Prophylaxis Of Bleeding Research Articles

A211 INCREASED RATES OF PPI DEPRESCRIPTION OVER TIME IN PATIENTS WITH UPPER GI BLEEDS

Abstract Background Proton Pump Inhibitors (PPIs) are commonly used for various indications, including prophylaxis of upper GI bleeding. We aimed to assess if there has been more PPI deprescription in recent years in patients treated for Upper GI Bleeds (UGIB). Aims Our study aimed to assess the frequency of PPI deprescription in patients treated with endoscopic therapy for UGIBs. We hypothesized that there was a higher rate of PPI deprescription in recent years. Methods This retrospective cohort study analyzed patients who received endoscopic treatment for UGIB between the years 2015-2022. All patients who were treated with endoscopic therapy for an UGIB from two academic GI practices were included. PPI deprescription was defined as a 50% dose reduction, frequency reduction or complete medication discontinuation in the past 3 months or longer in established PPI users. To assess trends, the cohort was divided into group 1 (2015-2018) and group 2 (2019-2022). Data were analysed using SPSS and chi-squared testing was used to compare categorical variables. Results Data were collected from 301 UGIB treated endoscopically. The mean age was 66.4 ± 13.5 years with 64% males and 36% females. Patients from group 1 had a deprescription rate of 2% (2/101 cases). Patients from group 2 (2019-2022) had a deprescription rate of 16% (32/200 cases) (pampersand:003C0.001). Conclusions There was a higher rate of PPI deprescription in patients treated for UGIB in the second time period. Reasons for the increased rate of PPI deprescription require further investigation. Chi-Squared of PPI Deprescription for entire cohort Fisher Exact test: P value ampersand:003C0.001 Funding Agencies None

Continuing Medical Education Questions: February 2024.

Article Title: A Randomized Controlled Trial of Propranolol Use During Ligation Program for Secondary Prophylaxis of Esophageal Variceal Bleeding.

Management of varices but not anticoagulation is associated with improved outcome in patients with HCC and macrovascular tumour invasion

Background & aimsThe value of bleeding prophylaxis and anticoagulation in patients with hepatocellular carcinoma (HCC) and macrovascular tumour invasion (MVI) is unclear. We evaluated the impact of anticoagulation on thrombosis progression, bleeding events, and overall mortality, and assessed the efficacy of adequate management of varices as recommended for patients with cirrhosis.MethodsHCC patients with MVI who had Child-Turcotte-Pugh A-B7 were included between Q4/2002 and Q2/2022. Localization of the tumour thrombus and changes at 3–6 months were evaluated by two radiologists. Univariable and multivariable logistic/Cox regression analyses included time-dependent variables (i.e., anticoagulation, systemic therapy, non-selective beta blocker treatment).ResultsOf 124 patients included (male: n = 110, 89%), MVI involved the main portal vein in 47 patients (38%), and 49 individuals (40%) had additional non-tumorous thrombus apposition. Fifty of 80 patients (63%) with available endoscopy had varices. Twenty-four individuals (19%) received therapeutic anticoagulation and 94 patients (76%) were treated with effective systemic therapies. The use of therapeutic anticoagulation did not significantly affect the course of the malignant thrombosis at 3–6 months. Systemic therapy (aHR: 0.26 [95%CI: 0.16–0.40]) but not anticoagulation was independently associated with reduced all-cause mortality. In patients with known variceal status, adequate management of varices was independently associated with reduced risk of variceal bleeding (aHR: 0.12 [95%CI: 0.02–0.71]). In the whole cohort, non-selective beta blockers were independently associated with reduced risk of variceal bleeding or death from any cause (aHR: 0.69 [95%CI: 0.50–0.96]).ConclusionAdequate bleeding prophylaxis and systemic anti-tumour therapy but not anticoagulation were associated with improved outcomes in patients with HCC and MVI.

Real-World Efficacy and Safety of Plasma-Derived Von Willebrand Factor-Containing Factor VIII Concentrates in Patients With Von Willebrand Disease in Italy.

