High-Dose Proton Pump Inhibitors Are Superior to Standard-Dose Proton Pump Inhibitors in High-Risk Patients With Bleeding Ulcers and High-Risk Stigmata After Endoscopic Hemostasis.

INTRODUCTION: To define the best cutoff of the Glasgow-Blatchford score (GBS) for identifying high- and low-risk rebleeding patients with bleeding ulcers and high-risk stigmata after endoscopic hemostasis and compare the efficacy of high-dose and standard-dose intravenous proton pump inhibitors (HD-IVPs and SD-IVPs, respectively) in this patient population. METHODS: We retrospectively reviewed the data of 346 patients with bleeding ulcers and high-risk stigmata who underwent endoscopic hemostasis between March 2014 and September 2018 in our center and were divided into an HD-IVP group and an SD-IVP group. Propensity score-matching analysis was performed to control for selection bias and other potential confounders. Recurrent bleeding rates were calculated according to the GBS. RESULTS: Overall, 346 patients meeting the inclusion criteria were enrolled, with 89 patients in the SD-IVP group and 89 patients in the HD-IVP group after matching with all baseline characteristics balanced (P > 0.05). GBS = 8 was the best cutoff for identifying high-risk rebleeding patients (GBS ≥ 8) with a significant difference (P = 0.015) in recurrence rate between the SD-IVP (17/61, 27.9%) and HD-IVP (7/65, 10.8%) groups and low-risk rebleeding patients (GBS < 8) with no difference (P = 1) in recurrence rate between the SD-IVP (2/28, 7.1%) and HD-IVP (2/24, 8.3%) groups. DISCUSSION: The best cutoff for identifying high-risk and low-risk rebleeding patients with bleeding ulcers and high-risk stigmata after endoscopic hemostasis was GBS = 8. Although HD-IVP is more effective than SD-IVP in high-risk patients, they are equally effective in low-risk patients.

Diagnostic Values of Blood Count Values and Ratios in Distinguishing between Peptic Ulcer Bleeding and Esophagogastric Variceal Bleeding.

BACKGROUND: To investigate the diagnostic values of blood count values and ratios in distinguishing between peptic ulcer bleeding (PUB) and esophagogastric variceal bleeding (EGVB). METHODS: Due to acute hematemesis and or melaena, 57 patients diagnosed with PUB (PUB group) and 33 cases with EGVB (EGVB group) were enrolled in this retrospective study. The levels of peripheral blood leukocyte counts (leukocyte), neutrophil counts (neutrophil), lymphocyte counts (lymphocyte), platelet counts (platelet), neutrophil to lymphocyte ratio (NLR), and platelet to lymphocyte ratio (PLR) were recorded and compared between the two groups. Student's t-test of independent samples was adopted for comparing the mean between the two groups. Model discrimination was evaluated using the area under the receiver operating characteristic curve (AUC). Comparison of AUC was performed using the Z-test. RESULTS: The levels of leukocyte, neutrophil, lymphocyte, platelet, and PLR were significantly increased in PUB group compared with EGVB group (all p < 0.05), while there was no significant statistical difference of NLR (p > 0.05); moreover, AUCs in distinguishing PUB from EGVB were 0.859, 0.811, 0.760, 0.952, and 0.687 for leukocyte, neutrophil, lymphocyte, platelet, and PLR, respectively, and significant differences were observed between platelet and any parameter of the rest (all p < 0.05); finally, the cutoff values were 8 x 109/L in distinguishing between PUB and EGVB (specificity 78.95%, sensitivity 87.88%, and Youden index 0.668) for leukocyte, 5.3 x 109/L (specificity 70.18%, sensitivity 81.82%, and Youden index 0.520) for neutrophil, 1.2 x 109/L (specificity 84.21%, sensitivity 60.61%, and Youden index 0.448) for lymphocyte, 131 x 109/L (specificity 92.98%, sensitivity 90.91%, and Youden index 0.839) for platelet, and 88 (specificity 70.18%, sensitivity 63.64%, and Youden index 0.338) for PLR. CONCLUSIONS: Leukocyte, neutrophil, lymphocyte, platelet and PLR are useful and potential biomarkers in distinguishing between PUB and EGVB; moreover, platelet can demonstrate more accurate and reliable diagnostic value.

Misoprostol Heals Small Bowel Ulcers in Aspirin Users With Small Bowel Bleeding.

