken. The INR-Plt index was computed using the formula: [INR/platelet counts (1000/μL)] × 100. The clinical outcomes evaluated consisted of mortality rates and the Modified Rankin Scale (mRS) at discharge. An unfavorable outcome was defined as an mRS score from 4 to 6., Results: The study found a significant correlation between the INR-Plt index and hospital mortality (odds ratio: 4.31, 95% CI: 1.07-17.31, P = 0.04). There was a 43% rise in mortality risk for every 0.1 unit increase in the INR-Plt index. Kaplan-Meier survival curves illustrated a considerably lower survival rate at discharge for patients with an INR-Plt index >0.8 (log-rank test: P = 0.047). Regarding unfavorable outcomes, the INR-Plt index was not a significant factor according to logistic regression analyses., Conclusions: The INR-Plt index is a predictor of hospital mortality in patients with spontaneous supratentorial ICH. A higher INR-Plt index value is associated with an increased risk of mortality, underlining the potential usefulness of this composite index in guiding clinical decision-making and enabling risk stratification., (Copyright © 2024 Elsevier Inc. All rights reserved.)

Background: The influence of child characteristics on warfarin dosing has been reported; however, there is no consensus on the nature and extent of this effect., Objectives: To investigate the impacts of the demographic and clinical characteristics of children on the warfarin dose required to achieve a therapeutic international normalization ratio (INR)., Methods: This retrospective cohort study included children aged 3 months to 14 years old who were prescribed warfarin for 3 months or longer with a "stable INR." The primary outcome was the total daily dose (TDD) and total weekly dose of warfarin required to achieve a therapeutic INR target., Results: We included 127 patients with a mean age of 7.7 ± 3.7 years and a median weight of 22 (IQR, 16-33) kg. Of the sample, 55 patients (43.3%) required a TDD of ≤0.1 mg/kg. The TDD for children younger than 5 years, 5 to 10 years, and older than 10 years were 0.14 ± 0.06 mg/kg, 0.12 ± 0.05 mg/kg, and 0.096 ± 0.04 mg/kg, respectively ( P  = .002). Overweight and obese children required a smaller TDD than normal-weight children: 0.09 ± 0.05 vs 0.13 ± 0.05 mg/kg ( P  = .004), which was similar for underweight children. A lower body surface area (<0.5 m 2 ) required a higher dose. All the other variables did not affect warfarin doses. The incidence of a subtherapeutic or supratherapeutic INR was independent of demographic or clinical variables., Conclusion: The study confirmed that the patient demographics affect the daily warfarin dose required to achieve the INR target. However, they do not have any predictive value for the incidence of out-of-range-INR., (© 2024 The Author(s).)

Background: Thromboplastin calibration is essential to determine the international sensitivity index required to calculate the international normalized ratio (INR). The procedure for calibration recommended by the World Health Organization (WHO) calls for the selection of patients on stable anticoagulation in the range of 1.5 to 4.5 INR. These patients are difficult to be recruited as the conventional therapeutic interval for warfarin is 2.0 to 3.0. A possible solution could be including patients with less intense anticoagulation in the calibration., Objectives: We sought to investigate the impact of this amended procedure on the parameters of calibration., Methods: Eight data sets from previous calibrations of a rabbit thromboplastin that included patients on anticoagulation as required by WHO were used for this pilot study. Parameters of calibration as determined by the full data sets are identified as "full calibrations" and are considered reference. Each of the data sets were used to recalculate the calibration parameters after including patients with INRs of <4.0, <3.5, or <3.0, which were identified as "trimmed calibrations" and compared with those from the full calibrations., Results: There was marginal variation of the international sensitivity index, CV, and INR that can be hardly of practical significance. CV was the most affected parameter, which increased from the full to the trimmed <3.0 calibration, but never exceeded the 3% cutoff value recommended by WHO., Conclusions: Should the results of this pilot study be confirmed for the calibration of other thromboplastins, revision of the WHO recommendations to include patients with INR from 1.5 to 4.0 is warranted., Competing Interests: Declaration of competing interests There are no competing interests to disclose., (Copyright © 2022 International Society on Thrombosis and Haemostasis. Published by Elsevier Inc. All rights reserved.)

