In small-intestinal angiodysplasia with recurrent bleeding, thalidomide reduced bleeding episodes at 1 y.

SOURCE CITATION: Chen H, Wu S, Tang M, et al. Thalidomide for recurrent bleeding due to small-intestinal angiodysplasia. N Engl J Med. 2023;389:1649-1659. 37913505.

Severe thrombocytopenia associated to bevacizumab in a patient with scleroderma, gastrointestinal angiodysplasias and refractory gastrointestinal bleeding.

This case report discusses the medical history of a 64-year-old woman diagnosed with scleroderma and diffuse gastrointestinal angiodysplasia. The patient received bevacizumab (BVZ) therapy to address gastrointestinal bleeding that was unresponsive to endoscopic treatment. Subsequently, she developed severe thrombocytopenia. Although there were suspicions of an immune-mediated mechanism resulting from BVZ treatment, the laboratory results did not provide conclusive evidence. The patient underwent transfusions, received gamma globulin, and was treated with Romiplostim. Over time, her platelet levels gradually improved, and the bleeding was successfully controlled. It's worth noting that BVZ-induced thrombocytopenia is a relatively rare yet severe adverse effect. Recognizing and understanding the mechanisms behind thrombocytopenia is essential for developing safer treatment approaches. Further research is required to identify potential risk factors associated with this condition.

Standard of Care Versus Octreotide in Angiodysplasia-Related Bleeding (the OCEAN Study): A Multicenter Randomized Controlled Trial.

BACKGROUND & AIMS: Gastrointestinal angiodysplasias are vascular anomalies that may result in transfusion-dependent anemia despite endoscopic therapy. An individual patient data meta-analysis of cohort studies suggests that octreotide decreases rebleeding rates, but component studies possessed a high risk of bias. We investigated the efficacy of octreotide in reducing the transfusion requirements of patients with angiodysplasia-related anemia in a clinical trial setting. METHODS: The study was designed as a multicenter, open-label, randomized controlled trial. Patients with angiodysplasia bleeding were required to have had at least 4 red blood cell (RBC) units or parental iron infusions, or both, in the year preceding randomization. Patients were allocated (1:1) to 40-mg octreotide long-acting release intramuscular every 28 days or standard of care, including endoscopic therapy. The treatment duration was 1 year. The primary outcome was the mean difference in the number of transfusion units (RBC + parental iron) between the octreotide and standard of care groups. Patients who received at least 1 octreotide injection or followed standard of care for at least 1 month were included in the intention-to-treat analyses. Analyses of covariance were used to adjust for baseline transfusion requirements and incomplete follow-up. RESULTS: We enrolled 62 patients (mean age, 72 years; 32 men) from 17 Dutch hospitals in the octreotide (n = 31) and standard of care (n = 31) groups. Patients required a mean number of 20.3 (standard deviation, 15.6) transfusion units and 2.4 (standard deviation, 2.0) endoscopic procedures in the year before enrollment. The total number of transfusions was lower with octreotide (11.0; 95% confidence interval [CI], 5.5-16.5) compared with standard of care (21.2; 95% CI, 15.7-26.7). Octreotide reduced the mean number of transfusion units by 10.2 (95% CI, 2.4-18.1; P = .012). Octreotide reduced the annual volume of endoscopic procedures by 0.9 (95% CI, 0.3-1.5). CONCLUSIONS: Octreotide effectively reduces transfusion requirements and the need for endoscopic therapy in patients with angiodysplasia-related anemia. CLINICALTRIALS: gov, NCT02384122.

Glanzmann's thrombasthenia associated with gastrointestinal angiodysplasias successfully treated with bevacizumab.