BACKGROUND & AIMS: There is no effective treatment for aspirin-induced small bowel ulcer bleeding. We performed a double-blind, randomized, placebo-controlled trial to determine whether misoprostol can heal small bowel ulcers in patients with small bowel bleeding who require continuous aspirin therapy. METHODS: We performed a prospective study of 84 aspirin users with small bowel bleeding who required continued aspirin therapy in Hong Kong and Japan. Patients with small bowel ulcers or multiple erosions, detected by capsule endoscopy, were randomly assigned to groups that received either misoprostol (200 µg, 4 times daily; n = 42) or placebo (n = 42) for 8 weeks. All patients continued taking aspirin (100 mg, once daily). The primary end point was complete ulcer healing at follow-up capsule endoscopy. Secondary end points included changes in hemoglobin level and number of ulcer/erosions from baseline. RESULTS: Complete healing of small bowel ulcers was observed in 12 patients in the misoprostol group (28.6%; 95% CI, 14.9%-42.2%) and 4 patients in the placebo group (9.5%; 95% CI, 0.6%-18.4%), for a difference in proportion of 19.0% (95% CI, 2.8%-35.3%; P = .026). The misoprostol group had a significantly greater mean increase in hemoglobin than the placebo group (mean difference, 0.70 mg/dL; 95% CI, 0.05-1.36; P = .035). The reduction in medium number of ulcers or erosions was significantly greater in the misoprostol group (from 6.5 [range, 1-85] to 2 [range, 0-25]) than in the placebo group (from 7 [range, 1-29] to 4 [range, 0-19] (P = .005). CONCLUSIONS: In a double-blind, randomized, placebo-controlled trial, we found misoprostol to be superior to placebo in promoting healing of small bowel ulcers among aspirin users complicated by small bowel ulcer bleeding who require continuous aspirin therapy. However, use of misoprostol alone would provide only limited protection against aspirin on the small bowel. ClinicalTrials.gov ID NCT01998776.

Management of non variceal upper gastrointestinal bleeding: position statement of the Catalan Society of Gastroenterology. / Manejo de la hemorragia digestiva alta no varicosa: documento de posicionamiento de la Societat Catalana de Digestologia.

In recent years there have been advances in the management of non-variceal upper gastrointestinal bleeding that have helped reduce rebleeding and mortality. This document positioning of the Catalan Society of Digestologia is an update of evidence-based recommendations on management of gastrointestinal bleeding peptic ulcer.

Similar Efficacy of Proton-Pump Inhibitors vs H2-Receptor Antagonists in Reducing Risk of Upper Gastrointestinal Bleeding or Ulcers in High-Risk Users of Low-Dose Aspirin.

BACKGROUND & AIMS: It is not clear whether H2-receptor antagonists (H2RAs) reduce the risk of gastrointestinal (GI) bleeding in aspirin users at high risk. We performed a double-blind randomized trial to compare the effects of a proton pump inhibitor (PPI) vs a H2RA antagonist in preventing recurrent upper GI bleeding and ulcers in high-risk aspirin users. METHODS: We studied 270 users of low-dose aspirin (≤325 mg/day) with a history of endoscopically confirmed ulcer bleeding at 8 sites in Hong Kong and Japan. After healing of ulcers, subjects with negative results from tests for Helicobacter pylori resumed aspirin (80 mg) daily and were assigned randomly to groups given a once-daily PPI (rabeprazole, 20 mg; n = 138) or H2RA (famotidine, 40 mg; n = 132) for up to 12 months. Subjects were evaluated every 2 months; endoscopy was repeated if they developed symptoms of upper GI bleeding or had a reduction in hemoglobin level greater than 2 g/dL and after 12 months of follow-up evaluation. The adequacy of upper GI protection was assessed by end points of recurrent upper GI bleeding and a composite of recurrent upper GI bleeding or recurrent endoscopic ulcers at month 12. RESULTS: During the 12-month study period, upper GI bleeding recurred in 1 patient receiving rabeprazole (0.7%; 95% confidence interval [CI], 0.1%-5.1%) and in 4 patients receiving famotidine (3.1%; 95% CI, 1.2%-8.1%) (P = .16). The composite end point of recurrent bleeding or endoscopic ulcers at month 12 was reached by 9 patients receiving rabeprazole (7.9%; 95% CI, 4.2%-14.7%) and 13 patients receiving famotidine (12.4%; 95% CI, 7.4%-20.4%) (P = .26). CONCLUSIONS: In a randomized controlled trial of users of low-dose aspirin at risk for recurrent GI bleeding, a slightly lower proportion of patients receiving a PPI along with aspirin developed recurrent bleeding or ulcer than of patients receiving an H2RA with the aspirin, although this difference was not statistically significant. ClincialTrials.gov no: NCT01408186.

