Hemostatic Technologies Research Articles

External Bleeding and Advanced Biomacromolecules for Hemostasis.

Hemorrhage is a significant medical problem that has been an active area of research over the past few decades. The human body has a complex response to bleeding that leads to blood clot formation and hemostasis. Many biomaterials based on various biomacromolecules have been developed to either accelerate or improve the body's natural response to bleeding. This review examines the mechanisms of hemostasis, types of bleeding, and the in vitro or in vivo models and techniques used to study bleeding and hemostatic materials. It provides a detailed overview of the diverse hemostatic materials, including those that are highly absorbent, wet adhesives, and those that accelerate the biochemical cascade of blood clotting. These materials are currently marketed, under preclinical testing, or being researched. In exploring the latest advancements in hemostatic technologies, this paper highlights the potential of these materials to significantly improve bleeding control in clinical and emergency situations.

Efficacy and safety of CounterFlow in animal models of hemorrhage

LAY SUMMARY The efficacy of current hemostatic technologies is limited by several factors. Outward blood flow washes hemostatic drugs away from the wound, and hemostatic drugs often require focus, training, and time to use correctly, are highly specific to one type of injury, or pose severe safety risks. CounterFlow is a novel product that could potentially save military and civilian lives by stopping heavy bleeding from a variety of organs and other bodily locations that current technology cannot easily treat. Upon contact with blood, CounterFlow releases bursts of gas to safely self-propel bio-degradable clot-forming and clot-stabilizing drugs against blood flow, delivering them to the source of bleeding. This unique mechanism allows CounterFlow to be applied quickly to a wide assortment of wounds and to act effectively with little management after application. CounterFlow was tested in multiple animal models representing common and deadly bleeding scenarios, including internal bleeding, care under fire without compression, and surgical bleeding, and it was found to outperform current care options by stopping bleeds faster and increasing survival times. CounterFlow is also safe to use and biocompatible. This narrative review summarizes studies testing the effectiveness and safety of CounterFlow, discusses useful applications, and describes future plans for the product.

Engineered Hemostatic Biomaterials for Sealing Wounds

Hemostatic biomaterials show great promise in wound control for the treatment of uncontrolled bleeding associated with damaged tissues, traumatic wounds, and surgical incisions. A surge of interest has been directed at boosting hemostatic properties of bioactive materials via mechanisms triggering the coagulation cascade. A wide variety of biocompatible and biodegradable materials has been applied to the design of hemostatic platforms for rapid blood coagulation. Recent trends in the design of hemostatic agents emphasize chemical conjugation of charged moieties to biomacromolecules, physical incorporation of blood-coagulating agents in biomaterials systems, and superabsorbing materials in either dry (foams) or wet (hydrogel) states. In addition, tough bioadhesives are emerging for efficient and physical sealing of incisions. In this Review, we highlight the biomacromolecular design approaches adopted to develop hemostatic bioactive materials. We discuss the mechanistic pathways of hemostasis along with the current standard experimental procedures for characterization of the hemostasis efficacy. Finally, we discuss the potential for clinical translation of hemostatic technologies, future trends, and research opportunities for the development of next-generation surgical materials with hemostatic properties for wound management.

Fabrication of thrombin loaded TEMPO-oxidized cellulose nanofiber-gelatin sponges and their hemostatic behavior in rat liver hemorrhage model

Excessive blood loss due to trauma or major surgical intervention can be life threatening which necessitates rapid hemorrhage management for the prevention of such bleeding related sufferings. Broad interest in developing new hemostatic technologies have been paid for bleeding control but none of them found completely satisfactory especially in terms of rapid clotting, absorbability, porosity, cost effectiveness and safety. To address these issues, a combination of active and passive hemostatic materials from biological sources could be a wise choice. Therefore, plant-derived TEMPO-oxidized nanocellulose (TOCN)/biopolymer gelatin (G) sponge was successfully prepared in co-operation with intrinsic blood coagulation enzyme thrombin (Th) via freeze drying method and their application as rapid hemostatic dressing was investigated. Morphological and in vitro characteristics of the samples were evaluated where uniformity, porosity, swelling, degradation behavior had direct relationship with the percent gelatin incorporation. In vitro hemocompatibility and cyto-compatibility of these sponges were confirmed as well. Among the samples, TOCN 2.5G-Th sponge exhibited excellent hemostatic effect, rapid absorbability, minimum clotting time (1.37 ± 0.152 min) and reduction of blood loss was ensured through rat liver punch biopsy model. The results demonstrated that, Th enhanced blood coagulation, platelet and red blood cell aggregation following application of biopolymer TOCN 2.5G-Th sponge compared with samples devoid of Th. In short, the functional, cost effective and nontoxic sponge developed via facile preparation could potentially be used as an absorbable biomaterial to achieve immediate hemostasis. Highlights Plant-derived TEMPO-oxidized nanocellulose (TOCN) and biopolymer gelatin (G) was successfully used to prepare a hemostatic sponge in combination with intrinsic blood coagulation enzyme thrombin (Th). The TG sponge combines the advantages of TOCN and gelatin, exhibiting biocompatibility, biodegradability and superior blood-absorption performance. The TOCN 2.5G-Th sponge improves plasma absorption, red blood cell adhesion, aggregation, platelet adhesion and activation leading to enhanced hemostasis effect and shorter hemostasis time in vitro and in vivo

