CC BY-NC-ND 4.0 · Endosc Int Open 2022; 10(08): E1136-E1146
DOI: 10.1055/a-1836-8962
Review

Hemostatic powders for gastrointestinal bleeding: a review of old, new, and emerging agents in a rapidly advancing field

1   Department of Medicine, University of British Columbia, Vancouver, BC, Canada
,
Daljeet Chahal
2   Division of Gastroenterology, Mount Sinai Hospital, New York, New York, United States
,
Nabil Ali-Mohamad
3   Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
4   Faculty of Medicine, University of British Columbia, Vancouver, BC, Canada
,
Christian Kastrup
3   Michael Smith Laboratories, University of British Columbia, Vancouver, BC, Canada
5   Blood Research Institute, Versiti, Milwaukee, Wisconsin, United States
,
Fergal Donnellan
6   Division of Gastroenterology, University of British Columbia, Vancouver General Hospital, Vancouver, BC, Canada
› Author Affiliations

Abstract

Background and study aims Hemostatic powders are increasingly used to address limitations in conventional endoscopic techniques for gastrointestinal bleeding. Various agents exist with different compositions, characteristics, efficacy, and adverse events (AEs). We sought to review existing hemostatic powders, from preclinical to established agents.

Methods A literature review on hemostatic powders for gastrointestinal bleeding was undertaken through a MEDLINE search from 2000–2021 and hand searching of articles. Relevant literature was critically appraised and reviewed for mechanism of action, hemostasis and rebleeding rate, factors associated with hemostatic failure, and AEs.

Results The most established agents are TC-325 (Hemospray), EndoClot, and Ankaferd Blood Stopper (ABS). These agents have been successfully applied to a variety of upper and lower gastrointestinal bleeding etiologies, in the form of primary, combination, salvage, and bridging therapy. Few AEs have been reported, including visceral perforation, venous embolism, and self-limited abdominal pain. Newer agents include CEGP-003 and UI-EWD, which have shown results similar to those for the older agents in initial clinical studies. All aforementioned powders have high immediate hemostasis rates, particularly in scenarios not amenable to conventional endoscopic methods, but are limited by significant rates of rebleeding. Other treatments include TDM-621 (PuraStat) consisting of a liquid hemostatic agent newly applied to endoscopy and self-propelling thrombin powder (CounterFlow Powder), a preclinical but promising agent.

Conclusions Rapid development of hemostatic powders and growing clinical expertise has established these agents as a valuable strategy in gastrointestinal bleeding. Further research will continue to refine the efficacy and applicability of these agents.



Publication History

Received: 15 January 2022

Accepted: 20 April 2022

Article published online:
15 August 2022

© 2022. The Author(s). This is an open access article published by Thieme under the terms of the Creative Commons Attribution-NonDerivative-NonCommercial License, permitting copying and reproduction so long as the original work is given appropriate credit. Contents may not be used for commercial purposes, or adapted, remixed, transformed or built upon. (https://creativecommons.org/licenses/by-nc-nd/4.0/)

