Recurrent obscure gastrointestinal bleeding: Dilemmas and success with pharmacological therapies. Case series and review

The present article describes three difficult cases of recurrent bleeding from obscure causes, followed by a review of the pitfalls and pharmacological management of obscure gastrointestinal bleeding. All three patients underwent multiple investigations. An intervening complicating diagnosis or antiplatelet drugs may have compounded long-term bleeding in two of the cases. A bleeding angiodysplasia was confirmed in one case but was aggravated by the need for anticoagulation. After multiple transfusions and several attempts at endoscopic management in some cases, long-acting octreotide was associated with decreased transfusion requirements and increased hemoglobin levels in all three cases, although other factors may have contributed in some. In the third case, however, the addition of low-dose thalidomide stopped bleeding for a period of at least 23 months.     

Changes in efficiency and resource utilization after increasing experience with double balloon enteroscopy

AIM: To investigate changes in efficiency and resource utilization as a single endoscopist’s experience increased with each subsequent 100 double balloon enteroscopy (DBE) procedures.METHODS: We reviewed consecutive DBE procedures performed by a single endoscopist at our center over 4 years. DBE was employed when the clinician deemed the procedure was needed for disease management. The approach (oral, anal or both) was chosen based on suspected location of the target lesion. All DBE was performed in a standard endoscopy room with a portable fluoroscopy unit. Fluoroscopy was used to aid in shortening the small intestine and reducing bowel loops. For oral DBE, measurements were taken from the incisors. For anal DBE, measurements were taken from the anal verge. Enteroscopy continued until the target lesion was reached, until the entire small intestine was examined, or until no further progress was deemed possible. The length of small intestine examined (cm), procedure duration (min), and fluoroscopy time (s) were analyzed for sequential groups of 100 DBE. Sub-groups of diagnostic and therapeutic procedures were analyzed using multivariable linear regression.RESULTS: 802 consecutive DBE procedures were analyzed. For oral DBE, median [interquartile range (IQR)] length of small bowel examined was 230.8 cm (range: 210-248 cm) and for anal DBE was 143.5 cm (range: 100-180 cm). No significant increase in length examined was noted for either the oral or anal approach with advancing position in series. In terms of duration of procedure, the median (IQR) for oral DBE was 86 min (range: 71-105 min) and for anal DBE was 81.3 min (range: 67-105 min). When comparing by the position in series, there was a significant (P value < 0.001) decrease in procedure duration for both upper and lower procedures with increasing experience. Median (IQR) time of exposure to fluoroscopy for oral DBE was 190 s (114-275) compared to anal DBE which was 196.4 s (312-128). This represented a significant (P value < 0.001) decrease in the amount of fluoroscopy used with increasing position in series. For both oral and anal DBE, fluoroscopy time was reduced by greater than 50% over the course of 802 total procedures performed. Sub-group analysis was conducted on therapeutic and diagnostic groups. Out of 802 procedures, a total of 434 were considered therapeutic. Argon plasma coagulation was by far the most common therapeutic intervention performed. There was no evidence of a difference in length examined or fluoroscopy exposure among oral DBE for diagnostic and therapeutic procedures, P = 0.91 and P = 0.32 respectively. The median (IQR) for length was 235 cm (range: 178-280 cm) for diagnostic vs 230 cm (range: 180-275 cm) for therapeutic procedures; additionally, fluoroscopy time median (IQR) was 180 s (range: 110-295 s) and 162 s (range: 102-263 s) for no intervention and intervention. However, there was a significant difference in procedure duration among oral DBE (P < 0.001). The median (IQR) was 80 min (range: 60-97 min) and 94 min (range: 77-110 min) for diagnostic and therapeutic interventions respectively.CONCLUSION: For a single endoscopist, increased DBE experience with number of performed procedures is associated with increased efficiency and decreased resource utilization.     

Controversy of proton pump inhibitor and clopidogrel interaction: a review

A proton pump inhibitor (PPI) is often co-prescribed with clopidogrel to reduce the gastrointestinal risk of bleeding ulcers in patients following acute coronary syndrome or a stent implant. However, the safety issue of such practice has been scrutinized after some studies reporting an increased incidence of cardiovascular events and mortality, although there have also been contrary research reports. This has lead to a warning statement from the US Food and Drug Administration cautioning the concomitant use of PPI and clopidogrel. This review examines the evidence of PPI as gastroprotective agent, histamine H(2) antagonists as an alternative therapy, the influence of PPI on the antiplatelet effect of clopidogrel, and the controversies of various studies.     

