thromboxane-b2 and Gastrointestinal-Hemorrhage

Uncertainty remains regarding the impact of enteric-coated (EC) aspirin as it relates to the reduction of cardiovascular risk. We hypothesize that EC formulation based on a previous report may blunt aspirin response as evidenced by reduced Thromboxane A2 (TXA 2) levels in diabetic patients. Thus, it was imperative to ascertain and validate the effect of the EC formulation of Aspirin on the Thromboxane B2 (TXB2) level.. An open-label consecutive randomized interventional controlled trial. Patients with newly diagnosed ischemic stroke who are just about to start Aspirin were assessed for eligibility and inclusion in our trial. Consecutive patients (admitted to the stroke unit of Hamad General Hospital, Hamad Medical Corporation, Doha, Qatar) will be randomized to receive either EC aspirin or plain Aspirin. They will be required to continue taking them throughout the study (3 days). Demographics and laboratory records of the study participants will be abstracted from online records. Further study variables will be obtained manually in designated case record forms (CRF). The primary outcomes are the incidence of aspirin non-responders (level of residual serum TXB2 associated with elevated thrombotic risk (<99.0% inhibition or TXB2 >3.1 ng/mL) within 72 h after three daily aspirin doses). Whereas secondary outcomes are the incidence of GIT bleeding of various preparations of Aspirin. The study was approved by MRC and IRB of Hamad Medical Corporation (MRC number: 01-18-156).. This trial will determine potential differences in the efficacy of EC Aspirin and plain Aspirin on the Thromboxane B2 level. Additionally, it will ascertain the tolerability and safety of both formulations of Aspirin in patients with newly diagnosed ischemic stroke. These results will either support the current notion of no difference between the two formulations. However, if a difference is found, this will invite for future trials exploring clinical outcomes occurrence between various formulations.. Clinicaltrials.gov NCT04330872 registered on April 2, 2020.

Topics: Adolescent; Adult; Aged; Aspirin; Blood Platelets; Brain Ischemia; Female; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Platelet Aggregation Inhibitors; Single-Blind Method; Socioeconomic Factors; Stroke; Tablets, Enteric-Coated; Thromboxane B2; Young Adult

Topics: Administration, Sublingual; Animals; Aspirin; Biomarkers; Collagen; Double-Blind Method; Drug Compounding; Fibrinolytic Agents; Gastric Mucosa; Gastrointestinal Hemorrhage; Humans; Platelet Aggregation Inhibitors; Rats; Thromboxane B2

1. Gastric damage induced by low-dose aspirin and the protective effect of enteric-coating was assessed in healthy volunteers in a double-blind placebo-controlled cross-over trial using Latin square design. Each was administered placebo, plain aspirin 300 mg daily, plain aspirin 600 mg four times daily, enteric-coated aspirin 300 mg daily, or enteric-coated aspirin 600 mg four times daily for 5 days. Gastric damage was assessed endoscopically, and gastric mucosal bleeding measured. 2. Aspirin 300 mg daily and 600 mg four times daily caused significant increases in gastric injury compared with placebo. Gastric mucosal bleeding was significantly more with the high dose, with a trend towards increased gastric erosions, compared with the low dose. 3. Enteric-coating of aspirin eliminated the injury caused by low dose aspirin and substantially reduced that caused by the higher dose. 4. All dosages and formulations caused similar inhibition of gastric mucosal prostaglandin E2 synthesis. 5. Serum thromboxane levels were suppressed equally with plain and enteric-coated aspirin. 6. In this short-term study in healthy volunteers, gastric toxicity from aspirin was largely topical, independent of inhibition of prostaglandin synthesis, and could be virtually eliminated by the use of an enteric-coated preparation.

