Bleeding Complications In Patients Research Articles

#2988 Use of rivaroxaban for prevention of thrombotic events in patients with nephrotic syndrome

Abstract Background and Aims Patients with nephrotic syndrome are at increased risk of thrombotic events. The risk of thromboembolism is particularly high in patients with primary membranous nephropathy, elderly patients and patients with severe hypoalbuminemia. Although increased incidence of thrombosis is a well reported complication associated with nephrotic syndrome, management strategies are not well established. Use of aspirin seems to be insufficient to prevent venous thromboembolism. Use of warfarin and low-molecular-weight heparins is inconvenient for outpatients. The aim of the trial was to evaluate effectiveness and safety of rivaroxaban in venous thromboembolism prophylaxis in patients with nephrotic syndrome. Method The randomized single-center trial was performed from October 2020 to November 2023. 30 adult patients with nephrotic syndrome due to primary glomerular diseases and glomerular filtration rate more than 60 ml/min were divided into two groups. The treatment group (n = 15) received 10-20 mg of rivaroxaban daily. The control group (n = 15) had no anticoagulation therapy. Thrombotic events and bleedings were recorded. Results Patients in both groups received immunosuppressive treatment of nephrotic syndrome according to primary disease. Rivaroxaban was prescribed for the entire treatment period until the onset of remission. Patients with membranous nephropathy were equally represented in both study groups (4 per group). No thromboembolic events were recorded in both groups. As well as there were no bleeding complications in patients who received rivaroxaban. Conclusion Rivaroxaban might be a possible alternative to warfarin and low-molecular-weight heparins in prevention of thrombosis in nephrotic syndrome. However, indications for anticoagulant prophylaxis, its duration and discontinuation are still not clear. Future studies should address the question regarding the utility of primary thromboprophylaxis.

Transfemoral-only transcatheter aortic valve replacement: A single center experience of 400 consecutive patients.

In transcatheter aortic valve replacement (TAVR),transfemoral (TF) access offers several advantages over alternative access routes. Advances in sheaths and valve delivery technology have catalyzed the feasibility of TF-TAVR, even in challenging anatomies. Report procedural characteristics and outcomes of a TAVR program aiming for a 100% TF access rate. Consecutive patients undergoing TAVR were enrolled in a prospective registry. Equipment used to facilitate TF-access in challenging anatomies included low-profile sheaths, dilatators, peripheral balloons, covered and uncovered self-expandingand balloon-expandable stents, and intravascular lithotripsy (IVL). A total of 400 patients with a mean age of 81 ± 6 years (42% female) were analyzed. Minimal iliofemoral artery diameter (MLD) of the main access side was <5 mm in 42 (10.5%), extreme tortuosity was present in 65 (16.3%), and severe calcification in 59 (14.8%). TF-access was successful in 399 (99.8%) patients. A transaxillary access was used in one patient. In multivariable analysis, an MLD < 5 mm was the strongest predictor for vascular complications (11.9% vs. 3.9%, OR: 3.86, 95% CI: 1.38-10.8, p = 0.01). Such patients also had more major/life-threatening bleeding (14.2% vs. 3.1%, p < 0.001) and required more planned and unplanned peripheral interventions to enable TFaccess (35.8% vs. 3.4%, p < 0.001). Our study shows that utilization of dedicated sheaths, peripheral balloons, stents, and IVL enables TAVR via TF access in >99% of patients. However, rates of vascular and bleeding complications in patients with narrow iliofemoral arteries (MLD < 5 mm) were high.

Direct oral anticoagulant-associated bleeding complications in patients with gastrointestinal cancer and venous thromboembolism

BackgroundDirect oral anticoagulants (DOACs) have become widely used for cancer-associated venous thromboembolism (VTE). However, DOAC-associated bleeding complications remain challenging, especially in patients with gastrointestinal (GI) cancer. This study aimed to compare the bleeding outcomes between patients with upper or lower GI cancers and those without GI cancer. MethodsUsing the COMMAND VTE Registry-2 database, which is a multicenter registry enrolling 5197 consecutive acute symptomatic VTE patients among 31 centers in Japan between January 2015 and August 2020, we identified 1149 active cancer patients with DOACs (upper GI cancer: N=88; lower GI cancer: N=114; non-GI cancer: N=947). The primary outcome was major bleeding during anticoagulation therapy, which was evaluated in the competing risk regression model. ResultsThe upper GI cancer group had a lower mean body weight, and most often had anemia. The cumulative 5-year incidence of major bleeding was higher in the upper GI cancer group (upper GI cancer: 22.4%, lower GI cancer: 15.4%, and non-GI cancer: 11.6%, P=0.015). The most frequent major bleeding site in the upper GI cancer group was the upper GI (53%), followed by the lower GI (24%). After adjusting for the confounders, the excess risk in upper GI cancer relative to non-GI cancer remained significant for major bleeding (adjusted subhazard ratio, 2.25; 95%CI, 1.31-3.87, P=0.003), but that in lower GI cancer was insignificant. ConclusionsUpper GI cancer, but not lower GI cancer, as compared to non-GI cancer was associated with a higher risk for major bleeding during anticoagulation therapy with DOACs.Clinical Trial Registration: URL: http://www.umin.ac.jp/ctr/index.htmUnique identifier: UMIN000044816.

