Hemostatic Success Research Articles

Evaluating the safety and efficacy of a novel polysaccharide hemostatic system during surgery: A multicenter multispecialty prospective randomized controlled trial

BackgroundOperative blood loss is associated with postoperative morbidity and mortality in surgery. Hemostatic agents are used as adjuncts for hemostasis during surgery and help to prevent postoperative bleeding. We evaluated the safety and efficacy of an investigational polysaccharide hemostatic (PH) topical product compared to a U.S. Food and Drug Administration (FDA)-approved control in clinical use comprising microporous polysaccharide hemospheres (MPH) to achieve hemostasis of bleeding surfaces during surgery. Study designThis prospective multicenter trial enrolled patients undergoing open elective cardiac, general, or urologic surgery. Patients were stratified by bleeding severity and therapeutic area, then randomized 1:1 to receive PH or MPH. Bleeding assessments occurred intraoperatively using a novel bleeding assessment methodology. Primary endpoint was noninferiority as compared with control via effective hemostasis at 7 min. Patients were monitored and followed daily in the postoperative period until time of discharge and again at 6 weeks. Overall survival was assessed in oncology patients at 24 months. Safety of PH vs. MPH was determined by comparing relative incidence of adverse events. ResultsAcross 19 centers, 324 (161 PH, 163 MPH) patients were randomized (48 % general surgery, 27 % cardiac surgery, and 25 % urologic surgery). PH was noninferior to MPH and met the primary endpoint of hemostatic success at 7 min at a non-inferiority margin of 10 %. No significant differences were found in adverse event rates. Six deaths were reported within the 6-week follow-up period. No difference in overall survival was observed at 2 years (76 % PH vs. 74 % MPH, P = .66) for patients undergoing cancer operations. ConclusionAcross three therapeutic areas, PH was noninferior to MPH at all hemostasis assessment time points with no safety concerns. PH is an effective alternative to MPH for hemostasis during surgery.ClinicalTrials.gov Identifier: NCT02359994

Turn over the new leaf of the treatment in peptic ulcer bleeding: a review of the literature.

Peptic ulcer bleeding is the most common cause of upper gastrointestinal bleeding, which has a high mortality risk. The standard therapy for acute peptic ulcer bleeding combines medication administration and endoscopic therapies. Both pharmacologic and endoscopic therapies have developed continuously in the past few decades. Proton pump inhibitors (PPIs) already reached a high efficacy in ulcer healing and have been widely used in the past few decades. Endoscopic hemostasis, which includes local epinephrine injection, heater probe coagulation, use of hemostatic clips, and/or band ligation, is highly effective with an overall hemostatic success rate of 85%-90%. However, 10%-20% of patients could not be cured by the current standard combination treatment. Recurrent ulcer bleeding, despite an initial successful hemostasis, is also a big problem for longer hospitalization stays, higher mortality, and higher complication rates, especially for malignant ulcer bleeding. How to manage all types of peptic ulcer bleeding and how to prevent early recurrent peptic ulcer bleeding remain unresolved clinical problems. Recently, several novel medications and endoscopic methods have been developed. Potassium competitive acid blockers have shown a stronger and longer acid suppression than PPI. Hemostatic powder spray and hemostatic gel emulsion are novel hemostatic weapons with emerging evidence, which are potential missing pieces of the puzzle. This literature review will go through the development of endoscopic hemostasis to the prospects of novel endoscopic treatments.

The immunogenicity, safety, and efficacy of N8-GP in previously untreated patients with severe hemophilia A: pathfinder6 end-of-trial results

