Endoscopic hemostatic powder spray: Current evidence and clinical applications

Abstract

Hemostatic powder, as an emerging endoscopic hemostatic technique, has demonstrated significant potential in the management of gastrointestinal bleeding (GIB). It offers advantages such as ease of operation and a generally favorable safety profile in the reported studies, particularly in complex anatomy, unclear visual fields, or locations where conventional hemostatic methods are difficult to apply. However, there remains a lack of systematic understanding regarding the specific characteristics and applicable scope of different hemostatic powders. This article reviews existing clinical studies on commonly used hemostatic powders in GIB-related diseases, comprehensively summarizing their current applications, efficacy, and safety profiles. This review highlights the distinct mechanisms and clinical niches for different powders, proposing a stratified management approach for their use. However, its technical characteristics and operator dependency mean that it should be used cautiously in certain high-risk bleeding scenarios, or as part of a combined hemostatic strategy rather than as a first-line monotherapy.

Key Words: Gastrointestinal bleeding; Endoscopic hemostasis; Endoscopy; Hemostatic powder; Hemospray

Core Tip: Hemostatic powder is an emerging endoscopic modality for gastrointestinal bleeding that enables rapid, technically simple hemostasis in difficult or anatomically complex bleeding sites. Given the uneven, largely observational evidence base, it is best positioned as a rescue, bridging, or adjunctive option in selected scenarios rather than routine first-line monotherapy. This minireview compares the mechanisms and clinical evidence of available powders and proposes a provisional recommendation.

INTRODUCTION

Gastrointestinal bleeding (GIB) is a common acute and critical condition in clinical practice. Its typical clinical manifestations include hematemesis, melena, and hematochezia, often accompanied by signs of hemodynamic instability, such as hypotension and tachycardia. Severe cases can be life-threatening[1]. Although the overall incidence of GIB has declined slightly, upper GIB (UGIB) still exhibits a notably high incidence rate of 15.0-172.0 per 100000 person-years. The incidence of lower GIB (LGIB) ranges from 20.5 to 87.0 per 100000 person-years[2]. GIB can result from a diverse array of underlying diseases or factors, including peptic ulcer disease, esophagogastric varices, malignancy, diverticular disease, the use of antiplatelet and anticoagulant agents, and complications following surgical or endoscopic procedures[3,4]. Among these causes, bleeding from peptic ulcers and diverticular bleeding are the most common sources, accounting for approximately 32%-36% and 26%-33% of cases, respectively[4].

With the continuous advancement of endoscopic techniques, the primary methods for achieving endoscopic hemostasis can be broadly classified into injection therapy (epinephrine or sclerosant), mechanical therapy (hemostatic clip or band ligation), and thermal therapy (coagulation forceps), among others[5]. Traditional endoscopic therapies possess several limitations. For instance, thermal coagulation techniques increase the risk of complications such as perforation and post-polypectomy coagulation syndrome when applied to relatively thin-walled areas of the bowel. Furthermore, devices like clips are unsuitable for fibrotic tissue or complex anatomical structures. A proportion of patients experience initial hemostasis failure or recurrent bleeding[6]. In addition, certain bleeding lesions are challenging to manage due to complex anatomy, limited endoscopic visibility, or fragile tissue. For such lesions, conventional hemostatic techniques not only demand considerable technical expertise but also carry a higher risk of failure[7].

The advent and application of hemostatic powders have provided a novel option for endoscopic hemostasis. Characterized by ease of application and a favorable safety profile, hemostatic powders serve as both a salvage therapy following rebleeding and a prophylactic measure. Furthermore, hemostatic powders exhibit promising potential in surgery and for managing bleeding associated with other disease processes[8-10]. The use of hemostatic powder may reduce technical dependency, and current endoscopy-specific guidelines suggest it as a temporizing or rescue option for selected bleeding scenarios[1,11,12]. Their ease of application may reduce technical dependence and has been proposed as a potential emergency alternative in settings with limited endoscopic expertise; however, available studies were conducted in endoscopy-equipped centers, and their feasibility and outcomes in primary care or low-endoscopy-capacity institutions remain to be established. To date, multiple hemostatic powders with distinct mechanisms of action have been developed and have undergone separate clinical investigations, as summarized in Tables 1 and 2.

Table 1 Characteristics of commercially available and investigational hemostatic powders.

