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Type 1 von Willebrand disease (VWD) is associated with a reduction in qualitatively normal von Willebrand factor (VWF). Current diagnostic guidelines only take into consideration the contribution of basal VWF levels, despite a lack of correlation with bleeding severity. Defects in stimulated VWF release, which occurs after hemostatic challenge, may contribute to bleeding in type 1 VWD, but the pathogenic mechanisms are poorly defined. In this study, a layered multiomic approach including messenger RNA (mRNA) and microRNA (miRNA) sequencing was used to evaluate transcriptome-wide differences between type 1 VWD- and control-derived endothelial colony forming cells (ECFCs) during basal and stimulated VWF release. ECFCs from 8 patients with type 1 VWD and 4 other patients were included in this study as controls. VWF protein analysis revealed heterogenous responses to stimulation among type 1 VWD and control ECFCs. During basal VWF release, 64 mRNAs and 7 miRNAs were differentially regulated between type 1 VWD and control ECFCs, and 65 putatively pathogenic miRNA-mRNA interactions were identified. During stimulated VWF release, 190 mRNAs and 5 mRNAs were differentially regulated between type 1 VWD and control ECFCs, and 110 putatively pathogenic miRNA-mRNA interactions were identified. Five gene ontology terms including coagulation, regulation of cell shape, and regulation of cell signaling were also differentially regulated in type 1 VWD ECFCs during stimulated release. To our knowledge, we have shown for the first time that transcriptome-wide differences exist between type 1 VWD and control ECFCs. These differences may contribute to bleeding in type 1 VWD, and further investigation may reveal novel biomarkers and therapeutic targets.

OBJECTIVE: To provide recommendations for management of patients presenting with elevated self-administered bleeding assessment tool (Self-BAT) scores or other bleeding symptoms in a primary care setting. SOURCES OF INFORMATION: Primary research sources, clinical review articles, and interviews with research staff, hematologists, and family physicians were used to create the poster tools and reference guide resources. MAIN MESSAGE: Recommendations to manage a patient with an elevated Self-BAT score or other bleeding symptoms include reviewing the results of the Self-BAT to clarify relevant symptoms, performing initial diagnostic laboratory tests, and doing basic symptom management. Clinical judgment should be used when determining whether referral to a hematologist is necessary, but referral should be considered if the bleeding score is abnormal or if initial management options are ineffective. Some bleeding symptoms warrant evaluation by a gastroenterologist, obstetrician-gynecologist, or otolaryngologist. CONCLUSION: Primary care providers should conduct a thorough review of the Self-BAT results and associated management recommendations when working with a patient presenting with an elevated score or other bleeding manifestations. A review consists of the clarification of relevant symptoms, appropriate initial laboratory workups, and patient education. Treatment options for symptom management should be explored while recognizing the threshold for referral to a hematologist.

OBJECTIF: Présenter des recommandations sur la prise en charge des patients qui ont obtenu des scores élevés avec l’outil d’autoévaluation des saignements (Self-BAT) ou qui présentent d’autres symptômes hémorragiques, en milieu de soins primaires. SOURCES DE L’INFORMATION: Des sources de recherche primaire, des articles de revues cliniques, et des entrevues avec du personnel de recherche, des hématologues et des médecins de famille ont servi à produire les ressources sous forme d’affiches et d’un guide de référence. MESSAGE PRINCIPAL: Parmi les recommandations sur la prise en charge d’un patient dont les scores au Self-BAT sont élevés ou qui présente d’autres symptômes hémorragiques figurent les suivantes : passer en revue les résultats du Self-BAT pour clarifier les symptômes pertinents, effectuer les tests diagnostiques de laboratoire initiaux et gérer les symptômes de base. Il faut se servir de son jugement clinique pour déterminer la nécessité d’une demande de consultation en hématologie, mais il y a lieu d’envisager une telle démarche si les scores liés aux saignements sont anormaux ou si les options de gestion initiales ne sont pas efficaces. Il est justifié que certains symptômes hémorragiques soient évalués par un gastroentérologue, un obstétricien-gynécologue ou un otorhinolaryngologiste. CONCLUSION: Les professionnels des soins primaires devraient examiner rigoureusement les résultats du Self-BAT et les recommandations de prise en charge connexes dans le cas d’un patient qui a un score élevé ou présente d’autres manifestations hémorragiques. L’examen comprend la clarification des symptômes pertinents, les analyses de laboratoire pertinentes laboratoire et l’éducation du patient. Les options thérapeutiques pour la gestion des symptômes devraient être envisagées, tout en le reconnaissant lorsqu’il s’impose de demander une consultation en hématologie.

