Intracranial haemorrhage in patients with atrial fibrillation on anticoagulants

ESC CardioMed ◽  
2018 ◽  
pp. 976-978
Author(s):  
Heinrich Mattle ◽  
Marcel Arnold ◽  
Urs Fischer
Keyword(s):  
Risk Factors ◽  
Intracranial Haemorrhage ◽  
Early Recognition ◽  
Vitamin K Antagonists ◽  
Factor Xa ◽  
Bleeding Risk ◽  
Risk Of Bleeding ◽  
Anticoagulation Treatment ◽  
Life Saving

Anticoagulants increase the risk of bleeding. Rarely, they become devastating instead of preventing thrombosis and embolism. Intracranial haemorrhagic complications in particular can be disabling or fatal. Careful monitoring of anticoagulation and treatment of risk factors are important to reduce the bleeding risk and, if haemorrhage occurs nonetheless, early recognition and management can be life-saving and reduce long-term sequelae. Controlling the intensity of anticoagulation, treatment of hypertension, avoiding concomitant use of other antithrombotic drugs, and observing drug–drug interactions minimize the bleeding risk of anticoagulants. In case of anticoagulation-related intracranial haemorrhage, immediate normalization of coagulation is the cornerstone of treatment in addition to general measures. Prothrombin complex concentrate serves as the best antidote against vitamin K antagonists, idarucizumab to reverse the effect of dabigatran, and andexanet alfa to antagonize the inhibition of factor Xa.

Bleeding risk in anticoagulated patients with atrial fibrillation

ESC CardioMed ◽  
2018 ◽  
pp. 2195-2198
Author(s):  
Margaret C. Fang
Keyword(s):  
Risk Factors ◽  
Atrial Fibrillation ◽  
Intracranial Haemorrhage ◽  
Vitamin K Antagonists ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Bleeding Risk ◽  
Clinical Risk Factors ◽  
Anticoagulation Management ◽  
Clinical Risk

Bleeding is the primary complication associated with chronic anticoagulant treatment of atrial fibrillation and can range from minor, clinically insignificant bleeds to life-threatening events. Anticoagulants increase an individual’s bleeding risk by approximately 2–2.5-fold. The absolute rates of bleeding vary depending on the presence or absence of specific clinical risk factors, as well as the type of anticoagulant and the quality of anticoagulation management. There are many clinical risk factors for bleeding including older age, hypertension, prior bleeding, anaemia, and kidney impairment. Concomitant use of other medications, in particular other antithrombotic/antiplatelet drugs, also significantly raises bleeding risk. Intracranial haemorrhage, a relatively uncommon but widely feared complication of anticoagulants, results in a 30-day mortality of about 40%. Risk factors for intracranial haemorrhage include advanced age, elevated blood pressure, a history of cerebrovascular disease, and cerebral amyloid angiopathy. A number of risk stratification schemes have been developed in order to better estimate the risk of anticoagulant-related bleeding. Most of the risk schemes were developed and validated in patients taking vitamin K antagonists, but have increasingly been applied to populations taking the newer direct oral anticoagulants. Although bleeding risk tools can be useful to assist in counselling patients about their bleeding risk, in general, these risk schemes are only moderately predictive and are probably best applied to patients who are considered reasonable candidates for anticoagulation and who are on the lower end of ischaemic stroke risk.

Risk Factors for Bleeding during Treatment of Acute Venous Thromboembolism

1996 ◽  
Vol 76 (05) ◽  
pp. 682-688 ◽  
Author(s):  
Jos P J Wester ◽  
Harold W de Valk ◽  
Karel H Nieuwenhuis ◽  
Catherine B Brouwer ◽  
Yolanda van der Graaf ◽  
...  
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Surface Area ◽  
Body Surface Area ◽  
Body Surface ◽  
Small Body ◽  
Bleeding Risk ◽  
Risk Scores ◽  
Risk Of Bleeding ◽  
Acute Venous Thromboembolism