Glanzmann's Thrombasthenia (GT) is a rare hemorrhagic condition caused by a platelet surface receptor disorder of the glycoprotein (GP) IIb/IIIa. Symptoms of GT are various forms of hemorrhages, such as purpura, epistaxis and menorrhagia. Gastrointestinal bleeding (GIB) is a rare expression of the condition and may occur due to traumas in the GI tract or as a consequence of gastrointestinal angiodysplasia (GIADs). In this case report, we present a middle-aged woman with recurrent GIB consequent to GIADs with persistent melena and iron deficiency anemia. After several unsuccessful therapeutic interventions, the patient was studied by the hereditary hemorrhagic telangiectasia's (HHT - Osler-Weber-Rendu disease) unit, where she received bevacizumab, showing a complete improvement in symptoms as well as a reduction in her GIADs. This case shows that bevacizumab could be a possible line of treatment for patients with coagulation disorders with GIADs.

Thalidomide for Recurrent Bleeding Due to Small-Intestinal Angiodysplasia.

BACKGROUND: Recurrent bleeding from the small intestine accounts for 5 to 10% of cases of gastrointestinal bleeding and remains a therapeutic challenge. Thalidomide has been evaluated for the treatment of recurrent bleeding due to small-intestinal angiodysplasia (SIA), but confirmatory trials are lacking. METHODS: We conducted a multicenter, double-blind, randomized, placebo-controlled trial to investigate the efficacy and safety of thalidomide for the treatment of recurrent bleeding due to SIA. Eligible patients with recurrent bleeding (at least four episodes of bleeding during the previous year) due to SIA were randomly assigned to receive thalidomide at an oral daily dose of 100 mg or 50 mg or placebo for 4 months. Patients were followed for at least 1 year after the end of the 4-month treatment period. The primary end point was effective response, which was defined as a reduction of at least 50% in the number of bleeding episodes that occurred during the year after the end of thalidomide treatment as compared with the number that occurred during the year before treatment. Key secondary end points were cessation of bleeding without rebleeding, blood transfusion, hospitalization because of bleeding, duration of bleeding, and hemoglobin levels. RESULTS: Overall, 150 patients underwent randomization: 51 to the 100-mg thalidomide group, 49 to the 50-mg thalidomide group, and 50 to the placebo group. The percentages of patients with an effective response in the 100-mg thalidomide group, 50-mg thalidomide group, and placebo group were 68.6%, 51.0%, and 16.0%, respectively (P<0.001 for simultaneous comparison across the three groups). The results of the analyses of the secondary end points supported those of the primary end point. Adverse events were more common in the thalidomide groups than in the placebo group overall; specific events included constipation, somnolence, limb numbness, peripheral edema, dizziness, and elevated liver-enzyme levels. CONCLUSIONS: In this placebo-controlled trial, treatment with thalidomide resulted in a reduction in bleeding in patients with recurrent bleeding due to SIA. (Funded by the National Natural Science Foundation of China and the Shanghai Municipal Education Commission, Gaofeng Clinical Medicine; ClinicalTrials.gov number, NCT02707484.).

Effectiveness of aortic valve replacement in Heyde syndrome: a meta-analysis.

AIMS: Heyde syndrome is the co-occurrence of aortic stenosis, acquired von Willebrand syndrome, and gastrointestinal bleeding. Aortic valve replacement has been demonstrated to resolve all three associated disorders. A systematic review and meta-analysis were performed to obtain best estimates of the effect of aortic valve replacement on acquired von Willebrand syndrome and gastrointestinal bleeding. METHODS AND RESULTS: A literature search was performed to identify articles on Heyde syndrome and aortic valve replacement up to 25 October 2022. Primary outcomes were the proportion of patients with recovery of acquired von Willebrand syndrome within 24 h (T1), 24-72 h (T2), 3-21 days (T3), and 4 weeks to 2 years (T4) after aortic valve replacement and the proportion of patients with cessation of gastrointestinal bleeding. Pooled proportions and risk ratios were calculated using random-effects models. Thirty-three studies (32 observational studies and one randomized controlled trial) on acquired von Willebrand syndrome (n = 1054), and 11 observational studies on gastrointestinal bleeding (n = 300) were identified. One study reported on both associated disorders (n = 6). The pooled proportion of Heyde patients with acquired von Willebrand syndrome recovery was 86% (95% CI, 79%-91%) at T1, 90% (74%-96%) at T2, 92% (84%-96%) at T3, and 87% (67%-96%) at T4. The pooled proportion of Heyde patients with gastrointestinal bleeding cessation was 73% (62%-81%). Residual aortic valve disease was associated with lower recovery rates of acquired von Willebrand syndrome (RR 0.20; 0.05-0.72; P = 0.014) and gastrointestinal bleeding (RR 0.57; 0.40-0.81; P = 0.002). CONCLUSION: Aortic valve replacement is associated with rapid recovery of the bleeding diathesis in Heyde syndrome and gastrointestinal bleeding cessation. Residual valve disease compromises clinical benefits.