(565) - Role of Acquired Von Willebrand Syndrome in the Development of Bleeding Complications in Patients Treated Using Right Ventricular Microaxial Flow Pump Devices: A Retrospective Cohort Study

(565) - Role of Acquired Von Willebrand Syndrome in the Development of Bleeding Complications in Patients Treated Using Right Ventricular Microaxial Flow Pump Devices: A Retrospective Cohort Study

Effects of thienopyridine class antiplatelets on bleeding outcomes following robot-assisted radical prostatectomy.

This study aimed to assess the effects of thienopyridine-class antiplatelet agents (including ticlopidine, clopidogrel, and prasugrel) on bleeding complications in patients who underwent robot-assisted radical prostatectomy. This cohort study used a database for robot-assisted radical prostatectomy at 23 tertiary centers nationwide between 2011 and 2022. Patients who received thienopyridines (thienopyridine group) were compared with those who received aspirin monotherapy (aspirin group). The primary outcome was the incidence of bleeding complications. High-grade complications were defined as Clavien-Dindo grade III or higher. The risks of these outcomes were evaluated using inverse probability of treatment weighted regression models. The study results demonstrated that thienopyridine therapy was associated with a higher risk of overall bleeding complications (OR: 3.62, 95%CI 1.54-8.49). The increased risks of the thienopyridine group were detected for low-grade bleeding complications (OR: 3.20, 95%CI 1.23-8.30) but not for high-grade bleeding complications (OR: 5.23, 95%CI 0.78-34.9). The increased risk of bleeding complications was not observed when thienopyridine was discontinued (OR: 2.52, 95%CI 0.83-7.70); however, it became apparent when it was continued perioperatively (OR: 4.35, 95%CI 1.14-16.61). In conclusion, thienopyridine increased the incidence of bleeding complications, particularly low-grade bleeding complications, following robot-assisted radical prostatectomy. These bleeding effects emerged when thienopyridine was continued perioperatively.

The Effect of Out-of-Hours Admission on Mortality in Patients Who Underwent Thrombectomy Due to Ischemic Stroke.

It is important to investigate the factors that may delay the diagnosis and treatment process of ischemic stroke. The aim of this study was to investigate whether in-hospital mortality increased in patients who presented to the emergency department out-of-hours and underwent thrombectomy. A total of 59 patients who applied to the emergency department between January 1, 2018 and November 1, 2021 and underwent thrombectomy due to ischemic stroke were included in the study. Patient age, gender, thrombectomy success (successful recanalization), in-hospital mortality status, intracranial hemorrhage status after thrombectomy, and out-of-hours admission status were recorded and compared according to out-of-hours admission status. Twenty-seven (45.8%) patients were male, and the median age was 74 (61-81) years. Forty-two (71.2%) patients applied to the emergency department out-of-hours. In-hospital mortality occurred in 27 (45.8%) patients. There was no statistically significant difference in out-of-hours admission status between the non-survivor group and the survivor group (non-survivor: 24 [75%]; survivor: 18 [66.7%], p = 0.481). Nor was a statistically significant difference found in the intracranial hemorrhage complication rate of the patients admitted out-of-hours compared to the patients admitted during working hours (out-of-hours: 17 [40.5%]; during working hours: 6 [35.3%], p = 0.712). No statistically significant difference was found in the rate of in-hospital mortality and intracranial bleeding complications in patients who underwent thrombectomy out of working hours compared to during working hours.

Thrombotic and bleeding complications in patients with AL amyloidosis.

Haemostatic abnormalities and deregulated coagulation are common complications in AL amyloidosis. The relevant risks of thromboembolic and haemorrhagic events have not been thoroughly evaluated. To describe clinically significant thrombotic/haemorrhagic events in 450 consecutive patients with AL amyloidosis. Venous thromboembolic events (VTEs) were reported in 6% and arterial embolic events (AEEs) in 5% of patients, respectively, during a 55-month median follow-up. Lower albumin, lower eGFR, higher BM infiltration, soft tissue involvement, IMiD-based therapy and prior thrombosis were associated with VTE risk. Prior thrombosis was the only independent prognostic variable (HR 9.3, p = 0.001). Coronary arterial disease, prior AEE, 24-h proteinuria and higher platelet counts were associated with AEE risk. Significant bleeding events were reported in 9%, and associated mortality was 19%. Liver involvement, higher serum creatinine and higher baseline VWF:Ag levels were linked to bleeding risk. Using competing risk analysis, the cumulative probability of thrombosis/bleeding was higher during the first year following diagnosis, but a stable lower risk for both events remained for the duration of follow-up. In AL amyloidosis patients, the risk of thrombotic/arterial embolic events is significant, but the bleeding risk is also high. A multiparametric assessment is required to initiate anti-thrombotic or anti-platelet therapy appropriately.

