Severe upper gastrointestinal bleeding is halted by endoscopically delivered self-propelling thrombin powder: A porcine pilot study

Abstract

Background and study aims Hemostatic powders have emerged recently to treat upper gastrointestinal bleeding (UGIB). Previously, we developed a novel self-propelling thrombin powder (SPTP) that effectively manages external pulsatile arterial bleed without compression, by effervescing and carrying thrombin into the wound. Here, we tested if SPTP, sprayed endoscopically, can manage severe UGIB in a live porcine model. Materials and methods Anesthetized pigs underwent laparotomy to insert the gastroepiploic vascular bundles into the stomach lumen via a gastrotomy. Bleeding was initiated endoscopically in the stomach by needle knife. SPTP was delivered to the site of bleeding from a CO2-powered spray device using a 7 FR catheter. Successful primary hemostasis, time to hemostasis, and the mass of SPTP delivered were measured. Results Hemostasis was achieved at all bleeding sites using SPTP. Mean time to hemostasis was 4.2 ± 0.9 minutes (mean ± standard error of the mean, n = 12). The average mass of SPTP delivered was 2.4 ± 0.6 g. Conclusions In this pilot study, SPTP successfully stopped 12 cases of severe UGIB, demonstrating early promise asa novel hemostatic powder.

Percutaneous delivery of self-propelling thrombin-containing powder increases survival from noncompressible truncal hemorrhage in a swine model of coagulopathy and hypothermia

“…17 In addition, SPTP managed nasal bleeding in a sheep model without thrombosis or pulmonary embolism for up to 15 days postrecovery. 20 Self-propelling thrombin-containing powder appeared safe in this acute study and has been shown to be safe previously in multiple models, [17][18][19][20][21][22] but the long-term impact of SPTP on animals needs to be evaluated. This includes the breakdown of residual SPTP, which is expected to occur within several days, and evaluating its potential for forming adhesions.…”

“…Self-propelling thrombin-containing powder was prepared at a concentration of 1,000 IU of thrombin per gram as previously described. 17,22 Briefly, CaCO 3 microparticles (3 μm; American Elements, Los Angeles, CA), recombinant thrombin (Baxter, Deerfield, IL), and other excipients were suspended at 100% w/v in saline (10 g/L NaCl, 3 g/L glycine, pH 7.4). The particles were mixed and lyophilized.…”

“…17 Self-propelling thrombin-containing powder, or CounterFlow, consists of calcium carbonate (CaCO 3 ) microparticles, thrombin, and TXA, which reacts in blood to generate CO 2 . [17][18][19][20][21][22] CO 2 formation propels thrombin and TXA through large volumes of pooled blood within the abdomen, reaching wound sites to trigger coagulation, and locally inhibit fibrinolysis. In vivo proof of concept that SPTP could manage NCTH was demonstrated previously where a handheld spray device and catheter were deployed to deliver SPTP into the closed abdomen of swine.…”

“…Self-propelling thrombin-containing powder (SPTP) is a new hemostatic agent which is administered into the abdomen using a minimally invasive procedure and could complement current approaches for managing NCTH 17 . Self-propelling thrombin-containing powder, or CounterFlow, consists of calcium carbonate (CaCO 3 ) microparticles, thrombin, and TXA, which reacts in blood to generate CO 2 17–22 . CO 2 formation propels thrombin and TXA through large volumes of pooled blood within the abdomen, reaching wound sites to trigger coagulation, and locally inhibit fibrinolysis.…”

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

“…As it has high hemostatic potential from thrombin, the mechanism of SPTP is likely well-suited to higher risk gastrointestinal bleeding with exposed vessels. In a porcine model of Forrest class Ia and Ib upper gastrointestinal bleeding, hemostasis was successfully achieved at all sites 81 . Previous non-gastrointestinal bleeding studies showed that SPTP is safe and well-tolerated with no evidence of toxicity or thromboembolism 77 78 .…”