scholarly journals Predicting anticoagulant-related bleeding in patients with venous thromboembolism: a clinically oriented review

2014 ◽  
Vol 45 (1) ◽  
pp. 201-210 ◽  
Author(s):  
Frederikus A. Klok ◽  
Judith Kooiman ◽  
Menno V. Huisman ◽  
Stavros Konstantinides ◽  
Mareike Lankeit

Diagnosis of venous thromboembolism (VTE) requires prompt treatment with anticoagulants in therapeutic doses. Since these drugs are associated with the occurrence of haemorrhage, identification of patients at increased risk of major bleeding is of utmost clinical importance for defining the optimal treatment regimen and duration of anticoagulation. Current suggested prediction scores for bleeding risk in VTE patients have been derived from observational studies of moderate quality, or from patients with various indications for therapeutic anticoagulation other than VTE. To date, none of the scores have been adequately validated in cohorts that underwent dedicated monitoring and independent adjudication of bleeding complications. In addition, while the scarce available evidence has focused on patients treated with heparins and/or vitamin K antagonists, risk stratification scores for bleeding complications in VTE patients treated with non-vitamin K dependent anticoagulants have not yet been developed. This clinically oriented review covers the incidence and risk factors of anticoagulation-related bleeding in VTE patients treated with different anticoagulant drugs as well as the available bleeding-prediction scores. Further, we attempt to provide guidance for bleeding-prevention in clinical practice and speculate on developments in the near future that may fundamentally change our current thinking on VTE management.

Author(s):  
Andrea N. Frei ◽  
Odile Stalder ◽  
Andreas Limacher ◽  
Marie Méan ◽  
Christine Baumgartner ◽  
...  

Abstract Background In elderly patients with venous thromboembolism (VTE), the decision to extend anticoagulation beyond 3 months must be weighed against the bleeding risk. We compared the predictive performance of 10 clinical bleeding scores (VTE-BLEED, Seiler, Kuijer, Kearon, RIETE, ACCP, OBRI, HEMORR2HAGES, HAS-BLED, ATRIA) in elderly patients receiving extended anticoagulation for VTE. Methods In a multicenter Swiss cohort study, we analyzed 743 patients aged ≥65 years who received extended treatment with vitamin K antagonists after VTE. The outcomes were the time to a first major and clinically relevant bleeding. For each score, we classified patients into two bleeding risk categories (low/moderate vs. high). We calculated likelihood ratios and the area under the receiver operating characteristic (ROC) curve for each score. Results Over a median anticoagulation duration of 10.1 months, 45 patients (6.1%) had a first major and 127 (17.1%) a clinically relevant bleeding. The positive likelihood ratios for predicting major bleeding ranged from 0.69 (OBRI) to 2.56 (Seiler) and from 1.07 (ACCP) to 2.36 (Seiler) for clinically relevant bleeding. The areas under the ROC curves were poor to fair and varied between 0.47 (OBRI) and 0.70 (Seiler) for major and between 0.52 (OBRI) and 0.67 (HEMORR2HAGES) for clinically relevant bleeding. Conclusion The predictive performance of most clinical bleeding risk scores does not appear to be sufficiently high to identify elderly patients with VTE who are at high risk of bleeding and who may therefore not be suitable candidates for extended anticoagulation.


2021 ◽  
Vol 8 ◽  
Author(s):  
Eve Cariou ◽  
Kevin Sanchis ◽  
Khailène Rguez ◽  
Virginie Blanchard ◽  
Stephanie Cazalbou ◽  
...  

