Retroclival subdural hematoma associated with warfarin: A case report

Retroclival subdural hemorrhage is a rare entity. Apart from trauma, it may occur due to rupture of an aneurysm, pituitary apoplexy and spontaneously. Very few cases are associated with bleeding disorders.A 62-year-old female patient who was under warfarin treatment was found to have subdural hemorrhage in the retroclival area. Headache complaint was rapidly relieved by steroid treatment. She fully recovered in a month. Spontaneous retroclival hemorrhage is rarely associated with anticoagulant agents. Though it’s hardly a lethal condition, steroids can provide quick pain relief.

Warfarin Treatment Is Associated to Increased Internal Carotid Artery Calcification

Background: Long-term treatment with the vitamin K antagonist warfarin is widely used for the prevention of venous thrombosis and thromboembolism. However, vitamin K antagonists may promote arterial calcification, a phenomenon that has been previously studied in coronary and peripheral arteries, but not in extracranial carotid arteries. In this observational cohort study, we investigated whether warfarin treatment is associated with calcification of atherosclerotic carotid arteries.Methods: Overall, 500 consecutive patients underwent carotid endarterectomy, 82 of whom had received long-term warfarin therapy. The extent of calcification was assessed with preoperative computed tomography angiography, and both macroscopic morphological grading and microscopic histological examination of each excised carotid plaque were performed after carotid endarterectomy.Results: Compared with non-users, warfarin users had significantly more computed tomography angiography-detectable vascular calcification in the common carotid arteries (odds ratio 2.64, 95% confidence interval 1.51–4.63, P < 0.001) and even more calcification in the internal carotid arteries near the bifurcation (odds ratio 18.27, 95% confidence interval 2.53–2323, P < 0.001). Histological analysis revealed that the intramural calcified area in plaques from warfarin users was significantly larger than in plaques from non-users (95% confidence interval 3.36–13.56, P = 0.0018).Conclusions: Long-lasting warfarin anticoagulation associated with increased calcification of carotid atherosclerotic plaques, particularly in locations known to be the predilection sites of stroke-causing plaques. The clinical significance of this novel finding warrants further investigations.

Differential Impact of Dietary Vitamin K (phylloquinone) on Coagulation Factor Activities and Clotting Times in Warfarin-Treated Rats

Objectives Investigate the impact of variable vitamin K (VK) intakes on the coagulation activities of four VK-dependent factors and clotting times, in warfarin-treated rats. Methods Male Wistar rats were randomly allocated to a AIN-93 based diet containing low (L: 80 mcg/kg/d), adequate (A: 750 mcg/kg/d) or enriched (E: 2000 mcg/kg/d) phylloquinone (K1) containing diet (n = 24/diet group). After one week, half the animals from each diet group were randomly allocated to receive 0.2 mg warfarin/kg/d through drinking water (W gp) or plain water (C gp), for 10 weeks. Coagulation activity (%) was assessed for factors II, VII, IX and X, and clotting times were based on prothrombin [PT (sec)] and activated thromboplastin times [APTT (sec)]. Measures were obtained at the end of the study and were conducted in the hospital clinical laboratory using standard procedures. Diet effects within C and W groups were investigated using one-way ANOVA and uncorrected Fisher post-hoc tests. Results Warfarin treatment resulted in significantly higher clotting times (PT and APTT) in all diet groups when compared to corresponding C groups (p < 0.05), the highest increase being observed in the L, followed by A and E groups, each diet being statistically different from each other (p < 0.01). Warfarin treatment also resulted in statistically significant decreases in activities of all coagulation factors although the impact of the diets varied according to factors: FVII and FX, between L and E groups only; FIX, between L and A, and L and E groups; FII, between all diet groups; (p < 0.05 in all cases). Conclusions Results from this study confirm the impact of dietary VK on coagulation factor activities and resulting clotting times, and suggest that for a given dose of W, this impact will depend on VK intake levels. Currently, individuals undergoing warfarin treatment are advised to aim for stable daily VK intakes. Results from this study provide data supporting this recommendation. Funding Sources This study was funded by CIHR and MHI Foundation.

