Role of hemostatic powders in the management of lower gastrointestinal bleeding: A review

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1 bs_bs_banner doi: /jgh REVIEW Role of hemostatic powders in the management of lower gastrointestinal bleeding: A review Fadi H Mourad and Rupert W Leong * Gastroenterology and Liver Services, Concord Repatriation General Hospital, Sydney, New South Wales, Australia Key words Ankaferd Blood Stopper, EndoClot, endoscopy, Hemospray, hemostasis, lower gastrointestinal hemorrhage. Accepted for publication 22 January Correspondence Fadi H Mourad, Gastroenterology and Liver Services, Concord Repatriation General Hospital, Hospital Road, Concord, NSW 2137, Australia. fmourad@aub.edu.lb Declaration of conflict of interest: Both authors have no conflict of interest related to this paper. Abstract Despite the recent advances in endoscopic hemostatic techniques, the management of lower gastrointestinal bleeding could be sometimes challenging. Hemostatic powders such as Hemospray, EndoClot, and Ankaferd Blood Stopper have found their way into digestive endoscopy and are licenced in many countries especially for use in upper gastrointestinal bleeding. We reviewed the literature on the use of these hemostatic powders in different situations in lower gastrointestinal bleeding and looked at the success rate and rebleeding rate. Most of the data are derived from case reports, retrospective and prospective with absence of any randomized controlled trials. Hemostatic powders were used as primary or salvage therapy to control bleeding from polypectomy site, colonic tumors, diverticula, arteriovenous malformations, radiation proctitis, ischemic colitis, and surgical intestinal anastomosis. The rate of immediate control of bleeding is in the range of % with a recurrence rate of 3 13% except for radiation proctitis bleeding where rebleeding rate can be as high as 77%. Although there are many advantages for the use of local hemostatic agents in lower gastrointestinal bleeding, future randomized controlled trials comparing them with conventional s are needed. Introduction Gastrointestinal bleeding is a major cause of morbidity and mortality worldwide resulting in a hospitalization rate of 21 per adults and a mortality rate of 2% to 4%. 1,2 The incidence of lower gastrointestinal bleeding (LGIB) has increased over the years with the aging population and the increased use of nonsteroidal antiinflammatory drugs (NSAIDs), antiplatelets, and anticoagulants. 3 The causes of significant LGIB include colonic polyps and tumors, diverticular disease, colitis, ischemia, radiation, rectal ulcers, arteriovenous malformations (AVMs), and endoscopic polypectomy. Despite the high success rate in controlling LGIB with the recent advances in endoscopic hemostatic techniques including injection therapy, argon plasma coagulation (APC), cautery, thermocoagulation, and clips, endoscopic management could be sometimes challenging. Problems that may be encountered by the endoscopist include difficulties in obtaining an en face view of the bleeding site for injection or clipping, the large surface area of bleeding from malignant lesions, the inability to localize the site of bleeding, and the failure of stopping severe arterial or venous bleeding using the available topical endoscopic techniques especially in anticoagulated patients. 4 Therefore, there is a need for agents that can instantaneously stop bleeding upon contact with the bleeding site. Many hemostatic agents have been used in surgery over the years, and a few agents such as clotting factors have been occasionally used in endoscopy. 5 Recently, new hemostatic agents have found their way to digestive endoscopy, and some have been approved for use in some countries. 