[A case of Heyde's syndrome in a patient hospitalized for acute myocardial infarction]. / Un caso di sindrome di Heyde in una paziente ricoverata per infarto miocardico acuto.

We here describe the case of an 84-year-old woman with a history of ischemic heart disease, paroxysmal atrial fibrillation, and severe aortic stenosis, admitted to the coronary care unit of our hospital for an ST-elevation myocardial infarction secondary to in-stent thrombosis and treated with primary percutaneous coronary intervention. On admission, the patient was on chronic therapy with apixaban for atrial fibrillation, and reported no history of bleeding. However, the day after the administration of the loading doses of aspirin and clopidogrel, the patient developed multiple episodes of rectal bleeding and melena, requiring blood transfusions. The endoscopic work-up was negative for bleeding lesions in the upper gastrointestinal tract and in the colon, but with a blood leakage from the ileocecal valve, prompting the diagnostic suspicion of an ileal bleeding secondary to angiodysplasia. Considering the well-known link between severe aortic stenosis and ileal angiodysplasia (i.e. Heyde's syndrome), the patient, already in the waiting list for elective transcatheter aortic valve implantation, underwent the procedure during the index hospitalization. The procedure was performed in the absence of complications and the patient was discharged with a personalized antithrombotic therapy. In the following weeks, no further episodes of bleeding were reported.

Did angiodysplasia associated with heyde's syndrome disappear spontaneously?: a case report.

BACKGROUND: Heyde's syndrome can be easily overlooked or misjudged in clinical practice because it shares common clinical manifestations with multiple diseases as well as limited accuracy of several corresponding examinations for diagnosing Heyde's triad. Moreover, aortic valve replacement is often delayed in these patients due to the contradiction between anticoagulation and hemostasis. Herein, we present a rare case of atypical Heyde's syndrome. The patient's severe intermittent gastrointestinal bleeding was not completely cured even through a local enterectomy. In the absence of direct evidence of acquired von Willebrand syndrome (AVWS) or angiodysplasia, her long-standing gastrointestinal bleeding was finally stopped after receiving transcatheter aortic valve implantation (TAVI). CASE PRESENTATION: A 64-year-old female suffered from refractory gastrointestinal bleeding and exertional dyspnoea. A local enterectomy was performed owing to persistent hemorrhage and repeated transfusions; subsequently, histological examination revealed angiodysplasia. Heyde's syndrome was not suspected until 3 years later, at which time the patient started bleeding again and was also found to have severe aortic valve stenosis upon echocardiography. TAVI was consequently performed when the patient was in a relatively stable condition even though the predisposition to bleed, but there was no evidence of angiodysplasia and AVWS during angiography at that time. The patient's above symptoms were significantly relieved after TAVI and followed up for 2 years without any significant ischemic or bleeding events. CONCLUSIONS: The visible characteristics of angiodysplasia or a shortage of HMWM-vWFs should not be indispensable for the clinical diagnosis of Heyde's syndrome. Enterectomy could be a bridging therapy for aortic valve replacement in patients with severe hemorrhage, and TAVI may be beneficial for moderate to high surgical-risk patients even if they have a potential risk of bleeding.

