Impact of anticoagulation status on recanalization and outcome of cerebral venous thrombosis

Effective anticoagulation status may determine the recanalization and outcome of cerebral venous thrombosis (CVT). We report impact of anticoagulation status on recanalization and outcome of CVT. This is a retrospective study on 126 patients with CVT diagnosed on magnetic resonance venography (MRV). Their clinical features and risk factors were noted. The data were retrieved from a prospectively maintained registry, and international normalized ratio (INR) was noted after discharge till 3 months. All the patients were on acenocoumarol. Based on INR value, patients were categorized as Group A (effective anticoagulation INR within the therapeutic range or above) and Group B (ineffective anticoagulation INR > 50% below the therapeutic range). A repeat MRV at 3 months was done for recanalization. Outcome at 3 months was evaluated using modified Rankin Scale (mRS), and categorized as good (mRS ≤ 2) and poor (mRS 2 or more) 101(80.2%) patients were in group A and 25(19.8%) in group B. Their demographic, risk factors, magnetic resonance imaging (MRI) and MRV findings were comparable. On repeat MRV, recanalization occurred in 22/24(91.7%); 15(88%) in group A and 7(100%) in group B. Recanalization was independent of coagulation status. Seven (5.6%) patients died and 107(84.9%) had good outcome; 85(84.2%) in group A and 22(88%) in group B. Kaplan Meier analysis also did not reveal survival or good outcome benefits between the groups. In CVT, outcome and recanalization at 3 months are not dependent on coagulation status. Further prospective studies are needed regarding duration of anticoagulant and its impact on recanalization and outcome.     

Safety of dental implant surgery in patients undergoing anticoagulation therapy: a prospective case-control study

Objectives: Several studies have described oral surgical procedures in patients receiving anticoagulant therapy, but no prospective studies on dental implant surgery during anticoagulant treatment are currently available, and only a limited number of case reports refer to endosseous dental implant treatment in these patients. In the setting of oral surgery, it has been suggested that anticoagulant treatment is not required when the International Normalized Ratio (INR) is <4 and local haemostatic measures are applied. The purpose of this preliminary study was to evaluate the incidence of bleeding complications following surgical implant therapy in a group of 50 consecutive patients receiving oral anticoagulant therapy (warfarin) without interruption or modifications to their therapy (group A). Materials and methods: One hundred and nine otherwise healthy patients comparable for age, sex, extent and site of the implant surgical procedure formed the control group (group B). In both groups, a standard protocol of local haemostasis, including non‐reabsorbable sutures and compressive gauzes soaked with tranexamic acid, was applied. Surgeons, blind to the group allocation, performed all the procedures in an outpatient setting. Results: Two and three late‐bleeding complications were reported in group A and group B, respectively, without significant difference in the bleeding risk (relative risk = 1.45; P= 0.65; 95% confidence interval 0.2506–8.4271). These complications were managed using a compressive gauze soaked with tranexamic acid at the site of the surgical wound. Conclusion: According to our preliminary results, local haemostasis in dental implant surgery is able to prevent bleeding complications in patients on oral anticoagulants, allowing these surgical procedures to be performed on an outpatient basis. To cite this article:
Bacci C, Berengo M, Favero L, Zanon E. Safety of dental implant surgery in patients undergoing anticoagulation therapy: a prospective case–control study.
Clin. Oral Impl. Res. 22 , 2011; 151–156.
doi: 10.1111/j.1600‐0501.2010.01963.x     

Main haplotypes and mutational analysis of vitamin K epoxide reductase (VKORC1) in a Swedish population: a retrospective analysis of case records

BACKGROUND: Vitamin K epoxide reductase (VKORC1) is the site of inhibition by coumarins. Several reports have shown that mutations in the gene encoding VKORC1 affect the sensitivity of the enzyme for warfarin. Recently, three main haplotypes of VKORC1; *2, *3 and *4 have been observed, that explain most of the genetic variability in warfarin dose among Caucasians. OBJECTIVES: We have investigated the main haplotypes of the VKORC1 gene in a Swedish population. Additional objective was to screen the studied population for mutations in the coding region of VKORC1 gene. PATIENTS/METHODS: Warfarin doses and plasma S- and R-warfarin of 98 patients [with a target International Normalized Ratio (INR) of 2.0-3.0] have been correlated to VKORC1 haplotypes. Controls of 180 healthy individuals have also been haplotyped. Furthermore, a retrospective analysis of case records was performed to find any evidence indicating influence of VKORC1 haplotypes on warfarin response in the first 4 weeks (initiation phase) and the latest 12 months of warfarin treatment. RESULTS AND CONCLUSIONS: Our result shows that VKORC1*2 is the most important haplotype for warfarin dosage. Patients with VKORC1*2 haplotype had more frequent visits than patients with VKORC1*3 or *4 haplotypes, higher coefficient of variation (CV) of prothrombin time-INR and higher percentage of INR values outside the therapeutic interval (i.e. 2.0-3.0) than patients with VKORC1*3 or *4 haplotypes. Also, there was a statistically significant difference in warfarin dose (P < 0.001) and R-warfarin plasma levels (P < 0.01) between VKORC1*2 and VKORC1*3 or 4 haplotypes. Patients with VKORC1*2 haplotype seem to require much lower warfarin doses than other patients.     

