Topical Hemostatic Agents Research Articles

Efficacy of novel endoscopic hemostatic agent for bleeding control and prevention: Results from a prospective, multicenter national registry.

Background and study aims Topical hemostatic agents emerged as a new treatment modality for gastrointestinal bleeding. The aim of this study was to assess the safety and efficacy of PuraStat for control of active bleeding and for prevention of bleeding after different operative endoscopy procedures. Patients and methods A national, multicenter, observational registry was established to collect data from ten Italian centers from June 2021 to February 2023. Demographics, type of application (active gastrointestinal bleeding or prevention after endoscopic procedures, site, amount of gel used, completeness of coverage of the treated area), outcomes (rates of intraprocedural hemostasis and bleeding events during 30-day follow-up), and adverse events (AEs) were prospectively analyzed. Results Four hundred and one patients were treated for active gastrointestinal bleeding or as a preventive measure after different types of operative endoscopy procedures. Ninety-one treatments for active bleeding and 310 preventive applications were included. In 174 of 401 cases (43.4%), PuraStat was the primary treatment modality. Complete coverage was possible in 330 of 401 (82.3%) with difficulty in application in seven of 401 cases (1.7%). Hemostasis of active bleedings was achieved in 90 of 91 patients (98.9%). In 30-day follow-up 3.9% patients in whom PuraStat was used for prophylaxis had a bleeding event compared with 7.7% after hemostasis. No AEs related to the use of PuraStat were reported. Conclusions PuraStat is a safe and effective hemostat both for bleeding control and for bleeding prevention after different operative endoscopy procedures. Our results suggest that the possible applications for the use of PuraStat may be wider compared with current indications.

TC-325 superiority in Malignant Gastrointestinal Bleeding - An Individual Patient Data Meta-analysis of Randomized Trials.

The efficacy of topical hemostatic agents, recommended for peptic ulcer bleeding, remains poorly characterized in malignant gastrointestinal bleeding (GIB). We performed an individual patient data (IPD) meta-analysis assessing the efficacy of topical hemostatic agents in malignant GIB. The literature was searched using OVID MEDLINE, EMBASE, and ISI Web of Sciencedatabases (database inception to November 2023). Only randomized controlled trials (RCTs) comparing topical hemostatic agents to conventional endoscopic modalities in malignant GIB were included. Original RCT patient-level data were obtained. PRISMA guidelines were followed. Quality of the evidence was evaluated using the revised Cochrane risk of bias tool, and certainty of evidence with the GRADE approach. The primary outcome was immediate hemostasis; secondary outcomes were 30-day rebleeding and the composite measure of further bleeding (persistent bleeding or 30-day rebleeding). Other outcomes were all-cause mortality, adverse events, and need for additional non-endoscopic treatment. Odds ratios (ORs) from endpoint comparisons were pooled using logistic regression models. Overall, 985 citations were identified; 3 RCTs (n=160 patients) were included with all assessing TC-325 (Hemospray™). TC-325 achieved immediate hemostasis more often than conventional endoscopic modalities (OR=46.6 (5.89; 369.1)) (low level certainty). Thirty-day rebleeding (OR=0.28 (0.11; 0.70)) and further bleeding (OR=0.11 (0.05; 0.26)) were both significantly lower with TC-325 (very low level certainty). All-cause mortality and need for additional non-endoscopic treatment did not differ between groups. No adverse events were reported. Subgroup analysis confirmed TC-325 superiority in patients with upper GIB. TC-325 appears superior to conventional endoscopic therapy in managing patients with malignant GIB. TC-325 results in improvements in immediate hemostasis, 30-day rebleeding and further bleeding, based on very low-to-low certainties of evidence.

Novel Honeycomb Nanoclay Frameworks With Hemostatic and Antibacterial Properties.