Background: Atrial arrhythmia (AA) is common among patients with cardiac amyloidosis (CA), who have an increased risk of intracardiac thrombus. The aim of this study was to explore the prognostic impact of vitamin K-antagonists (VKA) and direct oral anticoagulants (DOAC) in patients with CA.Methods and Results: 273 patients with CA and history of AA with long term anticoagulation−69 (25%) light chain amyloidosis (AL), 179 (66%) wild-type transthyretin amyloidosis (ATTRwt) and 25 (9%) variant transthyretin amyloidosis (ATTRv)–were retrospectively included between January 2012 and July 2020. 147 (54%) and 126 (46%) patients received VKA and DOAC, respectively. Patient receiving VKA were more likely to have AL with renal dysfunction, higher NT-proBNP and troponin levels. Patients with ATTRwt were more likely to receive DOAC therapy. There were more bleeding complications among patients with VKA (20 versus 10%; P = 0.013) but no difference for stroke events (4 vs. 2%; P = 0.223), as compared to patients with DOAC. A total of 124 (45%) patients met the primary endpoint of all-cause mortality: 96 (65%) and 28 (22%) among patients with VKAs and DOACs, respectively (P < 0.001). After multivariate analysis including age and renal function, VKA was no longer associated with all-cause mortality.Conclusion: Among patients with CA and history of AA receiving oral anticoagulant, DOACs appear to be at least as effective and safe as VKAs.


2020 ◽  
Vol 73 (11) ◽  
pp. 2528-2534
Author(s):  
Dagmara Wojtowicz ◽  
Anna Tomaszuk-Kazberuk ◽  
Jolanta Małyszko ◽  
Marek Koziński

Non-vitamin K antagonist oral anticoagulants (NOACs) are currently recommended for oral anticoagulation in patients with non-valvular atrial fibrillation. In the setting, NOACs effectively prevent from stroke and systemic embolic events. In spite of the favorable safety profile of NOACs when compared with vitamin K antagonists, the use of any kind of anticoagulation is associated with an increased risk of bleeding. However, there is still a lack of direct comparisons of effectiveness and safety among NOACs. The results of indirect comparisons and meta-analyses suggest that the risk of various types of hemorrhagic complications differ among the particular NOACs. Management of bleeding in patients under NOAC therapy can be challenging because of limited availability of antidotes and the lack of routine laboratory test monitoring the NOAC anticoagulant effect. In case of life-threatening or critical site bleeding, reversal of NOAC anticoagulant activity is essential together with immediate implementation of causative treatment. Moreover, some patients on chronic NOAC therapy may require urgent surgery or invasive procedures. Specific reversal agents for NOACs have been developed, i.e. more widely available idarucizumab for the factor IIa inhibitor (dabigatran) and andexanet alfa for the factor Xa inhibitors (rivaroxaban, apixaban, edoxaban) with limited availability. This review summarizes the occurrence and management of NOAC-related bleeding complications with a particular emphasis on hematuria.


2015 ◽  
Vol 113 (04) ◽  
pp. 881-890 ◽  
Author(s):  
Nic J. G. M. Veeger ◽  
Nakisa Khorsand ◽  
Hanneke C. Kluin-Nelemans ◽  
Hilde A. M. Kooistra ◽  
Karina Meijer ◽  
...  

SummaryVitamin K antagonists (VKA) are widely used in atrial fibrillation and venous thromboembolism (VTE). Their efficacy and safety depend on individual time in the therapeutic range (iTTR). Due to the variable dose-response relationship within patients, also patients with initially stable VKA treatment may develop extreme overanticoagulation (EO). EO is associated with an immediate bleeding risk, but it is unknown whether VKA treatment will subsequently restabilise. We evaluated long-term quality of VKA treatment and clinical outcome after EO. EO was defined as international normalized ratio (INR) ≥ 8.0 and/or unscheduled vitamin K supplementation. We included a consecutive cohort of initially stable atrial fibrillation and venous thromboembolism patients. In EO patients, the 90 days pre- and post-period were compared. In addition, patients with EO were compared with patients without EO using a matched 1:2 cohort. Of 14,777 initially stable patients, 800 patients developed EO. The pre-period was characterised by frequent overanticoagulation, and half of EO patients had an inadequate iTTR (< 65 %). After EO, underanticoagulation became more prevalent. Although the mean time between INR-measurements decreased from 18.6 to 13.2 days, after EO inadequate iTTR became more frequent (62 %), p-value < 0.001. A 2.3 times (95 % confidence interval [CI] 2.0–2.5) higher risk for iTTR< 65 % after EO, was accompanied by increased risk of bleeding (hazard ratio [HR] 2.1;CI 1.4–3.2), VKA-related death 17.0 (HR 17.0;CI 2.1–138) and thrombosis (HR 5.7;CI 1.5–22.2), compared to the 1600 controls. In conclusion, patients continuing VKA after EO have long-lasting inferior quality of VKA treatment despite intensified INR-monitoring, and an increased risk of bleeding, thrombosis and VKA-related death.Note: There have been no previous presentations, reports or publications of the complete data that appear in the article. Parts of the data in this article have been presented as a poster at the American Society of Hematology (ASH) congress 2013, New Orleans, United States.