A mussel-inspired supramolecular hydrogel with robust tissue anchor for rapid hemostasis of arterial and visceral bleedings

In recent years, the developed hemostatic technologies are still difficult to be applied to the hemostasis of massive arterial and visceral hemorrhage, owing to their weak hemostatic function, inferior wet tissue adhesion, and low mechanical properties. Herein, a mussel-inspired supramolecular interaction-cross-linked hydrogel with robust mechanical property (308.47 ± 29.20 kPa) and excellent hemostatic efficiency (96.5% ± 2.1%) was constructed as a hemostatic sealant. Typically, we combined chitosan (CS) with silk fibroin (SF) by cross-linking them through tannic acid (TA) to maintain the structural stability of the hydrogel, especially for wet tissue adhesion ability (shear adhesive strength = 29.66 ± 0.36 kPa). Compared with other materials reported previously, the obtained CS/TA/SF hydrogel yielded a lower amount of blood loss and shorter time to hemostasis in various arterial and visceral bleeding models, which could be ascribed to the synergistic effect of wound closure under wet state as well as intrinsic hemostatic activity of CS. As a superior hemostatic sealant, the unique hydrogel proposed in this work can be exploited to offer significant advantages in the acute wound and massive hemorrhage with the restrictive access of therapeutic moieties.

Autoplasma as a Hemostatic Agent for Endoscopic Surgery of Hollow Organs

Introduction. To maximize the effectiveness of hemostatic technologies, it is necessary to optimize local hemostasis through hybrid and controlled approaches, as well as to improve the conditions for tissue surgical dissection preventing perforation of hollow organs. This study is aimed at assessing the efficacy of stopping bleeding and the safety of resection of digestive hollow organs in experimental models of trauma to abdominal organs in laboratory animals.Materials and methods. Experiments were carried out in vivo on 20 rabbits. All animals were divided into 4 experimental groups (5 animals each): I — the control group, in which no methods for stopping bleeding were used; II — the group, in which infiltration of the wall of a hollow organ with saline solution was used; III — the group, in which physical hemostasis was applied using an electrosurgical unit and an argon plasma coagulation apparatus; IV — the group, animals in which underwent controlled local biological hemostasis using autoplasma. Prior to laparotomy, 2–3 ml of whole blood was taken from the rabbit’s ear for preliminary preparation of autoplasma. The prepared autoplasma was introduced into the area of resection or other operation of the mucous membrane of the rabbit’s digestive tract.Results and discussion. Although no statistical difference in the time of stopping bleeding was observed between the control (I) and saline (II) groups, one more episode of bleeding was noted in group II. Preventive local administration of autoplasma (group IV) was established to have a high hemostatic potential. As expected, electrocoagulation was more effective than saline; however, hemostasis achieved by means of argon plasma coagulation is characterized by rapid formation of a necrotic zone, which may lead to undesirable consequences in the long-term period.Conclusion. Preventive local administration of autoplasma and recombinant human protein has a high hemostatic potential in animals. In comparison, electrocoagulation is less effective due to the rapid filling of the pathological focus with blood.

Polymeric Hydrogel Systems as Emerging Biomaterial Platforms to Enable Hemostasis and Wound Healing

Broad interest in developing new hemostatic technologies arises from unmet needs in mitigating uncontrolled hemorrhage in emergency, surgical, and battlefield settings. Although a variety of hemostats, sealants, and adhesives are available, development of ideal hemostatic compositions that offer a range of remarkable properties including capability to effectively and immediately manage bleeding, excellent mechanical properties, biocompatibility, biodegradability, antibacterial effect, and strong tissue adhesion properties, under wet and dynamic conditions, still remains a challenge. Benefiting from tunable mechanical properties, high porosity, biocompatibility, injectability and ease of handling, polymeric hydrogels with outstanding hemostatic properties have been receiving increasing attention over the past several years. In this review, after shedding light on hemostasis and wound healing processes, the most recent progresses in hydrogel systems engineered from natural and synthetic polymers for hemostatic applications are discussed based on a comprehensive literature review. Most studies described used in vivo models with accessible and compressible wounds to assess the hemostatic performance of hydrogels. The challenges that need to be tackled to accelerate the translation of these novel hemostatic hydrogel systems to clinical practice are emphasized and future directions for research in the field are presented.

