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RADA16 as a novel hemostatic and regenerative agent in urology: European Association of Urology endourology up-to-date overview.

PURPOSE OF REVIEW: Self-assembling peptide (SAP) hydrogels represent a novel class of synthetic biomaterials with growing relevance in surgery. Among them, the ion-complementary peptide RADA16 has gained attention as an athermal, transparent, and biocompatible hemostatic agent. While its use is increasingly reported in multiple surgical specialties, evidence specific to urology remains fragmented. This review aims to summarize the physicochemical properties, mechanisms of action, and current clinical evidence for RADA16-based hydrogels, with a particular focus on urological applications. RECENT FINDINGS: RADA16 rapidly self-assembles into a transparent, extracellular-matrix-like nanofibrillar hydrogel upon exposure to physiological fluids, providing effective local hemostasis without reliance on the coagulation cascade. Preclinical and clinical data from other surgical fields demonstrate rapid bleeding control, favorable safety, and potential regenerative effects. Emerging urological evidence suggests that RADA16 is effective in managing hemorrhagic cystitis, radiation-induced hematuria, and bleeding during prostate surgery, including robot-assisted radical prostatectomy and benign prostate surgery. Beyond hemostasis, RADA16 may support wound healing and promotion of re-epithelialization. However, the current evidence base is limited by small sample sizes, lack of comparative studies, heterogeneous methodologies, and short follow-up. SUMMARY: RADA16-based hydrogels represent a promising adjunctive hemostatic option in urology, offering technical advantages such as transparency, absence of thermal injury, minimal swelling, and applicability in confined or high-risk settings. Robust prospective, comparative, and cost-effectiveness studies are required to define its definitive role in routine urological practice.

Humans↗

Use of chitosan as a biomaterial: studies on its safety and hemostatic potential.

Chitosan, a mucopolysaccharide of marine origin, was studied for its safety and hemostatic potential. Its surface was treated with glutaraldehyde, carbodiimide, and plasma glow discharge to elicit effects of enzyme degradation. Of the seven enzymes used, leucine amino peptidase caused maximum degradation. Autoclaving appeared to be an ideal sterilizing method as it caused least decrease in tensile strength and effected a negligible rate of hemolysis. Sterilizing with glutaraldehyde with a physiologic pH retained the maximum tensile strength of chitosan. In vivo toxicity tests indicated that it is nontoxic, and the sterilized films were free of pyrogen. Coagulation and hemagglutination tests showed that the hemostatic mechanism of chitosan seems to be independent of the classical coagulation cascade and appears to be an interaction between the cell membrane of erythrocytes and chitosan.

Animals↗

An in vitro evaluation of the hemostatic activity of topical agents.

An in vitro method has been developed for human non-anticoagulated blood to evaluate the enhancing effect of hemostatic agents on both plasmatic and cellular activation of the coagulation cascade. The coagulation time and the sequential generation of fibrinopeptide A (FpA) have been used as parameters. The kinetics of generation of FpA has been modelized and mathematically analyzed using the latence time, the slope of the linear part of the curve, and the time necessary to reach half maximal amplitude of FpA in the tube. A maximal amplitude of FpA in the tube. A very precise evaluation of the hemostatic activity of five different molecules, four being collagenous in nature, is given.

Analysis of Variance↗

Effect of local hemostatics on bone induction in rats: a comparative study of bone wax, fibrin-collagen paste, and bioerodible polyorthoester with and without gentamicin.

Local hemostatics for osseous tissue should preferably be absorbable and biocompatible and should not inhibit osteogenesis. The tissue response and effect on demineralized bone-induced heterotopic osteogenesis in the abdominal muscle of 120 male Wistar rats by different local hemostatics were evaluated by light microscopy and 85Sr uptake analyses. Non-absorbable bone wax of 88% beeswax and absorbable bovine fibrin-collagen paste both significantly inhibited osteoinduction, whereas a bioerodible polyorthoester drug delivery system with or without 4% gentamicin did not. Bone wax was not absorbed and induced a chronic foreign body reaction. Fibrin-collagen paste induced less inflammation with numerous monocytes and macrophages with engulfed material. Bioerodible polyorthoester caused a very moderate tissue reaction and was mostly resorbed at week 4.

Absorption↗

Structural design of the dry fibrin sealant dressing and its impact on the hemostatic efficacy of the product.

