PATIENTS REFERRED FOR BLEEDING SYMPTOMS OF UNKNOWN CAUSE: DOES EVALUATION OF THROMBIN GENERATION CONTRIBUTE TO DIAGNOSIS?

IntroductionPatients with mild to moderate bleeding symptoms referred for coagulation investigation sometimes never receive a definitive diagnosis. Bleed assessment tools have been developed and validated to assess the severity of symptoms. Global coagulation assays, e.g., the thrombin generation test (thrombogram) have a potential to identify hemostatic defects that are not detected in specific assays.Material and MethodsOne hundred and eighty-five patients referred to our centre because of bleeding symptoms were evaluated using the bleeding assessment tool (BAT) described by Tosetto and colleagues in 2006. Blood samples were investigated for thrombin generation (TG) capacity (Technoclone) , in platelet poor (PPP) plasma , and specific clotting factors, i.e, von Willebrand factor, factor VIII and IX, as well as INR, APTT, platelet count, and platelet adhesion.ResultsOf the 185 patients, five women were diagnosed with mild von Willebrand disease and one male with mild hemophilia A. The remaining 179 subjects (76% females and 24% males with average ages of 33 and 28 years, respectively) were evaluated further. In the total cohort and among women, peak TG, and lag time correlated with bleeding score (p=0.01 and p=0.04, respectively with correlation coefficients). No such correlations were found among males. Discussion and conclusion Although our study showed some correlation between TG and bleeding score, results are generally consistent with a previous report which failed to demonstrate the value of TG measurement in a similar setting. In conclusion, the complexity of the mechanisms underlying clinical bleeding complicates the ability to use TG tests as reliable predictors of bleeding. Mild congenital bleeding disorders, especially VWD, should be specifically screened for in patients with mild/moderate symtoms.

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

Mediterranean Journal of Hematology and Infectious Diseases ◽

10.4084/mjhid.2013.051 ◽

2013 ◽

Vol 5 (1) ◽

pp. e2013051 ◽

Cited By ~ 4

Author(s):

Alberto Tosetto

Keyword(s):

Correct Diagnosis ◽

Von Willebrand Disease ◽

Assessment Tools ◽

Bleeding Tendency ◽

Clinical Markers ◽

Web Based ◽

Bleeding Score ◽

Bleeding History ◽

Von Willebrand ◽

Willebrand Factor

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.

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Epidural Analgesia Use in Women with Von Willebrand Disease

Blood ◽

10.1182/blood.v124.21.1529.1529 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1529-1529

Author(s):

Leslie Skeith ◽

M. Dawn Goodyear ◽

Natalia Rydz ◽

Man-Chiu Poon

Keyword(s):