Risk factors for bleeding complications in patients undergoing extracorporeal cardiopulmonary resuscitation following out-of-hospital cardiac arrest: a secondary analysis of the SAVE-J II study

BackgroundBleeding is the most common complication in out-of-hospital cardiac arrest (OHCA) patients receiving extracorporeal cardiopulmonary resuscitation (ECPR). No studies comprehensively described the incidence rate, timing of onset, risk factors, and treatment of bleeding complications in OHCA patients receiving ECPR in a multicenter setting with a large database. This study aimed to analyze the risk factors of bleeding during the first day of admission and to comprehensively describe details of bleeding during hospitalization in patients with OHCA receiving ECPR in the SAVE-J II study database.MethodsThis study was a secondary analysis of the SAVE-J II study, which is a multicenter retrospective registry study from 36 participating institutions in Japan in 2013–2018. Adult OHCA patients who received ECPR were included. The primary outcome was the risk factor of bleeding complications during the first day of admission. The secondary outcomes were the details of bleeding complications and clinical outcomes.ResultsA total of 1,632 patients were included. Among these, 361 patients (22.1%) had bleeding complications during hospital stay, which most commonly occurred in cannulation sites (14.3%), followed by bleeding in the retroperitoneum (2.8%), gastrointestinal tract (2.2%), upper airway (1.2%), and mediastinum (1.1%). These bleeding complications developed within two days of admission, and 21.9% of patients required interventional radiology (IVR) or/and surgical interventions for hemostasis. The survival rate at discharge of the bleeding group was 27.4%, and the rate of favorable neurological outcome at discharge was 14.1%. Multivariable logistic regression analysis showed that the platelet count (< 10 × 104/μL vs > 10 × 104/μL) was significantly associated with bleeding complications during the first day of admission (adjusted odds ratio [OR]: 1.865 [1.252–2.777], p = 0.002).ConclusionsIn a large ECPR registry database in Japan, up to 22.1% of patients experienced bleeding complications requiring blood transfusion, IVR, or surgical intervention for hemostasis. The initial platelet count was a significant risk factor of early bleeding complications. It is necessary to lower the occurrence of bleeding complications from ECPR, and this study provided an additional standard value for future studies to improve its safety.

Machine learning algorithm to predict postoperative bleeding complications after lateral decubitus percutaneous nephrolithotomy.

Bleeding is a serious complication following percutaneous nephrolithotomy (PCNL). This study establishes a predictive model based on machine learning algorithms to forecast the occurrence of postoperative bleeding complications in patients with renal and upper ureteral stones undergoing lateral decubitus PCNL. We retrospectively collected data from 356 patients with renal stones and upper ureteral stones who underwent lateral decubitus PCNL in the Department of Urology at Peking University First Hospital-Miyun Hospital, between January 2015 and August 2022. Among them, 290 patients had complete baseline data. The data was randomly divided into a training group (n = 232) and a test group (n = 58) in an 8:2 ratio. Predictive models were constructed using Logistic Regression, Random Forest, and Extreme Gradient Boosting (XGBoost). The performance of each model was evaluated using Accuracy, Precision, F1-Score, Receiver Operating Characteristic curves, and Area Under the Curve (AUC). Among the 290 patients, 35 (12.07%) experienced postoperative bleeding complications after lateral decubitus PCNL. Using postoperative bleeding as the outcome, the Logistic model achieved an accuracy of 73.2%, AUC of 0.605, and F1 score of 0.732. The Random Forest model achieved an accuracy of 74.5%, AUC of 0.679, and F1 score of 0.732. The XGBoost model achieved an accuracy of 68.3%, AUC of 0.513, and F1 score of 0.644. The predictive model for postoperative bleeding after lateral decubitus PCNL, established based on machine learning algorithms, is reasonably accurate. It can be utilized to predict postoperative stone residue and recurrence, aiding urologists in making appropriate treatment decisions.

Comparison of Discriminative Ability of Bleeding Risk Criteria and Scores for Predicting Short- and Mid-Term Major Bleeding Events in Patients Undergoing Percutaneous Coronary Intervention.