Plasma-derived von Willebrand factor-containing factor VIII concentrates (pd-VWF/FVIII-C) are the mainstay of treatment in von Willebrand disease (VWD). Real-world data on efficacy and safety of these pd-VWF/FVIII-C are required. To retrospectively evaluate the efficacy and safety of pd-VWF/FVIII-C (Fanhdi® and Alphanate®, Grifols) in clinical practice in Italy. A multicentric, observational, retrospective study at 10 Italian centers was conducted. Eligible patients diagnosed with inherited VWD (ISTH criteria) were treated with either Fanhdi® or Alphanate® for bleeding episodes, prevention of surgical bleeding and secondary long-term prophylaxis (SLTP) according to clinical practice with medical records collected from January 2007 to December 2019. Efficacy/safety of pd-VWF/FVIII-C was assessed according to FDA-agreed objective criteria following regulatory procedures. Fifty-seven patients (M/F: 21/36) were enrolled in the study with the following VWD types: VWD1 (n = 29, 52%), VWD2A (n = 10, 18%), VWD2B (n = 7, 12%), VWD2M (n = 2, 4%), VWD2N (n = 1, 2%), VWD2 unclassified (n = 1, 2%), and VWD3 (n = 7, 12%). These pd-VWF/FVIII-C were used to manage 58 bleeding episodes (n = 24 patients), 100 surgeries (n = 47 patients), and 7 SLTP (n = 6 patients). Global clinical efficacy with these pd-VWF/FVIII-C was reported to be excellent/good in 85% of bleeding episodes, 98% of surgeries, and 100% of SLTP. As far as safety, no adverse-drug-related episodes, immunogenic or thrombotic events were reported. This study confirmed that Fanhdi® and Alphanate® were effective and safe in the management of bleeding episodes, the prevention of bleeding during surgeries and for SLTP in Italian patients with inherited VWD.

Statins, metformin, and RAS inhibitors did not reduce variceal bleeding risk and mortality in a large, real-life cohort of patients with cirrhosis.

Previous experimental and clinical studies suggested a beneficial effect of statins, metformin, angiotensin-converting-enzyme inhibitors and angiotensin II receptor blockers (RASi) on portal hypertension. Still, their effects on hard cirrhosis-related clinical endpoints, such as variceal bleeding and bleeding-related mortality, remain to be investigated. Thus, we recorded the use of statins, metformin and RASi in a large cohort of cirrhotic patients undergoing endoscopic band ligation (EBL) for primary (PP, n = 440) and secondary bleeding prophylaxis (SP, n = 480) between 01/2000 and 05/2020. Variceal (re-) bleeding and survival rates were compared between patients with vs. without these co-medications. A total of 920 cirrhotic patients with varices were included. At first EBL, median MELD was 13 and 515 (56%) patients showed ascites. Statins, metformin and RASi were used by 49 (5.3%), 74 (8%), and 91 (9.9%) patients, respectively. MELD and platelet counts were similar in patients with and without the co-medications of interest. Rates of first variceal bleeding and variceal rebleeding at 2 years were 5.2% and 11.7%, respectively. Neither of the co-medications were associated with decreased first bleeding rates (log-rank tests in PP: statins p = 0.813, metformin p = 0.862, RASi p = 0.919) nor rebleeding rates (log-rank tests in SP: statin p = 0.113, metformin p = 0.348, RASi p = 0.273). Similar mortality rates were documented in patients with and without co-medications for PP (log-rank tests: statins p = 0.630, metformin p = 0.591, RASi p = 0.064) and for SP (statins p = 0.720, metformin p = 0.584, RASi p = 0.118). In clinical practice, variceal bleeding and mortality rates of cirrhotic patients were not reduced by co-medication with statins, metformin or RASi. Nevertheless, we recommend the use of these co-medications by indication, as they may still exert beneficial effects on non-bleeding complications in patients with liver cirrhosis.

The role of variceal bleeding primary prophylaxis in the management of extrahepatic portal vein obstruction in children

Extrahepatic portal vein obstruction is a major cause of pediatric symptomatic portal hypertension and can lead to profuse variceal hemorrhaging. Purpose - to evaluate the role of primary prophylaxis of the variceal bleeding in children with extrahepatic portal vein obstruction. Materials and methods. A one-center prospective cohort clinical study involved 120 patients with extrahepatic portal vein obstruction who underwent primary or secondary variceal bleeding prophylaxis in 2016-2021. The laboratory, ultrasound, and endoscopy data before and after treatment were collected and evaluated. Results. Variceal bleeding episodes occurred in 5.8% (n=3) of patients who underwent primary prophylaxis and rebleeding occurred in 27.9% (n=19) of those who underwent secondary prophylaxis. Bleeding episodes occurred less frequently in patients from primary prophylaxis group (p=0.013). In patients treated endoscopically (n=53, 44.17%) Variceal bleeding appeared less frequently (n=3, 5.66%) after treatment compared to patients who underwent surgery (n=67 (55.83%), 19 had rebleeding (28.35%)) (p=0.001). In 69.17% patients (n=83) esophageal varices eradication was achieved: in 53.01% (n=44) patients from the primary prophylaxis group and 46.99% (n=39) from the secondary prophylaxis group. Bleeding episodes occurred less frequently after the eradication achievement (p<0.001). The primary prophylaxis led to varices eradication more often than secondary (p=0.003). The varices recurrence episodes rates after the eradication achievement were not different between groups (p=0.51). Conclusions. Primary prophylaxis can reduce the bleeding risk in extrahepatic portal vein obstruction with high risk of variceal bleeding. The prophylaxis by endoscopic variceal banding is an important bridge in the treatment for pediatric patients with portal hypertension that along with portosystemic shunting could potentially improve prophylactic treatment results. The Committee on Clinical Investigation of Bogomolets National Medical University approved this study (Protocol No.141, 27.01.2021). All the studies were conducted according to implemented guidelines in consideration of GCP-ICH and Declaration of Helsinki. The written informed consent of all participants’ parents/guardians was achieved. No conflict of interests was declared by the authors.