Summary Objective: Identification of risk factors for bleeding and prospective evaluation of two bleeding risk scores in the treatment of acute venous thromboembolism. Design: Secondary analysis of a prospective, randomized, assessor-blind, multicenter clinical trial. Setting: One university and 2 regional teaching hospitals. Patients: 188 patients treated with heparin or danaparoid for acute venous thromboembolism. Measurements: The presenting clinical features, the doses of the drugs, and the anticoagulant responses were analyzed using univariate and multivariate logistic regression analysis in order to evaluate prognostic factors for bleeding. In addition, the recently developed Utrecht bleeding risk score and Landefeld bleeding risk index were evaluated prospectively. Results: Major bleeding occurred in 4 patients (2.1%) and minor bleeding in 101 patients (53.7%). For all (major and minor combined) bleeding, body surface area ≤2 m2 (odds ratio 2.3, 95% Cl 1.2-4.4; p = 0.01), and malignancy (odds ratio 2.4, 95% Cl 1.1-4.9; p = 0.02) were confirmed to be independent risk factors. An increased treatment-related risk of bleeding was observed in patients treated with high doses of heparin, independent of the concomitant activated partial thromboplastin time ratios. Both bleeding risk scores had low diagnostic value for bleeding in this sample of mainly minor bleeders. Conclusions: A small body surface area and malignancy were associated with a higher frequency of bleeding. The bleeding risk scores merely offer the clinician a general estimation of the risk of bleeding. In patients with a small body surface area or in patients with malignancy, it may be of interest to study whether limited dose reduction of the anticoagulant drug may cause less bleeding without affecting efficacy.

scholarly journals Bleeding Risk in Non-Valvular Atrial Fibrillation Patients Receiving Direct Oral Anticoagulants and Warfarin: A Systematic Review and Meta-Analysis of Observational Studies

Blood ◽  
2019 ◽  
Vol 134 (Supplement_1) ◽  
pp. 3672-3672 ◽  
Author(s):  
Yimin Pearl Wang ◽  
Rohan Kehar ◽  
Alla Iansavitchene ◽  
Alejandro Lazo-Langner
Keyword(s):  
Major Bleeding ◽  
Lower Risk ◽  
Observational Studies ◽  
Meta Analysis ◽  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Bleeding Risk ◽  
Risk Of Bleeding ◽  
Significant Difference

Introduction: The standard oral anticoagulant therapy administered to non-valvular AF patients has typically been Vitamin K Antagonists (VKA) particularly warfarin. In recent years, Direct Oral Anticoagulants (DOACs) including Direct Thrombin Inhibitors (DTI) and Direct Factor Xa inhibitors (FXa inhibitors) have become an alternative to warfarin. Randomized trials comparing warfarin and DOACs showed comparable effectiveness without significant additional major bleeding risk. However, bleeding events in RCTs may differ from those in daily use due to the routine exclusion of patients with a higher risk of bleeding from many studies. We aimed to assess bleeding risk between DOACs and warfarin in AF patients in observational studies and we also sought to determine differences between patients that were experienced or naïve to oral anticoagulants. Methods: A systematic literature search was conducted in the OVID MEDLINE® and EMBASE® electronic databases. Observational studies and randomized control trials (RCT) from 1990 to January 2019 were retrieved and examined by two independent reviewers. A pooled effect hazard ratio (HR) was calculated using a random effects model using the generic inverse variance method. Subgroup analyses according to previous exposure to anticoagulants, study type, funding type and DOAC type were conducted. The primary outcome was major bleeding risk. The secondary outcome was clinically relevant non-major bleeding. All studies must have used an established or validated definition of major bleeding. Results: The initial literature search identified 3359 potentially eligible citations. After primary screening, 150 articles were eligible for full text review and there were 35 studies including 2,356,201 patients that met the inclusion criteria. Overall, patients on DOACs were less likely to experience a bleeding event compared to warfarin (HR 0.78, 95%CI 0.71, 0.85, P<0.001). The results were consistent when analyzing patients receiving DTIs or FXa inhibitors (DTI: HR 0.76, 95% CI 0.67,0.87; FXa inhibitors: HR 0.79, 95% CI 0.69,0.89). However, among patients receiving factor Xa inhibitors, there was a significant difference in the risk of bleeding according to individual drug. Among patients receiving rivaroxaban the risk of bleeding was similar to warfarin (HR 0.98, 95%CI 0.91,1.06, p=0.60) whereas in those receiving apixaban there was a 40% reduction in the risk of bleeding compared to warfarin (HR 0.60, 95%CI 0.50,0.71, p<0.001) (Figure 1). Three studies reported information according to previous anticoagulant exposure. The overall pooled hazard ratio was 0.68 (95% CI 0.55, 0.82 p<0.001) in favor of patients on DOACs. In the subgroup analysis of previous anticoagulant use, the risk of bleeding was lower for DOACs compared to warfarin in both the experienced population (HR 0.70, 95%CI 0.51, 0.96) and the naïve population (HR 0.64, 95% CI 0.47,0.87). However, heterogeneity was moderate to high among both subgroups. Conclusion: This review and meta-analysis of observational studies including over 2.3 million patients showed that overall DOACs have a lower risk of major bleeding and clinically relevant non-major bleeding compared to warfarin. Most importantly, although the pooled effect estimate did not differ between DTIs and FXa inhibitors, among patients receiving FXa inhibitors there was a significant difference between individual agents. Patients on apixaban had a significantly lower risk of bleeding compared to warfarin in contrast to patients on rivaroxaban who had a similar risk. Disclosures No relevant conflicts of interest to declare.

