Hemostasis Using Prothrombin Complex Concentrate in Patients Undergoing Cardiac Surgery: Systematic Review with Meta-Analysis.

OBJECTIVE: The purpose of present study was to comprehensívely explore the efficacy and safety of prothrombín complex concentrate (PCC) to treat massíve bleedíng in patíents undergoing cardiac surgery. METHODS: PubMed®, Embase, and Cochrane Líbrary databases were searched for studíes ínvestigating PCC administratíon duríng cardiac surgery published before September 10, 2022. Mean dífference (MD) wíth 95% confidence interval (CI) was applíed to analyze continuous data, and dichotomous data were analyzed as risk ratio (RR) with 95% CI. RESULTS: Twelve studies were included in the meta-analysis. Compared with other non-PCC treatment regimens, PCC was not assocíated with elevated mortality (RR=1.18, 95% CI=0.86-1.60, P=0.30, I2=0%), shorter hospital stay (MD=-2.17 days; 95% CI=-5.62-1.28, P=0.22, I2=91%), reduced total thoracic drainage (MD=-67.94 ml, 95% CI=-239.52-103.65, P=0.44, I2=91%), thromboembolíc events (RR=1.10, 95% CI=0.74-1.65, P=0.63, I2=39%), increase ín atríal fibríllatíon events (RR=0.73, 95% CI=0.52-1.05, P=0.24, I2=29%), and myocardial infarction (RR=1.10, 95% CI=0.80-1.51, P=0.57, I2=81%). However, PCC use was associated with reduced intensive care unit length of stay (MD=-0.81 days, 95% CI=-1.48- -0.13, P=0.02, I2=0%), bleeding (MD=-248.67 ml, 95% CI=-465.36- -31.97, P=0.02, I2=84%), and intra-aortic balloon pump/extracorporeal membrane oxygenation (RR=0.65, 95% CI=0.42-0.996, P=0.05, I2=0%) when compared with non-PCC treatment regimens. CONCLUSION: The use of PCC in cardiac surgery did not correlate with mortality, length of hospítal stay, thoracic drainage, atríal fibríllatíon, myocardíal ínfarction, and thromboembolíc events. However, PCC sígnificantly improved postoperatíve intensíve care unít length of stay, bleedíng, and intra-aortic balloon pump/ extracorporeal membrane oxygenation outcomes ín patients undergoing cardíac surgery.

The hemostatic and comforting effects of oral adhesive bandages in tooth extraction: a randomized controlled clinical study.

OBJECTIVES: To compare oral adhesive bandages with the classic compression method and evaluate the clinical efficacy of this wound dressing material in improving postoperative comfort, wound healing, and hemostasis in tooth extraction. MATERIALS AND METHODS: The study was designed as a randomized controlled clinical trial. A total of 120 patients were recruited and randomly assigned to the study group and the control group. In the study group, oral adhesive bandages were used as wound dressing. In the control group, patients bit on cotton balls and gauze, as usual. Hemorrhage, comfort, and healing levels were evaluated at postoperative 1 h, 24 h, and 7 days. The adhesion time of the oral adhesive bandages was also recorded. RESULTS: The average adhesion time of the oral adhesive bandages was 26.6 h. At postoperative 1 and 24 h, the hemostatic levels of the oral adhesive bandage group were significantly higher than those of the control group. The oral adhesive bandage group also reported significantly higher comfort scores than the control group. Both groups had similar healing levels and side effects. But the mean score for wound healing was slightly higher in the oral adhesive bandage group. CONCLUSIONS: Oral adhesive bandages were more effective than cotton balls and gauze in providing hemostatic and comfort effects on extraction wounds. CLINICAL RELEVANCE: Oral adhesive bandages possess clinical value in the management of extraction wounds.

Post-Translational Oxidative Modifications of Hemostasis Proteins: Structure, Function, and Regulation.