Effects of different omeprazole dosing on gastric pH in non-variceal upper gastrointestinal bleeding: A randomized prospective study.

OBJECTIVE: We aimed to identify the best method of omeprazole (OME) application with respect to intragastric pH, cytochrome P450 2C19 (CYP2C19) genotype and phenotype. METHODS: The patients with non-variceal upper gastrointestinal bleeding (NVUGIB) were prospectively enrolled. After the achievement of endoscopic hemostasis, the patients were randomized to 40-mg intravenous (i.v.) OME bolus injection every 12 h or 8-mg/h continuous i.v. infusion for 72 h after an 80-mg i.v. OME bolus administration. The intragastric pH was recorded for 72 h. The CYP2C19 variant alleles (*2, *3, *17) were analyzed and the serum concentrations of OME and 5-hydroxyomeprazole (5-OH OME) were determined. RESULTS: Altogether 41 Caucasians (18 in the OME infusion [OI] group and 23 in the OME bolus [OB] group) were analyzed. The median percentage of time with an intragastric pH > 4.0 was higher in the infusion group than in the OB group over 48 h (100% vs 96.6%, P = 0.009) and 72 h (100% vs 87.6%, P = 0.006), and that at an intragastric pH >6.0 was higher in the OI group than the OB group over 72 h (97.9% vs 63.5%, P = 0.04). Helicobacter pylori infection was correlated with the fastest increase in intragastric pH, especially in the OI group. In both groups, CYP2C19 genotypes (*1/*1, *1/*17, *17/*17) had no essential effect on intragastric pH. CONCLUSIONS: In patients with NVUGIB, OME i.v. bolus followed by continuous infusion is more effective than OME i.v. bolus every 12 h in maintaining higher intragastric pH, regardless of CYP2C19 genetic polymorphisms. H. pylori infection accelerates the initial elevation of intragastric pH.

[State of immune and cytokine status in acute ulcerative gastroduodenal bleeding].

The paper analyzes the results of a survey of 37 patients with acute ulcerative gastroduodenal hemorrhage. During endoscopy found that 7 patients the cause of bleeding was gastric ulcer, duodenal ulcer in 27 and 3 concomitant ulcer. Hemostasis was evaluated by J. Forrest and the severity of blood loss was assessed by the A.A. Shalimov: with blood loss was mild in 11 patients, the average degree--12 and with severe--14. In all patients on admission in the peripheral blood were studied state of cellular, humoral and cytokine profile: CD3+, CD4+, CD8+, CD4+/CD8 + and CD19+, FI, FF, CEC, IgA, M, G, TNF-α, IFN-γ, IL-1, IL-2, IL-4, IL-6, IL-8 and IL-10. In general patients with on admission revealed significant changes in the immune and cytokine status. In cellular immunity occurs immunosuppression. Disturbances in humoral immunity manifests itself in increased levels of lymphocytes in blood loss and hardships of all multi-directional changes in the concentration of immunoglobulins depending on the amount of blood loss. When there is an imbalance in cytokine status, the depth of which depends on the degree of blood loss.

Patient characteristics with high or low blood urea nitrogen in upper gastrointestinal bleeding.

AIM: To examine characteristics of patients with blood urea nitrogen (BUN) levels higher and lower than the normal limit. METHODS: Patient records between April 2011 and March 2014 were analyzed retrospectively. During this time, 3296 patients underwent upper endoscopy. In total, 50 male (69.2 ± 13.2 years) and 26 female (72.3 ± 10.2 years) patients were assessed. Patients were divided into two groups based on BUN levels: higher than the normal limit (21.0 mg/dL) (H) and lower than the normal limit (L). One-way analysis of variance was performed to reveal differences in the variables between the H and L groups. Fisher's exact test was used to compare the percentage of patients with gastric ulcer or gastric cancer in the H and L groups. RESULTS: White blood cell count was higher in the H group than in the L group (P = 0.0047). Hemoglobin level was lower in the H group than in the L group (P = 0.0307). Glycated hemoglobin was higher in the H group than in the L group (P = 0.0264). The percentage of patients with gastric ulcer was higher in the H group (P = 0.0002). The H group contained no patients with gastric cancer. CONCLUSION: Patients with BUN ≥ 21 mg/dL might have more severe upper gastrointestinal bleeding.