Epidural Analgesia ◽

Von Willebrand Factor ◽

Safety Data ◽

Von Willebrand Disease ◽

Activity Levels ◽

Third Trimester ◽

Bleeding Score ◽

Von Willebrand ◽

Willebrand Factor

Abstract There is little safety data available on the use of epidural analgesia during pregnancy in women with von Willebrand disease (VWD), a common disorder comprising up to 0.1% of the population. Despite physiological increases in von Willebrand factor antigen and activity levels to normal or near levels during third trimester in Type 1 VWD patients, epidural analgesia use is varied and often withheld. We conducted a cross-sectional questionnaire in order to further characterize the local practice and provide additional safety data on epidural use in the VWD population. We invited all women with VWD followed by the Southern Alberta Rare Blood and Bleeding Disorders Comprehensive Care Program to participate in an online or paper questionnaire. The questionnaire was part of a larger study identifying pregnancy complications in VWD, with additional questions collected on the diagnosis and severity of VWD, epidural use and associated outcomes, as well as the perceived contraindications of epidural analgesia. All questions were pre-tested by hematologists, obstetricians and laypeople. With patient consent, supplemental data was collected from clinic and hospital records. We included patients who were 18 years of age or older with a diagnosis of VWD, defined as von Willebrand factor (VWF) antigen and activity levels less than 50 percent or a historical diagnosis, in combination with a bleeding score of 4 or more (condensed MCMDM-1 bleeding questionnaire). Patients were excluded if they had no past pregnancies, no mailing address, or had an alternative bleeding disorder. Confidence intervals for proportions were calculated using the Wilson’s score method. Of the 98 women with VWD who met the study inclusion criteria, 31 (32%) completed the questionnaire. There were 25 (81%) diagnosed with Type 1, 5 (16%) with Type 2, and 1 (3%) with Type 3 VWD. The mean bleeding score was 10.3 (SD 3.6). There were a total of 83 pregnancies (mean 2.7, range 1-6), with 60 deliveries assessed because of 20 pregnancy losses, 2 elective terminations, and 1 patient currently pregnancy. Of the 60 deliveries, the rate of epidural use was 28.3% (95% confidence interval 18.5-40.8, n=17). All epidural analgesia use was reported in women with Type 1 VWD. Of the 43 pregnancies without an epidural, the stated reasons were as follows: 10 because of concern for bleeding (23.3%), 25 because of personal preference (58.1%), 7 ‘other’ (16.3%), and 1 participant without a response (2.3%). In the 10 pregnancies where an epidural was not used due to bleeding concerns, 6 patients had Type 1 VWD and 1 patient had Type 2N VWD. The outcome of epidural use in the VWD population was reassuring, 2 women reported their epidural analgesia to be ineffective, and 4 women reported neurological symptoms such as numbness, tingling or weakness. All neurological symptoms were temporary with no persistent deficits or documented complication of bleeding. Due to the retrospective nature of this study, VWF antigen and activity levels at the time of delivery were not available, limiting the conclusions that can be made on the safety of epidural use based on VWF levels. It is our local practice to proceed with epidural analgesia if a patient’s VWF antigen and activity levels measured in third trimester are greater than 50%. For VWF levels less than 50%, epidural analgesia would only be considered with appropriate DDAVP or factor concentrate replacement. In summary, our local rate of epidural use was close to 30% in the VWD population, which was primarily composed of Type 1 VWD patients. Outcome data is reassuring, but a larger cohort study is needed to further quantify rare risks such as neuraxial bleeding. Disclosures No relevant conflicts of interest to declare.

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Unraveling the Influence of Common von Willebrand factor variants on von Willebrand Disease Phenotype: An Exploratory Study on the Molecular and Clinical Profile of von Willebrand Disease in Spain Cohort

Thrombosis and Haemostasis ◽

10.1055/s-0040-1702227 ◽

2020 ◽

Vol 120 (03) ◽

pp. 437-448

Author(s):

Nina Borràs ◽

Iris Garcia-Martínez ◽

Javier Batlle ◽

Almudena Pérez-Rodríguez ◽

Rafael Parra ◽

...

Keyword(s):

Von Willebrand Factor ◽

Phenotypic Variability ◽

Substantial Effect ◽

Von Willebrand Disease ◽

Clinical Profile ◽

Single Nucleotide Variants ◽

Hereditary Factors ◽

Bleeding Score ◽

Von Willebrand ◽

Willebrand Factor

AbstractThe clinical diagnosis of von Willebrand disease (VWD), particularly type 1, can be complex because several genetic and environmental factors affect von Willebrand factor (VWF) plasma levels. An estimated 60% of the phenotypic variation is attributable to hereditary factors, with the ABO blood group locus being the most influential. However, recent studies provide strong evidence that nonsynonymous single nucleotide variants (SNVs) contribute to VWF and factor VIII phenotypic variability in healthy individuals. This study aims to investigate the role of common VWF SNVs on VWD phenotype by analyzing data from 219 unrelated patients included in the “Molecular and Clinical Profile of von Willebrand Disease in Spain project.” To that end, generalized linear mixed-effects regression models were fitted, and additive and epistatic analyses, and haplotype studies were performed, considering five VWD-related measures (bleeding score, VWF:Ag, VWF:RCo, factor VIII:C, and VWF:CB). According to these analyses, homozygotes: for p.Thr789Ala(C) would be expected to show 39% higher VWF:Ag levels; p.Thr1381Ala(C), 27% lower VWF:Ag levels; and p.Gln852Arg(C), 52% lower VWF:RCo levels. Homozygotes for both p.Thr789Ala(C) and p.Gln852Arg(T) were predicted to show 185% higher VWF:CB activity, and carriers of two copies of the p.Thr1381Ala(T)/p.Gln852Arg(T) haplotype would present a 100% increase in VWF:RCo activity. These results indicate a substantial effect of common VWF variation on VWD phenotype. Although additional studies are needed to determine the true magnitude of the effects of SNVs on VWF, these findings provide new evidence regarding the contribution of common variants to VWD, which should be taken into account to enhance the accuracy of the diagnosis and classification of this condition. ClinicalTrials.gov identifier: NCT02869074.

