scholarly journals How I assess and manage the risk of bleeding in patients treated for venous thromboembolism

Blood ◽  
2020 ◽  
Vol 135 (10) ◽  
pp. 724-734 ◽  
Author(s):  
Frederikus A. Klok ◽  
Menno V. Huisman

Abstract For patients with venous thromboembolism (VTE), prediction of bleeding is relevant throughout the course of treatment, although the means and goal of this prediction differ between the subsequent stages of treatment: treatment initiation, hospital discharge, 3-month follow-up, and long-term follow-up. Even in the absence of fully established risk prediction schemes and outcome studies using a prediction scheme for treatment decisions, the present evidence supports screening for and targeting of modifiable risk factors for major bleeding, as well as the application of decision rules to identify patients at low risk of bleeding complications, in whom long-term anticoagulant treatment is likely safe. Moving forward, prediction tools need to be incorporated in well-designed randomized controlled trials aiming to establish optimal treatment duration in patients at high risk of recurrent VTE. Moreover, the benefit of their longitudinal assessment rather than application as stand-alone baseline assessments should be studied, because changes in bleeding risk over time likely constitute the best predictor of major bleeding. We provide the state-of-the-art of assessing and managing bleeding risk in patients with acute VTE and highlight a practical approach for daily practice illustrated by 2 case scenarios.

2014 ◽  
Vol 112 (09) ◽  
pp. 511-521 ◽  
Author(s):  
Marta Bellesini ◽  
Matteo Nicola Dario Di Minno ◽  
Nicola Mumoli ◽  
Fulvio Pomero ◽  
Massimo Franchini ◽  
...  

SummaryBleeding is a common and feared complication of oral anticoagulant therapy. Several prediction models have been recently developed, but there is a lack of evidence in patients with venous thromboembolism (VTE). The aim of this study was to validate currently available bleeding risk scores during long-term oral anticoagulation for VTE. We retrospectively included adult patients on vitamin K antagonists for VTE secondary prevention, followed by five Italian Anticoagulation Clinics (Cuneo, Livorno, Mantova, Napoli, Varese), between January 2010 and August 2012. All bleeding events were classified as major bleeding (MB) or clinically-relevant-non-major-bleeding (CRNMB). A total of 681 patients were included (median age 63 years; 52.0% female). During a mean follow-up of 8.82 (± 3.59) months, 50 bleeding events occurred (13 MB and 37 CRNMB), for an overall bleeding incidence of 9.99/100 patient-years. The rate of bleeding was higher in the first three months of treatment (15.86/100 patient-years) than afterwards (7.13/100 patient-years). The HAS-BLED showed the best predictive value for bleeding complications during the first three months of treatment (area under the curve [AUC] 0.68, 95% confidence interval [CI] 0.59–0.78), while only the ACCP score showed a modest predictive value after the initial three months (AUC 0.61, 95%CI 0.51–0.72). These two scores had also the highest sensitivity and the highest negative predictive value. None of the scores predicted MB better than chance. Currently available bleeding risk scores had only a modest predictive value for patients with VTE. Future studies should aim at the creation of a new prediction rule, in order to better define the risk of bleeding of VTE patients.


EP Europace ◽  
2021 ◽  
Vol 23 (Supplement_3) ◽  
Author(s):  
A Briosa E Gala ◽  
MTB Pope ◽  
C Monteiro ◽  
M Leo ◽  
TR Betts

