Bleeding Score as a Preoperative Predictor of Postoperative Bleeding in Type 1 Von Willebrand Disease.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 1019-1019 ◽  
Author(s):  
Laura R. Goldberg ◽  
Margaret V. Ragni
Keyword(s):  
Family History ◽  
Postoperative Bleeding ◽  
Von Willebrand Disease ◽  
Chi Square ◽  
Exact Test ◽  
Bleeding Score ◽  
Chi Square Analysis ◽  
Bleeding History ◽  
Von Willebrand

Abstract Type 1 Von Willebrand Disease (VWD) is the most common congenital bleeding disorder, affecting 1% of the population, and caused by a quantitative deficiency of Von Willebrand Factor (VWF). In addition to mucosal bleeding, VWD patients often suffer postoperative bleeding, leading to significant morbidity. Thus, a preoperative diagnosis could potentially reduce postoperative bleeding. Because symptoms correlate poorly with VWD assays, subject to extragenic effects and lab variability, diagnosis is difficult. The bleeding score (BS) is a simple quantitative tool recently developed to rate bleeding symptom severity, with 99% specificity for VWD. To determine the potential utility of BS in predicting postoperative bleeding in VWD, we evaluated preoperative BS by retrospective review of type 1 VWD patients who suffered postoperative bleeding prior to diagnosis. Preoperative clinical bleeding symptoms and VWD assays, including VWF:RCo, VWF:Ag, and FVIII:C, were obtained. The severity of clinical bleeding symptoms present prior to surgery was rated by the 4-point BS scale: 0 = no/trivial; 1 = present; 2 = intervention required; 3 = replacement therapy. Statistical analysis was by chi square analysis and Fisher’s exact test for categorical data, and by student t test for continuous data. Of 260 registered type 1 VWD patients, 71 (27.3 %) experienced surgical bleeding prior to a diagnosis of VWD. Of these 56 (78.9%) were female, 48 (67.6%) were adults (≥ 18 yr), and 61 (85.9%) had a family bleeding history. The surgeries included general, gynecologic, genitourinary, and otolaryngologic procedures. The median preop BS, 3 in females and 4 in adults, was significantly higher than in males and children, each median 1, p<0.01, respectively. A BS ≥ 3 would have identified only 59.1% patients before surgery, but as many as 90.1%, if combined with one abnormal VWD test; 94.4%, with family bleeding history; or 97.2% with both family history and one abnormal VWD test. The proportion of children identified by BS was significantly lower than in adults, 26.1% vs 75.0 % with BS > 3, p = 0.001. Yet this significantly improved by combining BS with family history, 91.3% vs 95.8%, not different from adults, p = 0.591. We conclude that obtaining a preoperative BS and family bleeding history may reduce postoperative bleeding and promote timely diagnosis among individuals with type 1 VWD patients, particularly children. Preoperative Bleeding Score in Type 1 VWD Patients with Postoperative Bleeding Male Female Age < 18 Age ≥ 18 All N = 15 N = 56 N = 23 N = 48 N = 71 τp = .001, as compared with under 18 yr; σp = .007, as compared with males; ζ p > 0.5 as compared with age under 18 or males, respectively. BS≥1 10/15 (66.7%) 54/56 (96.4%) 18/23 (78.3%) 46/48 (95.8%) 64/71 (90.1%) BS≥3 4/15 (26.7%) 38/56 (67.8%)σ 6/23 (26.1%) 36/48 (75.0%)τ 42/71 (59.1%) BS≥5 2/15 (13.3%) 17/56 (30.3%) 2/23 (8.7%) 17/48 (35.4%) 19/71 (26.7%) Abnl VWF:RCo 8/15 (53.3%) 19/56 (33.9%) 6/23 (26.1%) 19/48 (39.6%) 27/71 (38.0%) Abnl VWD Test 11/15 (73.3%) 41/56 (73.2%) 16/23 (69.6%) 36/48 (75.0%) 52/71 (73.2%) Fam Bld History 15/15 (100%) 47/56 (83.9%) 21/23 (91.3%) 40/48 (83.3%) 61/71 (85.9%) BS≥3 ± Abnl VWD Test 13/15 (86.7%) 51/56 (91.1%) 18/23 (78.3%) 46/48 (95.8%) 64/71 (90.1%) BS≥3 ± Fam Hx 15/15 (100.0%) 52/56 (92.8%)ζ 21/23 (91.3%) 46/48 (95.8%)ζ 67/71 (94.4%) BS≥3 ± Fam Hx ± Abnl VWD Test 15/15 (100.0%) 54/56 (96.4%) 22/23 (95.6%) 47/48 (97.9%) 69/71 (97.2%)

scholarly journals Impact of Two Immobilized GPIbα Assays in the Diagnosis of Von Willebrand Disease