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Fibrin-Dependent Platelet Procoagulant Activity Requires GPIb Receptors and von Willebrand Factor

Blood ◽

10.1182/blood.v93.2.564 ◽

1999 ◽

Vol 93 (2) ◽

pp. 564-570 ◽

Cited By ~ 67

Author(s):

S. Béguin ◽

R. Kumar ◽

I. Keularts ◽

U. Seligsohn ◽

B.S. Coller ◽

...

Keyword(s):

Von Willebrand Factor ◽

Thrombin Generation ◽

Platelet Rich Plasma ◽

Von Willebrand Disease ◽

Procoagulant Activity ◽

Increased Risk ◽

Coagulation Proteins ◽

A Minor ◽

Von Willebrand ◽

Willebrand Factor

Abstract Thrombin generation in platelet-rich plasma (PRP) involves complex interactions between platelets and coagulation proteins. We previously reported that the addition of fibrin to PRP enhances tissue-factor initiated thrombin generation by ≈ 40%, and the current studies were designed to assess the mechanism(s) underlying thrombin generation in the absence and presence of fibrin. Blocking platelet GPIIb/IIIa + vβ3 receptors with a monoclonal antibody (MoAb) inhibited basal thrombin generation, but did not affect the enhancement produced by fibrin. In contrast, blocking GPIb with any of three different MoAbs had no effect on basal thrombin generation, but essentially eliminated fibrin enhancement of thrombin generation. When thrombin generation was tested in PRP deficient in von Willebrand factor (vWF), both basal and fibrin-enhanced thrombin generation were markedly reduced, and the addition of factor VIII did not normalize thrombin generation. Botrocetin, which induces the binding of vWF to GPIb, enhanced thrombin generation. In all studies, the ability of PRP to support thrombin generation correlated with the production of platelet-derived microparticles and serum platelet-derived procoagulant activity. Thus, two separate mechanisms, both of which depend on vWF, appear to contribute to platelet-derived procoagulant activity: one is independent of fibrin and relies primarily on GPIIb/IIIa, but with a minor contribution from vβ3; and the other is fibrin-dependent and relies on GPIb. These data may have implications for understanding the mechanisms of the abnormalities in serum prothrombin times reported in Bernard-Soulier syndrome, hemorrhage in von Willebrand disease (vWD), and the increased risk of thrombosis associated with elevated vWF levels.

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How I treat von Willebrand disease

Blood ◽

10.1182/blood-2009-01-153296 ◽

2009 ◽

Vol 114 (6) ◽

pp. 1158-1165 ◽

Cited By ~ 57

Author(s):

Francesco Rodeghiero ◽

Giancarlo Castaman ◽

Alberto Tosetto

Keyword(s):

Molecular Basis ◽

Normal Subjects ◽

Von Willebrand Disease ◽

Optimal Management ◽

Multicenter Studies ◽

Bleeding Score ◽

Bleeding History ◽

Von Willebrand ◽

Willebrand Factor ◽

Ristocetin Cofactor

Abstract Recent multicenter studies have clarified the molecular basis underlying the different von Willebrand disease (VWD) types, all of which are caused by the deficiency and/or abnormality of von Willebrand factor (VWF). These studies have suggested a unifying pathophysiologic concept. The diagnosis of VWD, remains difficult because its clinical and laboratory phenotype is very heterogeneous and may overlap with normal subjects. Stringent criteria are therefore required for a clinically useful diagnosis. In this paper, we delineate a practical approach to the diagnosis and treatment of VWD. Our approach is based on the critical importance of a standardized bleeding history that has been condensed into a final bleeding score and a few widely available laboratory tests, such as VWF ristocetin cofactor activity, VWF antigen and factor VIII. This approach would help identify those subjects who will probably benefit from a diagnosis of VWD. The next step involves performing a trial infusion with desmopressin in all patients who fail to exhibit an enhanced responsiveness to ristocetin. On the basis of these results and through a series of illustrative examples, the clinician will be able to select the best approach for the optimal management of VWD, according to the patient's characteristics and clinical circumstances.

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The Management of Bleeding Risk in Von Willebrand Disease: Should Blood Group O Make a Difference?

