Using a novel hemostatic peptide solution to prevent bleeding after endoscopic submucosal dissection of a gastric tumor

BACKGROUND Endoscopic mucosal dissection has become the standard treatment for early gastric cancer.However,post-endoscopic submucosal dissection(ESD)ulcer occurs in 4.4%of patients.This study hypothesized whether applying PuraStat,a novel hemostatic peptide solution,prevents post-ESD bleeding.AIM To investigate the preventive potential of PuraStat,a hemostatic formulation,against bleeding in post-ESD gastric ulcers.METHODS Between May 2022 and March 2023,101 patients(Group P)underwent ESD for gastric diseases at our hospital and received PuraStat(2 mL)for post-ESD ulcers.We retrospectively compared this group with a control group(Group C)com-prising 297 patients who underwent ESD for gastric diseases at our hospital between April 2017 and March 2021.P values<0.05 on two-sided tests indicated significance.RESULTS Post-ESD bleeding occurred in 6(5.9%)(95%CI:2.8-12.4)and 20(6.7%)(95%CI:4.4-10.2)patients in Groups P and C,respectively,with no significant between-group difference.The relative risk was 1.01(95%CI:0.95-1.07).The lesser curvature or anterior wall was the bleeding site in all 6 patients who experienced postoperative bleeding in Group P.In multivariate analysis,the odds ratios for resection diameter≥50 mm and oral anticoagulant use were 6.63(95%CI:2.52-14.47;P=0.0001)and 4.04(1.26-0.69;P=0.0164),respectively.The adjusted odds ratio of post-ESD bleeding and PuraStat was 1.28(95%CI:0.28-2.15).CONCLUSION PuraStat application is not associated with post-ESD bleeding.However,the study suggests that gravitational forces may affect the effectiveness of applied PuraStat.

Design of Collagen-Based Hemostatic Material for Use in Plastic and Reconstructive Surgery

This study aims to develop collagen-based hemostatic materials. The sheet-shaped collagen sponge was manufactured by freeze-vacuum drying the aqueous solution of collagen (Col) and heat-denatured collagen (Col’) at a composition ratio of 2/1. The both sides or one side of sponge was treated with ultraviolet (UV) irradiation for 15 minutes to introduce intermolecular crosslinks between collagen molecules. The elution behavior of collagen sponge was investigated by immersing the sponge in water for a predetermined time and then by measuring the weight change. The double-sided UV-irradiated sponge showed very slow elution properties. On the other hand, the single-sided UV-irradiated sponge showed initially fast elution and subsequent very slow elution properties. Such initially fast elution of collagen molecules from the surface without UV-irradiation allows an adhesion of collagen sponge to the wound surface and results in hemostatic effect. In addition, the water absorption and retention properties of sponge were investigated by placing the hydrated sponge on a mesh for a predetermined time and then by measuring the weight change. The double-sided UV-irradiated sponge absorbed 81 times more water than own weight and showed a value of 45 times even after 7 days. The single-sided UV-irradiated sponge absorbed 80 times more water than own weight and showed a value of 39 times even after 7 days. The sponge with high water absorption and retention properties allows a wound healing effect because such sponge can absorb large amounts of blood plasma and exudates containing various cell growth factors. The double-sided UV-irradiated sponge is a good candidate for the wound dressing. On the other hand, the single-sided UV-irradiated sponge is a good candidate for the hemostatic material.

Hemostatic effect of topical hemocoagulase spray in digestive endoscopy

AIM: To evaluate the hemostatic effect of topical hemocoagulase spray in digestive endoscopy.METHODS: Eighty-nine patients who developed oozing bleeding during endoscopic treatment from September 2014 to October 2014 at Center for Digestive Endoscopy, Tianjin Medical University General Hospital were randomly divided into either a study group(n = 39) or a control group(n = 50). The study group was given topical hemocoagulase spray intraoperatively, while the control group was given traditional 8% norepinephrine spray. Hemostatic efficacy was compared between the two groups. Bleeding site, wound cleanliness and perforation were recorded, and the rates of perforation and late bleeding were compared.RESULTS: Successful hemostasis was achieved in 39(100%) patients of the study group and in 47(94.0%) patients of the control group, and there was no significant difference in the rate of successful hemostasis between the two groups. Compared with the control group, after topical hemocoagulase spray in the study group, the surgical field was clearer, the bleeding site was more easily identified, and the wound was cleaner. There was no significant difference in the rate of perforation between the study and control groups(16.7% vs 35.0%, P = 0.477), but the rates oflate bleeding(0% vs 15.8%, P = 0.048) and overall complications(P = 0.032) were significantly lower in the study group.CONCLUSION: Topical hemocoagulase spray has a definite hemostatic effect for oozing bleeding in digestive endoscopy, and this method is convenient, safe, and reliable. It is expected to become a new method for endoscopic hemostasis.