Variations in Practice Among Cirrhotic Patients With Portal Vein Thrombosis and Esophageal Varices: A North American Survey Study.

There exists variation regarding the approach to anticoagulation and variceal hemorrhage (VH) prophylaxis among patients with cirrhosis and portal vein thrombosis (PVT). A survey was distributed to gastroenterology and hepatology providers to assess the approach to anticoagulation and VH prophylaxis among patients with PVT in cirrhotic patients. Providers were more likely to start anticoagulation if the patient was listed for liver transplantation, was symptomatic, or had superior mesenteric vein thrombosis. For prevention of first VH, many providers opt for combination therapy with both nonselective beta blockers and variceal ligation. Although providers agree on the clinical scenarios that merit initiation of anticoagulation, practice variation was identified in the means of preventing first VH.

B-Blockers in Liver Cirrhosis: A Wonder Drug for Every Stage of Portal Hypertension? A Narrative Review.

In cirrhotic patients, non-selective b-blockers (NSBBs) constitute the reference treatment of choice as monotherapy or combined with band ligation for the prevention of first variceal bleeding and rebleeding, respectively. Furthermore, the last Baveno VII guidelines recommended carvedilol, a b-blocker with additional anti-a1 receptor activity, in all compensated cirrhotics with clinically significant portal hypertension, to prevent liver decompensation. Interestingly enough, NSBBs have been reported to have a potentially positive impact on the short-term mortality of patients with acute-on-chronic liver failure. However, concerns remain about the use of b-blockers in the presence of severe complications, such as refractory ascites, hepatorenal syndrome, spontaneous bacterial peritonitis, or established cirrhotic cardiomyopathy. In addition, it has not been verified yet whether carvedilol supersedes all the other NSBBs in every stage of liver disease, even when severe complications have developed. Therefore, this review aims to illustrate recent data regarding the potential role of b-blockers across all stages of liver disease, beyond the primary and secondary prophylaxis of variceal bleeding, and address the authors' proposals on the use of NSBBs concerning the severity of liver disease and the patient's performance status.

Improving primary prophylaxis of variceal bleeding by adapting therapy to the clinical stage of cirrhosis. A competing-risk meta-analysis of individual participant data.

Non-selective β-blockers (NSBBs) and endoscopic variceal-ligation (EVL) have similar efficacy preventing first variceal bleeding. Compensated and decompensated cirrhosis are markedly different stages, which may impact treatment outcomes. We aimed to assess the efficacy of NSBBs vs EVL on survival in patients with high-risk varices without previous bleeding, stratifying risk according to compensated/decompensated stage of cirrhosis. By systematic review, we identified RCTs comparing NSBBs vs EVL, in monotherapy or combined, for primary bleeding prevention. We performed a competing-risk, time-to-event meta-analysis, using individual patient data (IPD) obtained from principal investigators of RCTs. Analyses were stratified according to previous decompensation of cirrhosis. Of 25 RCTs eligible, 14 failed to provide IPD and 11 were included, comprising 1400 patients (656 compensated, 744 decompensated), treated with NSBBs (N = 625), EVL (N = 546) or NSBB+EVL (N = 229). Baseline characteristics were similar between groups. Overall, mortality risk was similar with EVL vs. NSBBs (subdistribution hazard-ratio (sHR) = 1.05, 95% CI = 0.75-1.49) and with EVL + NSBBs vs either monotherapy, with low heterogeneity (I2 = 28.7%). In compensated patients, mortality risk was higher with EVL vs NSBBs (sHR = 1.76, 95% CI = 1.11-2.77) and not significantly lower with NSBBs+EVL vs NSBBs, without heterogeneity (I2 = 0%). In decompensated patients, mortality risk was similar with EVL vs. NSBBs and with NSBBs+EVL vs. either monotherapy. In patients with compensated cirrhosis and high-risk varices on primary prophylaxis, NSBBs significantly improved survival vs EVL, with no additional benefit noted adding EVL to NSBBs. In decompensated patients, survival was similar with both therapies. The study suggests that NSBBs are preferable when advising preventive therapy in compensated patients.

