The Immediate Effect of COVID-19 Vaccination on Anticoagulation Control in Patients Using Vitamin K Antagonists

Abstract Background: In January 2021, the Dutch vaccination programme against SARS-CoV-2 was started. Clinical studies have shown that systemic reactions occur in up to 50% of vaccine recipients. Therefore, COVID-19 vaccination could affect anticoagulation control, potentially leading to an increased risk of thrombotic events and bleeding complications. Aims: To investigate whether the BNT162b2 vaccine affects anticoagulation control in outpatients using Vitamin K antagonists (VKAs). Methods: A case-crossover study was performed in a cohort of outpatient VKA users from four Dutch anticoagulation clinics who received a BNT162b2 vaccine. INR results and VKA dosages before the first vaccination, the reference period, were compared with those after the first and second vaccination. Results: A total of 3148 outpatient VKA users were included, with a mean age (standard deviation (SD)) of 86.7 (8.7) years, of whom 43.8% were male, 67.0% used acenocoumarol and 33.0% phenprocoumon. We observed a decrease of 8.9% of INRs within range in the standard intensity group (target INR 2.0-3.0). There was both an increased risk of supratherapeutic [OR=1.34 (95% CI 1.08-1.67)] and subtherapeutic levels [OR=1.40 (95% CI 1.08-1.83)] after first vaccination. In the high-intensity group (target INR 2.5-3.5), the risk of a supratherapeutic INR was 2.3 times higher after first vaccination [OR=2.29 (95% CI 1.22-4.28)] and 3.3 times higher after second vaccination [OR 3.25 (95% CI 1.06-9.97). Conclusion: BNT162b2 was associated with an immediate negative effect on anticoagulation control in patients treated with vitamin K antagonists, so it is advisable to monitor the INR short after vaccination, even in stable patients. Figure 1 Figure 1. Disclosures Kruip: Daiichi Sankyo: Research Funding; Bayer: Honoraria, Research Funding.

Download Full-text

New Oral Anticoagulants vs. Vitamin K Antagonists Among Patients With Cardiac Amyloidosis: Prognostic Impact

Frontiers in Cardiovascular Medicine ◽

10.3389/fcvm.2021.742428 ◽

2021 ◽

Vol 8 ◽

Author(s):

Eve Cariou ◽

Kevin Sanchis ◽

Khailène Rguez ◽

Virginie Blanchard ◽

Stephanie Cazalbou ◽

...

Keyword(s):

Vitamin K ◽

Cardiac Amyloidosis ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Bleeding Complications ◽

Prognostic Impact ◽

Transthyretin Amyloidosis ◽

Increased Risk ◽

All Cause Mortality ◽

History Of

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.

Download Full-text

HEMATURIA AND OTHER KINDS OF BLEEDINGS ON NON-VITAMIN K ANTAGONIST ORAL ANTICOAGULANTS IN PATIENTS WITH ATRIAL FIBRILLATION: AN UPDATED OVERVIEW ON OCCURRENCE, PATHOMECHANISMS AND MANAGEMENT

Wiadomości Lekarskie ◽

10.36740/wlek202011135 ◽

2020 ◽

Vol 73 (11) ◽

pp. 2528-2534

Author(s):

Dagmara Wojtowicz ◽

Anna Tomaszuk-Kazberuk ◽

Jolanta Małyszko ◽

Marek Koziński

Keyword(s):

Atrial Fibrillation ◽

Vitamin K ◽

Anticoagulant Activity ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Vitamin K Antagonist ◽

Bleeding Complications ◽

Reversal Agents ◽

Limited Availability ◽

Increased Risk

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.

Download Full-text

Quality of Chronic Anticoagulation Control in Patients with Intracranial Haemorrhage due to Vitamin K Antagonists

Stroke Research and Treatment ◽

10.1155/2018/5613103 ◽

2018 ◽

Vol 2018 ◽

pp. 1-6

Author(s):

Carlos Estevez-Fraga ◽

Maria Molina-Sanchez ◽

Rodrigo Alvarez-Velasco ◽

Pablo Agüero-Rabes ◽

Leticia Crespo-Araico ◽

...

