Severity Of Bleeding Research Articles

Human Disabled-2 regulates thromboxane A2 signaling for efficient hemostasis in thrombocytopenia.

Understanding platelet protein functions facilitates better assessment of platelet disorders. Megakaryocyte lineage-restricted human Disabled-2 knock-in (hDAB2-KI) mice are generated to delineate the functions of hDab2, a regulator of platelet function, in the control of bleeding associated with thrombocytopenia. Here we show that hDab2-KI mice with thrombocytopenia display decreased bleeding time when compared to the control mice. hDab2 augments thromboxane A2 (TxA2) mimetic U46619- but not other agonists-stimulated granule secretion, integrin activation, and aggregation at a lower platelet concentration in vitro. Binding of hDab2 to phosphatidic acid (PA) facilitates formation of the PA-hDab2-AKT complex leading to an increase in U46619-stimulated AKT-Ser473 phosphorylation and the first wave of ADP/ATP release. Consistent with these findings, hDab2 expression in platelets from patients with immune thrombocytopenic purpura is positively correlated with U46619-stimulated ATP release, which in turn inversely correlated with their bleeding tendency. hDab2 appears crucial in regulating bleeding severity associated with thrombocytopenia by a functional interplay with ADP/ATP release underlying TxA2 signaling.

Management of intracavitary bleeding during ultra-early minimally invasive intracerebral hemorrhage evacuation.

Surgical evacuation of intracerebral hemorrhage (ICH) at early time points contributes to improved functional outcomes. However, ultra-early evacuation has been associated with postoperative rebleeding, a devastating complication that contributes to worse outcomes. Minimally invasive endoscopic techniques allow for intraoperative management of active bleeding, potentially allowing for safe and effective hemostasis at ultra-early time points. The authors proposed and prospectively assigned an intraoperative grading scale that quantified the severity of bleeding encountered intraoperatively. They hypothesized that ultra-early evacuation would correlate to increased intraoperative bleeding but not postoperative rebleeding or worse long-term clinical outcomes in a cohort of patients undergoing minimally invasive endoscopic evacuation. Patients presenting to a large healthcare system with spontaneous supratentorial ICH were triaged to a central hospital for potential surgical evacuation. Inclusion criteria for evacuation included age ≥ 18 years, premorbid mRS score ≤ 3, hematoma volume ≥ 15 mL, and presenting National Institutes of Health Stroke Scale score ≥ 6. A 5-point scale was developed and prospectively applied to grade the severity of bleeding encountered intraoperatively. A score of 1 indicated no active intraoperative bleeding. A score of 2 indicated minimal bleeding treated with irrigation alone. A score of 3 indicated bleeding that required cauterization to control. A score of 4 indicated bleeding that required irrigation or cauterization for at least 15 minutes to achieve hemostasis. A score of 5 indicated bleeding that required irrigation or cauterization for at least 1 hour. The authors evaluated 142 consecutive patients. The median bleeding score was 2 (IQR 2-4). Greater preoperative volume, concomitant intraventricular hemorrhage, and earlier time to evacuation were independently associated with increased bleeding score. Specifically, ultra-early evacuation within 5 hours was independently associated with a 2.4-point greater bleeding score as compared with evacuation thereafter (β = 2.41, 95% CI 1.44-3.38; p < 0.0001). Despite having higher intraoperative bleeding scores, patients undergoing ultra-early evacuation did not have an increased likelihood of postoperative rebleeding (14% vs 3%, p = 0.23), 30-day mortality (0% vs 6%, p = 0.99), or worse median 6-month mRS scores (4 [IQR 2-5] vs 4 [IQR 3-5], p = 0.51). Ultra-early evacuation within 5 hours of ictus is associated with increased intraoperative bleeding but not postoperative rebleeding or worse clinical outcomes. These findings suggest that the benefits of ultra-early evacuation can be explored without an increased risk of postoperative rebleeding when utilizing a minimally invasive endoscopic technique with good intraoperative visualization, active irrigation for targeted tamponade, and direct cauterization of bleeding vessels.

Short-term neurologic outcomes in pediatric extracorporeal membrane oxygenation are proportional to bleeding severity graded by a novel bleeding scale.