	Composition	Mechanism of action	Delivery system	Biodegradability and clearance	Advantages	Limitations
TC-325 (Hemospray®)	Inert mineral powder	Absorbs liquid, concentrates clotting factors, and forms a mechanical barrier	High-pressure CO2 cartridge	Non-absorbable and excreted	Broad coverage; effective for diffuse bleeding	Perforation risk with high CO2 pressure; catheter clogging
EndoClot®	Absorbable modified polymer	Absorbs liquid and accelerates the physiological coagulation cascade	Air compressor	Absorbable and degrades within 3 days	Low delivery pressure	Slow spraying; catheter clogging
Ankaferd Blood Stopper®	Standardized plant extracts	RBC aggregation, largely independent of classic coagulation	Syringe via catheter	Absorbable and excreted	Plant-derived; animal data suggest anti-infective, wound-healing-promoting, and antitumor activity	Limited clinical evidence
UI-EWD (NexPowder™)	Oxidized dextran and amino acid derivative	Forms highly adhesive hydrogel upon hydration	Integrated low-pressure air pump	Non-absorbable; excreted in about 66 hours	Employing liquid coating technology via a fluidized bed granulator; strong adhesion and good durability	Evidence primarily from Korean cohorts
CEGP-003 (CG-Bio)	Absorbable macromolecule with EGF	Forms gel and releases EGF	Alto-shooter gun system	Absorbable	Combined hemostatic and wound-healing functions	Limited clinical evidence
Self-Propelling Thrombin Powder	CaCO3, thrombin, tranexamic acid	CO2-bubble propelled; activates coagulation	CO2 pump	Absorbable	Self-propelled; against blood flow; suitable for pulsatile bleeding	Just preclinical and early-stage research
Polysaccharide Hemostatic Powder	Plant starch and carboxymethyl chitosan	Absorbs liquid and activates intrinsic coagulation factors	Air compressor	Absorbable	Rapid hemostasis; simple operation	Catheter clogging reported

EGF: Epidermal growth factor; RBC: Red blood cell; CO₂: Carbon dioxide; CaCO₃: Calcium carbonate.

Table 2 Summary of reported hemostasis and rebleeding rates of hemostatic powders by clinical scenario.

	Indication	Highest hemostasis rate, %	Lowest rebleeding rate, %	Reported study designs	Remarks
TC-325 (Hemospray®)	NVUGIB	100	2.1	Prospective[22,26], retrospective[19,20,21,34]	Hemostatic rate varies slightly across studies but remains generally high
	Variceal Bleeding	100	0	Prospective[15,16,18,48], case[13,17]	Demonstrates high hemostatic success rates as bridging therapy in emergency settings
	Peptic Ulcer Bleeding	95	15	Prospective[14,23,24], retrospective[25]	Not recommended as monotherapy, particularly to be avoided in Forrest Ia lesions
	Tumor Bleeding	100	2.1	Prospective[32,33], retrospective[28,35], case[29,30,43,44,46]	Highly effective for tumor oozing in palliative or bridging therapy, but limited sample size
	GIB in children	100	12	Prospective[38], retrospective[39], case[40]	Just performs well in small-scale studies but requires confirmation in larger trials
	Post-procedural Bleeding	100	0	Case[31,41,42,45]	Performs well in small-scale studies, requires confirmation in larger trials
	Diverticular bleeding	100	0	Retrospective[47]	Limited evidence but effective in selected cases
EndoClot®	GIB	86	11.4	Prospective[50,52], retrospective[53]	Hemostatic rate is stable
	Post-EMR Bleeding	78	4.7	Prospective[55]	Applicable in both prophylaxis and treatment of procedure-related bleeding
	Diverticular bleeding	100	0	Case[56]	Performs well in small-scale studies but requires confirmation in larger trials
Ankaferd Blood Stopper®	GIB	100	0	Prospective[61], retrospective[62], case[65]	Existing studies involve small sample sizes, although reported hemostatic rates are high
UI-EWD (NexPowder™)	NVUGIB	97	3.7	Prospective[71], retrospective[70,74]	High immediate hemostasis in a large Korean cohort
	LGIB	100	5.5	Retrospective[72,73]	Immediate hemostasis is high, but evidence is limited
	Tumor Bleeding	100	26.1	Retrospective[68], case[69]	Limited sample size but reported hemostatic rates are high
CEGP-003 (CG-Bio)	UGIB	100	8.6	Prospective[75,76]	Existing studies have relatively small sample sizes, but reported hemostasis rates are high
Polysaccharide Hemostatic Powder	GIB	100	0	Prospective[81,82,83]	Higher hemostatic rates achieved in Forrest IIa lesions
	Post-procedural Bleeding	100	0	Prospective[84,87,88,89], retrospective[86], case[80]	Well-documented and highly effective for post-ESD/EST bleeding

EMR: Endoscopic mucosal resection; ESD: Endoscopic submucosal dissection; EST: Endoscopic sphincterotomy; GIB: Gastrointestinal bleeding; LGIB: Lower gastrointestinal bleeding; NVUGIB: Non-variceal upper gastrointestinal bleeding; UGIB: Upper gastrointestinal bleeding.

In recent years, several reviews and clinical guidelines have summarized the use of topical endoscopic hemostatic agents, but most have focused on conventional products or specific bleeding etiologies, with insufficient attention paid to novel agents and the risk of bias in small‑sample studies. This review broadened the literature search to include more study types, such as case reports and animal experiments, aiming to provide a more comprehensive reference for clinical decision‑making and future research.