Hemostatic agents for prehospital hemorrhage control: a narrative review

Hemorrhage is the leading cause of preventable death in combat trauma and the secondary cause of death in civilian trauma.A significant number of deaths due to hemorrhage occur before and in the first hour after hospital arrival.A literature search was performed through PubMed,Scopus,and Institute of Scientific Information databases for English language articles using terms relating to hemostatic agents,prehospital,battlefield or combat dressings,and prehospital hemostatic resuscitation,followed by cross-reference searching.Abstracts were screened to determine relevance and whether appropriate further review of the original articles was warranted.Based on these findings,this paper provides a review of a variety of hemostatic agents ranging from clinically approved products for human use to newly developed concepts with great potential for use in prehospital settings.These hemostatic agents can be administered either systemically or locally to stop bleeding through different mechanisms of action.Comparisons of current hemostatic products and further directions for prehospital hemorrhage control are also discussed.

Efficient hemostatic method for endoscopic submucosal dissection of colorectal tumors

AIM:To evaluate a new hemostatic method using hemostatic forceps to prevent perforation and perioperative hemorrhage during colonic endoscopic submucosal dissection(ESD).METHODS:We studied 250 cases,in which ESD for colorectal tumors was performed at the Kyoto Prefectural University of Medicine or Nara City Hospital between 2005 and 2010.We developed a new hemostatic method using hemostatic forceps in December 2008 for the efficient treatment of submucosal thick vessels.ESD was performed on 126 cases after adoption of the new method(the adopted group)and the new method was performed on 102 of these cases.ESD was performed on 124 cases before the adoption of the new method (the unadopted group).The details of the new method are as follows:firstly,a vessel was coagulated using the hemostatic forceps in the soft coagulation mode according to the standard procedure,and the coagulated vessel was removed using the forceps in the"endocut" mode without perioperative hemorrhage.Secondly,the partial surrounding submucosa was dissected using the forceps in the endocut mode.In the current study,we evaluated the efficacy of this method.RESULTS:Coagulated vessels were successfully removed using the hemostatic forceps in all 102 cases without severe perioperative hemorrhage.Moderate perioperative hemorrhage occurred in five cases(4.9%);however,it was stopped by immediately reuse of the hemostatic forceps.The partial surrounding submucosa was dissected using the forceps in all 102 cases.In the adopted group,the median operation time was 105 min.The proportion of endoscopic en bloc resection was 92.8%(P<0.01)compared to 80.6%in the unadopted group.The postoperative hemorrhage and perforation rates were 2.3%and 2.3%.The rate of perforation was significantly lower than that in the unadopted group (9.6%,P<0.01).We evaluated the ease of use of this method by allowing our three trainees to performed ESD on 46 cases,which were accomplished without any severe hemorrhage.CONCLUSION:The new method effectively treated submucosal thick vessels and shows promise for the prevention of perforation and perioperative hemorrhage in colonic ESD.

A comparative study of TR Band and a new hemostatic compression device after transradial coronary catheterization

