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Bioconjugate Chemistry Jul 2015While there are currently many well-established topical hemostatic agents for field administration, there are still limited tools to staunch bleeding at less accessible... (Review)
Review
While there are currently many well-established topical hemostatic agents for field administration, there are still limited tools to staunch bleeding at less accessible injury sites. Current clinical methods to restore hemostasis after large volume blood loss include platelet and clotting factor transfusion, which have respective drawbacks of short shelf life and risk of viral transmission. Therefore, synthetic hemostatic agents that can be delivered intravenously and encourage stable clot formation after localizing to sites of vascular injury are particularly appealing. In the past three decades, platelet substitutes have been prepared using drug delivery vehicles such as liposomes and PLGA nanoparticles that have been modified to mimic platelet properties. Additionally, structural considerations such as particle size, shape, and flexibility have been addressed in a number of reports. Since platelets are the first responders after vascular injury, platelet substitutes represent an important class of intravenous hemostats under development. More recently, materials affecting fibrin formation have been introduced to induce faster or more stable blood clot formation through fibrin cross-linking. Fibrin represents a major structural component in the final blood clot, and a fibrin-based hemostatic mechanism acting downstream of initial platelet plug formation may be a safer alternative to platelets to avoid undesired thrombotic activity. This Review explores intravenous hemostats under development and strategies to optimize their clotting activity.
Topics: Administration, Intravenous; Amino Acid Sequence; Animals; Artificial Cells; Blood Platelets; Drug Discovery; Fibrin; Hemostasis; Hemostatics; Humans; Molecular Sequence Data; Peptides
PubMed: 25803791
DOI: 10.1021/acs.bioconjchem.5b00070 -
Marine Drugs Jan 2021In the current study, hemostatic compositions including a combination of chitosan and kaolin have been developed. Chitosan is a marine polysaccharide derived from...
In the current study, hemostatic compositions including a combination of chitosan and kaolin have been developed. Chitosan is a marine polysaccharide derived from chitins, a structural component in the shells of crustaceans. Both chitosan and kaolin have the ability to mediate a quick and efficient hemostatic effect following immediate application to injury sites, and thus they have been widely exploited in manufacturing of hemostatic composites. By combining more than one hemostatic agent (i.e., chitosan and kaolin) that act via more than one mechanism, and by utilizing different nanotechnology-based approaches to enhance the surface areas, the capability of the dressing to control bleeding was improved, in terms of amount of blood loss and time to hemostasis. The nanotechnology-based approaches utilized to enhance the effective surface area of the hemostatic agents included the use of Pluronic nanoparticles, and deposition of chitosan micro- and nano-fibers onto the carrier. The developed composites effectively controlled bleeding and significantly improved hemostasis and survival rates in two animal models, rats and rabbits, compared to conventional dressings and QuikClot Combat Gauze. The composites were well-tolerated as demonstrated by their in vivo biocompatibility and absence of clinical and biochemical changes in the laboratory animals after application of the dressings.
Topics: Animals; Bandages; Chitosan; Drug Design; Drug Evaluation, Preclinical; Female; Hemorrhage; Hemostasis; Hemostatics; Kaolin; Male; Nanocomposites; Rabbits; Rats; Rats, Sprague-Dawley
PubMed: 33499020
DOI: 10.3390/md19020050 -
Marine Drugs Apr 2021Uncontrolled bleeding is the main cause of mortality from trauma. Collagen has been developed as an important hemostatic material due to its platelet affinity function....
Uncontrolled bleeding is the main cause of mortality from trauma. Collagen has been developed as an important hemostatic material due to its platelet affinity function. A bath sponge skeleton is rich in collagen, also known as spongin. To understand the hemostatic effect of spongin, spongin materials, SX, SFM and SR were prepared from the bath sponge , and hemostatic experiments were performed. The SX, SFM and SR were significantly better than the positive control, type I collagen, in shortening the whole blood clotting time in vitro and hemostasis upon rat tail amputation. In a hemostatic experiment of rabbit common carotid artery injury, the hemostatic time and 3 h survival rate of the SFM group were 3.00 ± 1.53 min and 100%, respectively, which are significantly better than those of the commercial hemostat CELOX-A (10.33 ± 1.37 min and 67%, respectively). Additionally, the SFM showed good coagulation effects in platelet-deficient blood and defibrinated blood, while also showing good biocompatibility. Through a variety of tests, we speculated that the hemostatic activity of the SFM is mainly caused by its hyperabsorbency, high affinity to platelets and high effective concentration. Overall, the SFM and spongin derivates could be potential hemostatic agents for uncontrolled bleeding and hemorrhagic diseases caused by deficiency or dysfunction of coagulation factors.