METHODOLOGY/SEARCH STRATEGY

In March 2026, we performed a comprehensive literature search in PubMed, Web of Science, and the China National Knowledge Infrastructure (CNKI) using the following search terms: “hemostatic powder”, “Hemospray”, “TC-325”, “EndoClot^®”, “polysaccharide hemostatic powder”, “UI-EWD”, “CEGP-003”, “Ankaferd Blood Stopper^®”, “self-propelling thrombin powder”, “gastrointestinal bleeding”, “upper/lower gastrointestinal bleeding”, “variceal bleeding”, “peptic ulcer bleeding”, “tumor bleeding”, “post-endoscopic procedure bleeding”, and “coagulopathy”. These terms were combined using Boolean operators (AND/OR). The included study types comprised randomized controlled trials, multicenter or registry studies, prospective/retrospective cohorts, case series, case reports, and mechanism‑related animal studies. Conference abstracts, unpublished data, and preprints were not used as primary sources of evidence in this review.

We defined the review scope by product, population, and outcome. Products included all hemostatic powders evaluated for gastrointestinal endoscopy. The population covered patients with GIB of any etiology. Outcomes comprised immediate hemostasis, rebleeding at various intervals, need for rescue therapy, adverse events, and mortality. Animal studies were considered only if mechanistically informative.

TC-325 (Hemospray^®)

TC-325, a non-absorbable inert mineral powder, is propelled by a carbon dioxide (CO₂)-pressurized cartridge and sprayed onto the hemorrhagic area[13]. TC-325 possesses strong absorptive properties. Upon contact with moisture or tissue fluids from the wound, it rapidly dehydrates blood and transforms into a gel-state film coating that adheres to the wound surface. This achieves both hemostasis and early-stage mucosal protection. It demonstrates favorable safety profiles, as its minimal absorption and metabolism by mucosal tissues contribute to low toxicity[14].

TC-325 has demonstrated significant potential in the treatment of acute variceal bleeding (AVB). In a randomized controlled study involving 86 patients with AVB, clinical hemostatic failure occurred in 5/43 patients receiving TC-325 added to standard therapy vs 13/43 receiving standard therapy alone (12% vs 30%, P = 0.034)[15]. In the study by Ibrahim et al[16], TC-325 was administered to nine patients with AVB. The results demonstrated immediate hemostasis in all cases, with no incidence of rebleeding within 24 hours. Furthermore, of note, a case report demonstrated the successful use of TC-325 in the treatment of rectal variceal bleeding associated with alcoholic cirrhosis. During a follow-up period of up to six months post-procedure, no rebleeding was observed[17]. Although this observation is derived from a single case report and requires confirmation, this suggests that TC-325 may be applicable for hemostasis in scenarios beyond its conventional indications. For certain variceal bleeds at special anatomical sites, TC-325 could potentially serve as an effective alternative or bridging therapeutic option. TC-325 has also demonstrated promising efficacy in the treatment of non-variceal upper GIB (NVUGIB)[18,19]. Studies have shown that compared to conventional therapeutic approaches, TC-325 not only achieves a higher rate of initial hemostasis but also reduces the number of required interventions, shortens the treatment duration, and lowers overall treatment costs[20]. Notably, in the management of NVUGIB, TC-325 appears particularly suitable for high-risk cases, serving as a temporary hemostatic measure or a bridging modality to gain time for subsequent definitive treatment[21,22].

In a randomized controlled trial conducted by Kwek et al[23], the efficacy of TC-325 monotherapy was compared with the conventional combined technique of saline adrenaline injection followed by a mechanical clip or heater probe for the treatment of bleeding peptic ulcers. The results showed a rebleeding rate of 33.3% (3/9) in the TC-325 monotherapy group. Although this study had a small sample size, its findings provided critical clues regarding the potential scope of TC-325 in future clinical practice, suggesting that it may be more suitable as an adjunctive therapy or for specific patient subgroups in the management of ulcerative bleeding. Subsequently, a prospective study involving 202 patients demonstrated that TC-325 achieved an immediate hemostasis rate of 88% (178/202) across all types of peptic ulcer bleeding; it yielded even more favorable outcomes—particularly in terms of immediate hemostasis, rebleeding, and mortality rates—when combined with other endoscopic therapeutic modalities. These findings confirm the role of TC-325 as a valuable component of combination therapy for controlling peptic ulcer bleeding[24]. In addition to the aforementioned studies, a retrospective study further examined the role of TC-325 as an adjunctive treatment. The results indicated that when used as an adjunct to conventional therapy, TC-325 could help reduce the rebleeding rate in certain high-risk patients; it appeared to be particularly suitable for anatomical locations where conventional hemostatic techniques are difficult to apply[25]. The multicenter study by Haddara et al[26] demonstrated that, despite a 96.5% (195/202) immediate hemostasis rate in peptic ulcer bleeding, the rebleeding rate in Forrest Ia ulcers was 66.7% (10/15), making TC-325 unsuitable as a first-line therapy for this specific bleeding subtype. Conversely, TC-325 reveals superior efficacy in Forrest Ib ulcers, achieving an immediate hemostasis rate of up to 100% and a rebleeding rate of 11.5% (2/19)[14].