We compared the hemostatic efficacy of a production version of a dry fibrin sealant dressing (DFSD) to a prototype that was previously successful in large animal studies. The results were used to improve manufacturing processes. Grade-V liver injuries were induced in swine and treated with gauze sponges (GAU), the prototype dressings (DFSD-1), or the scaled-up production version dressings (DFSD-2 in experiment 1 and DFSD-3 in experiment 2). Blood loss, hemostasis, resuscitation volume, and 60-min survival were quantified. In experiment 1, the DFSD-1 treatment reduced blood loss (p < 0.01), increased hemostasis at 4 min (p < 0.05), and improved survival (p < 0.05) compared with GAU. The DFSHD-2 decreased blood loss (p < 0.05) but did not increase hemostasis or survival significantly. Based on these results, manufacturing processes were altered, producing DFSD-3. In experiment 2, the DFSD-1 and DFSD-3 were equally effective in reducing blood loss (p < 0.01) and resuscitation volume (p < 0.05) compared with GAU. Hemostasis occurred more frequently in both the DFSD-1 and DFSD-3 groups (p < 0.01) compared with GAU. The structural design of DFSD-2 did not meet the efficacy requirement for release of the product. The subsequent change incorporated in DFSD-3 improved all hemostatic parameters of the dressings equal to those of the prototype product.

Animals↗

The hemostatic effect of deacetylated chitin membrane on peritoneal injury in rabbit model.

In this study, we determined the effect of 80% deacetylated chitin (DAC-80) membrane on postsurgical bleeding after visceral and parietal peritoneal abrasion. Japanese white rabbits underwent a midline laparotomy followed either by a bilateral peritoneal sidewall abrasion (4 x 4 cm) or an abrasion of liver surface (3 x 2 cm). The injured surface was then covered with a 0.2 mm thick DAC-80 membrane. On postsurgical day 2, the rabbits were sacrificed and the amounts of postsurgical bleeding was determined by quantitating the number of red blood cells recovered in 50 ml peritoneal lavage fluid. The DAC-80 membrane was found to reduce postsurgical bleeding after the abrasion of liver surface (treated with DAC-80 membrane: 2.9 +/- 0.8; control: 24.6 +/- 5.9 x 10(8) cells/peritoneal cavity, P less than 0.005). This same hemostatic activity was not observed after application in the peritoneal sidewall abrasion model. We also measured plasminogen activator activity (PA) and urokinase inhibitory (PAI) activity in the spent culture media of macrophages recovered from the postsurgical peritoneal exudate. The DAC-80 membrane reduced the PA secretion from postsurgical macrophages after liver surface abrasion (treated with DAC-80: 2.8 +/- 0.7; control: 3.9 +/- 0.9 mPU/ml). The DAC-80 membrane also showed similar effects on PA secretion after peritoneal sidewall abrasion. No significant effects were found in the secretion of PAI by postsurgical macrophages in both surgical models. These findings suggest that the DAC-80 membrane may have hemostatic activity through the modulation of fibrinolytic activity of peritoneal exudative macrophages.

Adolescent↗

Control of upper gastrointestinal bleeding with a microcrystalline collagen hemostat.

A microcrystalline collagen hemostat (MCH) widely used in general surgery was tested in the control of bleeding from experimentally produced gastric ulcers. Five dogs had a gastrotomy and were given heparin. Using the standard "ulcer maker," three sets of three ulcers were made in the gastric mucosa of each animal. Blood from each ulcer was collected for a 5-min period to allow for stabilization of bleeding. MCH powder or slurry or no MCH was placed directly on one ulcer of each set in random order. The bleeding rate for the next 10 min was measured. Mean decrements in the bleeding rate for slurry MCH and dry MCH-treated ulcers were 87% and 81%, respectively, compared with 51% for controls, P less than 0.05. Twelve MCH-treated ulcers, but no control ulcer, stopped bleeding completely, P less than 0.01. Preliminary observations show that MCH slurry can be applied through an endoscope and may be hemostatically effective in man. MCH may have a role in the endoscopic control of gastrointestinal bleeding.

Animals↗

Hemostatic changes in patients with malignancy.