Georg Thieme Verlag KG
Rüdigerstraße 14, 70469 Stuttgart, Germany

 
  • References

  • 1 Gralnek IM, Barkun AN, Bardou M. Management of acute bleeding from a peptic ulcer. N Engl J Med 2008; 359: 928-937
  • 2 Rosenstock SJ, Møller MH, Larsson H. Improving quality of care in peptic ulcer bleeding: nationwide cohort study of 13,498 consecutive patients in the Danish Clinical Register of Emergency Surgery. Am J Gastroenterol 2013; 108: 1449-1457
  • 3 Barkun AN, Adam V, Lu Y. et al. Using Hemospray improves the cost-effectiveness ratio in the management of upper gastrointestinal nonvariceal bleeding. J Clin Gastroenterol 2018; 52: 36-44
  • 4 Laine L, Barkun AN, Saltzman JR. et al. ACG Clinical Guideline: Upper Gastrointestinal and Ulcer Bleeding. Am J Gastroenterol 2021; 116: 899-917
  • 5 Barkun AN, Almadi M, Kuipers EJ. et al. Management of nonvariceal upper gastrointestinal bleeding: guideline recommendations from the international consensus group. Ann Intern Med 2019; 171: 805
  • 6 Bustamante-Balén M, Plumé G. Role of hemostatic powders in the endoscopic management of gastrointestinal bleeding. World J Gastrointest Pathophysiol 2014; 5: 284-292
  • 7 Chen Y-I, Barkun AN. Hemostatic powders in gastrointestinal bleeding: a systematic review. Gastrointest Endosc Clin N Am 2015; 25: 535-552
  • 8 Facciorusso A, Straus Takahashi M, Eyileten Postula C. et al. Efficacy of hemostatic powders in upper gastrointestinal bleeding: A systematic review and meta-analysis. Dig Liver Dis 2019; 51: 1633-1640
  • 9 Facciorusso A, Bertini M, Bertoni M. et al. Effectiveness of hemostatic powders in lower gastrointestinal bleeding: a systematic review and meta-analysis. Endosc Int Open 2021; 9: E1283-E1290
  • 10 Sung JJY, Luo D, Wu JCY. et al. Early clinical experience of the safety and effectiveness of Hemospray in achieving hemostasis in patients with acute peptic ulcer bleeding. Endoscopy 2011; 43: 291-295
  • 11 Holster IL, Maat MPD, Ducharme R. et al. Sa1671 In vitro examination of the effects of the hemostatic powder (HemosprayTM) on coagulation and thrombus formation in humans. Gastrointest Endosc 2012; 75: AB240
  • 12 Smith LA, Stanley AJ, Bergman JJ. et al. Hemospray application in nonvariceal upper gastrointestinal bleeding: results of the Survey to Evaluate the Application of Hemospray in the Luminal Tract. J Clin Gastroenterol 2014; 48: e89-92
  • 13 Lau JYW, Pittayanon R, Kwek A. et al. Comparison of a hemostatic powder and standard treatment in the control of active bleeding from upper nonvariceal lesions. Ann Intern Med 2021;
  • 14 Sinha R, Lockman KA, Church NI. et al. The use of hemostatic spray as an adjunct to conventional hemostatic measures in high-risk nonvariceal upper GI bleeding (with video). Gastrointest Endosc 2016; 84: 900-906.e3
  • 15 Baracat FI, de Moura DTH, Brunaldi VO. et al. Randomized controlled trial of hemostatic powder versus endoscopic clipping for non-variceal upper gastrointestinal bleeding. Surg Endosc 2020; 34: 317-324
  • 16 Chen Y-I, Wyse J, Lu Y. et al. TC-325 hemostatic powder versus current standard of care in managing malignant GI bleeding: a pilot randomized clinical trial. Gastrointest Endosc 2020; 91: 321-328.e1
  • 17 Ibrahim M, El-Mikkawy A, Abdel Hamid M. et al. Early application of haemostatic powder added to standard management for oesophagogastric variceal bleeding: a randomised trial. Gut 2019; 68: 844-853