The incidence of bleeding from gastrointestinal malignancies has been increasing annually, while conventional hemostatic methods have shown suboptimal efficacy in such settings[27]. Consequently, researchers have evaluated the application of TC-325 in this context and observed favorable clinical outcomes[28-31]. In a pilot randomized trial of 20 patients with malignant GI bleeding, immediate hemostasis was achieved in 90% of patients treated with TC-325 vs 40% with standard endoscopic care (P = 0.057); recurrent bleeding within 180 days occurred in 20% vs 60% (P = 0.170)[32]. Another multicenter randomized trial of 106 patients, immediate hemostasis was achieved in 55/55 (100%) patients receiving TC-325 vs 35/51 (68.6%) receiving standard endoscopic treatment, and the 30-day rebleeding rate was significantly lower with TC-325 [1/48 (2.1%) vs 10/47 (21.3%); P = 0.003]. All 15 patients who crossed over to TC-325 after failed standard treatment achieved hemostasis[33]. These findings confirm that TC-325 can serve as a bridging therapeutic option when initial hemostasis is not feasible[26,34]. Among 15 patients with malignant GI bleeding, 12 died within 30 days of TC‑325 use, mostly due to cancer progression rather than the treatment; thus, TC‑325 may be a minimally invasive palliative option[35].

In pediatric critical care, although the overall incidence of GIB is lower than in adults, approximately 6.4%, its clinical course can be more fulminant. Once acute massive hemorrhage occurs, it rapidly becomes life-threatening, with a mortality rate as high as 21%. This underscores the need for extremely timely intervention[36]. Additionally, the pediatric gastrointestinal tract is characterized by a narrow lumen and delicate tissue, rendering conventional endoscopic hemostatic techniques technically challenging and associated with a higher risk. These factors impose significant limitations on their application in this population[37]. Against this background, TC-325 offers a potential therapeutic strategy for reducing mortality associated with GIB in children. In one comparative study, it achieved initial hemostasis, with rebleeding in 18% (3/17) vs 24% (7/29) with conventional endoscopic therapy (P = 0.69)[38]. Similarly, a retrospective series of children reported 100% (23/23) initial hemostasis, a 13% (3/23) rebleeding rate, and no adverse events[39]. In a notable case, an 11-month-old infant who continued to experience severe bleeding despite prophylactic treatment with octreotide and pantoprazole, the application of TC-325 achieved rapid hemostasis. This case highlights its clinical value in the management of special, refractory conditions[40]. Several small series and a case report have reported favorable hemostatic outcomes in children[38-40]; however, these data are preliminary, the comparison was not statistically significant, and confirmation in larger pediatric studies is required.

Beyond the studies mentioned above, multiple clinical case reports have also indicated that TC-325 demonstrates effective hemostasis in complex or high-risk bleeding scenarios where conventional hemostatic methods prove difficult to apply. For instance, following endoscopic sphincterotomy, when conventional clipping failed to achieve hemostasis, the application of TC-325 successfully controlled the bleeding without subsequent rebleeding or secondary biliary obstruction[41,42]. In a patient on long-term dual antiplatelet therapy following coronary stent implantation, bleeding from a giant gastrointestinal stromal tumor failed to respond to three sessions of conventional endoscopic hemostasis, but immediate hemostasis was ultimately achieved following the application of TC-325[43]. In a patient with a giant gastrointestinal stromal tumor located in the gastric fundus, the anatomical position and morphology precluded the use of metallic clips, while both thermal coagulation and epinephrine spray showed limited efficacy. Hemostasis was effectively achieved following treatment with TC-325 spray, with no recurrent bleeding observed during a 10-day follow-up period[44]. Additionally, TC-325 has also demonstrated favorable efficacy in managing delayed bleeding following polypectomy[45]. These cases collectively indicate the therapeutic potential of TC-325 in scenarios involving complex anatomical sites, high bleeding risk, or limitations of conventional approaches. Further studies suggest that it may also emerge as a novel therapeutic option for severe diverticular bleeding and small bowel hemorrhage; however, its definitive efficacy warrants confirmation through large-sample, prospective, controlled trials[46,47].

Previous studies have reported no serious adverse events or mortality during the 15-day follow-up period after its application[16,48]. As TC-325 delivers powdered hemostatic agent onto the wound surface via a high-pressure CO₂ cartridge, it generates elevated intraluminal pressure during application. Consequently, this mode of administration carries potential risks of procedure-related perforation, mucosal injury, or diverticulum formation, although their occurrence is relatively infrequent[49]. Catheter clogging may also occur during use; therefore, selecting a catheter with an appropriate diameter based on practical needs is recommended during the procedure[26].

In summary, TC-325 combines efficacy with safety, demonstrating excellent immediate hemostatic capability and low rebleeding rates across various GIB scenarios. It remains a viable adjunctive option in specific endoscopic hemostasis settings, notwithstanding the variable evidence base.