BackgroundThe pathfinder6 (NCT02137850) international phase 3 trial examined immunogenicity, safety, and efficacy of the extended half-life factor VIII (FVIII) replacement product N8-GP (turoctocog alfa pegol; Esperoct) in previously untreated patients (PUPs) with hemophilia A. ObjectivesWe present end-of trial results for extended PUP N8-GP treatment for up to a median (range) 2.5 (0.0; 7.4) years. Patients/MethodsLonger-term N8-GP treatment in PUPs with hemophilia A was examined. The prophylaxis regimen was ∼60 IU/kg N8-GP i.v. twice weekly, or every 3 or 7 days. The primary endpoint was the incidence of FVIII inhibitors. ResultsOverall, 81 patients received N8-GP and were included in this analysis. The inhibitor incidence was 30.0% (15.7% high-titer [>5 BU]) for the extension phase. Patients had a median (range) 2.9 (0.1; 7.2) years of prophylaxis following the pre-prophylaxis period. During prophylaxis, the median annualized bleeding rate (ABR) (interquartile range) was 1.4 (0.6; 3.5), 13% of patients experienced no bleeding episodes, and 55.1% of patients experienced no spontaneous bleeds. The proportion of patients without any spontaneous bleeding episodes increased after the first year of prophylaxis. The hemostatic success rate in the treatment of bleeding episodes was 87.6%. No additional safety concerns were observed in patients with previously reported observation of temporarily decreased incremental recovery (IR). ConclusionLong-term end-of-trial PUP N8-GP prophylaxis data indicate that PUPs respond well to long-term N8-GP treatment. The inhibitor incidence was consistent with previous results. Median ABR during prophylaxis was 1.4. There were no lasting clinical impacts or safety concerns for patients with an observation of temporarily decreased IR.

Hemostatic Efficacy of Algan Hemostatic Agent in Renal Vein Incision Model in Rats

Background: The aim of this study is to evaluate the acute hemostatic effects of liquid and powder forms of AHA in severe bleeding model of rat renal vein. Materials and Methods: 10-12 weeks old, 24 male Wistar albino rats were randomly divided into three groups of eight animals each as the control, AHA liquid, AHA powder. The left renal artery and vein were revealed with a 3 cm vertical incision and the tip of the injector was used to puncture renal vein, causing bleeding. In all animals, regular gauze patch was pressed over the incised area for 10 seconds as soon as the bleeding began. Immediately after removing the sponge; physiological saline, AHA liquid and powder were applied with compress to injured site of relevant groups for 2 minutes, respectively. The time was recorded by chronometer and the area was checked after two minutes. Hemostasis that was not achieved after three applications was accepted as failure. Results: Cessation of the bleeding failed in all rats after three successive 2-minute physiological saline impregnated gauze applications in control group. Among AHA-treated groups, significant hemostasis efficacy was obtained from the liquid form than that of powder. Within first two minutes, bleeding in renal veins of five rats was controlled successfully in liquid group whereas powder group achieved hemostatic success in four rats. Conclusions: The vessel incision model in our study revealed fast-acting physical hemostatic properties of the liquid and powder formulations of AHA in the renal vein. This natural applicable product could be used to induce hemostasis in rat models of bleeding caused by various renal damages or trauma, and it could also prevent local bleeding in humans. More studies are needed to compare the efficacy of different formulations of the polysaccharide-based herbal product in various organs and surgical models.

Safety and Hemostatic Effectiveness of SURGICEL® Powder in Mild and Moderate Intraoperative Bleeding.

This postmarket clinical study evaluated the safety and effectiveness of the novel adjunctive topical hemostat SURGICEL® Powder (SURGICEL®-P), a powdered form of oxidized regenerated cellulose. In a prospective, open-label, single-arm multicenter trial, adult surgical subjects with mild-to-moderate bleeding for which conventional hemostatic methods were impractical/ineffective were treated with SURGICEL®-P. Descriptive analyses included hemostatic success rate at 3, 5, and 10 min, rebleeding and thromboembolic events, SURGICEL®-P-related serious adverse events requiring surgical intervention, and SURGICEL®-P ease of use (questionnaire). In 8 centers, 103 subjects were enrolled with a median (range) age of 64.0 (33.0-88.0) years. Surgeries were open (53.4%) or laparoscopic/thoracoscopic (46.6%) and mostly urological (37.9%) and abdominal (32.0%) procedures. Bleeding sites included various tissue types, with a median (range) surface area of 4 (0.02-72.0) cm2. Hemostatic success rates were 77.7%, 87.4%, and 92.2% at 3, 5, and 10 min, respectively. In 7 subjects (6.8%), investigators reverted to standard of care. No safety signals were identified. Two deaths occurred with causes unrelated to SURGICEL®-P. Investigators favorably evaluated the ease of use of the SURGICEL®-P device. SURGICEL®-P is safe and effective in controlling mild-to-moderate bleeding in a broad range of surgical procedures. The trial was registered at https://clinicaltrials.gov as NCT03762200.

