Use Of Bleeding Assessment Tools Research Articles

Use of Bleeding Assessment Tools in the Diagnosis of Von Willebrand Disease: Are We Asking the Right Questions?

Introduction: Over the past decade there has been significant focus on the development of bleeding assessment tools (BATs) to address the challenge of quantifying bleeding symptoms and aid in diagnosis of bleeding disorders such as von Willebrand disease (VWD). Abnormal bleeding scores derived from BATs have been shown to discriminate between healthy subjects and those with VWD in both pediatric and adult populations.BATs used to quantify bleeding symptoms have been in circulation for the past decade and significant data have been collected from their use. The objective of our study was to use our legacy data to determine which questions from BATs are the strongest predictors of VWD diagnosis.Methods: Bleeding score data collected previously by our research team using three BATs (Pediatric Bleeding Questionnaire (PBQ), condensed MCMDM-1, ISTH-BAT) were collated and used for the analysis. Questions on the BATs relate to different bleeding symptoms and each symptom is scored based on its severity. Scores for each bleeding symptom were first sorted based on whether they indicated clinically significant bleeding (i.e., when medical attention was sought or bleeding was spontaneous) which varied with the symptom and BAT administered. Scores considered non-significant/trivial were set as the reference category. Multivariable logistic regression was then used to determine the symptoms that were the strongest predictors of VWD diagnosis (determined by laboratory data). Given that many of the bleeding symptoms are age- and sex-specific, these variables were included in the model.Results: 1167 participants were included in the analysis; 178 (15%) were VWD patients and 989 (85%) were healthy controls. Of the VWD patients, 60% had Type 1 VWD. The median age was 30 years (range: 5 months - 90 years) and approximately two-thirds of the participants were women (732/1167). The top three symptoms for which having clinically significant bleeding scores increased the odds of having VWD were Hemarthrosis (OR 10.2, 95% CI, 2.4-43.4), Other Bleeding [includes: hemorrhage at miscarriage, hematuria, subconjunctival bleeding, umbilical stump bleeding, cephalohematoma, cheek hematoma during breast/bottle feeding, post-circumcision, post-venipuncture bleeding and bleeding unspecified (OR 9.3, 95% CI 2.4-36.2)] and Cutaneous Bleeding (OR 8.4, 95% CI, 3.8-18.3). Muscle Hematoma, Gastrointestinal (GI) Bleeding and Central Nervous System (CNS) Bleeding were the only symptoms found not to significantly increase odds of VWD diagnosis.Conclusion: Our results showed that most of the symptoms assessed by existing BATs are significant predictors of VWD diagnosis, which suggests that a comprehensive bleeding history is necessary for understanding a patient's phenotype. However, we did find variability in the weighting of each symptom in relation to predicting VWD. This finding may inform the development of future BATs where a relative weighting could be given to each symptom. We also found that the symptoms of CNS bleeding, muscle hematoma, and GI bleeding did not significantly increase odds of VWD diagnosis. It is possible that future BATs could be streamlined by omitting questions related to these symptoms. Prospective validation of such a tool could be undertaken in further research. [Display omitted] DisclosuresJames:Shire: Research Funding; Bayer: Research Funding; CSL Behring: Research Funding.

Obstacles to Early Diagnosis and Treatment of Inherited von Willebrand Disease: Current Perspectives.

Von Willebrand disease (VWD), the most common inherited bleeding disorder, is highly heterogeneous, and its early diagnosis may be difficult, especially for mild cases and in qualitative von Willebrand factor (VWF) defects. Appropriate VWD diagnosis requires the combination of personal and/or family history of bleeding and abnormal VWF laboratory testing. The use of bleeding assessment tools has been helpful in standardizing bleeding history collection and quantification of bleeding symptoms to select patients who may benefit of further hemostatic testing. Type 1 and 3 VWD which represent quantitative VWD variants are relatively easy to diagnose. The diagnosis of type 2 VWD requires multiple assessments to evaluate the effects induced by the responsible abnormality on the heterogeneous functions of VWF. Sensitive and reproducible tests are needed to evaluate different VWF activities, starting from measuring VWF-platelet interaction. In the recent years, several increasingly sensitive, rapid and automated assays have been developed, but they are not widely available so far. Genetic testing for VWD diagnosis is not a common practice because VWF gene is very large and highly polymorphic and therefore it is used only in specific cases. It is evident that the early and correct VWD diagnosis allows optimal management of bleeding and situations at risk. Tranexamic acid, desmopressin, replacement therapy with plasma-derived concentrates with a variable content of VWF and FVIII, or the new recombinant VWF are the different therapeutic options available. Careful VWD classification guides treatment because desmopressin is widely used in type 1 while replacement therapy is the cornerstone of treatment for type 2 and 3 variants.

Advances in the diagnosis and treatment of Von Willebrand disease.

Von Willebrand disease (VWD) is the most common inherited bleeding disorder, yet diagnosis and management remain challenging. Development and use of bleeding assessment tools allows for improved stratification of which patients may require further assessment and which patients are most likely to require treatment of their VWD. New options for laboratory assessment of von Willebrand factor (VWF) activity include a new platelet-binding assay, the VWF:GPIbM, which is subject to less variability than the ristocetin cofactor activity assay, and collagen-binding assays that provide insight into a different function of VWF. Genetic testing may be helpful in some cases where a type 2 VWD variant is suspected but is usually not helpful in type 1 VWD. Finally, treatment options for VWD are reviewed, including the use of recombinant VWF. Despite these advances, still more work is required to improve diagnosis, treatment, and quality of life for affected patients.

Evaluation of the utility of the ISTH-BAT in haemophilia carriers: a multinational study.