Our laboratory recently developed a new class of high surface area, honeycomb Nanoclay Microsphere Framework absorbents (NMFs) that prompt rapid hemostasis. In the present work, we propose a novel approach to develop antibacterial Topical Hemostatic Agents (THAs) by anchoring silver nanoparticles (AgNPs) onto NMFs. This combination was obtained by a chemical co-reduction approach, followed by freeze-processing, and was shown to ensure stability and on-site delivery of AgNPs, without altering the hemostatic properties of NMFs. Silver-loaded NMFs showed no change in their unique architecture and led to a 55% increase in clot strength, compared to standard control plasma or commercially available THA, and a significant decrease in mean fibrin fiber diameter. Silver nanoparticles were successfully released when solubilized and prevented the growth of both Pseudomonas aeruginosa and Staphylococcus aureus at concentrations of 22 and 30 ppm of silver released, respectively. Overall, cell mortality was between 9.1 ± 5.1% and 6.3 ± 3.2%, depending on AgNP concentration, confirming a low cytotoxicity. Silver-loaded nanoclay microsphere frameworks appear to constitute promising candidates as topical hemostatic agents for secondary management of hemostasis when infection control is needed.

Evaluation of topical hemostatic agents (THA) used in perioperative period in thyroidectomy patients: assessment of ultrasonographic characteristics, resolution durations, and potential long-term complications

Evaluation of topical hemostatic agents (THA) used in perioperative period in thyroidectomy patients: assessment of ultrasonographic characteristics, resolution durations, and potential long-term complications

Efficacy of topical tranexamic acid soaked absorbable gelfoam in relieving post-extraction pain in warfarin patients: a randomized, triple-blinded, split-mouth, active-controlled clinical trial

BackgroundWarfarin patients who need dental extraction face the problem of bleeding and no sufficient hemostasis results in dry socket and postoperative pain. This study aimed to evaluate and compare the efficacy of the topical application of tranexamic acid-soaked absorbable Gelfoam (TXA-Gel) and saline-soaked absorbable Gelfoam (saline-Gel) in relieving postoperative pain following bilateral simple extraction of permanent mandibular molars in warfarin patients.MethodsThis was a randomized, triple-blinded, split-mouth, active-controlled clinical trial. It was performed at the Department of Oral and Maxillofacial Surgery, Faculty of Dentistry, Damascus University, between November 2021 and October 2023. 60 bilateral permanent mandibular molars, which were indicated for simple extraction in 30 warfarin patients randomly assigned into two groups according to the topical hemostatic agents after extraction used: Group 1: control group, saline-Gel (n = 30). Group 2: TXA-Gel (n = 30). A simple randomization method was performed by flipping a coin. The primary outcome measure was the visual analogue scale (VAS). The intensity of pain was evaluated at the baseline (t0), and on the 1st (t1), 2nd (t2), 3rd (t3), 4th (t4), 5th (t5), 6th (t6), and 7th (t7) days following extraction. The Kolmogorov–Smirnov test and the Mann-Whitney U test were performed. The level of significance was set at 0.05 (p < 0.05).ResultsThe mean vas scores was 4.17 ± 1.76 at t1 and decreased to 0.73 ± 0.78 at t7 in the TXA-Gel group. However, in the Gelfoam group, the mean vas scores was 4.83 ± 2.18 at t1 and decreased to 1.80 ± 1.00 at t7. The results of the Mann-Whitney U test showed that there was no statistically significant difference between the two groups at t1 (p = 0.236) and t2 (p = 0.155). However, there was a statistically significance difference at the rest time points (p < 0.05).ConclusionsTXA-Gel played a prominent role in alleviating post-extraction pain in warfarin patients.Trial registrationThe trail was retrospectively registered at the ISRCTN registry (ISRCTN71901901).

Evaluation of Haemostatic Potential and HPTLC Fingerprinting of Annona squamosa Linn. Bark Extract

Objectives: The present work focuses on exploring and evaluating the hemostatic property of Annona squamosa Linn. bark. Being a renewable resource, it has the potential to contribute to the hemostatic agent. Hemostatic efficacy of the cold and hot bark extract at different concentrations of 10, 50, 100 &amp; 250 mg/ml of saline were evaluated using whole blood clotting, platelet aggregation test, prothrombin time CAMAG HPTLC system. The hemostatic efficacy. At 250 mg/ml saline, both the extracts showed excellent hemostatic efficacy by clotting blood in 1.2 s and 3 s, respectively. The prothrombin time of cold and hot were 5 s and 5.1 s which were less than that of Liquiplastin partial prothrombin time which was Liquicelin E (13.85 s). Annona squamosa Linn. to be used as a topical hemostatic agent. Saponins, which are known to be antihemorrhagic, were detected by HPTLC. hemostatic efficacy of Annona squamosa Linn. bark was evaluated, which can contribute to the development of a fast-acting, cost-effective, easy-to-use, and sustainable topical hemostat. Keywords: Annona squamosa Linn, Hemostatic activity, Prothrombin time, Activated partial thromboplastin time, HPTLC fingerprint