Utility of microporous polysaccharide hemospheres in severe hepatic trauma: Experimental study of hemostatic strength and ease of use

BackgroundAnimal studies confirm the utility of hemostatics against standard packing following severe liver injury. We investigated the efficacy and ease of use of novel microporous polysaccharide hemosphere (MPH) compounds (Perclot®, Baxter) in the treatment of severe hepatic hemorrhage in pig. MethodsPigs were randomized to one of two equal treatment groups: MPH compounds (n=12) and Standard Packing (n=12). All animals underwent standardized surgical devascularization of the suprahepatic veins (grade V) to induce severe hepatic injury. Measures relating to the hemostatic success were monitored at 12, 60, 120 minutes and 24 hours post injury. ResultsAnimals allocated to treatment with MPH compounds were associated with higher survival rates at 24 hours than those undergoing standard packing: 66.7% vs, 0%, respectively (p=0.001). At 120 minutes MPH compounds were also associated with reduced blood loss, median (IQR) 1.16 (0.60) vs. 10.19 (5.77) mL/Kg, respectively: p<0.001) as well as higher invasive mean arterial pressures (iMAP) median (IQR) 39.12 (11.29) vs. 25.75 (14.28) mmHg, respectively: p=0.14) and hemoglobin levels median (IQR) 5.45 (2.50) vs. 6.45 (1.73) g/dL, respectively p=0.127). Overall, the application of MPH compounds required nearly half the time of standard packing median (IQR) 32.92 (6.51) vs. 67.75 (14.66) sec, respectively: p<0.001). ConclusionsThe data suggests that the use of MPH works in a severe hemorrhage in the liver of pigs, improving many variables in comparison to standard packing, including survival, blood loss and speed of application and we conclude that this offers a potential alternative for the treatment of hepatic injury. Further work is needed to corroborate these findings.

Value of multidetector computed tomography angiography and image analysis before bronchial artery embolization in the treatment of hemoptysis

Objective: To estimate the value of multidetector computed tomography angiography (MDCTA) and image analysis before bronchial artery embolization (BAE) in the treatment of hemoptysis. Methods: A total of 165 patients with hemoptysis who underwent BAE at the Department of Interventional Radiology of Xiangyang Central Hospital from August 2017 to June 2021 were retrospectively analyzed and divided into two groups: MDCTA group [with preoperative MDCTA, 88 patients,63 males and 25 females,aged 23 to 87(62.6±12.3) years] and control group [77 patients, 52 males and 25 females, aged 26 to 83 (59.8±12.7) years]. The number of bronchial arteries and non-bronchial systemic arteries, and clinical success rate were compared between the two groups. Comparisons within groups were performed using the t-test or nonparametric paired Wilcoxon test for quantitative data with paired design, while comparisons between groups were performed using the t-test for the mean of two independent samples or the nonparametric Mann-Whitney U test for independent samples and comparisons between groups were performed using the chi-square test. Results: The number of orthotopic and ectopic bronchial arteries found in BAE procedure in the MDCTA group was significantly higher than that in the control group [1.77±0.72 vs. 1.42±0.82, P=0.003; 0 (0, 0) vs. 0 (0, 0), P=0.033, respectively]; in the MDCTA group, the numbers of orthotopic and ectopic bronchial arteries found by MDCTA were significantly higher than those found in BAE procedure [2.22±0.63 vs. 1.77±0.72, P<0.001; 0 (0, 0) vs. 0 (0, 0), P=0.005, respectively]. The number of non-intercostal arteries found by MDCTA in the MDCTA group was significantly higher than that in the control group [0 (0, 0) vs. 0 (0, 0), P=0.038]. Hemostatic success was significantly higher in the MDCTA group than that in the control group (88.6% vs. 68.8%, P=0.002). Conclusions: MDCTA and image analysis help to detect more bronchial arteries and improve the hemostatic success rate before bronchial artery embolization in the treatment of hemoptysis.