There has been increasing recognition in recent years that female carriers of haemophilia manifest abnormal bleeding; however, data on the use of bleeding assessment tools in this population are lacking. Our objective was to validate the ISTH-BAT in haemophilia carriers to describe bleeding symptoms and allow for comparisons with factor levels and other patient groups. This was a prospective, observational, cross-sectional study performed by members of Global Emerging HEmostasis Panel(GEHEP). Unselected consecutive haemophilia carriers were recruited and a CRF and the ISTH-BAT were completed by study personnel. A total of 168 haemophilia carriers were enrolled: 155 haemophilia A and 13 haemophilia B. The mean age was 40years (range: 20-82). Carriers had higher mean bleeding scores (BS) compared with age-matched controls (n=46; 5.7 vs. 1.43; P<0.0001) and Type 3 VWD OC (n=32; 3.0; P=0.009), but lower BS compared with women with Type 1 VWD (n=83; 8.7; P<0.0001). Fifteen carriers reported haemarthrosis, and of those six had normal FVIII/FIX levels. There was a significant but weak negative correlation between BS and factor level (Spearman's r2 =-0.36, P<0.001). Our results show that haemophilia carriers experience abnormal bleeding, including haemarthrosis. Overall, BS in women with Type 1 VWD>haemophilia carriers>Type 3 VWD OC>controls. Understanding the performance of the ISTH-BAT in this population is a critical step in future research aimed at investigating the underlying pathophysiology of abnormal bleeding, with the ultimate goal of optimizing treatment.

The accuracy of a patient or parent-administered bleeding assessment tool administered in a paediatric haematology clinic.

Classifying and describing bleeding symptoms is essential in the diagnosis and management of patients with mild bleeding disorders (MBDs). There has been increased interest in the use of bleeding assessment tools (BATs) to more objectively quantify the presence and severity of bleeding symptoms. To date, the administration of BATs has been performed almost exclusively by clinicians; the accuracy of a parent-proxy BAT has not been studied. Our objective was to determine the accuracy of a parent-administered BAT by measuring the level of agreement between parent and clinician responses to the Condensed MCMDM-1VWD Bleeding Questionnaire. Our cross-sectional study included children 0-21 years presenting to a haematology clinic for initial evaluation of a suspected MBD or follow-up evaluation of a previously diagnosed MBD. The parent/caregiver completed a modified version of the BAT; the clinician separately completed the BAT through interview. The mean parent-report bleeding score (BS) was 6.09 (range: -2 to 25); the mean clinician report BS was 4.54 (range: -1 to 17). The mean percentage of agreement across all bleeding symptoms was 78% (mean κ=0.40; Gwet's AC1=0.74). Eighty percent of the population had an abnormal BS (defined as ≥2) when rated by parents and 76% had an abnormal score when rated by clinicians (86% agreement, κ=0.59, Gwet's AC1=0.79). While parents tended to over-report bleeding as compared to clinicians, overall, BSs were similar between groups. These results lend support for further study of a modified proxy-report BAT as a clinical and research tool.

THE ROLE OF BLEEDING HISTORY AND CLINICAL MARKERS FOR THE CORRECT DIAGNOSIS OF VWD

Quantification of the bleeding severity by use of bleeding assessment tools (BAT) and bleeding score (BS) has been consistently shown to improve the clinical diagnosis of von Willebrand disease (VWD) while helping researchers establish phenotype/genotype correlations. Subjects with a BS equal or higher than 3 may be consider having a bleeding tendency, and should be referred for a laboratory investigation, particularly for VWD. In the diagnosis of type 1 VWD, the use of the BS has been shown to be highly specific (>95%) with reported sensitivities ranging from 40 to 100%. The BS is related to all available measurements of von Willebrand factor activity, including the PFA-100 closure time. Therefore, in clinical practice the use of BAT should always be the first step to standardize the assessment of patients with suspected VWD. The use of the recent ISTH consensus BAT is suggested to harmonize the collection of bleeding symptoms in patients with a suspected or confirmed hemostatic disorder, particularly VWD. The ISTH BAT is also coupled with a Web-based repository of bleeding symptoms, therefore providing an integrated framework for collaboration in the field of clinical evaluation of VWD and mild bleeding disorders.

O.422 The use of BOC (Bio-Oss Collagen) in orthognathic surgery

Platelets are a critical component for effecting hemostasis and wound healing. Disorders affecting any platelet pathway mediating adhesion, activation, aggregation and procoagulant surface exposure can result in a bleeding diathesis. Specific diagnosis even with advanced techniques which are unavailable to most centers is often difficult. Inherited platelet function disorders therefore represent a heterogeneous and complex collection of disorders with a spectrum of bleeding severity, from relatively mild (and easily missed or misdiagnosed) to severe bleeding phenotype with salient diagnostic features. We advocate the use of bleeding assessment tools to help identification of patients and more importantly for assessment of individual patient bleeding phenotype to guide management decisions for treating and preventing bleeding. The complex management of these patients is best coordinated in a multidisciplinary comprehensive care clinic setting expert in managing bleeding disorders and associated complications, with particular attention to the physical and psychosocial health of patients and their families. Depending on the bleeding phenotype, the location and severity of bleeding, and the nature of an invasive procedure, available treatment modalities range from conservative measures using local pressure, topical thrombin, fibrin sealant, antifibrinolytics etc. to the use of systemic haemostatics such as desmopressin (DDAVP), platelets and recombinant human activated factor VII (rFVIIa). This review will provide opinions on the practical aspects and general management of inherited platelet function disorders, with discussion on the mechanism of action, and the pros and cons of various hemostatic agents. Finally, the prospect of curative treatment for patients with severe bleeding phenotype refractory to available treatments and with poor quality of life will be briefly discussed.