This study aimed to characterize the severity of bleeding and its association with short-term neurologic outcomes in pediatric ECMO. Multicenter retrospective cohort study of pediatric ECMO patients at 10 centers utilizing the Pediatric ECMO Outcomes Registry (PEDECOR) database from December 2013-February 2019. Subjects excluded were post-cardiac surgery patients and those with neonatal pathologies. A novel ECMO bleeding scale was utilized to categorize daily bleeding events. Poor short-term neurologic outcome was defined as an unfavorable Pediatric Cerebral Performance Category (PCPC) or Pediatric Overall Performance Category (POPC) (score of >3) at hospital discharge. This study included 283 pediatric ECMO patients with a median (interquartile range [IQR]) age of 1.3years [0.1, 9.0], ECMO duration of 5days [3.0, 9.5], and 44.1% mortality. Unfavorable PCPC and POPC were observed in 48.4% and 51.3% of patients at discharge, respectively. Multivariable logistic regression analysis included patient's age, cannulation type, duration of ECMO, need for cardiopulmonary resuscitation, acute kidney injury, new infection, and vasoactive-inotropic score. As the severity of bleeding increased, there was a corresponding increase in the likelihood of poor neurologic recovery, shown by increasing odds of unfavorable neurologic outcome (PCPC), with an adjusted odds ratio (aOR) of 0.77 (confidence interval [CI] 0.36-1.62), 1.87 (0.54-6.45), 2.97 (1.32-6.69), and 5.56 (0.59-52.25) for increasing bleeding severity (grade 1 to 4 events, respectively). Similarly, unfavorable POPC aOR (CI) was 1.02 (0.48-2.17), 2.05 (0.63-6.70), 5.29 (2.12-13.23), and 5.11 (0.66-39.64) for bleeding grade 1 to 4 events. Short-term neurologic outcomes in pediatric ECMO are proportional to the severity of bleeding events. Strategies to mitigate bleeding events could improve neurologic recovery in pediatric ECMO.

Prophylactic Proton Pump Inhibitors in Upper Gastrointestinal Bleeding: Impact and Underprescription in a French Multicentric Cohort.

Appropriate prescription of Proton pump inhibitors (PPIs) remains an important concern amid the rising overuse. A gap exists in the literature regarding the benefit of PPI prophylaxis and the consequences of underprescription in patients at risk for upper gastrointestinal bleeding (UGIB). This study aims to describe the characteristics of hemorrhage in relation to PPI use in patients experiencing UGIB, with a focus on high-risk individuals requiring gastroprotection. Data from a French multicentric cohort of patients experiencing UGIB were analyzed. Patients using PPI were compared to those without PPI considering bleeding etiologies and outcomes of peptic ulcer disease (PUD)-related hemorrhage. The rate of PPI use and its effect on bleeding characteristics in high-risk populations, defined based on international guidelines, were also assessed. Among 2497 included patients, 31.1% were on PPI at bleeding onset. PPI users exhibited a significantly lower rate of PUD-related bleeding in comparison with those without PPI (24.7 vs 40.8%, respectively, p < 0.0001). Similar difference was observed in high-risk populations, of whom, only 40.3% had gastroprotection with PPI before bleeding onset. PPI prophylaxis, however, did not influence the severity of bleeding in the general study population or in high-risk groups. Multivariate analysis identified age, comorbidities, and having more than two anti-thrombotic agents as predictors of severe bleeding. PPI users appear to have a lower rate of bleeding ulcers compared to non-users. However, underprescription in high-risk groups raises the need for standardized care to ensure appropriate PPI use.

Comparison of postoperative bleeding in pediatric tonsillectomy versus tonsillotomy