Evaluating the Safety and Efficacy of a Novel Polysaccharide Hemostatic System for Multidisciplinary Application: A Multicenter Prospective Randomized Controlled Trial

Introduction: Operative blood loss is associated with postoperative morbidity and mortality. Hemostatic agents are used as adjunctive methods for hemostasis during surgery and to prevent postoperative bleeding. We evaluated safety and efficacy of an investigational polysaccharide hemostatic (PH) device, compared with an FDA-approved control in clinical use comprising microporous polysaccharide hemospheres (MPH), to achieve hemostasis of bleeding surfaces during surgery. Methods: This prospective multicenter trial enrolled patients undergoing open elective cardiac, general, or urological operation. Patients were stratified by bleeding severity and therapeutic area, then randomized 1:1 to receive PH or MPH. Bleeding assessments occurred intraoperatively using a novel bleeding assessment methodology. Primary endpoint was non-inferiority as compared with control via effective hemostasis at 7 minutes. Patients were followed postoperatively, discharge, and 6-weeks. Survival was assessed in oncology patients at 24-months. Safety of PH vs MPH was determined by comparing relative incidence of adverse events. Results: Across 19 centers, 324 (161 PH, 163 MPH) patients were randomized; approximately half underwent general surgery, while 25% each underwent cardiac and urologic surgery. PH met the primary endpoint of hemostatic success at 7-minutes demonstrating efficacy of PH was non-inferior to MPH. No significant differences were found in adverse event rates or supplementary safety measures. Six deaths were reported through 6-week follow-up. There was no difference in survival at 2 years (76% (PH) vs 74% (MPH), p = 0.66) for patients undergoing cancer operation. Conclusion: Across 3 therapeutic areas, PH was noninferior to MPH at all hemostasis assessment time points. No safety concerns were identified.

Effectiveness of Hemopatch® versus Surgicel® Original to control mild and moderate liver bleeding

BackgroundAdjunct hemostats can be of use in certain surgical settings. We compared the effectiveness of two hemostats, Hemopatch® and Surgicel® Original in controlling bleeding from liver lesions in an experimental model.MethodsControl of grades 1 (mild) and 2 (moderate) bleeding (according to the Validated Intraoperative Bleeding [VIBe] SCALE) was assessed for 10 min after Hemopatch® (n = 198) or Surgicel® Original (n = 199) application on 397 liver surface lesions. The primary endpoint was hemostatic success (reaching VIBe SCALE grade 0 at 10 min). The secondary endpoint was time to hemostasis (time to reach and maintain grade 0). A generalized linear mixed model and an accelerated failure time model were used to assess the primary and secondary endpoints, respectively.ResultsThe overall hemostatic success rate of Hemopatch® was statistically significantly superior to that of Surgicel® Original (83.8% versus 73.4%; p = 0.0036; odds ratio [OR] 2.38, 95% confidence interval [CI] 1.33–4.27) and time to hemostasis was reduced by 15.9% (p = 0.0032; 95% CI 0.749–0.944). Grade 2 bleeds treated with Hemopatch® had statistically significantly higher hemostatic success (71.7% versus 48.5%; p = 0.0007; OR 2.97, 95% CI 1.58–5.58) and shorter time to hemostasis (49.6% reduction, p = 3.6 × 10–8); differences for grade 1 bleeds (hemostatic success rate or time to hemostasis) were not statistically significant.ConclusionsHemopatch® provided better control of VIBe SCALE bleeding compared to Surgicel® Original for Grade 2 bleeds in this porcine model, highlighting the importance of choosing a suitable hemostat to optimize control of bleeding during surgery.

Effects of Algan hemostatic agent foam in rat femoral artery injury model: A randomized animal trial

Background/Aim: Nowadays, many deaths are related to vessel injury-induced blood loss. Failure to control bleeding also increases the risk of death. This study aimed to investigate the hemostatic effects of the Algan Hemostatic Agent (AHA) foam application in a rat model in which severe femoral artery bleeding was induced.&#x0D; Methods: Fourteen rats were randomly assigned to two groups: (1) control (physiological saline) (n = 7) and (2) AHA foam (n = 7). The left femoral artery of the rats was incised and when the bleeding started, and the area was pressed with another sponge for 10 s in all rats. Afterwards, physiological saline solution impregnated gauze or AHA foam was placed over same area. A chronometer was started and area was checked after 2 min. If no bleeding occurred during the first 2 min of application, it was recorded as “successful”. If bleeding occurred, the same procedure was repeated up to three times. If hemostasis could not be achieved even after the third application, it was considered a failure, and “failed” was recorded. All animals were sacrificed under high anesthesia for least 10 min after the experiment.&#x0D; Results: Application of AHA resulted in complete (100%) control of bleeding in all rats within the first 2 min. In control group, hemostasis was achieved in 1 out of 7 (14.3%) rats by the third application. Failure was recorded for the remaining six rats. The hemostatic success rate of the AHA foam was significantly higher than the rates of control group (P = 0.005).&#x0D; Conclusion: AHA foam is a very effective hemostatic agent and can be applied easily on vascular trauma models. Further studies are needed to elucidate hemostatic features of AHA.