Von Willebrand disease.

von Willebrand disease (VWD) is the most common inherited bleeding disorder. The disorder is characterized by excessive mucocutaneous bleeding. The most common bleeding manifestations of this condition include nosebleeds, bruising, bleeding from minor wounds, menorrhagia or postpartum bleeding in women as well as bleeding after surgery. Other less frequent symptoms include gastrointestinal bleeding, haematomas or haemarthroses. VWD pathophysiology is complex and results from defects in von Willebrand factor (VWF) glycoprotein. Quantitative deficiencies are responsible for type 1 VWD with a partial decrease of VWF and type 3 with the complete absence of VWF. Qualitative abnormalities cause type 2 VWD, being further divided into types 2A, 2B, 2M and 2N. Although common, VWD is at risk of misdiagnosis, overdiagnosis and underdiagnosis owing to several factors, including complex diagnosis, variability of bleeding symptoms, presence of external variables (blood groups and other physiological modifiers such as exercise, thyroid hormones, oestrogens, and ageing), and lack of disease awareness among non-specialist health-care providers. Establishing the correct VWD diagnosis requires an array of specialized phenotypic assays and/or molecular genetic testing of the VWF gene. The management of bleeding includes increasing endogenous VWF levels with desmopressin or infusion of exogenous VWF concentrates (plasma-derived or recombinant). Fibrinolytic inhibitors, topical haemostatic agents and hormonal therapies are used as effective adjunctive measures.

Functional and structural neurodegenerative activities of Ankaferd BloodStopper in a mouse sciatic nerve model.

Traumatic and postoperative hemorrhages are life-threatening complications. Ankaferd BloodStopper (ABS) is a potent topical hemostatic agent to stop bleeding. However, ABS is associated with nerve toxicity. The present study aimed to investigate the functional and structural neurodegenerative effects of ABS in a mouse model. A total of 30 male BALB/c mice, aged 6-8 weeks, were randomly divided into control group (no treatment), a sham group (treated with saline) and an experimental group (treated with ABS). In the saline and the ABS groups, the right sciatic nerve was surgically exposed and treated with saline or ABS, respectively. No surgical procedure was performed in the control group. On day 7 post-treatment, functional changes of the sciatic nerve were evaluated by a horizontal ladder rung walking task. Structural changes were assessed with immunohistochemistry. In the horizontal ladder rung walking test, the gait impairment was proportional to the severity of sciatic nerve damage, with the ABS group showing a significantly higher rate of errors than the control and saline groups. Immunohistochemistry demonstrated extensive degeneration and deformation in the axons and myelin sheath of the sciatic nerve in the ABS group. The results provide compelling evidence for the neurotoxicity of ABS.

Antifibrinolytic and Adjunct Hemostatic Agents: The Pediatric Extracorporeal Membrane Oxygenation Anticoagulation CollaborativE Consensus Conference.

To derive systematic-review informed, modified Delphi consensus regarding antifibrinolytic and adjunct hemostatic agents in neonates and children supported with extracorporeal membrane oxygenation (ECMO) for the Pediatric ECMO Anticoagulation CollaborativE consensus conference. A structured literature search was performed using PubMed, EMBASE, and Cochrane Library (CENTRAL) databases from January 1988 to May 2021. Use of antifibrinolytics (epsilon-aminocaproic acid [EACA] or tranexamic acid), recombinant factor VII activated (rFVIIa), or topical hemostatic agents (THAs). Two authors reviewed all citations independently, with a third independent reviewer resolving conflicts. Eleven references were used for data extraction and informed recommendations. Evidence tables were constructed using a standardized data extraction form. Risk of bias was assessed using the Quality in Prognosis Studies tool. The evidence was evaluated using the Grading of Recommendations Assessment, Development, and Evaluation system. Forty-eight experts met over 2 years to develop evidence-based recommendations and, when evidence was lacking, expert-based consensus statements for the management of bleeding and thrombotic complications in pediatric ECMO patients. A web-based modified Delphi process was used to build consensus via the Research And Development/University of California Appropriateness Method. Consensus was defined as greater than 80% agreement. One weak recommendation and three consensus statements are presented. Evidence supporting recommendations for administration of antifibrinolytics (EACA or tranexamic acid), rFVIIa, and THAs were sparse and inconclusive. Much work remains to determine effective and safe usage strategies.