4,6,7 The three available agents are Hemospray, EndoClot, and Ankaferd Blood Stopper (ABS). The aim of this study is to review the current literature on the use and outcome of hemostatic powders in the management of LGIB from different etiologies and determine their short-term and long-term effects on the control of bleeding and define their place in the armamentarium of endoscopic hemostatic techniques. Available hemostatic powders Hemospray (also named TC-325) (Cook Medical, Winston-Salem, NC, USA) is a mineral-based powder that was developed by the armed forces for control of bleeding in military operations. It is deployed via an endoscopic catheter 1 2 cm from the bleeding area using pressurized carbon dioxide as part of the delivery system. In contact with moisture or blood, Hemospray particles swell and become cohesive and adhesive, creating a barrier layer that covers the bleeding site and acts as tamponade achieving very rapid hemostasis, usually within seconds. Absorption of the fluid component of blood ultimately also leads to concentration of clotting factors and cellular elements. In addition, it has also been postulated that the powder may activate the clotting cascade along with aggregating platelets, forming a fibrin plug. 8 The mechanical barrier formed sloughs off from the mucosa within h. 9 As the powder swells and hardens only in the presence of moisture and disappears within a short period of time, its use in high-risk lesions such as in nonbleeding visible vessels is unlikely to decrease the risk of rebleeding. 6 Hemospray is currently approved in Canada; Mexico; and several countries in the Caribbean, South America, Europe, and Asia for upper gastrointestinal tract use. In Europe, Hemospray is not licenced for use in the lower gastrointestinal tract, and therefore, its current use in LGIB is offlabel. Hemospray is not approved by the Food and Drug Agency in the USA. 1445

2 EndoClot (AMP; EndoClot Plus Inc., Santa Clara, CA, USA) contains absorbable polysaccharide particles derived from plant starch. These particles are hydrophilic and thus absorb water from the blood and form a gel that contains concentrated red cells, platelets, and coagulation factors leading to accelerated coagulation. The interaction of the polymer particles with blood produces a matrix that seals the bleeding tissue. 6,7 The substance is delivered through a catheter inserted into the operating channel of the endoscope and propelled by an air compressor onto the bleeding lesion. AMP is currently approved in Turkey, Europe, Malaysia, and Australia despite the presence of only a few published and case reports. ABS (Ankaferd Health Products Ltd., Istanbul, Turkey) is composed of a standardized mixture of plants. ABS does not affect an individual clotting factor, but its mechanism of action involves its interaction with endothelium and blood cells leading to a rapid (< 1 s) formation of an encapsulated protein network behaving as an anchor for erythrocyte aggregation. Although this integrates the classic coagulation cascade, but ABS does not directly act on coagulation factors and platelets. Currently, ABS experience is limited mostly to Turkey and is not Food and Drug Agency approved. 4,10,11 The use of hemostatic powders in lower gastrointestinal bleeding Post-polypectomy bleed. Bleeding following endoscopic polypectomy is the most common complication of colonic polypectomy, occurring in % of polypectomies. 12,13 Bleeding may occur immediately following polypectomy or be delayed for hours or days. Usually, it stops spontaneously, but occasionally may need endoscopic intervention using metallic clips or cautery. In rare situations, bleeding cannot be stopped by known endoscopic techniques. Soulellis and colleagues 14 were the first to report Hemospray as salvage therapy in two patients with postpolypectomy bleeding who failed to respond to clip and thermal therapy. Bleeding did not recur during follow up at 14 and 104 days. Hemospray was also used in few case reports and case series as primary or salvage therapy for post-polypectomy bleeding in further 12 patients (Table 1). The immediate success rate in stopping bleeding was 100%, but two cases of recurrent bleeding were reported; this was stopped by clip in one patient 16 and by embolization in the second patient. 18 In a prospective series of 82 patients who underwent endoscopic mucosal resection of colorectal lesions, EndoClot powder was sprayed on the mucosal defect irrespective of post-resection bleeding. 