Severity Of Bleeding Research Articles

Abnormal uterine bleeding (clinical lecture)

Abnormal uterine bleeding (AUB) not related to pregnancy has been one of the leading reasons for visiting a gynecologist for many years. The incidence of AUB is approximately 30% among patients of reproductive age and can increase to 70% during the perimenopausal period. Recurrent AUB leads to the development of iron deficiency anemia, significantly reducing the quality of life, and also resulting in additional costs for hygiene products.
 This clinical lecture provides a modern classification of AUB. It focuses on the main mechanisms of development of this pathology in adolescence and reproductive age. The causes of AUB are analyzed, and the classification, symptomatology, and clinical presentation of the studied conditions are presented. The lecture covers international criteria for pathologic uterine bleeding, clinical criteria for assessing bleeding severity according to MansfieldVodeJorgensen scale and estimation of blood loss volume according to Algover index. Detailed consideration is given to the issues of differential diagnosis, general principles of therapy, and indications for traditional, hormonal, and surgical hemostasis. The lecture also outlines the algorithm of diagnostic search for patients in the adolescent, reproductive, postmenopausal age groups, as well as for patients on the background of menopausal hormonal therapy.

Effects of Herbal Products on Menorrhagia: A Systematic Review and Meta-analysis

Context: Menorrhagia is an important healthcare challenge. Complementary and alternative medicine therapies are strategies with potential positive effects on menorrhagia. Objectives: The aim of this study was to systematically assess the effects of herbal products on menorrhagia. Methods: This was a systematic review and meta-analysis. PubMed, Scopus, Web of Science, Embase, Cochrane Library, Barekat Gostar, Scientific Information Database (SID), Magiran, and IranDoc international and Iranian databases, in addition to the Google Scholar search engine, were searched without any time or language limitation (updated until 02.07.2022). Eligible studies were combined through the random-effects model based on their sample sizes, mean scores, and standard deviations. Data analysis was performed at a significance level of less than 0.05 using STATA software (version 14.0). Results: Nineteen trials on 1715 women (856 and 859 subjects in the control and intervention groups, respectively) were reviewed. After the intervention, menstrual bleeding severity in the first, second, and third cycles (P < 0.001) and the number of menstrual days in the first (P < 0.001), second (P < 0.001), and third (P = 0.487) menstrual cycles significantly decreased in the herbal products group. There were no significant between-group differences regarding the bleeding severity at the pretest (P < 0.001) and in the third cycle (P < 0.001) and the number of menstrual days at the pretest (P = 0.131) and in the second (P < 0.001) and third cycles (P = 0.014). However, the bleeding severity in the intervention group was significantly less than the control group in the first (P < 0.001) and second cycles (P < 0.001), and the number of menstrual days in the intervention group was significantly less than the control group in the first cycle (P = 0.004). Conclusions: Herbal products are effective in significantly reducing bleeding severity and the number of menstrual days among women with menorrhagia, and their effects reduce over time.

Hyperlipidemia in immune thrombocytopenia: a retrospective study

BackgroundImmune thrombocytopenia (ITP) is an autoimmune hemorrhagic disease characterized by low platelet count and bleeding manifestations. However, some patients also suffered from atherosclerosis or even infarction. Apart from activated platelets, lipid metabolism takes a large part in the formation of atherosclerosis and metabolic syndrome. The lipid metabolic state in ITP patients is still unknown.MethodsWe retrospectively reviewed 302 hospitalized ITP patients in our cohort, comparing their blood lipids, bleeding symptoms, metabolic diseases and treatment responses.ResultsWe found a high proportion of ITP patients suffered from hyperlipidemia, and other metabolic diseases including cardiovascular or cerebral atherosclerosis or infarction, hypertension, and type 2 diabetes. Hyperlipidemia was associated with severe bleeding and treatment refractoriness in ITP. Statins could alleviate thrombocytopenia and bleeding severity, and facilitate ITP treatment, while improving hyperlipidemia in ITP patients.ConclusionsOur present study demonstrated that lipid metabolism might play an indispensable role in ITP pathogenesis and development.