2012 ◽  
Vol 32 (01) ◽  
pp. 37-39 ◽  
Author(s):  
C. Bode ◽  
M. Moser

SummaryAtrial fibrillation is one of the most frequent reasons for therapeutic anticoagulation in everyday practice. Oral vitamin K antagonists such as Marcumar have been state of the art anticoagulants to prevent thrombembolic events in patients with atrial fibrillation and additional risk factors. But these drugs are accompanied by disadvantages such as increased bleeding risk and impaired quality of life caused by interactions with food or other medications as well as frequent controls of INRs.The new anticoagulants apixaban, rivaroxaban and dabigatran are direct antagonists of coagulation factors (FXa or FIIa) and demonstrate a promising risk/benefit profile in large clinical trials compared with vitamin K antagonists.Their approval for clinical use will open up new therapeutic perspectives for patients with atrial fibrillation and indication for anticoagulation.


2015 ◽  
Vol 114 (11) ◽  
pp. 1076-1084 ◽  
Author(s):  
Franziska Michalski ◽  
Luise Tittl ◽  
Sebastian Werth ◽  
Ulrike Hänsel ◽  
Sven Pannach ◽  
...  

SummaryAtrial fibrillation (AF) patients treated with well-controlled vitamin K antagonists (VKAs) may benefit less from non-vitamin K antagonist oral anticoagulants (NOACs) because they are supposed to be at low risk of thromboembolic and bleeding complications. However, little is known about the selection, management, and outcome of such “stable” VKA patients in current practice. We assessed characteristics, VKA persistence and 12 months' outcome of AF patients selected for VKA continuation. On March 1, 2013, the Dresden NOAC registry opened recruitment of patients continuing on VKA for sites that had been actively recruiting AF patients treated with NOACs in the prior 18 months. Patient characteristics were compared with those of NOAC patients from the same sites. Four hundred twenty-seven VKA patients had a significantly lower bleeding risk profile compared with 706 patients selected for NOAC treatment. For VKA, international normalised ratio time-in-therapeutic range before enrolment was 71% and increased to 75% during a mean follow-up of 15 months. Rates of stroke/transient ischaemic attack/systemic embolism were 1.3/100 patient-years (intention-to-treat) and 0.94/100 patient-years (as-treated). On-treatment rate of ISTH major bleeding was 4.15/100 patient-years (95% CI 2.60–6.29) with a case-fatality rate of 16.3% (all-cause mortality at day 90 after major bleeding). In conclusion, in daily care, AF patients selected for VKA therapy are healthier than those treated with NOAC, demonstrate a high quality of anticoagulant control and very low stroke rates. However, despite adequate patient selection and INR control, the risk of major VKA bleeding is unacceptably high and bleeding outcome is poor.