Background: Patients with cirrhosis are increasingly using direct oral anticoagulants (DOACs) in therapeutic doses for the treatment of portal vein thrombosis or for concomitant atrial fibrillation. DOACs may affect routine diagnostic tests of coagulation including the international normalized ratio (INR). The INR is a part of the model of end-stage liver disease (MELD) score, a validated score that predicts the mortality risk in patients with cirrhosis and is used to prioritize patients for liver transplantation. DOAC-induced increases in the INR may thus lead to artificial inflation of the MELD score., Objective: We studied the effect of DOACs on INR prolongation in patients with cirrhosis., Methods: We spiked plasma from 20 healthy individuals and 20 patients at the start of liver transplantation with DOACs in concentrations representing peak therapeutic levels. In addition, we studied INR increases in healthy controls and patients with mild cirrhosis who received the DOAC edoxaban for 1 week for study purposes., Results: In controls and patients, the INR increased by an ex vivo addition of a DOAC, and the INR increase in patients was proportional to the baseline INR values. The increase in INR translated to a median increase of between 3 and 10 MELD points, depending on the DOAC used. In controls and patients alike, the INR increased on the ingestion of edoxaban, which translated to an increase in 5 MELD points., Conclusions: Taken together, DOACs result in an INR increase that translates to clinically meaningful increases in MELD points in patients with cirrhosis, and precautions to avoid artificial inflation of the MELD score in these patients are warranted., (© 2023 The Author(s).)

Background: Patients with antiphospholipid syndrome (APS) receive anticoagulant therapy with vitamin K antagonists (VKAs) to prevent recurrent thrombosis. VKA treatment requires strict monitoring with an international normalized ratio (INR). It is known that lupus anticoagulants (LAs) can lead to elevated INR results with point-of-care-testing (POCT) devices, which could result in inadequate adaptation of anticoagulant therapy., Objective: To determine discrepancies between POCT-INR and laboratory-INR in patients who are LA-positive on VKA therapy., Methods: Paired INR testing was performed with 1 POCT device (CoaguChek XS) and 2 laboratory assays (Owren and Quick method) in 33 patients with LA-positive APS on VKA in a single-center cross-sectional study. Patients were tested for anti-β2-glycoprotein I, anticardiolipin, and antiphosphatidylserine/prothrombin immunoglobulin (Ig) G and IgM antibodies. Agreement between assays was evaluated with Spearman's correlation, Lin's correlation coefficient, and Bland-Altman plots. Agreement limits were considered satisfactory if differences were ≤20% as determined by the Clinical and Laboratory Standards Institute., Results: We found poor agreement between POCT-INR and laboratory-INR based on Lin's concordance correlation coefficient (ρ c ) of 0.42 (95% CI, 0.26-0.55) between POCT-INR and Owren-INR, a ρ c of 0.64 (95% CI, 0.47-0.76) between POCT-INR and Quick-INR, and a ρ c of 0.77 (95% CI, 0.64-0.85) between Quick-INR and Owren-INR. High anti-β2-glycoprotein I IgG antibody titers correlated with INR disagreement between POCT-INR and laboratory-INR., Conclusion: There is a disagreement between INR values measured with the CoaguChek XS and laboratory-INR in a proportion of patients with LA. Consequently, laboratory-INR monitoring should be preferred over POCT-INR monitoring in patients with LA-positive APS, especially in patients with high anti-β2-glycoprotein IgG antibody titers., (© 2022 The Authors.)

Introduction: Clinicians often order the international normalized ratio (INR) and activated partial thromboplastin time (APTT) to evaluate for the possibility of inherited bleeding disorders despite sensitivities and specificities of 1%-2%. The most accurate tool to evaluate for bleeding disorders is a validated bleeding assessment tool (BAT). Our aim was to reduce coagulation testing by >50% in a large family practice in Ontario, Canada., Methods: We conducted an implementation study from May 2016 to February 2020. Iterative interventions included introduction of a validated BAT into the electronic medical record (EMR); removal of the APTT as a prepopulated selection from the laboratory requisition; and education targeting family medicine teams and laboratory personnel. The primary outcome was the rate of pre- and post-APTT testing. Creatinine testing was the control. Data were analyzed via an interrupted time series analysis using Stata 13., Results: Immediately following education of the laboratory personnel on coagulation testing, the APTT rate level dropped by 1.26 tests per 100 patient visits per month ( p  < 0.001) and was sustained until the end of the study. Meanwhile, the PT/INR and creatinine testing rate levels did not change (rate level = -0.02 per 100 visits per month, p  = 0.79 and 0.49, p  = 0.22 respectively). There was good uptake of the BAT following integration and 18/88 (20%) obtained a referral to hematology after BAT completion., Conclusions: Multidisciplinary, iterative interventions reduced APTT testing and enabled the use of BATs to guide hematology referrals in a large family practice., (© 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Background: Vitamin K antagonists (VKA) are the most widely used anticoagulants for the prevention of thrombotic events. Several renal adverse effects have been associated with the use of VKA. The main aim of our study was to explore the association between international normalized ratio (INR) levels and microscopic hematuria in patients with VKA., Methods: We performed a cross-sectional study of patients treated with VKA that attended the outpatient clinic for routine INR control. A simple urinalysis was performed on the day of the INR control and the precise number of red cells in the urine sediment was quantified. Demographic data, kidney function tests, comorbidities, anticoagulant dose and concomitant treatment were registered., Results: A total of 337 patients were included with median INR levels of 2.6 (IQR 2.1-3.3). 11.9% of the patients presented microscopic hematuria (≥14 RBCs/µl). There was a significant correlation between INR levels and the number of red blood cells in the urine sediment (r = 0.201, p = 0.024). In the univariate analysis, microscopic hematuria was associated with having an INR >3.5 (19% vs. 10.2%, p = 0.046), bacteriuria (15.2% vs. 3.6%, p = 0.015), leukocyturia (14.8% vs. 6.6%, p =  0.026), hypertension (16.2% vs. 9.5%, p = 0.053), and the use of renin-angiotensin system (RAS) blockers (6.9% vs. 17.2%, p = 0.004). Multivariate logistic regression showed an association between microscopic hematuria and RAS blockade (OR 0.38, CI 95% 0.163-0.886, p = 0.025), independent from INR levels, hypertension, leukocyturia or bacteriuria., Conclusions: INR overdose was significantly associated with the presence of microscopic hematuria. RAS blockade is an independent protective factor for the presence of microscopic hematuria in anticoagulated patients., Competing Interests: Declaration of Competing Interest The authors declare that they have no conflicts of interest to disclose., (Copyright © 2022 Southern Society for Clinical Investigation. Published by Elsevier Inc. All rights reserved.)