Usefulness of prognostic indices in upper gastrointestinal bleeding

Upper gastrointestinal haemorrhage remains a significant cause of hospital admission, with mortality rates up to 14%. In order to standardise and improve care, various scoring systems (e.g. Rockall, Blatchford and Baylor) have been developed to identify those individuals at high risk of requiring treatment (transfusion, endoscopic or surgical intervention) or of re-bleeding or death. There is also increasing interest in the utilisation of scoring systems to identify individuals at low risk of complications, as these may be discharged early, possibly with outpatient endoscopy. Most scoring systems are developed to predict outcomes in non-variceal bleeding. However, several indices are used to predict the outcome of advanced liver disease, including Child-Pugh and the Model of End-Stage Liver Disease (MELD). This chapter reviews all these aspects of the various scoring systems.     

Multiple Stomas for Recurrent Life-Threatening Gastrointestinal Bleeding: Report of a Case

Acute lower gastrointestinal hemorrhage is an uncommon and severe symptom. The overall mortality rate ranges from 5 to 12 percent and can approach 40 percent for persistent or recurring bleedings. We report a case of a patient with severe recurrent lower bleeding in whom, despite several repeated explorations and a blind subtotal colectomy, no lesion could be found. Multiple (n = 4) leveled stomas of the small bowel with succus entericus reinfusion were required to localize and treat the cause of the bleeding. This case report is followed by a review of the literature of the management of lower gastrointestinal bleeding. Reprints are not available.     

Intracranial haemorrhage in patients with congenital haemostatic defects

Summary. We investigated 52 of 457 patients with congenital factor deficiencies with 57 episodes of intracranial haemorrhage (ICH) between 1998 and 2007. There were 38 severe haemophiliacs, 6 with factor XIII deficiency, 5 with factor X deficiency, 2 factor V‐deficient patients, and 1 with type 3 von Willebrand disease (VWD). The median age was 8 years (range 1 month–22 years). Most patients were below 15 years of age (86.5%). All patients with factor X deficiency were between 1 and 5 months of age. ICH was the primary bleeding episode leading to detection of factor deficiency in 19.2% (five patients with severe haemophilia and all patients with factor X deficiency). Trauma caused bleeding in 66%. None of the patients with factor X deficiency had history of prior trauma. Surgery was performed in five patients with subdural haematomas, all of whom survived. Conservative factor replacement with 100% correction for 3 days followed by 50–60% correction for 7 days was possible in 60% patients. Seizures requiring prolonged therapy were noted in eight patients. Death was recorded in 15 patients (29%). Inadequate therapy in the form of delay or insufficient replacement was noted in 7/15 deaths. ICH was seen in 11.3% of all patients with coagulation factor deficiencies. Factor X deficiency presented with ICH at an earlier age. Inadequate replacement therapy including delayed treatment caused nearly 50% of all deaths. Most patients can be managed satisfactorily with adequate replacement therapy alone, with surgery being reserved for those with worsening neurological conditions.     

Transcatheter embolization of a giant pancreatic pseudoaneurysm: A tale of two bleeds and one thrombus!

Erosion of a peripancreatic artery into the pseudocyst as a result of enzymatic digestion of vessel wall gives rise to a pancreatic pseudoaneurysm (PSA), which is a rare complication seen in patients with chronic pancreatitis.¹ Angiographic embolization as a treatment method for acute hemorrhage from pancreatic PSA has become increasingly popular. Here we report a unique case with bleeding from a giant pancreatic PSA where the single PSA had blood supply originating from the branches of both the celiac artery and superior mesenteric artery.     

Prophylaxis of hepatic encephalopathy in acute variceal bleed: a randomized controlled trial of lactulose versus no lactulose