BACKGROUND: Heavy menstrual bleeding (HMB) affects a significant number of women with bleeding disorders and has a negative impact on their quality of life. OBJECTIVE: This retrospective study examined the management of patients with inherited bleeding disorders who used medical treatments, alone or in combination, for HMB. METHODS: Chart review was performed on women attending the Women with Bleeding Disorders Clinic in Kingston, Ontario, between 2005 and 2017. Data collected included patient demographics, the reason for presentation and diagnosis, medical history, treatments, and patient satisfaction. RESULTS: One hundred nine women were included in this cohort. Of these, only 74 (68%) were satisfied with medical management, and only 18 (17%) with first-line therapy. Treatments included combined contraceptives (oral pill, transdermal patch, and vaginal ring), progesterone-only pills, tranexamic acid, 52-mg levonorgestrel intrauterine system (LIUS), depomedroxyprogesterone acetate, and desmopressin, either alone or in combination. Satisfactory control of HMB occurred most often with the LIUS. CONCLUSION: In this cohort, managed in a tertiary care Women with Bleeding Disorders Clinic, only 68% of patients had successful control of HMB with medical treatment, and a minority were satisfied with first-line therapy. These data clearly highlight the need for additional research, including treatment approaches and novel therapies for this population.

Clinicians often order the international normalized ratio (INR) and activated partial thromboplastin time (APTT) to evaluate for the possibility of inherited bleeding disorders despite sensitivities and specificities of 1%-2%. The most accurate tool to evaluate for bleeding disorders is a validated bleeding assessment tool (BAT). Our aim was to reduce coagulation testing by50% in a large family practice in Ontario, Canada.We conducted an implementation study from May 2016 to February 2020. Iterative interventions included introduction of a validated BAT into the electronic medical record (EMR); removal of the APTT as a prepopulated selection from the laboratory requisition; and education targeting family medicine teams and laboratory personnel. The primary outcome was the rate of pre- and post-APTT testing. Creatinine testing was the control. Data were analyzed via an interrupted time series analysis using Stata 13.Immediately following education of the laboratory personnel on coagulation testing, the APTT rate level dropped by 1.26 tests per 100 patient visits per month (Multidisciplinary, iterative interventions reduced APTT testing and enabled the use of BATs to guide hematology referrals in a large family practice.

BACKGROUND: von Willebrand Factor (VWF) is synthesized by vascular endothelial cells and megakaryocytes. The VWF propeptide is critical for multimerization and acts as an intra-molecular chaperone for mature VWF in sorting to its storage organelles, Weibel-Palade bodies (WPBs). In the Canadian Type 3 VWD study, almost half of the identified variants were in the VWF propeptide and these were associated with an increased bleeding phenotype. OBJECTIVE: To investigate VWF propeptide variants that cause quantitative von Willebrand disease (VWD) by utilizing patient-derived endothelial colony-forming cells (ECFCs). PATIENTS/METHODS: ECFCs were isolated from five Type 3 VWD patients from four families with the following variants: 1) homozygous p.Asp75_Gly178del (deletion of exons 4 and 5 deletion; Ex4-5del); 2) homozygous p.Cys633Arg; 3) homozygous p.Arg273Trp, and 4) p.Pro293Glnfs*164 and p.Gln419* inherited in the compound heterozygous state. Additionally, ECFCs were isolated from six family members (two Type 1 VWD, four unaffected). RESULTS: ECFCs from the Type 3 patient with the compound heterozygous genotype exhibited a true null VWF cellular phenotype, with negligible VWF detected. In contrast, the other three propeptide variants presented a similar expression pattern in homozygous ECFCs where VWF was synthesized but not packaged in WPBs, and variant VWF had an increased association with the endoplasmic reticulum (ER) marker, protein disulfide-isomerase (PDI), indicating an ER-retention phenotype. The biosynthetic phenotype was similar but to a lesser degree in heterozygous ECFCs expressing the non-null variants. CONCLUSION: This study further elucidates the importance of the VWF propeptide in the VWD phenotype using patient-derived cells.

