Long-Term Prophylaxis In Children, Adolescents and Young Adults with Von Willebrand Disease – First Results of a Cohort Study

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 714-714
Author(s):  
Susan Halimeh ◽  
Anne Kruempel ◽  
Hannelore Rott ◽  
Nadja Bogdanova ◽  
Ulrich Budde ◽  
...  
Keyword(s):  
Young Adults ◽  
Replacement Therapy ◽  
Von Willebrand Disease ◽  
Recurrent Bleeding ◽  
On Demand ◽  
Bleeding Episodes ◽  
Children And Young Adults ◽  
Bleeding Score ◽  
Von Willebrand

Abstract Abstract 714 In children and young adults with von Willebrand disease [vWD] replacement therapy with von Willebrand factor (vWF)/factor VIII concentrates is increasingly performed as “prophylactic” therapy. Between 2000 and 2008, 82 consecutively enrolled children, adolescents and young adults with clinically meaningful bleeding episodes [spontaneous, peri- or postoperative] were diagnosed with vWD [type 1: 42/82; type 2: 24/82; type 3: 13/82; acquired: 3/82]. Here we report results of prophylaxic VWF replacement therapy in 32 patients [female: n=15; >Tanner 2: 9/15] with VWD type 1 [n=4], 2 [n=15] and 3 [n=13] in which a prophylactic treatment regimen was performed. Decision on prophylaxis was based on i) a pre-diagnostic bleeding score, and ii) on recurrent bleeds associated with microcytic anemia after diagnosis in patients with on-demand VWD therapy. Patients were treated with Humate P® (n=8; once switched to Wilfact®) or Wilate® (n=24). Median [min-max] dose was 40 (20-47) IU/kg, 23 patients were substituted twice weekly, 7 were treated three times, and two children 4 times per week. Within a six-months-period hemoglobin concentrations returned to normal values. Median [min-max] duration of prophylaxis was 3 years [1.0-9.0]. Recurrent bleeding episodes stopped in 31/32 patients, inhibitor development occurred in one. Following a 12-months observation period the bleeding frequency/bleeding score was significantly reduced, compared to pre-prophylaxis/pre-diagnostic values. The use of prophylactic VWF replacement therapy is an effective and well tolerated treatment modality, highly beneficial for children and young adults with vWD with recurrent bleeding events on on-demand therapy. Disclosures: No relevant conflicts of interest to declare.

Long-term secondary prophylaxis in children, adolescents and young adults with von Willebrand disease

2011 ◽  
Vol 105 (04) ◽  
pp. 597-604 ◽  
Author(s):  
Susan Halimeh ◽  
Anne Krümpel ◽  
Hannelore Rott ◽  
Nadja Bogdanova ◽  
Ulrich Budde ◽  
...  
Keyword(s):  
Replacement Therapy ◽  
Von Willebrand Disease ◽  
Recurrent Bleeding ◽  
On Demand ◽  
Bleeding Episodes ◽  
Bleeding Score ◽  
Type 3 ◽  
Von Willebrand

SummaryIn patients with von Willebrand disease (VWD) replacement therapy with factor VIII/von Willebrand (VWF) concentrates is increasingly applied as prophylactic regimen. Since 2000, 82 consecutively enrolled patients with clinically relevant bleeding episodes (spontaneous, peri- or postoperative) were diagnosed with VWD [type 1: 42/82; type 2: 24/82; type 3: 13/82; acquired: 3/82]. In all patients, decision for initiating prophylaxis was based on a bleeding score > 2 prior to diagnosis, concomitant with recurrent bleeds associated with anaemia in patients with on-demand VWD therapy. We report results on secondary prophylactic VWF replacement therapy applied in 32 patients [children n=13; adolescents n=7; adults n=12] with VWD [type 1: 4; type 2: 15; type 3: 13], 15 of which were females, and nine of these at the reproductive period. Eight patients were treated with Humate P→ or Wilate→ (n=24). Median [min-max] dose [vWF:RCo] was 40 [20–47] IU/kg, 23 patients were given substitution therapy twice weekly, seven patients three times a week, and two children four times per week. Within a 12-month-period haemoglobin concentrations returned to normal values. Median duration of prophylaxis was three years. Recurrent bleeding episodes stopped in 31 of 32 patients, whereas inhibitors developed in one. Following a 12-month observation period the monthly bleeding frequency and the bleeding score was significantly reduced [3 vs. 0.07; 3 vs. 0: p< 0.001], compared to the preprophylaxis/pre-diagnostic values. The use of secondary prophylactic VWF replacement therapy is an effective tolerated treatment modality, highly beneficial for patients with VWD, who present with recurrent bleeding events during on-demand therapy.