Background: Vitamin K antagonists (VKAs) are frequently prescribed to patients with congenital heart disease (CHD) for atrial arrhythmias or Fontan palliation, but there is a paucity of data regarding time spent in the therapeutic range (TTR). We sought to determine the TTR in patients with CHD and atrial arrhythmias or Fontan palliation prescribed VKAs and explore associations with thromboembolic and bleeding events., Methods: A multicentre North American cohort study was conducted on patients with CHD who received VKAs for sustained atrial arrhythmia or Fontan palliation. TTR was calculated using the Rosendaal linear interpolation method. Generalized estimating equations were used to explore factors associated with time outside the therapeutic range., Results: A total of 567 patients, aged 33 ± 17 years, 56% female, received VKAs for 11.5 ± 8.4 years for atrial arrhythmias (63.0%) or Fontan palliation (58.0%). CHD was simple, moderate, and complex in 10.8%, 20.3%, and 69.0%, respectively. Site investigators perceived good control over international normalized ratio (INR) levels in most patients (75.3%), with no or minor compliance or adherence issues (85.6%). The mean TTR was 41.9% (95% confidence interval [CI], 39.0%-44.8%). Forty-seven (8.3%) and 34 (6.0%) patients had thromboembolic and bleeding events, respectively. Thromboembolic events were associated with a higher proportion of time below the therapeutic range (31.3% vs 19.1%, P = 0.003) and bleeding complications with a higher proportion of time above the therapeutic range (32.5% vs 19.5%, P = 0.006)., Conclusions: Patients with CHD who receive VKAs spend < 42% of their time with INR levels in the therapeutic range, with repercussions regarding thromboembolic and bleeding complications., (Copyright © 2022 Canadian Cardiovascular Society. Published by Elsevier Inc. All rights reserved.)

Patients who undergo heart valve replacements with mechanical valves need to take Vitamin K Antagonists (VKA) drugs (Warfarin, Nicoumalone) which has got a very narrow therapeutic range and needs very close monitoring using PT-INR. Accessibility to physicians to titrate drugs doses is a major problem in low-middle income countries (LMIC) like India. Our work was aimed at predicting the maintenance dosage of these drugs, using the de-identified medical data collected from patients attending an INR Clinic in South India. We used artificial intelligence (AI) - machine learning to develop the algorithm. A Support Vector Machine (SVM) regression model was built to predict the maintenance dosage of warfarin, who have stable INR values between 2.0 and 4.0. We developed a simple user friendly android mobile application for patients to use the algorithm to predict the doses. The algorithm generated drug doses in 1100 patients were compared to cardiologist prescribed doses and found to have an excellent correlation., Competing Interests: Declaration of competing interest The authors declare the following financial interests/personal relationships which may be considered as potential competing interests: Dr. Harikrishnan S. and all authors has applied for a patent #Indian Patent No. 202141037246 for a related device pending to SCTIMST, Trivandrum and NIT, Calicut., (Copyright © 2022 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)

Background: Several studies have shown that in patients treated with vitamin K antagonists (VKAs) time spent in therapeutic range (TTR) is lower in females than in males. This retrospective study has evaluated a possible association among over-anticoagulation and gender, type and indications to VKAs, TTR and bleeding. Moreover, the decrease of the INR level, after VKAs withdrawal, was considered., Methods: From December 2020 to January 2004, 1230 patients with venous thromboembolism or atrial fibrillation were enrolled. Age, gender, type of VKAs, clinical indications, INR values and bleeding events were recorded. TTR was calculated considering the entire period of treatment., Results: A total of 1616 and 1759 over-anticoagulation episodes were found in males and females, respectively. The median INR value was 4.5 (4.0-19.04). Thirty-two percent of the patients did not have an overdose throughout the observation period. The median number of over-anticoagulation per year was significantly higher in females (0.39-year) than in males (0.28-year). After 24 h of VKAs withdrawal, INRs were similar in both genders. Logistic regression analysis showed that the episodes of over-anticoagulation per year were associated with females, atrial fibrillation, warfarin therapy, follow-up length longer than 4 years, and TTR <73%, but were not associated to bleeding episodes., Conclusion: The higher number of over-anticoagulation can explain the lower TTR in females. An excess of anticoagulation is not associated with bleeding events. The recovery of INR performs better when acenocoumarol is used, therefore, in patients who present several episodes of over-anticoagulation, acenocumarolo could replace warfarin., (Copyright © 2022 Elsevier B.V. All rights reserved.)