Absorbable hemostatic hydrogels comprising composites of sacrificial templates and honeycomb-like nanofibrous mats of chitosan

The development of hemostatic technologies that suit a diverse range of emergency scenarios is a critical initiative, and there is an increasing interest in the development of absorbable dressings that can be left in the injury site and degrade to reduce the duration of interventional procedures. In the current study, β-cyclodextrin polyester (CDPE) hydrogels serve as sacrificial macroporous carriers, capable of degradation under physiological conditions. The CDPE template enables the assembly of imprinted chitosan honeycomb-like monolithic mats, containing highly entangled nanofibers with diameters of 9.2 ± 3.7 nm, thereby achieving an increase in the surface area of chitosan to improve hemostatic efficiency. In vivo, chitosan-loaded cyclodextrin (CDPE-Cs) hydrogels yield significantly lower amounts of blood loss and shorter times to hemostasis compared with commercially available absorbable hemostatic dressings, and are highly biocompatible. The designed hydrogels demonstrate promising hemostatic efficiency, as a physiologically-benign approach to mitigating blood loss in tissue-injury scenarios.

Deneysel parsiyel splenektomi modelinde sıçanlarda algan hemostatik ajanın kanama kontrolünde etkinliğinin araştırılması

Objective: Algan hemostatic agent (AHA) is a plant-basedhemostatic agent produced in Turkey. Although, there is a greatimprovement in the hemostatic technologies, more effectivehemostatic products are required to be produced. The aim ofthis study was to demonstrate the efficacy of AHA in a partialsplenectomy model in rats. In addition, in this model, postoperativeabdominal adhesion was evaluated.Materials and Methods: In this study 5-7 weeks old 64rats were used. Rats were randomly divided into 8 groups, eachconsisting of eight rats (4 groups heparinized and 4 groups nonheparinized).Experimental splenectomy was performed and thegauze impregnated with saline was applied to the control group forthe hemorrhage control, the gauze impregnated with liquid AHA,gel and powder form of AHA, was applied to the experimentalgroups.Results: The time to reach complete homeostasis wassignificantly shorter in all AHA groups compared to the controlgroup. The powder and the gel forms of AHA stopped the bleedingin heparinized and non-heparinized groups in 1 second. The AHAfluid (sponge) form stopped the bleeding in the first applicationin the control group less than 10 seconds and the second timeapplication was not necessary. The bleeding was able to becontrolled in the heparinized control group (saline impregnatedsponge) by 55 seconds and in the non-heparinized control groupby 38 seconds.Conclusion: This study showed that AHA is a highly effectivehemostatic agent, which would be beneficial in controllinghemorrhage.

Biomaterials and Advanced Technologies for Hemostatic Management of Bleeding.

Bleeding complications arising from trauma, surgery, and as congenital, disease-associated, or drug-induced blood disorders can cause significant morbidities and mortalities in civilian and military populations. Therefore, stoppage of bleeding (hemostasis) is of paramount clinical significance in prophylactic, surgical, and emergency scenarios. For externally accessible injuries, a variety of natural and synthetic biomaterials have undergone robust research, leading to hemostatic technologies including glues, bandages, tamponades, tourniquets, dressings, and procoagulant powders. In contrast, treatment of internal noncompressible hemorrhage still heavily depends on transfusion of whole blood or blood's hemostatic components (platelets, fibrinogen, and coagulation factors). Transfusion of platelets poses significant challenges of limited availability, high cost, contamination risks, short shelf-life, low portability, performance variability, and immunological side effects, while use of fibrinogen or coagulation factors provides only partial mechanisms for hemostasis. With such considerations, significant interdisciplinary research endeavors have been focused on developing materials and technologies that can be manufactured conveniently, sterilized to minimize contamination and enhance shelf-life, and administered intravenously to mimic, leverage, and amplify physiological hemostatic mechanisms. Here, a comprehensive review regarding the various topical, intracavitary, and intravenous hemostatic technologies in terms of materials, mechanisms, and state-of-art is provided, and challenges and opportunities to help advancement of the field are discussed.

The Clot Thickens…

Ultra-deformable synthetic platelets stop bleeding in minutes.