Background: This study aimed to compare the discriminative ability of the Japanese Version of High Bleeding Risk (J-HBR), Academic Research Consortium for High Bleeding Risk (ARC-HBR), and Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Antiplatelet Therapy (PRECISE-DAPT) scores for predicting major bleeding events. Methods and Results: Between January 2017 and December 2020, 646 consecutive patients who underwent successful percutaneous coronary intervention (PCI) were enrolled. We scored the ARC-HBR and J-HBR criteria by assigning 1 point to each major criterion and 0.5 point to each minor criterion. The primary outcome was major bleeding events, defined as Bleeding Academic Research Consortium type 3 or 5 bleeding events. According to the J-HBR, ARC-HBR, and PRECISE-DAPT scores, 428 (66.3%), 319 (49.4%), and 282 (43.7%) patients respectively had a high bleeding risk. During the follow-up period (median, 974 days), 44 patients experienced major bleeding events. The area under the curve (AUC) using the time-dependent receiver operating characteristic curve for major bleeding events was 0.84, 0.82, and 0.83 within 30 days and 0.86, 0.83, and 0.80 within 2 years for the J-HBR, ARC-HBR, and PRECISE-DAPT scores, respectively. The AUC values did not differ significantly among the 3 bleeding risk scores. Conclusions: The J-HBR score had a discriminative ability similar to the ARC-HBR and PRECISE-DAPT scores for predicting short- and mid-term major bleeding events.

The predictive value of PRECISE-DAPT score for long-term mortality in patients with acute coronary syndrome complicated by cardiogenic shock.

Besides its primary clinical utility in predicting bleeding risk in patients with acute coronary syndrome (ACS), the PRECISE-DAPT (Predicting Bleeding Complications in Patients Undergoing Stent Implantation and Subsequent Dual Anti-Platelet Therapy) score may also be useful for predicting long-term mortality in ACS patients presenting with cardiogenic shock (CS) since several studies have reported an association between the score and certain cardiovascular conditions or events. The aim of the present study was to evaluate the utility of the PRECISE-DAPT score for predicting the long-term all-cause mortality in patients (n = 293) with ACS presenting with CS. The PRECISE-DAPT score was calculated for each patient who survived in hospital, and the association with long-term mortality was studied. Median follow-up time was 2.7years. The performance of the final model was determined with measurements of its discriminative power (Harrell's and Uno'sC indices and time-dependent area under the receiver operating characteristic curve [AUC]) and predictive accuracy (coefficient of determination [R2] and likelihood ratio χ2). Hazard ratios (HRs) were used to assess the relationship between the variables of the model and long-term all-cause death. All-cause death occurred in 197 patients (67%). There was apositive association between the PRECISE-DAPT score (change from 17 to38 was associated with anHR of 2.42 [95% CI: 1.59-3.68], R2 = 0.209, time-dependent AUC = 0.69) and the risk of death such that in the adjusted survival curve, the risk of mortality increased as the PRECISE-DAPT score increased. The PRECISE-DAPT score may be auseful easy-to-use tool for predicting long-term mortality in patients with ACS complicated by CS.

OUTCOMES OF WARFARIN THERAPY FOR SECONDARY PREVENTION OF ISCHEMIC STROKE: A RETROSPECTIVE, FOLLOW-UP STUDY

Aim: Anticoagulant prophylaxis is recommended because cardioembolic ischemic stroke is associated with worse functional outcomes, increased recurrence rates, and higher mortality. This study aimed to investigate the rates of recurrent ischemic attacks and bleeding complications in patients receiving warfarin following ischemic stroke. Method: In this retrospective analysis, a total of 181 individuals who were initiated on warfarin therapy following an ischemic stroke were included in the study. These patients were subsequently monitored for a duration spanning from 1 month to as long as 16 years. The acute ischemic stroke diagnosis was established using the Trial of Org 10172 in Acute Stroke Treatment classification criteria. Patient follow-up periods, international normalized ratio (INR) levels, ischemic events, and bleeding were recorded and evaluated. Results: In the patient cohort, 97 (53.6%) were women and 84 (46.4%) were men. The recurrent ischemic stroke rate was 7.2%, major bleeding rate was 3.3%, and minor bleeding rate was 12.7%. While the average INR value during recurrent ischemic stroke was 1.69±0.31, the average INR value during bleeding complications was observed to be 3.15±1.38. The rate of minor bleeding was related to duration of warfarin use and non-valvular atrial fibrillation. Conclusion: Our results show that long-term warfarin use and non-valvular atrial fibrillation are risk factors for bleeding.

The Impact of Preoperative Antithrombotic Therapy on the Risks for Thrombo-ischemic Events and Bleeding among Patients Undergoing Elective Spine Surgery.