  • 18 Leblanc S, Vienne A, Dhooge M. et al. Early experience with a novel hemostatic powder used to treat upper GI bleeding related to malignancies or after therapeutic interventions (with videos). Gastrointest Endosc 2013; 78: 169-175
  • 19 Holster IL, Kuipers EJ, Tjwa ETTL. Hemospray in the treatment of upper gastrointestinal hemorrhage in patients on antithrombotic therapy. Endoscopy 2013; 45: 63-66
  • 20 Sulz MC, Frei R, Meyenberger C. et al. Routine use of Hemospray for gastrointestinal bleeding: prospective two-center experience in Switzerland. Endoscopy 2014; 46: 619-624
  • 21 Yau AHL, Ou G, Galorport C. et al. Safety and efficacy of Hemospray® in upper gastrointestinal bleeding. Can J Gastroenterol Hepatol 2014; 28: 72-76
  • 22 Chen Y-I, Barkun A, Nolan S. Hemostatic powder TC-325 in the management of upper and lower gastrointestinal bleeding: a two-year experience at a single institution. Endoscopy 2015; 47: 167-171
  • 23 Haddara S, Jacques J, Lecleire S. et al. A novel hemostatic powder for upper gastrointestinal bleeding: a multicenter study (the “GRAPHE” registry). Endoscopy 2016; 48: 1084-1095
  • 24 Giles H, Lal D, Gerred S. et al. Efficacy and safety of TC-325 (Hemospray™) for non-variceal upper gastrointestinal bleeding at Middlemore Hospital: the early New Zealand experience. N Z Med J 2016; 129: 38-43
  • 25 Hagel AF, Albrecht H, Nägel A. et al. The Application of Hemospray in gastrointestinal bleeding during emergency endoscopy. Gastroenterol Res Pract 2017; 2017: e3083481
  • 26 Cahyadi O, Bauder M, Meier B. et al. Effectiveness of TC-325 (Hemospray) for treatment of diffuse or refractory upper gastrointestinal bleeding - a single center experience. Endosc Int Open 2017; 5: E1159-E1164
  • 27 Arena M, Masci E, Eusebi LH. et al. Hemospray for treatment of acute bleeding due to upper gastrointestinal tumours. Dig Liver Dis 2017; 49: 514-517
  • 28 Pittayanon R, Rerknimitr R, Barkun A. Prognostic factors affecting outcomes in patients with malignant GI bleeding treated with a novel endoscopically delivered hemostatic powder. Gastrointest Endosc 2018; 87: 994-1002
  • 29 Ramírez-Polo AI, Casal-Sánchez J, Hernández-Guerrero A. et al. Treatment of gastrointestinal bleeding with hemostatic powder (TC-325): a multicenter study. Surg Endosc 2019; 33: 2349-2356
  • 30 Hookey L, Barkun A, Sultanian R. et al. Successful hemostasis of active lower GI bleeding using a hemostatic powder as monotherapy, combination therapy, or rescue therapy. Gastrointest Endosc 2019; 89: 865-871
  • 31 Rodríguez de Santiago E, Burgos-Santamaría D, Pérez-Carazo L. et al. Hemostatic spray powder TC-325 for GI bleeding in a nationwide study: survival and predictors of failure via competing risks analysis. Gastrointest Endosc 2019; 90: 581-590.e6
  • 32 Alzoubaidi D, Hussein M, Rusu R. et al. Outcomes from an international multicenter registry of patients with acute gastrointestinal bleeding undergoing endoscopic treatment with Hemospray. Digest Endosc 2020; 32: 96-105
  • 33 Chahal D, Lee JGH, Ali-Mohamad N. et al. High rate of re-bleeding after application of Hemospray for upper and lower gastrointestinal bleeds. Dig Liver Dis 2020; 52: 768-772
  • 34 Hussein M, Alzoubaidi D, Lopez M-F. et al. Hemostatic spray powder TC-325 in the primary endoscopic treatment of peptic ulcer-related bleeding: multicenter international registry. Endoscopy 2021; 53: 36-43