EndoClot^®

EndoClot^® is a powder formulation containing absorbable hemostatic polysaccharides, which is delivered to the wound site via a dedicated catheter with the assistance of a continuous airflow. This airflow is generated by a connected compressor, ensuring uniform distribution of the powder and preventing premature coagulation within the catheter[50,51]. The hemostatic mechanism of EndoClot^® parallels that of TC-325. Upon application, its contained absorbable modified polymer (AMP) particles absorb moisture from the wound surface, thereby concentrating local coagulation factors, platelets, and red blood cells. This accelerates the physiological coagulation cascade and promotes the formation of an adherent gel-like mechanical barrier over the wound[52]. As a modified starch polysaccharide, EndoClot^® is free from human- or animal-derived proteins and possesses low allergenic potential. Studies have shown that EndoClot^® typically detaches from the wound site within three days without leaving residual eschar. The AMP particles it contains can be easily rinsed away with saline irrigation. Therefore, if hemostatic efficacy is suboptimal, the powder can be reapplied[53].

EndoClot^® achieves favorable outcomes in treating GIB, with an immediate success rate of 39/56 following initial application. However, 17/56 of patients required additional treatment after the initial application, and its overall hemostatic rate is slightly lower compared to that of TC-325[50]. In patients undergoing endoscopic mucosal resection and endoscopic submucosal dissection (ESD), the most common complications are intraoperative bleeding and delayed postoperative bleeding[54]. For immediate postprocedural bleeding, EndoClot^® achieves rapid and effective hemostasis, and follow-up examination at 30 days showed wound healing[55].

EndoClot^® also demonstrates potential in the management of diverticular bleeding. Grassia et al[56] reported a case of severe colonic diverticular hemorrhage successfully treated by filling the diverticulum with EndoClot^®. This suggests that for small, deep diverticular bleeding, hemostatic powder filling may serve as a simple and effective hemostatic strategy, yet whether it is comparable to mechanical clip closure requires further study.

No procedure-related adverse events were reported in the current study. During application, the catheter tip should be maintained at a sufficient distance from the bleeding site to prevent catheter clogging[50,51]. Notably, EndoClot^® powder is delivered via a catheter using compressor-generated airflow. This process is characterized by a slow application rate and low intracavitary pressure. Therefore, for lesions with suspected concealed perforation or deep wounds, EndoClot^® is recommended over TC-325[53].

Ankaferd Blood Stopper^®

Ankaferd Blood Stopper^® (ABS) is a novel natural hemostatic agent composed of extracts from several traditional medicinal plants, including Thymus vulgaris, Glycyrrhiza glabra, Vitis vinifera, Alpinia officinarum, and Urtica dioica[57]. In addition to its hemostatic effects, ABS has been demonstrated to possess multiple biological activities, including antitumor, antibacterial, anti-inflammatory, and tissue-healing promotion properties in vitro. The hemostatic mechanism of ABS differs from the traditional coagulation pathway; it primarily induces the formation of a network through erythrocyte aggregation, mediated by fibrinogen gamma chains, to seal the wound. This unique mechanism allows ABS to manage refractory bleeding where conventional hemostatic methods may fail[57-60].

In a prospective trial involving 30 patients with GIB of diverse etiologies, ABS achieved a hemostatic success rate of 26/30 (87%). No rebleeding occurred in any patient during the observation period[61]. ABS also demonstrated efficacy in cases refractory to conventional hemostatic methods. A retrospective study involving 26 such patients reported successful immediate hemostasis in all cases[62].

Experimental studies have examined the effects of orally administered high-dose Ankaferd on the gastrointestinal tract[63]. As its mechanism does not depend on activation of coagulation factors, a lower thrombotic risk has been hypothesized; no procedure-related thrombotic events were reported in the available studies[64]. Although a single case report documented the occurrence of a gastrointestinal perforation on the third day following its application, this event was primarily attributed to the progression of the patient’s underlying gastroduodenal amyloidosis rather than to the agent itself[65].

UI-EWD (NexPowder^™)

UI-EWD (NexPowder^™) is formulated from biocompatible natural polymers, oxidized dextran, and succinic acid-modified amino acids. Upon aqueous exposure, the powder undergoes instantaneous cross-linking via a Schiff base reaction, resulting in the formation of a strongly adhesive hydrogel[66]. Employing liquid coating technology via a fluidized bed granulator, UI-EWD prevents catheter occlusion and powder dispersion during delivery to the bleeding sites, thereby ensuring unimpeded endoscopic procedures[67]. Its specially designed spraying apparatus also facilitates layered accumulation of the powder. The main air pump continuously expels the powder at a pressure of 9 psi, enabling uniform application and precise control over the spraying duration[68]. In terms of application, the UI-EWD hydrogel adheres to most ulcers for over 18 hours, with an adhesion rate of approximately 80%. By 42 hours, the adhesion rate remains at approximately 50%. These results further indicate the significant hemostatic potential of UI-EWD[66].