Background: Patients with chronic liver disease (CLD) often present with an elevated international normalized ratio (INR). Although elevated INR reflects a higher risk of hemorrhage among warfarin users, its clinical significance in CLD patients is less clear., Objectives: We used Veterans Health Administration data to quantify the association between INR and (non-variceal) hemorrhage in patients with CLD compared to warfarin users., Methods: We performed a multivariate competing risk analysis to study the association between INR and hemorrhage in the two cohorts. We used an interaction term between INR and cohort (CLD/warfarin users) to test if INR had different effects on hemorrhage in the two cohorts., Results: Data from 80 134 patients (14, 412 with CLD and 65, 722 taking warfarin) were analyzed. The effect of INR on the risk of hemorrhage differed between CLD patients and warfarin users (interaction P < .001). As INR increased above 1.5, the adjusted hazard ratio (aHR) for hemorrhage in CLD patients increased to 2.25 but remained fairly constant with further elevation of INR values. In contrast, the risk of hemorrhage in patients taking warfarin remained low with INR in the subtherapeutic (INR <2.0) and therapeutic ranges (INR 2.0-3.0), and increased exponentially with INR in the supratherapeutic range (aHR 1.64 with INR >3.0-3.5, and 4.70 with INR >3.5)., Conclusions: The relationship between INR and risk of hemorrhage in CLD patients is different from that in warfarin users. Caution should be exercised extrapolating data from warfarin users to make clinical decisions in CLD patients., (© 2022 International Society on Thrombosis and Haemostasis.)

Introduction: The aim of our study was to compare the time spent within the target INR or Time in Therapeutic Range (TTR) of patients treated with fluindione to that of patients treated with warfarin for non-valvular atrial fibrillation (NVAF) and followed in general practice, with the hypothesis of a better TTR with warfarin, which is the VKA most commonly prescribed in France., Method: Liberal nurses and general practitioners working in the Auvergne region recruited patients treated with fluindione or warfarin for NVAF. Patients' INRs (International Normalized Ratios) were recorded by medical analysis laboratories for 6 months. The primary endpoint was TTR, the secondary endpoint the number of hemorrhagic and/or thromboembolic events., Results: Of the 342 participants with a mean age of 75.3 ± 9.8 years, 239 (70%) were treated with fluindione and 103 (30%) with warfarin. The mean number of INRs achieved per patient was 9.2 ± 4.0 in the fluindione group and 9.3 ± 4.0 in the warfarin group (p=0.73). The median TTR of fluindione was 81.9% [63.5; 94.1] and that of warfarin was 81.3% [65.6; 92.6] (p=0.98). Twenty-eight of 263 patients reported hemorrhage (10.6%) and 4 reported thromboembolic events (0.8%), with no significant difference between the groups., Conclusion: The TTRs of patients treated for NVAF with fluindione versus warfarin do not differ significantly over an observation period of 6 consecutive months in a patient population comparable to that of the publications in this field. However, these TTRs are significantly higher than those reported in the literature, with no difference between the two treatments. The TTRs of patients treated for VANF with fluindione versus warfarin do not differ significantly over a 6-month observation period in a patient population comparable to that of the publications in this indication., Competing Interests: Conflits d'intérêts aucun, (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Background: The optimal prophylactic preprocedural management of patients with coagulopathy due to liver disease is not known., Objectives: Our objective was to compare the efficacy and safety of fresh frozen plasma (FFP) with prothrombin complex concentrate (PCC) in the preprocedural management of patients with coagulopathy of liver disease., Methods: We conducted a systematic review to examine published evidence regarding treatment with FFP or PCC in adults with coagulopathy of liver disease undergoing an invasive procedure. Direct comparisons and single-arm studies were eligible. Efficacy outcomes included major bleeding, mortality, and correction of prothrombin time (PT) and/or international normalized ratio (INR). Safety outcomes included thrombosis and transfusion-related complications., Results: A total of 95 articles were identified for full-text review. Nine studies were eligible and included in the review. No randomized trials comparing FFP versus PCC were identified. Only two studies directly compared FFP versus PCC. In these studies, PCC appeared to result in higher rates of correction of PT/INR, but bleeding outcomes were not different. In the single-arm studies, bleeding events appeared low overall. Volume overload was the most common recorded adverse event in patients receiving FFP. Thromboembolic events occurred rarely, but exclusively in the PCC group. Due to heterogeneity in study definitions and bias, meta-analysis was not possible. Our study found no evidence to favor a specific product over another., Conclusions: Insufficient data exist on the effects of FFP versus PCC administration before invasive procedures in patients with coagulopathy of liver disease to make conclusions with respect to relative efficacy or safety., Competing Interests: AC has served as a consultant for Synergy; has received royalties from UpToDate; and his institution has received research support on his behalf from Alexion, Bayer, Novartis, Novo Nordisk, Pfizer, Sanofi, and Spark. AMP receives research funding from Novo Nordisk and Sanofi Genzyme. In the past 24 months, MC has served as a consultant for Precision Biologicals, Hemostasis Reference Laboratory, and Syneos Health; and has prepared educational materials and/or participated in educational sessions for Pfizer, CSL Behring, and Diagnostica Stago. MC receives royalties from UpToDate and has relationships with various not‐for‐profit entities, including the American Society of Hematology., (© 2022 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