Topics: Animals; Blood Coagulation; Blood Coagulation Tests; Carotid Artery Injuries; Collagen; Disease Models, Animal; Hemorrhage; Hemostasis; Hemostatics; Molecular Structure; Platelet Activation; Platelet Function Tests; Porifera; Rabbits; Rats; Structure-Activity Relationship
PubMed: 33921176
DOI: 10.3390/md19040220 -
Journal of Thrombosis and Haemostasis :... Aug 2012Understanding the mechanism of action of normal hemostasis and how the bypassing agents recombinant activated factor VII (rFVIIa; NovoSeven) and plasma-derived activated... (Review)
Review
Understanding the mechanism of action of normal hemostasis and how the bypassing agents recombinant activated factor VII (rFVIIa; NovoSeven) and plasma-derived activated prothrombin complex concentrate (Factor Eight Inhibitor Bypassing Agent [FEIBA]) control abnormal bleeding is imperative for healthcare professionals who treat patients with hemophilia and other bleeding disorders. A cell-based model has improved our understanding of in vivo mechanisms of hemostasis and the basis of the bleeding tendency in hemophilia. Bypassing agents do not restore the normal pathways of hemostasis in hemophilia, but rather boost thrombin generation in spite of a lack of platelet surface FVIIIa-FIXa ('tenase') activity. Thus, the common clinical laboratory coagulation assays do not reflect the clinically relevant hemostatic activity of bypassing agents, and no validated assay is available with which to measure the in vivo efficacy of these agents or predict individual patient responses to treatment. Global hemostasis assays measuring overall coagulation capacity have potential for assessment of the effects of bypassing agents. This review will focus on the mechanisms of clotting and their relationship to understanding the mechanisms of action of the bypassing agents in vivo and the methodologies that are emerging to monitor the clinical efficacy of bypassing agent therapy.
Topics: Animals; Blood Coagulation Factors; Blood Coagulation Tests; Drug Monitoring; Factor VIIa; Hemophilia A; Hemostasis; Hemostatics; Humans; Predictive Value of Tests; Recombinant Proteins; Treatment Outcome
PubMed: 22632160
DOI: 10.1111/j.1538-7836.2012.04793.x -
Trials Jul 2021Endometriosis (EMS) can be implanted everywhere, especially in pelvic organs. EMS can be asymptomatic, but it can result in pelvic pain and infertility by inducing local...
Preservation of the ovarian reserve and hemostasis during laparoscopic ovarian cystectomy by a hemostatic agent versus suturing for patients with ovarian endometriosis: study protocol for randomized controlled, non-inferiority trial (PRAHA-2 trial).
BACKGROUND
Endometriosis (EMS) can be implanted everywhere, especially in pelvic organs. EMS can be asymptomatic, but it can result in pelvic pain and infertility by inducing local inflammation and pelvic adhesion. The prevalence of EMS is about 10% in reproductive-age women and higher in women with pelvic pain or infertility. For young patients with ovarian EMS, laparoscopic ovarian cystectomy is effective in relieving pelvic pain and preventing local recurrence. However, there is a concern that the ovarian reserve would decrease after the operation because of the removal of a part of the normal ovarian tissue and thermal damage during hemostasis, which depends on the types of hemostasis such as bipolar electrocoagulation, suturing, and the use of a hemostatic agent. In this study, we aim to evaluate the protective effect for the ovarian reserve and hemostasis between a hemostatic agent and suturing during laparoscopic ovarian cystectomy for patients with ovarian EMS.
METHODS
This study is a randomized controlled, non-inferiority trial, where a total of 90 patients with ovarian EMS will be randomly assigned to the experimental (hemostatic agent) and control (suturing) groups. In the control group, a barbed suture will be applied for hemostasis, whereas a hemostatic agent will be applied in the experimental group. If two methods are insufficient, bipolar electrocoagulation will be applied for complete hemostasis. As the primary endpoint, the reduction rate of serum anti- Müllerian hormone (AMH) levels reflecting the ovarian reserve will be compared between the two groups 12 weeks after surgery. As secondary endpoints, we will compare the reduction rate of AMH level 48 weeks after surgery, the time required to complete hemostasis, the success rate of hemostasis within 10 min, and adverse events associated with operation.