Background Von Willebrand Disease (VWD) is a common inherited bleeding disorder. Patients with VWD suffering from severe bleeding may benefit from the use of secondary long-term prophylaxis. Aim Systematically summarize the evidence on the clinical outcomes of secondary long-term prophylaxis in patients with VWD and severe recurrent bleedings. Methods We searched Medline and EMBASE through October 2019 for relevant randomized clinical trials (RCTs) and comparative observational studies (OS) assessing the effects of secondary long-term prophylaxis in patients with VWD. We used Cochrane Risk of Bias (RoB) tool and the RoB for Non-Randomized Studies of interventions (ROBINS-I) tool to assess the quality of the included studies. We conducted random-effects meta-analyses and assessed the certainty of the evidence using the Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach. Results We included 12 studies. Evidence from one placebo controlled RCT suggested that VWD prophylaxis as compared to no prophylaxis reduced the rate of bleeding episodes (Rate ratio [RR], .24; 95% confidence interval [CI], .17–.35; low certainty evidence), and of epistaxis (RR, .38; 95%CI, .21–.67; moderate certainty evidence), and may increase serious adverse events RR 2.73 (95%CI .12–59.57; low certainty). Evidence from four before-and-after studies in which researchers reported comparative data suggested that VWD prophylaxis reduced the rate of bleeding (RR .34; 95%CI, .25–.46; very low certainty evidence). Conclusion VWD prophylaxis treatment seems to reduce the risk of spontaneous bleeding, epistaxis, and hospitalizations. More RCTs should be conducted to increase the certainty in these benefits.

von Willebrand Disease (VWD) is associated with significant morbidity because of excessive bleeding. Early diagnosis and treatment are important to prevent and treat these symptoms. We systematically reviewed the accuracy of any von Willebrand factor (VWF) activity assay in the diagnosis and classification of patients for VWD. We searched Cochrane Central, MEDLINE, and EMBASE for eligible studies. The risk of bias was assessed using the Quality Assessment of Diagnostic Accuracy Studies (QUADAS)-2 and the certainty of evidence using the GRADE framework. We pooled estimates of sensitivity and specificity. The review included 77 studies that evaluated the use of newer tests of VWF platelet binding activity (VWF:GPIbR, VWF:GPIbM) and VWF:RCo for the diagnosis of VWD (13 studies), VWF propeptide to VWF:Ag ratio, and desmopressin trial for the diagnosis of type 1C VWD (5 studies), VWF multimer analysis and VWF:CB/VWF:Ag ratio for the classification of type 2 VWD (11 studies), genetic testing and ristocetin-induced platelet aggregation to diagnose type 2B VWD (14 studies), genetic testing and FVIII:VWF binding to diagnose type 2N VWD (17 studies). Based on available diagnostic test accuracy, there appear to be comparable test accuracy results between newer tests of platelet binding activity of VWF function and VWF:RCo. The findings of these reviews support VWF multimer analysis or VWF:CB/VWF:Ag to diagnose type 2 VWD. The desmopressin trial test with 1- and 4-hour postinfusion blood work is the test of choice to confirm increased VWF clearance in patients with suspected VWD type 1C. Additionally, genetic testing is most useful in diagnosing type 2B VWD and has a role in the diagnostic algorithm of suspected type 2N VWD.