Bleeding from tumors often leads to rebleeding when treated with conventional endoscopic techniques. This phenomenon is associated with factors such as tumor size, tissue friability, pathological angiogenesis, or tumor-induced necrosis[67]. In a retrospective series of 41 patients with tumor bleeding, UI-EWD achieved immediate hemostasis in 97.5% overall (100% with monotherapy, n = 23), but 28-day rebleeding reached 22.5%; therefore, its efficacy needs prospective confirmation[68]. A case report described successful hemostasis with a hemostatic powder in a patient with active bleeding from a malignant lesion, suggesting feasibility, although single-case observations cannot support quantitative efficacy data[69].

A multicenter retrospective study enrolling 135 patients with GIB indicated that UI-EWD was effective for managing peptic ulcer bleeding, delayed post-operative bleeding, and tumor bleeding, achieving success rates of up to 97%[70]. 72-hour rebleeding (2.9% vs 11.3%, P = 0.005) and the 30-day cumulative rebleeding rate (7.0% vs 18.8%) were significantly reduced (5.5% vs 17%, P = 0.04)[71]. A retrospective study also reported a lower 28-day rebleeding rate with UI-EWD than with conventional therapy alone (n = 112; 5.5% vs 17%, P = 0.039)[72].

LGIB accounts for approximately 20% of all GIB cases and is less common than UGIB, yet it is still associated with a certain mortality rate. In the hemostatic management of refractory lower GIB, data on UI-EWD are mainly from retrospective, single-center studies, which have reported high immediate hemostasis rates[73]. Beyond this, evidence suggests that UI-EWD may serve as a primary option for initial hemostasis in cases of post-polypectomy bleeding where conventional endoscopic methods, such as clips or thermal therapy, are ineffective or contraindicated[72,74].

In terms of safety, UI-EWD contains no human- or animal-derived components. This material is not absorbed by the body and is excreted via the small intestine approximately 66 hours after ingestion[66]. Clinically, UI-EWD demonstrated a favorable safety profile. Although catheter clogging occurred in two patients during application, no powder-related adverse events were reported[74].

CEGP-003

CEGP-003 (CG-Bio) is a hemostatic material composed of absorbable macromolecules containing epidermal growth factor. Similar to other hemostatic powders, it functions by binding with moisture at the wound site to form a gel-like covering layer. This layer isolates the wound from digestive fluid erosion while effectively inducing hemostasis and promoting tissue healing. The material is delivered via a dedicated Alto-shooter gun. This delivery system consists of a main body housing the powder, a 10-Fr delivery catheter, and a gas-powered activation device, facilitating precise endoscopic application[75].

Studies have demonstrated that CEGP-003 provides reliable hemostatic efficacy, comparable to that of epinephrine injection. It achieved an initial hemostasis rate of 100% (35/35) vs 89.2% (34/37) for epinephrine (P = 0.115), with a rebleeding rate of approximately 8.6%[75]. A multicenter, large-sample prospective trial further confirmed its clinical potential as an initial hemostatic modality [96.3% (104/108) vs 91.8% (101/110), P = 0.252]. However, the rebleeding rate was 14.4%, and the trial results indicated that using CEGP-003 as initial hemostatic treatment should be carefully monitored for rebleeding after initial treatment[76]. Current clinical evidence on the use of CEGP-003 for GIB remains limited, and no associated adverse events have been reported in the published literature to date.

Self-propelling thrombin powder

Self-propelling thrombin powder (SPTP), a powder composed of calcium carbonate microparticles, thrombin, and tranexamic acid, reacts with blood to generate CO₂. These bubbles facilitate the propulsion of thrombin and tranexamic acid through the blood, thereby triggering the coagulation cascade and inhibiting fibrinolysis[77]. The generated bubbles propel the powder against the bloodstream towards the bleeding source, making it particularly suitable for diffuse bleeding. SPTP demonstrated effective hemostatic efficacy in animal models, where 3-5 g of powder successfully treated Forrest Ib ulcer bleeding with no rebleeding observed over 3 days[78]. Ali-Mohamad et al[79] demonstrated that the hemostatic efficacy of SPTP for Forrest Ia bleeding was comparable to that for Forrest Ib in a porcine model. This study provides preliminary evidence for the potential of SPTP in managing critical GIB. Furthermore, its mechanism of action may address the limitation of current hemostatic powders being easily washed away or proving ineffective in cases of active arterial hemorrhage; this remains hypothetical and requires clinical confirmation.

To date, the hemostatic efficacy of SPTP for GIB has been validated predominantly in animal models. Its clinical translation and practical application outcomes still await confirmation by future studies.