19 Twenty lesions in 18 cases showed bleeding after endoscopic mucosal resection. Hemostasis was successfully achieved in 18 lesions (90%) with a single round of spray. The bleeding from the other two lesions was controlled by combined hot biopsy forceps and two rounds of EndoClot. No complications were observed. The effectiveness of ABS for colonic post-polypectomy bleeding was shown in five patients by Karaman et al. 20 ABS was used as a first choice in three cases and as salvage therapy in two patients after failed attempts with other endoscopic interventions. Bleeding following polypectomy was stopped with ABS application in all of the cases without any complication or rebleeding in the following 72 h. In a recent by Kurt et al., 21 ABS application was successful in stopping post-polypectomy active bleeding in a total of three patients. In one of these patients, 40 ml of ABS was used as salvage therapy after failure of epinephrine injection and hemoclips in controlling bleeding postsubmucosal dissection for a rectal polyp (Table 1). Neoplastic lower gastrointestinal bleed. Colon cancer is an important cause of LGIB and occurs in 2 9% of cases of hematochezia. 22 Endoscopic hemostasis can sometimes be achieved by endoscopic means, but in general, the tumor will continue to ooze from its large surface area, and rebleeding rate is expectedly high. The ability to cover large areas of bleeding without touching tissue may make hemostatic powder use perfectly adapted for malignant gastrointestinal bleeding keeping in mind that the definite treatment is surgical excision of the neoplasm. The role of the endoscopist is therefore to buy time for the surgeon and oncologist to decide on further management. Theoretically, Hemospray powder is a good alternative as it covers the whole surface area of the tumor and thus can stop bleeding. A few cases have been reported in the literature about the use of this modality with very good success rate. Hemospray was used in four cases of tumors at various sites of the colon as primary or salvage therapy, 17,18,23 and EndoClot was successfully used in one patient with sigmoid colon tumor followed by surgery. 24 In addition, ABS as primary treatment was able to achieve hemostasis within seconds in five patients with rectal carcinoma with no adverse events reported (Table 2). Diverticular and other vascular bleed. Bleeding from colonic diverticula is the most common cause of acute LGIB, accounting for approximately 26 40% of cases. 1,2 Bleeding is arterial and can occur either at the dome or at the neck of the diverticulum. Usually, it is difficult to identify the active bleeding site or suggestive stigmata such as adherent clot or a visible vessel. Endoscopic treatments such as epinephrine injection, contact thermal therapy, endoscopic clipping, and band ligation can be used, but it seems that clips are safer and can serve to locate the area of bleeding for possible embolization. 28 However, clips are not always successfully placed. In a study by Kaltenbach et al.,successful endoscopic hemostasis was achieved in 21 (88%) out of 24 patients with active diverticular bleeding using clips as monotherapy or in combination with epinephrine injection. There was no early rebleeding, but late rebleeding ( 30 days following initial endoscopic hemostasis) occurred in 24%. 29 Holster et al. 18 reported the use of Hemospray in one patient with diverticular bleed with good hemostasis, but bleeding recurred 24 h later necessitating the use of a clip with success. ABS was used as a primary therapy in stopping diverticular bleed within few minutes in two patients, one of them was on warfarin. There was no recurrence of bleeding in both patients after 60 days follow up. 30 Bleeding from AVMs and other vascular lesions are unusual causes of acute LGIB. Hemospray was successfully used in one case of bleeding from AVM 17 and two patients with Dieulafoy lesions. 14,17 In one patient on clopidogrel with bleeding from a sigmoid Dieulafoy lesion, salvage therapy with Hemospray successfully stopped the bleeding after epinephrine injection and application of five clips failed to stop the bleeding. 14 Finally, 1446

