Clinical Efficacy and Safety of Wilate®, A New Generation, High-Purity VWF/FVIII-Concentrate with Optimized Pharmacokinetic Properties in the Treatment of Von Willebrand Disease.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 1795-1795
Author(s):  
Jerzy Windyga ◽  
Antoaneta Zarkova ◽  
Olaf Walter ◽  
Guenter Auerswald
Keyword(s):  
Clinical Efficacy ◽  
Surgical Procedures ◽  
High Purity ◽  
Clinical Judgment ◽  
Von Willebrand Disease ◽  
Average Dose ◽  
Efficacy And Safety ◽  
New Generation ◽  
Type 3 ◽  
Von Willebrand

Abstract Purpose: Wilate® represents a new generation VWF/FVIII-concentrate for the treatment of von Willebrand patients with high purity and two independent virus inactivation steps. The high purity of the product was developed to preserve the functionality of Wilate®’s VWF/FVIII complex at a physiological ratio of about 1:1. Methods: A prospective multicenter study is conducted in 47 VWD patients to investigate the pharmacokinetics (PK) and clinical efficacy and safety of Wilate® in acute bleedings and surgical prophylaxis. For PK studies, plasma levels of VWF:RCo, FVIII:C, VWF:Ag were measured up to 72 hrs after injection of 50 IU of FVIII/kgBW. Clinical efficacy and tolerability was rated on a four-point scale. Final decisions on dosing were based on the investigators’ clinical judgment. Summary of results: Mean half-life of VWF:RCo in type 3 patients (n=9) was 17.1 hrs. Mean recovery for VWF:RCo was 1.5 [% per IU/kg] and 2.0 [% per IU/kg] for FVIII:C. The clearance for VWF:RCo was 2.5 [ml/h/kg] for all and 3.9 [ml/h/kg] in type 3 patients. 33 patients have been treated for a total number of 658 bleeds. Of these, 31 patients (69%) were type 3 patients. The average dose/kgBW/ED was calculated to 29.3 IU FVIII:C. Furthermore efficacy and safety was studied in 16 patients undergoing 24 surgical procedures. The overall efficacy (achievement of haemostasis) of Wilate® was rated as excellent or good for 23/24 procedures (96%). One patient with a laparoscopic cholecystectomy required two additional blood transfusions. The tolerability was assessed as very good/good by investigators and patients in all surgical cases. Conclusion: Wilate® documented favourable PK-properties in VWD patients. The interim results of these prospective clinical studies demonstrate the safety and efficacy of the double-virus-inactivated Wilate® for the treatment of acute bleeding episodes and surgical procedures in patients with VWD.

Efficacy, Safety and Tolerability of a Novel High-Purity, Double Virus-Inactivated VWF/FVIII-Concentrate in the Treatment of Von Willebrand Disease (VWD) - Clinical Experience in the Treatment of Bleeding and Surgery.

Blood ◽  
2007 ◽  
Vol 110 (11) ◽  
pp. 2144-2144
Author(s):  
B.A. Schwartz ◽  
J. Windyga ◽  
M. von Depka ◽  
O. Walter ◽  
M. Jansen ◽  
...  
Keyword(s):  
Clinical Efficacy ◽  
Surgical Procedures ◽  
Von Willebrand Disease ◽  
Efficacy And Safety ◽  
Open Label ◽  
Prophylactic Regimen ◽  
Acute Bleeding ◽  
Good Efficacy ◽  
Bleeding Episodes ◽  
Type 3