Blood ◽

10.1182/blood.v124.21.2829.2829 ◽

2014 ◽

Vol 124 (21) ◽

pp. 2829-2829

Author(s):

Joan Cox Gill ◽

Veronica H Flood ◽

Pamela A Christopherson ◽

Daniel B Bellissimo ◽

Kenneth D Friedman ◽

...

Keyword(s):

Blood Group ◽

Von Willebrand Factor ◽

Sequence Variation ◽

Gene Sequence ◽

Von Willebrand Disease ◽

Sequence Change ◽

Bleeding Score ◽

Von Willebrand ◽

Willebrand Factor

Abstract Type 1 von Willebrand disease (VWD) is a common inherited bleeding disorder characterized by a quantitative deficiency of von Willebrand factor (VWF) and excessive mucocutaneous bleeding. It is well known that von Willebrand factor (VWF) levels are significantly lower in persons with ABO blood group O and that there is a significantly higher prevalence of blood group O in patients with a diagnosis of type 1 VWD. This raises a question important to the clinical care of patients with low VWF; is there a difference in bleeding risk in patients with a deficiency of VWF on the basis of blood group O versus those with a deficiency of VWF due to a sequence variation in the VWF gene. To explore this question, we examined index cases enrolled in the Zimmerman Program for the Molecular and Clinical Biology of VWD with a quantitative deficiency of VWF including those with a phenotypic diagnosis of low VWF [von Willebrand factor antigen (VWF:Ag) or von Willebrand factor ristocetin cofactor activity (VWF:RCo)≤ 50 U/dL and >40 U/dL], type 1 VWD (VWF:Ag or VWF:RCo≤40 U/dL) and type 1C VWD (VWF:Ag ≤30 U/dL and VWF propeptide/Ag ratio >3 indicating increased clearance of VWF). VWF:Ag, VWF:RCo, VWF propeptide and multimer distribution were analyzed in the clinical hemostasis laboratory at the BloodCenter of Wisconsin. Full length VWF gene sequencing including intron-exon boundaries was performed for all index cases. Bleeding symptoms were scored utilizing the ISTH, MCMDM1 and PBQ bleeding assessment tools. Since there was a high correlation among bleeding scores with these three methods, the ISTH score was utilized for this analysis. Complete data were available for 91 subjects with low VWF, 161 subjects with type 1 VWD, 53 subjects with type 1C VWD and 74 normal control subjects. Median ages were not different among the diagnostic groups. As expected based on previous reports, the groups of VWD patients with lower VWF:Ag values (Mean±1SD) had an increased percentage of subjects with an identified sequence variation; low VWF group, VWF:Ag 50.4±8.4, 38% with sequence variation; Type 1 VWD, VWF:Ag 30.8±11.6, 70% with sequence variation; and Type 1C VWD, VWF:Ag 9.8±5.9, 83% with sequence variation. The low VWF group and the type 1 VWD groups both had a significantly increased frequency of subjects with blood group O (70 – 80%) vs. nonO (19-30%) in comparison to those with type 1C in whom the frequency of blood group O (57% ) vs. nonO (43%) was not different than that in the normal control population (43% O vs. 57% nonO). This suggests that the type 1 and low VWF groups have a significant proportion of subjects with low VWF on the basis of blood group O alone. Since those subjects with a diagnosis of low VWF or Type 1 VWD who have no identifiable sequence variation are more likely to be affected by blood group O alone, we examined the ISTH bleeding scores in subjects with similar VWF levels and blood group O with and without an identifiable VWF gene sequence variation. We found that there was no difference in the ISTH bleeding scores in blood group O subjects regardless of the presence of a VWF gene sequence variation; low VWF, no sequence change (N=45), median bleeding score 6.0 vs. 5.0 with sequence change (N=27); type 1 VWD, no sequence change (N=39), median bleeding score 5.0 vs. 5.0 with sequence change (N=73); type 1C VWD, no sequence change (N=6), median bleeding score 7.0 vs. 7.0 with sequence change (N=24). There were no differences in median bleeding scores in blood group O vs. nonO groups, and none in the nonO groups with or without sequence variation in any of the VWD phenotypic diagnostic categories. There were no significant differences in bleeding scores by gender in any of the diagnostic categories. In conclusion, we found no differences in ISTH bleeding scores in the groups of subjects most likely to have low VWF on the basis of blood group O alone, i.e., those with blood group O and no identifiable VWF gene sequence variation compared to those with VWF gene sequence variations. Thus, management of persons with VWF deficiency should be based on baseline VWF levels and not modified in those with blood group O. Disclosures No relevant conflicts of interest to declare.