Abstract Funding Acknowledgements Type of funding sources: None. Introduction Left atrial appendage occlusion (LAAO) is a well-established stroke prevention strategy in patients with non-valvular atrial fibrillation (AF) and high risk of bleeding or contra-indication to oral anticoagulation (OAC). Despite encouraging randomised control trial and international registry safety and efficacy data, long-term outcome data remains sparce. Purpose This study sought to evaluate the long-term outcomes in ‘real-world’ AF patients undergoing left atrial appendage occlusion in a large UK tertiary centre. Methods This retrospective study included all patients that had a LAAO device implanted in our institution from January 2010 to December 2020. Medical notes, electronic patient records, procedural and imaging reports were reviewed. Annual bleeding risk was extrapolated from the Swedish National Cohort study according to CHA2DS2-VASc and HASBLED score. Results During the study period a total of 225 patients underwent LAAO device implant. Seventy-two percent were male, age 74 ± 8 years, BMI 27 ± 6 kg/m2, CHA2DS2-VASc score 4.4 ± 1.2, HASBLED score 3.2 ± 0.8 and at high risk of stroke (98 ischaemic strokes and 129 haemorrhagic strokes) and bleeding (151 life-threatening bleeding episodes). Three different LAAO devices were used: 136 Watchman, 54 Watchman FLX and 35 Amplatzer Cardiac plugs. Three patients (1.3%) had fatal complications related to the procedure. At discharge, 10% were taking single antiplatelet (ATP), 79% dual-antiplatelet (DAPT), 1.4% OAC, 3.6% ATP and OAC, 3.1% DAPT and OAC, 1.3% were not taking any anti-thrombotic. Nine (4%) patients had device-related thrombus on follow-up transoesophageal echocardiography with no significant difference between devices (5.0%, 2.8% and 6.7% p = 0.8, respectively) and anticoagulation strategy (p = 0.7). Over a total follow-up of 889 patient-years (mean follow-up 3.9 ± 3.7 years), 24 (10.4%) patients died, 55 patients (6.2/100 patient-years) suffered an adverse event, 15 ischaemic strokes (1.7/100 patient-years) and 20 non-procedural major bleeding episodes (2.3/100 patient-years) occurred. Compared to estimated annual stroke and bleeding risk adjusted for CHA2DS2-VASc and HASBLED score, our cohort had a 79% and 65% relative risk reduction in ischaemic stroke and major bleeding, respectively. Conclusion In this cohort of "real-world" high-risk patients, major bleeding and thromboembolic rate remained low on long-term follow-up. Abstract Figure 1


2008 ◽  
Vol 100 (09) ◽  
pp. 435-439 ◽  
Author(s):  
Javier Trujillo-Santos ◽  
José Nieto ◽  
Gregorio Tiberio ◽  
Andrea Piccioli ◽  
Pierpaolo Micco ◽  
...  

SummaryCancer patients with acute venous thromboembolism (VTE) have an increased incidence of recurrences and bleeding complications while on anticoagulant therapy. Methods RIETE is an ongoing registry of consecutive patients with acute VTE. We tried to identify which cancer patients are at a higher risk for recurrent pulmonary embolism (PE), deep vein thrombosis (DVT) or major bleeding. Up to May 2007, 3, 805 cancer patients had been enrolled in RIETE. During the first three months of follow-up after the acute, index VTE event, 90 (2.4%) patients developed recurrent PE, 100 (2.6%) recurrent DVT, 156 (4.1%) had major bleeding. Forty patients (44%) died of the recurrent PE,46 (29%) of bleeding. On multivariate analysis, patients aged <65 years (odds ratio [OR]: 3.0; 95% confidence interval [CI]: 1.9–4.9), with PE at entry (OR: 1.9; 95% CI: 1.2–3.1), or with <3 months from cancer diagnosis to VTE (OR: 2.0; 95% CI: 1.2–3.2) had an increased incidence of recurrent PE. Those aged <65 years (OR: 1.6; 95% CI: 1.0–2.4) or with <3 months from cancer diagnosis (OR: 2.4; 95% CI: 1.5–3.6) had an increased incidence of recurrent DVT. Finally, patients with immobility (OR: 1.8; 95% CI: 1.2–2.7), metastases (OR: 1.6; 95% CI: 1.1–2.3), recent bleeding (OR: 2.4; 95% CI: 1.1–5.1), or with creatinine clearance <30 ml/ min (OR: 2.2; 95% CI: 1.5–3.4), had an increased incidence of major bleeding. With some variables available at entry we may identify those cancer patients withVTE at a higher risk for recurrences or major bleeding.


2010 ◽  
Vol 2010 ◽  
pp. 1-7 ◽  
Author(s):  
L. Testa ◽  
G. G. L. Biondi Zoccai ◽  
M. Valgimigli ◽  
R. A. Latini ◽  
S. Pizzocri ◽  
...  

Thienopyridines are a class of drug targeting the platelet adenosine diphosphate (ADP) 2 receptor. They significantly reduce platelet activity and are therefore clinically beneficial in settings where platelet activation is a key pathophysiological feature, particularly myocardial infarction. Ticlopidine, the first of the class introduced to clinical practice, was soon challenged and almost completely replaced by clopidogrel for its better tolerability. More recently, prasugrel and ticagrelor have been shown to provide a more powerful antiplatelet action compared to clopidogrel but at a cost of higher risk of bleeding complications. Cangrelor, a molecule very similar to ticagrelor, is currently being evaluated against clopidogrel. Considering the key balance of ischemic protection and bleeding risk, this paper discusses the background to the development of prasugrel, ticagrelor, and cangrelor and aims to characterise their risk-benefit profile and possible implementation in daily practice.