Abstract Introduction: Wilate is a highly purified, double viral inactivated, VWF/FVIII-concentrate developed for the treatment of VWD. A program of prospective studies was conducted in VWD patients to investigate the clinical efficacy and safety of Wilate® in acute bleeding episodes, prophylaxis and surgical procedures. Methods: In these prospective open label studies 70 VWD patients (37 VWD of type 3) were treated with the VWF/FVIII concentrate Wilate and followed to assess clinical efficacy and tolerability. Dosing and monitoring were performed using FVIII assays. This is standard practice in most of the study sites and was feasible because of the product’s physiological 1:1 ratio and parallel PK profiles of FVIII and VWF. Dosing decisions were based on established guidelines and the investigators’ clinical judgment. The efficacy of the product was rated on a four-point scale by the investigator. Results: Bleeding- 43 patients (25 of type 3) were treated for a total number of 1088 bleeding episodes (BE). The median dose per exposure day (ED) was calculated to be 31 IU VWF/FVIII:C/kg and were treated for a median of 1.2 days, with excellent or good efficacy achieved in 96% of treatments. Surgery- Efficacy and safety was also studied in 31 VWD patients who underwent 54 elective or urgent surgical procedures of which 27 were classified as major; the overall efficacy was rated as excellent or good in most cases (94%), with a mean dose per infusion being 34 IU VWF/FVIII:C/kg. Pediatric Use- A total of 8 children below 12 years of age with 310 BE s were treated, with an excellent/good efficacy in 98% of bleedings. Prophylaxis- 19 patients were on a prophylactic regimen for more than 10 consecutive weeks (total of 2,338 ED), with an overall reduction of bleeding frequency. Tolerability - Out of 5,662 rated infusions in all studies, the tolerability was assessed as “very good” or “good” in 99% of the cases. Conclusions: The results of the prospective clinical trial program demonstrate the safety, efficacy and tolerability of this VWF/FVIII concentrate for the treatment of acute bleeding episodes, prophylaxis and surgical procedures in patients with VWD.

scholarly journals Efficacy and safety of a VWF/FVIII concentrate (wilate®) in inherited von Willebrand disease patients undergoing surgical procedures

Haemophilia ◽  
2016 ◽  
Vol 23 (2) ◽  
pp. 264-272 ◽  
Author(s):  
A. Srivastava ◽  
M. Serban ◽  
S. Werner ◽  
B. A. Schwartz ◽  
C. M. Kessler ◽  
...  
Keyword(s):  
Surgical Procedures ◽  
Von Willebrand Disease ◽  
Efficacy And Safety ◽  
Von Willebrand

Clinical Efficacy and Safety Versus Biological Response of Desmopressin (DDAVP) In Inherited Von Willebrand Disease (VWD) Types 1 and 2: Initial Results From the International Study Group on DDAVP In VWD In a Cohort of 229 Patients

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 238-238
Author(s):  
Augusto B. Federici ◽  
Alfonso Iorio ◽  
Giancarlo Castaman
Keyword(s):  
Clinical Efficacy ◽  
Demographic Data ◽  
Biological Response ◽  
Working Party ◽  
Von Willebrand Disease ◽  
Efficacy And Safety ◽  
Inclusion Criteria ◽  
Excessive Bleeding ◽  
Baseline Levels ◽  
Von Willebrand