  • 35 Hussein M, Alzoubaidi D, O’Donnell M. et al. Hemostatic powder TC-325 treatment of malignancy-related upper gastrointestinal bleeds: International registry outcomes. J Gastroenterol Hepatol 2021; 36: 3027-3032
  • 36 Becq A, Houdeville C, Tran Minh M-L. et al. Experience with the use of a hemostatic powder in 152 patients undergoing urgent endoscopy for gastrointestinal bleeding. Clin Res Hepatol Gastroenterol 2021; 45: 101558
  • 37 Facciorusso A, Bertini M, Bertoni M. Efficacy of hemostatic powders in lower gastrointestinal bleeding: Clinical series and literature review. Dig Liver Dis 2021; 53: 1327-1333
  • 38 Kwek BEA, Ang TL, Ong PLJ. et al. TC-325 versus the conventional combined technique for endoscopic treatment of peptic ulcers with high-risk bleeding stigmata: A randomized pilot study. J Dig Dis 2017; 18: 323-329
  • 39 Vitali F, Naegel A, Atreya R. et al. Comparison of Hemospray® and EndoclotTM for the treatment of gastrointestinal bleeding. World J Gastroenterol 2019; 25: 1592-1602
  • 40 Paoluzi OA, Cardamone C, Aucello A. et al. Efficacy of hemostatic powders as monotherapy or rescue therapy in gastrointestinal bleeding related to neoplastic or non-neoplastic lesions. Scand J Gastroenterol 2021; 1-8
  • 41 Ng JL, Marican M, Mathew R. Topical haemostatic powder as a novel endoscopic therapy for severe colonic diverticular bleeding. ANZ J Surg 2019; 89: E56-E60
  • 42 Chahal D, Sidhu H, Zhao B. et al. Efficacy of Hemospray (TC-325) in the treatment of gastrointestinal bleeding: an updated systematic review and meta-analysis. J Clin Gastroenterol 2021; 55: 492-498
  • 43 Hagel AF, Raithel M, Hempen P. et al. Multicenter analysis of endoclot as hemostatic powder in different endoscopic settings of the upper gastrointestinal tract. J Physiol Pharmacol 2020;
  • 44 Moosavi S, Chen YI, Barkun AN. TC-325 application leading to transient obstruction of a post-sphincterotomy biliary orifice. Endoscopy 2013; 45: E130
  • 45 Baracat FI, Tranquillini CV, Brunaldi VO. et al. Hemostatic powder: a new ally in the management of postsphincterotomy bleeding. VideoGIE 2017; 2: 303-304
  • 46 Yii RSL, Chuah KH, Poh KS. et al. Retained endoscope: an unexpected but serious complication of Hemospray® . Dig Dis Sci 2021;
  • 47 VitraMed. EndoClot® Polysaccharide Hemostatic System (EndoClot® PHS). EndoClot. https://www.vitramed.com/products/EndoClot/EndoClotPHS
  • 48 Wang Y, Xu M, Dong H. et al. Effects of PerClot® on the healing of full-thickness skin wounds in rats. Acta Histochem 2012; 114: 311-317
  • 49 Beg S, Al-Bakir I, Bhuva M. et al. Early clinical experience of the safety and efficacy of EndoClot in the management of non-variceal upper gastrointestinal bleeding. Endosc Int Open 2015; 3: E605-E609
  • 50 Prei JC, Barmeyer C, Bürgel N. et al. EndoClot polysaccharide hemostatic system in nonvariceal gastrointestinal bleeding: results of a prospective multicenter observational pilot study. J Clin Gastroenterol 2016; 50: e95-e100
  • 51 Kim YJ, Park JC, Kim EH. et al. Hemostatic powder application for control of acute upper gastrointestinal bleeding in patients with gastric malignancy. Endosc Int Open 2018; 6: E700-E705
  • 52 Hahn KY, Park JC, Lee YK. et al. Efficacy of hemostatic powder in preventing bleeding after gastric endoscopic submucosal dissection in high-risk patients. J Gastroenterol Hepatol 2018; 33: 656-663