Gastrointestinal bleeding in von Willebrand patients: special diagnostic and management considerations.

INTRODUCTION: Severe and recurrent gastrointestinal (GI) bleeding caused by angiodysplasia is a significant problem in patients with von Willebrand disease (VWD) and in those with acquired von Willebrand syndrome (AVWS). At present, angiodysplasia-related GI bleeding is often refractory to standard treatment including replacement therapy with von Willebrand factor (VWF) concentrates and continues to remain a major challenge and cause of significant morbidity in patients despite advances in diagnostics and therapeutics. AREAS COVERED: This paper reviews the available literature on GI bleeding in VWD patients, examines the molecular mechanisms implicated in angiodysplasia-related GI bleeding, and summarizes existing strategies in the management of bleeding GI angiodysplasia in patients with VWF abnormalities. Suggestions are made for further research directions. EXPERT OPINION: Bleeding from angiodysplasia poses a significant challenge for individuals with abnormal VWF. Diagnosis remains a challenge and may require multiple radiologic and endoscopic investigations. Additionally, there is a need for enhanced understanding at a molecular level to identify effective therapies. Future studies of VWF replacement therapies using newer formulations as well as other adjunctive treatments to prevent and treat bleeding will hopefully improve care.

Von Willebrand disease (VWD) is the most common inherited bleeding disorder. It is caused by problems with von Willebrand factor (VWF), a protein in blood that helps stop bleeding. People with VWD either have low levels of VWF or VWF that does not work properly. The disease causes bleeding symptoms in 1 in 1000 individuals. Three main types of VWD exist. Depending on the type, people can have minimal symptoms or serious bleeding that needs hospital care.Patients with severe VWD may often experience repeated bleeding from the gastrointestinal tract. This is usually due to the formation of abnormal fragile vessels (malformations) called angiodysplasia, which have been linked to the absence or abnormal function of VWF. These fragile vessels are very difficult to find and diagnose. At present, available treatments for angiodysplasia, including long-term VWF replacement therapy, are not very effective. As a result, VWD patients with angiodysplasia have a poor quality of life.More research is needed to better evaluate current treatments and explore the contribution of abnormal VWF in the development of angiogenesis and angiodysplasia in VWD which may reveal new targets for treatment.

Real-world healthcare costs and resource utilization in patients with von Willebrand disease and angiodysplasia.

OBJECTIVE: To describe the economic burden among VWD patients with angiodysplasia compared to VWD patients without angiodysplasia and the general population. METHODS: This was a retrospective analysis using the Merative MarketScan Commercial and Medicare Databases® (January 2011-September 2020). Selected patients had ≥1 medical claim for VWD or low VWF, ≥1 medical claim for AGD, and ≥3 GI-related bleeding episodes within a year. HCRU and all-cause costs were compared with the VWD (only) and the general cohorts. RESULTS: The mean total all-cause costs were $150,101 among patients with VWD and angiodysplasia (n = 34), higher compared to $48,249 among matched VWD patients without angiodysplasia (n = 136) and $31,029 among matched individuals of the general population [n = 136; p-value < 0.0001]. The differences in costs between groups were primarily due to inpatient care. During the 12-month follow-up, VWD patients with symptomatic (n = 35), asymptomatic (n = 81), and suspected (n = 378) angiodysplasia had an average of 4.1, 0.6, and 3.8 gastrointestinal (GI) bleeds, respectively. Desmopressin, VWF concentrates, and aminocaproic acid were the most frequent treatments used. The most frequent procedures to treat GI-related bleeding and underlying lesions were blood transfusion and laser therapy. CONCLUSIONS: Despite recent therapeutic advances, there is room for considerable reduction of the disease burden in patients with VWD and angiodysplasia.