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 1524-1524
Author(s):  
Silmara Lima Montalvão ◽  
Sandra Martins Silva Soares ◽  
Marina P Colella ◽  
Joyce M Annichino-Bizzacchi ◽  
Samuel de Souza Medina ◽  
...  
Keyword(s):  
Sensitivity And Specificity ◽  
False Positive ◽  
New Technologies ◽  
Von Willebrand Disease ◽  
The Other ◽  
Bleeding Score ◽  
Bleeding History ◽  
Von Willebrand ◽  
Positive Results

Abstract The diagnosis of von Willebrand Disease (VWD) remains a challenge of daily hematology practice. Ristocetin cofactor activity (VWF:RCo) is an important parameter for the diagnosis of VWD and is also essential for its management. However, reproducibility of the available tests for VWF:RCo is still a major issue, as evidenced by coefficient of variations (CV) as high as 30%, 45% and 27% in the ECAT, NEQAS and PALQ external quality assessment program. Classical methods to measure VWF:RCo include light-transmission platelet agregometry (LPA) and visual agglutination with formaldehyde fixed human platelet (VA), and more recently, VWF activity based on automated latex immunoassay (LIA). The glycoprotein (GP) Ibα is the main receptor for von Willebrand factor (VWF) in the platelet membrane. Currently, two automated methods with immobilized GPIbα have been developed to improve the sensitivity and specificity of VWF:RCo. One of them is performed with ristocetin while the other one uses a mutant GPIbα with gain of function and does not require ristocetin. This study aims to compare the two assays using immobilized GPIbα with other four assays for VWF functional determination, in patients with confirmed and under investigation for VWD. We evaluated six different VWF functional assays: VWF:RCo LPA (Chrono-Log); VA (Siemens); VA in house (with ristocetin from Chrono-Log); automated-LIA (Hemosil); in comparison to two assays using immobilized GPIbα with or without ristocetin, the GPIbα-ristocetin (Hemosil), and GPIbα-mutant (Siemens Innovance). Reference ranges for each method were established in 20 healthy adults. Plasma samples collected at the same time from 40 individuals were used in this comparative study, with 25 type 1 VWD, 2 type 3 VWD, and 13 under investigation. Diagnosis of VWD was based on bleeding history (evaluated by MCMDM-1VWD Bleeding Score), historical levels of VWF antigen (VWF:Ag) by ELISA, and VWF:RCo (assayed by LTA or VA) obtained from medical records. Statistical analysis were performed based on linear regression (Spearman correlation), agreement test (Altman Bland), and chi-square test using Prism 6.0. When all 40 patients were evaluated for both methods, GPIbα-ristocetin and GPIbα-mutant, we observed a good coefficient of correlation (r = 0.8954; p<0.0001). However, when 7 type 1 VWD patients, and 1 under investigation case were evaluated for the six methods, the two using immobilized GPIbα showed lower median (16.78 ± 4.62 with GPIbα-ristocetin, and 16.28 ± 4.29 with GPIbα-mutant), when compared with the other four assays (LTA: 22.38 ± 5.5; VA in house: 21.45 ± 4.87; VA Siemens: 22.65 ± 4.9; and LIA: 24.19 ± 9.0). In this group, when the bleeding score (BS) were ≥ 5, the VWF functional results were lower than 25 IU/dL, using all six methods (figure). Among 13 individuals under VWD investigation, GPIbα-ristocetin and GPIbα-mutant showed good agreement with the LTA/VA results and clinical history, and we could concluded that 4 have VWD, and for 4 individuals VWD was excluded. However, 2 individuals with no history of bleeding presented abnormal results for GPIbα-ristocetin and GPIbα-mutant, showing probably false positive results. One patient with no bleeding history, and abnormal LTA/VA results had normal GPIbα-ristocetin and GPIbα-mutant results, demonstrating poor reproducibility and precisian of the classical methods. On the other hand, two patient with BS 6, the diagnosis of VWD was demonstrating only by immobilized GPIbα methods. The VWF:RCo is a cumbersome assay and can be affected by polymorphisms present in the ristocetin binding site of VWF. Recently, new technologies have been developed to improve the VWF functional evaluation. It is consensus that methodologies using platelets are more accurate than other methods. Therefore, immobilized GPIbα has the objective to improve the sensitivity and specificity. Besides good results of concordance between immobilized GPIbα in the group of VWD patients and for 62% individual under investigation, we also observed false positive results related with these methods. The presence or absence of ristocetin on the immobilized GPIbα setting appear not engender different results in this study. In general, this new technologies present better precision compared to VA and LTA. Figure 1 Figure 1. Disclosures No relevant conflicts of interest to declare.