Reactive oxygen species (ROS) are constantly generated in a living organism. An imbalance between the amount of generated reactive species in the body and their destruction leads to the development of oxidative stress. Proteins are extremely vulnerable targets for ROS molecules, which can cause oxidative modifications of amino acid residues, thus altering structure and function of intra- and extracellular proteins. The current review considers the effect of oxidation on the structural rearrangements and functional activity of hemostasis proteins: coagulation system proteins such as fibrinogen, prothrombin/thrombin, factor VII/VIIa; anticoagulant proteins - thrombomodulin and protein C; proteins of the fibrinolytic system such as plasminogen, tissue plasminogen activator and plasminogen activator inhibitor-1. Structure and function of the proteins, oxidative modifications, and their detrimental consequences resulting from the induced oxidation or oxidative stress in vivo are described. Possible effects of oxidative modifications of proteins in vitro and in vivo leading to disruption of the coagulation and fibrinolysis processes are summarized and systematized, and the possibility of a compensatory mechanism in maintaining hemostasis under oxidative stress is analyzed.

Unresolved hemostasis issues in haemophilia.

Despite rapid technological advancement in factor and nonfactor products in the prevention and treatment of bleeding in haemophilia patients, it is imperative that we acknowledge gaps in our understanding of how hemostasis is achieved. The authors will briefly review three unresolved issues in persons with haemophilia (PwH) focusing on the forgotten function that red blood cells play in hemostasis, the critical role of extravascular (outside circulation) FIX in hemostasis in the context of unmodified and extended half-life FIX products and finally on the role that skeletal muscle myosin plays in prothrombinase assembly and subsequent thrombin generation that could mitigate breakthrough muscle hematomas.

Guidelines for the management of coagulation disorders in patients with cirrhosis.

Coagulation management in the patient with cirrhosis has undergone a significant transformation since the beginning of this century, with the concept of a rebalancing between procoagulant and anticoagulant factors. The paradigm that patients with cirrhosis have a greater bleeding tendency has changed, as a result of this rebalancing. In addition, it has brought to light the presence of complications related to thrombotic events in this group of patients. These guidelines detail aspects related to pathophysiologic mechanisms that intervene in the maintenance of hemostasis in the patient with cirrhosis, the relevance of portal hypertension, mechanical factors for the development of bleeding, modifications in the hepatic synthesis of coagulation factors, and the changes in the reticuloendothelial system in acute hepatic decompensation and acute-on-chronic liver failure. They address new aspects related to the hemorrhagic complications in patients with cirrhosis, considering the risk for bleeding during diagnostic or therapeutic procedures, as well as the usefulness of different tools for diagnosing coagulation and recommendations on the pharmacologic treatment and blood-product transfusion in the context of hemorrhage. These guidelines also update the knowledge regarding hypercoagulability in the patient with cirrhosis, as well as the efficacy and safety of treatment with the different anticoagulation regimens. Lastly, they provide recommendations on coagulation management in the context of acute-on-chronic liver failure, acute liver decompensation, and specific aspects related to the patient undergoing liver transplantation.

Sex dimorphisms in coagulation: Implications in trauma-induced coagulopathy and trauma resuscitation.

Trauma-induced coagulopathy (TIC) is one of the leading causes of preventable death in injured patients. Consequently, it is imperative to understand the mechanisms underlying TIC and how to mitigate this mortality. An opportunity for advancement stems from the awareness that coagulation demonstrates a strong sex-dependent effect. Females exhibit a relative hypercoagulability compared to males, which persists after injury and confers improved outcomes. The mechanisms underlying sex dimorphisms in coagulation and its protective effect after injury have yet to be elucidated. This review explores sex dimorphisms in enzymatic hemostasis, fibrinogen, platelets, and fibrinolysis, with implications for resuscitation of patients with TIC.

The interaction of platelet-related factors with tumor cells promotes tumor metastasis.

Platelets not only participate in thrombosis and hemostasis but also interact with tumor cells and protect them from mechanical damage caused by hemodynamic shear stress and natural killer cell lysis, thereby promoting their colonization and metastasis to distant organs. Platelets can affect the tumor microenvironment via interactions between platelet-related factors and tumor cells. Metastasis is a key event in cancer-related death and is associated with platelet-related factors in lung, breast, and colorectal cancers. Although the factors that promote platelet expression vary slightly in terms of their type and mode of action, they all contribute to the overall process. Recognizing the correlation and mechanisms between these factors is crucial for studying the colonization of distant target organs and developing targeted therapies for these three types of tumors. This paper reviews studies on major platelet-related factors closely associated with metastasis in lung, breast, and colorectal cancers.

Process optimization and character evaluation of Bletilla striata polysaccharide (BSP) and chitosan (CS) composite hemostatic sponge (BSP-CS).