[Mucosal changes in the periulcer zone and endocrine system in patients with gastroduodenal ulcer, complicated by hemorrhage].

Examination of patients, suffering gastroduodenal ulcer, complicated by hemorrhage, was conducted, using clinical, microbiological, immunohistochemical methods and chromatomassspectrography. Enhanced activity of inducible NO-synthase, contamination of periulcer zone with microorganisms Klebsiella pneumoniae, Streptococcus beta-haemoliticus, enhancement of contents of catecholamines and serotonin in the blood serum were revealed. These changes are most expressed in severe blood loss, unstable local endoscopic hemostasis, high risk of a recurrent hemorrhage occurrence. The data obtained permit to prognosticate severity of a pathologic process course and to improve the treatment programe.

Endogenous heparinoids detected by anti-Xa activity are present in blood during acute variceal bleeding in cirrhosis. A prospective study.

BACKGROUND & AIMS: Endogenous heparinoids have been detected by thromboelastography and quantified by clotting based anti-Xa activity assays in patients with cirrhosis, but their presence in variceal bleeding has not been established yet. METHODS: Clotting based anti-Xa activity was measured in A) 30 cirrhotics with variceal bleeding, B) 15 non-cirrhotics with peptic ulcer bleeding, C) 10 cirrhotics without infection or bleeding, and D) 10 cirrhotics with hepatocellular carcinoma (HCC). RESULTS: Anti-Xa activity was not detected in ulcer bleeders or in cirrhotics without infection or bleeding but was present in seven (23%) variceal bleeders (median levels: 0.03 u/mL (0.01-0.07)) and was quantifiable for 3 days in six of seven patients. Four of seven variceal bleeders with anti-Xa activity present had HCC (p=0.023). Age, creatinine, platelet count and total infections the second day from admission were significantly correlated with the presence of measureable anti-Xa levels (p=0.014, 0.032, 0.004 and 0.019, respectively). In the HCC group, anti-Xa activity was present in three patients (30%) [median levels: 0.05 u/mL (0.01-0.06)]. CONCLUSIONS: In this study, variceal bleeders and 30% of the patients with HCC had endogenous heparinoids that were detected by a clotting based anti-Xa activity assay, whereas there was no anti Xa activity present in patients with cirrhosis without infection, or bleeding or HCC, nor in those with ulcer bleeding. Thus, the anti Xa activity is likely to be a response to bacterial infection and/or presence of HCC in cirrhosis.

[Prognostication of gastroduodenal ulcer course complicated by hemorrhage].

Dynamics of the blood serum level of serotonin in the patients, suffering gastroduodenal ulcer, Complicated by hemorrhage, was analyzed. The highest level of serotonin was observed in gastric ulcer, complicated by hemorrhage. These changes correlate with the blood loss severity enhancement, the achievement of a nonstable state of endoscopic hemostasis, high activity of inducible NO-synthase (iNOS) of periulcerative mucosa. The obtained data analysis permits to prognosticate the pathological process course and to improve the program of treatment.

Stress ulcer prophylaxis, thromboprophylaxis and coagulation management in patients with hip fractures.

Hip fracture in older patients is a major health concern. 20-25 % of hip fracture patients will die in the first year after the trauma (Lane, Clin Orthop Relat Res 471(8):2711, 2013). Postoperative venous thrombosis and gastrointestinal stress-ulcer bleeding are frequent complications with a high case-fatality rate particularly in older patients. Thromboprophylaxis and stress ulcer prophylaxis are important and well established measures to decrease postoperative complications and the mortality rate in this high-risk population.The working group on orthogeriatrics of the Austrian Society on Geriatrics and Gerontology (ÖGGG) is composed of geriatricians who work as trauma surgeons, internists, anaestesists and nurses. A thorough literature search was done, using the terms "orthogeriatrics" and "hip fracture" in combination with "stress ulcer", "gastrointestinal bleeding" and "thrombosis", "thromboprophylaxis". The data was collected, discussed and evaluated in several adjustment meetings of the group and summarized in this article.