A cross-sectional study was conducted to predict time in therapeutic range (TTR) using clinical history, examination, and socioeconomic data. Study included warfarin-receiving patients from outpatient-clinic. In 203 patients studied, mean warfarin start-dose was 2.55 mg/day and maintenance-dose/week was 30.79 mg. Body mass index (BMI) (p = 0.03), warfarin maintenance dose/day (p = 0.02), and comorbidity presence (p = 0.04) were significantly associated with TTR. Occupation (p = 0.53), income (p = 0.83), education (p = 0.55), and socioeconomic score (p = 0.73) showed non-significant association with TTR. A TTR predicting nomogram was built from clinical history and examination findings., Competing Interests: Declaration of competing interest None., (Copyright © 2022 Cardiological Society of India. Published by Elsevier, a division of RELX India, Pvt. Ltd. All rights reserved.)

Background: Prior to the COVID-19 pandemic, warfarin users were required to complete in-person training in order to participate in approved international normalized ratio (INR) patient self-testing (PST) programs. To minimize in-person contact during the pandemic, a federal waiver of the in-person training requirement allowed new patients to begin PST after completing virtual training. However, it was uncertain whether such patients achieved comparable levels of INR control to patients receiving in-person training., Methods: INR results for patients receiving virtual training upon PST commencement between April 1, 2020, and December 31, 2020, were compared to those of patients initiating PST with in-person training between April 1, 2019, and December 31, 2019. The primary outcome was the difference in warfarin time in therapeutic range (TTR) between the groups, with secondary outcomes including differences in the percentages of INR values within individually prescribed INR range and of critical INR values., Results: The records of 33,683 patients were included in the analysis (13,568 in the "In-Person" sample; 20,115 in the "Virtual" sample). Patients in the Virtual sample achieved a TTR of 66.78%, compared to the In-Person sample (64.19%; absolute difference 2.59; 95% confidence interval [CI] = 2.50-2.68, p < 0.001). The TTR values were also statistically significantly higher in all subgroups evaluated across categories of patient age, gender, geography, and indication. Similarly favorable results were achieved for INR values in range and critical values., Conclusion: Virtual education for PST for warfarin therapy is effective and should continue to be an option for patients and providers throughout the pandemic, and possibly beyond., (Published by Elsevier Inc.)

Background: An ideal definition of early allograft dysfunction (EAD) after live donor liver transplantation (LDLT) remains elusive. The aim of the present study was to compare the diagnostic accuracies of existing EAD definitions, identify the predictors of early graft loss due to EAD, and formulate a new definition, estimating EAD-related mortality in LDLT recipients., Methods: Consecutive adult patients undergoing elective LDLT were analyzed. Patients with technical (vascular, biliary) complications and biopsy-proven rejections were excluded., Results: There were 19 deaths due to EAD of a total of 304 patients. On applying the existing definitions of EAD, we revealed their limitations of being either too broad with low specificity or too restrictive with low sensitivity in patients with LDLT. A new definition of EAD-LDLT (total bilirubin >10 mg/dL, international normalized ratio [INR] > 1.6 and serum urea >100 mg/dL, for five consecutive days after day 7) was derived after doing a multivariate analysis. In receiver operator characteristics analysis, an AUC for EAD-LDLT was 0.86. The calibration and internal cross-validation of the new model confirmed its predictability., Conclusion: The new model of EAD-LDLT, based on total bilirubin >10 mg/dL, INR >1.6 and serum urea >100 mg/dL, for five consecutive days after day 7, has a better predictive value for mortality due to EAD in LDLT recipients., (© 2021 Indian National Association for Study of the Liver. Published by Elsevier B.V. All rights reserved.)