Abstract Abstract 238 Background: Desmopressin (DDAVP) is the treatment of choice for most patients with mild-moderate forms of von Willebrand Disease (VWD) because it can induce the release of von Willebrand Factor (VWF) from cellular compartments. However, despite the widespread use of DDAVP since 1977, there are only a few prospective clinical trials aimed at determining benefits and limits of this approach. Aims and design of the study: To correlate efficacy and safety with biological response of DDAVP in a large cohort of VWD1 and VWD2 patients followed-up for 24 months in a prospective observational study organized on behalf of the Working Party on DDAVP in VWD of the ISTH-SSC on VWF and of Italian Association of Hemophilia Centers (AICE). The study is registered at the EMEA with number EudraCT-2005-004496-38. Patients and Methods: VWD patients were enrolled after obtaining Ethical approval from local IRB. Inclusion criteria: inherited VWD without any age restriction, with previous diagnosis of VWD1 and VWD2 according to ISTH recommendations. Biological response: At enrollment patients were exposed to 0.3 ug/kg DDAVP intravenous injection and to blood withdrawal for measuring VWF/FVIII activities before and after 0.5, 1, 2 and 4 hours. Complete: both VWF:RCo and FVIII:C >50 IU/dL at 2 hours; partial: VWF:RCo or FVIII:C <50 IU/dL but increased at least 3-fold; absent: neither criterion. Clinical Response. Excellent: no excessive bleeding; Good: excess bleeding without need for VWF concentrate; Poor: excess bleeding with need for VWF concentrate. Statistical analyses were performed only on confirmed patients after the blind and independent evaluation by 2 members of the Steering Committee on these criteria: VWD=baseline levels of VWF:RCo <55 U/dL; VWD2= baseline VWF:RCo/Ag ratio≤ 0.6; VWD1 accelerated clearance: rapid increase of VWF:RCo/FVIII after 0.5–1 hrs with return to baseline levels after 2–4 hrs. Results: 229/268 (85%) patients enrolled at 13 participating Centers in Argentina, Brazil, Canada, Germany, Italy and Hungary were found to meet the inclusion criteria. Demographic data and lab tests (mean+SD) at baseline were as follows: Among VWD2, VWD2A(n=15), VWD2B(n=1), VWD2M(n=12), VWD2N(n=3) were identified. Biological response was complete, partial and absent in 89%, 10% and 1% of VWD and correlated with baseline levels of VWF:RCo<30 U/dL (Fisher's exact =0.001). Among VWD1, those (n=15) with C1130F and R1205H mutations showed accelerated clearance. During the 24-month follow-up, 62/86 (72%) patients received >1 injection of DDAVP for bleedings (n=102), deliveries (n=13), dental extractions (n=27), minor/major surgeries (n=46). Total number of injections was 652 with median, range/episode during bleedings (2,1-12), deliveries (3,1-3), dental extractions (1,1-6), surgeries (3.6,1-11). Clinical efficacy was excellent/good in bleedings (92%), deliveries (85%), dental extractions (100%), surgeries (91%). Poor efficacy was observed in 6 cases with VWD2A (n=4) during GI bleedings (n=3) or abdominal surgery (n=1) and VWD1 (n=2) during deliveries and surgery. Side effects observed in 16 patients were mainly minor, such as headache, facial flushing and tachycardia; water retention was reported in 2 cases (1 delivery, 1 surgery) only after >6 injections of the drug. Conclusions: Based on the results of this prospective clinical trial, we confirm that DDAVP is an effective and safe drug at low costs for managing patients with VWD1 and VWD2 once tested for their biological response: therefore it should be always considered as the first approach during bleedings and major/minor surgeries in responsive VWD patients. Disclosures: Federici: CSL Behring: Honoraria, Research Funding.

Safety and Effectiveness of Desmopressin for the Management of Delivery and Major Surgery in Patients with Mild-Moderate Von Willebrand Disease: Final Analysis of the Prodeswil Study

Blood ◽  
2015 ◽  
Vol 126 (23) ◽  
pp. 759-759
Author(s):  
Augusto Bramante Federici ◽  
Giancarlo Castaman ◽  
Alfonso Iorio ◽  
Emily Oliovecchio ◽  
Prodeswil Investigators
Keyword(s):  
Side Effects ◽  
Clinical Efficacy ◽  
Oral Surgery ◽  
Biological Response ◽  
Von Willebrand Disease ◽  
Major Surgery ◽  
Efficacy And Safety ◽  
Inclusion Criteria ◽  
Bleeding Episodes ◽  
Von Willebrand