Potential novel role of the human amniotic membrane as a sustainable hemostat.

Acute hemorrhage can cause significant morbidity and mortality arising from trauma, bleeding disorders, surgical procedures, or obstetric complications. Surgical hemostasis methods may fail to stop acute bleeding due to the complex bleeding dynamics of each bleeding type. Therefore, developing safe and effective topical hemostatic agents remains crucial. The human amniotic membrane (hAM) has established clinical evidence of effectiveness in promoting wound healing and tissue regeneration. Despite its unique biological and immunologic properties and its structural composition of established hemostatic elements, the hemostatic role of hAM has not been yet explored. The present study aimed to investigate this potential role and to describe the development protocol and characterization of hAM-derived topical hemostat. Surface electron microscope (SEM) imaging and Fourier transform infrared (FTIR) spectroscopy were used for characterization, and mouse models with induced peritoneal and tail wound bleeding were employed to evaluate the hemostatic effectiveness using physiological studies, in comparison to a chitosan-based combat-scale hemostat. The hAM hemostat showed a distinctive composition by SEM and FTIR. Applying equal masses of the hAM hemostat, the commercial hemostat, or a combination reduced peritoneal wound bleeding time to averages of 108.4, 86.2, and 76.8 s, respectively, compared to the control group (300 s). Tail wound bleeding times were similarly reduced with no significant difference between the hAM and the commercial hemostat (P values = 0.29, 0.34 in peritoneal and tail wounds, respectively). Neither hemostat affected coagulation time. This study describes a simple cost-effective preparation protocol for a hAM-based hemostatic agent. The long-recognized safety, sustainability, and immunotolerance advantages of hAM can establish superiority over commercial hemostats with reported safety concerns. Robust research validation in larger-scale bleeding models is required for wider applications and severe bleeding types.

Dry as a desert: a surgical tour of topical hemostatic agents

Dry as a desert: a surgical tour of topical hemostatic agents

Evaluation of Efficacy and Safety of Topical Hemostatic Agents in controlling Obstetric and Gynecologic Hemorrhage

Evaluation of Efficacy and Safety of Topical Hemostatic Agents in controlling Obstetric and Gynecologic Hemorrhage

Impact of microporous polysaccharide haemostatic agent on patients undergoing mastectomy or axillary dissection on seroma formation and timing of drain removal

Background: Seroma formation is a known complication following mastectomy and axillary lymph node dissection (ALND) leading to morbidity and financial implications for patients. ARISTATM AH has been designed to prevent postoperative seromas formation in vitro. Methods: We performed a single institution, single surgeon retrospective study from January 2017 to December 2022 in patients undergoing mastectomy/axillary dissection to evaluate seroma formation rates and timing of drain removal. Results: A total of 72 cases were included in our retrospective review of electronic medical records. Of these, 40 patients underwent ipsilateral mastectomies with sentinel node biopsies, 8 patients underwent bilateral mastectomies, and 18 patients underwent axillary dissections without concurrent mastectomy. Our analysis showed a non-significant decrease in seroma formation when ARISTATM AH was used intra-operatively (10%) compared to standard care (24%), (p=0.14). The ARISTATM AH group had a statistically significantly longer mean drain removal time than the standard care group (12.9 vs 7.6 days, p=0.002). Conclusions: There was a trend towards lower seroma formation and a significantly longer requirement for drain placement after mastectomy in ARISTATM AH group. Further research including randomised controlled multi-centre study evaluating the benefit of topical haemostatic agents in reducing seroma formation in breast surgery is warranted.