2017 ◽  
Vol 44 (04) ◽  
pp. 348-352 ◽  
Author(s):  
Reinhard Raggam ◽  
Franz Hafner ◽  
Alexander Avian ◽  
Gerald Hackl ◽  
Gerhard Cvirn ◽  
...  

AbstractThe aim of this study was prospective evaluation of the performance of the HAS-BLED score in predicting major bleeding complications in a real-world outpatient cohort, during long-term anticoagulation for venous thromboembolism (VTE), treated with a broad spectrum of anticoagulants. We analyzed 111 outpatients objectively diagnosed with VTE and treated long-term with various anticoagulants. Patients were grouped in three cohorts based on the anticoagulant regimen. Calculation of the HAS-BLED score and documentation of bleeding events were performed every 6 months for 1 year. Patients with a HAS-BLED score ≥ 3 had an increased risk for major bleeding events (odds ratio [OR]: 13.05, 95% confidence interval [CI]: 0.96–692.58, p = 0.028) and a trend to higher risk for minor bleeding events as well (OR: 2.25, 95% CI: 0.87–5.85, p = 0.091) when compared with patients with a HAS-BLED score < 3.This indicates that a HAS-BLED score ≥ 3 allows for identification of patients with VTE on long-term anticoagulation at an increased risk for major bleeding events, irrespective of the anticoagulant agent used.


2017 ◽  
Vol 117 (06) ◽  
pp. 1164-1170 ◽  
Author(s):  
Frederikus A. Klok ◽  
Stefano Barco ◽  
Stavros V. Konstantinides

SummaryOne of the main determinants of establishing the optimal treatment duration of patients with venous thromboembolism (VTE) is the risk of major bleeding during long-term anticoagulant therapy. The 6-variable VTE-BLEED score was recently developed to enable estimation of this bleeding risk. This study aimed at externally validating VTE-BLEED. This was a post-hoc study of the randomised, double-blind, double-dummy, Hokusai-VTE study that compared edoxaban versus warfarin for treatment of VTE. VTE-BLEED was calculated in all 8,240 study patients. The numbers of adjudicated major bleeding events during ‘stable anticoagulation’, i. e. occurring after day 30, in patients with low (total score <2 points) and high risk of bleeding (total score ≥2 points) were compared for the overall study population, patients randomised to edoxaban or warfarin, and for important patient subcategories. During ‘stable’ anticoagulation, major bleeding occurred in 1.02% (40/3,903) and 0.82% (32/3,899) of patients treated with warfarin and edoxaban, respectively. For the overall study population, the risks of bleeding in the low and high risk groups were 0.51% and 2.03%, respectively, for an odds ratio (OR) of 4.04 (95% confidence interval [CI]: 2.51–6.48). ORs were 5.04 (95%CI: 2.62–9.69) and 3.09 (95%CI: 1.54–6.22) for warfarin and edoxaban, respectively. VTE-BLEED was consistently able to identify patients at a 2.5- to 11-fold higher bleeding risk across all the predefined subcategories, as well as for the treatment period between day 30 to day 180, and beyond day 180. In conclusion, patients identified as high risk by VTE-BLEED had a four-fold increased risk of bleeding during the chronic phase of treatment.Supplementary Material to this article is available online at www.thrombosis-online.com.


2022 ◽  
Vol 12 ◽  
Author(s):  
Yi-hu Yi ◽  
Song Gong ◽  
Tian-lun Gong ◽  
Ling-yun Zhou ◽  
Can Hu ◽  
...  

Background: There is controversy over whether use of new oral anticoagulants (NOACs) associates with increased hemorrhage risk compared with non-NOAC. Meanwhile, determining which NOAC to use remains unclear. We aimed to summarize the evidence about NOACs in venous thromboembolism (VTE) prevention for patients with total hip and knee arthroplasty (THA and TKA).Methods: We searched RCTs assessing NOACs for VTE prophylaxis in adults undergoing THA and TKA in Medline, Embase, and Cochrane up to May 2021. Primary outcomes were VTE [included deep vein thrombosis (DVT) and pulmonary embolism (PE)], major VTE, and major bleeding. The rank probabilities of each treatment were summarized by the surface under the cumulative ranking curve area (SUCRA).Results: 25 RCTs with 42,994 patients were included. Compared with non-NOAC, NOACs were associated with a decreased risk of VTE (RR 0.68; 95% CI 0.55–0.84) and major VTE (RR = 0.52; 95% CI 0.35–0.76). Additionally, rivaroxaban, apixaban, and edoxaban but not dabigatran and betrixaban, did confer a higher efficacy compared with non-NOAC. None of the individual NOACs increased the risk of bleeding, while apixaban and betrixaban were even associated with a decreased risk of bleeding. In the comparison of different NOACs, rivaroxaban was associated with the greatest benefits in VTE (SUCRA = 79.6), DVT (SUCRA = 88.8), and major VTE (SUCRA = 89.9) prevention. Furthermore, subgroup analysis confirmed that NOACs associated with a higher efficacy tendency in patients with follow-up duration &lt;60 days than follow-up duration ≥60 days.Conclusion: Evidence suggests that NOACs exert more benefits on VTE prophylaxis, and none of the individual NOACs increased hemorrhage compared with non-NOAC. Among various NOACs, rivaroxaban is recommended in patients with lower bleeding risk, and apixaban is recommended in patients with higher bleeding risk.Systematic Review Registration: [https://www.crd.york.ac.uk/prospero/], identifier [CRD42021266890].