Cost Effectiveness Strategy to Predict Postoperative Bleeding in Von Willebrand Disease.

Blood ◽  
2008 ◽  
Vol 112 (11) ◽  
pp. 1295-1295
Author(s):  
Daniel Delitto ◽  
Margaret V. Ragni ◽  
Kenneth J Smith
Keyword(s):  
Cost Effectiveness ◽  
Incremental Cost ◽  
Postoperative Bleeding ◽  
Bleeding Risk ◽  
Von Willebrand Disease ◽  
Test Series ◽  
Surgical Bleeding ◽  
Bleeding History ◽  
Von Willebrand

Abstract Von Willebrand disease (VWD) is the most common congenital bleeding disorder, affecting up to 1% of the population. In type 1 VWD, which accounts for 65% of the disease, bleeding may be mild and up to 50% may have a normal screening APTT. Thus, in many the diagnosis may be missed and excess bleeding may occur postoperatively, which could potentially be prevented if reliable preoperative predictors existed. In order to assess possible predictors of postoperative bleeding and determine a cost-effective strategy to predict postoperative bleeding in patients with type 1 VWD, we constructed a decision tree model to test various screening strategies, including bleeding severity score (BSS), VWD assays (VWF:RCo; VWF:Ag, VIII:C), platelet function (PFA-100), and family bleeding history (Fam Hx), alone and in combination, in various sequence. For the model, sensitivity and specificity of coagulation tests, BSS, and family bleeding history were determined on 129 subjects with type 1 VWD, including 74 experiencing postoperative bleeding prior to diagnosis and 55 experiencing no postoperative bleeding prior to diagnosis. BSS was determined for each subject at the time of diagnosis (but prior to surgical bleeding), based on abstracted outpatient medical records. Testing, transfusion, and hospitalization costs were based on local costs, and DDAVP cost was based on average wholesale price. Outcomes were testing strategy cost and strategy effectiveness, as measured by postoperative bleeding risk. It was assumed that all patents testing positive, based on a given strategy, would receive preoperative DDAVP and be 100% protected from bleeding; and that those who developed postoperative bleeding would require three days of hospitalization and receive a transfusion. In the base case analysis, with VWD prevalence of 1%, BSS 3 3 and the Test Series (any of VWF:RCo VWF:Ag, F.VIII) dominates over all other strategies, based on having the highest sensitivity. When prevalence is varied 0–1%, the strategy of BSS 3 3 and the Test Series seems a reasonable choice if prevalence is 3 1%. At 1% prevalence, the incremental cost-effectiveness ratio (ICER) is about $103,000 which is at the edge of what may be considered economically reasonable. However, the ICER, for this strategy falls fairly rapidly, and is &lt; $100,000 when prevalence is 3 1.03%. We also varied the proportion requiring hospitalization or transfusion to 5% and 1%, respectively, but these did not significantly affect the results. In conclusion, in individuals with BSS 3 3, proceeding with the Test Series (VWF:RCo, VWF:Ag, F.VIII) is a clinically and economically reasonable strategy for those in whom DDAVP should be given to prevent surgical bleeding, when the bleeding risk is 3 1%. Strategy Cost Incremental Cost Effectiveness Incremental Effectiveness ICER BSS ≥ 3 & Test Series $1,296.10 0.055 Fam Hx $1,703.90 $407.70 0.087 −0.032 (Dominated) Fam Hx & Test Series $2,187.50 $891.40 0.111 −0.056 (Dominated) Fam Hx or BSS ≥ 3 & Test Series $2.435.40 $1,139.30 0.127 −0.072 (Dominated) Test Series $2,508.60 $1,212.50 0.132 −0.077 (Dominated) BSS ≥ 3 $2.974.30 $1,678.10 0.171 −0.116 (Dominated) BSS ≥ 5 $5,966.10 $4.669.90 0.364 −0.309 (Dominated) No Testing or Rx $9,238.30 $7.942.20 0.574 −0.519 (Dominated)