Anticoagulation Treatment in Venous Thromboembolism: Options and Optimal Duration

2021 ◽  
Vol 27 ◽  
Author(s):  
Stavrianna Diavati ◽  
Marios Sagris ◽  
Dimitrios Terentes-Printzios ◽  
Charalambos Vlachopoulos
Keyword(s):  
Risk Factors ◽  
Venous Thromboembolism ◽  
Anticoagulation Therapy ◽  
Factor Xa ◽  
Coagulation Cascade ◽  
Clinical Genetic ◽  
Vein Thrombosis ◽  
Anticoagulation Treatment ◽  
Molecular Pathophysiology ◽  
Deep Vein

: Venous thromboembolism (VTE), clinically presenting as deep-vein thrombosis (DVT) or pulmonary embolism (PE), constitutes a major global healthcare concern with severe complications, long-term morbidity and mortality. Although several clinical, genetic and acquired risk factors for VTE have been identified, the molecular pathophysiology and mechanisms of disease progression remain poorly understood. Anticoagulation has been the cornerstone of therapy for decades, but there still are uncertainties regarding primary and secondary VTE prevention, as well as optimal therapy duration. In this review we discuss the role of factor Xa in coagulation cascade and the different choices of anticoagulation therapy based on patients’ predisposing risk factors and risk of event recurrence. Further, we compare newer agents to traditional anticoagulation treatment, based on most recent studies and guidelines.

Long-term quality of VKA treatment and clinical outcome after extreme overanticoagulation in 14,777 AF and VTE patients

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 ◽  
...  
Keyword(s):  
Atrial Fibrillation ◽  
Venous Thromboembolism ◽  
Clinical Outcome ◽  
Vitamin K ◽  
Vitamin K Antagonists ◽  
P Value ◽  
Risk Of Bleeding ◽  
Increased Risk

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.

Ankle injuries

2013 ◽  
Author(s):  
Bill Ribbans ◽  
Cathy Speed
Keyword(s):  
Risk Factors ◽  
Early Recognition ◽  
The Body ◽  
Ankle Injuries ◽  
Modifiable Risk Factors ◽  
Full Potential ◽  
Common Region

The ankle is the most common region of the body to be injured in sport. However, injuries sustained at this site are commonly neglected, resulting in potentially significant long-term functional and structural sequelae.Effective prophylactic strategies to minimize ankle injuries in specific sports should be developed. Addressing modifiable risk factors should be an important aspect of conditioning regimes for most sports, and early recognition and management of injuries is vital for preventing the development of chronic pathology limiting the attainment of an athlete’s full potential....

A Concept for Long-Term Anticoagulation Based On the Individual Risk of Lethal Pulmonary Embolism (PE) and Lethal Bleeding Using Oral Anticoagulants.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 4174-4174
Author(s):  
Rainer B. Zotz ◽  
Christoph Sucker ◽  
Andrea Gerhardt
Keyword(s):  
Risk Factors ◽  
Oral Anticoagulation ◽  
Factor V Leiden ◽  
Bleeding Risk ◽  
Individual Risk ◽  
Factor V ◽  
Benefit Analysis ◽  
Initial Event ◽  
Risk Benefit Analysis

Abstract Abstract 4174 Objectives Indications for an indefinite oral anticoagulation are a matter of debate in patients with a first unprovoked proximal DVT. Methods An individual risk-benefit analysis is made using published prospective studies by determining the patient-specific lethal risk of bleeding under oral anticoagulation compared with the estimation of lethal PE-risk by type of initial thrombosis (spontaneous vs. secondarily caused, with or without PE). Results According to this risk-benefit analysis, long-term oral anticoagulation is indicated to prevent lethal PE in all patients with low risk of bleeding (1% per year, 0.1 % lethal bleeding per year) in the risk group with lethal PE > 0.2 % per year. This risk group includes patients with idiopathic proximal thrombosis and PE in the initial event (also without thrombophilic risk factors) and patients with an idiopathic initial event without PE, who have relevant thrombophilic risk factors with a relative risk ≥ 2, such as antithrombin deficiency, homozygous factor V Leiden or a combined heterozygous factor V Leiden and prothrombin G20210A mutation. In case of a higher bleeding tendency (0.3% lethal bleeding per year in a patient group with 1-2 bleeding risk factors like age >65 or diabetes) other risk-benefit estimations are present. Conclusions Our individual risk stratification is in contrast to current therapy recommendations, which generally consider long-term oral anticoagulation for patients with an idiopathic initial proximal DVT with a low bleeding risk, but do not specify these in individual cases. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Slightly elevated international normalized ratio predicts bleeding episodes in patients treated with direct oral anticoagulants