Author(s):  
Faizan Khan ◽  
Alvi Rahman ◽  
Tobias Tritschler ◽  
Marc Carrier ◽  
Clive Kearon ◽  
...  

Background: The long-term risk of major bleeding after discontinuing anticoagulant therapy for a first unprovoked venous thromboembolism (VTE) is uncertain. Objectives: To determine the incidence of major bleeding up to 5 years after discontinuing anticoagulation for a first unprovoked VTE. Methods: We searched MEDLINE, EMBASE, and Cochrane CENTRAL (from inception to January 2021) to identify relevant randomized controlled trials (RCTs) and prospective cohort studies reporting major bleeding after discontinuing anticoagulation in patients with a first unprovoked VTE who had completed ≥3 months of initial treatment. Unpublished data on major bleeding events and person-years were obtained from authors of included studies to calculate study-level incidence rates. Random-effects meta-analysis was used to pool results across studies. Results: Of 1123 records identified by the search, 20 studies (17 RCTs) and 8740 patients were included in the analysis. During 13 011 person-years of follow-up after discontinuing anticoagulation, the pooled incidence of major bleeding (n=41) and fatal bleeding (n=7) per 100 person-years was 0.35 (95% confidence interval [CI], 0.20-0.54) and 0.09 (95% CI, 0.05-0.15). The 5-year cumulative incidence of major bleeding was of 1.0% (95% CI, 0.4%-2.4%). The case-fatality rate of major bleeding after discontinuing anticoagulation was 19.9% (95% CI, 10.6%-31.1%). Conclusions: Patients with a first unprovoked VTE have a non-trivial risk of major bleeding once anticoagulants are discontinued. Estimates from this study can help clinicians counsel patients about the incremental risk of major bleeding with extended anticoagulation to guide decision making about treatment duration for unprovoked VTE.


Blood ◽  
2014 ◽  
Vol 123 (7) ◽  
pp. 955-956
Author(s):  
Bill Giannakopoulos ◽  
Steven Krilis

In this issue of Blood, Kolyada and colleagues elegantly demonstrate the therapeutic utility of a novel, synthetically constructed molecule, the A1 dimer (A1-A1), in preventing anti-β2 glycoprotein I (anti-β2GPI) autoantibody-mediated thrombosis in 2 distinct murine antiphospholipid syndrome (APS) thrombosis models. Current therapies for thrombotic APS entail long-term anticoagulation, with the associated risk of bleeding complications. The findings presented by Kolyada et al raise the possibility of perhaps using this agent to treat thrombotic APS patients in the future, allowing for a reduction in bleeding risk.1


2008 ◽  
Vol 14 (2) ◽  
pp. 149-158 ◽  
Author(s):  
Sylvia Haas ◽  
Alex C. Spyropoulos

Venous thromboembolism (VTE) is a significant, but underestimated, cause of morbidity and mortality in long-term care settings. VTE risk increases significantly with age and is further increased by comorbidities common to this group; however, advancing age and limited mobility alone are insufficient to warrant pharmacological prophylaxis. Recognizing those at increased VTE risk during an acute illness is crucial for appropriate and timely prophylaxis. Warfarin is used for the long-term secondary prevention of VTE, whereas unfractionated and low-molecular-weight heparins are used for primary prophylaxis. The elderly are at increased risk for bleeding complications, because of the high frequency of comorbidities and comedications. Attention to dosing is recommended for those with severely impaired renal function, low body weight, or perceived to be at high bleeding risk. This review addresses the role of risk assessment in the decision of when to provide prophylaxis to an individual in long-term care and highlights key management issues for those prescribed prophylaxis.


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