Continuous Warfarin Administration Versus Heparin Bridging Therapy in Post Colorectal Polypectomy Hemorrhage: A Study Protocol for a Multicenter Randomized Controlled Trial (WHICH Study)

Mortality and Outcome in Patients Older Than 80 Years of Age Undergoing Burr-Hole Drainage of Chronic Subdural Hematoma

Anticoagulants are used to prevent thromboembolic events. Direct oral anticoagulants (DOAC) are our new choice; however, their effect on bleeding risk for endoscopic treatment has not been reported. We aimed to assess the clinical effect of DOAC compared to warfarin for gastric endoscopic submucosal dissection (ESD). We retrospectively studied 97 patients on anticoagulants and treated 108 gastric neoplasms with ESD in three referral institutes. Twenty-four patients were taking DOAC, including dabigatran (12), rivaroxaban (11), and apixaban (one) and 73 were taking warfarin. In the DOAC group, delayed bleeding rate was significantly higher in patients on rivaroxaban than in patients on dabigatran (45% vs 0%, P<0.05) without relation to heparin bridge therapy (HBT). In the warfarin group, 78% of patients underwent HBT, and delayed bleeding rate was significantly higher in patients with HBT than in those without (36% vs 0%, P<0.05). Delayed bleeding rate increased as intake of antithrombotic agents increased (P<0.05). HBT period was shorter (P<0.05) in DOAC because DOAC achieve the maximum effect quicker, and hospitalization period was shorter (P<0.05), compared with warfarin. Multivariate analysis showed that HBT (OR, 10.7), rivaroxaban (OR, 6.00) and multiple antithrombotic agents (OR, 4.35) were independent delayed bleeding risk factors. The DOAC effect differs in each agent. Dabigatran is a feasible alternative to warfarin for shortening the hospitalization period and decreasing delayed bleeding rate, although rivaroxaban has a significantly higher delayed bleeding risk.

Patients (pts.) with atrial fibrillation (AF) and atrial thrombi are known to have an increased risk for cerebral embolism. However, little is known about the clinical course of atrial thrombi and the incidence of cerebral embolism in those patients during anticoagulation therapy. The high sensitivity of MR imaging (MRI) including diffusion-weighted imaging (DWI) suggests that this technique could provide an improved estimate of cerebral embolism associated with the presence of left atrial thrombi. The aims of this prospective study were to evaluate 1) the prevalence of clinically silent and apparent cerebral embolism in pts. with newly diagnosed AF and atrial thrombi using MRI/DWI, 2) the long-term fate of atrial thrombi under continues anticoagulation therapy and 3) the incidence of cerebral embolism during a follow-up period of 12 months with continuous anticoagulation therapy. The study group consisted of 32 pts. with 1) newly diagnosed AF and evidence of left atrial (LA) thrombi detected by TEE and 2) a new start of anticoagulation therapy [International Normalized Ratio (INR) 2.0 - 3.0]. 19 pts. with 1) newly diagnosed AF and no evidence of atrial thrombi and 2) an equivalent anticoagulation regimen served as the control group. In both groups a) MRI/DWI studies of the brain (weeks 0, 4, 8, 12, 20, 28, 36, 44, and 52), b) transesophageal echocardiographic studies (TEE) for assessment of LA-Thrombi (weeks 0 and 52) and c) clinical neurological assessments (weeks 0, 20 and 52) were performed. In the study group (AF and LA-Thrombi) 11 out of 32 pts. (34 %) displayed signs of acute (n = 8) or chronic (n = 3) cerebral embolism in the initial MRI studies. In 4 out of 32 pts. (13 %), MRI/DWI depicted new or additional cerebral emboli (n = 12) during the follow-up period despite continuous anticoagulation therapy. 2 (n = 2/4; 50 %) of these patients had clinically apparent neurological deficits. In the control group 1 out of 19 pts. (5 %) showed evidence of chronic cerebral embolism as assessed by MRI/DWI at the beginning of the study (week 0). No embolic cerebral lesions were detected during the 12-month follow-up. Within 12 months only 63 % (n = 20/32) of LA thrombi in the study group resolved completely under anticoagulation. 1. The incidence of clinically inapparent cerebral emboli in pts. with newly diagnosed AF and atrial thrombi is much higher than the incidence of clinically apparent emboli and has been underestimated in the past. 2. New cerebral embolism may occur even with continued effective anticoagulation therapy in 13 % of pts. 3. Only 63 % of atrial thrombi resolve completely within 12 months under anticoagulation therapy.