Physicians have difficulty recognizing and diagnosing disorders of primary hemostasis. The root of this may lie in their education, where students are often taught hemostasis using static graphics. We aimed to create a didactic animation on primary hemostasis for medical students to be used in North American medical schools. To promote widespread use of the animation, we surveyed hemostasis educators from Canada and the US on the animation’s learning objectives. The animation’s script and storyboard were developed using the Animation Processing Model (APM), a psychological processing model that addresses the perceptual limitations of learners. This animation is the first biomedical animation to use the APM in its design. Furthermore, this is the first didactic hemostasis animation which sought peer consensus for its learning objectives.

Introduction: von Willebrand disease (VWD) is an inherited bleeding disorder caused by a quantitative or qualitative dysfunction of von Willebrand factor. Clinicians, patients and other stakeholders have many questions about the diagnosis and management of the disease. Aim: To identify topics of highest importance to stakeholders that could be addressed by guidelines to be developed by the American Society of Hematology (ASH), the International Society on Thrombosis and Haemostasis (ISTH), the National Hemophilia Foundation (NHF) and the World Federation of Hemophilia (WFH). Methods: A survey to determine and prioritize topics to be addressed in the collaborative development of guidelines for VWD was distributed to international stakeholders including patients, caregivers and healthcare providers (HCPs). Representatives of the four organizations coordinated the distribution strategy. The survey focused on both diagnosis and management of VWD, soliciting 7-point Likert-scale responses and open-ended comments, in English, French and Spanish. We conducted descriptive analysis with comparison of results by stakeholder type, gender and countries' income classification for the rating questions and qualitative conventional content data analysis for the open-ended responses. Results: A total of 601 participants responded to the survey (49% patients/caregivers and 51% healthcare providers). The highest priority topics identified were diagnostic criteria/classification, bleeding assessment tools and treatment options for women and surgical patients. In contrast, screening for anaemia and differentiating plasma-derived therapy versus recombinant therapies received lower ratings. Conclusion: This survey highlighted areas of importance to a diverse representation of stakeholders in the diagnosis and management of VWD, providing a framework for future guideline development and implementation.

Introduction From 2012 to 2014, a total of 17 family child care homes participated in a multisector, community-wide initiative to prevent obesity. Strategies included staff workshops, materials, site visits, and technical assistance regarding development and implementation of nutrition policies. The purpose of the evaluation was to examine the impact of the initiative on family child care home nutrition-related policies and practices and child dietary intake. Study design Pre- and post-intervention without control group. Measures taken at baseline and follow-up included structured observations and questionnaires regarding nutrition policies, practices, and environments; documentation of lunch foods served on 5 days; and lunch plate waste observations on 2 days. Paired t-tests were used to determine the significance of change over time. Setting/participants Seventeen family child care homes in a low-income diverse community in Northern California; children aged 2–5 years who attended the family child care homes. Main outcome measures Change in nutrition-related policies and practices, lunch foods served and consumed. Results Data was collected at 17 sites for an average of 5.2 children aged 2–5 years per site per day at baseline and 4.6 at follow-up for a total of 333 plate waste observations. There were significant increases in staff training, parental involvement, and several of the targeted nutrition-related practices; prevalence of most other practices either improved or was maintained over time. There were significant increases in the number of sites meeting Child and Adult Care Food Program meal guidelines, variety of fruit and frequency of vegetables offered, and reductions in frequency of juice and high-fat processed meats offered. Adequate portions of all food groups were consumed at both time points with no significant change over time. Conclusions A simple, policy-focused intervention by a child care resource and referral agency was successful at reinforcing and improving upon nutrition-related practices at family child care homes. Children consumed adequate, but not excessive, portions of the balanced meals served to them, suggesting there is no reason to offer unhealthy options. Supplement information This article is part of a supplement entitled Building Thriving Communities Through Comprehensive Community Health Initiatives, which is sponsored by Kaiser Permanente, Community Health.