Alterations of hemostasis commonly accompany the progression of malignant disease and every known component of the hemostatic mechanism may be affected by this disease process. Nearly all patients with an active neoplasm will exhibit at least subtle biochemical changes in hemostasis, and a minority of these patients will also develop clinical thrombosis or hemorrhage. In this paper, we will review intravascular coagulation and fibrinolysis, thrombocytopenia, and thrombocytosis, as well as more rare thrombotic and hemorrhagic events resulting from the direct interactions of neoplasms, or of their products, with the individual elements of hemostatic mechanisms. Thrombotic and hemorrhagic events resulting from the induction of autoimmune or thrombotic microangiopathic syndromes are also discussed. This review focuses on the clinical thrombotic and bleeding syndromes that may occur as a result of this interaction between neoplasia and hemostasis.

Hemorrhage↗

The Angio-Seal hemostatic puncture closure device. Concept and experimental results.

The Angio-Seal hemostatic puncture closure device is the culmination of development efforts dating from 1986. Development was driven to solve problems of delivering a multi-piece bioabsorbable puncture closure assembly through an introducer, the precise placement of the device in the vessel, the mastery of molding tiny absorbable polymer components, the manufacture of collagen hemostatic sponges having strong tear strength, and the testing of very large samples to establish safety and efficacy. Improvements included in the new 6F device to improve deployment reliability are also discussed.

Animals↗

Intracerebral hemorrhage: natural history and rationale of ultra-early hemostatic therapy.

Stroke is a major health problem worldwide, causing high morbidity and mortality. Intracerebral hemorrhage (ICH) accounts for 15% of stroke cases in the US and Europe and up to 30% in Asian populations. It is less treatable than other forms of stroke and causes higher morbidity and disability. Data suggest that early hematomy growth is the principal cause of early neurological deterioration after ICH. Prospective and retrospective studies indicate that early hematoma growth occurs in 18-38% of patients scanned within 3 h of ICH onset, and that hematoma volume is an important predictor of 30-day mortality. As hematoma growth in acute ICH is a dynamic process, intervention with ultra-early hemostatic therapy could lead to minimization and even prevention of early hematomy growth. Recombinant activated factor VII (rFVIIa, 'NovoSeven'), a powerful initiator of hemostasis, is approved for the treatment of bleeding in patients with hemophilia and inhibitors and may also promote hemostasis in patients with normal coagulation. rFVa acts locally at the bleeding site without activating systemic coagulation and may be a valuable therapy during the hyperacute stage of ICH. A randomized, double-blind, placebo-controlled, dose-ranging trial is currently in progress to investigate the potential of rFVIIa as an ultra-early hemostatic therapy to prevent or minimize hematoma growth in ICH patients without coagulopathy.

Aprotinin↗

Randomized trial comparing Quixil surgical sealant with Kaltostat hemostatic dressing to control suture line bleeding after carotid endarterectomy with ePTFE patch reconstruction.

Following carotid endarterectomy (CEA), patch angioplasty provides a significant reduction in the risk of perioperative complications. The expanded polytetrafluoroethylene (ePTFE) patch is strong, is resistant to infection, and has low thrombogenicity; but it remains unpopular because of its tendency of prolonged bleeding at the suture line. We aimed to investigate whether the application of Quixil sealant to the suture line could improve the time to achieve hemostasis and reduce local blood loss when compared to a standard topical hemostat Kaltostat. A prospective, randomized trial of 20 patients undergoing CEA was undertaken. Patients were randomized to receive either Quixil sealant (treatment group) or topical Kaltostat (controls) as a hemostatic agent to the patch suture line. Hemostasis was defined as no bleeding at the suture line for 1 minute. Statistical analysis was performed using the Mann-Whitney test. The two groups had a similar age and sex distribution. The mean age was 71 years, and there were seven men and three women in each group. The time to achieve hemostasis was significantly lower in the Quixil group (median 2.5 minutes, range 1-4 minutes) compared to the controls (median 17 minutes, range 7-59 minutes) (p < 0.001). Blood loss after clamp release was also significantly reduced in the Quixil group; median 24.5 ml (range 5.5-105.0 ml) versus 203 ml (range 54.5-817.0 ml) (p < 0.001). This study has demonstrated that Quixil human surgical sealant is an effective sealant of ePTFE patch suture holes and does not compromise the patch repair. It could be used during other vascular procedures involving ePTFE.

Aged↗

Stent-grafts in the management of hemorrhagic complications related to hemostatic closure devices: report of two cases.