AHA Scientific Statement: Guide to anticoagulant therapy: heparin: a statement for healthcare professionals from the American Heart Association.

In older populations, oral anticoagulation therapy (OAT) is underused by physicians, mainly because of fear of bleeding complications. The aim of this study was to determine the incidence of bleeding complications and associated risk factors in a large heterogeneous group of older patients. Combined retrospective and prospective cohort study conducted in geriatric and internal medicine departments. All patients 80 years or older discharged with the recommendation of OAT were followed up for a mean +/- SD of 28.8 +/- 36.3 months. The rate of bleeding events and the quality of anticoagulation were compared across a wide range of demographic and clinical variables and cognitive and functional status. In addition, we assessed the quality of education given to the patient or caregiver on the use of OAT. Among 15 387 patients 80 years or older, 323 (2.1%) were discharged with the recommendation of OAT. The rate of major bleedings was 2.4 events per 1000 patient-months. Socioeconomic and cognitive variables and functional impairments were not associated with an increased rate of bleeding. In multivariate analysis, insufficient education on OAT as perceived by the patient or caregiver (odds ratio [OR], 8.83), polypharmacy (OR, 6.14), and international normalized ratio values above the therapeutic range (OR, 1.08) were the only significant predictive factors for bleeding complications. The rate of bleeding complications, especially major bleedings, was low in this large group of older patients, many with comorbidities and cognitive and functional impairments. Insufficient OAT education was the major factor that predicted bleeding. Therefore, improving and fostering better methods of OAT education may further reduce bleeding complications.

Comparison of postoperative bleeding in pediatric tonsillectomy versus tonsillotomy