The role of emicizumab in acquired hemophilia A.

Acquired hemophilia is a rare bleeding disorder that predominantly affects older people with potential underlying comorbidities, including cardiovascular and thrombotic risk factors. The current standard therapies with hemostatic agents for acute bleeding and immunosuppression often require inpatient management, are not approved for routine bleeding prophylaxis, and contribute to the high mortality in this population. Emicizumab is a factor VIII (FVIII) mimetic approved for bleeding prophylaxis in congenital hemophilia A with and without FVIII inhibitors. Given subcutaneously, it may allow easier outpatient bleeding prophylaxis and reduce intensity of immunosuppression. This article summarizes the currently available data on the efficacy and safety of emicizumab in acquired hemophilia A.

Impact of the COVID-19 pandemic on the attitude of parents to the use of vitamin K in newborns for prevention of bleeding due to vitamin K deficiency

Introduction and objective: The COVID-19 pandemic has significantly impacted the global healthcare system and all aspects of medical education. In this study, the knowledge of parents about the prophylactic use of vitamin K in newborns and infants, and the method of prophylaxis of vitamin K deficiency bleeding was assessed. Materials and methods: Data for the study were collected by conducting an online survey of 232 parents. They were assigned to two groups: group 1, responding before the COVID-19 pandemic, and group 2, responding during the COVID-19 pandemic. Results: Vitamin K was administered intramuscularly in 99% of cases in group 1 and 57% in group 2 (significant relationship – p < 0.001). Half of group 2 mistakenly thought that vitamin K was given orally after childbirth. This answer was given by 20% of people from group 1 (p < 0.001). Conversely, the correct answer (intramuscular injection) was given by 52% of respondents in group 1 and 46% in group 2. More parents in the pre-pandemic group knew the symptoms of vitamin K deficiency in the body (54% vs. 25%; p = 0.006), when compared to the parents surveyed during the pandemic. Almost half of group 2 (46%) and 23% of group 1 also reported that oral vitamin K supplementation is recommended after childbirth (p = 0.001). Conclusions: Based on the study, it can be concluded that parents’ knowledge of the prevention of vitamin K deficiency is low. The COVID-19 pandemic has had an adverse effect on the public awareness and education regarding vitamin K deficiency bleeding prophylaxis commonly used in Poland. There is a link between the emergence of the COVID-19 pandemic and parents’ perspectives on the intramuscular administration of vitamin K for the purpose of preventing deficiency.

Emicizumab for the Treatment of Acquired Hemophilia A: Consensus Recommendations from the GTH-AHA Working Group.

Acquired hemophilia A (AHA) is a severe bleeding disorder caused by autoantibodies against coagulation factor VIII (FVIII). Standard treatment consists of bleeding control with bypassing agents and immunosuppressive therapy. Emicizumab is a bispecific antibody that mimics the function of activated FVIII irrespective of the presence of neutralizing antibodies. Recently, the GTH-AHA-EMI study demonstrated that emicizumab prevents bleeds and allows to postpone immunosuppression, which may influence future treatment strategies. To provide clinical practice recommendations on the use of emicizumab in AHA. A Delphi procedure was conducted among 33 experts from 16 German and Austrian hemophilia care centers. Statements were scored on a scale of 1 to 9, and agreement was defined as a score of ≥7. Consensus was defined as ≥75% agreement among participants, and strong consensus as ≥95% agreement. Strong consensus was reached that emicizumab is effective for bleed prophylaxis and should be considered from the time of diagnosis (100% consensus). A fast-loading regimen of 6 mg/kg on day 1 and 3 mg/kg on day 2 should be used if rapid bleeding prophylaxis is required (94%). Maintenance doses of 1.5 mg/kg once weekly should be given (91%). Immunosuppression should be offered to patients on emicizumab if they are eligible based on physical status (97%). Emicizumab should be discontinued when remission of AHA is achieved (97%). These GTH consensus recommendations provide guidance to physicians on the use of emicizumab in AHA and follow the results of clinical trials that have shown emicizumab is effective in preventing bleeding in AHA.

Real-world data on the use of emicizumab in patients with haemophilia A with and without inhibitors in Singapore.