Turoctocog alfa pegol (N8‐GP) in severe hemophilia A: Long‐term safety and efficacy in previously treated patients of all ages in the pathfinder8 study

BackgroundN8‐GP (turoctocog alfa pegol; Esperoct) is a glycoPEGylated human recombinant factor VIII (FVIII). ObjectivesPathfinder8 (NCT01480180) was a phase 3, multinational, open‐label, nonrandomized trial to investigate the long‐term safety and efficacy of N8‐GP in people of all ages with severe hemophilia A previously treated with N8‐GP. Patients/MethodPatients were recruited from the completed phase 3 pathfinder2 and pathfinder5 trials to receive intravenous N8‐GP prophylaxis for up to 104 weeks, administered every 7 days, twice weekly, or three times weekly. Primary and secondary end points were the number of adverse events (AEs) reported and efficacy of treatment, respectively. ResultsOverall, 160 patients were exposed to N8‐GP for a mean of 179 exposure days and 681 calendar days (≈1.9 years) per patient. In total, 119 patients experienced 510 AEs, corresponding to a rate of 1.71 AEs per patient‐year of exposure; 97.5% of AEs were mild or moderate in severity, and no AEs led to withdrawal. No patients developed FVIII inhibitors during the trial. The Poisson estimate of mean annualized bleeding rate for all bleeds (excluding surgery) and across all regimens was 1.10 (median, 0.00), and for spontaneous bleeds was 0.61 (median, 0.00). Most (55.6%) patients experienced no bleeds that required FVIII treatment (excluding perioperative bleeds). The estimated hemostatic success rate for the treatment of 322 bleeding episodes (excluding surgery) was 95.8%, including missing values as failure. ConclusionsLong‐term prophylactic use of N8‐GP appeared safe and efficacious across all age groups in people with severe hemophilia A previously treated with N8‐GP.

Endoscopic management of delayed bleeding after polypectomy of small colorectal polyps: two or more clips may be safe.

BackgroundThe resection of small colorectal polyps (≤10 mm) is routine for endoscopists. However, the management of one of its main complications, namely delayed (within 14 days) postpolypectomy bleeding (DPPB), has not been clearly demonstrated. We aimed to assess the role of coloscopy in the management of DPPB from small colorectal polyps and identify the associated factors for initial hemostatic success.MethodsWe conducted a retrospective study of 69 patients who developed DPPB after the removal of colorectal polyps of ≤10 mm and underwent hemostatic colonoscopy at the Sixth Affiliated Hospital of Sun Yat-sen University (Guangzhou, China) between April 2013 and June 2021. Demographics, clinical variables, and colonoscopic features were collected independently. We applied univariate and multivariate analyses to assess factors associated with initial hemostatic success.ResultsGeneral colonoscopy without oral bowel preparation was successfully performed in all the patients, with a median duration of 23.9 (12.5–37.9) minutes. Among 69 patients, 62 (89.9%) achieved hemostasis after initial hemostatic colonoscopy and 7 (10.1%) rebled 2.7 ± 1.1 days after initial colonoscopic hemostasis and had rebleeding successfully controlled by one additional colonoscopy. No colonoscopy-related adverse events occurred. Multivariate analysis showed that management with at least two clips was the only independent prognostic factor for initial hemostatic success (odds ratio, 0.17; 95% confidence interval, 0.03–0.91; P = 0.04). All the patients who had at least two clips placed at the initial hemostatic colonoscopy required no further hemostatic intervention.ConclusionsColonoscopy is a safe, effective, and not too time-consuming approach for the management of patients with DPPB of small colorectal polyps and management with the placement of at least two hemoclips may be beneficial.

Comparison of initial tumor responses to transarterial bland embolization and drug-eluting beads-transarterial chemoembolization in the management of hepatocellular carcinoma: a propensity-score matching analysis.