Evaluation of the validated intraoperative bleeding scale in liver surgery: study protocol for a multicenter prospective study.

Surgical hemostasis has become one of the key principles in the advancement of surgery. Hemostatic agents are commonly administered in many surgical specialties, although the lack of consensus on the definition of intraoperative bleeding or of a standardized system for its classification means that often the most suitable agent is not selected. The recommendations of international organizations highlight the need for a bleeding severity scale, validated in clinical studies, that would allow the selection of the best hemostatic agent in each case. The primary objective of this study is to evaluate the VIBe scale (Validated Intraoperative Bleeding Scale) in humans. Secondary objectives are to evaluate the scale's usefulness in liver surgery; to determine the relationship between the extent of bleeding and the hemostatic agent used; and to assess the relationship between the grade of bleeding and postoperative complications. Prospective multicenter observational study including 259 liver resections that meet the inclusion criteria: patients scheduled for liver surgery at one of 10 medium-high volume Spanish HPB centers using an open or minimally invasive approach (robotic/laparoscopic/hybrid), regardless of diagnosis, ASA score <4, age ≥18, and who provide signed informed consent during the study period (September 2023 until the required sample size has been recruited). The participating researchers will be responsible for collecting the data and for reporting them to the study coordinators. This study will allow us to evaluate the VIBe scale for intraoperative bleeding in humans, with a view to its subsequent incorporation in daily clinical practice. https://clinicaltrials.gov/ct2/show/NCT05369988?term = serradilla&draw = 2&rank = 3, [NCT0536998].

Short-Term Outcomes of Double Omentopexy in One Anastomosis Gastric Bypass Surgery: A Controlled Clinical Trial

ABSTRACT Purpose: This study aims to assess the efficacy of implementing a novel technique of reinforcement of gastric pouch and remnant stomach staple line with Double Omentopexy (DO) in patients undergoing One-Anastomosis Gastric Bypass (OAGB) surgery and evaluate its impact in reducing the early postoperative complications. Materials and Methods: The 123 patients were allocated into two groups: 61 in the standard OAGB group and 62 in OAGB with DO group. The primary outcomes are postoperative complications (including early postoperative bleeding, leakage, gastric twist, reflux, etc.) and hospital stay. The secondary outcome is excess body weight loss. Follow-up visits were planned after discharge: at two weeks, two months, and three months postoperatively. Results: Postoperative complications were significantly lower, 3 (4.84%) in OAGB with DO compared with 10 (16.39%) in standard OAGB (P =0.037). There was no statistically significant difference in the incidence of early postoperative bleeding, deep vein thrombosis, biliary reflux, and gall bladder stone (P &gt;.05). No patient had leakage in either group. The mean operative time was significantly longer (68.66 ± 6.68 min) in OAGB with the DO group when compared with the standard OAGB group (62.16 ± 7.54 min) (P &lt;.001). Conclusion: Applying the DO technique may be a good measure to be added during OAGB to decrease the incidence of potential postoperative complications, especially the rate and severity of bleeding.

Elevated first-trimester PAPP-A is a marker in high-risk pregnancies with an increased risk of placenta accreta in predicting adverse outcomes.

Our work aims to determine whether there is an association between first-trimester serum pregnancy-associated plasma protein A (PAPP-A) multiples of the median (MoM) value and placenta previa with or without placenta accreta spectrum disorders (PAS) in women. A retrospective analysis was performed on 267 patients who had first-trimester screening test results for aneuploidy, including nonadherent placenta previa (n=106), placenta previa with PAS (n=60), and control group (healthy pregnant women with previous cesarean section and normal placental location, n=101). To assess the significant difference between these groups, PAPP-A MoMs were compared. The median PAPP-A MoM of 1.96 in placenta previa with PAS was significant (>0.88) in nonadherent placenta previa and 0.89 in the control group (p<0.001). Serum PAPP-A was found to be significantly associated with the severity of bleeding, such that patients with severe bleeding of 1,500 mL or more (n=54) had a higher mean PAPP-A MoM (1.93±0.69; p<0.001). Furthermore, the mean PAPP-A MoM was found to be 1.96±0.74 in the hysterectomy group and 0.89±0.47 in the conservative management group, and the difference was found to be significantly higher (p<0.001). Elevated PAPP-A values in the first trimester of pregnancy may be a useful marker for identifying women at higher risk of PAS and adverse outcomes.