Keyword(s):

Atrial Fibrillation ◽

Vitamin K ◽

Stroke Unit ◽

Intracranial Haemorrhage ◽

Vitamin K Antagonists ◽

Prosthetic Valves ◽

Increased Risk ◽

Study Population ◽

Anticoagulation Control

Introduction. Patients treated with vitamin K antagonists (VKA) are at increased risk of intracranial haemorrhage (ICH). The purpose of our study was to determine the quality of previous anticoagulation control in patients with VKA-associated ICH. Materials and Methods. We prospectively assessed every consecutive patient admitted to our stroke unit with VKA-associated ICH between 2013 and 2016. Demographic, clinical, and radiological variables, as well as consecutive international normalized ratios (INR) during 7 previous months, were extracted. Time in therapeutic range (TTR), time over range (TOR), time below range (TBR), and percentage of INR within range (PINRR) were calculated. Results and Discussion. The study population comprised 53 patients. Mean age was 79 years; 42% were women. Forty-eight patients had atrial fibrillation (AF) and 5 mechanical prosthetic valves. Therapeutic or infratherapeutic INR on arrival was detected in 64.4% of patients (95% CI 2.7 to 3.2). TTR was 67.8% (95% CI: 60.2 to 75.6 %) and PINRR was 75% (95% CI: 49.9-100). TOR was 17.2% (95% CI: 10.4 to 23.9% ) and TBR was 17% (95% CI: 10.6 to 23.9%). Conclusion. VKA-associated ICH happens usually in the context of good chronic anticoagulation control. Newer risk assessment methods are required.

Download Full-text

Selective serotonin reuptake inhibitor use is associated with major bleeding during treatment with vitamin K antagonists: results of a cohort study

10.22541/au.163482037.74714743/v1 ◽

2021 ◽

Author(s):

Sanne Bakker ◽

Louise Burggraaf ◽

MJHA Kruip ◽

Felix van der Meer ◽

WM Lijfering ◽

...

Keyword(s):

Vitamin K ◽

Major Bleeding ◽

Serotonin Reuptake ◽

Selective Serotonin Reuptake Inhibitors ◽

Cox Regression ◽

Conditional Logistic Regression ◽

Vitamin K Antagonists ◽

Selective Serotonin ◽

Bleeding Complications ◽

Increased Risk

Aims: To determine whether Selective serotonin reuptake inhibitors (SSRIs) cause major bleeding during vitamin K antagonist (VKA) treatment and investigate the possible mechanisms behind this interaction. Methods: Information on SSRI use and bleeding complications was obtained from patient records at the Anticoagulation Clinics of Leiden and Rotterdam of VKA initiators between 2006 and 2018. Conditional logistic regression and time-dependent Cox regression were used to estimate the effect of SSRIs on a high INR (≥ 5) within 2 months after SSRI initiation and on major bleeding during the entire period of SSRI use, respectively. SSRI use was stratified for (non-)CYP2C9 inhibitors. Results: 58,918 patients were included, of whom 1504 were SSRI users. SSRI initiation versus non-use was associated with a 2.41-fold (95% confidence interval [CI] 2.01-2.89) increased risk for a high INR, which was 3.14-fold (95%CI 1.33-7.43) among CYP2C9 inhibiting SSRIs. SSRI use versus non-use was associated with a 1.22-fold (95%CI 0.99-1.50) increased risk for major bleeding in all SSRI users, which was 1.31-fold (95%CI 0.62-2.72) in CYP2C9 inhibiting SSRIs compared to non-users. Conclusion: SSRIs are associated with an increased risk of high INR and major bleeding. These risks were slightly more elevated for CYP2C9 inhibiting SSRI users, suggesting that this was due to a pharmacokinetic interaction (by CYP2C9 inhibition) as well as a pharmacodynamic effect of SSRIs on platelet activation.