Transarterial bland embolization (TABE) is widely used to treat the spontaneous rupture of hepatocellular carcinoma (HCC), and can lead to ischemic necrosis of the tumor. In this study, we used the propensity-score matching (PSM) method to compare the initial responses of treatment-naïve HCC patients to TABE and drug-eluting beads-transarterial chemoembolization (DEB-TACE), and the safety of these treatments. Patients with treatment-naïve HCC, who had been admitted to 2 medical centers from January 2016 to December 2020, were enrolled as the research subjects. The data of 26 patients treated with TABE for ruptured HCC and 52 patients treated with DEB-TACE for primary HCC were collected according to our inclusion and exclusion criteria, and a PSM analysis was conducted to assess the safety and effectiveness of these two interventional techniques 1 month postoperatively. In relation to ruptured HCC, TABE had a hemostatic success rate of 97.0%. Before PSM, the TABE group had a larger maximum tumor diameter (P<0.05), a higher proportion of multiple tumors (P<0.05), a higher proportion of Child-Pugh class B (P<0.05), and a higher proportion of Barcelona Clinic Liver Cancer (BCLC) stage B (P<0.05) than the DEB-TACE group. After PSM, the baseline characteristics of these two groups were well balanced, and there was no significant difference in patients' initial therapeutic responses and tumor recurrence rates (both P>0.05). The multivariate regression analysis showed that tumor size was an independent predictor of the objective response rate (ORR) [odds ratio (OR): 3.312; 95% CI: 0.152-5.944; P<0.05]. Tumor number and BCLC stage also affected ORR; however, ORR was not significantly correlated with the interventional technique (TABE vs. DEB-TACE; P>0.05). The incidences of post-embolization syndrome (PES) and 48-h hepatotoxicity were significantly lower in the TABE group than the DEB-TACE group (both P<0.05), but there was no significant difference in hepatotoxicity after 1 month (P>0.05). TABE is highly effective at managing hemorrhage from ruptured HCC. The initial therapeutic response of HCC to TABE is similar to that to DEB-TACE; however, TABE is associated with lower hepatotoxicity and fewer adverse effects, which paves the way for subsequent treatments and systemic therapies.

Endoscopic thermocoagulation hemostasis for acute non-varicose upper gastrointestinal hemorrhage: a randomized controlled study.

This study evaluated the application of the bipolar electrocoagulation catheter via a peripheral-to-central (3 + 1) technique, relative to directly pressing only at the center of the bleeding site (direct-stroke), to effect endoscopic hemostasis of acute non-varicose gastrointestinal bleeding (ANVUGIB). Patients (n = 148) with endoscopically diagnosed ANVUGIB were randomly apportioned to receive treatment by 3 + 1 (n = 78) or direct-stroke (n = 70) application of the bipolar electrocoagulation catheter. The 3 + 1 strategy required pressing at3 narrowly restricted sites equidistant peripheral and center to the site of bleeding. The rates of initial success, hemostasis time, and number of compressions were compared according to intention-to-treat (ITT) or per protocol (PP). The ITT (PP) rate of initial hemostatic success in patients receiving the 3 + 1 catheter was 91.02% (95.9%); and for the direct-stroke group was 71.42% (76.9%). For Forrest IIa lesions specifically, these rates were respectively 91.70% (97.1%) and 63.9% (67.6%). The ITT (PP) hemostasis times of the 3 + 1 and direct-stroke groups were 10.96 ± 3.28 (10.65 ± 2.90) and 14.27 ± 6.58 (14.12 ± 6.67) min; and the number of compressions numbered 5.73 ± 1.98 (5.42 ± 1.46) and 6.47 ± 2.82 (6.16 ± 2.47). During thermocoagulation treatment of ANVUGIB via bipolar electrocoagulation catheter, the 3 + 1 strategy showed a significantly higher rate of successful initial hemostasis relative to the direct-stroke technique, and shorter hemostasis time, with no increase in total procedural steps.

Combinations of fibrinolytic gene polymorphisms (plasminogen activator inhibitor type 1 4G/5G, factor XIII Val34Leu and angiotensin-converting enzyme I/D) in women with idiopathic infertility.

