French Multicenter Study for Post-Marketing Survey of WILFACTIN®: A Von Willebrand Factor Concentrate with a Low FVIII Content.

Blood ◽  
2006 ◽  
Vol 108 (11) ◽  
pp. 4052-4052
Author(s):  
Annie Borel-Derlon ◽  
Jenny Goudemand ◽  
Chantal Rothschild ◽  
Catherine Chatelanaz ◽  
Françoise Bridey ◽  
...  
Keyword(s):  
Interim Analysis ◽  
Von Willebrand Disease ◽  
Safety And Efficacy ◽  
Patients Âgés ◽  
Post Marketing ◽  
Bleeding Episodes ◽  
The Mean ◽  
Type 3 ◽  
Von Willebrand

Abstract This non-interventional study is designed to evaluate the safety and efficacy of WILFACTIN® when used for up to 3 years of treatment of bleeding episodes at hospital, for home-self treatment or prevention of surgical bleeding by patients with von Willebrand disease (VWD). The study is set up according to the Note for guidance CPMP/BPWG/220/02. Thirty six French centers enrolled 65 patients. Data from 48 patients (26 females, 22 males) were available for this 19-month interim analysis. Patients ages ranged from 11 months to 83.5 years (median, 38.5 years): 8 had type 1, 25 type 2, and 15 type 3 VWD. Baseline VWF:RCo and FVIII:C levels were less than 20 IU/dl in 37 and 20 patients respectively. The mean observation period was 155 days. A total of 1094 infusions were administered in 39 patients, 15% for spontaneous or trauma bleeds, 23% for invasive or surgical procedures, 59% for long-term prophylaxis and 3% short-term prophylaxis. The mean infusion dosage (VWF:RCo IU/kg body weight) ranged from 35.5 to 77.7 for 10 major bleeds, 23.9 to 53.2 for 25 surgeries and 27.2 to 58.2 for 8 patients with long-term prophylaxis treatment. The majority of subjects for long-term prophylaxis had type 3 VWD (6/8) and all were more than 12 years old. Indications for prophylaxis have included mucosal bleeds for 5 patients and joint bleeds for 3 patients. The number of prophylactic infusions ranged between 1 to 3 per week and these regimens, guided by the bleeding pattern of each patient, yielded favorable results in the prevention of bleeding episodes. Only 7 bleeds occurred less than 72 hours following infusion (7/642 infusions). To date (April 2006), one patient experienced 2 non serious possibly drug-related adverse events: moderate blood pressure increase with chest pain. No cases of thrombosis were reported following treatment. No cases of VWF inhibitor development. The results of this interim analysis of post-marketing survey confirm the safety and efficacy of WILFACTIN® for treatment of VWD, particularly for home self-treatment including long-term prophylaxis, and validate the results documented in previously reported clinical trials.

scholarly journals Long-Term Prophylaxis in Patients with Von Willebrand Disease and Recurrent Bleeding in Italy

Blood ◽  
2014 ◽  
Vol 124 (21) ◽  
pp. 5056-5056 ◽  
Author(s):  
Piercarla Schinco ◽  
Cultrera Dorina ◽  
Federica Valeri ◽  
Alessandra Borchiellini ◽  
Cristina Teruzzi ◽  
...  
Keyword(s):  
Conflicts Of Interest ◽  
Von Willebrand Disease ◽  
Recurrent Bleeding ◽  
Severe Bleeding ◽  
Bleeding Tendency ◽  
Transfusion Requirements ◽  
Bleeding Episodes ◽  
Type 3 ◽  
Von Willebrand

