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.

Improvement in gastrointestinal bleeding after septal myectomy for hypertrophic cardiomyopathy.

OBJECTIVE: Patients with obstructive hypertrophic cardiomyopathy may have occult gastrointestinal bleeding. In this study, we analyzed outcomes of septal myectomy in patients who had a history of gastrointestinal bleeding preoperatively to understand patient characteristics and impact of septal reduction on recurrent gastrointestinal bleeding. METHODS: We analyzed 73 adult patients who had a history of gastrointestinal bleeding before transaortic septal myectomy for obstructive hypertrophic cardiomyopathy and compared outcomes to 219 patients without gastrointestinal bleeding preoperatively. RESULTS: Patients with preoperative history of gastrointestinal bleeding were older (median (IQR) age, 65 (59-69) years, P < .001) and were more likely to have systemic hypertension (70% vs 53%, P = .020) and coronary artery disease (25% vs 13%, P = .026). Preoperatively, patients with gastrointestinal bleeding had a larger left atrial volume index (median, 53 mL/m2; interquartile range, 42-67; P = .006) and greater right ventricular systolic pressure (median, 36 mm Hg; interquartile range, 32-49; mm Hg, P = .005) but no significant difference in severity of outflow tract obstruction (P = .368). There were no perioperative deaths. The estimated 5- and 10-year survivals were 96.6% and 81.8%, respectively. At a median of 3.4 (interquartile range, 1.9-9.1) years after septal myectomy, 11 patients (15%) had recurrence of gastrointestinal bleeding, which was attributed to angiodysplasia or unknown causes in 6 patients (8%). CONCLUSIONS: Patients with a preoperative history of gastrointestinal bleeding have favorable short- and long-term outcomes after septal myectomy for obstructive hypertrophic cardiomyopathy. Remission of gastrointestinal bleeding was observed in 85% of patients postprocedure, and only 8% of the patients had recurrent gastrointestinal bleeding due to angiodysplasia or unknown causes.

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.

Angiodysplasia of the appendix: a diagnostic challenge and the importance of colonoscopy.

The case report discusses the challenges in diagnosing gastrointestinal bleeding of unknown origin, with angiodysplasia (AD) of the appendix being a rare cause. The report presents a case of a man in his late 60s who presented with vomiting, diarrhoea and rectal bleeding. As a result of the bleeding, the patient developed a type II myocardial infarction (MI), which had to be simultaneously managed further complicating the diagnostic process. Despite a normal CT angiogram, ongoing bleeding led to suspicion of AD, which was diagnosed using colonoscopy with limited bowel preparation. The patient underwent an open appendicectomy and was found to have AD of the tip of the appendix as the cause of the bleeding. The case highlights the limitations of CT angiography in haemodynamically unstable patients and subsequent importance of colonoscopy with bowel preparation in diagnosing rare causes of bleeding, even with limited bowel preparation, and the potential life-threatening consequences of untreated AD.

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.).

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.

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.

Gastrointestinal Angiodysplasia in Patients with Severe Aortic Stenosis: The Endoscopic Features of Heyde's Syndrome.

INTRODUCTION: Aortic stenosis (AS) is sometimes associated with gastrointestinal bleeding, and this phenomenon is known as Heyde's syndrome. Such bleeding is most often considered to originate from gastrointestinal angiodysplasias, but the frequency and endoscopic features of such bleeding remain unclear. This study aimed to determine the frequency and endoscopic features of gastrointestinal angiodysplasia in patients with severe AS. PATIENTS AND METHODS: In this multicenter, retrospective study, we evaluated consecutive patients who underwent transcatheter aortic valve implantation (TAVI) with severe AS from May 2016 to December 2019. We extracted the data on the clinicopathological features according to the status of anemia, the proportion of patients who underwent gastrointestinal endoscopic examinations and demonstrated gastrointestinal angiodysplasia, and identified the endoscopic features associated with such patients. RESULTS: In 325 patients, the rates of moderate/severe anemia (hemoglobin < 11 g/dL) were 52%. Regarding medicine, there were no significant differences between the patients with and without moderate/severe anemia. Patients were examined by esophagogastroduodenoscopy (21%), colonoscopy (12%), and balloon-assisted enteroscopy or small bowel capsule endoscopy (1.5%). Patients with moderate/severe anemia had significantly more angiodysplasia (38.3% vs. 7.7%; p < 0.0001) and active bleeding (23.4% vs. 0%; p < 0.01). Angiodysplasia was detected in 21 patients (stomach, n = 9; small intestine, n = 5, and colon, n = 10). CONCLUSIONS: The results suggest, for the first time, that patients with severe AS who underwent TAVI and moderate/severe anemia frequently had gastrointestinal angiodysplasia and active bleeding throughout the entire gastrointestinal tract.

Diagnostic accuracy of artificial intelligence-aided capsule endoscopy (TOP100) in overt small bowel bleeding.

BACKGROUND: Capsule endoscopy (CE) is the first-choice exploration in case of overt small bowel bleeding (SBB). An early CE is known to increase diagnostic yield, but long reading times may delay therapeutics. The study evaluates the diagnostic performance of the artificial intelligence tool TOP100 in patients with overt SBB undergoing early CE with Pillcam SB3. METHODS: Patients who underwent early CE (up to 14 days from the bleeding episode) for suspected overt SBB were included. One experienced endoscopist prospectively performed standard reading (SR) and a second blind experienced endoscopist performed a TOP100-based reading (TR). The primary endpoint was TR diagnostic accuracy for lesions with high bleeding potential (P2). RESULTS: A total of 111 patients were analyzed. The most common clinical presentation was melena (64%). CE showed angiodysplasias in 40.5% of patients (45/111). In per-patient analysis, TR showed a sensitivity of 90.48% (95% CI 82.09-95.80), specificity of 100% (95% CI 87.23-100) with a PPV of 100% (95% CI 94.01-100), NPV of 77.14% (95% CI 63.58-86.71) and diagnostic accuracy of 92.79 (86.29-96.84). At multivariate analysis, adequate intestinal cleansing was the only independent predictor of concordance between TR and SR (OR 2.909, p = 0.019). The median reading time for SR and TR was 23 min (18.0-26.8) and 1.9 min (range 1.7-2.1), respectively (p < 0.001). CONCLUSIONS: TOP100 provides a fast-reading mode for early CE in case of overt small bowel bleeding. It identifies most patients with active bleeding and angiodysplasias, aiding in the prioritization of therapeutic procedures. However, its accuracy in detecting ulcers, varices and P1 lesions seems insufficient.

[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.