Comparison of blood loss between intra-articular microporous polysaccharide hemospheres powder and tranexamic acid following primary total knee arthroplasty

Total knee arthroplasty (TKA) is associated with substantial blood loss and tranexamic acid (TXA) effectively reduces postoperative bleeding. Although it is known that there is no difference between intravenous or intra-articular (IA) injection, the general interest is directed towards topical hemostatic agents regarding thromboembolic events in high-risk patients. This study aimed to compare the blood conservation effects of IA MPH powder and TXA in patients undergoing primary TKA. We retrospectively analyzed 103 patients who underwent primary TKA between June 2020 and December 2021. MPH powder was applied to the IA space before capsule closure (MPH group, n = 51). TXA (3 g) was injected via the drain after wound closure (TXA group, n = 52). All patients underwent drain clamping for three postoperative hours. The primary outcome was the drain output, and the secondary outcomes were the postoperative hemoglobin (Hb) levels during the hospitalization period and the perioperative blood transfusion rates. An independent Student’s t-test was used to determine differences between the two groups. The drain output in the first 24 h after surgery was significantly higher in the MPH group than in the TXA group. The postoperative Hb levels were significantly lower in the MPH group than in the TXA group. In patients with simultaneous bilateral TKA, there was a significant difference in the blood transfusion volumes and the rates between groups. It is considered that IA MPH powder cannot replace IA TXA because of an inferior efficacy in reducing blood loss and maintaining postoperative Hb levels in the early postoperative period after primary TKA. Moreover, in the case of simultaneous bilateral TKA, we do not recommend the use of IA MPH powder because it was notably less effective in the field of transfusion volume and rate.

Efficacy and feasibility of the RADA16 self-assembling peptide, PuraStat® for haemostasis in laparoscopic gynaecological surgery: A pilot study.

Bleeding after laparoscopic gynaecological surgery remains a potential complication. We assessed RADA16 (PuraStat®), a topical self-assembling peptide haemostatic agent, in a pilot study of 46 women undergoing laparoscopic gynaecological surgery. The primary outcome was intraoperative haemostatic efficacy for resection site bleeding. Haemostasis was achieved in all intraoperative bleeding situations (40/40 participants: 100%) with no clinically significant surgical bed bleeding or complications. Mean volume and time required to achieve haemostasis were 6 mL and 14 sec, respectively. This study suggests that PuraStat® is a safe, effective haemostatic agent in laparoscopic gynaecological surgery. Randomised controlled trials are warranted to confirm these findings.

Topical Hemostatic Agents and Risk of Postoperative Hemorrhage After Transoral Robotic Surgery.

Objective: Postoperative hemorrhage is the most common complication of transoral robotic surgery (TORS). The available research literature on topical hemostatic agents is deficient, despite their wide use. This study aims to evaluate the frequency and severity of hemorrhagic events after TORS procedures, performed with various topical hemostatic agents. Methods: This study was planned as a retrospective review to identify postoperative hemorrhage events in a database of all consecutive adult patients who required TORS from January 1, 2015, to April 1, 2020. All procedures were performed in one single institution by the same surgeon. In 2017, bovine gelatin matrix with thrombin (BgMT) was replaced by the porcine gelatin matrix with thrombin (PgMT) for all procedures. Postoperative hemorrhage was identified, along with hemostatic agents employed and other variables. Results: A cohort of 80 TORS procedures was obtained from a population of 78 individuals (60 males:18 females). BgMT was used in 28 procedures (35%), and five cases of postoperative hemorrhage were identified (17.8%), two of them were severe. PgMT was used in 52 procedures (65%) just observing one minor hemorrhagic event (1.92%). Although a significant difference was observed for total events between groups (P = .0183), there was no difference between major or severe hemorrhagic events (P = .1196). The overall rate of major and severe postoperative hemorrhage in the study population was 2.5% (n = 80). Conclusions: This is the first study to evaluate topical hemostatic agents during TORS procedures. The PgMT group had a reduced incidence of total postoperative hemorrhages, although there was no difference in the number of severe hemorrhagic events. The overall simplicity and cost-effectiveness of these agents would support their use, particularly considering the potential risk associated with airway hemorrhage.

A Comparative Review of Two Major Topical Hemostasis Agents in Spine Surgery

Achieving adequate hemostasis in spine surgery is critical for both the patient and surgeon. Currently, there are two major topical hemostatic matrix agents used in spine surgery—Floseal (Baxter Healthcare, Deerfield, Illinois, USA) and Surgiflo (Ethicon Inc., Raritan, New Jersey, USA). While both products have been shown to be effective at achieving hemostasis, there is no consensus supporting the use of one agent over another in spine surgery. There are studies comparing outcomes and cost between Floseal and Surgiflo, but a significant portion of the studies have industry affiliations. Generally, existing literature reports low to moderate cost savings in favor of one agent or the other, with no clinically significant differences in other patient-based outcomes such as postoperative hematomas. Animal model studies also suggest unique complications, including epidural fibrosis and associated nerve root compression with use of a flowable topical hemostatic agent. Further non-industry-affiliated studies are warranted to compare efficacy, patient outcomes, cost analyses, and possible unique complications associated with the two hemostatic agents.