The complex relationship between C4b Binding Protein, warfarin and antiphospholipid antibodies

Background: Low levels of total C4b Binding Protein (C4BPt), a circulating inhibitor of the classical/lectin complement pathways, were observed in patients with antiphospholipid antibodies (aPL) and during warfarin treatment. Objectives: To investigate the associations between aPL and C4BPt in patients with persistently positive (++) aPL, with/without clinical manifestations and systemic lupus erythematosus (SLE), and in controls. Furthermore, we explored the impact of anticoagulation on C4BPt and in relation to complement activation. Methods: In a cross-sectional design we investigated defined subgroups: primary (p) antiphospholipid syndrome (APS, N=67), aPL++ individuals without clinical manifestations (aPL carriers, N=15), SLE-aPL++ (N=118, among them, secondary (s) APS, N=56), aPL negative (-) SLE (SLE-aPL-, N=291) and 322 controls. Clinical characteristics, including treatment, were tabulated. C4BPt was determined with a magnetic bead method. Complement proteins (C1q, C2, C3, C4, C3a, C3dg, sC5b-9, Factor I) were measured. A mediation analysis was performed to decompose the total effect of aPL++ on C4BPt into the direct and indirect effects of aPL++ through warfarin. Results: Overall, C4BPt is 20% decreased in aPL++ patients, regardless SLE, APS, clinical manifestations and aPL profile. C4BPt levels associate positively with complement proteins C1q, C2, C3, C4, and negatively with complement activation product C3dg. In the SLE group, warfarin treatment contributes to approximately half of the C4BPt reduction (9%) Conclusion: Both antiphospholipid antibodies and warfarin are associated with C4BPt reduction. Complement activation in aPL ++ patients may partly be explained by impaired inhibition through depressed C4BPt levels. Further studies are needed to understand the clinical implication

Evaluation of Bleeding Rate and Time in Therapeutic Range in Patients Using Warfarin Before and During the COVID-19 Pandemic—Warfarin Treatment in COVID-19

The treatment process of patients using warfarin is expected to be hindered during the COVID-19 pandemic. Therefore we investigated whether the time in therapeutic range (TTR) and bleeding complications were affected during the COVID-19 pandemic. 355 patients using warfarin were included between March 2019 to March 2021. Demographic parameters, INR (international normalized ratio), and bleeding rates were recorded retrospectively. The TTR value was calculated using Rosendaal’s method. The mean age of the patients was 61 ± 12 years and 55% of them were female. The mean TTR value during the COVID-19 pandemic was lower than the pre-COVID-19 period (56 ± 21 vs 68 ± 21, P < 0.001). Among the patients, 41% had a lack of outpatient INR control. During the COVID-19 pandemic, 71 (20%) patients using VKA suffered bleeding. Among patients with bleeding, approximately 60% did not seek medical help and 6% of patients performed self-reduction of the VKA dose. During the COVID-19 pandemic, TTR values have decreased with the lack of monitoring. Furthermore, the majority of patients did not seek medical help even in case of bleeding.

Safety performance of rivaroxaban versus warfarin in patients with atrial fibrillation and advanced chro­nic kidney disease

Aim To evaluate safety of using rivaroxaban in patients with stage 4 chronic kidney disease (CKD) or transient, stable decline of glomerular filtration rate (GFR) to 15–29 ml /min / 1.73 m2 in the presence of atrial fibrillation (AF).Material and methods This multicenter prospective, randomized study included patients admitted to cardiology departments from 2017 through 2019. Of 10 224 admitted patients 109 (3 %) patients with AF and stage 4 CKD or a stable decline of GFR to 15–29 ml /min / 1.73 m2 were randomized at 2:1 ratio to the rivaroxaban 15 mg /day (n=73) treatment group or to the warfarin treatment group (n=36). The primary endpoint was development of BARC and ISTH major, minor, and clinically relevant minor bleeding. Mean follow-up duration was 18 months.Results Patients receiving warfarin had a significantly higher incidence of BARC (n=26 (72.2 %) vs. n=31 (42.4 %), р<0.01) and ISTH (n=22 (61.1 %) vs. n=27 (36.9 %), p<0.01) minor bleeding and all ISTH clinically relevant (minor clinically relevant and major bleedings) n=10 (27.7 %) vs. n=8 (10.9 %), р=0.03]. The number of repeated hospitalizations was 65 (43% of patients) in the rivaroxaban treatment group and 27 (48% of patients) in the warfarin treatment group (р=0.57), including 24 (36.9 %) and 11 (40.7 %) emergency admissions in the rivaroxaban and warfarin treatment groups, respectively (р=0.96). Significant improvement of changes in creatinine clearance and GFR (by CKD-EPI and Cockroft-Gault) was observed in the rivaroxaban treatment group.Conclusion The study provided evidence for a more beneficial safety profile of rivaroxaban compared to warfarin in patients with AF and advanced CKD.

Pharmacist-led interventions might improve quality of life among older adult patients receiving warfarin treatment in rural areas: results from a randomized controlled trial

The authors have requested that this preprint be withdrawn due to author disagreement.