PB0220 Clinical Presentation and Bleeding Severity in Women with Autosomal Inherited Bleeding Disorders and Hemophilia Carriers: Real-Life Data from the Spanish Registry

PB0220 Clinical Presentation and Bleeding Severity in Women with Autosomal Inherited Bleeding Disorders and Hemophilia Carriers: Real-Life Data from the Spanish Registry

Clinical Implications of Discrepancy between One-Stage Clotting and Chromogenic Factor IX Activity in Hemophilia B.

Discrepancy in factor IX activity (FIX:C) between one-stage assay (OSA) and chromogenic substrate assay (CSA) in patients with hemophilia B (PwHB) introduces challenges for clinical management. To study the differences in FIX:C using OSA and CSA in moderate and mild hemophilia B (HB), their impact on classification of severity, and correlation with genotype. Single-center study including 21 genotyped and clinically characterized PwHB. FIX:C by OSA was measured using ActinFSL (Siemens) and CSA by Biophen (Hyphen). In addition, in vitro experiments with wild-type FIX were performed. Reproducibility of CSA was assessed between three European coagulation laboratories. FIX:C by CSA was consistently lower than by OSA, with 10/17 PwHB having a more severe hemophilia type by CSA. OSA displayed a more accurate description of the clinical bleeding severity, compared with CSA. A twofold difference between OSA:CSA FIX:C was present in 12/17 PwHB; all patients had genetic missense variants in the FIX serine protease domain. Discrepancy was also observed with diluted normal plasma, most significant for values below 0.10 IU/mL. Assessment of samples with low FIX:C showed excellent reproducibility of the CSA results between the laboratories. FIX:C was consistently higher by OSA compared with the CSA. Assessing FIX:C by CSA alone would have led to diagnosis of a more severe hemophilia type in a significant proportion of patients. Our study suggests using both OSA and CSA FIX:C together with genotyping to classify HB severity and provide essential information for clinical management.

Application of thromboelastography to predict the severity of bleeding after chimeric antigen receptor (CAR)-T cell therapy in patients with hematological malignancy.

We aim to analyze the predictive value of thromboelastography on bleeding severity of patients with chimeric antigen receptor (CAR)-T cell therapy. A total of 80 patients with refractory/relapsed hematological malignancy were enrolled and divided into two groups: the severe bleeding group and the non-severe bleeding group. The thromboelastography data was collected on the day of CAR-T infusion and the 3rd, 7th, 10th, 13th, 17th, and 20th day after CAR-T cell infusion. The patients of the severe bleeding group had lower platelet (p < .007), maximum amplitude (p = .002), coagulation index (p = .005), and longer coagulation time (p = .019). Increasing trend in reaction time and coagulation time and decreasing trend in Alpha, maximum amplitude, and coagulation index on Days 0-10, opposite on Days 10-20. Univariate logistic regression analysis and multivariable logistic regression analysis showed maximum amplitude on the 3rd day after CAR-T cell infusion (MA3) (OR = 0.9; 95% CI = 0.84-0.95; p < .001) and cytokine release syndrome grade (OR = 2.57; 95% CI = 1.35-5.32; p = .006) were significantly associated with high bleeding severity. Thromboelastography was considered to be a good predictor of bleeding severity.

Bleeding in Critically Ill Children With Malignancy or Hematopoietic Cell Transplant: A Single-Center Prospective Cohort Study.