Dose-Finding Study: Rational Proceeding in Patients with VWD,

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 3326-3326
Author(s):  
Susan Halimeh ◽  
Hannelore Rott ◽  
Ulrike Nowak-Gottl
Keyword(s):  
Replacement Therapy ◽  
Conflicts Of Interest ◽  
Dose Finding ◽  
Recurrent Bleeding ◽  
Bleeding Events ◽  
Prophylactic Regimen ◽  
On Demand ◽  
Bleeding Episodes ◽  
Bleeding Score ◽  
Type 3

Abstract Abstract 3326 In patients with von Willebrand's disease (VWD) replacement therapy with factor VIII/VWF concentrates is increasingly applied as prophylactic regimen. Since 2000, 82 consecutively enrolled patients with clinically relevant bleeding episodes were diagnosed with VWD. In all patients, decision for initiating prophylaxis was based on a bleeding score >2 prior to diagnosis, concomitant with recurrent bleedings associated with anemia in patients with on-demand therapy. We report results on secondary prophylactic VWF replacemment therapy applied 13 children, 7 adolescents and 4 adults (n=24) with VWD type 1 (n=4), 2 (n=12) and the severe type 3 (n=8). Based on individual 24h VWF:RCo recoveries [aim: 0.01 to 0.02 IU/ml > baseline] median dose was 40 [min. 20- max. 47] IU/kg, 15 patients were give substitution therapy semiweekly, 7 patients thrice weekly and 2 children four times per week. Within a 12-months-period hemoglobin conentrations returned to normal values. Median duration of prophylaxis was 3 years. Recurrent bleeding episodes stopped in 23/24 patients. One female type 3 patient additionally needed locally applied tranexamic acid [tooth bruising]. Following a 12-months observation period the monthly bleeding frequency and the bleeding score was significantly reduced [3 vs. 0.07; 3 vs. 0: p< 0.001], compared to the pre-prophylaxis/ pre-diagnostic values. Conclusion: The use of secondary prophylactic VWF replacement therapy with FVIII/VWF concentrate is an effective tolerated treatment modality, highly benefical for patients with VWD, who present recurrent bleeding events during an on-demand therapy. Disclosures: No relevant conflicts of interest to declare.

The bleeding score predicts clinical outcomes and replacement therapy in adults with von Willebrand disease

Blood ◽  
2014 ◽  
Vol 123 (26) ◽  
pp. 4037-4044 ◽  
Author(s):  
Augusto B. Federici ◽  
Paolo Bucciarelli ◽  
Giancarlo Castaman ◽  
Maria G. Mazzucconi ◽  
Massimo Morfini ◽  
...  
Keyword(s):  
Replacement Therapy ◽  
Clinical Outcomes ◽  
Von Willebrand Disease ◽  
Adult Patients ◽  
On Demand ◽  
Key Points ◽  
Bleeding Score ◽  
Von Willebrand

Key Points The bleeding score helps to predict clinical outcomes in adult patients with von Willebrand disease. High bleeding scores correlate with intensive on-demand therapy and may identify cases requiring regular prophylaxis.

scholarly journals Replacement Therapy in Patients with Von Willebrand Disease—Indications and Monitoring

2019 ◽  
Vol 39 (04) ◽  
pp. 326-338
Author(s):  
Ulrike Nowak-Göttl ◽  
Wolfgang Miesbach ◽  
Jürgen Koscielny ◽  
Carl-Erik Dempfle ◽  
Marc Maegele ◽  
...  
Keyword(s):  
Replacement Therapy ◽  
Von Willebrand Disease ◽  
Spontaneous Bleeding ◽  
Surgical Interventions ◽  
Bleeding Episodes ◽  
Repeated Dosing ◽  
Von Willebrand ◽  
Willebrand Factor ◽  
Trough Levels ◽  
Very High