scholarly journals No Association Between Normalization of VWF Levels and Bleeding Phenotype in Patients with Type 1 VWD - from the Win Study

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 2577-2577 ◽  
Author(s):  
Johan Boender ◽  
Jeroen Eikenboom ◽  
Karin Fijnvandraat ◽  
Waander van Heerde ◽  
Karina Meijer ◽  
...  
Keyword(s):  
Family History ◽  
Blood Group ◽  
Research Funding ◽  
Von Willebrand Disease ◽  
Younger Adults ◽  
Bleeding Score ◽  
Von Willebrand ◽  
Index Cases ◽  
Over Time

Abstract Von Willebrand factor (VWF) levels vary over time and increase throughout life in both healthy individuals and patients with von Willebrand disease (VWD). Especially in type 1 VWD patients, this increase may result in normalization of VWF levels. It is not yet known if normalization of VWF levels ameliorates bleeding symptoms in VWD patients. We have recently shown that elderly type 1 VWD patients had similar bleeding tendency as younger adults.1 However, many elderly patients in this study had relatively low VWF levels and many younger adults had relatively high VWF levels.1 The aim of the current study was to investigate the association between normalization of VWF levels and the bleeding phenotype in type 1 VWD patients. We included patients from the nationwide cross-sectional "Willebrand in the Netherlands" Study, with lowest historical VWF antigen (VWF:Ag) and/or VWF activity (VWF:Act) ≤30 U/dL. At inclusion, blood was sampled for central measurement of VWF:Ag and VWF:Act and VWF to collagen binding (VWF:CB). Central measurements were available in 367 type 1 VWD patients. Based on these central measurements, patients were divided into three groups: definite VWD (central VWF:Ag and/or VWF:Act and/or VWF:CB ≤30 U/dL, n=152); low VWF (central VWF:Ag and/or VWF:Act and/or VWF:CB 31-50 U/dL , n=120) and historical VWD with presently normalized levels (central VWF:Ag and VWF:Act and VWF:CB ≥51 U/dL, n=95). Age differed between groups: median age was 43 years in definite VWD patients, 45 years in low VWF and 50 years in historical VWD patients (p<0.01). No difference in sex distribution was found, see table 1. Of definite VWD patients, 59% had blood group O compared with 77% of low VWF and 73% historical VWD patients (p<0.01). A variant in the VWF gene was most common in definite VWD patients: 55/76 (72%) patients in whom mutation analysis was performed had a variant compared with 22/41 (54%) low VWF and 13/41 (32%) historical VWD patients (p<0.001). Of definite VWD patients, 72% had a positive family history, compared with 39% of low VWF and 27% of historical VWD patients (p<0.001). In contrast, 69% of historical VWD patients were index cases, compared with 67% of "low VWF" and 39% of definite VWD patients (p<0.001). Median Tosetto Bleeding Score (BS) did not differ between the three groups as it was respectively 9, 8 and 9 in definite VWD patients , low VWF patients and historical VWD patients (p=NS), see table 1. The incidence of bleeding episodes requiring treatment with desmopressin or clotting factor concentrate in the year prior to inclusion also did not differ between groups as it was 18% in definite VWD, 22% in "low VWF" and 27% in historical VWD patients (p=NS). In many countries VWF levels 60 IU/dL are used as the cut-off value for abnormal VWF levels. Using this value as cut-off between low VWF and historical VWD, 151 (42%) patients had low VWF and 64 (17%) patients had historical VWD. Using this cut-off value had no major effect on bleeding phenotype or patient characteristics (data not shown). In conclusion, patients with higher VWF levels at the time of study were older and less often had a variant in the VWF gene. More historical VWD patients were index cases, underlining their negative family history. In contrast, blood group O was more common in patients with normalized VWF levels, suggesting that factors outside the VWF gene have a more important effect on VWF levels in this group. Importantly, the bleeding score was similar in all groups. The bleeding score is a reflection of bleeding symptoms that have occurred throughout one's life and may therefore not detect changes in bleeding phenotype over time. Importantly, the bleeding incidence requiring treatment in the year prior to inclusion was also similar in all groups, regardless of VWF levels. Our study suggests that normalization of VWF levels is not associated with the bleeding phenotype in type 1 VWD patients. However, this study is limited by its retrospective design and prospective studies are required to assess the bleeding phenotype and bleeding rate in more detail and to identify patients at increased or decreased risk of bleeding. 1Sanders YV, Giezenaar MA, Laros-van Gorkom BA, et al. von Willebrand disease and aging: an evolving phenotype. J Thromb Haemost. 2014;12(7):1066-1075. Disclosures Boender: CSL Behring: Research Funding. Eikenboom:CSL Behring: Research Funding. Fijnvandraat:CSL Behring: Research Funding; Bayer: Research Funding. Meijer:Bayer: Honoraria, Research Funding; Baxter: Research Funding; Pfizer: Research Funding; Sanquin: Honoraria, Research Funding; Boehringer Ingelheim: Honoraria; Bristol-Myers Squibb: Honoraria. Mauser-Bunschoten:Baxter: Research Funding; Bayer: Research Funding; CSL Behring: Research Funding; Novo Nordisk: Research Funding; Griffols: Research Funding; Sanquin: Research Funding. Cnossen:Novo Nordisk: Research Funding; CSL Behring: Other: Travel Funding, Research Funding; Pfizer: Research Funding; Novartis: Research Funding; Baxalta: Research Funding; Bayer: Research Funding. Laros-van Gorkom:CSL Behring: Research Funding. van der Bom:CSL Behring: Research Funding; Novo Nordisk: Research Funding; Pfizer: Research Funding; Bayer: Research Funding; Baxalta: Research Funding. Leebeek:UniQure: Consultancy; Netherlands Hemophilia Foundation: Research Funding; Baxter: Research Funding; CSL Behring: Research Funding.