During normal pregnancy depressed fibrinolytic system is caused by changes in many factors, which could be influenced by different gene polymorphisms. The aim of this study was to investigate the combination of fibrinolysis-related gene polymorphisms in women with idiopathic infertility. We genotype polymorphisms 4G/5G in plasminogen activator inhibitor type 1 (PAI-1), Val34Leu in factor XIII (FXIII) and I/D in angiotensin-converting enzyme (ACE) gene. The patients group consisted of 83 females with idiopathic infertility, while the control group included 121 females with at least one born child. The alleles and genotypes distributions showed no significant differences between analyzed groups. Although higher frequency of PAI-1 5G5G genotype in patients did not reach statistical significance, 5G5G genotype of PAI-1 in combination with ValVal genotype of FXIII leads to higher risk for infertility (P < 0.05). In addition, when we added ACE I/D polymorphism in analysis, the 4G in PAI-1 and D allele in ACE, showed protective effect in combination with FXIII polymorphism (P < 0.05). The finding that combined homozygosity of 5G of PAI-1, commonly associated with greater fibrinolytic activity and bleeding tendency, in combination with Val genotype of FXIII impose a risk for female idiopathic infertility. The protective effect of alleles 4G (PAI-1) and D (ACE) suggest that different combinations of polymorphisms influencing fibrinolysis could lead to better established hemostatic balance and reproductive success. Further analyses, with larger number of samples, as well as assessment of additional biochemical parameters of fibrinolysis, should be performed to clarify the role of gene polymorphisms on fibrinolysis and consequently their influence on reproductive success.

A multicenter, prospective, randomized clinical trial of marine mussel-inspired adhesive hemostatic materials, InnoSEAL Plus.

PurposeInnoSEAL Plus is an adhesive, coagulant-free hemostatic material that mimics the adhesion mechanism of marine mussels. This study reports on the safety and efficacy of InnoSEAL Plus for patients with hemorrhage after hepatectomy despite first-line hemostasis treatments.MethodsThis is a multicenter, prospective, single-blinded, randomized clinical trial involving 96 hepatectomy patients. TachoSil was used as a comparator group. Three-minute and 10-minute hemostatic success rates were monitored. Rebleeding rates were also observed. Safety was assessed by recording all novel undesirable symptoms.ResultsInnoSEAL Plus showed a 3-minute hemostasis rate of 100%, while TachoSil had a rate of 98.0% (48 of 49 patients), demonstrating that the 2 had similar hemostatic efficacies. The difference in efficacy between the test and comparator group was 2.04%, and the lower limit of the one-sided 97.5% confidence interval was −1.92%; as this is greater than the noninferiority limit of −23.9%, the 2 treatments were equivalent. Meanwhile, the 10-minute hemostatic success rate was the same in both groups (100%). No rebleeding occurred in either group. In the safety evaluation, 89 patients experienced adverse events (45 in the test group and 44 in the comparator group). The difference between the 2 groups was not significant. No death occurred after application of the test or comparator group product.ConclusionGiven that InnoSEAL Plus is a coagulation factor-free product, the hemostasis results are encouraging, especially considering that TachoSil contains a coagulation factor. InnoSEAL Plus was found to be a safe and effective hemostatic material for control of bleeding in hepatectomy patients.

A randomized controlled trial to compare the efficacy of regenerated and non-regenerated oxidized cellulose gauze for the secondary treatment of local bleeding in patients undergoing hepatic resection.

PurposeOxidized cellulose is available in many forms, but manufactured using either a regenerated or non-regenerated process. In this study, we evaluated the effects of 2 different hemostatic agents for the treatment of local bleeding in patients undergoing hepatic resection.MethodsThis was a monocentric, parallel-group, randomized, and controlled clinical trial to compare oxidized regenerated cellulose gauze (ORCG) with oxidized non-regenerated cellulose gauze (ONRCG) in patients undergoing hepatectomy. The primary endpoint was the time to hemostasis at the target bleeding site. The secondary endpoints were the postoperative drainage volume on the first 2 days after surgery and the hospital stay.ResultsThere was no significant difference between the ORCG and ONRCG groups in time to hemostasis from column analysis (238.8 ± 121.6 seconds vs. 193.7 ± 85.3 seconds, P = 0.068), and there were no differences in the rates of hemostatic success between the 2 groups at 120 seconds (18.4% vs. 24.3%; odds ratio [OR], 0.703; 95% confidence interval [CI], 0.231–2.136) and 300 seconds (71.1% vs. 89.2%; OR, 0.298; 95% CI, 0.085–1.041). However, the ONRCG group was superior to the ORCG group in hemostasis according to the survival analysis (log-rank test, P = 0.044). Moreover, there were also no significant differences between the 2 groups in postoperative drainage volume on the first 2 days (P = 0.436, P = 0.381) and hospital stay (P = 0.537, P = 0.200).ConclusionONRCG was not inferior to ORCG as a hemostatic agent in patients undergoing liver resection.