Diathermy power settings as a risk factor for hemorrhage after tonsillectomy

Postoperative pancreatic fistula is a common and serious complication following pancreaticoduodenectomy. Duct-to-mucosa pancreaticojejunostomy has been used in many centers to reconstruct pancreatic digestive continuity following pancreatoduodenectomy, however, its efficacy and safety are uncertain. To assess the benefits and harms of duct-to-mucosa pancreaticojejunostomy versus other types of pancreaticojejunostomy for the reconstruction of pancreatic digestive continuity in participants undergoing pancreaticoduodenectomy, and to compare the effects of different duct-to-mucosa pancreaticojejunostomy techniques. We searched the Cochrane Library (2021, Issue 1), MEDLINE (1966 to 9 January 2021), Embase (1988 to 9 January 2021), and Science Citation Index Expanded (1982 to 9 January 2021). We included all randomized controlled trials (RCTs) that compared duct-to-mucosa pancreaticojejunostomy with other types of pancreaticojejunostomy (e.g. invagination pancreaticojejunostomy, binding pancreaticojejunostomy) in participants undergoing pancreaticoduodenectomy. We also included RCTs that compared different types of duct-to-mucosa pancreaticojejunostomy in participants undergoing pancreaticoduodenectomy. Two review authors independently identified the studies for inclusion, collected the data, and assessed the risk of bias. We performed the meta-analyses using Review Manager 5. We calculated the risk ratio (RR) for dichotomous outcomes and the mean difference (MD) for continuous outcomes with 95% confidence intervals (CIs). For all analyses, we used the random-effects model. We used the Cochrane RoB 1 tool to assess the risk of bias. We used GRADE to assess the certainty of the evidence for all outcomes. We included 11 RCTs involving a total of 1696 participants in the review. One RCT was a dual-center study; the other 10 RCTs were single-center studies conducted in: China (4 studies); Japan (2 studies); USA (1 study); Egypt (1 study); Germany (1 study); India (1 study); and Italy (1 study). The mean age of participants ranged from 54 to 68 years. All RCTs were at high risk of bias. Duct-to-mucosa versus any other type of pancreaticojejunostomy We included 10 RCTs involving 1472 participants comparing duct-to-mucosa pancreaticojejunostomy with invagination pancreaticojejunostomy: 732 participants were randomized to the duct-to-mucosa group, and 740 participants were randomized to the invagination group after pancreaticoduodenectomy. Comparing the two techniques, the evidence is very uncertain for the rate of postoperative pancreatic fistula (grade B or C; RR 1.45, 95% CI 0.64 to 3.26; 7 studies, 1122 participants; very low-certainty evidence), postoperative mortality (RR 0.77, 95% CI 0.39 to 1.49; 10 studies, 1472 participants; very low-certainty evidence), rate of surgical reintervention (RR 1.12, 95% CI 0.65 to 1.95; 10 studies, 1472 participants; very low-certainty evidence), rate of postoperative bleeding (RR 0.85, 95% CI 0.51 to 1.42; 9 studies, 1275 participants; very low-certainty evidence), overall rate of surgical complications (RR 1.12, 95% CI 0.92 to 1.36; 5 studies, 750 participants; very low-certainty evidence), and length of hospital stay (MD -0.41 days, 95% CI -1.87 to 1.04; 4 studies, 658 participants; very low-certainty evidence). The studies did not report adverse events or quality of life outcomes. One type of duct-to-mucosa pancreaticojejunostomy versus a different type of duct-to-mucosa pancreaticojejunostomy We included one RCT involving 224 participants comparing duct-to-mucosa pancreaticojejunostomy using the modified Blumgart technique with duct-to-mucosa pancreaticojejunostomy using the traditional interrupted technique: 112 participants were randomized to the modified Blumgart group, and 112 participants were randomized to the traditional interrupted group after pancreaticoduodenectomy. Comparing the two techniques, the evidence is very uncertain for the rate of postoperative pancreatic fistula (grade B or C; RR 1.51, 95% CI 0.61 to 3.75; 1 study, 210 participants; very low-certainty evidence), postoperative mortality (there were no deaths in either group; 1 study, 210 participants; very low-certainty evidence), rate of surgical reintervention (RR 1.93, 95% CI 0.18 to 20.91; 1 study, 210 participants; very low-certainty evidence), rate of postoperative bleeding (RR 2.89, 95% CI 0.12 to 70.11; 1 study, 210 participants; very low-certainty evidence), overall rate of surgical complications (RR 1.10, 95% CI 0.80 to 1.51; 1 study, 210 participants; very low-certainty evidence), and length of hospital stay (15 days versus 15 days; 1 study, 210 participants; very low-certainty evidence). The study did not report adverse events or quality of life outcomes. The evidence is very uncertain about the effects of duct-to-mucosa pancreaticojejunostomy compared to invagination pancreaticojejunostomy on any of the outcomes, including rate of postoperative pancreatic fistula (grade B or C), postoperative mortality, rate of surgical reintervention, rate of postoperative bleeding, overall rate of surgical complications, and length of hospital stay. The evidence is also very uncertain whether duct-to-mucosa pancreaticojejunostomy using the modified Blumgart technique is superior, equivalent or inferior to duct-to-mucosa pancreaticojejunostomy using the traditional interrupted technique. None of the studies reported adverse events or quality of life outcomes.