To determine the incidence of bleeding in critically ill children with malignancy and to describe associated patient characteristics, interventions, and clinical outcomes. Prospective cohort study. PICU in a specialized cancer hospital. Children with malignancy or hematopoietic cell transplant 0-18 years of age were admitted to the PICU from November 2020 to November 2021. None. Patient demographic data, laboratory values, and PICU outcome data were collected. Bleeding was classified according to the Bleeding Assessment Scale in Critically Ill Children. Ninety-three bleeding patients were enrolled, and a total of 322 bleeding days were recorded. The median (interquartile range [IQR]) age was 5.8 (2.9-11.8) years and 56% (52/93) of the patients were male. There were 121 new bleeding episodes, in 593 at-risk person-days, translating into a 20% incidence rate per day (95% CI, 17-24%). The incidence of severe, moderate, and minimal bleeding was 2% (95% CI, 1-3), 4% (95% CI, 3-6), and 14% (95% CI, 12-17), respectively. Of the new bleeding episodes, 9% were severe, 25% were moderate and 66% were minimal. Thrombocytopenia was the only laboratory value independently associated with severe bleeding ( p = 0.009), as compared to minimal and moderate bleeding episodes. History of radiation therapy was independently associated with severe bleeding ( p = 0.04). We failed to identify an association between a history of stem cell transplant ( p = 0.49) or tumor type ( p = 0.76), and bleeding severity. Patients were transfused any blood product on 28% (95% CI, 22-34) of the bleeding days. Severe bleeding was associated with increased length of mechanical ventilation ( p = 0.003), longer PICU stays ( p = 0.03), and higher PICU mortality ( p = 0.004). In this prospective cohort of children with malignancy, the incidence rate of bleeding was 20%. Most events were classified as minimal bleeding. Low platelet count and radiation therapy were variables independently associated with severe bleeding episodes.

Incidence, Predictors, and Prognostic Impact of Bleeding Events After TAVR According to VARC-3 Criteria

BackgroundThe updated Valve Academic Research Consortium (VARC) definition for bleeding events after transcatheter aortic valve replacement (TAVR) lacks of clinical validation. ObjectivesThe aim of this study was to determine the incidence, predictors, and clinical impact of bleeding events following TAVR as defined by recent VARC-3 criteria. MethodsA total of 2,384 consecutive patients with severe symptomatic aortic stenosis undergoing TAVR were included. Early (at index hospitalization) and late (after hospital discharge) bleeding complications were defined according to VARC-3 criteria as type 1, 2, 3, or 4. Baseline, procedural, and follow-up (24 [IQR: 12-43] months) data were prospectively collected. ResultsBleeding events occurred in 761 patients (31.9%): types 1, 2, 3, and 4 in 169 (22.2%), 399 (52.4%), 149 (19.6%), and 44 (5.8%) patients, respectively. The primary vascular access site and gastrointestinal locations were the most common bleeding sources among early and late bleeding events, respectively. Female sex, thoracotomy access, larger (14-F) sheath use, and dual antiplatelet therapy determined an increased risk of early bleeding events (P < 0.02 for all). The use of the radial artery for secondary access was associated with a significant risk reduction of early bleeding (P < 0.001). Type 2 and type 3 events were associated with an increased mortality risk at 30-day (HR: 2.94 [95% CI: 1.43-6.03; P = 0.003] and HR: 4.91 [95% CI: 2.19-11.03; P < 0.001], respectively) and 1-year (HR: 1.86 [95% CI: 1.28-2.69; P = 0.001] and HR: 2.28 [95% CI: 1.41-3.66; P = 0.001], respectively) follow-up. A similar prognostic pattern was observed when applying VARC-2 criteria but with a much lower global incidence of early bleeding events (19% vs 27%; P < 0.001). ConclusionsBleeding events after TAVR were associated with poorer short- and long-term survival. The magnitude of this correlation was proportional to bleeding severity defined according to VARC-3 criteria. Further studies on bleeding prevention following TAVR are warranted to improve procedural safety and patient prognosis.

Delaying Cardiac Catheterization in Favor of Endoscopy in Non-ST Elevation Myocardial Infarction Patients Is Associated with Worse Outcomes: A Nationwide Analysis.