The objective of this scoping review is to summarize the current use of pharmacokinetics for tailoring prophylaxis in hemophilia patients switching between clotting factor products. Patients with hemophilia may require switching of clotting factor concentrates due to a variety of factors, but there have been perceived risks associated with switching, such as inhibitor development or suboptimal protection due to inadequate dosing while titrating treatment. Studies that look at patients switching from one clotting factor concentrate to another are categorized in terms of their primary and/or secondary objectives, notably biosimilarity and comparative pharmacokinetic studies and inhibitor development studies. Research on how best to switch concentrates with respect to dosing regimen are lacking, and currently a trial-and-error approach is used for dosing the new factor concentrate. In the future, studies looking at the predictability of pharmacokinetics (PK) of a new factor concentrate based on individual PK knowledge of the original factor concentrate may offer clinical benefit by providing a safer switching approach and protocol.

Introduction Reaching preschool-aged children to establish healthy lifestyle habits, including physical activity, is an important component of obesity prevention efforts. However, few studies have examined family child care homes where nearly 1 million children receive care. Study design A pre- and post-intervention evaluation without a control group was conducted to evaluate what changes occurred in family child care homes that participated in the Healthy Eating and Active Living project, a multicomponent obesity prevention initiative, focused on community-driven policy and environmental change in neighborhoods within Kaiser Permanente service areas. Setting/participants From 2012 to 2014, a total of 17 family child care homes in Northern California participated in the intervention. Intervention A physical activity workshop for child care staff and technical assistance to develop a policy to promote physical activity and other healthy behaviors. Main outcome measures Pre and post observations, questionnaires, and physical activity logs were completed to assess change in physical activity resources available in the family child care homes, the amount of child screen time offered, type and amount of physical activity offered to children, and implementation of physical activity best practices. Results Between baseline and follow-up, providers significantly increased both the number of structured, adult-led activities (2.6 vs 3.2 activities per day) and the number of structured, adult-led minutes of activity in which children participated (49 vs 83 minutes per day). Providers also improved screen time practices and made improvements to the physical activity environment. Conclusions In this study, a community-based organization designed and implemented multicomponent strategies tailored for participating family child care homes. The successful implementation of the intervention likely contributed to implementation of practices that increased opportunities for physical activity for the young children attending these family child care homes. Supplement information This article is part of a supplement entitled Building Thriving Communities Through Comprehensive Community Health Initiatives, which is sponsored by Kaiser Permanente, Community Health.

Guidelines state that Ringer’s lactate (RL) should not be co-administered with packed red blood cells (PRBC) due to a potential risk of clotting. The purpose of this study was to determine whether RL causes clotting in PRBC with the currently used preservative, saline-adenine-glucose-mannitol (SAGM). Phase 1: Samples from 12 units of SAGM-PRBC were diluted from 0-97.5% with RL and normal saline (NS), incubated for 30 min, and passed through 40 μm filters. Additional samples were frozen and batch analyzed using an enzyme-linked immunosorbent assay (ELISA) to measure prothrombin activation fragment 1 + 2 (F1 + 2), indicative of thrombin generation. Packed red blood cells were also diluted, flushed with crystalloid using a rapid transfusion model, and filtered. Phase 2: Eight further units were serially diluted with RL and incubated for 30, 60, 120, 180, and 240 min. Fresh samples were analyzed by filtration and ELISA. Phase 1: No clotting was seen during filtration or using the transfusion model with NS or RL. The F1 + 2 ranged from 2.28 to 154.37 pmol·L−1 in NS dilutions and from 2.80 to 1675.93 pmol·L−1 in RL dilutions, indicating coagulation in some samples. Phase 2: No clotting was observed within 60 min by filtration or ELISA. However, 4 of the 8 units showed clots in the filters of some dilutions between 120 and 240 min. No clotting was detected at any dilution of RL with SAGM- preserved PRBC within 60 min, but clotting was detected with extended incubation. The results indicate RL can be safely co-administered with PRBC during rapid transfusion (