Background and Aims: Acute variceal bleed (AVB) is an important precipitating factor for development of hepatic encephalopathy (HE). However, there is paucity of data on the role of lactulose for prevention of HE after AVB. We evaluated the role of lactulose for prophylaxis of HE after AVB. Methods: Consecutive patients of cirrhosis with AVB enrolled. Patients included if >18 years old and had no HE at the time of presentation. Patients were randomized to receive lactulose (Group‐L) or no lactulose (Group‐P) along with standard treatment of AVB as per Baveno 4 guidelines. Primary endpoint was development of overt HE as per West Haven criteria within 120 h of randomization. Results: Seventy patients were randomized into group‐L (Gp‐L, n = 35) and group‐P (Gp‐P, n = 35). There was no significant difference in baseline characteristics between the two groups. Characteristics of variceal bleed were also similar (Gp‐L vs Gp‐P [mean arterial pressure 81.0 ± 10.5 vs 79.5 ± 9.9 mmHg], Hb [8.4 ± 1.5 vs 9.3 ± 2.3 g/dL], blood transfusion requirement [1.6 ± 1.1 vs 1.3 ± 0.9 units], time to endoscopy [6.3 ± 2.8 vs 7.0 ± 3.1 h], and esophageal source of bleed [92% vs 88%]). Nineteen (27%) patients developed HE; five patients (14%) in Gp‐L and 14 patients (40%) in Gp‐P, P = 0.03. The median grade of HE was 2 (range 2–4) and median time interval of development of HE after randomization was 2 days (range 1–4). Nine patients (13%) died; three (8.5%) patients in Gp‐L and six (17%) patients in Gp‐P, P = 0.23. Patients who developed HE had significantly higher baseline Child‐Turcotte‐Pugh score score (10.2 ± 1.2 vs 9.4 ± 1.4 P = 0.04), model for end stage liver disease score (18.2 ± 3.9 vs 15.4 ± 4.5 P = 0.02), arterial ammonia level (112.2 ± 22.7 vs 94.8 ± 17.6 umol/L, P = 0.001), baseline total leukocyte count (10 505.2 ± 8911.9 vs 5784.3 ± 3387.0 P = 0.002), total bilirubin (3.4 ± 1.3 vs 2.1 ± 1.8 mg%, P = 0.008) as compared to patients who did not develop HE. On multivariate analysis only baseline arterial ammonia, blood requirement during hospital stay and lactulose therapy were predictors of development of HE. Conclusions: Lactulose is effective in prevention of HE in patients with cirrhosis and acute variceal bleed.     

Micronized purified flavonidic fraction compared favorably with rubber band ligation and fiber alone in the management of bleeding hemorrhoids

PURPOSE: The aim of this study was to assess the role of micronized purified flavonidic fraction in the management of bleeding nonprolapsed hemorrhoids. METHODS: Patients were randomly assigned to receive ispaghula husk alone, rubber band ligation plus ispaghula husk, or micronized purified flavonidic fraction plus ispaghula husk. Other colorectal diseases were excluded by colonoscopy. Blinded observers noted the time for bleeding to stop completely, recurrences, and treatment complications. RESULTS: A total of 162 patients were randomly assigned with no significant differences in the age and gender distributions among the groups. Hemorrhoidal bleeding was relieved most expediently in the micronized purified flavonidic fraction plus ispaghula husk group (ispaghula husk alone n=66, mean (standard error of the mean) 10.6 (2.3) days; rubber band ligation plus ispaghula husk n=57, 5.6 (1.1) days; micronized purified flavonidic fraction plus ispaghula husk (n=39, 3.9 (1.2) days;P=0.03). However, there were no significant differences in the recurrences at six months of follow-up (ispaghula husk alone n=8 (12 percent); rubber band ligation plus ispaghula husk n=12 (21 percent); micronized purified flavonidic fraction plus ispaghula husk n=2 (5.1 percent);P=0.075). No complications or side-effects were noted. CONCLUSIONS: micronized purified flavonidic fraction used with fiber supplements rapidly and safely relieved bleeding from nonprolapsed hemorrhoids.Poster presentation at The American Society of Colon and Rectal Surgeons' 100th Anniversary and Tripartite Meeting, Washington, D.C., May 1 to 6, 1999.     

Primary prophylaxis of gastroesophageal variceal bleeding: consensus recommendations of the Asian Pacific Association for the Study of the Liver

The Asian Pacific Association for the Study of the Liver (APASL) set up a Working Party on Portal Hypertension in 2002, with a mandate to develop consensus guidelines on various clinical aspects of portal hypertension relevant to disease patterns and clinical practice in the Asia-Pacific region. Variceal bleeding is a consequence of portal hypertension, which, in turn, is the major complication of liver cirrhosis. Primary prophylaxis to prevent the first bleed from varices is one of the most important strategies for reducing the mortality in cirrhotic patients. Experts predominantly from the Asia-Pacific region were requested to identify the different aspects of primary prophylaxis and develop the consensus guidelines. The APASL Working Party on Portal Hypertension evaluated the various therapies that have been used for the prevention of first variceal bleeding. A 2-day meeting was held on January 12 and 13, 2007, at New Delhi, India, to discuss and finalize the consensus statements. Only those statements that were unanimously approved by the experts were accepted. These statements were circulated to all the experts and were subsequently presented at the annual conference of the APASL at Kyoto, Japan, in March 2007.     