  • 53 Huang R, Pan Y, Hui N. et al. Polysaccharide hemostatic system for hemostasis management in colorectal endoscopic mucosal resection. Digest Endosc 2014; 26: 63-68
  • 54 Park JC, Kim YJ, Kim EH. et al. Effectiveness of the polysaccharide hemostatic powder in non-variceal upper gastrointestinal bleeding: Using propensity score matching. J Gastroenterol Hepatol 2018; 33: 1500-1506
  • 55 Beyazit Y, Kekilli M, Haznedaroglu IC. et al. Ankaferd hemostat in the management of gastrointestinal hemorrhages. World J Gastroenterol 2011; 17: 3962-3970
  • 56 Haznedaroglu BZ, Haznedaroglu IC, Walker SL. et al. Ultrastructural and morphological analyses of the in vitro and in vivo hemostatic effects of Ankaferd Blood Stopper. Clin Appl Thromb Hemost 2010; 16: 446-453
  • 57 Kurt M, Onal IK, Akdogan M. et al. Ankaferd Blood Stopper for controlling gastrointestinal bleeding due to distinct benign lesions refractory to conventional antihemorrhagic measures. Can J Gastroenterol 2010; 24: 380-384
  • 58 Kurt M, Akdogan M, Onal IK. et al. Endoscopic topical application of Ankaferd Blood Stopper for neoplastic gastrointestinal bleeding: A retrospective analysis. Digest Liver Disease 2010; 42: 196-199
  • 59 Gungor G, Goktepe MH, Biyik M. et al. Efficacy of ankaferd blood stopper application on non-variceal upper gastrointestinal bleeding. World J Gastrointest Endosc 2012; 4: 556-560
  • 60 Karaman A, Baskol M, Gursoy S. et al. Endoscopic topical application of Ankaferd Blood Stopper® in gastrointestinal bleeding. J Altern Complement Med 2012; 18: 65-68
  • 61 Ozaslan E, Purnak T, Yildiz A. et al. Bleeding due to slippage of elastic band during variceal ligation: successful use of Ankaferd blood stopper. Indian J Gastroenterol 2010; 29: 166-168
  • 62 Tuncer I, Doganay L, Ozturk O. Instant control of fundal variceal bleeding with a folkloric medicinal plant extract: Ankaferd Blood Stopper. Gastrointest Endosc 2010; 71: 873-875
  • 63 Beyazit Y, Akdogan M, Sayilir A. et al. Successful topical application of Ankaferd blood stopper in a patient with life-threatening fundal variceal bleeding despite cyanoacrilate injection. Clin Res Hepatol Gastroenterol 2012; 36: e9-11
  • 64 Ibis M, Kurt M, Onal IK. et al. Successful management of bleeding due to solitary rectal ulcer via topical application of Ankaferd blood stopper. J Altern Complement Med 2008; 14: 1073-1074
  • 65 Shorbagi A, Sivri B. Successful management of a difficult case of radiation proctopathy with Ankaferd BloodStopper: a novel indication (with video). Gastrointest Endosc 2010; 72: 666-667
  • 66 Ozaslan E, Purnak T, Yildiz A. et al. The effect of Ankaferd blood stopper on severe radiation colitis. Endoscopy 2009; 41: E321-E322
  • 67 Karaman A, Torun E, Gürsoy S. et al. Efficacy of Ankaferd Blood Stopper in postpolypectomy bleeding. J Altern Complement Med 2010; 16: 1027-1028
  • 68 Aslan E, Akyüz Ü, Pata C. The use of Ankaferd in diverticular bleeding: two case reports. Turk J Gastroenterol 2013; 24: 441-443
  • 69 Turhan N, Kurt M, Shorbagi A. et al. Topical Ankaferd Blood Stopper administration to bleeding gastrointestinal carcinomas decreases tumor vascularization. Am J Gastroenterol 2009; 104: 2874-2877
  • 70 Beyazit Y, Onder FO, Torun S. et al. Topical application of ankaferd hemostat in a patient with gastroduodenal amyloidosis complicated with gastrointestinal bleeding. Blood Coagulat Fibrinol 2013; 24: 762-765