Polysaccharide Hemostatic Powder

Polysaccharide Hemostatic Powder (PHP) is primarily composed of a complex of plant-derived starch and carboxymethyl chitosan. It is prepared from purified plant starch via an emulsification-crosslinking process. The powdered material induces aggregation of platelets, red blood cells, and fibrin on the particle surfaces, leading to the formation of a highly concentrated aggregate that generates an “instant gel”. Concurrently, it activates intrinsic coagulation factors, thereby contributing to hemostasis[80,81].

PHP demonstrates favorable hemostatic efficacy in managing GIB across various underlying etiologies[81]. A prospective trial involving 216 patients indicated that for peptic ulcer bleeding, PHP is non-inferior to conventional hemostatic methods. Notably, an initial hemostasis success rate of 100% (P = 0.023) was achieved in Forrest IIa patients[82]. Furthermore, PHP achieves favorable hemostatic outcomes even in patients with Forrest I lesions[83]. Although hemostasis for post-endoscopic sphincterotomy bleeding poses a technical challenge when using a side-viewing duodenoscope due to complex anatomy and suboptimal visualization, PHP demonstrates excellent efficacy in this setting. Significant results were observed in terms of immediate hemostasis rate (100% vs 92.3%, P = 0.022), time to hemostasis (50.77 s vs 62.81 s, P = 0.011), and overall treatment success rate (100% vs 90.4%; P = 0.022)[84].

The most common complications following endoscopic polypectomy are intraprocedural and postprocedural bleeding[85]. Multiple studies have confirmed that PHP demonstrates effective hemostasis, rapid time to hemostasis, and a significant reduction in procedure time, while also markedly lowering the incidence of postprocedural rebleeding[86-88]. Small single‑center studies have reported varied roles for PHP in endoscopic resection. In colorectal polypectomy/ESD and gastric ESD, intraprocedural PHP achieved 100% hemostasis (vs 93% without) and eliminated delayed bleeding (0 vs 4/84)[86]. In upper GI ESD, PHP reduced delayed rebleeding compared with thrombin powder (0 vs 4 cases, P < 0.05)[87], and a gastric ESD trial showed prophylactic PHP significantly decreased delayed bleeding with comparable ulcer healing[88]. Given the heterogeneous study designs, procedure types, and roles, these results cannot be pooled.

Compared to TC-325, it is delivered via an air compressor, utilizing relatively lower pneumatic pressure, which reduces the risk of tissue injury and perforation[82,83]. Catheter occlusion events were observed during use. No serious adverse events other than catheter occlusion were reported in this study[89].

Others

Beyond those discussed above, several additional hemostatic powders have also demonstrated efficacy in the management of GIB. We did not discuss additional hemostatic powders in detail because the published evidence was limited to case reports, small series, or preclinical data[90].

CONCLUSION

As an emerging endoscopic hemostatic technique, hemostatic powder is characterized by its ease of operation and high safety profile. It is suitable for bleeding sites with anatomical complexities, limited visual fields, or locations difficult to manage with conventional methods, thereby revising the emergency management paradigm for gastrointestinal hemorrhage. The use of hemostatic powder significantly reduces technical dependency, has been proposed as a potential emergency option for primary medical institutions, and has been recommended in guidelines across multiple countries[1,11,12]. Current studies indicate that hemostatic powder is widely employed in cases such as esophageal variceal bleeding, malignant tumor bleeding, delayed postprocedural bleeding after endoscopic therapy, and peptic ulcer bleeding, demonstrating both high hemostatic efficacy and a favorable safety profile. Figure 1 visually illustrates the application of hemostatic powder for different types of GIB.

Figure 1 Conceptual schematic diagram. The application of hemostatic powder for different types of gastrointestinal bleeding.

TC-325 primarily relies on its strong physical water-absorbing and concentrating properties to achieve mechanical blockade. This process is independent of the patient’s intrinsic coagulation function and has been hypothesized to be particularly useful in patients with coagulopathies, such as those on anticoagulant therapy. EndoClot^® rapidly expands in volume upon absorbing moisture, forming a highly viscous gel. This gel layer is flexible and adheres well to tissues; however, its efficacy may be reduced in patients with poor coagulation function. PHP, a pure plant-based absorbable polysaccharide, can form a stable matrix network that reinforces and stabilizes the developing blood clot. The mechanism of action of ABS is the most distinctive—it induces protein aggregation to form a protein mesh, a property hypothesized to preserve efficacy in patients with coagulation disorders, although direct human evidence is limited. UI-EWD solidifies via a Schiff base reaction, forming multiple crosslinks both within the hydrogel and at the hydrogel-tissue interface, thereby achieving strong adhesion. This mechanism minimizes airborne dispersion during application. In contrast, CEGP-003 incorporates active components such as growth factors into its hemostatic barrier, aiming to synergistically promote the transition from hemostasis to wound healing. For acute bleeding in patients on potent anticoagulants or with poor coagulation status, hemostatic powders whose action is independent of the coagulation cascade, such as TC-325 or ABS, may be considered on mechanistic grounds. For oozing bleeding from routine surgical wounds in patients with essentially normal coagulation function, polysaccharide-based hemostatic powders such as EndoClot^®, PHP, or UI-EWD can provide effective hemostasis while leveraging the additional benefits of biomaterials. In cases of chronic ulcers or wounds requiring enhanced healing, composite products with prohealing functions may offer greater long-term advantages.