2020 ◽  
Vol 48 (6) ◽  
pp. 030006051989443
Author(s):  
Priya Bhardwaj ◽  
Louise Breum Petersen ◽  
Tomas Sorm Binko ◽  
Jan Roland Petersen ◽  
Gitte Gleerup Fornitz
Keyword(s):  
Oral Anticoagulants ◽  
Direct Oral Anticoagulants ◽  
Factor Xa ◽  
Bleeding Risk ◽  
International Normalized Ratio ◽  
Direct Factor ◽  
Risk Of Bleeding ◽  
Increased Risk ◽  
Direct Factor Xa Inhibitors ◽  
Bleeding Episodes

Introduction Patients treated with direct oral anticoagulants (DOACs) are at increased bleeding risk. It is therefore of increasing interest to identify predictors of bleeding episodes to increase safety during treatment with DOACs. Methods This retrospective cohort study systematically reviewed medical records of 235 patients treated with either apixaban, rivaroxaban or dabigatran for non-valvular atrial fibrillation or venous thromboembolism and collected data on the international normalized ratio (INR) and all bleeding episodes. Results INR ≥ 1.5 was significantly associated with increased risk of minor and major bleeding events in patients treated with direct factor Xa inhibitors. This association was not present in patients treated with dabigatran. However, a high negative predictive value was identified for INR < 1.5 for all drugs. The relative risks of bleeding episodes in patients with INR ≥ 1.5 and INR < 1.5 were 5.1 and 0.20, respectively. Conclusions Our results demonstrate a strong correlation between INR and risk of bleeding episodes during DOAC treatment. INR < 1.5 was a strong negative predictor for low bleeding risk independent of indication or choice of drug, and INR ≥ 1.5 was associated with increased risk of bleeding episodes in patients treated with direct factor Xa-inhibitors.

scholarly journals The Inhibitory Effect of Protamine on Platelets is Attenuated by Heparin without Inducing Thrombocytopenia in Rodents

Marine Drugs ◽  
2019 ◽  
Vol 17 (9) ◽  
pp. 539
Author(s):  
Joanna Miklosz ◽  
Bartlomiej Kalaska ◽  
Kamil Kaminski ◽  
Malgorzata Rusak ◽  
Krzysztof Szczubialka ◽  
...  
Keyword(s):  
Factor Xa ◽  
Bleeding Risk ◽  
Inhibitory Effect ◽  
Antiplatelet Activity ◽  
Short Term ◽  
Platelet Factor ◽  
Antithrombotic Activity ◽  
Formation Number ◽  
Induced Aggregation

Protamine sulfate (PS) is a polycationic protein drug obtained from the sperm of fish, and is used to reverse the anticoagulant effect of unfractionated heparin (UFH). However, the interactions between PS, UFH, and platelets are still not clear. We measured the platelet numbers and collagen-induced aggregation, P-selectin, platelet factor 4, β-thromboglobulin, prostacyclin metabolite, D-dimers, activated partial thromboplastin time, prothrombin time, anti-factor Xa, fibrinogen, thrombus weight and megakaryocytopoiesis in blood collected from mice and rats in different time points.. All of the groups were treated intravenously with vehicle, UFH, PS, or UFH with PS. We found a short-term antiplatelet activity of PS in mice and rats, and long-term platelet-independent antithrombotic activity in rats with electrically-induced thrombosis. The antiplatelet and antithrombotic potential of PS may contribute to bleeding risk in PS-overdosed patients. The inhibitory effect of PS on the platelets was attenuated by UFH without inducing thrombocytopenia. Treatment with UFH and PS did not affect the formation, number, or activation of platelets, or the thrombosis development in rodents.