Abstract INTRODUCTION: Von Willebrand disease (VWD) is a congenital bleeding disorder caused by Von Willebrand factor (VWF) deficiency or abnormalities. Apart from administration of desmopressin in mild-moderate cases, replacement therapy with VWF/Factor VIII (FVIII) concentrates is the therapy of choice for short-term prophylaxis (STP) during surgery or clinical interventions and it is the conventional approach for Long-Term Prophylaxis (LTP) in patients with severe bleeding tendency. However, LTP with FVIII/VWF concentrates is not always effective and in some cases. Repeated infusions of FVIII/VWF concentrates may increase the risk of thromboembolic events due to FVIII:C overload. The aim of this analysis was to evaluate the effectiveness of LTP with a VWF concentrate almost devoid of FVIII:C ( vWF conc.) vs VWF/FVIII concentrate in VWD patients with a heavy bleeding phenotype. METHODS: A retrospective analysis on four VWD patients [type 3 (n= 1), type 2M (n= 1) and type 1 (n= 2)] was carried out in two Italian Hemophilia Centers. These Centers have clinical experience with VWD patients with severe bleeding tendency, on LTP, who switched from VWF/FVIII concentrates to vWF conc. in order to obtain a better control of the bleedings. The patients were included in the analysis if they fulfilled the following criteria: periodical bleeding episodes and previous prophylaxis with VWF/FVIII concentrates. The patients had been previously treated with VWF/FVIII concentrates (prophylaxis: 35-50 IU/Kg/3 times per week; bleeding episodes: 30-50 IU/Kg/day as long as needed), before starting prophylaxis with vWF conc. (prophylaxis: 30-50 IU/Kg/2 times per week and in one case 30 IU/Kg/3 times per week; bleeding episodes: 30-50 IU/Kg/day as long as needed). Data on number of bleeding episodes and hospital admittances, hemoglobin, FVIII:C levels, and number of transfusions were collected. Data after 1 year’s prophylaxis with vWF conc. were compared with those after 1 year’s prophylaxis with VWF/FVIII concentrates. RESULTS: The number of all bleeding episodes decreased by 96% (mean 14 to 0,5 episodes) and all patients showed a consistent reduction of their own bleeding frequency. Hemoglobin and FVIII:C levels respectively increased by a mean of 2,8 gr/dl (from 8,05 gr/dl to 10,85 gr/dl) and 40% (from 17% to 57%) after LTP with vWF conc. The patient transfusion requirements (number of packed red blood cell concentrate-PRBC) dropped from a mean of 3.5 to zero, and the number of ordinary hospitalizations and day hospital admittances decreased by 100% after LTP with vWF conc. (mean of 15 to 0). CONCLUSIONS: Our analysis suggests that LTP with a VWF concentrate almost devoid of FVIII is effective and well tolerated highly beneficial for patients both in terms of reduction of bleeding episodes and reduction of number of days spent in hospital with an obvious improvement of the quality of life. A collection of clinical data from a larger population of patients is required to confirm and support these results. Disclosures No relevant conflicts of interest to declare.

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.

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.

Prevalence and Determinants of Bleeding in Severe Von Willebrand Disease Type 3: Results of Retro/Prospective Studies in a Cohort of 105/52 Italian Patients.

Blood ◽  
2009 ◽  
Vol 114 (22) ◽  
pp. 3494-3494
Author(s):  
Augusto B. Federici ◽  
Paolo Bucciarelli ◽  
Alfonso Iorio ◽  
Giancarlo Castaman ◽  
Maria Gabriella Mazzucconi ◽  
...  
Keyword(s):  
Prospective Studies ◽  
Disease Type ◽  
Von Willebrand Disease ◽  
Free Survival ◽  
Risk Of Bleeding ◽  
Major Interest ◽  
Bleeding Episodes ◽  
One Year ◽  
Type 3 ◽  
Von Willebrand