3 Table 1 Patients characteristics, lesion location, and outcome of the use of various hemostatic powders in post-polypectomy bleeding Report type n Age Sex Location Powder Amount Primary/Salvage Control of bleeding Y/N Reference Retrospective 1 79 M Cecum Hemospray 20 g S clip Y Soulellis M Rectosigmoid Hemospray 30 g S thermal, clip Y Soulellis Retrospective 1 70 F Rectum Hemospray 5 20 g S clip, epinephrine Y Holster M Rectum Hemospray 5 20 g S epinephrine Y Holster F Transverse colon Hemospray 5 20 g S clip Y Embolization 24 h later Holster F Ascending colon Hemospray 5 20 g P Y Holster Case report 1 50 F Rectum Hemospray P Y Curcio Case report 1 66 M Sigmoid Hemospray > 20 g S clips Y Ivekovic Clips 1 week later Retrospective 6 Colon Hemospray P Y Chen Prospective ±13 Colonic EndoClot 3 g P Y Success rate 90% Hot forceps and repeat EndoClot in 2 patients Huang Retrospective 1 Colon ABS 5 6 ml P Y Karaman Colon ABS 5 6 ml P Y Karaman Colon ABS 5 6 ml P Y Karaman Colon ABS 5 6 ml S Y Karaman Colon ABS 5 6 ml S Y Karaman Retrospective 1 58 M Colon ABS 3 ml P Y Kurt F Rectum ABS 10 ml P Y Kurt M Rectum ABS 40 ml S clips, epinephrine Y Kurt ABS, Ankaferd Blood Stopper; F, female; M, male; N, no; P, primary; S, salvage; Y, yes. 1447

4 Table 2 Patients characteristics, lesion location, and outcome of the use of various hemostatic powders in colonic tumors bleeding Report type n Age Sex Location Powder Amount Primary/Salvage Control of bleeding Y/N Reference Prospective 1 Anus Hemospray 20 g P Y Sulz Retrospective series 1 79 M Cecum Hemospray 20 g P Y Holster Retrospective 1 Colon Hemospray 20 g P Y Chen Sigmoid EndoClot 2 g P Y Rebled surgery Case report 1 78 F Rectum ABS 3 ml P Y Surgery Prei Turhan Retrospective 3 Rectum ABS 5 14 ml P Y Kurt Case report 1 66 M Rectum ABS 5 ml P Y Beyazit ABS, Ankaferd Blood Stopper; F, female; M, male; N, no; P, primary; S, salvage; Y, yes. Table 3 Patients characteristics, location, and outcome of the use of various hemostatic powders in diverticular and other vascular bleeding Report type n Age Sex Location Source Powder Amount Primary/Salvage Control of bleeding Y/N Reference Retrospective 1 75 M Descending colon Diverticula Hemospray 20 g P Y 24-h-later clips Holster Case report 1 67 M Descending colon Diverticula ABS 4 ml Y Aslan Case report 1 85 F Descending colon Diverticula ABS 2 ml Y Aslan Retrospective 1 82 M Sigmoid Dieulafoy Hemospray 20 g S clips epinephrine Y Soulellis Retrospective 1 Colon Dieulafoy Hemospray Y Chen Colon AVM Hemospray Y Chen Case report 1 72 M Rectosigmoid Portal hypertensive colopathy Hemospray P Y Smith ABS, Ankaferd Blood Stopper; AVM, arteriovenous malformation; F, female; M, male; N, no; P, primary; S, salvage; Y, yes. 1448

5 Smith et al. 31 reported the use of Hemospray in a patient bleeding from portal hepatic colopathy with a significant decrease in blood transfusion requirements on follow up (Table 3). Bleed secondary to radiation colitis. Radiation proctitis occurs in 5 20% of patients who receive pelvic radiation. The main symptoms of chronic radiation proctitis are hematochezia ranging from mild to life-threatening bleeding. Treatment options vary from observation in mild disease to medical management with 5-aminosalicylic acid (5-ASA) and sucralfate; to endoscopic treatment with bipolar, heater probe or APC, or local application of formalin; and finally to surgical treatment in severe refractory cases. 32 The best results of endoscopic treatment were reached in a prospective nonrandomized trial using APC with a success rate reaching 98% in decreasing bleeding. 33 Occasionally, bleeding cannot be controlled during endoscopy, and therefore, there is a need for a technique to stop the bleeding during these situations. Hemocoagulation may be an alternative treatment of radiation proctitis as it does not require precise localization of bleeding site, and simple spraying of the powder over the rectal mucosa may be sufficient to control the bleeding. Hemospray was used in two patients with radiation proctitis. In the first patient, APC failed to stop the bleeding, and therefore, Hemospray was used with success, and sessions of APC were then continued 14 days later. 