scholarly journals Social participation is reduced in type 3 Von Willebrand disease patients and in patients with a severe bleeding phenotype

Haemophilia ◽  
2021 ◽  
Author(s):  
Eva K. Kempers ◽  
Calvin B. Kwawegen ◽  
Joke Meris ◽  
Saskia E. M. Schols ◽  
Karin P. M. Galen ◽  
...  
Keyword(s):  
Social Participation ◽  
Von Willebrand Disease ◽  
Severe Bleeding ◽  
Type 3 ◽  
Von Willebrand

scholarly journals Clustering of Bleeding Symptoms in Patients Previously Diagnosed As Type 3 Von Willebrand Disease: Results from a Large Cohort of Type 3 Von Willebrand Disease (the 3Winters-Ips Project)

Blood ◽  
2018 ◽  
Vol 132 (Supplement 1) ◽  
pp. 2465-2465
Author(s):  
Alberto Tosetto ◽  
Zahra Badiee ◽  
Mohammad-Reza Baghaipour ◽  
Luciano Baronciani ◽  
Javier Battle ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Advisory Board ◽  
Von Willebrand Disease ◽  
Severe Bleeding ◽  
Advisory Committees ◽  
Bleeding Score ◽  
Type 3 ◽  
Von Willebrand

Abstract Patients with type 3 von Willebrand Disease (VWD) usually have markedly reduced FVIII/VWF levels and very severe bleeding manifestations but, because of their rarity, their bleeding phenotype is poorly described. We aimed at evaluating the distribution of bleeding symptoms in patients with type 3 VWD, comparing them with previously available data from a cohort of type 1 patients, and describing site-specific clustering of bleeding symptoms in these patients. We analyzed clinical data from the type 3 Von Willebrand International RegistrieS Inhibitor Prospective Study (3WINTERS-IPS),a no-profit, investigators initiated, multicenter, European-Iranian observational, retrospective and prospective study on patients with diagnosis of type 3 VWD. Aims of the 3WINTERS-IPS is 3-fold: a) to identify the main phenotypic and molecular characteristics of a large cohort of VWD patients; b) to evaluate the risk factors responsible for the severe bleeding phenotype; c) to assess the efficacy and safety of the treatment with VWF concentrates with or without FVIII including the risk of anti-VWF antibodies. Retrospective information on bleeding symptoms at presentation was collected using the MCMDM-1 VWD bleeding questionnaire, and bleeding severity summarized as bleeding score. Individual bleeding symptoms were considered as relevant when having a score >1 (hence requiring medical attention). Data was compared with that retrieved from the MCMDM-1 VWD study database on patients affected by type 1 VWD (index cases and affected family members). The study enrolled a total of 260 patients, of which we analysed 243 patients with available bleeding score at recruitment. The median age at study inclusion was 29 years (interquantile range, 26.5 years); 140 were females (53.8%). There were 108 patients of Iranian descent, while the remaining of patients were from Europe. The median number of bleeding symptoms was 5, and the median bleeding score was 15 (interquantile range, 13). Only 7/243 patients (2.8%) had a single bleeding symptom. Epistaxis was the most frequent relevant symptom, being present in 195 patients (80.2%), followed by menorrhagia in 99 females (70.7%). Males had a higher frequency of hemarthroses and hematomas than females (53.4% vs 42.1% and 40.8% vs 27.1%, respectively). When comparing the clinical presentation of type 3 vs. type 1 VWD, clearly increased bleeding scores were evident for all age-classes and even in paediatric cases. The association between symptoms having a relative frequency >20% is presented in the circle diagram, showing that some symptoms appeared to cluster with others in a variable degree (e.g., menorrhagia with epistaxis, hemarthrosis or oral cavity bleeding; post-extraction bleeding again with epistaxis, hemarthrosis or oral cavity bleeding; surgical bleeding or gastrointestinal bleeding with epistaxis alone). These findings confirm the severity of type 3 VWD and extend the knowledge of symptoms distribution in the widest available cohort of type 3 VWD patients. Disclosures Tosetto: Stago, Novo-Nordisk, BMS: Speakers Bureau; Werfen: Other: Member of Advisory Board, Speakers Bureau. Berntorp:Octapharma: Consultancy; CSL Behring: Consultancy; Shire: Consultancy, Other: honoraria for lecturing . Eikenboom:CSL: Research Funding. Mazzucconi:Baxalta-Shire: Consultancy, Speakers Bureau; Bayer: Consultancy, Speakers Bureau; Novartis,: Consultancy, Speakers Bureau; Amgen: Consultancy, Speakers Bureau; Novo Nordisk: Consultancy, Speakers Bureau; CSL Behring: Consultancy, Speakers Bureau. Oldenburg:Pfizer: Honoraria, Membership on an entity's Board of Directors or advisory committees; Biogen Idec: Honoraria, Membership on an entity's Board of Directors or advisory committees; Chugai: Honoraria, Membership on an entity's Board of Directors or advisory committees; Grifols: Honoraria, Membership on an entity's Board of Directors or advisory committees; Roche: Honoraria, Membership on an entity's Board of Directors or advisory committees; Shire: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Octapharma: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Novo Nordisk: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; CSL Behring: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Biotest: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Bayer: Honoraria, Membership on an entity's Board of Directors or advisory committees, Research Funding; Swedish Orphan Biovitrum: Honoraria, Membership on an entity's Board of Directors or advisory committees, Speakers Bureau. Peyvandi:Kedrion: Consultancy; Ablynx: Other: Member of Advisory Board, Speakers Bureau; Shire: Speakers Bureau; Roche: Speakers Bureau; Shire: Speakers Bureau; Kedrion: Consultancy; Kedrion: Consultancy; Ablynx: Other: Member of Advisory Board, Speakers Bureau; Grifols: Speakers Bureau; Roche: Speakers Bureau; Octapharma US: Honoraria; Octapharma US: Honoraria; Sobi: Speakers Bureau; Ablynx: Other: Member of Advisory Board, Speakers Bureau; Kedrion: Consultancy; Shire: Speakers Bureau; Roche: Speakers Bureau; Roche: Speakers Bureau; Novo Nordisk: Speakers Bureau; Shire: Speakers Bureau; Ablynx: Other: Member of Advisory Board, Speakers Bureau; Grifols: Speakers Bureau; Shire: Speakers Bureau; Ablynx: Other: Member of Advisory Board, Speakers Bureau; Grifols: Speakers Bureau; Novo Nordisk: Speakers Bureau; Octapharma US: Honoraria; Octapharma US: Honoraria; Sobi: Speakers Bureau; Grifols: Speakers Bureau; Grifols: Speakers Bureau; Kedrion: Consultancy; Sobi: Speakers Bureau; Roche: Speakers Bureau; Novo Nordisk: Speakers Bureau; Novo Nordisk: Speakers Bureau; Novo Nordisk: Speakers Bureau; Sobi: Speakers Bureau; Octapharma US: Honoraria; Sobi: Speakers Bureau. Schneppenheim:SHIRE: Consultancy; CSL Behring: Consultancy. Tiede:Alnylam, Bayer, Biogen Idec, Biotest, Bristol-Myers-Squibb, Boehringer Ingelheim, CSL Behring, Leo Pharma, Novo Nordisk, Octapharma, Pfizer, Roche, Shire, and SOBI: Consultancy; Alnylam, Bayer, Biogen Idec, Biotest, Bristol-Myers-Squibb, Boehringer Ingelheim, CSL Behring, Leo Pharma, Novo Nordisk, Octapharma, Pfizer, Roche, Shire, and SOBI: Honoraria; Alnylam, Bayer, Biogen Idec, Biotest, Bristol-Myers-Squibb, Boehringer Ingelheim, CSL Behring, Leo Pharma, Novo Nordisk, Octapharma, Pfizer, Roche, Shire, and SOBI: Research Funding.

Coinheritance of Severe von Willebrand Disease With Glanzmann Thrombasthenia

2010 ◽  
Vol 16 (5) ◽  
pp. 529-532 ◽  
Author(s):  
Firdos Ahmad ◽  
Meganathan Kannan ◽  
Kamal Kishor ◽  
Renu Saxena
Keyword(s):  
Replacement Therapy ◽  
Dna Analysis ◽  
Von Willebrand Disease ◽  
Severe Bleeding ◽  
Glanzmann Thrombasthenia ◽  
Truncating Mutation ◽  
Coagulation Tests ◽  
Hemostatic Disorders ◽  
Type 3 ◽  
Von Willebrand

A 35-years old male patient presented severe bleeding was diagnosed to have type 3 von Willebrand disease (VWD) and carrier for Glanzmann thrombasthenia (GT). Propositus and family members were studied through basic coagulation tests and genomic DNA analysis. Two offspring of the family were diagnosed to have GT through platelet aggregation along with VWD carrier. The patient with VWD was found positive for homozygous truncating mutation R1659X in VWF gene, and all offspring were heterozygous carriers of null allele. Hence, propositus was a carrier of GT with severe type 3 VWD and wife was a carrier of GT. Thus, it is concluded that there is importance of careful studies of patients even from nonconsanguineous families to exclude unusual coinheritance of congenital hemostatic disorders. If single replacement therapy in patient not responding well then probably co-expression of coagulopathies required and multiple replacement therapy should be given according to clinical and laboratory features.