Topics: Adult; Aspirin; Dinoprostone; Dose-Response Relationship, Drug; Double-Blind Method; Female; Gastric Mucosa; Gastrointestinal Hemorrhage; Humans; Male; Salicylates; Stomach Diseases; Tablets, Enteric-Coated; Thromboxane B2

We carried out a pilot study in 15 hemodialysis patients with recurrent vascular access thrombosis to examine whether the combination of low dose aspirin (85 mg once daily) and sulfinpyrazone (200 mg three times daily) is safe and effective in the prevention of vascular access thrombosis. Hemostatic measurements were performed prior to and after four weeks of starting the drug combination. Baseline values for fibrinopeptide A were elevated in all patients while those for platelet factor 4, fibrinogen, antithrombin III and protein C were generally within normal limits. A major reduction in the frequency of vascular access thrombosis from 0.114 per month to 0.04 per month was noted during combined drug treatment (p less than 0.001). Although in vitro platelet aggregation to various stimuli was markedly suppressed and platelet thromboxane B2 formation was almost completely inhibited in patients on aspirin/sulfinpyrazone, this was not associated with a significant further prolongation of the bleeding time. A relatively high rate of complications, particularly mild gastrointestinal bleeding, was noted in patients on aspirin/sulfinpyrazone that could not be predicted on the basis of pre-treatment hemostatic test results.

Topics: Aspirin; Blood Coagulation Tests; Blood Platelets; Catheters, Indwelling; Drug Evaluation; Drug Therapy, Combination; Gastrointestinal Hemorrhage; Humans; Pilot Projects; Platelet Aggregation; Platelet Aggregation Inhibitors; Recurrence; Renal Dialysis; Sulfinpyrazone; Thrombosis; Thromboxane B2

Sucralfate has been shown to prevent the formation of acute gastric lesions induced by nonsteroidal antiinflammatory drugs such as aspirin (ASA) in animals, but little is known about the prevention by this agent of ASA-induced gastric damage in humans. This report describes the effects of sucralfate on mucosal formation of prostaglandins (PG), gastric microbleeding and DNA loss in intact and ASA-challenged stomach. Two groups of 12 healthy volunteers were used in a double-blind, placebo controlled trial to assess the effects of sucralfate 1.0g qid on the stomach in subjects without (group A) and with administration of 2.5g ASA during 2 days (group B). Sucralfate treatment during 4 days significantly reduced spontaneous gastric bleeding and DNA loss in group A and prevented blood loss caused by ASA in group B. The protective effects of sucralfate on spontaneous gastric blood loss were accompanied by increased mucosal biosynthesis and luminal release of PGE2 and 6-keto-PGF1 alpha with decreased release of TXB2. In ASA-treated subjects mucosal generation and luminal release of PG and TXB2 were greatly suppressed and sucralfate treatment did not influence these PGs in spite of the decreased mucosal damage. It is concluded that sucralfate has a potent protective action on spontaneous and ASA-treated gastric bleeding in man and that this protection may be partly due to the increased mucosal biosynthesis of prostaglandins.

Topics: 6-Ketoprostaglandin F1 alpha; Adult; Aspirin; Clinical Trials as Topic; Dinoprostone; DNA; Double-Blind Method; Gastric Mucosa; Gastrointestinal Hemorrhage; Humans; Male; Prostaglandins; Prostaglandins E; Sucralfate; Thromboxane B2

Two groups A and B each comprising 12 healthy young male subjects were used in a double blind, placebo controlled trial to assess the effects of 1.0 g sucralfate qid on prostaglandin (PG) generation and mucosal integrity in the intact and aspirin-treated stomach. Mucosal formation and luminal release of PGE2, 6-keto-PGE1 alpha and thromboxane B2, gastric microbleeding and DNA loss (integrity indicators) and basal and pentagastrin induced acid secretion were measured after placebo and sucralfate treatment in subjects without (group A) and with administration of 2.5 g aspirin (group B). Sucralfate significantly reduced spontaneous gastric microbleeding and DNA loss in group A and prevented blood loss but not DNA loss caused by aspirin in group B. The protective effects of sucralfate on spontaneous gastric microbleeding were accompanied by increased mucosal biosynthesis and luminal release of PGE2 and 6-keto-PGF1 alpha with a reduction in release of thromboxane B2. In aspirin treated subjects both mucosal generation and luminal release of prostaglandins and thromboxane B2 were greatly suppressed although sucralfate treatment did not influence these prostaglandins in spite of the reduction in mucosal damage. It is concluded that sucralfate has a potent protective action on spontaneous and aspirin treated gastric microbleeding in man and that this protection may be partly because of the increased mucosal biosynthesis of prostaglandins.