Single 225μg/Kg Dose Treatment with Eptacog Beta (Factor VIIa, Recombinant) Results in Rapid Hemostasis in Joint Bleeds for Persons with Hemophilia Α or Β with Inhibitors: A PERSEPT1 Subset Analysis

Single 225μg/Kg Dose Treatment with Eptacog Beta (Factor VIIa, Recombinant) Results in Rapid Hemostasis in Joint Bleeds for Persons with Hemophilia Α or Β with Inhibitors: A PERSEPT1 Subset Analysis

Turoctocog alfa is safe for the treatment of Indian patients with hemophilia A: Guardian 10 trial results

BackgroundHemophilia A is an X chromosome–linked bleeding disorder caused by the deficiency of coagulation factor VIII (FVIII). The majority of the Indian population with hemophilia A use plasma‐derived clotting factors and, in some instances, fresh frozen plasma and cryoprecipitate. Safer and more efficient treatment options are needed for this group of patients. ObjectivesTo assess the safety of turoctocog alfa, a third‐generation recombinant FVIII molecule, for the treatment and prophylaxis of bleeding episodes in previously treated Indian patients with moderate or severe hemophilia A. Patients/MethodsThis single‐country, multicenter, open‐label, nonrandomized trial enrolled 60 patients who received prophylactic treatment with turoctocog alfa for 8 weeks, which corresponded to a minimum of 20 exposure days. Confirmed development of FVIII inhibitors during the 8‐week treatment period was evaluated. Other assessments included frequencies of adverse drug reactions (ARs), serious adverse reactions, drug‐related allergic reactions, and infusion reactions during the 12‐week period after the first treatment; hemostatic effect of turoctocog alfa for the treatment of bleeding episodes; and total annualized dose of turoctocog alfa administered during the 8‐week treatment period. ResultsNo incidence of FVIII inhibitors was detected. No safety concerns such as ARs, serious ARs, or drug‐related allergic reactions were noted. The hemostatic success rate for the treatment of bleeding episodes with turoctocog alfa was 81.6%. ConclusionsThe trial results demonstrated that turoctocog alfa is a safe treatment option for the prophylaxis and treatment of bleeding episodes in previously treated adolescent and adult patients with hemophilia A in the Indian population.

Clinical and procedure characteristics in patients treated with polytetrafluoroethylene-covered stents after coronary perforation: a CIRC-8U multicenter registry and literature review.

This study aimed at identifying the clinical characteristics and in-hospital outcomes of patients treated with polytetrafluorethylene (PTFE)-covered stents after coronary interventions in a multicenter registry. Subjects with coronary artery perforation were selected from 31,262 consecutive patients who underwent coronary interventions in the hospital registries. Subjects were divided into two groups: those with a PTFE-covered stent implantation and those without a PTFE-covered stent implantation. Clinical characteristics and in-hospital outcomes were compared between the two groups. Data for 82 consecutive coronary perforations (15 PTFE-covered stents and 67 non-PTFE-covered stents) were extracted from each hospital registry. The PTFE-covered stent group had a higher prevalence of perforations due to pre-dilatation before stenting or post-dilatation after stenting (80% vs. 10.4%; p < 0.001), more Ellis classification III perforations (66.6% vs. 28.4%; p = 0.019), longer perforation to hemostasis time (74min vs. 10min; p < 0.001), lower hemostatic success rates (73.3% vs. 94.0%; p = 0.015), and higher in-hospital mortality (26.7% vs. 6.0%; p = 0.015) than the non-PTFE-covered stent group. Although the prevalence of intravascular ultrasound (IVUS) usage was high during coronary interventions (86.7%), IVUS was performed in less than half the cases just before coronary perforations (47%) in the PTFE-covered stent group. Patients requiring PTFE-covered stents are more likely to be observed after balloon dilatation before or after stenting and have a poor prognosis. Careful coronary intervention is needed when IVUS image acquisition is not achieved in addition to proper evaluation of IVUS. Furthermore, if coronary artery perforation occurs, it is important to determine the need for a prompt PTFE-covered stent.