Abstract Introduction. Despite the fact that desmopressin (DDAVP) is considered the treatment of choice in the majority of patients with inherited von Willebrand disease (VWD), there are still open questions about the efficacy and safety of the use of DDAVP to manage recurrent bleeding episodes, delivery and major surgery. In fact, to avoid tachyphylaxis and possible side effects with repeated DDAVP injections, VWF concentrates are usually preferred to manage delivery and major surgery also in VWD patients proven to be DDAVP-responsive. No prospective data have been reported so far to correlate biological response with DDAVP clinical efficacy in VWD and guide clinical practice. Design, aims and methods. ProDesWilis an investigator-driven Pro spective study on D esmopressin e fficacy and s afety of patients with inherited von Wil lebrand disease assessed at enrolment for DDAVP biological response during a test-infusion. Inclusion criteria: VWD diagnosis without any age restriction according to bleeding score >4, VWF activity levels <45U/dL, and at least another affected member in the family. DDAVP Biological Response: VWD were classified as complete, partial or no-responders as previously reported (Blood 2008;111:3531). Treatment regimens: DDAVP given intravenously or subcutaneously (0.3 ug/Kg) or by nasal spray (4 ug/Kg) according to preparations available in different countries with or without standard doses of anti-fibrinolytic agents (Epsilon-amino-caproic acid, EACA or tranexamic acid, TA). In case of major surgery, DDAVP was used together with TA using a 3dayOn-4dayOff-3dayOn schedule. DDAVP efficacy-safety evaluated with criteria currently used for VWF concentrates, with poor efficacy defined when VWF concentrates were needed. Patients were prospectively followed up for 24 months by ProDesWil Investigators who reported detailed information about DDAVP therapy used for bleeds, deliveries, oral and minor/major surgeries Results. 268 patients were enrolled in this 24-month prospective study. DDAVP-biological response: 225/268 (85%) patients met inclusion criteria as VWD1(n=184), VWD1C (n=14), VWD2A(n=15), VWD2M(n=12). The 14 VWD1C with accelerated clearance carried C1130F and R1205H mutations. DDAVP biological response was complete, partial and absent in 89%, 10% and 1% of all VWD. DDAVP clinical efficacy and safety: during the 24-month follow-up 84/225 (37.3%) received DDAVP for bleeding episodes (n=104), oral surgeries (n=33), deliveries (n=12), other minor/major surgeries (n=25). Total DDAVP injections were 652 with median, range/episode during bleeds (2,1-12), oral surgeries (1,1-10), deliveries (3,1-13), minor/major surgeries (3.6,1-16). Clinical efficacy was excellent/good in bleeds (93.3%), oral surgery (100%), deliveries (91.7%), minor/major surgeries (92.3%). All VWD treated for oral surgery with (75%) and without (25%) EACA/TA had excelled/good outcomes. Efficacy was rated excellent/good in 96/104 bleeds, with 8 episodes rated poor during menorrhagia (n=4) in 2 VWD1 and 2 VWD2A, during nose (n=2) and gastrointestinal (n=2) bleeds in 3 VWD2A and 1 VWD1C. 11/12 deliveries had excellent/good outcome with poor response in only one VWD1C who required VWF concentrates after caesarean section. All the 11/25 cases with minor surgeries had excellent outcomes. Among the 14/25 major surgeries [abdominal (n=5), hysterectomy (n=3), tonsillectomy (n=3), orthopaedic and others (n=3)] 2 episodes (partial resection of kidney in VWD2A and tonsillectomy in VWD1) were rated poor. Side effects (16 cases) were mainly minor (flushing, headache, tachycardia) with water retention reported only in 2 patients who received >12 doses of DDAVP for delivery or major surgery. Conclusions: DDAVP is an effective, safe and cheap treatment for managing patients with mild-moderate VWD who showed complete biological response to this drug. Therefore, DDAVP must be always recommended as first line therapy in responsive VWD not only in bleeds and oral surgery but also in deliveries and major surgeries. On the other hands, DDAVP should be used with caution in VWD2A and VWD1 with partial response. The additional use of EACA/TA should be considered especially when DDAVP is required for more than 4 days. Disclosures No relevant conflicts of interest to declare.

Efficacy and safety of a new generation von Willebrand factor/factor VIII concentrate (Wilate®) in the management of perioperative haemostasis in von Willebrand disease patients undergoing surgery

2011 ◽  
Vol 105 (06) ◽  
pp. 1072-1079 ◽  
Author(s):  
Mario von Depka-Prondzinski ◽  
Jerzy Windyga ◽  
Keyword(s):  
Factor Viii ◽  
Von Willebrand Factor ◽  
Perioperative Management ◽  
Von Willebrand Disease ◽  
Major Surgery ◽  
Open Label ◽  
New Generation ◽  
Type 3 ◽  
Von Willebrand ◽  
Willebrand Factor