  • 71 Bang BW, Lee DH, Kim HK. et al. CEGP-003 Spray has a similar hemostatic effect to epinephrine injection in cases of acute upper gastrointestinal bleeding. Dig Dis Sci 2018; 63: 3026-3032
  • 72 Bang B, Lee E, Maeng J. et al. Efficacy of a novel endoscopically deliverable muco-adhesive hemostatic powder in an acute gastric bleeding porcine model. PLoS One 2019; 14: e0216829
  • 73 Medtronic. NexpowderTM* Endoscopic Hemostasis System. https://www.medtronic.com/covidien/en-gb/products/therapeutic-endoscopy/nexpowder-endoscopic-hemostasis-system.html
  • 74 Park J-S, Bang BW, Hong SJ. et al. Efficacy of a novel hemostatic adhesive powder in patients with refractory upper gastrointestinal bleeding: a pilot study. Endoscopy 2019; 51: 458-462
  • 75 Park J-S, Kim HK, Shin YW. et al. Novel hemostatic adhesive powder for nonvariceal upper gastrointestinal bleeding. Endosc Int Open 2019; 7: E1763-E1767
  • 76 Shin J, Cha B, Park J-S. et al. Efficacy of a novel hemostatic adhesive powder in patients with upper gastrointestinal tumor bleeding. BMC Gastroenterol 2021; 21: 40
  • 77 Baylis JR, Yeon JH, Thomson MH. et al. Self-propelled particles that transport cargo through flowing blood and halt hemorrhage. Sci Adv 2015; 1: e1500379
  • 78 Baylis JR, Finkelstein-Kulka A, Macias-Valle L. et al. Rapid hemostasis in a sheep model using particles that propel thrombin and tranexamic acid. Laryngoscope 2017; 127: 787-793
  • 79 Baylis JR, St John AE, Wang X. et al. Self-propelled dressings containing thrombin and tranexamic acid improve short-term survival in a swine model of lethal junctional hemorrhage. Shock 2016; 46: 123-128
  • 80 Baylis JR, Lee MM, St John AE. et al. Topical tranexamic acid inhibits fibrinolysis more effectively when formulated with self-propelling particles. J Thromb Haemost 2019; 17: 1645-1654
  • 81 Ali-Mohamad N, Cau M, Baylis J. et al. Severe upper gastrointestinal bleeding is halted by endoscopically delivered self-propelling thrombin powder: A porcine pilot study. Endosc Int Open 2021; 9: E693-E698
  • 82 Masuhara H, Fujii T, Watanabe Y. et al. Novel infectious agent-free hemostatic material (TDM-621) in cardiovascular surgery. Ann Thorac Cardiovasc Surg 2012; 18: 444-451
  • 83 PuraStat®. 3-D Matrix. https://3dmatrix.com/products/purastat/
  • 84 Subramaniam S, Kandiah K, Chedgy F. et al. A novel self-assembling peptide for hemostasis during endoscopic submucosal dissection: a randomized controlled trial. Endoscopy 2021; 53: 27-35
  • 85 Branchi F, Klingenberg-Noftz R, Friedrich K. et al. PuraStat in gastrointestinal bleeding: results of a prospective multicentre observational pilot study. Surg Endosc 2022; 36: 2954-2961
  • 86 White K, Henson CC. Endoscopically delivered Purastat for the treatment of severe haemorrhagic radiation proctopathy: a service evaluation of a new endoscopic treatment for a challenging condition. Frontline Gastroenterol 2021; 12: 608-613
  • 87 Yoshida M, Goto N, Kawaguchi M. et al. Initial clinical trial of a novel hemostat, TDM-621, in the endoscopic treatments of the gastric tumors. J Gastroenterol Hepatol 2014; 29: 77-79
  • 88 de Nucci G, Reati R, Arena I. et al. Efficacy of a novel self-assembling peptide hemostatic gel as rescue therapy for refractory acute gastrointestinal bleeding. Endoscopy 2020; 52: 773-779