Abstract Abstract 3494 Poster Board III-431 Background von Willebrand disease type 3 (VWD3) is due to virtually complete deficiency of the von Willebrand factor (VWF) and, for this reason, has been also described as “severe VWD”. Although rare (1-5 cases per million population), VWD3 is of major interest because of its severe clinical presentation, the need for replacement therapy with VWF/FVIII concentrates and the risk of occurrence of anti-VWF inhibitors after the infusion of VWF/FVIII concentrates. Aims and design of the study to determine the prevalence and determinants of bleedings requiring therapy with VWF/FVIII concentrates in VWD3 patients, data were collected from the Italian registry on Hemophilia and Allied Disorders organized on behalf of the Italian Association of Hemophilia Centers (AICE). The VWD3 patients included in the registry were then followed up for one year by six Italian Centers and prospective data on number, type and management of bleeding episodes were analyzed. Methods VWD3 patients were diagnosed when VWF antigen was undetectable and factor VIII (FVIII) levels were reduced in plasma. Bleeding severity score (BSS) was calculated at enrollment. Gene deletions and mutations were searched for in all available DNA. 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 Italian registry, 105 VWD3 patients (5.7%) were identified among the 1850 VWD (Italian prevalence=1.75 per million). The entire cohort of VWD3 was characterized by the following demographic, clinical and laboratory parameters (median, range): gender (M/F)= 50/55; age=37 (3-65); BSS=18 (3-35); FVIII= 4 (2-18); anti-VWF inhibitors= 7 cases (6.7%) from 3 families. Molecular diagnosis was available in 65/105 cases with the following gene defects (pt-n): large deletion (7); small deletions and insertions (23); nonsense (9); splice site (8) and missense mutations (17). Mucosal bleedings (64%) were more frequent than hematomas and hemarthrosis (24%). At the time of the enrollment in the registry 95/105 (91%) VWD3 had been already exposed to VWF/FVIII concentrates because of bleeding and/or minor or major surgeries. In the prospective study, 52 VWD3 patients could be enrolled and 46 (88%) were treated in a year for 118 bleeding episodes and 27 minor or major surgeries. BSS>10 (6.8, 3.8-12.3) and FVIII<10U/dL (4.1, 2.4-7) were significantly associated with high risk of bleeding. The bleeding-free survival at one year calculated according to values of BSS and FVIII levels showed 4 different KM curves with the following results: 89% (BSS=5-10&FVIII>10U/dL); 64%(BSS>10&FVIII=5-10U/dL); 59% (BSS=5-10&FVIII<10U/dL); 18%(BSS>10&FVIII<5U/dL). A total of 192 injections of VWF/FVIII concentrates were used to treat bleeding and surgeries in VWD3. Patients with anti-VWF inhibitors were off therapy during this follow-up. Conclusions these retro/prospective studies performed for the first time in a relative large cohort of patients show that also VWD3 can be very heterogeneous. BSS & FVIII levels are good predictors of bleeding. Larger multicenter studies should be organized to identify possible additional modifiers influencing the risk of bleeding in VWD3. Disclosures: No relevant conflicts of interest to declare.

Regular Replacement Therapy as Prophylaxis In Severe Forms of Von Willebrand Disease: Initial Results From the Von Willebrand Disease Prophylaxis Network (VWD PN) Study Group

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 236-236
Author(s):  
Erik Berntorp ◽  
Thomas C. Abshire ◽  
Augusto B. Federici
Keyword(s):  
Quality Of Life ◽  
Research Funding ◽  
Von Willebrand Disease ◽  
Gi Bleeding ◽  
Total Group ◽  
Primary Indication ◽  
Type 3 ◽  
Von Willebrand