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

2013 ◽  
Vol 5 (1) ◽  
pp. e2013051 ◽  
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.

Major haemorrhage related to surgery in patients with type 1 and possible type 1 von Willebrand disease

2008 ◽  
Vol 100 (05) ◽  
pp. 797-802 ◽  
Author(s):  
Alicia Blanco ◽  
Roberto Chuit ◽  
Susana Meschengieser ◽  
Ana Kempfer ◽  
Cristina Farías ◽  
...  
Keyword(s):  
Family History ◽  
Surgical Procedures ◽  
Tooth Extraction ◽  
Positive Family History ◽  
Major Haemorrhage ◽  
Von Willebrand Disease ◽  
Bleeding Complications ◽  
Laboratory Test Results ◽  
Von Willebrand

SummaryPatients with von Willebrand disease (VWD) frequently bleed under a challenge. The aim of our study was to identify predictive markers of perioperative major haemorrhage in type 1 (VWF:RCo = 15–30 IU dl-1) and possible type 1 (VWF:RCo = 31–49 IU dl-1)VWD patients. We recorded perioperative bleeding complications previous to diagnosis and laboratory parameters in 311 patients with 498 surgical procedures. The patients were grouped according to the absence (A) or presence (B) of perioperative major haemorrhages. Eighty-one patients (26%) and 87 surgical procedures (17.5%) presented major haemorrhages associated with surgeries. There was no difference between the percentage of type 1 and possible type 1 VWD patients who had major haemorrhages (32.6% and 24.8% respectively; p=ns). No difference in the prevalence of O blood group, age, gender, positive family history and laboratory test results (FVIII and VWF) was observed, independent of the haemorrhagic tendency. Bleeding after tooth extraction was the most frequent clinical feature observed in patients with perioperative major haemorrhages. The bleeding score and the number of bleeding sites (≥3) were not predictors of major haemorrhage associated with surgery. Caesarean section and adenotonsillectomy showed the highest frequency of major haemorrhages (24.6% and 22.3%, respectively). In conclusion, type 1 and possible type 1VWD patients showed similar incidence of perioperative major haemorrhages. Laboratory tests and positive family history did not prove to be effective at predicting major haemorrhages in patients that had either type 1 or possible type 1 VWD. The history of bleeding after tooth extraction could define risk factors of major haemorrhage.