ObjectiveTonsillar surgery is a common intervention for pediatric obstructive sleep apnea and recurrent tonsillitis. This study compared postoperative bleeding incidence and severity following tonsillotomy and tonsillectomy at a single medical center. Study designA retrospective cohort study on 1984 pediatric patients (1–18 years old) who underwent surgery during 2004–2011 and 2019–2022. Tonsillectomy was performed during 2004–2011, while tonsillotomy was preferred for obstructive sleep apnea during 2019–2022. Tonsillectomy was performed using cold steel technique with complete removal of tonsillar tissue, while tonsillotomy was conducted using mono- or bipolar diathermy, preserving minimal tissue on the tonsillar capsule. SettingShaare-Zedek Medical Center, Faculty of Medicine, Hebrew University. MethodsOutcome measures included postoperative bleeding incidence and severity, surgery duration, hospitalization length, and readmission. ResultsTonsillotomy was conducted on 958 (48.3 %) patients, and tonsillectomy was performed on 1026 (51.7 %) patients. Obstructive sleep apnea was the only indication in 1553 (78.3 %) patients. Overall bleeding rate was lower following tonsillotomy (3.9 %) than tonsillectomy (9.5 %) (p < 0.001). Significantly more patients required surgical bleeding control post-tonsillectomy than post-tonsillotomy: 39 (3.7 %) vs. 5 (0.5 %), respectively (p < 0.001). Tonsillectomy resulted in higher readmission rates (11.8 % vs 6.1 %, p < 0.001), more blood transfusions (3 vs. 0), and higher postoperative hemoglobin diminution (1.57 ± 2 vs. 0.94 ± 1 g/dL, p = 0.035). The duration of the surgery was shorter for tonsillotomy (24.7 vs 26.5 min, p = 0.012). Tonsillectomy sustained higher bleeding rates for obstructive sleep apnea patients (7.0 % vs 3.9 %, p = 0.006). For recurrent tonsillitis patients, bleeding rates did not vary between year groups. Older age and tonsillectomy were the most significant risk factors for postoperative bleeding. ConclusionAmong children undergoing tonsillar surgery for obstructive sleep apnea, tonsillotomy was associated with a safer postoperative bleeding profile, reduced bleeding severity, and fewer readmissions compared to tonsillectomy.

Efficacy of a RADA-16 peptide hydrogel versus chitosan-based polymer in improving patient comfort during postoperative debridement: A randomized controlled trial.

Bioresorbable nasal packing is associated with a decreased incidence of adhesions and bleeding postoperatively after endoscopic sinus surgery (ESS). However, discomfort during postoperative debridement is still a major area of concern for patients. Our objective was to compare the efficacy of a peptide hydrogel to that of a chitosan-based polymer in reducing pain during debridement after ESS. A prospective, multicenter, randomized, blinded trial was conducted in adults undergoing bilateral total ethmoidectomy for chronic rhinosinusitis. Participants served as their own controls with each subject receiving the hydrogel in a randomized ethmoid cavity and chitosan-based polymer in the contralateral ethmoid cavity. Participants were evaluated at 1, 4, and 12weeks postoperatively. Pain during debridement as well as endoscopic evaluation of mucosal healing and hemostasis were measured. Thirty patients who underwent ESS were included in this trial. During the week 1 postoperative debridement, patients reported significantly less pain on the hydrogel-treated side compared to the chitosan-based polymer-treated side. There were no significant differences in bleeding severity, Lund-Kennedy scores, debridement time, or need for further intervention between the two groups. This study demonstrated the efficacy of a peptide hydrogel inminimizing pain during postoperative debridement.

Clinical and diagnostic evidence of benign endometrial pathology in postmenopausal patients

The objective: to study clinical and diagnostic features of the benign endometrial conditions in the postmenopausal women.Materials and method. 64 postmenopausal patients with various severity of postmenopausal vaginal bleeding were examined. All patients underwent clinical, radiological, laboratory and histological examinations, reproductive history data and body mass index indicators were evaluated. Of them 33 persons were diagnosed with complex endometrial hyperplasia without atypia, 16 women – endometrial polyp and 15 women – hyperplasia with atypia. Routine gynecological examination including abdominal and pelvic examination following transvaginal ultrasound examination for the determination of the uterine and ovarian volume as well, as the endometrial thickness were conducted. Patients included in the study underwent computer tomography and magnetic resonance imaging as indicated. All patients with endometrial pathology underwent endometrial biopsy by standard dilatation and curettage or Pipelle-biopsy with histological examination of the obtained material. The concentrations of follicle-stimulating hormone (FSH), luteinizing hormone (LH), dehydroepiandrosterone sulfate (DHEA-S), estradiol, estrone, progesterone, prolactin, and testosterone were determined in blood serum.Results. It was confirmed that in 87,5% of cases endometrial hyperplasia manifested with vaginal bleeding. Endometrial thickness in examined persons ranged from 14.1±1.6 mm in patients with atypical endometrial hyperplasia to 21.3±4.8 mm in patients with complex endometrial hyperplasia without atypia. The study of blood levels of hormones found that postmenopausal patients with endometrial hyperplasia have lower FSH concentration, LH/FSH ratio, estradiol, testosterone levels, with significantly high values of prolactin, DHEA-S and estrone. During the postmenopausal period, hyperplasia was developed in 10% of cases by the presence of bleeding, and 86.2% of cases by the presence of blood spotting. Conclusions. The study suggests that high body mass index, numerous artificial abortions, high blood levels of estrone, DHEA-S and prolactin as well as increased thickness of endometrium influence the frequency of endometrial hyperplasia in postmenopausal women.