Download Full-text

INR Stability, Clinical Importance, and Predictors in Patients With Atrial Fibrillation and Venous Thromboembolism Receiving Vitamin K Antagonists

Journal of Pharmacy Technology ◽

10.1177/8755122516661736 ◽

2016 ◽

Vol 32 (6) ◽

pp. 253-259

Author(s):

C. Michael White

Keyword(s):

Atrial Fibrillation ◽

Venous Thromboembolism ◽

Vitamin K ◽

Systematic Reviews ◽

Randomized Clinical Trials ◽

Vitamin K Antagonists ◽

Bleeding Event ◽

The United States ◽

Bleeding Complications ◽

Anticoagulation Clinics

Objective: Compare and contrast systematic reviews/meta-analyses assessing the time in the therapeutic range (TTR) for vitamin K antagonists (VKAs), clinical impact, and predictors. Data Sources: OVID MEDLINE search (1980-June 1, 2016) using the terms “vitamin K antagonist or warfarin” and “systematic review or meta-analysis” with backwards citation tracking from procured articles. Study Selection and Data Extraction: Search results were limited to systematic reviews assessing TTR with VKAs in patients with atrial fibrillation (AF) or venous thromboembolism (VTE). Data Synthesis: Six systematic reviews assessed TTR (4 in AF, 2 in VTE), and 3 of those assessed control at the time of a thrombotic or bleeding event (2 in AF, 1 in VTE). In patients on VKAs, greater TTR is correlated with fewer thromboembolic events and bleeding complications. VKA naïve patients have a harder time maintaining TTR than those with a previous knowledge of the likely therapeutic dose. Patients in the United States spend less TTR than those in other countries. Randomized clinical trials and anticoagulation clinics achieve greater TTR than those treated outside of these settings. The overall TTR has not improved from the first systematic reviews to the newest ones even though they were conducted 10 years apart and contained many new studies. Also, TTR in AF and VTE is similar. Conclusions: TTR is an important metric of VKA efficacy and safety and needs to be optimized. Many factors such as being VKA naïve can compromise TTR, and the use of anticoagulation clinics to optimize therapy is an important approach.

Download Full-text

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

European Respiratory Journal ◽

10.1183/09031936.00040714 ◽

2014 ◽

Vol 45 (1) ◽

pp. 201-210 ◽

Cited By ~ 37

Author(s):

Frederikus A. Klok ◽

Judith Kooiman ◽

Menno V. Huisman ◽

Stavros Konstantinides ◽

Mareike Lankeit

Keyword(s):

Venous Thromboembolism ◽

Vitamin K ◽

Vitamin K Antagonists ◽

Clinical Importance ◽

Bleeding Risk ◽

Bleeding Complications ◽

Current Thinking ◽

Therapeutic Anticoagulation ◽

Increased Risk ◽

Therapeutic Doses

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.

Download Full-text

Subtherapeutic Anticoagulation Control under Treatment with Vitamin K-Antagonists—Data from a Specialized Coagulation Service

Thrombosis and Haemostasis ◽

10.1055/s-0039-1692175 ◽

2019 ◽

Vol 119 (08) ◽

pp. 1347-1357 ◽

Cited By ~ 2

Author(s):

Jürgen H. Prochaska ◽

Christoph Hausner ◽

Markus Nagler ◽

Sebastian Göbel ◽

Lisa Eggebrecht ◽

...

Keyword(s):