Quantitation of Bleeding Symptoms in Children with von Willebrand Disease (VWD) or a Platelet Function Disorder: Use of a Standardized Pediatric Bleeding Score.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2137-2137 ◽  
Author(s):  
T.T. Biss ◽  
V.S. Blanchette ◽  
M. Bowman ◽  
D.S. Clark ◽  
M. Silva ◽  
...  
Keyword(s):  
Platelet Function ◽  
Dense Granule ◽  
Von Willebrand Disease ◽  
Number Of Patients ◽  
Kingston General Hospital ◽  
Bleeding Score ◽  
Sick Children ◽  
Bleeding History ◽  
Score Range

Abstract Obtaining an accurate bleeding history is an essential step in the diagnosis of a bleeding disorder, which is often made during childhood. A bleeding history is usually taken in an informal manner, with the interpretation of the responses dependent on the experience of the observer. The development of standardized bleeding questionnaires has improved objectivity and allowed the determination of quantitative scores according to the severity of mucocutaneous bleeding. In adults, using the International Society on Thrombosis and Haemostasis (ISTH) Bleeding Questionnaire for Diagnosis of Type 1 VWD, a bleeding score of &gt;3 in males and &gt;5 in females is considered abnormal (Rodeghiero et al., J Thromb Haemost2005:3;2619). Children have often not been exposed to hemostatic challenges and may have low scores despite significant bleeding disorders. Symptoms specific to childhood, such as post-circumcision bleeding, umbilical stump bleeding and cephalohematoma may be of greater significance in this patient group. Thus, we adapted the ISTH Bleeding Questionnaire for use in pediatrics, with a symptom-specific grade of -1 to 4 (Tosetto et al., J Thromb Haemost2006:4;766). Bleeding scores were determined by interview of parents/children for 80 children with a previous diagnosis of VWD or a platelet function disorder at The Hospital for Sick Children, Toronto, or Kingston General Hospital, Kingston. 62 children had a diagnosis of VWD and 18, a disorder of platelet function (Glanzmann thrombasthenia: 3; dense granule defect: 2; MYH9-related thrombocytopenia: 2; Hermansky-Pudlak syndrome: 1; unspecified: 10). 45 children were female and 35, male (median age: 10 yrs (range: 9 mo-17 yrs)), with a median age of females of 12 yrs (range: 0–17) and of males, 9 yrs (range: 1–17). Bleeding scores ranged from 0–28 (median: 7), with a median score in females of 7 and in males, 8. Bleeding scores according to diagnosis and age are shown in Tables 1 and 2, respectively. The most frequent reasons for a positive score of ≥2 were epistaxis (43% of patients), bleeding from minor wounds (38%), bleeding after dental extraction (31%) and excessive bruising (26%). Menorrhagia requiring treatment occurred in 47% of menstruating females. Bleeding from the umbilical stump, post-circumcision bleeding and cephalohematoma were reported in 10%, 6% and 4% of patients, respectively. In summary, we have used a standardized bleeding questionnaire, adapted for use in pediatrics, with an accompanying score to quantify bleeding symptoms in children with confirmed VWD or a platelet function disorder. Bleeding scores were lowest in the youngest age group (0–3 yrs), and were slightly higher in males than in females. Bleeding occurred early in childhood, i.e. post-circumcision bleeding and bleeding from the umbilical stump. This standardized pediatric bleeding questionnaire/score may be useful in clinical practice in the assessment of children presenting with symptomatic bruising and bleeding. Diagnosis Type 1 VWD Type 2 VWD Type 3 VWD Platelet function disorder Number of patients 48 8 6 18 Median bleeding score (range) 6 (0–18) 10 (0–17) 14 (9–28) 9 (1–19) Age (years) 0–3 4–6 7–9 10–12 13–15 16–18 Number of patients 7 13 18 16 14 12 Median bleeding score (range) 2 (0–9) 10 (0–16) 6 (0–19) 9.5 (1–28) 6 (2–18) 12 (6–21)