Retrospective matched analysis. To evaluate the effect of antithrombotic drug therapy on the rates of thrombo-ischemic or bleeding events 90 days following elective spine surgery. Thrombo-ischemic and bleeding complications in patients undergoing spine surgery are major causes of morbidity. Many patients who pursue elective spine surgery are concurrently receiving antithrombotic therapy for unrelated conditions; however, at this time, the effects of preoperative antithrombotic use on postoperative bleeding and thrombosis are unclear. Using an all-payer claims database, patients who underwent elective cervical and lumbar spine interventions between January 1, 2010, and June 30, 2018, were identified. Individuals were categorized into groups taking and not taking antithrombotics. A 1:1 analysis was constructed based on comorbidities found to be independently associated with bleeding or ischemic complications using logistic regression models. The primary outcomes were the rates of thrombo-ischemic events and bleeding complications. A total of 660,866 patients were eligible for inclusion. Following the matching procedure, 56,476 patient records were analyzed, with 28,238 in each group. The antithrombotic agent group had significantly greater odds of developing any 90-day thromboischemic event after surgery: deep vein thrombosis (odds ratio [OR], 3.61; 95% confidence interval [CI], 3.06-4.25), pulmonary embolism (OR, 3.93; 95% CI, 3.34-4.62), myocardial infarction (OR, 6.20; 95% CI, 5.69-6.76), and ischemic stroke (OR, 3.76; 95% CI, 3.31-4.27). In addition, the antithrombotic agent group had an increased likelihood of experiencing hematoma (OR, 1.54; 95% CI, 1.35-1.76) and need for transfusion (OR, 2.61; 95% CI, 2.29-2.96). Patients taking antithrombotic medications before elective surgery of the cervical and lumbar spine had increased risks of both ischemic and bleeding events. Spine surgeons should carefully consider these implications when appraising patients for surgery, given the lack of guidelines on perioperative management of antithrombotic agents.

Risk analysis of gastrointestinal bleeding in patients with acute ST-segment elevation myocardial infarction undergoing primary percutaneous coronary intervention

Objective: Of all spontaneous bleeding complications in patients with acute ST-elevation myocardial infarction (STEMI), upper gastrointestinal bleeding (UGIB) is the most common and of specific interest, because it can be prevented by several prophylactic measures. The purpose of this study was to investigate the in-hospital incidence, associated outcomes, and predictors of UGIB after STEMI. Methods: In this retrospective study, we analyzed the records of 2 791 patients with acute STEMI admitted to Beijing Anzhen Hospital Affiliated to Capital Medical University between January 2018 and January 2022. The patients were divided into the UGIB group (n=61) and non-UGIB group (n=2 730) according to the presence or absence of upper gastrointestinal hemorrhage, respectively. Baseline clinical conditions, coronary lesions, in-hospital deaths, and in-hospital adverse events were compared between the two groups. Logistic regression analysis was also performed for risk factors that could lead to UGIB. Results: The in-hospital incidence of UGIB after STEMI was 2.2% (61/2 791). Hospital stay was significantly longer in the UGIB group [8(6, 12) days vs. 5 (4, 7) days, Z=3.28, P<0.001] and in-hospital mortality was significantly higher in the UGIB group than in the non-UGIB group (9.8% vs. 0.8%, χ2=0.63, P=0.001). Patients with UGIB were significantly older than those without UGIB (63±11 years vs. 58±11 years, t=-3.75, P<0.001). The serum creatinine level of UGIB patients was significantly higher than that of non-UGIB patients [(80(62, 98) mmol/L vs. 73(64, 84) mmol/L, Z=1.68, P=0.007], the red blood cell count of UGIB patients was significantly lower than that of non-UGIB patients [4.1(3.8, 4.6)×1012/L vs. 4.6(4.2, 4.9)×1012/L, Z=2.61,P<0.001], and the hemoglobin concentration of UGIB patients was significantly lower than that of non-UGIB patients [129(109, 141) g/L vs. 141(130, 152) g/L, Z=2.52,P<0.001]. Brain natriuretic peptide levels were significantly higher in UGIB patients than in non-UGIB patients [331(165, 644) ng/L vs. 181(89, 333) ng/L, Z=2.42,P<0.001]. Logistic regression analysis showed that age (OR=1.045, 95%CI 1.009-1.082, P=0.013); hemoglobin (OR=1.594, 95%CI 1.150-2.210, P=0.005); hematocrit (OR=0.181, 95%CI 0.060-0.546, P=0.002); and mean hemoglobin concentration (OR=0.845, 95%CI 0.752-0.951, P=0.005) were independent risk factors for UGIB in patients with STEMI. Logistic regression analysis of risk factors for in-hospital death revealed that concurrent UGIB was an independent risk factor for in-hospital death in patients with STEMI (OR=2.954, 95%CI 0.635-13.751, P=0.024). Conclusions: The incidence of in-hospital UGIB in STEMI patients was 2.2%, and the in-hospital mortality rate of STEMI complicated with UGIB increased to 9.8%. Concurrent UGIB was an independent risk factor for in-hospital death in patients with STEMI. The most important predictors of in-hospital UGIB in patients with STEMI were age, hemoglobin, hematocrit, and mean hemoglobin concentration.