[Dynamics of catecholamines in serum of patients with gastroduodenal ulcers complicated by hemorrhage].

The dynamics of the catecholamines content in the blood serum of the patients, suffering gastroduodenal ulcer, complicated by hemorrhage, was analyzed. The biggest raising of the investigated index level was observed in patients while presence of gastric cancer, complicated by hemorrhage. These changes correlate with the blood loss severity enhancement, the state of unstable endoscopic hemostasis, high activity of the inducible NO-synthase of the peri-ulceral zone mucosa. The data obtained permit to prognosticate the pathological process and to improve the treatment program.

Intravenous non-high-dose pantoprazole is equally effective as high-dose pantoprazole in preventing rebleeding among low risk patients with a bleeding peptic ulcer after initial endoscopic hemostasis.

BACKGROUND: Many studies have shown that high-dose proton-pumps inhibitors (PPI) do not further reduce the rate of rebleeding compared to non-high-dose PPIs but we do not know whether intravenous non-high-dose PPIs reduce rebleeding rates among patients at low risk (Rockall score < 6) or among those at high risk, both compared to high-dose PPIs. This retrospective case-controlled study aimed to identify the subgroups of these patients that might benefit from treatment with non-high-dose PPIs. METHODS: Subjects who received high dose and non-high-dose pantoprazole for confirmed acute PU bleeding at a tertiary referral hospital were enrolled (n = 413). They were divided into sustained hemostasis (n = 324) and rebleeding groups (n = 89). The greedy method was applied to allow treatment-control random matching (1:1). Patients were randomly selected from the non-high-dose and high-dose PPI groups who had a high risk peptic ulcer bleeding (n = 104 in each group), and these were then subdivided to two subgroups (Rockall score ≥ 6 vs. < 6, n = 77 vs. 27). RESULTS: An initial low hemoglobin level, serum creatinine level, and Rockall score were independent factors associated with rebleeding. After case-control matching, the significant variables between the non-high-dose and high-dose PPI groups for a Rockall score ≥ 6 were the rebleeding rate, and the amount of blood transfused. Case-controlled matching for the subgroup with a Rockall score < 6 showed that the rebleeding rate was similar for both groups (11.1% in each group). CONCLUSION: Intravenous non-high-dose pantoprazole is equally effective as high-dose pantoprazole when treating low risk patients with a Rockall sore were < 6 who have bleeding ulcers and high-risk stigmata after endoscopic hemostasis.

Hematologic and laboratory parameters in patientis with peptic ulcer bleeding treated by two modalities of endoscopic haemostasis and proton pump inhibitors.

AIM: To compare two schedules (continuous infusion or bolus i.v. of PPI) in treatment after endoscopic homeostasis of bleeding ulcers. METHODS: Patients with gastrointestinal bleeding caused by peptic ulcer, or a recent history (< 24 h before presentation) were included in the study. All cases with actively bleeding ulcers were treated with epinephrine injection and/or thermal coagulation, and randomized to receive intravenous PPIs according to the continuous regimen (in continuous infusion) or the standard regimen (40 mg bolus twice a day for 3 days). RESULTS: 69 patients were treated. Bleeding recurred in 5 of 34 patients (14.7%) receiving the intensive regimen, and in 8 of 35 (22.8%) patients receiving the standard regimen. Hemoglobine rate in standard regimen group was 93,5 g/L (SD 23,8), and in intensive regimen group 106,6 g/L (SD 22,4) (p = 0.042). Total protein rate in the standard regimen group was 65,1 g/L (SD 7,3) and in the intensive regimen group 67,7 g/L (SD 8,15), (p = 0.525). Albumin rate in the standard regimen group was 31,0 g/L (SD 5,2), whereas in the intensive regimen group it was 34,8 g/L (SD 7,4), (p = 0.652). Globulin rate in the standard regimen group was 31,0 g/L (SD 5,2) and in the intensive regimen group 32,3 g/L (5,3), (p = 0.875). Fibrinogen rate in the standard regimen group was 11,1 (SD 2,6) and 10,8 g/L (SD 2,4 p = 0.622) in the intensive regimen group. A mean number of units of blood transfusion for patients in the intensive group was 2,18 (SD 0,8) and 1,34 (SD 1,02) in the standard group, with statistical level of difference p = 0.0004, using Student t-test. The duration of hospital stay was 6,4 days (SD 2,8) in the standard group and 5,8 days (SD 2,8) in the intensive group (p = 0.40). There were fewer surgical interventions in the intensive versus standard regimen. CONCLUSION: In patients with bleeding peptic ulcers with successful endoscopic hemostasis the standard IPP regimen had advantage for transfusion requirements, but no advantage with respect to in-hospital rates of re-bleeding, need for surgery, length of hospital stay, or death.