We report 2 cases of hemorrhagic complications related to use of the Angio-Seal hemostatic closure device that were successfully managed with stent-grafts. Two patients with subarachnoid hemorrhage were referred to our departments for endovascular treatment of ruptured intracranial aneurysms. The treatment was performed through a femoral access; the sheaths were removed immediately after the procedures, and the punctures sites closed by Angio-Seals. Both patients presented clinical signs of hypovolemic shock after treatment. The diagnosis of active bleeding through the puncture site was made by emergency digital subtraction angiography. The lesions were managed with stent-grafts. The use of stent-grafts proved to be efficient in the management of these life-threatening hemorrhagic complications following the use of the Angio-Seal hemostatic closure device.

Adult↗

Diet and hemostatic factors.

The coagulation, fibrinolytic, and platelet activating systems are complex and interact extensively, and with other systems such as inflammation. Key reactions often require biomembranes, suggesting that dietary lipids, to the extent that they influence membrane composition, may have important regulatory roles. Also, recent evidence suggests that both postprandial and fasting lipoproteins may be associated with either factor levels or activation state or both. This issue has added importance because several hemostatic and fibrinolytic factors are known CVD risk factors. Although there are associations between fasting lipid levels and several coagulation and fibrinolytic factors, the mechanisms are unclear, as are the implications for intervention. In general, postprandial lipids are at least somewhat procoagulant because they activate factor VII. It remains to be demonstrated, however, that this postprandial activation has important clinical correlates. Dietary supplementation with marine omega-3 fatty acids does prolong the bleeding time and may decrease thrombotic potential; however, other than this, little is known about the direct effects of dietary fatty acids on hemostatic and fibrinolytic activities. Much work is needed in carefully controlled studies to expand our knowledge in this important area.

Blood Coagulation↗

Hemostatic wrapping of ruptured liver in two postpartum patients.

A variety of surgical techniques with variable success rates have been reported in the management of the spontaneously ruptured liver in pregnancy. We managed two cases of postpartum ruptured liver by wrapping the liver in hemostatic material. Hemostatic encapsulation effectively controlled massive bleeding of ruptured livers in two postpartum patients.

Adult↗

Evaluation of hemostatic agents in experimental splenic lacerations.

Avitene, Collastat, Gelfoam, and Surgicel were evaluated for their effectiveness in the control of hemorrhage from an experimental splenic laceration. Effectiveness was determined by measuring the amount of blood loss per kilogram of body weight until complete hemostasis was achieved and by determining mortality from hemorrhage. The study group in which Collastat, a collagen hemostatic sponge, was used had the smallest amount of blood loss. This group was also the only one with no deaths from breakthrough bleeding. The degrees of reaction in the spleens of the surviving animals 3 weeks after treatment were not significantly different when each of the various agents were compared. We believe that Collastat is the preferred topical hemostatic agent.

Animals↗

Comparative efficacy of topical hemostatic agents in a rat kidney model.

The efficacies of four topical hemostatic agents were compared in a rat model employing a standardized renal injury. The materials used to effect hemostasis were oxidized cellulose, microfibrillar collagen powder, positively charged modified collagen, and single donor heterologous fibrin glue. Animals that were treated only with surgical gauze served as controls. Hemostasis was achieved by application of one of the topical hemostatic agents plus moderate digital pressure. The time necessary to achieve complete hemostasis was recorded for each animal. Control animals bled profusely and suffered an increased postoperative mortality rate compared with the experimental animals. Microscopic studies demonstrated progressive healing of the injuries with varying degrees of inflammation and scar formation. Fibrin glue was by far the most effective agent in controlling hemostasis. The collagen materials, though effective, required a longer time to control bleeding and did not differ statistically in their activity from one another.

Administration, Topical↗

Hemostatic radiotherapy in carcinoma of the uterine cervix.

OBJECTIVE: To evaluate the treatment of hemorrhagic carcinoma of the uterine cervix with hemostatic radiotherapy (external and intracavitary radiotherapy). METHOD: Twenty cases of refractory hemorrhagic carcinoma of the uterine cervix receiving hemostatic radiotherapy between April 1987 and May 1992 were analyzed. The age of the patients ranged between 30 and 60 years with a median of 42 years. RESULTS: The mean tumor volume was 130 mm3; all cases were classified as FIGO stage IIb (n = 8), IIIb (n = 11) or IVa (n = 1). Radiotherapy was carried out either by the external or intracavitary technique. The control of hemorrhage was 100% within 12-48 h after radiotherapy. However 85% of patients failed locally in the form of residual, recurrent pelvic or metastatic disease, within 24 months of follow-up. CONCLUSION: Hemorrhagic cervical cancer has a poor prognosis.

Adult↗