Risk of dentoalveolar surgery postoperative bleeding in patients taking direct oral anticoagulants and vitamin K antagonists: A prospective observational study.

The aim of this study was to evaluate whether direct oral anticoagulants (DOAC) and vitamin K antagonists (VKA) increase the risk of postoperative bleeding after dentoalveolar surgery. Patients were classified into two groups: one taking DOAC and the other taking VKA with a therapeutic INR range. The control group comprised non-anticoagulated subjects. Participants were matched regarding dentoalveolar procedure. The primary predictor was anticoagulant status. The primary outcome was postoperative bleeding. The DOAC group comprised 77 patients, while the VKA group and control group each consisted of 103 participants. In each group, 103 dentoalveolar surgical procedures were conducted. Postoperative bleeding was recorded in 3/103 (2.9%), 5/103 (4.8%), and 1/103 (0.97%) occasions in the DOAC, VKA, and control groups, respectively, without significant difference (χ2; p = 0.54). The fully adjusted odds ratio for postoperative bleeding was 0.14 (CI 0.01-1.61; p = 0.05) for patients taking DOAC and 0.19 (CI 0.02-1.65; p = 0.285) for those taking VKA compared with non-anticoagulated controls. In conclusion, there was no increase in risk for clinically significant postoperative bleeding after dentoalveolar surgery in patients taking DOAC or VKA compared with non-anticoagulated subjects. Dentoalveolar surgery in patients taking DOAC and VKA can be performed safely without therapy cessation. The study was registered at Clinicaltrials.gov (NCT04505475).

Influence of decreased fibrinolytic activity and plasminogen activator inhibitor-1 4G/5G polymorphism on the risk of venous thrombosis.

: Objective of our study is to determine whether decreased fibrinolytic activity or plasminogen activator inhibitor (PAI)-1 4G/5G polymorphism influence the risk of venous thrombosis.Our case-control study included 100 patients with venous thrombosis, and 100 random controls. When patients were compared with random controls, unconditional logistic regression was used to calculate odds ratios (ORs) with 95% confidence intervals (CIs).Decreased fibrinolytic activity yielded a 2.7-fold increase in risk for venous thrombosis than physiological fibrinolytic activity (OR 2.70; 95% CI 1.22-5.98), when comparing patients with random controls. Adjustment for several putative confounders did not change the estimate (OR 3.02; 95% CI 1.26-7.22). Analysis of venous thrombotic risk influenced by PAI-1 genotype, showed no influence of PAI-1 4G/5G gene variant in comparison with 5G/5G genotype (OR 0.57 95% CI; 0.27-1.20).Decreased fibrinolytic activity increased, whereas PAI-1 4G/5G polymorphism did not influence venous thrombosis risk in this study.

Risk factors for bleeding after oral surgery in patients who continued using oral anticoagulant therapy.

BACKGROUND: The authors assessed the incidence of postoperative bleeding in patients who were highly anticoagulated and in patients who underwent extensive oral surgical procedures and who continued using oral anticoagulant therapy. METHODS: The authors placed 125 patients receiving anticoagulant therapy into 1 of 3 groups. Group A had 54 patients who were highly anticoagulated (international normalized ratio [INR] ≥ 3.5) in whom up to 3 teeth were extracted. Group B had 60 patients with INR 2.0 to less than 3.5 in whom higher-risk dentoalveolar surgery (extraction of more than 3 teeth or other oral surgery procedure involving raising a mucoperiosteal flap, osteotomy, or biopsy) was performed. Group C had 11 patients whose INR values were 3.5 or higher and who required higher-risk dentoalveolar surgery. Eighty-five healthy participants who underwent surgical procedures similar to those performed in group A and group B were the control group. RESULTS: Two patients in group A (3.7%), 3 in group B (5.0%), and 2 in group C (18.2%) experienced postoperative bleeding. In the control group, a single bleeding event (1.2%) occurred. All cases of hemorrhage were mild and easily controlled using local hemostatic measures. CONCLUSIONS: Dental extractions in patients who are highly anticoagulated (INR, 3.5-4.2), as well as more extensive oral surgical procedures in patients who are therapeutically anticoagulated, can be performed safely without interruption or modification of the therapy. PRACTICAL IMPLICATIONS: Tooth extractions and even more extensive surgical procedures can be performed safely in patients who continue using anticoagulant therapy if proper local hemostatic measures are used and if no other coagulopathies are present.

Vitamin supplementation on the risk of venous thrombosis: results from the MEGA case-control study.

BACKGROUND: Whether vitamin supplements decrease venous thrombosis risk is controversial. Previous reports did not all take confounding fully into account, either by randomization or by extensive adjustment. OBJECTIVE: The aim of our study was to determine whether vitamin supplementation decreases the risk of venous thrombosis. DESIGN: A large case-control study included 2506 patients with venous thrombosis, 2506 partner controls, and 2684 random-digit dialing (RDD) controls. When patients were compared with RDD controls, unconditional logistic regression was used to calculate ORs with 95% CIs. When patients were compared with partner controls, conditional logistic regression was used, providing further adjustment for unmeasured confounding. RESULTS: Vitamin use yielded a 37% lower risk of venous thrombosis than no vitamin use (OR: 0.63; 95% CI: 0.57, 0.70) when comparing patients with RDD controls. Adjustment for several putative confounders did not change the estimate (OR: 0.68; 95% CI: 0.61, 0.77). The fully adjusted ORs for vitamin A, vitamin B-6, vitamin B-12, folic acid, vitamin C, vitamin D, vitamin E, and multivitamin use were in the same range. However, when patients were compared with partner controls, ORs attenuated to unity. Results were similar for provoked and unprovoked events, as well as for deep vein thrombosis and pulmonary embolism. CONCLUSIONS: After extensive adjustments, vitamin supplementation was no longer associated with a decreased risk of venous thrombosis in this study. Previous positive results may have been spurious as a result of uncontrolled confounding.