Background: This is the 2nd update to the 9th edition of these guidelines. We provide recommendations on 17 PICO (Population, Intervention, Comparator, Outcome) questions, four of which have not been addressed previously., Methods: We generate strong and weak recommendations based on high-, moderate-, and low-certainty evidence, using GRADE (Grading of Recommendations, Assessment, Development, and Evaluation) methodology., Results: The panel generated 29 guidance statements, 13 of which are graded as strong recommendations, covering aspects of antithrombotic management of VTE from initial management through secondary prevention and risk reduction of postthrombotic syndrome. Four new guidance statements have been added that did not appear in the 9th edition (2012) or 1st update (2016). Eight statements have been substantially modified from the 1st update., Conclusion: New evidence has emerged since 2016 that further informs the standard of care for patients with VTE. Substantial uncertainty remains regarding important management questions, particularly in limited disease and special patient populations., (Copyright © 2021. Published by Elsevier Inc.)

Background: Coagulopathy has been reported in severely ill patients with coronavirus disease 2019 (COVID-19). It is unclear whether outpatients with COVID-19 who are treated with vitamin K antagonists (VKAs) have unstable anticoagulation., Objective: To assess the stability of VKA therapy in patients with COVID-19 through a case-crossover study., Methods: Between February and July 2020, we included patients who tested positive for COVID-19 from two anticoagulant clinics in the Netherlands. We collected international normalized ratios (INRs) determined between 26 weeks before infection and 12 weeks after. Time in therapeutic range (TTR) and the variance growth rate (VGR) were calculated within patients., Results: Fifty-one patients with COVID-19 (mean age, 84 years) were included, of whom 15 (29%) were men. Mean TTR in the 26 weeks before COVID-19 was 80% (95% confidence interval [CI], 75-85) compared to 59% (95% CI, 51-68) in the 6 weeks after infection. Mean TTR difference was -23% (95% CI, -32 to -14) with a time above therapeutic range of 38% (95% CI, 30-47) in the 6 weeks after infection. The TTR rose again to 79% (95% CI, 69-89) between 6 and 12 weeks after infection. Also, VGR increased, with a mean increase of 4.8 (95% CI, 2.1-7.5) in the 6 weeks after infection. In the 26 weeks before infection, we registered 19 of 641 (3%) of INR ≥5.0 compared with 35 of 247 (14%) in the 6 weeks after (risk ratio, 4.4; 95% CI, 2.7-7.3)., Conclusions: COVID-19 is associated with a strong decrease in TTR and in therapeutic stability in patients taking VKAs. Additional monitoring in these patients is advised to maximize therapeutic stability., (© 2021 The Authors. Research and Practice in Thrombosis and Haemostasis published by Wiley Periodicals LLC on behalf of International Society on Thrombosis and Haemostasis (ISTH).)

Objectives: D-dimer elevations, suggesting a pro-thrombotic state and coagulopathy, predict adverse outcomes in coronavirus disease 2019 (COVID-19). However, the clinical significance of other coagulation markers, particularly the international normalized ratio (INR), is not well established. We conducted a systematic review and meta-analysis of the INR in COVID-19., Methods: A literature search was conducted in PubMed, Web of Science and Scopus, between January 2020 and February 2021, for studies reporting INR values, measures of COVID-19 severity, and mortality (PROSPERO registration number: CRD42021241468)., Results: Thirty-eight studies in 7440 COVID-19 patients with low disease severity or survivor status during follow up (50 ​% males, mean age 57 years) and 2331 with high severity or non-survivor status (60 ​% males, mean age 69 years) were identified. The INR was significantly prolonged in patients with severe disease or non-survivor status than in patients with mild disease or survivor status (standard mean difference, SMD, 0.60; 95 ​% confidence interval, CI 0.42 to 0.77; p ​< ​0.001). There was extreme between-study heterogeneity (I 2  ​= ​90.2 ​%; p ​< ​0.001). Sensitivity analysis, performed by sequentially removing each study and re-assessing the pooled estimates, showed that the magnitude and direction of the effect size was not modified. The Begg's and Egger's t-tests did not show publication bias. In meta-regression, the SMD of the INR was significantly associated with C-reactive protein (p ​= ​0.048) and D-dimer (p ​= ​0.001)., Conclusions: Prolonged INR values were significantly associated with COVID-19 severity and mortality. Both INR prolongation and D-dimer elevations can be useful in diagnosing COVID-19-associated coagulopathy and predicting clinical outcomes., Competing Interests: Declaration of competing interest The authors declare no conflict of interests., (Copyright © 2021 Medical University of Bialystok. Published by Elsevier B.V. All rights reserved.)