DISCUSSION
We expect that the protective effect for the ovarian reserve and hemostasis may be comparable between the two methods, suggesting that a hemostatic agent may be preferred considering that it is easy to use during laparoscopic ovarian cystectomy.
TRIAL REGISTRATION
ClinicalTrials.gov NCT04643106 . Registered on 22 November 2020.
Topics: Anti-Mullerian Hormone; Cystectomy; Endometriosis; Female; Hemostasis; Hemostatics; Humans; Laparoscopy; Neoplasm Recurrence, Local; Ovarian Reserve; Randomized Controlled Trials as Topic; Sutures
PubMed: 34289889
DOI: 10.1186/s13063-021-05431-1 -
International Journal of Gynaecology... Feb 2017To determine if the use of intraoperative hemostatic agents was a risk factor for post-operative adverse events within 30 days of patients undergoing hysterectomy. (Observational Study)
Observational Study
OBJECTIVE
To determine if the use of intraoperative hemostatic agents was a risk factor for post-operative adverse events within 30 days of patients undergoing hysterectomy.
METHOD
A population-based retrospective cohort study included data from patients undergoing hysterectomy for any indication between January 1, 2013, and December 31, 2014, at 52 hospitals in Michigan, USA. Any individuals with missing covariate data were excluded, and multivariable logistic regression and propensity score-matching were used to estimate the rate of post-operative adverse events associated with intra-operative hemostatic agents independent of demographic and surgical factors.
RESULTS
There were 17 960 surgical procedures included in the analysis, with 4659 (25.9%) that included the use of hemostatic agents. Hemostatic agent use was associated with an increase in predicted hospital re-admissions (P=0.007). Among all hysterectomy approaches, and after adjusting for demographic and surgical factors, hemostatic agent use during robotic-assisted laparoscopic hysterectomy was associated with an increased predicted rate of blood transfusions (P=0.019), an increased predicted rate of pelvic abscess diagnoses (P=0.001), an increased predicted rate of hospital re-admission (P=0.001), and an increased predicted rate of re-operation (P=0.021).
CONCLUSION
Hemostatic agents should be used carefully owing to associations with increased post-operative re-admissions and re-operations when used during hysterectomy.
Topics: Adult; Blood Transfusion; Female; Hemostatics; Humans; Hysterectomy; Laparoscopy; Logistic Models; Michigan; Middle Aged; Multivariate Analysis; Patient Admission; Pelvic Infection; Postoperative Complications; Reoperation; Retrospective Studies; Risk Factors
PubMed: 28099744
DOI: 10.1002/ijgo.12037 -
Journal of Vascular Surgery Jun 2021Hemostatic agents are routinely used in vascular surgery to complement proper suture techniques and decrease the risk of perioperative bleeding. A relative lack of...
BACKGROUND
Hemostatic agents are routinely used in vascular surgery to complement proper suture techniques and decrease the risk of perioperative bleeding. A relative lack of comparative research studies have left surgeons with the option of choosing hemostatic agents based on their personal experience. The present review has highlighted the efficacy and safety of hemostatic agents and categorized them according to their primary mechanism of action and cost.
METHODS
A systematic search strategy encompassing hemostatic agent products was deployed in the PubMed database. Single-center and multicenter, randomized, controlled trials with >10 patients were included in the present study.
RESULTS
We reviewed 12 studies on the efficacy and safety of hemostatic agents compared with manual compression or other hemostatic agents. Using the time to hemostasis as the primary end point, all studies had found hemostatic agents to be significantly more efficient than manual compression. Likewise, adhesives (high pressure sealants) and dual agents (containing biologically active and absorbable components) were found to be more efficient, but costlier, than agents with either biologically active or absorbable components only. Agents with porcine or bovine constituents were found to trigger anaphylactic reactions in rare cases. Additionally, the absence of fibrin stabilizing factor XIII in a brand of fibrin sealant was speculated to reduce the affinity of the fibrin sealant for the expanded polytetrafluoroethylene graft. The cost of agents varied greatly depending on their active ingredient.