Emicizumab is a bispecific monoclonal antibody that mimics the function of factor VIII by binding to factor IXa and factor X to achieve haemostasis in haemophilia A. The long half-life and subcutaneous mode of administration makes emicizumab a compelling treatment option for bleeding prophylaxis. There is still limited real-world data on its use and management considerations, especially during surgical procedures. The objective of the study is to describe the real-world experience of emicizumab in a cohort of adult and paediatric haemophilia A patients in Singapore, including its use in the periprocedural setting. This was an observational study conducted at the 2 main haemophilia treatment centres in Singapore. All haemophilia A patients who commenced treatment with emicizumab before 1 July 2022 were recruited. A total of 18 patients with haemophilia A were included in this study. Ten (55.6%) patients had active inhibitors. The median annual bleeding rate for all patients before emicizumab use was 4.5 events (interquartile range [IQR] 2.8-8.3) compared with 0 events (IQR 0-0) after emicizumab was commenced (P=0). There were no adverse events of venous or arterial thrombosis, thrombotic microangiopathy, or death. A total of 6 procedures in 5 patients were performed during the study period with no major bleeding complications. Emicizumab effectively protects against bleeding in haemophilia A patients with and without inhibitors, including in children less than 12 years old. More studies are required to address clinical nuances, such as periprocedural management and the role of immune tolerance in patients with inhibitors on emicizumab.

Unlocking Insights: A Single Centre Patient-Reported Outcome Experience in Patients with Severe Hemophilia a without Inhibitors on Emicizumab

Introduction: Emicizumab (Hemlibra®) prophylaxis has been demonstrated to be more effective at decreasing bleeding episodes than the factor VIII infusions that had previously been used as bleeding prophylaxis. Emicizumab has been available in Canada for persons with hemophilia A with baseline FVIII <1% without inhibitors as a form of prophylaxis since October 2021. Previous work by our team used the Patient-Reported Outcomes, Burdens and Experiences (PROBE) survey to assess outcomes following the initiation of Emicizumab in our local population, which demonstrated a positive overall trend in composite scores generated by the survey following treatment initiation. The PROBE instrument includes the EQ5D5L instrument as a generic quality of life assessment, which consists of 5 dimensions. Aims: The explicit aim of this study was to assess changes in EuroQuol-5D-5L (EQ5D5L) index utility scores and dimensions as well as Visual Analog Scores (VAS) scores at 3 and 6 months following Emicizumab introduction to gain insight into the clinical impact beyond bleeding rates. Methods: In partnership with the PROBE Investigators, individualized non-identifying survey links were generated by the clinic and provided to all transitioning patients who then consented within the PROBE link to complete the survey. Responses were shared with the clinic and decoded to allow identification. Previously, composite scores for the relevant patients were identified at 0, 3 and 6 months to assess the patient-reported clinical trajectory following Emicizumab introduction. Here, the EQ5D5L scores were analyzed using descriptive statistics and the minimal clinically important difference (MCID) was calculated for each EQ5D5L dimensions (MCID is a change between 2-4) and the VAS (MCID is a change of 10). Results: 65/85 (76%) of eligible patients ≥ 18 years of age in British Columbia transitioned as of June 1, 2023. 54 patients (mean age 39.3, median 36 with a total age range of 19-59) completed a baseline PROBE survey as part of usual clinical care prior to the Emicizumab transition. 26 patients completed PROBE surveys at 0 and 3 months and 11 patients completed PROBE surveys at 0-, 3- and 6-month intervals. Mean baseline PROBE (/1), EQ5D5L (/1) and VAS (/100) scores were 0.779 (SD 0.15), 0.789 (SD 0.15) and 72.01 (SD 18.65), respectively. EQ5D5L domains are each scored /5 where higher numbers corresponded to worse outcomes; the 5 domains include mobility, self-care, usual activities, pain/discomfort, and anxiety/depression. At 3 months, the MCID for EQ5D5L domains was met by 1 person in both usual activities and anxiety/depression. At 6 months, the MCID was met by 1 person in each of the subsections of the EQ5D5L and by 2 individuals in the usual activities dimension. Higher VAS scores correspond to better health. At 3 months, the MCID for VAS was met by 42% (11/26) with the majority (7/11) observed to have a higher VAS score than at baseline. At 6 months, the MCID was met by 45% (5/11) with the majority (4/5) having a higher VAS score than at baseline. Conclusion: Within our small cohort, EQ5D5L index utility scores consistently improved at 3 and 6 months from the time of Emicizumab initiation. Of the EQ5D5L domains, the MCID was met at 3 months in both usual activities and anxiety/depression by 1 person and in all parameters at 6 months by at least 1 person. Analysis of the VAS scores indicated a consistent perceived improvement by 42% at 3 months and in the majority participants at 6 months. Using the EQ5D5L was feasible to better understand the patient experience for those with Hemophilia A without inhibitors following Emicizumab introduction and provides insight into the specific patient-reported outcomes that are impacted by this treatment transition.