Sorafenib was suggested to cause drug-drug interaction (DDI) with the common anticoagulant, warfarin based on published studies. The inhibition on CYP2C9 enzyme was thought to be the mechanism, but further studies are warranted. Thus, a mechanistic PBPK/PD model for warfarin enantiomers was developed to predict DDI potential with sorafenib, aiming at providing reference for the rational use of both drugs. PBPK models of warfarin enantiomers were constructed by Simcyp software. A mechanistic PK/PD model was built in NONMEM software. PBPK model of sorafenib was fitted via a top-down method. The final PBPK/PD model of warfarin enantiomers was verified and validated by different dosing regimens, ethnicities and genetic polymorphisms, and used to perform DDI simulations between warfarin racemate and sorafenib among general populations and sub-populations with various CYP2C9 and VKORC1 genotypes. Results suggested low DDI risk between warfarin and sorafenib for general populations. Potentially serious consequence was seen for those carrying both CYP2C9 ∗2 and ∗3 and VKORC1 A/A genotypes. This PBPK/PD modeling approach for warfarin enantiomers enabled DDI evaluation with sorafenib. Close monitoring and warfarin dosage adjustment were recommended for patients carrying mutant genotypes. The novel model could be applied to investigate other drugs that may interact with warfarin., Competing Interests: Declaration of competing interest The authors declare that there are no conflicts of interest., (Copyright © 2020 The Japanese Society for the Study of Xenobiotics. Published by Elsevier Ltd. All rights reserved.)

Background: Patients undergoing hepatectomy can have elevated INR and may have venous thromboembolism (VTE) prophylaxis withheld as a result. We sought to examine the association between preoperative INR elevation and VTE following hepatectomy., Methods: Hepatectomies captured in the American College of Surgeons National Surgical Quality Improvement Program registry between 2007 and 2016 were analyzed. Univariable and multivariable models examined the effect of incremental increases in preoperative INR on 30-day VTE, perioperative transfusion, serious morbidity, and mortality, adjusting for potential confounders., Results: We included 25,220 elective hepatectomies (62.4% partial lobectomies, 10.1% left hepatectomies, 18.6% right hepatectomies, 9.2% trisegmentectomies). The median age of the patients was 60 years and 49% were male. INR was elevated in 3089 patients (12.2%): 1.1-1.2 in 8.1%, 1.2-1.4 in 3.3%, and 1.4-2.0 in 0.9%. Incremental elevations in INR were independently associated with increasing risk for postoperative VTE [odds ratio (OR) 1.15, 95% confidence intervals 1.01-1.31], perioperative transfusion [OR 1.35 (1.28-1.43)], serious morbidity [OR 1.35 (1.28-1.43)], and mortality [OR 1.76 (1.56-1.98)]., Conclusion: Elevation in preoperative INR was counter-intuitively associated with increased risk of both VTE and perioperative transfusion following hepatectomy. The role of perioperative thromboprophylaxis warrants further investigation to determine optimal care in patients with elevated preoperative INR., (Copyright © 2020 International Hepato-Pancreato-Biliary Association Inc. Published by Elsevier Ltd. All rights reserved.)

Introduction: Vitamin K antagonist (VKA) related adverse events are the first cause for iatrogenic events in France, particularly due to the narrow therapeutic margin. The risk of bleeding increases significantly when the INR level is ≥5. The main objective of this study was to assess the prevalence of VKA overdose in a hospital setting (at D2 of hospital entry) and to evaluate physicians' adherence to clinical practice guidelines for the management of VKA overdose according to French National Authority for Health recommendations., Methods: This single-center retrospective observational study consisted in querying the computerized database of a Parisian hospital on 21275INR determinations (3995 patients, 6813 hospital stays) performed between 2013 and 2018., Results: An INR level ≥5 was noted during 350 (6%) of the hospital stays, in 331 patients (of whom 57% were women). The mean age of the patient population with an INR≥5 was 81.1 years. Infection, heart failure and renal failure were the most frequent acute medical conditions for hospital admission. Twenty-three patients (7%) had a bleeding complication, 11 of which were major bleeding complications. Older age was associated with the severity of bleeding complications. Fifteen in-hospital deaths (4%) were reported, not related to bleeding events. The management of VKA overdose did not comply with the recommendations in 43% of cases, in particular for the highest INRs (50% of noncompliance for an INR>6.4). Non-compliance with recommendations for VKA overdose was related to: the delay until the INR was checked (44% of cases); the indication for prescribing vitamin K (34% of cases); the dose or route of administration of vitamin K therapy (19% of cases); and the interruption or not of VKA therapy (12% of cases)., Conclusion: The management of VKA overdose in a hospital setting remains non-compliant with the recommendations in almost half of the cases, mainly due to the delayed INR control and inappropriate management of vitamin K therapy. Computerized alert system would be helpful for personalized patient management and improved pharmacovigilance to prevent iatrogenic VKA events., (Copyright © 2021 Elsevier Masson SAS. All rights reserved.)