Sex Differences in Intracranial Aneurysms: A Matched Cohort Study.

Background: Aneurysmal subarachnoid hemorrhage (SAH) predominantly affects women, accounting for 65% of cases. Women have a 1.3 times higher relative risk than men, with the incidence rising particularly in women aged 55-85 years. Women also have a higher prevalence of unruptured intracranial aneurysms (IAs), especially after the age of 50 years, and are at greater risk of aneurysm growth and rupture. This study aimed to isolate the influence of sex on rupture rate, bleeding severity, functional outcomes, and complications by using a matched cohort, while also examining the impact of sex on aneurysm localization and multiplicity. Methods: We utilized a retrospectively collected database of 300 patients with 511 IAs. Inclusion criteria included the availability of clinical data and 3D angiography for semi-automatic reconstruction of IA morphology. Female patients and their IA were matched with male patients according to clinical parameters and 21 morphological characteristics using an interactive visual exploration tool for multidimensional matching. Results: Contrary to previously published results, our study found no significant sex differences in rupture rates or vasospasm rates between male and female patients. The severity of SAH, functional outcomes, and complications such as hydrocephalus were also similar in women and men. However, women exhibited a higher prevalence of multiple aneurysms and distinct localization patterns. Conclusions: This study underscores the complex role of sex in IA development and rupture. Although sex-specific biological factors influence aneurysm characteristics, they do not necessarily translate into differences in clinical outcomes. Further research is needed to explore these factors and their impact on aneurysm development and management.

Clinical features and treatment of 70 children with lupus anticoagulant-hypoprothrombinemia syndrome: a retrospective study from a single center in China

BackgroundLupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) is a rare acquired bleeding disorder characterized by the presence of lupus anticoagulant (LA) and acquired hypoprothrombinemia. ObjectivesTo summarize the experience of diagnosis, clinical features, and treatment of lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS). MethodsA retrospective study of 70 children diagnosed with LAHPS from January 2019 to February 2024 at a single center was conducted. ResultsA total of 70 subjects (32 boys and 38 girls), with a mean age of 5.58 years, were included in the study. Among these subjects, 15 had autoimmune diseases (AIDs), 51 had infections, and 4 had unknown causes. Fifty-six of 70 (80%) subjects experienced bleeding with the median bleeding score of 4, 1 of 70 (1.4%) presented with thrombosis, and 13 of 70 (18.6%) were asymptomatic. All patients exhibited prolonged prothrombin time, significantly prolonged activated partial thromboplastin time, decreased factor (F)II activity (FII:C), and positive lupus anticoagulant. There was a weak negative correlation between the severity of bleeding and FII:C level (rs = −0.4283; P < .001). Patients with infection-associated LAHPS were younger than those with AIDs-associated LAHPS (P < .0001). In the study, LAHPS subjects are treated with corticosteroids as the first-line therapy, or in combination with immunosuppressants. Coagulation factor replacement therapy can effectively prevent and control bleeding events. After follow-up, lupus anticoagulant of all patients had turned negative within 12 weeks. And, prothrombin time and FII:C were completely normalized of all patients without recurrence of bleeding and without thrombosis. ConclusionChildren develop LAHPS most commonly after AIDs and infection. Most patients presented with mild to moderate bleeding. The severity of bleeding symptoms was not exactly parallel to the decreased FII:C level.

Clinical and Biochemical Differences in Patients Having Non-Variceal Upper Gastrointestinal Bleeding on NSAIDs, Oral Anticoagulants, and Antiplatelet Therapy.