Non-variceal upper gastrointestinal bleeding (NVUGIB) in non-ST-elevation myocardial infarction (NSTEMI) is associated with substantial morbidity and mortality. We evaluated inpatient outcomes of esophagogastroduodenoscopy (EGD) before cardiac catheterization in patients with NSTEMI and NVUGIB. We utilized the National Readmission Database (2016-2019) to identify all index hospitalizations with a primary diagnosis of NSTEMI and a secondary diagnosis of NVUGIB that underwent EGD before cardiac catheterization (cases). A matched comparison cohort of similar hospitalizations that undergo EGD after cardiac catheterization were identified (controls) after 1:1 propensity score matching for age, gender, cardiac comorbidities, causes, and severity of bleeding. A total of 796 cases were matched with 796 controls. There was a higher median length of hospital stay (8 vs. 5days, P = 0.01) and median hospital charges ($111,218 vs. $99,115, P = 0.002) for cases compared to controls. There was a higher all-cause inpatient mortality in cases compared to controls (5.5% vs. 3.9%, P = 0.26). Furthermore, there was a higher proportion of patients with ICU admission (7% vs. 3%, P < 0.001), septic shock (7.1% vs. 5.8%, P = 0.41), atrial fibrillation (27.1% vs. 19.8%, P < 0.001) and acute kidney injury (42.8% vs. 29.1%, P < 0.001) for cases compared to controls. Delaying cardiac catheterization in favor of EGD is associated with increased hospital stay, costs, and cardiac complications. Further studies are warranted to establish our findings.

Évolution du Shock Index obstétrical lors d’une hémorragie du post-partum selon le recours à la sulprostone

ObjectivesThe Shock Index (SI) is used in emergency medicine to assess the severity of active bleeding and in the postpartum context for postpartum haemorrhage (PPH). We investigated the diagnostic value of haemodynamic parameters (SI, heart rate (HR), systolic blood pressure (SBP), diastolic blood pressure (DBP) and mean arterial pressure (MAP)) in predicting subsequent use of uterotonic sulprostone treatment. MethodsThis was a retrospective study including parturients with PPH ≥ 500mL between January 2017 and December 2018. Hemodynamic parameters at the diagnosis of PPH were compared according to whether the patient required subsequent sulprostone treatment (sulprostone(+) group) or not (sulprostone(–) group). ResultsWe included in the analysis 147 patients. The SI was significantly higher in the sulprostone(+) group (0.92±0.28 vs. 0.83±0.22; p=0.04). The SBP (107.2±17.5 vs. 113.8±17.7mmHg; p=0.03), DBP (56.8±12,2 vs. 61.5±13,2mmHg; p=0.04), MAP (73.6±12.6 vs. 78.5±13.4mmHg; p=0.03) were significantly lower in the same group. No difference between AUC of these parameters to predict the use of sulprostone was found (AUC between 0.59 and 0.61). No significant difference was found for the HR between the two groups. ConclusionThe diagnostic value of SI appeared to be low and similar to other haemodynamic parameters in predicting the use of sulprostone.

Management of perimesencephalic nonaneurysmal subarachnoid hemorrhage: a national survey

Perimesencephalic nonaneurysmal subarachnoid hemorrhage (NASAH) is a rare type of subarachnoid hemorrhage (SAH), usually associated with minor complications compared to aneurysmal SAH. Up to date, data is scarce and consensus on therapeutic management and follow-up diagnostics of NASAH is often missing. This survey aims to evaluate the clinical management among neurosurgical departments in Germany. 135 neurosurgical departments in Germany received a hardcopy questionnaire. Encompassing three case vignettes with minor, moderate and severe NASAH on CT-scans and questions including the in-hospital treatment with initial observation, blood pressure (BP) management, cerebral vasospasm (CV) prophylaxis and the need for digital subtraction angiography (DSA). 80 departments (59.2%) answered the questionnaire. Whereof, centers with a higher caseload state an elevated complication rate (Chi2 < 0.001). Initial observation on the intensive care unit is performed in 51.3%; 47.5%, 70.0% in minor, moderate and severe NASAH, respectively. Invasive BP monitoring is performed more often in severe NASAH (52.5%, 55.0%, 71.3% minor, moderate, severe). CV prophylaxis and transcranial doppler ultrasound (TCD) are performed in 41.3%, 45.0%, 63.8% in minor, moderate and severe NASAH, respectively. Indication for a second DSA is set in the majority of centers, whereas after two negative ones, a third DSA is less often indicated (2nd: 66.2%, 72.5%, 86.2%; 3rd: 3.8%, 3.8%, 13.8% minor, moderate, severe). This study confirms the influence of bleeding severity on treatment and follow-up of NASAH patients. Additionally, the existing inconsistency of treatment pathways throughout Germany is highlighted. Therefore, we suggest to conceive new treatment guidelines including this finding.