Clinical significance of determining plasma homocysteine: case-control study on arterial and venous thrombotic patients.

AIM: To determine the differences in plasma homocysteine levels between three MTHFR 677 genotype subgroups in patients with thrombosis and in controls, as well as between patients with thrombosis and controls with the same MTHFR 677 genotype. METHODS: This case-control study was conducted in Clinical Center of Vojvodina, Novi Sad, from June to December 2011. We included 65 patients with either arterial or venous thrombosis (mean age, 40.97 ± 11.38 years) and 65 controls with no history or clinical evidence of any thrombotic event (mean age, 41.23 ± 11.12 years). Patients and controls were age- and sex-matched. RESULTS: In comparison with controls, thrombotic patients had significantly higher homocysteine levels (12.81 ± 4.94 µmol/L vs 9.82 ± 3.68 µmol/L; P<0.001) and significantly higher incidence of hyperhomocysteinemia (55% vs 22%; P<0.001; odds ratio [OR]=4.521). There were no significant differences in homocysteine levels between homozygous carriers, heterozygous carriers, and non-carriers of the MTHFR 677 mutation in either thrombotic patients (12.97 ± 5.40 µmol/L vs 12.55 ± 5.71 µmol/L vs 13.27 ± 1.71 µmol/L; P=0.100) or controls (10.07±2.50 µmol/L vs 10.25 ± 4.84 µmol/L vs 9.20 ± 2.44 µmol/L; P=0.651). However, in comparison with controls, homozygous carriers in thrombotic patient group did not have significantly higher levels of homocysteine (12.97 ± 5.40 µmol/L vs 10.07 ± 2.50 µmol/L; P=0.072), but heterozygous carriers (12.55 ± 5.71 µmol/L vs 10.25 ± 4.84 µmol/L; P=0.020) and non-carriers (13.27 ± 1.71 µmol/L vs 9.20 ± 2.44 µmol/L; P<0.001) did. There was no significant difference in homocysteine levels between patients with arterial and venous thrombosis (12.76 ± 3.60 µmol/L vs 12.86 ± 5.51 µmol/L; P=0.990) and between patients with one thrombotic event and those with recurrent thrombotic events (12.14 ± 3.20 µmol/L vs 15.25 ± 8.51 µmol/L; P=0.254). CONCLUSION: Plasma homocysteine levels have a greater clinical significance in the prevention of thrombosis and managing its complications than MTHFR 677 genotyping.

Fibrinolytic parameters, lipid status and lipoprotein(a) in ischemic stroke patients.

INTRODUCTION: Ischemic stroke is the third leading cause of mortality and morbidity in most countries in the world. Impaired fibrinolysis, as well as disordered lipid metabolism have been recognized as risk factors for this disease. OBJECTIVE: To study some of fibrinolytic parameters, lipid status and lipoprotein(a) - Lp(a) in ischemic stroke patients in Serbia and to examine associations between Lp(a) and fibrinolytic parameters. METHODS: Sixty ischemic stroke patients (case group, mean age 63.48 +/- 9.62 years) and 30 age and sex matched healthy controls (control group, mean age 60.2 +/- 7.96 years) were studied. RESULTS: A significantly longer euglobulin clot lysis time (219.7 +/- 78,8 min. vs 183.5 +/- 58,22 min; p = 0.005) and higher levels of plasminogen activator inhibitor-1 (PAI-1) (48.5 +/- 17.1 ng/ml vs 27.1 +/- 10.1 ng/ml; p = 6.2 x 10(-11)), tissue-type plasminogen activator antigen (t-PA) (11.1 +/- 7.14 ng/ml vs 6.0 +/- 3.66 ng/ml; p = 5.2 x 10(-5)) and D-dimer (382.27 +/- 504.22 ng/ml vs 116.12 +/- 88.81 ng/ml; p = 0.0002) were found in cases compared to controls. There were no significant differences in fibrinogen levels (4.30 +/- 0.84 g/l vs 4.09 +/- 0.64 g/l; p = 0.23) or plasminogen activity (92.67 +/- 11.37% vs 96.87 +/- 9.48%; p = 0.085). There was no significant difference in Lp(a) concentration between cases and controls (0.15 +/- 0.11 g/l vs 0.12 +/- 0.11 g/l; p = 0.261). However, in the cases, but not in the controls, multivariate analysis of associations between fibrinolytic parameters and Lp(a) showed the highest correlation between t-PA and PAI-1, and the latent effect of Lp(a) on t-PA and PAI-1. CONCLUSIONS: Our results show that there are important differences in the characteristics of the fibrinolytic mechanism in ischemic stroke patients compared to healthy population. The major differences are prolonged euglobulin clot lysis time and elevated PAI-1 and t-PA antigen in ischemic stroke patients. In addition, Lp(a) appears to be involved in the inhibition offibrinolysis in ischemic disease through a mechanism unrelated to its serum concentrations.