Abstract 236 The bleeding patterns of severe von Willebrand Disease (VWD), mainly type 3, adversely affect short- and long-term quality of life, and may be life threatening. The index case of VWD, described by Erik von Willebrand in 1926, was a girl who had a history of serious bleeds from mucous membranes and ankles, and died during her fourth menstrual period. There is no doubt that there is a role for long-term prophylaxis with VWF-containing concentrates, but the experience is scarce and restricted to a retrospective follow-up of 37 patients in Sweden, and a few other small cohorts in Europe. All studies have shown favorable results; however, unresolved issues remain, such as to whom prophylaxis should be given, optimal dose and dose interval, and when to start. The von Willebrand Disease Prophylaxis Network (VWD PN) was formed to investigate the role of prophylaxis in clinically severe VWD that is non-responsive to other treatment(s). The VWD International Prophylaxis (VIP) Study, a combination of prospective and retrospective studies, is an initiative of the VWD PN. Using a retrospective study design, the effect of prophylaxis on bleeding frequency was studied among 39 individuals enrolled from 11 centers in Europe and North America. Data were collected from center records, diaries, and bleeding logs. The period of study was one year prior to start of prophylaxis plus at least 6 months following onset of treatment. Subject demographics, VWD type, and primary bleeding indication for prophylaxis were collected. Annualized bleeding rates were calculated for the period prior to onset of prophylaxis, during prophylaxis for the total group, and by primary bleeding indication defined as the most frequent bleeding symptom. In 4 cases, data were not available to identify the primary indication. Differences (after – before) were calculated. The Wilcoxan Signed Rank test of the differences in the medians was used. The median age (range) at onset of prophylaxis was 29 years (2 to 76). Fifty-one percent were female and 49% male. The vast majority were of European descent, 84.6%, with 12.8% and 2.6% reported as Hispanic and of African descent, respectively. Type 3 VWD accounted for the largest number: 24 (61.5%). Two subjects (5.1%) were type 1, 7 (18.0%) type 2A, 5 (12.8%) type 2B, and 1 (2.6%) type 2M. The usual number of infusions of VWF during prophylaxis was 2 to 3 times per week, with a median usual dose of 45 U VWF:RCo per kg per infusion. The median (range) number of bleeding episodes per year prior to the onset of prophylaxis was 12 (2 – 54), compared to a median (range) of 4 (0 – 24) during prophylaxis, p<0.0001. Changes in bleeding for the total group, as well as the most common primary indications for prophylaxis, are shown in the figure. In 7 cases (not included in the figure) the bleeding pattern was mixed with no primary indication (N=3), or the primary indications occurred with low frequency (N=4). Annualized bleeding rates were lower during prophylaxis for all primary indications, and significantly so (p<0.05) for joint bleeding, epistaxis and GI bleeding. When we examined the effect of prophylaxis by age for subjects <18, and those ≥18, we found that it was similar in both groups. The median number of bleeds per year during prophylaxis was significantly lower, p=0.001 and p<0.0001 respectively, compared to the number prior to prophylaxis. While the primary indications of epistaxis and joint bleeding occurred with similar frequency in both age groups, GI bleeding and menorrhagia were not reported as the primary bleeding indication for prophylaxis for anyone <18. We conclude from this international, multi-center cohort that prophylactic treatment of VWD is efficacious. A network-initiated prospective study is underway, the objectives of which are to provide guidelines for dosing, and address issues of cost-effectiveness and quality of life. Disclosures: Berntorp: CSL Behring: Honoraria, Research Funding. Abshire:CSL Behring: Honoraria, Research Funding. Federici:CSL Behring: Honoraria, Research Funding.

scholarly journals Long-Term Outcome after Joint Bleeds in Von Willebrand Disease Compared to Haemophilia A: A Post Hoc Analysis

2018 ◽  
Vol 118 (10) ◽  
pp. 1690-1700 ◽  
Author(s):  
Karin van Galen ◽  
Merel Timmer ◽  
Piet de Kleijn ◽  
Frank Leebeek ◽  
Wouter Foppen ◽  
...  
Keyword(s):  
Von Willebrand Disease ◽  
Haemophilia A ◽  
Term Outcome ◽  
Long Term Outcome ◽  
Post Hoc Analysis ◽  
Joint Health ◽  
Post Hoc ◽  
Type 3 ◽  
Von Willebrand