CONCLUSIONS
Hemostatic agents appear to be highly effective at decreasing the risk of bleeding during surgical procedures. Although some hemostatic agents were demonstrated to achieve hemostasis faster than others, most are able to control bleeding within <10 minutes. Based on the limited data, the least expensive agents might suffice for limited suture lines used in routine procedures.
Topics: Blood Loss, Surgical; Cost-Benefit Analysis; Drug Costs; Hemostatic Techniques; Hemostatics; Humans; Postoperative Hemorrhage; Randomized Controlled Trials as Topic; Risk Assessment; Risk Factors; Suture Techniques; Time Factors; Treatment Outcome; Vascular Surgical Procedures
PubMed: 33253866
DOI: 10.1016/j.jvs.2020.10.081 -
Biomolecules Jun 2022The timely and effective control and repair of wound bleeding is a key research issue all over the world. From traditional compression hemostasis to a variety of new... (Review)
Review
The timely and effective control and repair of wound bleeding is a key research issue all over the world. From traditional compression hemostasis to a variety of new hemostatic methods, people have a more comprehensive understanding of the hemostatic mechanism and the structure and function of different types of wound dressings. Electrospun nanofibers stand out with nano size, high specific surface area, higher porosity, and a variety of complex structures. They are high-quality materials that can effectively promote wound hemostasis and wound healing because they can imitate the structural characteristics of the skin extracellular matrix (ECM) and support cell adhesion and angiogenesis. At the same time, combined with amino acid polymers with good biocompatibility not only has high compatibility with the human body but can also be combined with a variety of drugs to further improve the effect of wound hemostatic dressing. This paper summarizes the application of different amino acid electrospun wound dressings, analyzes the characteristics of different materials in preparation and application, and looks forward to the development of directions of poly(amino acid) electrospun dressings in hemostasis.
Topics: Amino Acids; Hemostasis; Hemostatics; Humans; Nanofibers; Wound Healing
PubMed: 35740919
DOI: 10.3390/biom12060794 -
American Journal of Hematology Aug 2007Desmopressin, a synthetic derivative of the antidiuretic hormone vasopressin, is the treatment of choice for most patients with von Willebrand disease and mild... (Review)
Review
Desmopressin, a synthetic derivative of the antidiuretic hormone vasopressin, is the treatment of choice for most patients with von Willebrand disease and mild hemophilia A. Moreover, the compound has been shown to be useful in a variety of inherited and acquired hemorrhagic conditions, including some congenital platelet function defects, chronic liver disease, uremia, and hemostatic defects induced by the therapeutic use of antithrombotic drugs such as aspirin and ticlopidine. Finally, desmopressin has been used as a blood saving agent in patients undergoing operations characterized by large blood loss and transfusion requirements, but studies suggest that this is not as effective as other methods. This review briefly summarizes the current clinical indications on the use of desmopressin as a hemostatic agent.
Topics: Deamino Arginine Vasopressin; Drug-Related Side Effects and Adverse Reactions; Hemophilia A; Hemorrhage; Hemostatics; Humans; von Willebrand Diseases
PubMed: 17492648
DOI: 10.1002/ajh.20940 -
Journal of Comparative Effectiveness... Dec 2022Bleeding during spine surgery is controlled using topical hemostatic agents. Studies have reported outcomes between Surgiflo and Floseal, the most widely used flowable...
Bleeding during spine surgery is controlled using topical hemostatic agents. Studies have reported outcomes between Surgiflo and Floseal, the most widely used flowable hemostatic matrices, but have not included the latest Surgiflo formulation which is more adherent to the bleeding surface than prior formulations. A propensity score-matched analysis was conducted using the Premier Healthcare Database to compare economic and clinical outcomes of adults undergoing inpatient spinal surgery between 2013 and 2018 receiving current Surgiflo or Floseal. This retrospective study included 28,910 patients in each group and found comparable outcomes for bleeding events, overall transfusion rate, inpatient mortality and readmissions between Surgiflo and Floseal. Surgiflo was associated with $430 (USD) lower hospitalization costs, shorter length of stay and shorter operating room time than Floseal.
Topics: Adult; Humans; Hemostatics; Retrospective Studies; Blood Loss, Surgical; Blood Transfusion; Databases, Factual
PubMed: 36306241
DOI: 10.2217/cer-2021-0218