Introduction: Upper gastrointestinal bleeding (UGIB) is among the most common causes of morbidity and mortality worldwide, accounting for major resource allocation and increasing incidence. This study aimed to evaluate the severity of non-variceal bleeding in patients at risk of bleeding through the use of NSAIDs, oral anticoagulants, and antiplatelet therapy. Material and Method: The study included 296 patients admitted in the Gastroenterology Department of the Municipal County Emergency University Hospital, Timisoara, between 01.01.2018 and 01.04.2020, and diagnosed via gastroscopy with non-variceal gastrointestinal bleeding. The patients were divided among four groups based on their use of different drugs known to induce UGIB, i.e., aspirin and clopidogrel, NOACs, NSAIDs, and anti-vitamin K drugs, respectively. Statistical analyses were performed based on ANOVA one-way tests for continuous variables and Chi-square tests for categorical variables with pairwise comparisons based on Bonferroni adjusted significance tests. Results: The results showed several parameters having statistical significance among the different groups of patients. Patients on NOACs had statistically significant lower hemoglobin levels, lower hematocrit values, lower erythrocytes, lower RDW and higher fibrinogen levels compared to patients on VKA. Discussion: Surprisingly, the results from our study suggest that the use of NOACs was associated with a higher risk of bleeding when compared to VKA, which differs from the existing literature. Conclusions: One of the important factors causing upper non-variceal bleeding can be iatrogenic, either due to antiplatelet drugs or anticoagulants, to which NSAID treatment is additionally associated for various reasons. In our study, the use of NOACs seemed to have a more severe bleeding spectrum with higher morbidity compared to VKA.

Comparative incidence and risk factors for gastrointestinal bleeding following percutaneous coronary intervention for coronary artery disease: Insights from the Keio Cardiovascular Registry in Japan

BackgroundIn patients with coronary artery disease (CAD) undergoing percutaneous coronary intervention (PCI), antiplatelet medication usage is crucial for preventing thrombotic events. However, it requires careful monitoring, especially because of the risk of life-threatening bleeding complications. In hemorrhagic complications, assessment of patient background and risk of gastrointestinal bleeding (GIB) remain limited for GIB that develops during long-term observation after hospital discharge. This study aimed to examine the incidence of GIB and patient characteristics in CAD post-PCI. MethodsAll CAD patients undergoing PCI for urgent, emergent, or elective indications were enrolled in the Keio Interhospital Cardiovascular Studies (JCD-KiCS)-PCI registry (January 2009 and December 2017) and followed up to 2 years after PCI discharge. From the JCD-KiCS PCI registry, 8864 patients (median [interquartile range [IQR]] age: non-GIB: 69.0 y [16 y], upper GIB (UGI): 72.0 y [15.5 y], lower GIB (LGI): 73.0 y [IQR: 13 y]) were categorized based on the occurrence of hospitalization-requiring GIB. Patient characteristics and detailed information regarding these GIB events, including the location (upper vs lower GI) and bleeding severity, were analyzed. ResultsOverall, 36 patients experienced UGI, while 85 patients experienced LGI. The rates of dual antiplatelet therapy (DAPT) and triple therapy were significantly different among the non-GIB (n = 8734), UGI (n = 36) and LGI (n = 85) groups (DAPT [aspirin + P2Y12 (clopidogrel/prasugrel/ticlopidine)]: 64 [76.2 %] in the LGI group vs 24 [68.6 %] in the UGI group vs 7330 [84.6 %] in the non-GIB group; triple therapy [aspirin + P2Y12 (clopidogrel/prasugrel/ticlopidine)] + oral anticoagulant (OAC) (warfarin/direct oral anticoagulant [DOAC]): 17 [20.2 %] in the LGI group vs 8 [22.9 %] in the UGI group vs 836 [9.6 %] in the non-GIB group; p < 0.001). In the LGI and UGI groups, aspirin and warfarin were used in 2 (2.4 %) and 2 (5.7 %) patients, respectively, but not in combination with DOAC. The 2-year post-PCI hospitalization incidence for GIB was 1.4 % (LGI, 1.0 %; UGI, 0.4 %). The most common causes were colonic diverticular hemorrhage (43.5 %) for LGI and duodenal ulcer (21.9 %) for UGI. No significant differences were found in the cumulative 2-year post-PCI risks between the LGI and UGI groups (log-rank p = 0.97). Most GIB events were Bleeding Academic Research Consortium 2-equivalent (hemoglobin decrease <3 g/dL). Notably, the use of OACs at PCI discharge, bleeding complications within 72 h, and preprocedural anemia were significantly correlated with an increased GIB risk. ConclusionsThe real-world incidence of LGI is two times higher than that of UGI in CAD patients undergoing PCI, and most events are mild. OAC use at PCI discharge is the strongest potential risk factor for GIB development.