SummaryThe aim of this study was to assess the efficacy of Wilate®, a new generation, plasma-derived, high-purity, double virus-inactivated von Willebrand factor (VWF) and factor VIII (FVIII) concentrate (ratio close to physiological 1:1) in the perioperative management of haemostasis in von Willebrand disease (VWD). Data for VWD patients who received Wilate® for perioperative management were obtained from four European, prospective, open-label, non-controlled, non-randomised, multicentre phase II or III clinical trials. A total of 57 surgical procedures were performed (major: n = 27; minor n = 30) in 32 patients. The majority of patients (n = 19, 59.4%) had type 3 VWD, 9 (28.1%) had type 2 VWD and four (12.5%) had type 1 VWD. During major surgery, median daily FVIII dose and mean number of infusions were 25 IU•kg-1 FVIII (VWF:RCô23 IU•kg-1) and 11.0, respectively. Corresponding values for minor surgery were 35 IU•kg-1 (VWF:RCo ~32 IU•kg-1) and 1.5. The efficacy of Wilate® was rated by the investigator as excellent or good in 51 of 53 (96%) procedures. Tolerability was rated as very good or good in 100% of major surgeries (27 of 27) and minor surgeries (29 of 29). Wilate® is an effective and well-tolerated VWF/FVIII replacement therapy in the perioperative management of haemostasis in patients with VWD. It can be administered at a similar FVIII dose, but at a lower VWF dose, as compared to older generation products. Clinical benefits were shown in a population with a high proportion of type 3 VWD patients.

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.

Efficacy and safety of a recombinant Von Willebrand Factor treatment in patients with inherited Von Willebrand Disease requiring surgical procedures

Haemophilia ◽  
2021 ◽  
Vol 27 (2) ◽  
pp. 270-276
Author(s):  
Dominique Desprez ◽  
Nicolas Drillaud ◽  
Claire Flaujac ◽  
Fabienne Volot ◽  
Brigitte Pan‐Petesch ◽  
...  
Keyword(s):  
Surgical Procedures ◽  
Von Willebrand Factor ◽  
Von Willebrand Disease ◽  
Efficacy And Safety ◽  
Von Willebrand ◽  
Willebrand Factor

scholarly journals Prospective Observation on the Use of Von Willebrand Factor (VWF) Concentrates in a Large Cohort of Type 3 Von Willebrand Disease (VWD): Interim (18-months) Analyses on 149 Cases Enrolled into the 3Winters-Ips Project