Pattern and Management of Intracranial Haemorrhage with Rivaroxaban or Dabigatran Compared to Vitamin K Antagonists - Results of the Prospective Dresden Noac Registry

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 1127-1127
Author(s):  
Sandra Marten ◽  
Luise Tittl ◽  
Katharina Daschkow ◽  
Jan Beyer-Westendorf
Keyword(s):  
Atrial Fibrillation ◽  
Vitamin K ◽  
Research Funding ◽  
Intracranial Haemorrhage ◽  
Vitamin K Antagonists ◽  
Bleeding Risk ◽  
Interventional Therapy ◽  
Phase Iii ◽  
Bayer Healthcare ◽  
Phase Iii Trials

Abstract Background: In recent phase-III trials, the rate of intracranial haemorrhage (ICH) - the most feared complication of anticoagulant therapy - was around 0.8% per year for patients treated with vitamin K antagonists (VKA) and consistently lower (around 0.3-0.5%) for patients treated with the non-VKA oral anticoagulants (NOACs) rivaroxaban and dabigatran However, patients in clinical trials present a selected population treated under a strict protocol in dedicated academic facilities. Consequently, the risk, management and outcome of ICH need to be evaluated in cohorts of patients treated with NOACs or VKA in daily care. Aim: To evaluate the rate of ICH in patients treated with NOAC compared to VKA patients. Patients and methods: The prospective NOAC registry was initiated in November 2011. A network of more than 230 physicians in the district of Saxony, Germany, enrol up to 3000 patients in the registry, which are prospectively followed by the central registry office for up to 60 months with central outcome event adjudication. For this analysis, every intracranial haemorrhage was identified in the database and ICH management and outcome were evaluated. Results: Until January 31th 2015, 2682 patients were registered and treated with dabigatran (348, mostly treated for atrial fibrillation), Rivaroxaban (1907; 1204 treated for atrial fibrillation and 703 for venous thromboembolism) or vitamin K antagonists (427; treated for atrial fibrillation). VKA patients had lower HAS-BLED scores compared to NOAC patients and were excellently managed with a time-in-therapeutic-range of 75%. During follow-up (mean follow-up duration 25.6 months) ICH occurred in 7/427(1.6%) of VKA treated patients and in 14/2255 (0.6%) of patients treated with NOAC, which translated into an annualized rate of 1.3 events/100 pt. years (95%-CI 0.5-2.7) for VKA and 0.4 events/100 pt. years (95%-CI 0.2-0.6) for NOAC (p=0.0039). Treatment of ICH consisted of PCC in 10 cases, plasma in 3 cases and surgical or interventional therapy in 7 cases (table 1, multiple treatments possible). As indicated, use of factor concentrates, plasma or other hemostatic agents or surgery was much more frequent in VKA patients compared to NOAC patients. Table 1. Cause and treatment of ICH ICH/total Spontaneous vs. traumatic ICH (n) treatment with PCC treatment with fresh frozen plasma treatment with other hemostatic agents no hemostatic treatment surgical or interventional therapy dabigatran 2/348 (0.6%) 2 vs. 0 0 0 0 2/2 (100%) 1/2 (50%) rivaroxaban 12/1907 (0.6%) 4 vs. 8 5/12 (41.7%) 2/12 (16.7%) 2/12 (16.7%) 7/12 (58.3%) 3/12 (25%) VKA 7/427 (1.6%) 2 vs. 5 5/7 (71.4%) 1/7 (14.3%) 4/7 (57.1%) 2/7 (28.6%) 3/7 (42.9%) At Day 90 after ICH, 7/21 patients were dead (2/7 or 28.6% of VKA patients and 5/14 or 35.7% of NOAC patients). The surviving 14 patients received the following antithrombotic agents: 5 (35.7%) rivaroxaban, 3 (21.4%) heparin, 1 (7.1%) apixaban, 1 (7.1%) VKA, 3 (21.4%) aspirin, 1 (7.1%) none.Following ICH, oral anticoagulation therapy was either interrupted (n=7; 6 NOAC vs. 1 VKA) or permanently discontinued (n=10; 6 NOAC vs. 4 VKA). Conclusion: Despite low bleeding risk and excellent INR control in our VKA cohort, the rate of ICH was higher than that of VKA patients treated in recent phase-III trials. Furthermore, ICH rates in our VKA cohort were significantly higher than those seen in our NOAC cohorts, which represented more patients with relevant comorbidities and higher bleeding risk. Consequently, the risk of ICH remains high even in "stable" VKA patients with good INR control and a preventive switch from VKA to NOAC may help to reduce ICH risk and should be discussed with the patient. Disclosures Marten: Bayer HealthCare: Honoraria. Beyer-Westendorf:Pfizer: Honoraria, Research Funding; Boehringer Ingelheim: Honoraria, Research Funding; Bristol-Myers Squibb: Honoraria, Research Funding; Bayer HealthCare: Honoraria, Research Funding.

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