Plasmin generation analysis in patients with bleeding disorder of unknown cause

AbstractBleeding disorder of unknown cause (BDUC) is a diagnosis of exclusion after evaluation of plasma coagulation and platelet function. Patients with BDUC (n = 375) recorded in the Vienna Bleeding Biobank were analyzed in comparison with healthy controls (HCs; n = 100) in this case-control study. Plasmin generation (PG) parameters were analyzed using calibrated fluorescence detection in citrated plasma. Turbidimetric plasma clot formation/lysis of 293 (78%) patients with BDUC and confocal microscopy of clots from representative patients with BDUC (n = 6) and HCs (n = 9) were assessed. In the PG analysis, patients with BDUC exhibited lower velocity and peak plasmin levels but a higher endogenous plasmin potential than HCs. Peak plasmin levels correlated with maximum clot absorbance but not with clot lysis time. Clot absorbance is an indicator of clot fiber density. Confocal microscopy analysis revealed a tendency towards thicker fibers in clots of patients with BDUC, which negatively correlated with peak plasmin (r = −0.561; P = .030). Peak plasmin correlated weakly with factor XIII, but not with other fibrinolytic factors (alpha2-antiplasmin, thrombin activatable fibrinolysis inhibitor, or plasminogen activator inhibitor 1) or bleeding severity. A model comprising fibrinogen and parameters of PG yielded high predictive power in discriminating between patients with BDUC and HCs across a fivefold stratified cross validation (80% of data; mean area under the curve [AUC], 0.847). The model generalized well to unseen data (20% of data; AUC, 0.856). Overall, patients with BDUC counterintuitively exhibited reduced peak plasmin levels, potentially related to altered clot structure.

Percutaneous coronary revascularization versus medical therapy in chronic coronary syndromes: An updated meta-analysis of randomized controlled trials.

Coronary artery disease (CAD) is a main cause of morbidity and mortality. The effectiveness of coronary revascularization in chronic coronary syndromes (CCS) is still debated. Our recent study showed the superiority of coronary revascularization over optimal medical therapy (OMT) in reducing cardiovascular (CV) mortality and myocardial infarction (MI). The recent publication of the ORBITA-2 trial suggested superiority of percutaneous coronary revascularization (PCI) in reducing angina and improving quality of life. Therefore, we aimed to provide an updated meta-analysis evaluating the impact of PCI on both clinical outcomes and angina in CCS. Relevant studies were screened in PubMed/Medline until 08/01/2024. Randomized controlled trials (RCTs) comparing PCI to OMT in CCS were selected. The primary outcome was CV death. Secondary outcomes were MI, all-cause mortality, stroke, major bleeding and angina severity. Nineteen RCTs involving 8616 patients were included. Median follow-up duration was 3.3 years. Revascularization significantly reduced CV death (4.2% vs. 5.5%; OR = .77; 95% CI .62-.96, p = .02). Subgroup analyses favoured revascularization in patients without chronic total occlusions (CTOs) (p = .052) and those aged <65 years (p = .02). Finally, a follow-up duration beyond 3 years showed increased benefit of coronary revascularization (p = .04). Secondary outcomes analyses showed no significant differences, except for a lower angina severity in the revascularization group according to the Seattle Angina Questionnaire (SAQ) (p = .04) and to the Canadian Cardiovascular Society (CCS) classification (p = .005). PCI compared to OMT significantly reduces CV mortality and angina severity, improving quality of life in CCS patients. This benefit was larger without CTOs, in patients aged <65 years and with follow-up duration beyond 3 years.

Clinical phenotypes and genotypes of congenital fibrinogen disorder: an analysis of 16 children