Effect of setting,monitoring intensity and patient experience on anticoagulation control: a systematic review and meta-analysis of the literature

ABSTRACT

Objectives: To investigate the relationship between time spent in the recommended target International Normalised Ratio (INR) range and the setting and intensity of anti­coagulant monitoring, in both treatment-experienced and treatment-naïve atrial fibrillation (AF) patients receiving oral anticoagulation (OAC) therapy for the prevention of ischaemic stroke.

Research design and methods: Systematic review of published studies on participants with atrial fibrillation on anticoagulation therapy. We compared frequent monitoring (well-controlled, according to a strict protocol) versus infrequent monitoring (frequency representative of routine clinical practice), specialised care versus usual care, and naïve versus prior anticoagulant use. Meta-analysis was performed using a random effects model.

Results: 36 studies were included, 22 (primary data) of AF patients managed in line with the consensus guidelines target INR range of 2.0–3.0, and 14 studies (secondary data) of mixed patient groups, including AF, with an INR target of 2.0–3.5. Both data sets were combined for sensitivity analysis. Pooled mean time in INR range was 59.1% (95% CI: 55.5, 62.8%) and 64.3% (95% CI: 60.5, 68.0%) for infrequent monitoring and frequent monitoring, respectively. Significantly more time was spent in range in specialist care settings compared to usual care: +11.3% (95% CI: 0.1–21.7%). Naïve OAC users spent less time in range 56.5% (95% CI: 45.5–67.5%) than existing users 61.2% (95% CI: 57.2–65.2%). All of these differences were found to be significant in the sensitivity analyses.

Conclusions: INR control is variable and dependent on monitoring intensity and duration of anticoagulant therapy.     

Influence of genetics and non-genetic factors on acenocoumarol maintenance dose requirement in Moroccan patients

What is known and Objective: Coumarin derivatives such as acenocoumarol represent the therapy of choice for the long‐term treatment and prevention of thromboembolic diseases. Many genetic, clinical and demographic factors have been shown to influence the anticoagulant dosage. Our aim was to investigate the contribution of genetic and non‐genetic factors to variability in response to acenocoumarol in Moroccan patients. Methods: Our study included 114 adult Moroccan patients, receiving long‐term acenocoumarol therapy for various indications. Tests for VKORC1 ‐1639G>A promoter polymorphism (rs9923231), CYP2C9*2 rs1799853, CYP2C9*3 rs1057910, and CYP4F2 rs2108622 alleles were undertaken using Taq Man^® Pre‐Developed Assay Reagents for allelic discrimination. The statistical analysis was performed using the SAS V9 statistical package. Results and Discussion: Genotyping showed that the allele frequencies for the SNPs studied were no different to those found in Caucasians population. A significant association was observed between the weekly maintenance dose and the VKORC1 (P = 0·0027) and CYP2C9 variant genotypes (P = 0·0082). A final multivariate regression model that included the target International Normalized Ratio, VKORC1 and CYP2C9 genotypes explained 36·2% of the overall interindividual variability in acenocoumarol dose requirement. What is new and Conclusion: Our study shows large interindividual variability in acenocoumarol maintenance dose requirement in our population. VKORC1 and CYP2C9 variants significantly affected acenocoumarol dose, in‐line with results in other populations. For the Moroccan population, the SNPs that have the largest effect on acecoumarol dose are CYP2C9 rs1799853, CYP2C9 rs1057910 and VKORC1 rs9923231.     

Oral Anticoagulation in Patients With Liver Disease

Patients with liver disease are at increased risks of both thrombotic and bleeding complications. Many have atrial fibrillation (AF) or venous thromboembolism (VTE) necessitating oral anticoagulant agents (OACs). Recent evidence has contradicted the assumption that patients with liver disease are “auto-anticoagulated” and thus protected from thrombotic events. Warfarin and non–vitamin K–antagonist OACs have been shown to reduce thrombotic events safely in patients with either AF or VTE. However, patients with liver disease have largely been excluded from trials of OACs. Because all currently approved OACs undergo metabolism in the liver, hepatic dysfunction may cause increased bleeding. Thus, the optimal anticoagulation strategy for patients with AF or VTE who have liver disease remains unclear. This review discusses pharmacokinetic and clinical studies evaluating the efficacy and safety of OACs in patients with liver disease and provides a practical, clinically oriented approach to the management of OAC therapy in this population.