Bletilla striata polysaccharide (BSP) and chitosan (CS) were chemically cross-linked using oxalyl chloride to prepare a composite hemostatic sponge (BSP-CS), and the process parameters were optimized using the Box-Behnken design (BBD) with response surface methodology. To optimize the performance of the hemostatic sponge, we adjusted the ratio of independent variables, the amount of oxalyl chloride added, and the freeze-dried volume. A series of evaluations were conducted on the hemostatic applicability of BSP-CS. The characterization results revealed that BSP-CS had a stable bacteriostatic effect on Escherichia coli, Staphylococcus aureus, and Pseudomonas aeruginosa within 72 h, and the bacteriostatic rate was above 30%. The CCK-8 cytotoxicity test demonstrated that BSP-CS had a certain effect on promoting cell proliferation of L929 cells. In the mouse tail-cutting experiment, the hemostasis time of BSP-CS was 463.0±38.16 s, shortened by 91.3 s on average compared with 554.3±34.67 s of the gauze group. The blood loss of the BSP-CS group was 28.47±3.74 mg, which was 34.7% lower than that of the control gauze group (43.6±3.83 mg). In the in vitro coagulation experiment, the in vitro coagulation index of the BSP-CS group was 97.29%±1.8%, which was reduced to 8.6% of the control group. The CT value of the BSP-CS group was 240±15 s, which was 155 s lower than that of the gauze group (355±31.22 s). All characterization results indicate that BSP-CS is an excellent hemostatic material.

Antibacterial adhesive based on oxidized tannic acid-chitosan for rapid hemostasis.

Currently, bacterial infections and bleeding interfere with wound healing, and multifunctional hydrogels with appropriate blood homeostasis, skin adhesion, and antibacterial activity are desirable. In this study, chitosan-based hydrogels were synthesized using oxidized tannic acid (OTA) and Fe3+ as cross-linkers (CS-OTA-Fe) by forming covalent, non-covalent, and metal coordination bonds between Fe3+ and OTA. Our results demonstrated that CS-OTA-Fe hydrogels showed antibacterial properties against Gram-positive bacteria (Staphylococcus aureus)and Gram-negative bacteria (Escherichia coli), low hemolysis rate (< 2 %), rapid blood clotting ability, in vitro (< 2 min), and in vivo (90 s) in mouse liver bleeding. Additionally, increasing the chitosan concentration from 3 wt% to 4.5 wt% enhanced cross-linking in the network, leading to a significant improvement in the strength (from 106 ± 8 kPa to 168 ± 12 kPa) and compressive modulus (from 50 ± 9 kPa to 102 ± 14 kPa) of hydrogels. Moreover, CS-OTA-Fe hydrogels revealed significant adhesive strength (87 ± 8 kPa) to the cow's skin tissue and cytocompatibility against L929 fibroblasts. Overall, multifunctional CS-OTA-Fe hydrogels with tunable mechanical properties, excellent tissue adhesive, self-healing ability, good cytocompatibility, and fast hemostasis and antibacterial properties could be promising candidates for biomedical applications.

Mechanically Robust Hemostatic Hydrogel Membranes with Programmable Strain-Adaptive Microdomain Entanglement for Wound Treatment in Dynamic Tissues.

Supramolecular hydrogels emerge as a promising paradigm for sutureless wound management. However, their translation is still challenged by the insufficient mechanical robustness in the context of complex wounds in dynamic tissues. Herein, we report a tissue-adhesive supramolecular hydrogel membrane based on biocompatible precursors for dressing wounds in highly dynamic tissues, featuring robust mechanical resilience through programmable strain-adaptive entanglement among microdomains. Specifically, the hydrogels are synthesized by incorporating a long-chain polyurethane segment into a Schiff base-ligated short-chain oxidized cellulose/quaternized chitosan network via acylhydrazone bonding, which readily establishes interpenetrating entangled microdomains in dynamic cross-linked hydrogel matrices to enhance their tear and fatigue resistance against extreme mechanical stresses. After being placed onto dynamic tissues, the hydrogel dressing could efficiently absorb blood to achieve rapid hemostasis. Moreover, metal ions released from ruptured erythrocytes could be scavenged by the Schiff base linkers to form additional ionic bonds, which would trigger the cross-linking of the short-chain components and establish abundant crystalline microdomains, eventually leading to the in situ stiffening of the hydrogels to endure heavy mechanical loads. Benefiting from its hemostatic capacity and strain adaptable mechanical performance, this hydrogel wound dressing shows promise for the clinical management of various traumatic wounds.