Bleeding Risk from Anticoagulant Thromboprophylaxis in Patients with Multiple Myeloma

Introduction: Patients with multiple myeloma (MM) have a high risk of venous thromboembolism (VTE) due to unique disease-related (i.e., vascular inflammation, hyperviscosity) and treatment-related factors (i.e., immunomodulatory drugs [IMiDs], high-dose dexamethasone). Thromboprophylaxis is recommended for most patients starting MM therapy. Anticoagulants are preferred over aspirin except in patients at low risk for VTE. However, compliance with prophylaxis guidelines is low. The risk of bleeding from thromboprophylaxis is not well described in these patients so an excessive perceived risk may influence clinicians' practice. We conducted a real-world analysis of bleeding complications from VTE prophylaxis in MM. Methods: The IBM MarketScan Commercial Claims Database was used to identify MM cases between 2013 and 2021. Cases required MM diagnosis from 1 inpatient or 2 outpatient claims, based on ICD-9 or ICD-10 codes, and MM-specific therapy started between 7 days before and 90 days after index diagnosis code, based on HCPCS codes and prescription records. Those with preexisting VTE, atrial fibrillation or stroke were excluded. Thromboprophylaxis was defined as at least 1 prescription for warfarin, low-molecular weight heparin (LMWH) or direct oral anticoagulants (DOAC) within 30 days of diagnosis. Major bleeding was defined as bleeding requiring hospitalization using inpatient ICD codes previously validated (Cunningham algorithm). Patients were followed from end of prophylaxis exposure window (index MM + 30 days) to first major bleeding event, disenrollment (due to death or other reasons) or December 31, 2021. Descriptive statistics were used to calculate rates of bleeding. Cox regression was used to assess the risk of bleeding from thromboprophylaxis and define risk factors associated with major bleeding. Results: We included 6,656 patients diagnosed and treated for MM, with mean age 62.7 years and 55.3% males. Although over 50% of the population would have had a high thrombotic risk based on consensus guidelines, concurrent anticoagulant prophylaxis was prescribed in only 6.6% (436). Prophylaxis agent of choice was warfarin in 23% (102), LMWH in 39% (169), and DOAC in 38% (165), respectively. There was a trend over time favoring DOAC over other agents (25% increase in DOAC use vs. other agents per year on average, p<0.01). Patients on prophylaxis had a higher rate of IMiD-based therapy (63.8% vs. 46.7%, p<0.01) and lower concomitant anti-platelet use (2.1% vs. 4.7%, p=0.01) than those not receiving prophylaxis. There were no differences in age/sex distribution, Charlson comorbidity index (CCI) or history of bleeding between groups. With a median 1.3 years follow-up, the incidence of major bleeding among MM patients receiving VTE prophylaxis was 1.4% or 7.8 bleeding events per 1,000 person-years. This was numerically but not statistically lower than the incident bleeding rate in patients not receiving prophylaxis: 1.8% or 10.1 events per 1,000 person-years. Table 1 shows risk factors for bleeding in this MM population, adjusting for age and sex, including higher age (per 10-year increase, HR 1.38), higher CCI (per SD increment, HR 1.18), history of bleeding (HR 1.54), hypertension (HR 1.87), and renal disease (HR 1.56). IMiD-based MM therapy was associated with decreased risk of bleeding (HR 0.69). Table 2 shows the estimated bleeding risk associated with prophylaxis across several models. No statistically significant association was identified between major bleeding and anticoagulant prophylaxis. Discussion: In a real-world analysis of commercial claims data, the risk of major bleeding associated with VTE prophylaxis in patients with MM undergoing cancer therapy is low and no significant increase in bleeding risk was identified for concurrent anticoagulant use. The rate of major bleeding events appears to be comparable between patients who receive VTE prophylaxis and those who do not. Nevertheless, underutilization of VTE prophylaxis is frequent. Higher CCI, bleeding history, hypertension, and renal disease were clinical factors associated bleeding risk, which may be included in models to help clinicians assess individual patient's risk and guide clinical decisions.

Athn Transcends Natural History Cohort Study of Bleeding Symptoms and Treatment Outcomes in Patients with Glanzmann Thrombasthenia