Hemophilic arthropathy in patients with von Willebrand disease

von Willebrand disease (VWD) affects approximately 1% of the population. Joint bleeds are not a predominant symptom of VWD, however they do occur. Especially in patients with severe VWD, joint bleeds have been described in up to 45% of the patients. Recurrent hemarthroses can lead to joint destruction which is the main cause of morbidity, as is observed in hemophilia patients. In VWD however, the occurrence, severity, onset, treatment and impact of arthropathy have not been well described. This literature review summarizes all publications on arthropathy in patients with hereditary VWD, published until 1-5-2012. Joint bleeds in VWD are associated with low FVIII levels and seem to occur at young age. Depending on the severity of VWD, arthropathy occurs in 2–30% of the patients. Radiological joint damage can be seen but has not systematically been studied. Arthropathy can affect daily functioning and interfere with the quality of life. For acute management of joint bleeds FVIII/VWF concentrates can be used in VWD patients unresponsive to desmopressin or desmopressin in responsive VWD patients. When severe joint bleeds have caused synovitis and arthropathy, chemical or radioactive synovectomy and surgical joint procedures seem feasible to prevent further joint damage. Additional research is needed to learn more about the severity, onset and impact of arthropathy in VWD. Ongoing studies will hopefully answer the question whether prophylactic treatment with coagulation factor concentrates should be considered standard of care in severe VWD to prevent arthropathy.     

Cytomegalovirus related fatal duodenal diverticular bleeding: Case report and literature review

Involvement of gastrointestinal tract by cytomegalovirus(CMV) is common. CMV infections mainly run their course without any clinical signs in immunocompetent hosts. In contrast, CMV can cause severe infections with serious consequences in a immunocompromised state typically associated with organ transplants, highly immunosuppressive cancer chemotherapy, advanced HIV infection or treatment with corticosteroids. The incidence and severity of these manifestations of CMV is directly proportional with the degree of cellular immune dysfunction, i.e., CD8+ Cytotoxic T-cell response. Clinical manifestations of CMV can become apparent in different situations including reactivation of CMV from latency, primary infection in a seronegative host, or exposure of a seropositive host to a new strain of CMV. As the clinical signs of CMV in immunodeficient patients are usually sparse, physicians should be highly vigilant about CMV infection, a treatable condition that otherwise is associated with significant mortality. Here we report a rare case of severe gastrointestinal CMV infection with sustained immunodeficiency secondary to treatment with steroids manifesting as fatal duodenal diverticular bleeding.     

Comparing bleed frequency and factor concentrate use between haemophilia A and B patients

Summary. Haemorrhagic manifestations in patients with haemophilia A and B are considered quite similar for comparable level of factor deficiency. We investigated the bleeding frequency and factor usage between HA and HB patients with comparable disease severities. We collected data on frequency of bleeds and factor concentrate utilization over 3 years, from January 2001 to December 2003. Information was gathered from home infusion logs recorded by patients or their parents, and treatment records from the Hemophilia Clinic or the Hospital Emergency Department. Data were available on 58 patients with severe HA (FVIII < 0.01 U mL^?1), 10 with moderate HA (FVIII < 0.05 U mL^?1), 15 with severe HB, and five with moderate HB who required treatment for episodic bleeds, postoperative haemostasis and for primary or secondary prophylaxis. The HA patients bled more frequently than HB patients (14.4 vs. 8.63 bleeds/patient/year), but used similar amounts of concentrate per year. HA patients underwent surgical procedures 3.2 times more frequently than HB patients to correct musculoskeletal complications. A total of 21 363 409 IU of recombinant FVIII was used by patients with HA (104 722 IU/patient/year) and 6 430 960 IU of recombinant factor IX, by patients with HB (107 182 IU/patient/year). The difference in factor concentrate usage is not statistically significant (P > 0.05). The decrease in bleed frequency in haemophilia B indicates that the conclusions from randomized trials of prophylaxis in HA may not be accurately applied to HB.     

An unusual case of late gastrointestinal bleeding after pancreatoduodenectomy

With more widespread application of and improved outcomes from pancreatoduodenectomy, late complications of this procedure are appearing more commonly in the clinical setting. Presented here is an unusual case of hemobilia secondary to cavernous portal vein transformation one year following pylorus-sparing pancreatoduodenectomy. Common and unusual causes of gastrointestinal bleeding following pancreatoduodenectomy are discussed.