Electrothermal bipolar vessel sealing system (LigaSure™) for hemostasis during thyroid surgery: a comprehensive review

Conventional hemostatic technologies utilized in thyroid surgery include clamp-and-tie, clips and monopolar and bipolar diathermy. Over the last decade, there has been a major shift towards utilizing newer hemostatic technologies, most notably the electrothermal bipolar vessel sealing systems (EBVS) and the Harmonic Scalpel® (Ethicon Endosurgery, OH, USA), for thyroid surgery. Since the first report of EBVS thyroidectomy in 2003, more than 50 studies have been published evaluating EBVS utilization for thyroid surgery. In addition to providing a historical perspective and exploring the principles of EBVS technology, this review aims to evaluate the current published data regarding EBVS utilization for thyroid surgery. In particular, a focus is given to LigaSure™ (Covidien, Dublin, Ireland) technology because it has been studied most thoroughly in the literature. This review will also evaluate studies comparing the EBVS with Harmonic Scalpel technology for thyroid surgery.

Comparison of lateral thermal damage of the human peritoneum using monopolar diathermy, Harmonic scalpel and LigaSure

New hemostatic technologies are often employed in open and laparoscopic surgery to reduce duration of surgery and complications. Monopolar diathermy, Harmonic scalpel and LigaSure are routinely used in open and laparoscopic surgery for tissue cutting and hemostasis. We compared lateral thermal damage following in vivo application of 3 commonly used instruments. We used monopolar diathermy, Harmonic scalpel and LigaSure to coagulate and divide the peritoneum of patients who underwent median laparotomy. After anesthesia, median supraumbilical laparotomy was performed, and the peritoneum of each patient was coagulated using different devices. Using light microscopy and morphometric imaging analysis, the width of tissue lateral thermal damage was measured from the point of the peritoneal incision. We included 100 patients in our study. After a peritoneal incision, the mean lateral thermal damage of monopolar diathermy, Harmonic scalpel (output power 3), Harmonic scalpel (output power 5) and LigaSure were 215.79 μm, 90.42 μm, 127.48 μm and 144.18 μm, respectively. The degree of lateral thermal spread varied by instrument type, power setting and application time. LigaSure and Harmonic scalpel were the safest and most efficient methods of tissue coagulation. Monopolar diathermy resulted in the greatest degree of thermal damage in tissues.

Principles and Safety Measures of Electrosurgery in Laparoscopy

Electrosurgical units are the most common type of electrical equipment in the operating room. A basic understanding of electricity is needed to safely apply electrosurgical technology for patient care. We reviewed the literature concerning the essential biophysics, the incidence of electrosurgical injuries, and the possible mechanisms for injury. Various safety guidelines pertaining to avoidance of injuries were also reviewed. Electrothermal injury may result from direct application, insulation failure, direct coupling, capacitive coupling, and so forth. A thorough knowledge of the fundamentals of electrosurgery by the entire team in the operating room is essential for patient safety and for recognizing potential complications. Newer hemostatic technologies can be used to decrease the incidence of complications.

Ligasure versus Ultracision® in thyroid surgery: a prospective randomized study

New hemostatic technologies (NT) are often employed in thyroid surgery in the effort to reduce operating time and complications. The aim of this study is to compare three different hemostatic techniques. This is a prospective randomized study. There were 150 patients, aged 56 +/- 14 years, randomized for total thyroidectomy with conventional technique (CT), Ligasure vessel sealing system (LI) or Harmonic Scalpel (HS) at the university surgical department. One hundred thirty-five patients had benign diseases; 15 had malignancies. Mean postoperative hospital stay was 2.6 days. Mean operation time was 113 +/- 31 min; in HS patients, it was significantly shorter (p < 0.001). Morbidity was 43.3%; mortality was nil. Morbidity was significantly different between CT and NT groups (p = 0.0002); HS and LI groups had a higher morbidity (p = 0.0001 and p = 0.02, respectively). Mean postoperative calcemia was 1.12 +/- 0.1 mmol/l with a significant difference between groups; NT patients had a significantly lower calcemia (p < 0.05). There was no difference in recurrent laryngeal nerve palsies and in intraoperative blood losses (p = ns). According to our experience, the only real advantage of new hemostatic technologies was a shorter operation time with HS.

Update and economic aspects of the harmonic scalpel in general surgery

BACKGROUND: The introduction of the harmonic scalpel appears to have had a considerable influence on conventional and minimally invasive surgery. METHODS: A review of the literature on the harmonic scalpel and its use in general surgery is presented. The costs of the harmonic scalpel are compared to other hemostatic technologies. RESULTS: The harmonic scalpel cuts and dissects tissues and vessels with a diameter of up to 3 mm via ultrasound vibration-induced denaturation of extracellular matrix proteins and formation of an insoluble gel. High-power ultrasonic dissection system facilitates and accelerates procedures in "open" and minimally invasive colorectal, hepato-, pancreatico-, biliary, upper gastrointestinal and endocrine surgery. Pitfalls include heat-induced tissue and organ injury. Economically, the harmonic scalpel is comparable to electrocoagulation and laparoscopic suture ligation. CONCLUSIONS: The harmonic scalpel represents a high-power ultrasound dissection system with a positive impact on operative technique and costs.