Risk Factors ◽

Vitamin K ◽

Cox Regression ◽

Statistical Significance ◽

Vitamin K Antagonists ◽

International Normalized Ratio ◽

Living Alone ◽

Cox Regression Analysis ◽

Increased Risk ◽

Anticoagulation Control

AbstractIn contrast to overanticoagulation, evidence on risk factors and outcome of subtherapeutic oral anticoagulation (OAC) with vitamin K-antagonists (VKAs) under optimum care is limited. We investigated the clinical phenotype, anticoagulation control, and clinical outcome of 760 VKA patients who received OAC therapy by a specialized coagulation service in the thrombEVAL study (NCT01809015). During 281,934 treatment days, 278 patients experience ≥ 1 episode of subtherapeutic anticoagulation control and had lower quality of OAC therapy compared to 482 patients without subtherapeutic international normalized ratio: 67.6%, interquartile range (IQR) 54.9%/76.8% versus 81.0%, IQR 68.5%/90.4%; p < 0.001. In Cox regression analysis with adjustment for age, sex, cardiovascular risk factors, comorbidities, and treatment characteristics, female sex (hazard ratio [HR], 1.4, 95% confidence interval [CI], 1.0/1.9; p = 0.03), diabetes (HR, 1.4, 95% CI, 1.0/2.0; p = 0.03), and living alone (HR, 1.5, 95% CI, 1.1/2.1; p = 0.009) were independent risk factors of subtherapeutic anticoagulation control, whereas atrial fibrillation (HR, 0.6, 95% CI, 0.4/0.9; p = 0.02) and self-management of OAC therapy (HR, 0.2, 95% CI, 0.1/0.6; p = 0.001) were protective. In addition, active smoking (HR, 1.7, 95% CI, 0.9/3.0; p = 0.086) and living in a nursing home (HR, 1.6, 95% CI, 0.8/3.2; p = 0.15) indicated an elevated risk at the borderline of statistical significance. For the prediction of recurrent subtherapeutic anticoagulation, living alone was the only independent risk factor (HR, 1.7, 95% CI, 1.1/2.5; p = 0.013). The present study suggests that women, diabetics, and patients living alone experience an increased risk of low-quality VKA therapy and might potentially benefit from treatment with direct-acting anticoagulants.

Download Full-text

Decreased Levels Of Procoagulant Phospholipids In Bleeding Patients With Overcoagulation By Vitamin K Antagonists

Blood ◽

10.1182/blood.v122.21.4768.4768 ◽

2013 ◽

Vol 122 (21) ◽

pp. 4768-4768

Author(s):

Patrick Van Dreden ◽

Dominique François ◽

Emmanuel Mathieu ◽

Matthieu Grusse ◽

Marc Vasse

Keyword(s):

Vitamin K ◽

Conflicts Of Interest ◽

Vitamin K Antagonists ◽

Factor Xa ◽

International Normalized Ratio ◽

Bleeding Complications ◽

Functional Assay ◽

Minor Bleeding ◽

Asymptomatic Patients ◽

Increased Risk

Background The major adverse effect of vitamin K antagonists (VKA) is the increased risk for bleeding complications. In addition to well-identified risk factors such as age, prior gastrointestinal tract bleeding, or hypertension, the intensity of anticoagulation evaluated by the International Normalized Ratio (INR) measurement is a major determinant of VKA-induced bleeding. However, for the same degree of VKA overcoagulation and comorbidities, some patient will bleed, whereas others remain asymptomatic. Therefore, identifying specific biological markers that identify patients at high risk of bleeding would have great clinical impact. Microparticles, derived from different cellular origins (endothelium, red blood cells, leukocytes, platelets or apoptotic tissues), can be detected in plasma and express procoagulant phospholipids (PPL). The presence of PPL has been associated with various diseases complicated by an hypercoagulable state. Therefore, we hypothesize that the procoagulant activity of PPL could protect against haemorrhage in patients with VKA overcoagulation. Patients and methods 53 consecutive patients who were referred to the emergency department of our institution and with an INR > 5 were enrolled in the study: 22 (10 females; 12 males, median age 82 years) were symptomatic (20 cases of minor bleeding, 2 cases of non-fatal major bleeding), whereas 31 (18 females, 13 males, median age 78 years) were asymptomatic. Median INR was 7.36 (range: 5 – 22.6) and 6.3 (range: 5 – 10.7) in symptomatic and asymptomatic patients, respectively (p = 0.17, not significant). PPL were evaluated using a factor Xa-based coagulation assay (STA-Procoag-PPL, Diagnostica Stago) in which shortened clotting times are associated with increased levels of PPL. We also quantified thrombomodulin (TM) by an ELISA assay (Asserachrom Thrombomodulin, Diagnostica Stago) and by a functional assay based on the ability of TM to activate Protein C in the presence of thrombin, since high plasma levels of TM were previously identified as a predictor of bleeding complications. Results Clotting times were significantly lower in asymptomatic patients than in bleeding patients [respective median values 36.5 seconds (range: 27.1 – 72.2) and 47.2 seconds (range : 30.5 – 72.8); p = 0.03. In contrast, there were no significant differences for TM levels, whatever the assay used (functional or immunological). Conclusion Increased PPL could contribute to decrease the haemorrhagic risk of patients treated by VKA. It is not clear if the decrease of PPL is directly responsible of the hemorrhagic syndrom, or if PPL are decreased because of a consumption during the hemorrhagic episode. In order to answer this question, it could be of interest to analyse if a prospective follow-up of this parameter could help to identify patients with an increased hemorrhagic risk when treated by VKA. Disclosures: No relevant conflicts of interest to declare.