To investigate the clinical phenotypes and genotypes of children with congenital fibrinogen disorder (CFD). A retrospective analysis was conducted on the clinical data of 16 children with CFD. Polymerase chain reaction was used to amplify all exons and flanking sequences of the FGA, FGB, and FGG genes, and sequencing was performed to analyze mutation characteristics. Among the 16 children, there were 9 boys (56%) and 7 girls (44%), with a median age of 4 years at the time of attending the hospital. Among these children, 9 (56%) attended the hospital due to bleeding events, and 7 (44%) were diagnosed based on preoperative examination. The children with bleeding events had a significantly lower fibrinogen activity than those without bleeding events (P<0.05). Genetic testing was conducted on 12 children and revealed a total of 12 mutations, among which there were 4 novel mutations, i.e., c.80T>C and c.1368delC in the FGA gene and c.1007T>A and C.1053C>A in the FGG gene. There were 2 cases of congenital afibrinogenemia caused by null mutations of the FGA gene, with relatively severe bleeding symptoms. There were 7 cases of congenital dysfibrinogenemia mainly caused by heterozygous missense mutations of the FGG and FGA genes, and their clinical phenotypes ranged from asymptomatic phenotype to varying degrees of bleeding. The clinical phenotypes of children with CFD are heterogeneous, and the severity of bleeding is associated with the level of fibrinogen activity, but there is a weak association between clinical phenotype and genotype.

Factor V haemostatic diathesis impairing thrombin activation, membrane binding and circulating antigen level due to a novel compound heterozygous mutation, Leu1821Ser and Gly2192Cys.

Congenital factor V (FV) deficiency is a rare clotting disorder affecting ∼1 in 1,000,000, with bleeding severity that ranges broadly for poorly understood reasons. To help understand the molecular basis of the observed phenotype in FV deficient patients, the genetics and biochemistry causing a patient's FV deficiency were evaluated. A 71-year-old female, who had serious life-long bleeding upon provocation and profound menorrhagia that lead to hysterectomy, was found to have 3% of normal plasma FV antigen with normal electrophoretic mobility. Platelet FV was similarly low, although the banding pattern was less fragmented than normal. Plasma clotting activity was <1% of normal. Familial inheritance and DNA sequence analysis from peripheral blood leukocytes were consistent with novel compound heterozygosity with missense mutations in exon XVII, Leu1821 to Ser (L1821S) and exon XXV, Gly2192 to Cys (G2192C). The respective single-mutation variants were expressed and purified. Explaining why the antigen level and activity were inequivalent, thrombin activation of recombinant (r) FV/L1821S was impaired, and rFV/G2192C was unable to bind to a procoagulant phospholipid membrane. These findings are consistent with the observed phenotype, highlighting the importance of understanding FV biochemical function to rationalize clinical bleeding severity when the circulating antigen level is discordant.

Real-time evaluation of active bleeding severity in soft-tissue hematomas via contrast-enhanced ultrasound: a case series.

Real-time evaluation of active bleeding severity in soft-tissue hematomas via contrast-enhanced ultrasound: a case series.

Unresolved issues of comorbid pathology in minors with urogenital inflammation

A holistic approach to the problem of copious and prolonged menstruation during puberty allows adequately predicting the situation and clearly determining the direction of therapeutic and diagnostic measures. This model of protection of reproductive health of minors is based on interdisciplinary interaction. Problematic interdisciplinary issues of modern medicine include the norm and pathology of microbiocenosis of the vulva and vagina and recurrence of abnormal uterine bleeding in minors. Based on the study of modern literature data, the relationship between disorders of genital microbiocenosis and reproductive disorders in minors is analyzed. The results of scientific research, including 19 Russian and 12 foreign studies, which are presented in large scientific databases, such as eLibrary, CyberLeninka, Science Direct, Scopus, and Google Scholar, have been analyzed. It has been shown that vaginitis remains the most common disease in minors. The importance of doctor’s timely actions in the field of predicting the development of vaginitis and its timely prevention in childhood is emphasized. Dysbiotic disorders of the vaginal microbiota are one of the leading triggers of menstrual cycle formation disorders, including recurrence of abnormal uterine bleeding. The latter requires monitoring and preventive measures. The method of hemostasis must be selected individually, depending on the severity of bleeding and the characteristics of the clinical course. Combined infectious pathology is characterized by a persistent course and the interaction of mechanisms of persistence of the infectious process and justifies the need to take into account all aspects of clinical manifestations and apply a personalized approach to the complex therapy of these conditions at the interdisciplinary level.