Objective: Transradial coronary catheterization has proved to be safe and effective in clinical practice. Various hemostatic compressive devices have been used in subsequent procedures. The objective of this study was to compare the efficacy and safety of a new hemostatic compression device and the widely used TR Band. Methods: A total of 118 patients were divided randomly into two groups: TR Band and the new hemostatic compression device. Efficacy of hemostasis, patient comfort, local vascular dysfunction, and radial artery occlusion(RAO) were evaluated and compared between groups. Results: Occurrence of errhysis or hematoma did not significantly differ between groups(13.6% vs. 11.9%, P = 0.782). Fewer patients had moderate to severe pain or moderate to severe numbness in the new hemostatic compression device group(1.7% vs. 22.0%; 1.7% vs. 18.6%, respectively). Pulse loss between distal artery and device was lower in the new hemostatic compression device group(5.1% vs. 22.0%, P = 0.007), and fewer patients experienced obstruction of venous reflux compared with the TR Band group(6.8% vs. 25.4%, P = 0.006). Combined incidence of RAO at discharge was 7.6%, and was lower in the new hemostatic compression device group(1.7% vs. 13.6%, P = 0.015). In contrast to the TR Band, application of the new hemostatic compression device was independently associated with lower incidence of RAO at discharge(odds ratio: 0.062, 95% confidence interval: 0.006–0.675, P = 0.022). Conclusions: Both the new hemostatic compression device and the TR Band can efficiently achieve hemostasis following transradial coronary catheterization. However, fewer patients felt discomfort with application of the new hemostatic compression device. Pulse loss in the artery distal to the compression device, obstruction of venous reflux, and RAO occurred significantly less often with application of the new device.

A new hemostatic clip for endoscopic surgery that can maintain blood flow after clipping

AIM: To develop a new hemostatic device for endoscopic surgery that can control the bleeding without completely occluding the bleeding vessel. METHODS: A hemostatic clip and its applier that can stanch bleeding while maintaining blood flow through the clipped vessel was introduced, and the performance of the proposed clip was evaluated using in vitro and in vivo experiments. RESULTS: During in vitro experiments, no leakage was found after clipping at cuts made in artificial vessels, and flow was maintained through the clipped artificial vessels. In experiments on rats, all the implanted clips occluded the target vessels successfully, and no bleeding or tissue damage was observed at the operative site after the rats were euthanized on postoperative day 7. In experiments on pigs, bleeding stopped immediately after partial clipping of a damaged vessel, and some amount of blood flow was consistently maintained through the clipped vessel after hemostasis. CONCLUSION: We believe that the proposed hemostatic clip and clip applier can enhance patient safety during laparoscopic surgery.

Endoscopic treatment of non-variceal gastrointestinal bleeding:hemoclips and other hemostatic techniques

Although the number of hospitalizations for non-variceal gastrointestinal bleeding has decreased inrecent years,acute upper gastrointestinalhemorrhage continues to be a common reason forhospital admission,and peptic ulcers account for atleast fifty percent of all cases.Despite the fact thatbleeding from ulcers ceases spontaneously inapproximately 80% of patients,it is still a

CoolClot,a novel hemostatic agent for controlling life-threatening arterial bleeding

BACKGROUND:Uncontrolled bleeding is the first leading cause of preventable death in the battlefield and the 2nd cause of mortality in civil accidents.Incompressible hemorrhage control is among the interventions that drastically increase the survival rate in wound individuals.We have previously shown that a certain mixture of bentonite and zeolite minerals can significantly decrease the bleeding in rats.METHODS:In this study,nine healthy hybrid dogs were selected and after induction of anesthesia with ether,either arterial puncture by a needle or arteriotomy was performed on both groin regions of the dogs.For control arteries(either the right or left femoral artery),only pressure by sterilized gauze was performed,while for the femoral arteries of the opposite side,our invented hemostatic agent,namely CoolClot,was topically used before applying the pressure.In the second stage of the study,to assess the coagulation time,blood samples were collected from 10 volunteer students.RESULTS:CoolClot significantly decreased the bleeding time in animals whose femoral arteries were cut or punctured.In the human phase of the study,the mean coagulation time in control blood samples was 253.4+44.1 seconds,whereas it was 149.5+50.0,162.3±74.6 and 143.4±114.6seconds,respectively in blood samples treated with bentonite,zeolite and CoolClot(P<0.05).CONCLUSIONS:As controlling bleeding after a life-threatening arterial damage is critical for increasing the chance of survival,the results obtained in this study indicate the significant efficacy of CoolClot in shortening the bleeding time.Our experiments also indicate that CoolClot can significantly reduce the clotting time in human blood samples.