14 In the second patient, immediate hemostasis was obtained with no recurrence of bleeding after 72 h, but no further information on follow up was provided 17 (Table 4). The first case of successful ABS application in radiation colitis was reported by Ozaslan et al. 34 in a 71-year-old woman. A total of 20 ml of ABS was used to control the bleeding from an ulcerated rectal lesion. Three further sessions were carried out on a weekly basis to complete the healing with no signs of rebleeding in the following days. ABS was also found to be useful in controlling radiation colitis bleeding after other medical and endoscopic techniques have failed, and therefore, it can help to better localize and target telangiectasias for APC treatment. 35 Kurt et al. 21 reported three patients with radiation colitis that was primarily managed with APC. Adjuvant application of ABS in these patients resulted in a more sustained control of bleeding. In a series of eight cases with severe radiation proctitis, multiple weekly sessions of ABS as a primary therapy were able to induce hemostasis in seven out of eight cases, but bleeding recurred in 1 8 days after each session 36 (Table 4). At the last follow up, ABS was found to induce healing of ulcers in four cases but had no effect on telangiectasias. Thus, it seems ABS has only a temporary effect in controlling bleeding secondary to radiation proctitis and should not be used as a definitive therapy in these situations. Colorectal ulcers bleed. Ulcers in the colon could be secondary to solitary rectal ulcers, idiopathic inflammation, NSAIDs Table 4 Patients characteristics and outcome of the use of various hemostatic powders in bleeding from radiation proctitis Report type n Age Sex Powder Amount Primary/Salvage Control of bleeding Y/N Reference Retrospective 1 69 M Hemospray 20 g S APC Y Soulellis F/U APC Prospective 1 Hemospray P Y Chen Case report 1 71 F ABS 20 ml P Y Osazlan more sessions Case report 1 70 F ABS 20 ml S APC Y Shorbagi Followed by APC Retrospective 1 71 M ABS 2 sessions 17 S APC Y Kurt ml 1 70 M ABS 15 ml S APC Y Kurt M ABS 15 ml S APC Y Kurt Prospective 1 65 M ABS 5 sessions 20 ml P Y Bleeding recurred in 3 days 1 61 M ABS 5 sessions ml P Y Bleeding recurred in 2 days 1 60 M ABS 7 sessions 30 ml P Y Bleeding recurred in 3 days 1 68 M ABS 5 sessions 20 ml P Y Bleeding recurred in 1 day 1 56 F ABS 7 sessions 20 ml P Y Bleeding recurred in 3 days 1 71 M ABS 5 sessions 20 ml P Y Bleeding recurred in 2 days 1 70 F ABS 5 sessions 20 ml P Y Bleeding recurred in 1 day 1 61 M ABS 5 sessions 20 ml P Y Bleeding recurred in 3 days ABS, Ankaferd Blood Stopper; APC, argon plasma coagulation; F, female; M, male; N, no; P, primary; S, salvage; Y, yes. 1449

6 use, infections, surgical anastomosis, or ischemia. Occasionally, it may be difficult to control bleeding from these ulcers especially when they are diffuse. Although bleeding from solitary rectal ulcers is usually mild and stops spontaneously, it is sometimes of concern as it may become recurrent and serious. Topical application of Hemospray 18 and ABS 37 onto the solitary rectal ulcer were found to be successful in controlling the bleeding. Kratt et al. 38 described an unusual case of serious bleeding from diffuse colonic ulcerations induced by NSAIDs; Hemospray was applied to the colonic segments and repeated in 2 days with control of bleeding and thus avoiding the need for surgery. Two cases of uncontrolled bleeding cecal ulcers secondary to cytomegalovirus 39 and H1N1, 40 one case of proctitis secondary to chemotherapy, 18 and one case of idiopathic ileocecal ulcer 17 were successfully treated with Hemospray (Table 5). Colonic ischemia may lead to colonic inflammation and mucosal damage with ulcerations leading commonly to LGIB that may be difficult to treat endoscopically because of the diffuse sites of bleeding. Granata et al. 41 described the successful treatment with Hemospray of four cases of bleeding from ischemic colitis after failure of conventional endoscopic techniques. All patients had large colonic ulcers (25 50 mm) and were on antithrombotic therapy. One patient had rebleeding and had a second Hemospray application 4 days after the first treatment. No rebleeding or complications occurred after 1-month follow up. EndoClot was also used in one patient with cecal ischemia with control of bleeding; however, the patient later on underwent a surgical excision of the ischemic bowel 24 (Table 5). Surgical intestinal anastomosis carries a risk of leakage or clinically significant bleeding with hemodynamic instability resulting in a reoperation rate of 4 8%. 