Topics: Adult; Aspirin; DNA; Double-Blind Method; Drug Evaluation; Gastric Acid; Gastric Mucosa; Gastrointestinal Hemorrhage; Humans; Male; Prostaglandins; Sucralfate; Thromboxane B2

Uncertainty remains regarding the impact of enteric-coated aspirin (EC-ASA) on secondary prevention of ischemic stroke compared to plain aspirin (P-ASA). Hence, this study was designed to investigate the effect of EC formulation on ASA response via evaluating thromboxane B2 (TXB2) levels in patients with suspected or newly diagnosed stroke.. A prospective cohort study on suspected or newly diagnosed ischemic stroke patients who are aspirin-naive was conducted. Patients were received either EC aspirin or plain aspirin for at least 3 days. The primary outcome was the proportion of aspirin non-responsiveness between two groups (level of residual serum TXB2 associated with elevated thrombotic risk (< 99.0% inhibition or TXB2 > 3.1 ng/ml) within 72 h after three daily aspirin doses, while secondary outcomes were the incidence of early gastrointestinal tract (GIT) bleeding with the various aspirin preparations. (Trial registration: Clinicaltrials.gov NCT04330872 registered on 02 April 2020).. Of 42 patients, ischemic strokes were confirmed in both P-ASA (81%) and EC-ASA (67%) arms. ASA non-responsiveness showed no significant difference between the two formulations (P-ASA vs. EC-ASA; 28.6% vs 23.8%; P = 0.726). Univariate and multivariate logistic regression analysis showed that patients treated with EC-ASA were more likely to have a lower rate of non-responders compared to P-ASA (unadjusted OR 0.78; 95% CI 0.20, 3.11); with the risk highest in type 2 diabetic patients with HBA1c > 6.5% (adjusted OR 6; 95% CI 1.02, 35.27; P = 0.047). No incidence of GIT bleeding observed throughout the study.. A significant proportion of ASA non-responsiveness was recorded regardless of ASA formulation administered. The increased risk of ASA non-responsiveness in diabetic patients needs further exploration by larger prospective studies.

Topics: Aspirin; Gastrointestinal Hemorrhage; Glycated Hemoglobin; Humans; Ischemic Stroke; Platelet Aggregation Inhibitors; Prospective Studies; Thromboxane B2

Peptic ulcers due to nonsteroidal anti-inflammatory drug (NSAID) use may have contributed to the static prevalence of ulcer disease in Asia.. We aimed to determine the current etiology of peptic ulcer disease in Singapore.. Consecutive patients undergoing esophagogastroduodenoscopy who had not been exposed to antibiotics, or antiulcer therapy within the past 6 months, and in whom peptic ulcers were found, were prospectively studied. Before endoscopy, patients were interviewed regarding the use of NSAID or aspirin. During endoscopy, antral biopsies were obtained for urease test and histology. Serum thromboxane B2 levels were compared with those of healthy volunteers.. Peptic ulcers were detected in 600 patients during a 2-year period. The ulcers were negative for Helicobacter pylori in 212 patients (35.3%) and these H. pylori negative ulcers were related to NSAID use in 68.9% of cases. On the basis of serum thromboxane B2 levels, 30.8% of the patients with non-H. pylori non-NSAID were considered to have consumed NSAID.. H. pylori negative peptic ulcer makes up a significant proportion of peptic ulcer in Singapore. Most of these ulcers were related to NSAID use. Serum thromboxane profile suggested surreptitious NSAID use in many of the non-H. pylori and apparently non-NSAID patients.

Topics: Adult; Anti-Inflammatory Agents, Non-Steroidal; Female; Gastrins; Gastrointestinal Hemorrhage; Humans; Male; Middle Aged; Peptic Ulcer; Prospective Studies; Singapore; Thromboxane B2

Topics: Blood Platelet Disorders; Blood Platelets; Child, Preschool; Female; Gastrointestinal Hemorrhage; Humans; Oxidoreductases; Thromboxane B2; Thromboxane-A Synthase