Evaluation of Hemostatic and Antihemolytic Effects of Aqueous Extract of Garcinia kola (Clusiaceae) Fresh Seeds

Objectives: Garcinia kola seeds (EAgk) (Clusiaceae) contain coagulant components use to pretreat aquaculture wastewater in Nigeria. This work was undertaken to assess the effects of EAgk on blood coagulation because of its contents. Methods: Five groups of four rats of both sexes (200 ± 5 g) received orally distilled water, phytomenadione (15 mg/kg b.w.) and garcinia kola seeds extract (250, 500 and 1000 mg/kg b.w.) for four days and after this period, bleeding time was measured by tail hemorrhage model. Activated partial thromboplastin time (aPTT) and platelet count were determined by coagulometer and hematological analyzer respectively. Blood red cells protection of EAgk was measured by the methods of 2,2’-Azobis(2-methylpropionamidine) dihydrochloride (AAPH)-induced hemolysis and inhibition of 2,2-Diphenyl-1-picryl hydrazyl (DPPH) radical and hydrogen peroxide. Results: EAgk at 1000 mg/kg b.w. induced a significant decrease in bleeding time from 420 ± 27.3 s to 157.5 ± 18.9 s. The platelet count of group of rat treated with EAgk (1000 mg/kg b.w.) increased significantly (p 0.05, n = 4). EAgk inhibited hemolysis, DPPH radical and hydrogen peroxide with IC50 values of 1.02 ± 0.2;3.2 × 10?2 ± 0.12 and 1.01 ± 0.5 mg/mg respectively. Conclusions: EAgk exhibits hemostatic effects, which could justify the presence of coagulant components in the extract. Erythrocytes’ protective activity of Garcinia kola seeds may be due to free radicals and hydrogen peroxide inhibition.

BIOLOGIC HEMOSTATIC GLUE IN GENERAL SURGERY

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CLINICAL USE OF BIOLOGICAL HEMOSTATIC GLUE IN NEUROSURGERY

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Hemostatic radiotherapy for bleeding gastrointestinal

Hemostatic radiotherapy is a non-invasive treatment for bleeding gastrointestinal(GI)tumors,promoting tumor shrinkage,blood supply reduction,and fibrotic tissue formation.It is effective in cases where traditional interventions are insufficient or contraindicated and can prevent recurrent bleeding in patients with GI bleeding histories.Hypofractionation schedules are also effective for tumor control and patient compliance.

Design and evaluation of a novel biopsy needle with hemostatic function

Biopsy is a method commonly used for early cancer diagnosis.However,bleeding complications of widely available biopsy are risky for patients.Safer biopsy will result in a more accurate cancer diagnosis and a decrease in the risk of complications.In this article,we propose a novel biopsy needle that can reduce bleeding during biopsy procedures and achieve stable hemostasis.The proposed biopsy needle features a compact structure and can be operated easily by left and right hands.A predictive model for puncture force and tip deflection based on coupled Eulerian–Lagrangian(CEL)method is developed.Experimental results show that the biopsy needle can smoothly deliver the gelatin sponge hemostatic plug into the tissue.Although the hemostatic plug bends,the overall delivery process is stable,and the hemostatic plug retains in the tissue without being affected by the withdrawal of the needle.Further experiments indicate that the specimens are well obtained and evenly distributed in the groove of the outer needle without scattering.Our proposed design of biopsy needle possesses strong ability of hemostasis,tissue cutting,and tissue retention.The CEL model accurately predicts the peak of puncture force and produces close estimation of the insertion force at the postpuncture stage and tip position.

Hemostatic materials in wound care

Blood plays an essential role in the human body.Hemorrhage is a critical cause of both military and civilian casualties.The human body has its own hemostatic mechanism that involves complex processes and has limited capacity.However,in emergency situations such as battlefields and hospitals,when the hemostatic mechanism of the human body itself cannot stop bleeding effectively,hemostatic materials are needed for saving lives.In this review,the hemostatic mechanisms and performance of the most commonly used hemostatic materials,(including fibrin,collagen,zeolite,gelatin,alginate,chitosan,cellulose and cyanoacrylate)and the commercial wound dressings based on these materials,will be discussed.These materials may have limitations,such as poor tissue adhesion,risk of infection and exothermic reactions,that may lessen their hemostatic efficacy and cause secondary injuries.High-performance hemostatic materials,therefore,have been designed and developed to improve hemostatic efficiency in clinical use.In this review,hemostatic materials with advanced performances,such as antibacterial capacity,superhydrophobicity/superhydrophilicity,superelasticity,high porosity and/or biomimicry,will be introduced.Future prospects of hemostatic materials will also be discussed in this review.

