Hemostasis: Role of PuraStat® in the prevention and management of gastrointestinal bleeding

Table 1 Limitations and disadvantages of methods used in endoscoping therapy of gastrointestinal bleeding

Endoscopic therapy method		Limitations/disadvantages	Ref.
Injection therapy	Epinephrine	May cause systematic effects on the cardiovascular system including hemodynamic changes. Comparing injecting actively bleeding ulcers at endoscopy with epinephrine alone or in combination with absolute alcohol shows initial hemostasis in 97.5% with epinephrine and 94.9% in the combination group. No significant differences between the groups in rebleeding (9 vs 6), emergency surgery (12 vs 9), transfusion needs, hospital stay (5 days vs 4 days), mortality (94 vs 7), or ulcer healing at 4 weeks (50 days vs 46 days). Systematic changes including severe hypertension, and ventricular tachycardia, following epinephrine injection. Endoscopic injection of a small volume (3-11 mL) of diluted epinephrine caused a rise in the plasma epinephrine concentration by 4-5 times above the basal level. Hypertensive emergency and ventricular tachycardia were reported. Rebleeding has been reported (10%-20%)	Schlag et al[31], Chung et al[32], von Delius et al[33], Sung et al[34], Stevens et al[35]
	Normal saline	Less effective compared to injecting epinephrine. It is usually used in patients with coronary artery disease. It may act by producing primary tamponade. It has no vasospasm effect. Rebleeding usually occurs if used alone	Pinkas et al[23]
	Sclerosant (e.g., polidocanol, ethanolamine, ethanol)	Polidocanol is not commonly used. It has no benefits over epinephrine. The incidence of complications from sclerotherapy vs banding in patients with esophageal varices were: Esophageal stricture formation 25.6% vs 1.9%, ulcer bleed 25.4% vs 5.7%, esophageal perforation 2.2% vs 0%, and massive esophageal hematoma 16% vs 0%	Bataller et al[36], Schmitz et al[37]
Ablation therapy	Thermotherapy and electrotherapy	Higher rebleeding rates after the use of contact thermal therapy for gastrointestinal-related tumor bleeding, despite initial successful hemostasis	Ofosu et al[38]
	APC	Endoscopic APC for treating hemorrhagic radiation proctitis was successful (79%), patients had self-limiting early complications (18.7%), late complications of rectal stenosis (3.3%). Depth of injection is unpredictable and may fail to stop bleeding	Siow et al[39]
	Laser phototherapy	Is becoming obsolete. A higher risk of gastrointestinal perforation. Less effective in stopping bleeding compared to other methods	Kay et al[29]
Mechanical therapy	Endoscopic clipping band ligation	Requires highly skilled endoscopist. Applications of the clips can be difficult with massive bleeding. Sometimes clips dislodge prematurely causing recurrent bleeding	Ji et al[30]

APC: Argon plasma coagulation.

Table 2 summarises the pharmacological and clinical aspects of PuraStat^® and hemostatic powder [Hemospray^® (TC-325)]

Item	PuraStat® (3-D Matrix-621)	Hemostatic powder spray [Hemospray® (TC-325)]	Ref.
Structure and active component	A synthetic hydrogel peptide. It is a 25% RADA16, a linear oligopeptide containing 16 amino acids as repeated 4-amino acids sequence containing R (positively charged arginine), A (hydrophobic alanine), and D (negatively charged aspartic acid) residues	A mineral-based hemostatic powder. It is calcium-based or silicate minerals	Sankar et al[41]
Human and animal proteins	N/A	N/A
Mechanisms of action	It forms an extracellular scaffold matrix when activated by the change in potential of hydrogen that occurs upon contact with blood	The granules once exposed to blood or tissue fluids; absorbs all the water causing its swelling and adherence to the bleeding sites	Uraoka et al[42], Sung et al[52]
Clinical uses	Used for upper and lower GI bleeding. Also, bleeding after EMR or esophageal and colonic submucosal dissection, and other surgical procedures	Primarily used for non-variceal GI bleeding	Stenson et al[47], Friedland et al[48], Wong et al[49], Gangner et al[50]
Application in endoscopic procedures	Applied via a catheter through an endoscope	The powder is delivered via a spray mechanism using inert gas e.g., nitrogen
Biocompatibility	Nontoxic	Biocompatible and nontoxic
Degradation	Is absorbable. It does not require removal after application	Is absorbable. It does not require removal after application
Immunogenicity	Nonimmunogenic	Nonimmunogenic
Clinical safety	Quite safe	Quite safe, and it washes out at 12 hours to 24 hours
Limitations and adverse effects	Less effective in massive and large bleeding areas. In a multicenter prophylactic randomised controlled trial testing its hemostatic prophylactic effect after EMR (large lesions in the duodenum and colorectum, no reduction in the rate of delayed bleeding observed)	Any type of moisture in the area will result in amalgamation of the powder which may block the delivery catheter. Not suitable for variceal bleeding	Drews et al[59]

EMR: Endoscopic mucosal resection; GI: Gastrointestinal; N/A: Not applicable.