Blood ◽  
2011 ◽  
Vol 118 (20) ◽  
pp. 5394-5400 ◽  
Author(s):  
Saskia Middeldorp

Abstract Venous thromboembolism (VTE) complicates ∼ 1 to 2 of 1000 pregnancies, with pulmonary embolism being a leading cause of maternal mortality and deep vein thrombosis an important cause of maternal morbidity, also on the long term. However, a strong evidence base for the management of pregnancy-related VTE is missing. Management is not standardized between physicians, centers, and countries. The management of pregnancy-related VTE is based on extrapolation from the nonpregnant population, and clinical trial data for the optimal treatment are not available. Low-molecular-weight heparin (LMWH) in therapeutic doses is the treatment of choice during pregnancy, and anticoagulation (LMWH or vitamin K antagonists postpartum) should be continued until 6 weeks after delivery with a minimum total duration of 3 months. Use of LMWH or vitamin K antagonists does not preclude breastfeeding. Whether dosing should be based on weight or anti-Xa levels is unknown, and practices differ between centers. Management of delivery, including the type of anesthesia if deemed necessary, requires a multidisciplinary approach, and several options are possible, depending on local preferences and patient-specific conditions.


2018 ◽  
Vol 45 (02) ◽  
pp. 205-214 ◽  
Author(s):  
Roberta Bottino ◽  
Anna Rago ◽  
Pierpaolo Micco ◽  
Antonio D' Onofrio ◽  
Biagio Liccardo ◽  
...  

AbstractAtrial fibrillation (AF) is commonly diagnosed in the setting of active cancer. Because of an increased risk of either thromboembolic events or bleeding, the decision to initiate therapeutic anticoagulation in patients with active cancer can be challenging. Moreover, little is still known about the optimal anticoagulation therapy in the setting of AF and cancer, and no guidelines are as yet available. Considering that nonvitamin K antagonist oral anticoagulants (NOACs) are recommended as alternatives to vitamin K antagonists for stroke prevention in AF patients with CHA2DS2-VASc score ≥2, the authors performed a systematic review of the current literature to describe the efficacy and safety of NOACs in AF patients with malignancy.


2017 ◽  
Vol 117 (07) ◽  
pp. 1432-1439 ◽  
Author(s):  
Joseph S. Biedermann ◽  
Willem M. H. Rademacher ◽  
Hendrika C. A. M. Hazendonk ◽  
Denise E. van Diermen ◽  
Frank W. G. Leebeek ◽  
...  

SummaryPatients on vitamin K antagonists (VKA) often undergo invasive dental procedures. International guidelines consider all dental procedures as low-risk procedures, while bleeding risk may differ between standard low-risk (e. g. extraction 1–3 elements) and extensive high-risk (e.g. extraction of >3 elements) procedures. Therefore current guidelines may need refinement. In this cohort study, we identified predictors of oral cavity bleeding (OCB) and evaluated clinical outcome after low-risk and highrisk dental procedures in patients on VKA. Perioperative management strategy, procedure risk, and 30-day outcomes were assessed for each procedure. We identified 1845 patients undergoing 2004 low-risk and 325 high-risk procedures between 2013 and 2015. OCB occurred after 67/2004 (3.3 %) low-risk and 21/325 (6.5 %) high-risk procedures (p=0.006). In low-risk procedures, VKA continuation with tranexamic acid mouthwash was associated with a lower OCB risk compared to continuation without mouthwash [OR=0.41, 95 %CI 0.23–0.73] or interruption with bridging [OR=0.49, 95 %CI 0.24–1.00], and a similar risk as interruption without bridging [OR=1.44, 95 %CI 0.62–3.64]. In high-risk procedures, VKA continuation was associated with an increased OCB risk compared to interruption [OR=3.08, 95 %CI 1.05–9.04]. Multivariate analyses revealed bridging, antiplatelet therapy, and a supratherapeutic or unobjectified INR before the procedure as strongest predictors of OCB. Non-oral cavity bleeding (NOCB) and thromboembolic event (TE) rates were 2.1 % and 0.2 %. Bridging therapy was associated with a two-fold increased risk of NOCB [OR=1.93, 95 %CI 1.03–3.60], but not with lower TE rates. In conclusion, predictors of OCB were mostly related to perioperative management and differed between low-risk and high-risk procedures. Perioperative management should be differentiated accordingly.


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