Background Glanzmann thrombasthenia (GT) is a rare, inherited, qualitative platelet disorder caused by a deficiency of one or both platelet surface proteins alpha IIb beta 3. This protein on the platelet functions as the fibrinogen receptor and is essential for hemostasis. Individuals with GT have lifelong bleeding episodes that can be frequent and severe often involving the muco-cutaneous membranes. GT is an autosomal recessive disorder with variations of the ITGA2B or ITGB3 genes. The prevalence of GT is estimated to be 1:1,000,000 in the general population. In populations with high consanguinity, the prevalence is higher. Reports of the impact of living with GT are lacking. Platelets have previously been the mainstay of treatment for severe bleeding and to manage surgical bleeding in people with GT. However, platelet transfusions carry a number of risks including allergic reactions (anaphylaxis, acute lung injury), pathogen transmission, and the formation of allo-antibodies. Primary bleeding prophylaxis is currently not available and all treatment for bleeding is reactive and on-demand. As potential new therapies emerge, clinicians require unbiased, long-term data on the safety and effectiveness of both current and new therapies. Therefore, we designed a registry of people with GT with the aims of assessing the bleeding rate and phenotype for people with this condition, as well as describing their lived experience. Rationale Due to the rare nature of GT, data within individual center registries are naturally limited. There is variation in the data held and method of collection. The aim of the study is to collect biospecimens, phenotypic characteristics, bleeding patterns, and treatment utilization, from people who have been diagnosed with GT. To achieve this, a comprehensive, multi-institutional, observational cohort study will be conducted to: Allow collection of longitudinal safety and clinical practice data for treatments in patients with GT, allowing monitoring of recently approved and well-established therapies; Aid new discovery, through the collection of biospecimens and phenotype data; Provide sufficient, unified data capture in participants with this rare disorder across the United States. Objectives To describe the bleeding phenotype in GT, including the frequency of bleeds, the Site of bleeds, and to describe real-world effectiveness of therapies used in GT, by evaluating; the frequency of bleeds, Patient reported outcomes, Healthcare and treatment utilization, To create a database for future research. Methods ATHN Transcends (NCT04398628) assesses the safety and effectiveness of contemporary therapies for people with inherited bleeding and clotting disorders. The primary aim of ATHN Transcends is to collect specific adverse events harmonized with the European Haemophilia Safety Surveillance (EUHASS). The study is constructed to allow the addition of specific modules. We have designed the GT module in ATHN Transcends to assess the safety and effectiveness of current therapy for GT. In addition, we will be collecting data around the actual bleeding rate in those who live with GT as well as more fully describing the lived experience of being impacted by GT. The study will be conducted through ATHN-affiliated centers who care for those impacted by GT. Study Design This study is a longitudinal, natural history, observational cohort study of approximately 50 participants with GT at 16 ATHN-affiliated treatment centers across the United States and a sub-cohort from one international ATHN Affiliate. The minimum planned duration of study participation for participants is approximately 18 months. Up to 10 pediatric subjects aged 2 years to <10 years, up to 10 aged 10 to <18 years, and a minimum of 30 adults >18 years with GT are expected to be enrolled. Each subject will complete a daily record for three months of bleeding event details, and any treatments. Summary ATHN Transcends has received central IRB approval and is currently being rolled out across participating American Thrombosis and Hemostasis Network (ATHN) Affiliates in the United States. Enrollment in the GT Module can begin as soon as a site opens ATHN Transcends to enrollment. Conclusion ATHN Transcends provides a real-world mechanism in which to collect safety and effectiveness data of contemporary therapies for people with GT. The GT Module of ATHN Transcends will allow collection of Good Clinical Practice-grade data.

Non-Cirrhotic Portal Hypertension: An Update of Diagnosis and Management

Portal hypertension is not the only caused by liver cirrhosis. Non-cirrhotic portal hypertension (NCPH) is characterized by elevated portal pressure in the absence of cirrhosis and is often underdiagnosed in daily clinical practice. The clinical manifestations of NCPH are similar to liver cirrhosis. The diagnosis of NCPH is still challenging due to the various underlying etiologies and often require either non-invasive or invasive examination. Laboratory examination, abdominal ultrasound, endoscopic procedure, hepatic venous gradient measurement, and liver biopsy have role in diagnosis of NCPH. The principle management of NCPH is to treat portal hypertension and its complications, such as prophylaxis and acute management of variceal bleeding, anticoagulants, surgery, splenectomy, and liver transplantation.

Optimal resting heart rate and ascites-related death in patients with cirrhosis and ascites using nonselective beta-blockers (ORCA).