The Power of a Standardized Bleeding Score in Diagnosing Pediatric Type 1 Von Willebrand Disease.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 1293-1293
Author(s):  
Paul D Marcus ◽  
Kidan G Nire ◽  
Linda Grooms ◽  
Jennifer Klima ◽  
Sarah O'Brien
Keyword(s):  
Platelet Function ◽  
Predictive Value ◽  
Care Setting ◽  
Tertiary Care ◽  
Bleeding Disorder ◽  
Von Willebrand Disease ◽  
The Mean ◽  
Bleeding Score ◽  
Von Willebrand

Abstract Abstract 1293 Poster Board I-315 INTRODUCTION Type I von Willebrand disease (VWD) is the most common inherited bleeding disorder. Repetitive testing of von Willebrand factor (VWF) levels is necessary before the diagnosis can be safely ruled out, as VWF levels fluctuate in response to genetic and environmental factors. A predictive bleeding score (BS) could reveal individuals that may benefit from repetitive testing and those for whom repetitive testing is unlikely to be of benefit. While a standardized questionnaire (the Vicenza score) was developed to evaluate hemorrhagic symptoms, it was never prospectively validated for a pediatric population in a tertiary care setting. SUBJECTS The study targeted children, ages 0 to 17 years, referred to the Hemostasis and Thrombosis Center (HTC) of Nationwide Children's Hospital for a coagulation evaluation as a result of bleeding symptoms, family history of a bleeding disorder and/or abnormal coagulation labs found during pre-operative screening. Children were excluded if they had a previously diagnosed bleeding disorder, if their caregiver did not speak English or if the child did not undergo VWF:Ag and VWF:RCo testing. METHODS Prior to the diagnosis or exclusion of a bleeding disorder in the child, caregivers consented to answer the questionnaire over the telephone. Descriptions of the Vicenza score are available online (http://www.euvwd.group.shef.ac.uk/bleed_score.htm). LABORATORY TESTING A single VWF:Ag or VWF:RCo <30 IU/dL was classified as “Definite Type 1 VWD” while levels from 30-50 IU/dL were classified as “Low VWF” (http://www.nhlbi.nih.gov/guidelines/vwd). Platelet function analysis (PFA-100) screened for platelet function defects, with some patients undergoing follow-up platelet aggregation studies and/or platelet electron microscopy. Laboratory studies from other institutions were excluded from analysis. Patients' medical records were reviewed after hematologic evaluation, and the resultant data was analyzed with STATA 10.1 (Stata Corp., College Station, TX). RESULTS A total of 104 children (52 females and 52 males) with a mean age of 7.53 years (range 1 month to 17 years) were included. At least one hemorrhagic symptom was present in 99 of the 104 children (95%) with the mean number of symptoms being 2.87 (range 0 to 7). The mean Vicenza score was 3.24 (range -1 to 13). Of the 104 children, 8 met criteria for “Definite Type 1 VWD,” 23 met criteria for “Low VWF,” 14 were diagnosed with a “Platelet Function Defect,” and 2 children had bleeding secondary to Ehlers Danlos syndrome. Children with non-bleeding disorders (e.g. Factor XII deficiency) or no laboratory evidence of a bleeding disorder were classified as “No Bleeding Disorder.” In general, the sensitivity, specificity, positive predictive value (PPV), negative predictive value (NPV) and positive diagnostic likelihood ratio of the bleeding questionnaire demonstrated poor predictive value in our patient population with the exception of high specificity in ruling out “Definite Type 1 VWD” (Table). The NPV was comparably high with both qualitative (>2 bleeding symptoms) and quantitative (BS ≥2) criteria. CONCLUSIONS The Vicenza score, previously validated in adults and in a pediatric primary care setting, appears to have limited predictive value in a pediatric tertiary care setting when evaluating patients with platelet function defects or low VWF levels. While the Vicenza score has a high NPV to exclude “Definite Type 1 VWD,” the use of simpler qualitative criteria is similarly predictive. Disclosures No relevant conflicts of interest to declare.

scholarly journals Wish-Qol Study - Assessment of Health-Related Quality of Life (HRQoL) and Health-Economic Aspects in Patients with Von Willebrand Disease (VWD) in France: Results of the Women Cohort