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2464-2464
Author(s):  
Augusto B Federici ◽  
Zahra Badiee ◽  
Mohammad-Reza Baghaipour ◽  
Giancarlo Castaman ◽  
Peyman Eshghi ◽  
...  
Keyword(s):  
Prospective Study ◽  
Research Funding ◽  
Advisory Board ◽  
Von Willebrand Disease ◽  
Large Cohort ◽  
Efficacy And Safety ◽  
The Mean ◽  
Type 3 ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Although rare, type 3 von Willebrand disease (VWD3) is of major interest because of its severe clinical presentation, the need for replacement therapy with von Willebrand Factor (VWF) concentrates and the risk of anti-VWF inhibitors. To better characterize the clinical and laboratory features of this rare inherited bleeding disorder, a large cohort of VWD3 patients has been enrolled into the type 3 Von Willebrand International RegistrieSInhibitor Prospective Study. 3WINTERS-IPS is a no-profit, investigators initiated, multicenter, European-Iranian (EU-IR) observational, retrospective and prospective study on patients with VWD3 diagnosis. One of the aims of 3WINTERS-IPS is to assess the efficacy and safety of VWF concentrates with or without FVIII, including the risk of anti-VWF antibodies, in a large cohort of centrally confirmed VWD3 patients. A total of 260 previously diagnosed VWD3 cases were enrolled into the study from 18-EU and 7-IR investigation sites (retrospective registries) and reassessed by 5 expert labs for phenotypic and genotypic analyses to confirm VWD3 diagnosis (central confirmation). Only 201/260 (77%) cases with centrally confirmed VWD3 diagnosis were included into the 24-month clinical observation (prospective phase) registered as NCT02460458 into Clinical-Trials.gov. All the clinical and laboratory data were reported by investigators into the database online organized by a CRO under the direct supervision of the Scientific Coordinators. Clinical results on the efficacy and safety of VWF concentrates during the first 18-month observation are currently available on 149/201 (74%) VWD3 patients (EU=62/IR=87) with the following sex (M/F) and age (Mean-SD, Median) distribution: 86/115 and 28.9-18, 27. Anti-VWF antibodies were confirmed in 16/201 (8%) VWD3: these patients are under treatment with recombinant FVIII without VWF or recombinant activated Factor VII. Being 3WINTERS-IPS a non-interventional study, the therapeutic approaches such as on demand (OD) or secondary long-term prophylaxis (SLTP) with the assigned VWF concentrates with or without FVIII (FANHDI, HAEMATE-P, WILATE, WILFACTIN) were decided by local investigators. The number of VWD3 treated OD/SLTP were 106/43 with more cases under SLTP at EU than at IR sites (28/15). Cases under OD/SLTP with bleeds were 73/106(69%) of OD and 21/43(48%) of SLTP. To compare the results of OD/SLTP groups, data obtained were divided by case number and by months to calculate the mean (range) annual bleeding rate (ABR). ABR observed so far in OD/SLTP is 4.3 (2.8-5.8)/3.1(1.4-3.8) with nose (29/28%), joint (19/24%), uterus (13/23%) bleeds being the most frequent sites. To manage (OD) or prevent (SLTP) bleeds the mean (range) consumption of VWF:RCo units of VWF concentrates per patient were 4800 (1800-15.500) and 8000 (5000-10.500) units, respectively. During follow-up VWD3 patients under OD/SLTP were exposed to 17/10 minor/major surgeries with 14.900 (9.500-22.000)/17.200 (12.800-31.000) VWF:RCo Units used per surgery. Efficacy of the different VWF concentrates was reported as good/excellent during bleeds and surgeries. No side effects related to VWF concentrates were reported by investigators: no additional anti-VWF antibodies were found after the use of VWF concentrates. Based on this interim analyses on the largest cohort of VWD3 currently under prospective observation, the frequency of spontaneous bleeds assessed by ABR seems lower than expected by the severe VWF defect of VWD3. So far, the use of SLTP seems to reduce the ABR. However, a longer prospective observation (from 2 to 5 years) with 3WINTERS-IPS-EXTENDED is required to characterize bleeding phenotype of VWD3 patients and to prepare recommendations on the appropriate use (OD/SLTP) of the VWF concentrates Disclosures Leebeek: Uniqure: Research Funding; Baxalta/Shire: Research Funding; CSL Behring: Research Funding. Peyvandi:Kedrion: Consultancy; Kedrion: Consultancy; Kedrion: Consultancy; Novo Nordisk: Speakers Bureau; Novo Nordisk: Speakers Bureau; Grifols: Speakers Bureau; Ablynx: Other: Member of Advisory Board, Speakers Bureau; Ablynx: Other: Member of Advisory Board, Speakers Bureau; Grifols: Speakers Bureau; Ablynx: Other: Member of Advisory Board, Speakers Bureau; Ablynx: Other: Member of Advisory Board, Speakers Bureau; Octapharma US: Honoraria; Roche: Speakers Bureau; Shire: Speakers Bureau; Ablynx: Other: Member of Advisory Board, Speakers Bureau; Kedrion: Consultancy; Grifols: Speakers Bureau; Kedrion: Consultancy; Novo Nordisk: Speakers Bureau; Grifols: Speakers Bureau; Grifols: Speakers Bureau; Novo Nordisk: Speakers Bureau; Roche: Speakers Bureau; Novo Nordisk: Speakers Bureau; Roche: Speakers Bureau; Roche: Speakers Bureau; Shire: Speakers Bureau; Sobi: Speakers Bureau; Roche: Speakers Bureau; Shire: Speakers Bureau; Shire: Speakers Bureau; Octapharma US: Honoraria; Sobi: Speakers Bureau; Sobi: Speakers Bureau; Shire: Speakers Bureau; Sobi: Speakers Bureau; Octapharma US: Honoraria; Octapharma US: Honoraria; Sobi: Speakers Bureau; Octapharma US: Honoraria. Eikenboom:CSL: Research Funding.