[Factors of the hemostasis system as biomarkers of severe course of acute viral infections]. / Faktory sistemy gemostaza kak biomarkery tyazhelogo techeniya ostrykh virusnykh infektsii.

The authors give literature review of hemostasis and immune system factors intraction as main biomarkers of a severe cause of viral infectious diseases. Pro-inflamatory cytokines as the main markers of inflammation, can serve both as biomarkers of the clinical severity of the infectious process and reflect the state of the hemostatic and fibrinolytic systems, since components of these systems are present in various structures of the central nervous system and affect the development of neurons and synaptic plasticity. An inverse correlation has been proven between the concentration of D-dimer and the oxygenation index, and the development of DIC is not associated with the presence of respiratory failure in patients with influenza type A, while the ferritin concentration directly reflects the severity of the disease. One of the markers of endothelial damage may be soluble thrombomodulin, which, however, is rarely used in routine clinical practice. Cytoflavin is a highly effective pathogenetic drug that affects various parts of the hemostasis system, has anti-ischemic, antioxidant, antihypoxic, immunocorrective effect, which is indicated for any generalized infectious disease since its debut.

Degradation-controlled tissue extracellular sponge for rapid hemostasis and wound repair after kidney injury.

Patients diagnosed with T1a cancer undergo partial nephrectomy to remove the tumors. In the process of removing the tumors, loss of kidney volume is inevitable, and current surgical methods focus solely on hemostasis and wound closure. Here, we developed an implantable form of decellularized extracellular matrix sponge to target both hemostasis and wound healing at the lesion site. A porous form of kidney decellularized matrix was achieved by fabricating a chemically cross-linked cryogel followed by lyophilization. The prepared kidney decellularized extracellular matrix sponge (kdES) was then characterized for features relevant to a hemostasis as well as a biocompatible and degradable biomaterial. Finally, histological evaluations were made after implantation in rat kidney incision model. Both gelatin sponge and kdES displayed excellent hemocompatibility and biocompatibility. However, after a 4-week observation period, kdES exhibited more favorable wound healing results at the lesion site. This suggests a promising potential for kdES as a supportive material in facilitating wound closure during partial nephrectomy surgery. KdES not only achieved rapid hemostasis for managing renal hemorrhage that is comparable to commercial hemostatic sponges, but also demonstrated superior wound healing outcomes.

Plant mucus-derived microgels: Blood-triggered gelation and strong hemostatic adhesion.

Arrest of bleeding usually applies clotting agents to trigger coagulation procedures or adhesives to interrupt blood flow through sealing the vessel; however, the efficiency is compromised. Here, we propose a concept of integration of hemostasis and adhesion via yam mucus's microgels. The mucus microgels exhibit attractive attributes of hydrogel with uniform size and shape. Their shear-thinning, self-healing and strong adhesion make them feasible as injectable bioadhesion. Exceptionally, the blood can trigger the microgels' gelation with the outcome of super extensibility, which leads to the microgels a strong hemostatic agent. We also found a tight gel adhesive layer formed upon microgels' contacting the blood on the tissue, where there is the coagulation factor XIII triggered to form a dense three-dimensional fibrin meshwork. The generated structures show that the microgels look like hard balls in the dispersed phase into the blood-produced fibrin mesh of a soft net phase. Both phases work together for a super-extension gel. We demonstrated the microgels' fast adhesion and hemostasis in the livers and hearts of rabbits and mini pigs. The microgels also promoted wound healing with good biocompatibility and biodegradability.

Antibacterial and self-healing sepiolite-based hybrid hydrogel for hemostasis and wound healing.

The process of wound healing necessitates a specific environment, thus prompting extensive research into the utilization of hydrogels for this purpose. While numerous hydrogel structures have been investigated, the discovery of a self-healing hydrogel possessing favorable biocompatibility, exceptional mechanical properties, and effective hemostatic and antibacterial performance remains uncommon. In this work, a polyvinyl alcohol (PVA) hybrid hydrogel was meticulously designed through a simple reaction, wherein CuxO anchored sepiolite was incorporated into the hydrogel. The results indicate that introduction of sepiolite greatly improves the toughness, self-healing and adhesion properties of the PVA hydrogels. CuxO nanoparticles endow the hydrogels with excellent antibacterial performance towards Staphylococcus aureus and Escherichia coli. The application of hybrid hydrogels for fast hemostasis and wound healing are verified in vitro and in vivo with rat experiments. This work thereby demonstrates an effective strategy for designing biodegradable hemostatic and wound healing materials.