Blood ◽  
2016 ◽  
Vol 128 (22) ◽  
pp. 1395-1395
Author(s):  
Annie Borel-Derlon ◽  
Jenny Goudemand ◽  
Dominique Desprez ◽  
Fabienne Volot ◽  
Yves Gruel ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Research Funding ◽  
Von Willebrand Disease ◽  
Female Group ◽  
Bleeding Score ◽  
Type 3 ◽  
Von Willebrand

Abstract Background: Von Willebrand disease (VWD) is the most common inherited bleeding disorder with a prevalence of 1% in the general population. VWD results from a deficiency in or a dysfunction of von Willebrand factor which is a protein that is necessary for normal platelet adhesion and protection of factor VIII from proteolysis in the circulation. Nevertheless, prevalence of the most symptomatic forms such as bleeds requiring replacement treatment and /or hospitalization is about 0.01%. Although VWD affects both genders, there is a higher proportion in females than in males.VWD seems to be more symptomatic in women because of their reproductive life. Women with VWD have an increased bleeding risk in numerous situations including anemia, menorrhagia, bleeding during pregnancy, postpartum hemorrhage and impairments in their quality of life (QoL).The prevalence of menorrhagia in women with VWD is 74-92%. According to the Francecoag Network, the referral-based prevalence of moderate-to-severe VWD patients is about 1,750 cases in France. Aim: Since the disease and its treatment can affect every-day life of patients and their families, a French HRQoL Study (WiSH-QoL) exploring this impact started 22 months ago. Methods: This non-interventional 5-year study evaluates patients HRQoL and costs of care in France. At least 350 patients will be followed for 24 months in minimum 30 centers. HRQoL is assessed with the generic SF-36 and the disease-specific VWD-QoL questionnaires. Bleeding severity was measured using the Tosetto Bleeding Score (BS). Results: Since October 2014, 245 patients have been included. We present here the first interim analysis with a focus on the female group. At the first interim analysis, data from 140 patients were documented: 91 adults with a median age of 40.0 years [18.3-78.0] and 49 children with a median age of 10.1 years [2.9-17.5]. VWD Types were already identified for 122 (87%) of these patients: 33 with VWD type 1 (27%) including 5 type 1 Vicenza; 76 type 2 (62%) and 13 type 3 (11%). The median Tosetto bleeding score reported for 124 patients (males and females) was +7 ranging from -1 to +28. From the 95 female patients, 70 were aged ≥18 years, 21 were adolescents between 8-17 years and 4 were girls below 4 years of age. Median age was 29.4 (range 4.3-78.0) years. A total of 25 women had type 1 VWD (31%), 49 had type 2 VWD (60%), and 7 had type 3 VWD (9%), for 14 patients VWD type is undetermined. The median Tosetto bleeding score of the female group was +8 ranging from -1 to +28. Out of 95 patients, 45 patients (47.4%) have received a concomitant treatment due to menorrhagia, such as iron therapy, oral contraceptive, levonorgestrel intrauterin system: 5/21 patients in the group between 8 and 17 years and 40/70 in the group ≥18 years. Out of the 60 women of childbearing potential defined as age between 15-50 years, 6 women were pregnant at time of inclusion. A total of 46 patients, aged 18 years or more have had obstetrical history prior to study inclusion. The mean number of childbirth was more than 2 i.e 2.39 range (1-8) per woman, 75% of these deliveries were natural delivery and 25% were caesarean section. Out of 108 deliveries, 28 (26%) were experienced with post-partum hemorrhages. Conclusions: With the results of the WiSH-QoL study, the first prospective study of von Willebrand disease conducted in France, especially the VWD-specific evaluation of HRQoL and treatment satisfaction a deeper insight will be gathered into the patients' daily life, their perception of well-being and their specific health care needs. With the additional domain 'pregnancy' included in the French version of the VWD-QoL questionnaire for female adult patients, it will possible to better understand how women may be affected by VWD during childbearing years. Disclosures Borel-Derlon: LFB: Other: Reference expert and national coordinator for VWD; Octapharma: Research Funding; NovoNordisk: Other: Expert for scientific committee; Shire - Baxalta: Research Funding. Chatelanaz:LFB Biomedicaments: Employment. Doriat-Robin:LFB Biomedicaments: Employment. von Mackensen:SOBI: Research Funding; Shire: Research Funding.

scholarly journals Epidural Analgesia Use in Women with Von Willebrand Disease

Blood ◽  
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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