Risk of Bleeding and Thrombosis with CAR T-Cell Therapy: A Scoping Review

Introduction: Chimeric antigen receptor (CAR) T-cell therapy is emerging as a novel and revolutionary therapy in the treatment of relapsed or refractory lymphoma and other hematological malignancies. Patients with hematological malignancies are at risk of bleeding and thrombosis due to multiple risks factors. As there is an ongoing exploration of the incidence and characteristics of bleeding and thrombosis after CAR T-cell therapy, there is no existing published data that incorporates both peer-reviewed and non-peer-reviewed literature. Aim: Assess the risk of bleeding and thrombosis in CAR T-cell recipients for hematological malignancies. Method: We conducted a systematic literature search in MEDLINE, EMBASE, and CENTRAL electronic databases from inception to October 2022 using a combination of subject headings and text words. We included studies that assessed thrombotic and bleeding complications in patients eighteen or older who underwent CAR T-cell therapy for a hematologic malignancy. Our search strategy yielded 14 studies in the form of abstracts and full-text articles. The review process consisted of two levels of screening: (1) a title and abstract review and (2) a full-text review. Result: Of 3354 records, we included 14 studies based on our inclusion criteria [figure 1]. Majorities of the studies were retrospective. Most of the patients in these studies received CAR T-cell therapy for refractory diffuse large B-cell lymphoma. Patients received at least 2 lines of therapy or more before CAR T-cell treatment. Different types of CAR T-cell therapy were used. Based on the included studies, the risk of bleeding was higher than thrombosis [figure 2]. Bleeding sites were variable, but gastrointestinal (GI) bleeding was predominant. In Ma et al, GI bleeding occurred in 11 (42.3%) patients. In Qi et al and Johnsrud et al, bleeding occurred in 44 (11%) and 12 (9.4%) patients respectively. Variable sites of thrombosis were noticed. In Hashmi et al incidence of thrombosis was 10.8%. Although there are some risk factors associated with bleeding and thrombosis in this population, the exact mechanism is still unknown. We think future studies to determine the exact mechanism of this toxicity and to assess the underlying risk factors would be crucial to decrease morbidity and mortality in this population and to develop risk assessment tools.

Management of Catheter-Related Upper Extremity Deep Vein Thrombosis in Patients with Cancer: A Systematic Review and Meta-Analysis

Background: Patients with cancer commonly require a central venous catheter (CVC) for delivery of cancer therapies and/or supportive care. The presence of a CVC is associated with an increased risk of venous thromboembolism (VTE). Despite the frequent occurrence, the optimal anticoagulation management and outcomes for patients with cancer and catheter-related upper extremity deep vein thrombosis (DVT) are unclear. Objective: We performed a systematic review and meta-analysis to evaluate the rates of recurrent VTE and bleeding complications in patients with cancer and catheter-related upper extremity DVT. Methods: We searched MEDLINE, Embase, Scopus, and CENTRAL (Cochrane) from inception to June 2, 2023. We aimed to include randomized controlled trials (RCTs) (if any), prospective and retrospective cohort studies, and case-control studies (including ≥ 10 patients) evaluating adult patients with cancer and catheter-related upper extremity DVT. The primary efficacy outcome was recurrent VTE, and the primary safety outcome was major bleeding as defined by individual studies. Secondary outcomes included clinically relevant non-major bleeding, total bleeding events, and all-cause mortality. By using R software (version 4.0.3), the incidence rates (with 95% confidence interval [CI]) of recurrent VTE and bleeding outcomes at different time points were pooled using random effects model. Results: After screening 4,264 records, we included 29 studies (N=2,848 patients) in the systematic review. There were no RCTs, 5 prospective cohort studies (including 260 patients), and 24 retrospective cohort studies. Most studies had modest sample size (N&amp;lt;100). Overall from 24 studies with reported tumor types, the most common malignancy was hematological malignancy (50.4%), followed by gastrointestinal (13.6%), breast (10.2%), and lung (5.5%) cancers. The median or mean follow-up duration varied widely from 1 to 20 months. Duration of anticoagulation also varied considerably with median or mean duration of 20 days to 6 months. The main long-term anticoagulant used was low-molecular-weight heparin (58.1%), followed by direct oral anticoagulants (24.3%). Only two studies (N=87 patients) specifically reported the management and associated outcomes after catheter removal. Thirteen studies (N=1105 patients) reported a 3-month recurrent VTE rate, with the pooled rate of 1% (95% CI 0-3%, I 2 = 0%) (Figure 1). Nine studies (N=811 patients) reported a 3-month major bleeding rate, with the pooled rate of 2% (95% CI 1-5%, I 2 = 0%) (Figure 2). We were unable to pool event rates beyond 3 months given high degree of heterogeneity in the follow-up duration, bleeding definition, and duration of anticoagulation. Conclusions: Our systematic review and meta-analysis demonstrated relatively low rates of recurrent VTE and major bleeding events within the first 3 months in patients with cancer and catheter-related upper extremity DVT. However, there was significant heterogeneity in the management and reporting after 3 months, and available data are poor to guide treatment strategies and duration of anticoagulation. The optimal management after catheter removal was also unclear. Future large prospective studies are needed.

The Additional Value of Activated Clotting Time-Guided Heparinization During Interventions for Peripheral Arterial Disease.