AbstractIn patients with von Willebrand disease (VWD), replacement therapy may be indicated in the case of spontaneous bleeding, surgical interventions and injuries/trauma or as a prophylaxis of spontaneous bleeding episodes. The deficient von Willebrand factor (VWF) is replaced with or without factor VIII (FVIII). Dual VWF/FVIII concentrates can be beneficial in the case of low FVIII level, while repeated dosing may lead to very high FVIII levels, with a potential thrombogenic effect in individual VWD patients. An excessive FVIII:C increase can be limited by using a VWF product with a low level of FVIII, achieving a haemostatic adequate FVIII:C increase after 6 to 12 hours. Replacement therapy in patients with VWD shall be individualised considering VWD type, history and risk of bleeding and risk of thrombosis, as well as indication and the individually variable VWF and FVIII increase. Deviations from the dosages and minimum trough levels mentioned in guidelines or recommendations can be considered in justified cases. The objective of this review is to provide recommendations for specific constellations of replacement therapy based on the VWD-specific guidelines available in Europe, the available evidence, own experiences and the consensus of the interdisciplinary German author group.

Incidence and Determinants of Bleeding in Different Types of von Willebrand Disease: Results of the First Prospective Multicenter Study on 814 Italian Patients.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 713-713 ◽  
Author(s):  
Augusto B. Federici ◽  
Paolo Bucciarelli ◽  
Giancarlo Castaman ◽  
Maria G. Mazzucconi ◽  
Massimo Morfini ◽  
...  
Keyword(s):  
Prospective Study ◽  
Von Willebrand Disease ◽  
Free Survival ◽  
Risk Of Bleeding ◽  
Bleeding Episodes ◽  
Mucosal Bleeding ◽  
One Year ◽  
Type 3 ◽  
Von Willebrand

Abstract Background. von Willebrand disease (VWD) is the most common inherited bleeding disorder and is due to quantitative and/or qualitative defects of von Willebrand factor (VWF). Despite the improved knowledge of the disorder, no data on the incidence and determinants of bleedings requiring specific treatments have been available thus far. Aims and design of the study: to determine the incidence and determinants of bleedings requiring therapy with DDAVP and/or VWF concentrates in VWD, a national registry was organized by using a database devised to collect detailed retrospective information. Patients included in the registry were followed up for one year and prospective data on number, type and management of bleeding episodes were analyzed. Methods: all patients were diagnosed following recommendations of the ISTH-SSC-SC on VWF with bleeding severity score (BSS) calculated at enrollment. Diagnoses of VWD were confirmed by the coordinating center using also multimeric analysis in plasma and mutations of VWF gene in all types 2 and 3. For different risk categories the incidence of bleeding (mucosal and non-mucosal bleeding) was calculated. Bleeding-free survival was computed with the Kaplan-Meier method and a Cox’s proportional hazard model was used to calculate the risk of bleeding (hazard ratio = HR) Results: In the retrospective study, 1,234/1,529 (81%) cases satisfied the inclusion criteria and were enrolled in the registry as types 1 (54%), 2 (40%) and 3 (6%).VWD diagnosis occurs in young adults (83%), mainly in women (57%). Mucosal bleeding (64%) are more frequent than hematomas or hemarthrosis (15%) but 73% of patients did not require transfusions. In the prospective study based on 814/1,234 (66%) cases of the registry (type 1=47%, 2=47%, 3=6%) 147/815 (18%) were treated in a year for 318 bleeding episodes and 87 minor or major surgeries. BSS >10 (6.8, 3.8–12.3), bleeding time >20 min (BT = 5.5, 3.1–9.8), VWF:RCo <10 U/dL (3.2, 1.7–5.9) and FVIII:C <20 U/dL (4.1, 2.4–7) were significantly associated with high risk of bleeding. By multivariate model including all the variables, BSS (5.5, 2.8–10.8) was the most significant determinant of bleeding. The bleeding-free survival at one year was significantly different in type 3 (52%) versus types 1 (96%) and 2 (91%) VWD. On the other hands, patients with VWF.RCo >30 U/dL and FVIII:C > 40 U/dL showed always BSS <5 with the lowest incidence of bleeding. A total of 292 DDAVP injections were used to manage bleeding and surgeries in types 1 (65%) and 2 (35%) VWD and 452 injections of VWF concentrates were used to treat bleeding and surgeries in type 3 (75%), type 2 (34%) and type 1 (15%) VWD. Conclusions: This prospective study confirms that BSS is an important predictive factor for clinical bleeding and the need for treatment. In cases with VWF.RCo >30 U/dL and FVIII:C >40 U/dL bleeding episodes are very rare, in agreement with their relatively low BSS.