Tissue adhesive hemostatic microneedle arrays for rapid hemorrhage treatment

Blood loss by hemorrhaging wounds accounts for over one-third of~5 million trauma fatalities worldwide every year.If not controlled in a timely manner,exsanguination can take lives within a few minutes.Developing new biomaterials that are easy to use by non-expert patients and promote rapid blood coagulation is an unmet medical need.Here,biocompatible,and biodegradable microneedle arrays(MNAs)based on gelatin methacryloyl(GelMA)biomaterial hybridized with silicate nanoplatelets(SNs)are developed for hemorrhage control.The SNs render the MNAs hemostatic,while the needle-shaped structure increases the contact area with blood,synergistically accelerating the clotting time from 11.5 min to 1.3 min in vitro.The engineered MNAs reduce bleeding by~92%compared with the untreated injury group in a rat liver bleeding model.SN-containing MNAs outperform the hemostatic effect of needle-free patches and a commercial hemostat in vivo via combining micro-and nanoengineered features.Furthermore,the tissue adhesive properties and mechanical interlocking support the suitability of MNAs for wound closure applications.These hemostatic MNAs may enable rapid hemorrhage control,particularly for patients in developing countries or remote areas with limited or no immediate access to hospitals.

Novel hemostatic agents based on gelatin-microbial transglutaminase mix

Hemostasis is a major challenge in surgical procedures and traumas. Conventional hemostatic methods have limited efficacy and may cause additional tissue damage. In this study, we designed a novel hemostatic agent based on the in situ gel formation of gelatin cross-linked by a novel microbial transglutaminase(mTGase), in which the amino acid sequences differed from commercial mTGases. The new hemostatic agent showed the same biochemical crosslinking chemistry as the final stages of the blood coagulation cascade while using gelatin as a "structural" protein(rather than fibrin) and a calcium-independent mTGase as the crosslinking catalyst(rather than factor XIIIa). In rat liver hemostasis models, the hemostatic agent not only showed a similar hemostatic effect as that of SURGIFLO~(positive control), but also stronger adhesion strength and elasticity than SURGIFLO~.Therefore, this biomimetic gelatin-mTGase mix hemostatic is a novel and effective surgical sealant.

Graphene-based hemostatic sponge

Graphene-based sponge is a novel hemostatic material prepared by chemical cross-link of graphene oxide. It has a fast fluid absorption capacity to quickly absorb blood from wounds, activate clotting pathways, and achieve rapid hemostasis. In addition, graphene-based sponge is also a good platform carrier.It can be prepared by organic cross-linking, compounding with inorganic clay, and adding bioactive factors to enhance coagulation stimulation. By these methods, the hemostatic performance of the sponge is further improved, which shows great potential for application in the field of trauma hemostasis. This article reviews the research progress of graphene-based sponges from three different preparation strategies(organic cross-linking, inorganic compounding and adding bioactive factor), summarizes their hemostatic mechanisms, and prospects the development of graphene-based hemostatic sponges.

A new hemostatic agent composed of Zn^(2+)-enriched Ca^(2+)alginate activates vascular endothelial cells in vitro and promotes tissue repair in vivo

To control capillary bleeding, surgeons may use absorbable hemostatic agents, such as Surgicel® and TachoSil®. Due to their slow resorption, their persistence in situ can have a negative impact on tissue repair in the resected organ. To avoid complications and obtain a hemostatic agent that promotes tissue repair, a zinc-supplemented calcium alginate compress was developed: HEMO-IONIC®. This compress is non-absorbable and is therefore removed once hemostasis has been achieved. After demonstrating the hemostatic efficacy and stability of the blood clot obtained with HEMO-IONIC, the impact of Surgicel, TachoSil, and HEMO-IONIC on cell activation and tissue repair were compared (i) in vitro on endothelial cells, which are essential to tissue repair, and (ii) in vivo in a mouse skin excision model. In vitro, only HEMO-IONIC maintained the phenotypic and functional properties of endothelial cells and induced their migration. In comparison, Surgicel was found to be highly cytotoxic, and TachoSil inhibited endothelial cell migration. In vivo, only HEMO-IONIC increased angiogenesis, the recruitment of cells essential to tissue repair (macrophages, fibroblasts, and epithelial cells), and accelerated maturation of the extracellular matrix. These results demonstrate that a zinc-supplemented calcium alginate, HEMO-IONIC, applied for 10 min at the end of surgery and then removed has a long-term positive effect on all phases of tissue repair.