Unfractionated heparin is widely used to lower the risk of arterial thromboembolic complications (ATECs) during interventions for peripheral arterial disease (PAD), but it is still unknown which heparin dose is the safest in terms of preventing ATECs and bleeding complications. This study aims to evaluate the incidence of complications during interventions for PAD and the relation between this incidence and different heparinization protocols. A retrospective analysis of a prospective multicenter cohort study was performed. Between June 2015 and September 2022, 355 patients who underwent peripheral interventions for PAD were included. All patients who were included before July 2018 received 5000 international units (IU) of heparin (group 1). Starting from July 2018, all included patients received an initial dose of 100 IU/kg, with potential additional heparin doses based on activated clotting time (ACT) values (group 2). Data on ACT values and complications within 30 days post-procedurally were collected. In total, 24 ATECs and 48 bleeding complications occurred. In group 1, 8.7% (n=11) of patients suffered from ATEC, compared with 5.7% (n=13) in group 2. Thirteen percent of patients (n=17) in group 1 had a bleeding complication, compared with 14% (n=31) in group 2. Arterial thromboembolic complications were more often found in patients with peak ACT values of <200 seconds, compared with ACT values between 200 and 250 seconds, 15% (n=6) versus 5.9% (n=9), respectively, p=0.048. Patients with peak ACT values >250 seconds had a higher incidence of bleeding complications compared with an ACT between 200 and 250 seconds, 24% (n=21) versus 9.8% (n=15), respectively, p=0.003. Forty-four percent of patients (n=23) in group 1 reached a peak ACT of >200 seconds, compared with 95% (n=218) of patients in group 2 (p=0.001). ATEC was found in 6.8% (n=24) and bleeding complications in 14% (n=48) of patients who underwent a procedure for PAD. There was a significantly higher incidence of ATECs in patients with a peak ACT value <200 seconds, and a higher incidence of bleeding complications in patients with a peak ACT value >250 seconds. The findings obtained from this study may serve as a basis for conducting future research on heparinization during procedures for PAD, with a larger sample size. Heparin is administered during arterial interventions for peripheral arterial disease (PAD) to decrease the risk of arterial (thrombo)embolic complications (ATEC) during or shortly following surgery. The effect of heparin is unpredictable in the individual patient, and the optimal dosage of this anticoagulant has not yet been established. Using the activated clotting time (ACT), the anticoagulatory effect of heparin can be monitored periprocedurally. Previous research on the incidence of both ATEC and bleeding complications, or on the optimal dosage of heparin administration, is scarce. This study aims to investigate the incidence of ATEC and bleeding complications between 2 different dosage protocols of heparin-a standard bolus of 5000 IU or ACT-guided heparinization-and thereby provide clarity on the optimal dose of heparin during peripheral arterial interventions for PAD.

Construction of a risk scoring system using clinical factors and RYR2 polymorphisms for bleeding complications in patients on direct oral anticoagulants.

Introduction: Bleeding is one of the most undesirable complications of direct oral anticoagulants (DOACs). While the ryanodine receptor (RYR2) has been related to cardiac diseases, research on bleeding complications is lacking. This study aimed to elucidate the association between RYR2 and bleeding risk to develop the risk scoring system in patients treated with DOACs. Methods: This study was a retrospective analysis of prospectively collected samples. We selected ten SNPs within the RYR2 gene, and two models were constructed (Model I: demographic factors only, Model II: demographic and genetic factors) in multivariable analysis. Independent risk factors for bleeding were used to develop a risk scoring system. Results: A total of 447 patients were included, and 49 experienced either major bleeding or clinically relevant non-major bleeding. In Model I, patients using rivaroxaban and experiencing anemia exhibited an increased bleeding risk after adjusting for covariates. Upon incorporating genetic factors into Model I, a significant association with bleeding was also observed in cases of overdosing on DOACs and in patients with a creatinine clearance (CrCl) < 30mL/min, in addition to rivaroxaban and anemia (Model II). Among genetic factors, RYR2 rs12594 GG, rs17682073 AA, rs3766871 GG, and rs6678625 T alleles were associated with bleeding complications. The area under the receiver operating characteristic curve (AUROC) of Model I was 0.670, whereas that of Model II increased to 0.803, demonstrating better performance with the inclusion of genetic factors. Using the significant variables in Model II, a risk scoring system was constructed. The predicted bleeding risks for scores of 0, 1-2, 3-4, 5-6, 7-8, and 9-10 points were 0%, 1.2%, 4.6%, 15.7%, 41.7%, and 73.3%, respectively. Conclusion: This study revealed an association between RYR2 and bleeding complications among patients taking DOACs and established a risk scoring system to support individualized DOAC treatment for these patients.