Assessment of hemostatic ability of biomaterial based on chitosan andEclipta prostrataL. extract.

The biomaterials based on chitosan andEclipta prostrataL. extract have been prepared by microemulsion method and solution method (with and without sodium tripolyphosphate (STPP) as a cross-linking agent). The main component inEclipta prostrataL. extract is flavonoid groups. The structure of the chitosan/extract biomaterials was studied by infrared spectroscopy. The chitosan/extract biomaterial using STPP cross-linker appeared an absorption band at 1152 cm-1attributed to the vibrations of C-O-P bonds, which proved that chitosan has crosslinked with STPP. The morphology of the biomaterials was investigated by the dynamic light scattering technique and field emission scanning electron microscopy. The obtained results showed that the particle size of the chitosan/extract biomaterials prepared by microemulsion method and solution method with STPP ranged from 68.06 nm to 1484 nm, with an average particle size of 304.9-1019 nm. The microemulsion method produced biomaterials with much smaller average particle size than the solution method using cross-linkers. The hemostatic ability of the biomaterials was better than that of the control sample based on the time of blood clotting formation and glomerular aggregation ability. The sample with the ratio ofE. prostrataL. extract: chitosan of 1:30 had the lowest hemostasis time (6 min 46 s) and its glomerular aggregation rate after 5 min was 13.05%. This indicated that the biomaterials based on chitosan andE. prostrataL. extract are promising for application in biomedicine as hemostatic materials.

Alginate based biomaterials for hemostatic applications: Innovations and developments.

Development of the efficient hemostatic materials is an essential requirement for the management of hemorrhage caused by the emergency situations to avert most of the casualties. Such injuries require the use of external hemostats to facilitate the immediate blood clotting. A variety of commercially available hemostats are present in the market but most of them are associated with limitations such as exothermic reactions, low biocompatibility, and painful removal. Thus, fabrication of an ideal hemostatic composition for rapid blood clot formation, biocompatibility, and antimicrobial nature presents a real challenge to the bioengineers. Benefiting from their tunable fabrication properties, alginate-based hemostats are gaining importance due to their excellent biocompatibility, with >85 % cell viability, high absorption capacity exceeding 500 %, and cost-effectiveness. Furthermore, studies have estimated that wounds treated with sodium alginate exhibited a blood loss of 0.40 ± 0.05 mL, compared to the control group with 1.15 ± 0.13 mL, indicating its inherent hemostatic activity. This serves as a solid foundation for designing future hemostatic materials. Nevertheless, various combinations have been explored to further enhance the hemostatic potential of sodium alginate. In this review, we have discussed the possible role of alginate based composite hemostats incorporated with different hemostatic agents, such as inorganic materials, polymers, biological agents, herbal agents, and synthetic drugs. This article outlines the challenges which need to be addressed before the clinical trials and give an overview of the future research directions.

Facile preparation of fatigue-resistant Mxene-reinforced chitosan cryogel for accelerated hemostasis and wound healing.

The development of highly effective chitosan-based hemostatic materials that can be utilized for deep wound hemostasis remains a considerable challenge. In this study, a hemostatic antibacterial chitosan/N-hydroxyethyl acrylamide (NHEMAA)/Ti3C2Tx (CSNT) composite cryogel was facilely prepared through the physical interactions between the three components and the spontaneous condensation of NHEMAA. Because of the formation of strong crosslinked network, the CSNT cryogel showed a developed pore structure (~ 99.07 %) and superfast water/blood-triggered shape recovery, enabling it to fill the wound after contacting the blood. Its capillary effect, amino groups, negative charges, and affinity with lipid collectively induced rapid hemostasis, which was confirmed by in vitro and in vivo analysis. In addition, CSNT cryogel showed excellent photothermal antibacterial activities, high biosafety, and in vivo wound healing ability. Furthermore, the presence of chitosan effectively prevented the oxidation of MXene, thus enabling the long-term storage of the MXene-reinforced cryogel. Thus, our hemostatic cryogel demonstrates promising potential for clinical application and commercialization, as it combines high resilience, rapid hemostasis, efficient sterilization, long-term storage, and easy mass production.