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Bleeding scores: are they really useful?

Hematology ◽

10.1182/asheducation.v2012.1.152.3798226 ◽

2012 ◽

Vol 2012 (1) ◽

pp. 152-156 ◽

Cited By ~ 30

Author(s):

Sarah H. O'Brien

Keyword(s):

Laboratory Testing ◽

Clinical Applications ◽

Von Willebrand Disease ◽

Assessment Tools ◽

Bleeding Disorders ◽

Clinical Markers ◽

Precise Quantification ◽

Bleeding Score ◽

Von Willebrand

Abstract Given the commonality of bleeding symptoms in the general population and the diagnostic limitations of available laboratory testing for mild bleeding disorders, there has been increasing interest in a more precise quantification of bleeding symptoms. The Vicenza bleeding score (and its successor, Molecular and Clinical Markers for the Diagnosis and Management of Type 1 von Willebrand disease [MCMDM-1 VWD]) and its pediatric counterpart, the Pediatric Bleeding Questionnaire, are validated research tools that have demonstrated their ability to discriminate between healthy subjects and those with VWD. These instruments collect data regarding both the presence and severity of a variety of bleeding symptoms and generate a bleeding score by summing the severity of all symptoms reported by a subject. More recent work demonstrates the promise of these tools as a diagnostic aid in the evaluation of patients with a suspected inherited mild bleeding disorder, as well as the development of a condensed score with increased clinical applicability. This review focuses on the development of these bleeding assessment tools, recent publications applying and refining these instruments, and current limitations of bleeding scores. Needed research studies and potential clinical applications of bleeding scores are also discussed. The ultimate goal would be for bleeding scores to be integrated with the results of standardized laboratory testing to allow for a universal diagnostic approach to patients with suspected bleeding disorders.

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Acquired Von Willebrand Syndrome Associated with B Cell Chronic Lymphoproliferative Disorders. Results from a Prospective Observational Study

Blood ◽

10.1182/blood.v124.21.1509.1509 ◽

2014 ◽

Vol 124 (21) ◽

pp. 1509-1509

Author(s):

Jean Baptiste Rabec ◽

Philippe Gautier ◽

Xavier Troussard ◽

Anne Claire Gac ◽

Sylvain Chantepie ◽

...

Keyword(s):