Polypectomy devices

Clinical outcome in patients with venous thromboembolism receiving concomitant anticoagulant and antiplatelet therapy

The authors evaluated the effects of acetylsalicylic acid (ASA) usage and transfusion of previously frozen apheresis platelets on postoperative hemorrhage, activities of daily living (ADL) score, and mortality rate in patients with acute hypertensive basal ganglia hemorrhage undergoing craniotomy. This was a prospective, double-blind, parallel, randomized controlled trial in patients with acute hypertensive basal ganglia hemorrhage, who had either not received ASA therapy (control) or received ASA therapy. The patients who received ASA therapy were divided according to the results of a platelet aggregation test into ASA-resistant, ASA-semiresponsive, and ASA-sensitive groups. All patients required an emergency craniotomy for hematoma removal after hospitalization. The patients who were sensitive to ASA were randomized to receive one of the following transfusion regimens of previously frozen apheresis platelets: no transfusion, 1 therapeutic dose before surgery, or 2 therapeutic doses (1 before surgery and 1 after 24 hours of hospitalization). The postoperative hemorrhage rate and the average postoperative hemorrhage volume were recorded and the ADL scores and mortality rate were measured during a 6-month follow-up period. The rate of postoperative hemorrhage, average postoperative hemorrhage volume, and mortality rate were significantly higher in the ASA-sensitive patients who received ASA therapy compared with patients who did not receive ASA therapy (all p < 0.005). The ADL scores were grouped into different grades and the number of cases in the lower grades was higher and the overall scores were poorer in patients who received ASA therapy compared with those who did not (all p < 0.005). After transfusion of previously frozen apheresis platelets, the postoperative hemorrhage rate, average postoperative hemorrhage volume, and mortality rate of the ASA-sensitive patients were significantly lowered (all p < 0.005), and the ADL scores and their classification level were better than those of patients who did not undergo transfusion (all p < 0.005). Transfusion of previously frozen apheresis platelets reduces the rate of postoperative hemorrhage, average postoperative hemorrhage volume, disability rate, and mortality rate in ASA-sensitive patients with acute hypertensive basal ganglia hemorrhage undergoing craniotomy.

Novel Oral Anticoagulants in Patients Undergoing Cranial Surgery.

Introduction The optimal perioperative antithrombotic management of patients receiving antithrombotic therapy (ATT) remains controversial. In this study, we investigated the safety and feasibility of laparoscopic hernia surgery in patients taking ATT, especially those with a preoperative continuation of single antiplatelet therapy (APT). Methods Three hundred ninety-six (396) patients who underwent laparoscopic hernia surgery between April 2014 and March 2023 in our institution were retrospectively reviewed. The patients were divided into two groups: patients who continued single aspirin monotherapy preoperatively (continued single aspirin therapy (cAPT) group; n = 118) and patients who did not receive APT preoperatively (non-APT group; n = 278). Our perioperative antithrombotic management included preoperative continuation of single aspirin therapy for patients with APT or interruption of oral anticoagulation therapy (ACT), bridging anticoagulation with unfractionated heparin or direct-acting oral anticoagulants (DOAC) replacement for patients with ACT. The primary outcome was postoperative bleeding complications (BC). Results There were four postoperative BCs (Clavien-Dindo classification≧Ⅱ) (1.0%) in the whole cohort, one (0.9%) in the cAPT group, and three (1.1%) in the non-APT group, which were not significantly differentiated (p = 0.8330). Multivariable analysis showed heparin or DOAC replacement was an independently and significantly risk factor for postoperative bleeding (p = 0.0029, odds ratio (OR) = 32.6). Continuation of preoperative aspirin was not a risk factor for postoperative BCs. No thromboembolic complications occurred in the whole cohort. Conclusion We can safely and feasibly perform laparoscopic hernia surgery under preoperative antithrombotic management, including the preoperative continuation of single aspirin therapy, without any increase in bleeding events. However, careful consideration is required for the patient who received heparin bridging or DOAC replacement.