Impact of bleeding events on mortality in patients with atrial fibrillation and silent left atrial thrombi: insight from the LAT trial

Abstract Background Thrombolytic therapy is important to prevent thromboembolism in patients with atrial fibrillation (AF) and left atrial (LA) thrombi. However, bleeding complications are a major concern. Purpose To investigate the incidence and prognosis of bleeding complications in patients with AF and silent LA thrombi. Methods An analysis was performed from the LAT trial, a multicenter observational study investigating outcomes of silent LA thrombi detected by trans-esophageal echocardiography (TEE) in AF patients. Of 17,436 patients who underwent TEE, 297 (median age, 70 years; 31% female, median CHA2DS2-VASc score of 4) were eligible for inclusion. Management of oral anticoagulants was at the physician’s discretion, and the follow-up period was set as 1-year. Major bleeding was defined as intracranial hemorrhage, bleeding requiring surgery or transfusion, or ≥4 g/dl decrease in hemoglobin level. Results Prescription rates of oral-anticoagulants at baseline and the final follow-up were 81.8% and 89.9%, respectively (p = 0.002). During a median follow-up of 385 (interquartile range, 365-411) days after the thrombi detection, the incidence of thromboembolism, major bleeding, and all-cause death was 5.7% (n = 17), 11.4% (n = 34) and 8.4 % (n = 25), respectively. Patients with thromboembolism were more likely experience subsequent death than those without thromboembolism (17.7% vs. 7.9%, log-rank p = 0.063). Similarly, patients with major bleeding more frequently experienced subsequent death than those without bleeding (20.6% vs. 6.8%, log-rank p = 0.002). Time-adjusted Cox regression analysis revealed a temporal association between major bleeding and subsequent death (hazard ratio, 3.72; 95% confidence interval 1.55–8.93; p = 0.003) as well as between thromboembolism and subsequent death (hazard ratio, 2.98; 95% confidence interval 0.89–9.99; p = 0.077). Conclusions In the LAT trial, about 10% of patients with AF and silent LA thrombi experienced major bleeding during 1-year follow-up. Not only thromboembolism but also major bleeding was strongly associated with subsequent death.

Post-menopause women show increased levels in risk prediction scores with age as dependent variable

Abstract Background Men and women differ in outcome after percutaneous coronary intervention (PCI). However, frequently used scores for ischemic risk prediction in patients with cardiovascular disease do not include sex related factors. In this study, we aimed to analyze sex related differences in risk score prediction in patients after PCI in dependence from age-determined menopause. Methods In this mono-center analysis, we compared frequently used risk prediction scores for post PCI patients (GRACE [Global Registry of Acute Coronary Events], PRECISE-DAPT [PREdicting bleeding Complications In patients undergoing Stent implantation and subsEquent Dual Antiplatelet Therapy], NCDR-mortality and PARIS [Patterns of Non-Adherence to Anti-Platelet Regimen in Stented Patients]-thrombotic score) in male versus female post PCI patients in dependence from menopause (age determined) and age itself. Three-year follow-up was conducted to assess the incidence of MACCE (major adverse cerebro- and cardiovascular events) including all-cause mortality, myocardial infarction and stroke. Receiver operating characteristic (ROC) analysis was conducted to analyze predictive capacity of each score. Results 1,001 patients post PCI were included (38% chronic coronary syndrome [CCS], 61% acute coronary syndrome [ACS]). Out of these, 765 were male and 306 were female. Women were slightly older (68.1±11.5 vs. 73.3±11.3 years, p&amp;lt;0.0001). Male and female patients did not differ in achieved levels of risk score below the age of 55. In contrast, in the subgroups &amp;gt;55 years, GRACE, PD-DAPT and NCDR Mortality scores were higher in woman compared to men (GRACE – 120.5±27.89 vs. 128.5±29.97, p&amp;lt;0.0001; PD-DAPT – 26.46±13.13 vs. 30.66±12.76, p&amp;lt;0.001; NCDR Mortality – 345.79±18.33 vs. 40.8±20.62, p&amp;lt;0.0001). Interestingly, PARIS thrombotic score was reduced (4.02±2.28 vs. 3.6±2.3, p=0.027). After Propensity score matching for age, GRACE, PD-DAPT and NCDR Mortality did no longer differ whereby PARIS thrombotic was reduced in female patients in this analysis as well. ROC revealed a moderate predictive capacity for MACCE for all scores in this post PCI cohort with a numerically higher predictive capacity for women (GRACEAUC – 0.625 vs. 0.662; PD-DAPTAUC 0.589 vs. 0.660, NCDR-mortalityAUC 0.625 vs. 0.667; PARIS-thromboticAUC 0.594 vs. 0.638). Conclusion In this single center analysis of post PCI patients with ACS and CCS, we could reveal that the GRACE, PD-DAPT and NCDR-mortality risk scores show higher values in post-menopause women compared to men whereby the PARIS-thrombotic score was reduced. We revealed age as major driver for this discrepancy. Moreover, women showed a numerically higher predictive accuracy for the occurrence of MACCE in line with the demonstrated worse outcome after PCI in several cohorts.