Clinical Use of a Von Willebrand Factor with a Low FVIII Content in Von Willebrand Disease Patients Undergoing Surgical Procedures or Deliveries: Results From 5 Prospective Multicenter Studies

Blood ◽  
2011 ◽  
Vol 118 (21) ◽  
pp. 383-383
Author(s):  
Annie Borel-Derlon ◽  
Augusto B. Federici ◽  
Jenny Goudemand ◽  
Catherine Chatelanaz ◽  
Celine Henriet ◽  
...  
Keyword(s):  
Surgical Procedures ◽  
Von Willebrand Disease ◽  
Surgical Prophylaxis ◽  
Multicenter Studies ◽  
Daily Dose ◽  
Median Daily Dose ◽  
Type 3 ◽  
Von Willebrand ◽  
Willebrand Factor

Abstract Abstract 383FN2 Introduction: Von Willebrand disease (VWD), the inherited bleeding disorder is related to a quantitative or functional defect of von Willebrand factor (VWF). As VWF serves as a carrier for factor VIII (FVIII) in plasma, some VWD types involve low FVIII binding and thus low FVIII levels. International consensus confirms that VWF:RCo is the main predictor in controlling bleeding from mucous membranes in VWD patients. On the other hand, it is recognized that FVIII is the main factor involved in surgical hemostasis. Conversely, high levels of FVIII may increase thrombogenic risk. Thus, the management of surgical procedures in all VWD types needs to be evaluated in terms of coadministration of exogenous FVIII. We report the efficacy and safety of a high purity plasma-derived, triple-secured, VWF concentrate with a low FVIII content (WILFACTIN/ WILLFACT) in preventive treatment of bleeding during surgical procedure and delivery in patients when desmopressin treatment alone is ineffective or contra-indicated. Methods: Five prospective multicenter studies including one post-marketing study were conducted between January 1999 and July 2009. Data from 4 completed prospective multicenter studies and data from one interim analysis were pooled and analyzed. The investigators were asked to assess efficacy according to the clinical response at time of hospital discharge. Results: One hundred and forty one patients (51 males, 90 females) with a mean age of 35 years (1–84) and body weight of 66 kg (10–120) underwent 215 procedures (206 surgeries and 9 deliveries by natural route). A total of 52 (37%) patients had basal FVIII:C levels <20% whereas 43 (30%) had >40%: 29 patients (21%) had type 1 VWD; 81 (57%), type 2; 27 (19%), type 3; and 4 (3%), unspecified. Dental procedures (54) represented a quarter of the procedures. Others were gyneco-obstetrical (45), orthopedic (37), digestive (35), general (28) and other location (16). As shown in Table 1, baseline FVIII levels were corrected before surgery if necessary, in 155/214* (72 %) of the procedures, either by capturing natural FVIII activity after a 12–24 h lag-time post VWF infusion (83 procedures) or by FVIII concentrate co-administered with WILFACTIN/ WILLFACT (72 procedures). The VWF concentrate was always administered alone after the procedure, due to enhanced stabilization of endogenous FVIII. For type 3, the median daily dose and mean number of infusions, including post-surgical prophylaxis, were 55 IU/kg and 6.0 respectively, while for type 1 and 2, the median daily dose was 47 and 53 IU/kg respectively and 4 infusions. Hemostatic efficacy was rated as excellent (114) or good (29) in 99% of evaluated procedures (n=144). Fifteen patients received packed red cells in addition to the concentrate. The overall tolerability was very good; neither VWF inhibitor nor thrombotic complications were reported. Conclusions: Based on prospective studies conducted in a large cohort of European patients (N=141), a VWF with a low FVIII content (WILFACTIN/WILLFACT) was shown to be effective and safe for the clinical management of patients with various types of VWD administered for surgical prophylaxis and delivery. Disclosures: No relevant conflicts of interest to declare.

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