Prospective Study ◽

B Cell ◽

Lymphoproliferative Disorders ◽

Von Willebrand Disease ◽

Acquired Von Willebrand Syndrome ◽

Bleeding Score ◽

Von Willebrand ◽

Willebrand Factor ◽

Undetermined Significance

Abstract Introduction. Whereas von Willebrand disease is the most common constitutional bleeding disorder, acquired von Willebrand syndrome (AVWS) is rare with an estimated prevalence between 0.04 to 0.5%(1). AVWS has been related in various pathophysiological conditions including cardiovascular diseases such as aortic stenosis, autoimmune and lymphoproliferative disorders. To our knowledge, the prevalence of AVWS in lymphoproliferative disorders has never been investigated. Methods. We conducted an observational monocentric prospective study in Caen university hospital to evaluate the incidence of AVWS in B cell chronic lymphoproliferative disorders (B-CLPD) and characterize its phenotype. Inclusion criteria were the presence of a BCLPD in patients with no personal or family history of bleeding. Every enrolled patients was tested for Biological parameters were measured including closure time, von Willebrand Antigen (VWF:Ag), ristocetin cofactor activity (VWF:RCo) and factor VIII procoagulant activity (FVIII:C). The bleeding phenotype was evaluated using Tossetto bleeding score(2). AVWS was suspected when patients presented a decrease of VWF:Ag and VWF:RCo and/or a VWF:RCo/VWF:Ag below 0.7. Results. A total of 147 patients were included with the following diagnosis: fifty five patients (37%) with chronic lymphocytic leukemia, 48 patients (33%) with monoclonal gammopathies of undetermined significance (MGUS), 22 patients (15 %) with non hodgkin B cell lymphoma, 9 patients (6 %) with multiple myeloma, 4 patients (3 %) with Waldenstrom macroglobulinemia and 9 patients with other B-CLPD. Closure times, with epinephrine and ADP, were prolonged for six patients (6/147, 4.1%) with median levels of VWF:Ag, VWF:RCo, FVIII:C and VWF:RCo/VWF:Ag ratio at 29.5 IU/dL [9-284], 11.4 IU/dL [1-140] , 42.5 [6-204] and 0.3 [0.04-0.84], respectively. Five of these 6 patients had MGUS and 1 patient presented a follicular lymphoma. Serum protein electrophoresis revealed a monoclonal component in 5 patients with a median concentration at 8.45 g/L [4.4-9.1]. Four out of these 6 patients presented mucocutaneous bleedings including menorragia, ecchymoses, epistaxis, gingival bleedings, post-operative bleedings and gastro intestinal bleedings. The median bleeding score of these six patients was 4.5 [-1 – 12]. In four patients, the biological phenotype was a type 2 von Willebrand disease, with decreased VWF:RCo/VWF:Ag ratio (<0.7), loss of high and intermediate molecular weight multimers and a decrease of von Willebrand binding to collagen (VWF:CB) (VWF:CB/VWF:Ag<0.6). Anti-von Willebrand factor inhibitor screening was negative for the six patients. Four of these 6 patients presented an accelerated clearance of VWF with increased von willebrand factor propeptide/VWF:Ag ratios. Table 1. Different proposed cutoffs with their prospective sensitivity, specificity, and likelihood ratios (LR). Cutoff > Sensitivity % 95% CI Specificity % 95% CI LR + LR - 503.50 100.00 66.37% to 100.0% 0.30 0.007557% to 1.652% 1.00 0.00 2514.00 88.89 51.75% to 99.72% 75.22 70.24% to 79.76% 3.59 0.15 5020.00 77.78 39.99% to 97.19% 85.67 81.46% to 89.24% 5.43 0.26 Conclusion: In this original prospective study, we observed AVWS for 4.1% of patients with B-CLPD. Monoclonal gammopathies of undetermined significance (MGUS) were associated with AVWS in 5 of 6 patients with AVWS. For patients with type 2 phenotypes, an increased clearance of VWF was the main mechanism of AVWS. The annual follow-up of these patients will give informations regarding the time of appearance and clinical informations for AVWS. Tiede A et al. Blood 2011. Tosetto A et al. Blood Rev 2007. Disclosures No relevant conflicts of interest to declare.

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Advances in the diagnosis and treatment of Von Willebrand disease

Blood ◽

10.1182/blood-2017-05-782029 ◽

2017 ◽

Vol 130 (22) ◽

pp. 2386-2391 ◽

Cited By ~ 31

Author(s):

Ruchika Sharma ◽

Veronica H. Flood

Keyword(s):

Treatment Options ◽

Von Willebrand Disease ◽

Assessment Tools ◽

Binding Assays ◽

Laboratory Assessment ◽

Von Willebrand ◽

Willebrand Factor

Abstract 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.

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Bleeding Scores for the Diagnosis of von Willebrand Disease

Seminars in Thrombosis and Hemostasis ◽

10.1055/s-0036-1597289 ◽

2017 ◽

Vol 43 (05) ◽

pp. 530-539 ◽

Cited By ~ 17

Author(s):

Mackenzie Bowman ◽

Paula James

Keyword(s):

Clinical Utility ◽

Von Willebrand Disease ◽

Assessment Tools ◽

Clinical Settings ◽

Future Directions ◽

The Past ◽

History Of ◽

Precise Quantification ◽

Bleeding Score ◽

Von Willebrand

AbstractObtaining a personal history of bleeding is a critical component to the diagnosis of von Willebrand disease (VWD). The collection of this information can be challenging for physicians, however, as the reporting and interpretation of bleeding symptoms is subjective. The need for more precise quantification of bleeding symptoms was recognized and the Vicenza Bleeding Questionnaire was developed in 2005. This questionnaire collects data regarding the presence and severity of bleeding symptoms and generates a bleeding score by summing the severity of all symptoms reported by a patient. Several subsequent bleeding assessment tools (BATs) have been developed based from this original questionnaire and there has been a surge in the use of BATs in various clinical settings for the diagnosis and evaluation of VWD. This review will discuss the evolution of BATs over the past decade, as well as their use and validation in various settings for the diagnosis and evaluation of VWD. Additionally, we will discuss the clinical utility of BATs, the limitations of these tools, and future directions.

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