Early Nonprocedural Bleeding After Left Atrial Appendage Occlusion

BackgroundPatients treated with left atrial appendage occlusion (LAAO) are at high bleeding risk. Intensive antithrombotic treatment is recommended after the procedure to prevent device-related thrombosis. ObjectivesThis study sought to evaluate the incidence, consequences, and predictors of early nonprocedural bleeding after LAAO. MethodsThis was a multicenter study including 1,649 patients undergoing LAAO in 9 centers. Early nonprocedural bleeding was defined as bleeding unrelated to the procedure occurring within 3 months after device implantation. The severity of bleeding was defined by the Valve Academic Research Consortium-2 classification. A sensitivity analysis was performed at 45 days. ResultsA total of 121 (7.3%) patients experienced early nonprocedural bleeding events, and 69 (57.0%) were classified as major bleeding (4.2% of patients). Independent predictors of early nonprocedural bleeding were dual antiplatelet therapy (DAPT) at discharge (adjusted HR [aHR]: 1.61; 95% CI: 1.12-2.33; P = 0.01), prior gastrointestinal bleeding (aHR: 2.15; 95% CI: 1.38-3.35; P < 0.001), and multiple locations of prior bleeding (aHR: 2.33; 95% CI: 1.34-4.05; P < 0.001). DAPT at discharge was predictive of both all and major nonprocedural bleeding at 3 months and 45 days. After a median follow-up of 2.3 years (Q1-Q3: 1.1-4.1 years), early nonprocedural bleeding was independently associated with an increased risk of all-cause death (aHR: 1.53; 95% CI: 1.15-2.06; P < 0.001). This heightened mortality risk was similar at 45 days. ConclusionsEarly nonprocedural bleeding after LAAO occurred in ∼7% of patients within 3 months, with more than one-half being classified as major bleeding. Regardless of severity, early nonprocedural bleeding was associated with increased mortality. DAPT at discharge determined an increased risk of early nonprocedural bleeding after LAAO. These results emphasize the importance of bleeding risk for determining antithrombotic strategies after LAAO.

Evaluation of patient perception and intraoperative bleeding in labial frenectomy: A comparision of diode laser and conventional scalpel techniques

: High frenal attachments are abnormalities corrected by surgical procedure called frenectomies. The scalpel technique is associated with pain, bleeding and postoperative discomfort. To overcome these shortcomings, in the recent times, diode lasers are gaining popularity due to less bleeding, pain during the procedure, healing outcome, and need for analgesics: To compare the bleeding during the procedure and postoperative pain in patients requiring labial frenectomy using conventional scalpel and diode laser techniques. Twenty patients with high labial frenum attachment requiring frenectomy were included in this study. Patients were randomly divided into Group A: scalpel group and Group B: diode laser group. Pain assessment using VAS, severity of intraoperative bleeding and number of analgesics used were recorded: The analysis showed that VAS score for pain was significantly lower in the laser group as compared to the scalpel group Bleeding was mild in laser group, where as in scalpel group showed moderate or severe bleeding scores Post operative use of analgesics was more in scalpel group than laser group Laser was found to be an effective alternate to scalpel in performing frenectomy procedures, more importantly it showed less bleeding, less pain perception and more patient acceptance during the procedure.

Bleeding assessment following central venous catheter placement, a direct comparison of prospective and retrospective analyses.

Reported bleeding incidences following central venous catheter (CVC) placement highly depend on methods of bleeding assessment. To determine the direction and magnitude of the bias associated with retrospective data collection, we used data from the PACER randomized controlled trial and a previous retrospective cohort study. A patient-level comparison of CVC-related bleeding severity was made among (1) the prospectively collected clinical bleeding assessment of the PACER trial, (2) centralized assessment of CVC insertion site photographs, and (3) retrospective chart review. Interrater reliability for photographic bleeding assessment and retrospective chart review was assessed using Cohen's κ. The magnitude of underreporting of both methods compared to prospective clinical bleeding assessment at different cutoff points of clinically relevant bleeding was assessed using McNemar's test. Interrater reliability was acceptable for both methods (κ = 0.583 and κ = 0.481 for photographic assessment and retrospective chart review, respectively). Photographic bleeding assessment led to significant underreporting of bleeding complications at all cutoff points. Retrospective chart review led to significant underreporting of minor bleeding complications, with an odds ratio (95% CI) of 0.17 (0.044-0.51) for the cutoff point grade 1 (i.e., self-limiting or requiring at most 20 min of manual compression) or higher. There was no significant underreporting of major bleeding complications with retrospective chart review. Centralized photographic bleeding assessment and retrospective chart review lead to biased bleeding assessment compared to prospective clinical bleeding assessment.