Summary von Willebrand's disease (VWD) patients undergoing major surgery are prophylactically treated to promote haemostasis. There is variability in perioperative clinical practice; however, most guidelines suggest replacing the deficient factor to a level of 1.0 IU mL−1 (or 100%). A review of the literature reveals a paucity of well constructed descriptive data quantifying the changes in coagulation that occur in response to surgical stress. The aim of this study was to quantify the changes in haemostatic variables occurring in response to elective orthopaedic surgery in normal individuals. Eligible subjects >18 years of age undergoing total hip or knee replacement were recruited. Blood samples were drawn at five time points: baseline, preoperatively, 30 min after surgical incision, 30 min postoperatively, postoperative day (POD) 1. Analyses included t-tests and repeated measures anova. Overall 30 patients, 21 women and 9 men, with a mean age of 65 were included in the final analysis. All von Willebrand factor (VWF) variables were seen to significantly decrease intraoperatively and increase postoperatively. VWF multimers showed a statistically significant decrease in high molecular weight multimers intraoperatively and an increase postoperatively. On subgroup analysis, age, gender and anaesthesia type were significantly correlated with changes in VWF parameters. Data presented in the current study establish a physiological baseline for VWF parameters in the normal population and demonstrate mean VWF/factor VIII levels greater than 1.0 IU mL−1 intraoperatively. As such, current management in VWD patients does not appear to mimic the normal physiological response to surgery.

Purpose: There have been numerous reports with evidence detailing the presence of non-stereoscopic or “monocular”clues in commonly used stereoacuity tests. The purpose of this study was to quantify the influence of monocularclues in the Titmus, Randot®, Randot® Special Edition, Randot® Preschool, Lang, Lang II, and Frisby stereoacuitytests. Stereoacuity testing is typically performed and/or interpreted by eye care professionals and other health/occupational professionals. Methods: Two separate prospective studies were conducted. The first assessed the monocular responses of 100subjects aged 8 to 67 with normal stereoacuity, and no previous exposure to any of the seven tests administered.The second assessed the monocular responses of 33 subjects aged 8 to 65 with longstanding, manifest, horizontalstrabismus of 20 prism diopters or greater, on the aforementioned stereotests. Results: Monocular clues were found to be present for the normal group on the Titmus (61%), Randot® (6%), Randot®Special Edition (5%), Randot® Preschool (7%), Lang (13%), and Lang II (37%). Monocular clues were found to be presentfor the strabismic group on the Titmus (100%), Randot® (9%), Randot® Special Edition (9%), Randot® Preschool (12%),Lang (3%), and Lang II (27%). There was no monocular identification for either group on the Frisby stereotest, butthere was minimal binocular identification by a subject with manifest strabismus. Conclusion: Monocular clues were present for both the normal and strabismic group on 6 of the 7 stereotestsinvestigated. Based on these findings the authors conclude that caution must be used when interpreting patientresponses on the 7 aforementioned stereotests.

Ringer's lactate (RL) may be preferable to normal saline (NS) for large volume resuscitation. Authorities recommend against its mixture with packed red blood cells (PRBC) due to a theoretical risk of clotting. The purpose of this study was to test whether RL, as compared with NS, leads to a risk of clotting when used to dilute AS-3 preserved PRBC in a clinically relevant model.Following Ethics Board approval, eight units of unused, unexpired AS-3 preserved PRBC were obtained. Four sets of two parallel studies were performed, comparing RL with NS as the diluent for PRBC. The mixtures were infused using gravity flow through standard blood filter tubing and fluid warmer, to simulate an intraoperative blood transfusion. A series of progressively more dilute samples was collected. These were filtered and analyzed macroscopically, then using enzyme-linked immunosorbent assay to quantify the amount of F1+2 (the breakdown products of thrombin generation).No filters in any of the NS and RL mixtures contained evidence of clot or debris. In the NS group, the F1+2 levels ranged from 2.7 to 38.0 pmol x L(-1). In the RL group, the F1+2 levels ranged from 3.2 to 289.7 pmol x L(-1). All of these values were below the physiologic levels determined in previous studies.In this simulation of intraoperative blood transfusion, RL did not lead to visible or molecular evidence of activation of the clotting cascade. The current study challenges recommendations that AS-3 PRBC should not be mixed with RL for rapid transfusion.