Nonselective beta-blockers (NSBBs) may exacerbate ascites by impairing cardiac function. This study evaluated the impact of achieving a heart rate target of 55-60 beats per minute (bpm) on ascites-related death and complications from worsening ascites in patients with cirrhosis and diuretic-responsive ascites using NSBBs. A retrospective study was conducted at the Faculty of Medicine Ramathibodi Hospital, Mahidol University (2012-2022) and analyzed patients with cirrhosis and diuretic-responsive ascites using NSBBs (propranolol/carvedilol) for variceal bleeding prophylaxis. The outcomes were incidence of ascites-related death and complications from worsening ascites, comparing the achievable target group (heart rate 55-60 bpm) and the unachievable target group (heart rate >60 bpm). A total of 206 patients were included in the study, with a median follow-up time of 20 months. The patients were divided into an achievable target group (n = 75, median heart rate = 58.0 bpm) and an unachievable target group (n = 131, median heart rate = 73.6 bpm). Propranolol was the most used NSBB (95.1%). The adjusted hazard ratio (HR) for ascites-related death from spontaneous bacterial peritonitis (SBP) or refractory ascites (RA) or hepatorenal syndrome (HRS) or hepatic encephalopathy (HE) showed no difference between the groups (adjusted HR 0.59 [0.23-1.54]; p = 0.28). Additionally, no significant difference was found in the incidence of complications between groups, including SBP, RA, HRS, and HE. Achieving a heart rate target of 55-60 bpm with NSBBs for variceal bleeding prophylaxis is safe in patients with diuretic-responsive ascites and cirrhosis.

Comparison of endoscopic ultrasound-guided primary and secondary prophylaxis for gastric variceal bleeding.

Endoscopic ultrasound (EUS)-guided injection of cyanoacrylate (CYA) for primary prophylaxis (PP) of gastric varices (GV) is controversial. This study evaluates the safety and efficacy of this intervention. Patients treated for PP of GV bleeding by EUS injection of CYA with or without coils were identified. Endoscopic techniques, outcomes, and adverse events (AEs) were reviewed and compared with a group treated for secondary prophylaxis (SP). Patients were followed until: (i) loss to follow-up; (ii) GV bleeding; (iii) interventional radiology or surgery decompression; (iv) liver transplant; or (v) death or comfort care. One hundred and nineteen patients (61 men; mean 59 ± 12 years) underwent EUS for PP (n = 24) or SP (n = 95). The PP group was treated with CYA alone (n = 18) or with coils (n = 4). Eight (33%) mild (n = 6) or moderate (n = 2) AEs and noindex GV bleeding occurred during a mean of 6.1 ± 5.9 months follow-up. Repeat EUS in 22 (92%) PP patients showed 7 (32%) residual GVs, which were retreated with CYA alone (n = 6) or with coils (n = 1). Two (29%) mild (n = 1) or moderate (n = 1) AEs occurred after repeat EUS and 1/22 (5%) index GV bleed occurred during a mean 23 ± 25 months follow-up. Compared to the SP group, the PP group had lower Model for End-stage Liver Disease (MELD) score(P = 0.03), fewer GV stigmata (P < 0.001), required less CYA (P = 0.019) during index EUS, and had a longer time between index and surveillance EUS (P = 0.014). The incidence of AEs and GV bleeding between the two groups were similar. Posttreatment GV bleeding and AEs are similar following EUS-guided primary and secondary GV prophylaxis.

Evaluating physicians' awareness and prescribing trends regarding proton pump inhibitors: a cross-sectional study.

Introduction: Proton pump inhibitors (PPIs) are commonly used to treat acid-related disorders. Their appropriate use depends on the correct indications from the clinician. Owing to the high incidence of use and misuse, PPIs have been identified as an essential pharmacological class for developing deprescribing recommendations. Therefore, assessing physicians' knowledge and practice regarding PPI usage is critical for paving the way toward targeted recommendations and efforts. Objective: This study aimed to assess Syrian physicians' perceptions of proton pump inhibitors adverse effects, their benefit in upper gastrointestinal bleeding (UGIB) prophylaxis, and how these perceptions are related to PPI prescription practice. Methods: A cross-sectional study was performed using a web-based questionnaire distributed among Syrian physicians in internal medicine between 28 November and 23 December 2022. The questionnaire assessed perceptions and experiences of PPIs, concerns about specific adverse effects, and their effectiveness for UGIB prophylaxis, in addition to the different scenarios used to determine the best practice for appropriate treatment to manage minimal, mild, moderate, and high-risk UGIB patients. Results: A total of 473 participants completed the questionnaire, with median age ±SD was (28.46 ± 4.58), and most participants (83.3%) were residents. Approximately half of the participants (45.5%) agreed that discussion assistance was provided to continue or terminate PPIs properly. Only 8.9% were very familiar with published evidence of PPI adverse effects. Bone weakening and vitamin B12 deficiency were the most frequently reported side effects (81.8% and 79.7%, respectively). However, dementia (0.4%) and mortality (1.9%) were the least reported adverse effects. More than half of the participants (64%) perceived using PPIs to prevent upper GI bleeding. Non-trainee physicians were less knowledgeable about appropriate GERD management than resident physicians (p < 0.001). Conclusion: The study showed a gap between Syrian physicians' perceptions and practices regarding PPI use, which necessitates spreading awareness of updated guidelines for PPI usage and their side effects.