Life-threatening upper gastrointestinal hemorrhage from a Cameron ulcer

Introduction: Acute upper gastrointestinal bleeding can be life-threatening; however, Cameron lesions are an uncommon etiology. These lesions should be suspected with a previous history or endoscopic evidence of hiatus hernia. Case Report: A male in his 60s presented to the emergency department with hematemesis and melena for two days. He had no prior medical, surgical, or endoscopic history and took no regular medications. He was resuscitated with packed red blood cell transfusion and treated with proton pump inhibitor infusion then transferred to operating theaters for endoscopic hemostasis. Cardiac arrest occurred after anesthetic induction and airway intubation, return of spontaneous circulation was achieved after cardiopulmonary resuscitation and further blood transfusion. At endoscopy a Cameron ulcer was noted in the hiatus hernia with overlying blood clot with no active hemorrhage, treated with Hemospray®. Conclusion: Patients presenting with acute upper gastrointestinal hemorrhage and shock need urgent upper gastrointestinal (UGI) endoscopy. Topical hemostatic agents are successful in controlling bleeding when challenging anatomy precludes use of banding or clip application.

Protective Topical Dual-Sided Nanofibrous Hemostatic Dressing Using Mussel and Silk Proteins with Multifunctionality of Hemostasis and Anti-Bacterial Infiltration.

Topical hemostatic agents are preferred for application to sensitive bleeding sites because of their immediate locoregional effects with less tissue damage. However, the majority of commercial hemostatic agents fail to provide stable tissue adhesion to bleeding wounds or act as physical barriers against contaminants. Hence, it has become necessary to investigate biologically favorable materials that can be applied and left within the body post-surgery. In this study, a dual-sided nanofibrous dressing for topical hemostasis is electrospun using a combination of two protein materials: bioengineered mussel adhesive protein (MAP) and silk fibroin (SF). The wound-adhesive inner layer is fabricated using dihydroxyphenylalanine (DOPA)-containing MAP, which promotes blood clotting by aggregation of hemocytes and activation of platelets. The anti-adhesive outer layer is composed of alcohol-treated hydrophobic SF, which has excellent spinnability and mechanical strength for fabrication. Because both proteins are fully biodegradable in vivo and biocompatible, the dressing would be suitable to be left in the body. Through in vivo evaluation using a rat liver damage model, significantly reduced clotting time and blood loss are confirmed, successfully demonstrating that the proposed dual-sided nanofibrous dressing has the right properties and characteristics as a topical hemostatic agent having dual functionality of hemostasis and physical protection.

Expert panel recommendations for topical hemostatic agent use in varied bleeding sites and situations during neuro-spine surgeries

Intraoperative bleeding poses a substantial challenge, particularly in neuro-spine surgeries leading to complications such as hematomas, infections, and hemodynamic instability. Despite their proven efficacy, use of topical hemostatic agents (THAs) lacks comprehensive published literature and guidelines particularly in the Indian setting. The present study provides the first-ever Indian expert panel recommendations for effective adjunct THA use in different intraoperative bleeding sites and situations in neuro-spine surgeries. A comprehensive approach, encompassing a literature review, followed by experience sharing in a meeting using a survey helped integrate expert opinions in the form of practical algorithms to guide THA selection. Our survey results revealed a strong inclination towards specific THAs, flowable gelatin + thrombin being choice of THA for difficult to access and problematic bleeding situations during tumor removal/resection, transsphenoidal hypophysectomy and skull-based procedures. Both oxidized regenerated cellulose (ORC)/Fibrillar and flowable gelatin + thrombin were recommended for continuous oozing. ORC/Fibrillar was preferred for arteriovenous and cavernous malformations. This expert-panel guidance on THA use aims to optimize hemostat use practices and improve surgical outcomes in neuro-spine surgery.