Download Full-text

Anticoagulants

Hämostaseologie ◽

10.5482/ha-1153 ◽

2011 ◽

Vol 31 (04) ◽

pp. 229-235 ◽

Cited By ~ 12

Author(s):

E. S. Eerenberg ◽

P. W. Kampuisen ◽

M. Levi

Keyword(s):

Vitamin K ◽

Vitamin K Antagonists ◽

Experimental Studies ◽

Real Life ◽

Coagulation Factor ◽

Patient Characteristics ◽

Bleeding Complications ◽

Increased Risk ◽

Newer Anticoagulants ◽

New Generation

SummaryAnticoagulants are effective in the prevention and treatment of a variety of arterial and venous thrombotic disorders but are associated with an increased risk of serious bleeding complications. Based on well documented studies of patients using vitamin K antagonists the incidence of major bleeding is 0.5%/year and the incidence of intracranial bleeding is 0.2%/year, however, in real life practice this incidence may be even higher. Risk factors for bleeding are the intensity of anticoagulation, the management strategy to keep the anticoagulant effect in the desired range, and patient characteristics. Recently, a new generation of anticoagulants have been developed and is currently evaluated in clinical trials. Initial results show a similar or superior efficacy over conventional anticoagulant agents with a good safety profile. In case of serious bleeding complications in a patient who uses vitamin K antagonists, this anticoagulant treatment can be quickly reversed by administration of vitamin K or coagulation factor concentrates. For the newer anticoagulants, quick reversal strategies are more cumbersome, although some interventions, including prothrombin complex concentrates, show promising results in initial experimental studies.

Download Full-text

Postoperative Bleeding Complications in Patients on Novel Oral Anticoagulants and Vitamin K Antagonist Following an Invasive Dental Procedure - A Review of Literature

Journal of Evolution of Medical and Dental Sciences ◽

10.14260/jemds/2021/621 ◽

2021 ◽

Vol 10 (35) ◽

pp. 3047-3052

Author(s):

Pavithra M ◽

Arvind Muthukrishnan

Keyword(s):

Vitamin K ◽

Vitamin K Antagonists ◽

Oral Anticoagulants ◽

Postoperative Bleeding ◽

New Drugs ◽

Current Evidence ◽

Bleeding Complications ◽

Novel Anticoagulants ◽

Increased Risk ◽

Significant Difference

The incidence of thromboembolic diseases is high. It is one of the leading causes of death and disability. Anticoagulants are used for preventing or reducing blood clot formation and treatment of other related thrombotic disorders. Vitamin K antagonists (VKA) were developed more than 60 years ago. Warfarin is the most commonly used VKA. The drawbacks of vitamin K antagonists were that it requires frequent monitoring and dose adjustments, food and drug interactions, narrow therapeutic range, diet restrictions. For the past 15 years, various new drugs have been introduced to overcome the disadvantages of vitamin K antagonists. In 2008, a new group of anticoagulants were introduced. They are known as novel anticoagulants (NOAC) or direct oral anticoagulants. They include dabigatran, apixaban, rivaroxaban and edoxaban. The major issue with NOAC is difficulty in monitoring the dose. A literature search was done on this topic. It is very important for the dentists to know the bleeding complications in patients under anticoagulant therapy. The dental treatment of patients who tend to have an increased risk of bleeding due to the use of anticoagulants and / or antiplatelet drugs raises a challenge in the daily practice of dental professionals. According to current evidence, there is no significant difference in postoperative bleeding between novel anticoagulants and vitamin K antagonists. The risk of thromboembolic events on stopping the anticoagulants should be assessed. Local haemostatic measures are shown to suffice to control possible bleeding secondary to dental treatments. KEY WORDS Anticoagulants; Apixaban; Dabigatran; Dentistry; Edoxaban; Rivaroxaban.

Download Full-text