Abstract 1296 Poster Board I-318 Background Patients with inherited bleeding disorders undergoing surgery typically receive therapy to correct the deficient factor to a level of ∼1.0 IU/mL. There is a paucity of well-constructed descriptive data quantifying the changes in coagulation that occur in response to surgical stress in normal individuals, however. Additionally, von Willebrand factor (VWF) and factor VIII (FVIII) are acute phase reactants, and thus, supratherapeutic levels of these proteins that might develop in response to the surgical stress would predispose patients to thrombotic events. Aim: With this in mind, our objective was to quantify the changes in hemostatic variables that occur in response to elective orthopedic surgery in normal individuals. Methods Eligible subjects > 18 years of age undergoing total knee or total hip replacement were recruited. Exclusion criteria included a known bleeding disorder, hormone replacement therapy, use of oral contraceptives or pregnancy. Following informed consent, blood samples were drawn at five time points: 1) baseline - in clinic 1-2 weeks pre-operatively (pre-op), 2) pre-op the morning of surgery – same day admitting center, 3) intra-operatively (intra-op) – 30 minutes after the start of surgery, 4) 30 minutes post-operatively (post-op) - recovery room, and 5) post-op day one (POD 1) – on the ward. Samples were analyzed for complete blood counts (CBC), prothrombin time (PT), activated partial thromboplastin time (aPTT), VWF antigen (VWF:Ag), VWF ristocetin cofactor activity (VWF:RCo), FVIII coagulant activity (FVIII:C) and whole blood thromboelastography (TEG) without tissue factor activation. Repeated measures analysis of variance was used to evaluate trends over time; paired samples t-tests were done to maximize the sample size for pairwise comparisons. Results 37 subjects were recruited (25 females, 12 males) with a mean age of 64 years (range 33 – 87). Means and ranges for all laboratory parameters are displayed in Table 1 in addition to statistical analysis of the change in all variables over the 5 time points. Statistically significant changes were seen in all variables except PTT and TEG angle. In general, VWF and FVIII indices decreased during surgery (presumably due to consumption) and then increased in the post-operative period (presumably due to a stress response). A great deal of variability was seen in post-operative levels of VWF and FVIII between individuals with some showing borderline low levels and some achieving very high levels. Conclusion These data establish a baseline on which to reconsider current strategies for the peri-operative management of patients with inherited bleeding disorders, and provide relevant information when considering the relative risks of bleeding or thrombosis associated with surgery. Disclosures No relevant conflicts of interest to declare.

Background: Careful assessment of bleeding history is the first step in the evaluation of patients with mild/moderate bleeding disorders, and the use of a bleeding assessment tool (BAT) is strongly encouraged. Although a few studies have assessed the utility of the ISTH-BAT in patients with inherited platelet function disorders (IPFD) none of them was sufficiently large to draw conclusions and/or included appropriate control groups. Objectives: The aim of the present study was to test the utility of the ISTH-BAT in a large cohort of patients with a well-defined diagnosis of inherited platelets disorder in comparison with two parallel cohorts, one of patients with type-1 von Willebrand disease (VWD-1) and one of healthy controls (HC). Patients/Methods: We enrolled 1098 subjects, 482 of whom had inherited platelet disorders (196 IPFD and 286 inherited platelet number disorders [IT]) from 17 countries. Results: IPFD patients had significantly higher bleeding score (BS; median 9) than VWD-1 patients (median 5), a higher number of hemorrhagic symptoms (4 versus 3), and higher percentage of patients with clinically relevant symptoms (score > 2). The ISTH-BAT showed excellent discrimination power between IPFD and HC (0.9