Treatment of Inherited Platelet Disorders: Current Status and Future Options.

Inherited platelet disorders (IPDs) comprise a heterogeneous group of entities that manifest with variable bleeding tendencies. For successful treatment, the underlying platelet disorder, bleeding severity and location, age, and sex must be considered in the broader clinical context. Previous information from the AWMF S2K guideline #086-004 (www.awmf.org) is evaluated for validity and supplemented by information of new available and future treatment options and clinical scenarios that need specific measures. Special attention is given to the treatment of menorrhagia and risk management during pregnancy in women with IPDs. Established treatment options of IPDs include local hemostatic treatment, tranexamic acid, desmopressin, platelet concentrates, and recombinant activated factor VII. Hematopoietic stem cell therapy is a curative approach for selected patients. We also provide an outlook on promising new therapies. These include autologous hematopoietic stem cell gene therapy, artificial platelets and nanoparticles, and various other procoagulant treatments that are currently tested in clinical trials in the context of hemophilia.

Health-related quality of life is impaired in bleeding disorders of unknown cause: results from the Vienna Bleeding Biobank

BackgroundBleeding disorder of unknown cause (BDUC) is a diagnosis of exclusion after extensive investigation of coagulation and platelet function and is commonly seen among patients with mild-to-moderate bleeding disorders. Despite increasing awareness among treating physicians, little is known about the health-related quality of life (HrQoL) in BDUC. ObjectivesTo investigate HrQoL in patients with BDUC in comparison to the general population and patients diagnosed with other established bleeding disorders. MethodsPatients with mild-to-moderate bleeding disorders from the Vienna Bleeding Biobank, a prospective cohort study, were contacted via mail and phone to complete the 36-Item Health Survey Questionnaire form. ResultsIn total, 333/657 (50.7%) patients completed the 36-Item Health Survey Questionnaire. Patients with BDUC (n = 207, 62%) had significantly impaired HrQoL both in physical (47.8 vs 49.2) and mental health parameters (42.9 vs 51.0) compared to the general population (n = 2914, 56% females), which remained after adjustment for sex and age in multivariable linear regression. The impairment in HrQoL, compared to patients with von Willebrand disease, platelet function defects, or mild clotting factor deficiencies, did not prevail after adjustment for age and sex. In patients with BDUC, age and the presence of at least 1 comorbidity were associated with impaired physical health but not sex or bleeding severity. Of all analyzed bleeding symptoms, only joint bleeding was associated with impaired physical health and gastrointestinal bleeding with mental health in BDUC. ConclusionThe impairments in HrQoL in patients with BDUC emphasize the burden of BDUC on mental and physical well-being, encouraging early recognition and better counseling of patients with BDUC.