42,43 It is not always possible to stop anastomotic bleed using the classical endoscopic techniques. 44 Gubler et al. 45 described four cases of anastomotic bleed in the early postoperative period who were successfully treated with Hemospray as primary or salvage therapy. However, one patient required three sessions of Hemospray application in 5 days with the use of bipolar coagulation to control bleeding of the colorectal anastomosis post-sigmoid resection. The use of Hemospray was also successful in the hemostatic control of anastomotic bleed in a further five patients in three different reports. 17,46,47 Finally, Hemospray was used to control bleeding in three patients with the unusual occurrence of post-colonic biopsies bleed 17 (Table 6). Safety and precautions Overall, the safety of hemostatic agents in LGIB appears to be excellent. This has been demonstrated in a wide variety of medical indications in animals and human studies. Abdominal pain is one of the side effects especially with the use of Hemospray under high pressure. There is a theoretical risk of intestinal perforation, embolization, and intestinal obstruction with the use of these agents. These side effects have not been directly linked to the use of hemostatic agents. Nevertheless, because of lack of large randomized trials and the limited experience in some of these agents, special caution should be taken when using them in situations where the wall of the colon is at high risk of perforation such as in diverticular bleed or in patients with colonic ischemia. It is very important to follow specific recommendation in the use of this. The catheter should be 1 2 cm away from the mucosa or any fluid to Table 5 Patients characteristics and outcome of the use of various hemostatic powders in bleeding from colonic ulcers of different etiologies and locations Reference Control of bleeding Y/N Report type n Age Sex Location Source Powder Amount Primary/Salvage 1 45 F Rectum Ulcer Hemospray 20 g P Y Holster Retrospective Kratt Case report 1 64 F Rectum Solitary rectal ulcer ABS 10 ml Y Ibis Case report 1 66 F Cecum, NSAIDs ulcers Hemospray Y Bleeding recurred in 2 days ascending, transverse Case report 1 Cecum CMV ulcer Hemospray Diez-Rodriguez F Cecum H1N1 ulcer Hemospray S fibrin glue Y Granata M Rectum Proctitis Hemospray 5 30 g P Y Holster Retrospective 1 Colon Ileocecal valve ulcer Hemospray Y Chen Granata Ischemic colitis Hemospray 20 g S epinephrine, clip Y 1 repeat after 4 days Cecum, ascending, descending colon, splenic flexure M 1F Retrospective Prei Cecum Ischemia EndoClot 2 g P Y Followed by surgery Prospective ABS, Ankaferd Blood Stopper; CMV, cytomegalovirus; F, female; M, male; N, no; NSAIDs, nonsteroidal anti-inflammatory drugs; P, primary; S, salvage; Y, yes. 1450

7 Table 6 biopsies Patients characteristics and outcome of the use of various hemostatic powders in bleeding from surgical colonic anastomosis and colonic Report type n Age Sex Location Powder Amount Primary/Salvage Control of bleeding Y/N Reference Retrospective 1 77 F Sigmoid resection Hemospray Maximum 20 g P Y Gubler F Delorme operation Hemospray Maximum 20 g P Y Gubler F Ileal J pouch Hemospray Maximum 20 g P Y Gubler anastomosis Recurrent bleeding Bipolar coagulation 1 60 M Sigmoid resection Hemospray Maximum 20 g P Y Gubler Retrospective 1 62 F Colonic anastomosis Hemospray 20 g P Y Holster Retrospective 2 Colonic anastomosis Hemospray P Y Chen Case report 2 Colonic anastomosis Hemospray P Y Hagel Case report 1 20 M Ileal pouch Hemospray P Y Martin Retrospective 3 Colonic biopsies Hemospray P Y Chen F, female; M, male; N, no; P, primary; S, salvage; Y, yes. Table 7 Summary of the effect of the