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 Cost-Effectiveness of Long-Term Prophylaxis Versus on-Demand Treatment with Von Willebrand Factor Concentrate in Severe Inherited Von Willebrand Disease

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 4-5
Author(s):  
Anushka Bhaskar ◽  
Nathan T. Connell
Keyword(s):  
Von Willebrand Disease ◽  
Base Case ◽  
Case Scenario ◽  
On Demand ◽  
Bleeding Episodes ◽  
The Cost ◽  
Von Willebrand ◽  
Mean Cost ◽  
Prophylaxis Strategy

Introduction: von Willebrand Disease (VWD) is the most common inherited bleeding disorder with significant variability in clinical phenotype. Patients with the most severe forms of VWD suffer from frequent bleeding complications including mucosal bleeding, gastrointestinal hemorrhage, hemarthrosis, and muscle hematomas. Long-term prophylaxis with von Willebrand factor (VWF) concentrate has been shown to reduce the frequency of bleeding episodes, but higher costs associated with regular VWF concentrate administration remains a barrier to access. Methods: We constructed a Markov state transition model to compare the cost-effectiveness of on-demand treatment (ODT) with long-term prophylaxis (PRO) from a United States (US) societal perspective with costs inflated to 2020 US dollars using the Consumer Price Index. Cycle-length was one month with a one-year time horizon and during each cycle, patients could experience either major (hemarthrosis, gastrointestinal bleeding, muscle hematoma), minor (epistaxis, other mucosal bleeding), or no bleeding. Model inputs for event probabilities, costs, and utility were obtained from previously published literature; while there are no specific utility data for these treatment strategies in VWD patients, we assumed they would be similar to published age-specific utilities used in hemophilia analyses and performed sensitivity analyses to assess these assumptions. The base case scenario was modeled on a 70 kg patient with severe VWD receiving plasma-derived VWF concentrate. In the PRO strategy, patients received 60 units/kg every 3 days. ODT patients were only treated for specific bleeding events (minor bleeding: 60 units/kg every 12 hours for 3 days in the outpatient setting; major bleeding: VWF concentrate 60 units/kg every 12 hours for 5 days in the hospital). Microsimulation of 1000 trials was performed using to calculate mean quality-adjusted life-years (QALYs) and costs associated with the two treatment strategies. TreeAge Pro 2017 (TreeAge Software, Williamstown, MA) was used to construct the model and perform analyses. Results: In the base-case scenario using plasma-derived VWF concentrate, on-demand treatment resulted in a mean cost of US$1,140,586 (± $65,215) generating 0.52 QALYs (±0.01) while the prophylaxis strategy resulted in a mean cost of US$918,329 (± $94,983) generating 0.8 QALYs (±0.04). The microsimulation was repeated to reflect the cost of recombinant VWF concentrate for prophylaxis and a single dose of recombinant factor VIII. Using recombinant VWF, on-demand treatment resulted in a mean cost of US$1,568,005 (± $94206) and generated 0.52 QALYs (±0.01) while the prophylaxis strategy resulted in a mean cost of US$1,343,715 (± $124,974) and generated 0.8 QALYs (±0.04). One-way sensitivity analysis of model inputs showed this result to be robust, as prophylaxis remained the preferred strategy at a willingness to pay (WTP) threshold of US$150,000/QALY for both plasma-derived and recombinant therapies (Figure). Conclusions: With greater effectiveness and lower total societal health care costs, the prophylaxis strategy dominated the on-demand treatment strategy. While the cost of long-term prophylaxis is primarily due to the high cost of VWF concentrate every 3 days, this strategy results in significantly fewer bleeding episodes per year resulting in more QALYs. Our findings suggest that when compared to on-demand treatment, long-term prophylaxis with VWF concentrate is a cost-effective strategy in patients with severe forms of VWD, which helps to avoid expensive hospitalizations and decreased quality of life due to bleeding episodes and their complications. Figure 1 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 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.

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.

Sign in / Sign up

Export Citation Format

Share Document