Predictors of rebleeding and mortality in patients with high-risk bleeding peptic ulcers.

BACKGROUND AND AIM: Patients with bleeding ulcers can have recurrent bleeding and mortality after endoscopic therapy. Risk stratification is important in the management of the initial patient triage. The aim of this study is to identify the clinical and laboratory risk factors for recurrent bleeding and mortality. METHODS: A prospective study was conducted in 390 consecutive patients with bleeding peptic ulcers and high-risk endoscopic stigmata, e.g., active bleeding, a non-bleeding visible vessel, adherent blood clot, and hemorrhagic dot. We tested 13 available variables for association with recurrent bleeding and 15 were tested for association with mortality. A logistic regression model was used to identify individual correlates associated with these adverse outcomes. RESULTS: Bleeding recurred in 46 patients (11.8%) within 3 days and 21 patients (5.4%) had in-hospital mortality. In the full-factor analysis model, the incidence of recurrent bleeding was significantly higher in five of the 13 investigated variables and mortality was significantly higher in two of the 15 variables. In the final analysis model, significant risk factors for recurrent bleeding within 3 days, with adjusted odds ratios (OR), were in-hospital bleeding (OR 3.3), initial hemoglobin level<10 g/dl (OR 3.3) and ulcer>or=2 cm (OR 2.0). In-hospital bleeding was the only independent risk factor for mortality (OR 8.3). CONCLUSION: The study emphasizes the role of ulcer size, anemia and in-hospital bleeding as the determining high-risk predictors for adverse outcomes for bleeding peptic ulcers.

Clarifying the relationship between ABO/Rhesus blood group antigens and upper gastrointestinal bleeding.

BACKGROUND AND AIM: The relationship between blood group antigens and peptic ulcer disease has been widely evaluated in the past. Data concerning the same association with upper gastrointestinal bleeding are very limited. We aimed to evaluate this association and we thought it was worthwhile to try to determine whether these components take some part in this complication. METHODS: The study population consisted of 1,098 adults (364 patients and 734 volunteer blood donors as controls). Demographic features, comorbid illnesses, and use of aspirin/nonsteroidal anti-inflammatory drugs (NSAIDs) were recorded. Blood groups were examined by gel centrifugation method. We included only patients with bleeding from peptic ulcer disease and erosive gastropathy. Ulcers were classified by using Forrest's classification system in terms of rebleeding risk. Helicobacter pylori was examined by histology. RESULTS: The gender distribution was similar in both groups. The ABO blood group phenotype distribution in patients and controls (respectively) was as follows: 46.2% versus 34.9% for group O, 32.4% versus 39.5% for group A, 15.7% versus 18.4% for group B, and 5.8% versus 7.2% for group AB. Blood group O was found to have higher frequency in the patient group than in the control group (P=0.004). Rh positivity was also higher in patients than in controls (P=0.007). H. pylori positivity was similar between blood groups among patients. The rebleeding and mortality rates between blood groups were also similar. CONCLUSION: ABO blood group O had an important role in patients with upper gastrointestinal bleeding. The impact of blood group on rebleeding and mortality may be a focus for further studies.

[The hemostasis system state in patients with ulcerous gastrointestinal bleedings].

In patients with gastrointestinal bleedings there occurs activation of the hemostasis system directed to arrest of bleeding. Short-term hypercoagulation directed to arrest of the bleeding gives place to hypocoagulative changes. Their degree and duration depend on the severity and rate of blood loss. The excessive intravascular activation of blood is accompanied by the formation of fibrin deposits not only in the area of the bleeding source but in other regions of the blood channel. There appears disseminated intravascular coagulation of blood deteriorating the reparative processes in the ulcer, initiating and maintaining generalized plasminemia which promotes the thrombus lysis in the ulcer crater and recurrent bleeding.