As an emerging endoscopic hemostatic technique, hemostatic powder still has certain limitations in clinical application. In clinical practice, the success of endoscopic hemostasis is determined primarily by the characteristics of the bleeding source, the patient's comorbidities and medication use, and the availability of appropriate instruments, rather than by the choice of any single hemostatic modality. For most patients with GIB, definitive hemostasis can be achieved with conventional endoscopic techniques. Hemostatic powders should therefore be positioned as an additional hemostatic option, reserved mainly for carefully selected scenarios such as diffuse oozing bleeding, tumor-related bleeding, delayed postprocedural bleeding, and anatomically inaccessible sites, where they may serve as a rescue, bridging, or adjunctive therapy rather than as a routine or first-line strategy. Available data show rebleeding rates of 33.3% with TC-325 in peptic ulcers and up to 66.7% in Forrest Ia lesions, and CEGP-003 as initial therapy has been identified as an independent risk factor for rebleeding[24,27,76]. Currently, several studies on hemostatic powders are methodologically limited in themselves. UIEWD is primarily based on Korean cohort data; due consideration should be given to differences in local treatment practices when extending its application to other regions. The broader adoption of hemostatic powders also depends on cost, product accessibility, device availability, and operator training. Economic data are limited to a United Kingdom analysis suggesting cost-effectiveness of first-line TC-325 in malignant GIB[20]; availability and regulatory approval vary across regions (Table 3), and use requires dedicated delivery hardware. Although technically simple to apply, effective and safe use still calls for endoscopist training.

Table 3 Regional availability of hemostatic powders used in gastrointestinal bleeding, European Conformity.

Product (manufacturer, origin)	Region(s) where marketed	Notes
TC-325 (Hemospray®; Cook Medical, United States)	United States, Canada, Europe, and other regions	Approved for endoscopic hemostasis in non-variceal upper GI bleeding; CE marking also reported for pediatric use
EndoClot® Polysaccharide Hemostatic System (EndoClot Plus, United States)	Europe, Türkiye, Malaysia, Australia	Country-level availability varies; no product-specific approval data identified for other regions
Ankaferd Blood Stopper® (ABS; AND Pharmaceuticals, Türkiye)	Türkiye (predominantly); limited availability elsewhere	Reported by the manufacturer as the first original locally licensed hemostatic medicinal product in Türkiye
UI-EWD (NexPowder™; Next Biomedical, Republic of Korea)	Republic of Korea, United States, Europe	FDA-cleared since 2022; most clinical evidence originates from Korean cohorts
CEGP-003 (CG Bio, Republic of Korea)	Republic of Korea	Availability and regulatory status outside the Republic of Korea not reported
Self-propelling thrombin powder (experimental agent)	None	Preclinical animal studies only
Polysaccharide hemostatic powder (multiple products)	China, Republic of Korea	Regulatory status differs according to the specific product

Regulatory information was compiled from the open United States Food and Drug Administration 510(k) database, manufacturer information, and published reviews. European Conformity marking is required for marketing in the European Union where a product is reported as marketed in Europe. “None” indicates that no reliable information was identified in the reviewed sources. ABS: Ankaferd Blood Stopper; CE: European Conformity; FDA: United States Food and Drug Administration; GI: Gastrointestinal.

Researchers should focus on advancing the precision of delivery systems to address existing operational challenges and mitigate potential risks. For instance, TC-325 employs a high-pressure CO₂ cartridge-driven delivery system; excessive pressure may increase the risk of tissue injury or perforation, while insufficient pressure can readily lead to catheter clogging. Future delivery systems could integrate the broad coverage of CO₂-driven mechanisms with the low-pressure stability of air compressors, incorporating anti-clogging designs to optimize the balance between safety and operability. Regarding formulation, an ideal hemostatic powder might be designed as a multifunctional composite product. It could simultaneously include rapid-dehydration components for immediate hemostasis, bioadhesive components to enhance barrier durability, and active substances such as growth factors to promote wound healing—thereby forming an integrated therapeutic sequence of hemostasis-barrier-repair. Artificial intelligence-assisted systems for identifying bleeding sites and calculating spray dosage have been proposed to reduce operator dependence and enhance standardization, but these concepts remain speculative, lack clinical validation, and are not currently viable clinical solutions. This will help refine clinical practice guidelines, expand the scope of indications, and promote the broader and more standardized application of this technology in clinical practice.

In conclusion, within the field of endoscopic hemostasis for GIB, hemostatic powder, as an emerging barrier-type hemostatic agent, demonstrates scenariospecific complementary value and developmental potential. However, its technical characteristics and operator-dependent nature necessitate cautious use in certain high-risk bleeding scenarios, where it may serve as part of a combined hemostatic strategy rather than as a first-line monotherapy.