various hemostatic powders in controlling lower gastrointestinal bleeding of different etiologies Hemospray EndoClot Ankaferd Blood Stopper n I.C. (%) Rec. (%) n I.C. (%) Rec. (%) n I.C. (%) Rec. (%) Post-polypectomy Cancer Diverticula Dieulafoy AVM Portal hypertensive colopathy Radiation Solitary rectal ulcers Colonic ulcers Ischemia Surgical anastomosis Colonic biopsies Unspecified Total AVM, arteriovenous malformation; I.C., immediate control of bleeding; Rec., recurrence of bleeding. avoid clogging of the catheter. In addition, with Hemospray, if the catheter is incorrectly applied with direct mucosal contact, a pressure of up to 55 mmhg may be delivered and therefore may increase the risk of perforation 14 especially in the presence of diverticula or in ischemic bowel. These hemostatic agents should be used only in actively bleeding lesions as they harden in contact with moisture; therefore, they cannot be used as prophylaxis in high-risk lesions for bleeding. In addition, hemostatic powders may obscure the view during endoscopy and prohibit any alternative hemostatic approach. 4 Summary and conclusion Published case reports and have shown that hemostatic agents are quite effective in controlling LGIB and they are helpful for diffuse bleeding with or without a clearly localized source. A total of 108 reported patients with LGIB of various etiologies were treated with one of the three different types of hemostatic powders (48 with Hemospray, 32 with Endostat, and 28 with ABS) (Table 7). Despite the current unavailability of randomized controlled trials, data from these retrospective and prospective case series indicate the rate of immediate control of bleeding to be in the range of %. The rate of recurrent bleeding necessitating further intervention is relatively low ranging from 3% to 13% except for radiation colitis in which rebleeding rate can be as high as 77%. Therefore, these results are encouraging for the use of hemostatic agents in LGIB. In practice, there are many advantages for their use. First, the application of these agents is simple and can be learned easily and quickly without a long learning curve and therefore can be used as a temporary measure to stop bleeding in 1451

8 regions where an experienced interventional endoscopist is not readily available. Second, this of hemostasis does not require en face position of bleeding site, and thus, it is a good alternative even in experienced hands facing technically difficultto-reach bleeding site. Third, it is particularly helpful when the surface area of bleeding is large and when the exact site of bleeding cannot be identified like in malignant colonic lesions or ischemic colitis. Application of Hemospray does not require direct targeting of a bleeding vessel as the powder is sprayed over a large surface area in multiple directions. Fourth, Hemostatic agents represent an effective alternative treatment modality for LGIB as a primary or a salvage or adjuvant therapy complementing conventional s. Fifth, hemostatic powders themselves are safe without any known toxicity and therefore can be used repeatedly in the same patient. No serious complications have been reported with their use. Sixth, they can be used in patients taking anticoagulants or antithrombotic medications. Seventh, the procedure is quick and can be completed rapidly in high risk patients. Finally, the use of hemostatic agents might be cost-effective in particular clinical settings and especially if surgical intervention can be avoided. Although Hemospray was found to improve cost-effectiveness in the management of upper gastrointestinal bleeding, 48 this finding cannot be extrapolated at the present time to LGIB. In order to more firmly establish topically applied hemostatic agents in the algorithm of endoscopic hemostatic therapy, future randomized controlled trials comparing them with conventional s are needed. References 1 Longstreth GF. Epidemiology and outcome of patients hospitalized with acute lower gastrointestinal hemorrhage: a population-based study. Am. J. Gastroenterol. 1997; 92: Oakland K, Guy R, Uberoi R et al. 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