Clinicians should consider the clinical impact of anticoagulant-related bleeding when deciding on the duration of anticoagulant therapy in patients with venous thromboembolism. To provide reliable estimates of the clinical impact of anticoagulant-related bleeding, defined as the case-fatality rate of major bleeding and the risk for intracranial bleeding. MEDLINE (January 1989 to May 2003), Cochrane Controlled Trial Registry, thromboembolism experts, and reference lists; English-language literature only. Randomized, controlled trials and prospective cohort studies that investigated patients with venous thromboembolism who received oral anticoagulant therapy (target international normalized ratio, 2.0 to 3.0) for at least 3 months and that reported major bleeding and death as primary study outcomes. Two reviewers independently extracted data on the number of anticoagulant-related major and intracranial bleeding episodes and on whether these events were fatal or nonfatal. The authors analyzed 33 studies involving 4374 patient-years of oral anticoagulant therapy. For all patients, the case-fatality rate of major bleeding was 13.4% (95% CI, 9.4% to 17.4%) and the rate of intracranial bleeding was 1.15 per 100 patient-years (CI, 1.14 to 1.16 per 100 patient-years). For patients who received anticoagulant therapy for more than 3 months, the case-fatality rate of major bleeding was 9.1% (CI, 2.5% to 21.7%), and the rate of intracranial bleeding was 0.65 per 100 patient-years (CI, 0.63 to 0.68 per 100 patient-years) after the initial 3 months of anticoagulation. The clinical impact of anticoagulant-related major bleeding in patients with venous thromboembolism is considerable, and clinicians should take this into account when deciding whether to continue long-term oral anticoagulant therapy in an individual patient.

BACKGROUND: When treating a new coronavirus infection, the prevention of venous thromboembolic complications in obese patients is of particular importance.&#x0D; AIM: To analyze various options for anticoagulant therapy in obese and non-obese patients in the treatment of a new coronavirus infection.&#x0D; MATERIAL AND METHODS: The patients were divided into two groups: the first group — obese patients — 151 (40.8%) people [average age 63 (56–69) years], the second group without obesity — 219 (59.2%) people [average age 63 (51.5–71.0) years], p=0.998. According to the prescribed anticoagulant and the presence of obesity, patients were divided into subgroups: subgroup 1 — non-obese + low-molecular-weight heparin (n=114), subgroup 2 — non-obese + unfractionated heparin (n=58), subgroup 3 — obesity + low-molecular-weight heparin (n=76), subgroup 4 — obesity + unfractionated heparin (n=66). Venous thrombotic complications and bleeding rates were assessed. Analysis of qualitative indicators was performed using Pearson χ2 and Fisher tests. The distribution of quantitative indicators was assessed using the Kolmogorov–Smirnov and Shapiro–Wilk tests (p 0.05). Due to the non-normal distribution of indicators, mean values were presented as median (Me) and interquartile range (Q1–Q3), and analysis was carried out using Wilcoxon, Mann–Whitney and Kruskal–Wallis tests.&#x0D; RESULTS: In nonobese patients, a comparable incidence of deep vein thrombosis was noted on low molecular weight heparin and unfractionated heparin — 1 (0.9%) case versus 3 (5.2%) cases (p=0.102). At the same time, there was a statistically significant difference in the frequency of pulmonary embolism without a source according to autopsy data — 2 (1.8%) versus 4 (6.9%) cases (p=0.004). In obese patients receiving unfractionated heparin, the incidence of this complication was higher and amounted to 9 (13.6%), and in patients receiving low molecular weight heparin — 2 (2.6%) cases (p=0.004). A higher incidence of bleeding was observed in patients with obesity compared to patients without it (10.6 vs 4.7% of cases, p=0.045). When analyzing hemorrhagic complications, it was found that the incidence of major and significant bleeding was higher in patients receiving unfractionated heparin rather than low molecular weight heparin (16.7 vs 5.3% of cases, p 0.001).&#x0D; CONCLUSION: The use of low molecular weight heparin in obese patients with new coronavirus infection was associated with a low incidence of pulmonary embolism and bleeding compared with patients receiving unfractionated heparin.