Study Objective: Explore how the introduction of 4-factor prothrombin complex concentrates (4F-PCC) protocols for reversing anticoagulation and the treatment of critical bleeding influenced blood product utilization., Design: A retrospective analysis of the utilization rate of plasma and 4F-PCC from September 2012 through December 2018., Setting: Blood bank and pharmacy records of a single large tertiary care medical center., Patients: Admitted patients except obstetric during the study period (n = 283,319)., Intervention: Five institutional protocols providing guidelines for 4F-PCC administration were deployed over a 3-year period., Measurements: The utilization rate of plasma and 4F-PCC was the primary outcome and analyzed using an interrupted time series analysis. Utilization of platelets and cryoprecipitate as well as the impact of the intervention on the service prescribing the blood products were evaluated as secondary outcomes. Data were evaluated using a segmented time series regression., Results: When adjusted for seasonality, the monthly rate of plasma administration was 24.7 ± 2.0 units per 100 admissions in the 6-month period prior to the 1st intervention (May-October 2013) and decreased to 9.9 ± 2.2 units per 100 admissions in the same six-month period following the 5th intervention (May-October 2018), median difference - 14.5, 95% CI -16.0 to -13.2, P < 0.001. During the 6-month period prior to the 1st intervention (May-October 2013) the monthly rate of 4-F PCC use was 1.2 ± 0.8 doses per 1000 admissions and increased to 2.8 ± 1.0 doses per 1000 admissions 6-months following the 5th intervention (May-October 2018), median difference 1.6, 95% CI 0.3 to 1.9, P = 0.014. The monthly utilization of platelets was decreased and cryoprecipitate slightly increased following the implementation of the PCC protocols., Conclusions and Relevance: Our findings demonstrate that establishing institutional protocols for the use of 4F-PCC to reverse the effects of anticoagulation and to treat critical bleeding with associated coagulopathy was associated with reduced plasma utilization., (Copyright © 2021 Elsevier Inc. All rights reserved.)

During warfarin management, variability in prothrombin time-based international normalized ratio (PT-INR) is caused, in part, by clinically inconsequential fluctuations in factor VII (FVII). The new factor II and X (Fiix)-prothrombin time (Fiix-PT) and Fiix-normalized ratio (Fiix-NR), unlike PT-INR, are only affected by reduced FII and FX. We assessed the incidence of thromboembolism (TE) and major bleeding (MB) in all 2667 patients on maintenance-phase warfarin managed at our anticoagulation management service during 30 months; 12 months prior to and 18 months after replacing PT-INR monitoring with Fiix-NR monitoring. Months 13 to 18 were predefined as transitional months. Using 2-segmented regression, a breakpoint in the monthly incidence of TE became evident 6 months after test replacement, that was followed by a 56% reduction in incidence (from 2.82% to 1.23% per patient-year; P = .019). Three-segmented regression did not find any significant trend in TE incidence (slope, +0.03) prior to test replacement; however, during months 13 to 18 and 19 to 30, the incidence of TE decreased gradually (slope, -0.12; R2 = 0.20; P = .007). The incidence of MB (2.79% per patient-year) did not differ. Incidence comparison during the 12-month Fiix and PT periods confirmed a statistically significant reduction (55-62%) in TE. Fiix monitoring reduced testing, dose adjustments, and normalized ratio variability and prolonged testing intervals and time in range. We conclude that ignoring FVII during Fiix-NR monitoring in real-world practice stabilizes the anticoagulant effect of warfarin and associates with a major reduction in TEs without increasing bleeding., (© 2021 by The American Society of Hematology.)

Background: The patency of a permanent arteriovenous catheter plays a significant role in the functioning of the catheter among patients dependent on the hemodialysis. Thrombosis formation is one of the most critical reasons for the short-term efficacy of the embedded catheters. The present study aimed to evaluate the efficacy and safety of warfarin for hemodialysis catheter failure prevention., Methods: This randomized clinical trial has been conducted on patients under hemodialysis using a permanent arteriovenous catheter. The patients were randomly allocated to the control group and the intervention group. The intervention group was treated with warfarin to achieve a target international normalized ratio (INR) of 1.5-2. The control group did not receive any treatment. The patients were followed for 12 months to assess the efficacy defined as the incidence of catheter clotting and safety defined as warfarin-related hemorrhage., Results: Eighty-six patients with end-stage renal disease under hemodialysis were included, among which 43 ones were allocated to the intervention group and the latter ones to the control group. The participants of both groups were similar in terms of demographic, clinical, and baseline laboratory characteristics. Four patients (9.3%) presented with warfarin-induced hematoma, among which the warfarin administration stopped for 5.33 ± 1.44 days and then restarted again. None of the patients was forced to cease warfarin therapy because of significant hemorrhages. The mean duration of catheter functioning was 8.30 ± 1.75 months in the intervention group versus 3.90 ± 1.12 months in the controls (P-value<0.001)., Conclusions: Based on the findings of the present study, the use of warfarin to achieve an INR level of 1.5-2 could effectively lead to a longer duration of permanent hemodialysis catheter functioning., (Copyright © 2020 Elsevier Inc. All rights reserved.)