AbstractLong-term outcome after joint bleeds in von Willebrand disease (VWD) (von Willebrand factor activity ≤ 30 IU/dL) could differ from moderate or severe haemophilia A (HA) (factor VIII [FVIII] 1–5 IU/dL or FVIII < 1 IU/dL). We performed a post hoc analysis on Haemophilia Joint Health Score (HJHS, 0–124), X-ray Pettersson scores (PS, 0–13/joint) and the Haemophilia Activities List (HAL, 0–100), using multivariable regression to adjust for age (rate ratio [RR] or odds ratio [OR] [95% confidence interval]). We included 48 VWD (median age, 47 years, type 3 VWD, n = 19), 39 moderate HA (median, 39 years) and 59 severe HA patients (median, 25 years) with documented joint bleeds. VWD patients suffered repeated bleeding (lifetime > 5/joint) less often than moderate and severe HA patients (52% vs. 77% vs. 98%). HJHS and PS in VWD were similar to moderate HA (median HJHS 5 vs. 6, RR 0.9 [0.5–1.4] and PS > 3 of ≥ 1 joint OR 0.3 [0.1–1.4]), but better than in severe HA patients (median HJHS 5 vs. 9, RR 1.8 [1.1–2.9]; PS > 3 in any joint OR 0.1 [0.0–0.3]). Self-reported limitations in activities were comparable across VWD, moderate HA (HAL score < 95: 67% vs. 49%; OR 1.4 [0.5–3.6]) and young adults with severe HA (67% vs. 48%; OR 1.7 [0.7–4.4]). Despite fewer joint bleeds, joint outcome after joint bleeds was similar in VWD and moderate HA patients. Type 3 VWD patients had worst joint outcome, comparable to younger intensively treated severe HA patients. Limitations in activities occurred as often in VWD as in both moderate and severe HA.

Treatment of von Willebrand disease with a high-purity factor VIII/von Willebrand factor concentrate: a prospective, multicenter study

Blood ◽  
2002 ◽  
Vol 99 (2) ◽  
pp. 450-456 ◽  
Author(s):  
Pier M. Mannucci ◽  
Juan Chediak ◽  
Wahid Hanna ◽  
John Byrnes ◽  
Marlies Ledford ◽  
...  
Keyword(s):  
Factor Viii ◽  
Von Willebrand Factor ◽  
High Purity ◽  
Bleeding Time ◽  
Von Willebrand Disease ◽  
Invasive Procedures ◽  
Bleeding Episodes ◽  
Type 3 ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Among patients with von Willebrand disease (VWD) who are unresponsive to desmopressin therapy, replacement with plasma-derived concentrates is the treatment of choice. Because prospective studies are lacking, such treatment has been largely empirical. A multicenter, prospective study has been conducted in 81 patients with VWD (15 patients with type 1, 34 with type 2, and 32 with type 3 disease) to investigate the efficacy of a high-purity factor VIII/von Willebrand factor (FVIII/VWF) concentrate for treatment of bleeding and surgical prophylaxis. Two preparations of the concentrate—one virally inactivated with solvent detergent, the other with an additional heat-treatment step—were evaluated. Pharmacokinetic parameters were similar for both preparations. Using pre-established dosages based on the results of pharmacokinetic studies, 53 patients were administered either preparation for the treatment of 87 bleeding episodes, and 39 patients were treated prophylactically for 71 surgical or invasive procedures. Sixty-five (74.7%) and 10 (11.5%) of the bleeding episodes were controlled with 1 or 2 infusions, respectively. Patients with severe type 3 VWD typically required more infusions and higher doses, at shorter time intervals, than did patients with generally milder types 1 and 2. Among patients undergoing surgical procedures, blood loss was lower than that predicted prospectively, and losses exceeding the predicted value did not correlate with the postinfusion skin bleeding time. In conclusion, the concentrate effectively stopped active bleeding and provided adequate hemostasis for surgical or invasive procedures, even in the absence of bleeding time correction.

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