INFILTRATION ANAESTHESIA FOR TYMPANOPLASTY: A COMPARISON OF DEXMEDETOMIDINE AND CLONIDINE AS ADJUVANTS TO LIGNOCAINE AND ADRENALINE

INFILTRATION ANAESTHESIA FOR TYMPANOPLASTY: A COMPARISON OF DEXMEDETOMIDINE AND CLONIDINE AS ADJUVANTS TO LIGNOCAINE AND ADRENALINE

Evaluation and management of acute epistaxis in the emergency department

Acute epistaxis, or nosebleed, is a common presentation in the emergency department (ED) that requires a systematic evaluation and prompt management. The assessment involves considering the severity of bleeding, identifying underlying causes, and implementing appropriate interventions. Modifiable risk factors, such as medication review, nasal hygiene, avoidance of nasal trauma, and humidification, should be addressed to prevent recurrence. Referral to specialists is necessary for cases of recurrent or severe bleeding, suspected underlying causes, or inadequate response to initial management. Collaboration between ED healthcare providers and specialists ensures comprehensive evaluation, specialized interventions, and long-term management. Regular follow-up appointments and patient education are essential for monitoring progress, adjusting treatment, and preventing complications. By employing a comprehensive approach, healthcare providers aim to alleviate distress, achieve hemostasis, identify underlying etiologies, and optimize patient outcomes in the ED.

Associations of multiple genetic variations with plasma levels of Von Willebrand Factor and clinical phenotype in Iranian patients with Von Willebrand disease type 1

BackgroundGenetic variations influence the Von Willebrand Factor plasma level and function. This study aims to evaluate the frequency and clinical phenotype effects of eight single nucleotide polymorphism candidates in four genes (VWF, STXBP5, CLEC4M, and ABO) in Iranian patients with VWD type 1. MethodThe study recruited 50 patients with VWD type 1 and 100 healthy individuals. The demographic data from all participants were collected, and the High-Resolution Melting technique was used to determine the frequency of specific single nucleotide polymorphisms. Bleeding scores were also obtained from all patients to assess how these genetic variations might affect the severity of their bleeding symptoms. ResultsThe study found notable variations in the occurrence of certain SNPs (rs7853989 and rs8176743 for ABO gene and rs1063856 and rs1063857 for VWF gene) between the control group and the patients. Additionally, the study discovered that two SNPs (rs868875 for CLEC4M gene and rs9390459 for STXBP5 gene) were significantly linked to the severity of bleeding, and two others (rs868875 for CLEC4M gene and rs8176746 for ABO gene) were associated with reduced levels of VWF antigen in the patients. ConclusionAccording to this study, the above-selected SNPs can cause variations in VWF plasma levels in patients with VWD type 1. Furthermore, the effects of SNPs on bleeding phenotype prove the role of these SNPs in the severity of bleeding manifestations in patients.

Bleeding with intensive versus guideline antiplatelet therapy in acute cerebral ischaemia

Intensive antiplatelet therapy did not reduce recurrent stroke/transient ischaemic attack (TIA) events as compared with guideline treatment in the Triple Antiplatelets for Reducing Dependency after Ischaemic Stroke (TARDIS) trial, but did increase the frequency and severity of bleeding. In this pre-specified analysis, we investigated predictors of bleeding and the association of bleeding with outcome. TARDIS was an international prospective randomised open-label blinded-endpoint trial in participants with ischaemic stroke or TIA within 48 h of onset. Participants were randomised to 30 days of intensive antiplatelet therapy (aspirin, clopidogrel, dipyridamole) or guideline-based therapy (either clopidogrel alone or combined aspirin and dipyridamole). Bleeding was defined using the International Society on Thrombosis and Haemostasis five-level ordered categorical scale: fatal, major, moderate, minor, none. Of 3,096 participants, bleeding severity was: fatal 0.4%, major 1.5%, moderate 1.2%, minor 11.4%, none 85.5%. Major/fatal bleeding was increased with intensive as compared with guideline therapy: 39 vs. 17 participants, adjusted hazard ratio 2.21, 95% CI 1.24–3.93, p = 0.007. Bleeding events diverged between treatment groups in the 8–35 day period but not in the 0–7 or 36–90 day epochs. In multivariate analysis more, and more severe, bleeding events were seen with increasing age, female sex, pre-morbid dependency, increased time to randomisation, prior major bleed, prior antiplatelet therapy and in those randomised to triple vs guideline antiplatelet therapy. More severe bleeding was associated with worse clinical outcomes across multiple physical, emotional and quality of life domains.Trial registrationISRCTN47823388.