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.

scholarly journals Bleeding in Patients with Clinically Severe Von Willebrand Disease: Preliminary Results of Athn 9, a Natural History Study of the Safety, Effectiveness, and Practice of Treatment for People with Severe Von Willebrand Disease (VWD)

Blood ◽  
2020 ◽  
Vol 136 (Supplement 1) ◽  
pp. 27-28
Author(s):  
Angela C. Weyand ◽  
Kenneth D Friedman ◽  
Sweta Gupta ◽  
Kristina M. Haley ◽  
Chunla He ◽  
...  
Keyword(s):  
Board Of Directors ◽  
Research Funding ◽  
Von Willebrand Disease ◽  
Heavy Menstrual Bleeding ◽  
Severe Bleeding ◽  
Advisory Committees ◽  
Type 3 ◽  
Von Willebrand

Background: Von Willebrand Disease (VWD) is the most common inherited bleeding disorder, thought to occur in ~0.1% of the population. VWD results from a quantitative (Type 1 or 3) or qualitative (Type 2) defect in von Willebrand Factor (VWF), a multifunctional plasma protein involved in primary and secondary hemostasis. Diagnosis of VWD can be difficult due to pre-analytical variables, a wide coefficient of variation in testing, and incomplete penetrance. Treatment of VWD is aimed at replacement of the defective or missing protein through plasma derived or recombinant VWF, release of endogenous VWF through desmopressin (DDAVP) or clot stabilization with anti-fibrinolytic therapy. Though individuals with mild VWD and bleeding symptoms are common, less is known regarding individuals with VWD and a clinically severe bleeding phenotype. Aims: To characterize the bleeding phenotype and treatment regimens in patients with clinically severe VWD in the United States. Study Design and Methods: ATHN 9 is sponsored by the American Thrombosis and Hemostasis Network (ATHN) and is being conducted at ATHN-affiliated sites across the US. Participants were identified by the site investigators with the projected goal to enroll 130 individuals. Inclusion criteria were patients with severe VWD defined as type 3 VWD, or VWF:RCo, VWF:GPIbM or VWF:Ag≤ 30% or patients with "clinically severe VWD" defined by VWF:RCo, VWF:GPIbM or VWF:Ag ≤ 40% a with severe bleeding phenotype (need for recurrent use of factor concentrates) and prior enrollment in the ATHN dataset national surveillance data collection project. Patients with platelet-type or acquired VWD were excluded. Laboratory assessment including a standardized diagnostic battery, VWF genetic analysis, and inhibitor testing, was performed by a central laboratory. Bleeding was assessed using the International Society for Thrombosis and Haemostasis (ISTH) Bleeding Assessment Tool (BAT) (normal adult 0-4, normal score <18 years 0-2) and the Pictorial Bleeding Assessment Chart (PBAC) if applicable. Results: Initial data on 35 participants was analyzed. Most were adult (69%), female (66%), Caucasian (86%) and non-Hispanic (89%). Just less than half (16/35, 45.7%) have completed diagnostic testing (Table 1). Half of the patients had Type 1, a quarter Type 3, and the remaining had Type 2 or unknown. The majority of patients (69%) had VWF GPIbM activity <30IU/dL, while 44% had an abnormally low FVIII level as well. The majority (26/35, 74.3%) had a known family history of VWD. Slightly over half (19/35, 54.2%) had previous surgery. Few participants (4/35, 11.4%) reported the presence of a target joint at enrollment, ankle being most common. The bleeding phenotype was significant but variable with a mean ISTH BAT score of 10.6 (range 0-39). With the exception of the youngest cohort (0-5 years of age, mean BAT score of 6, range 3-8), bleeding scores increased with age and all participants had abnormal scores. The most commonly endorsed symptoms were epistaxis, heavy menstrual bleeding (HMB), and post-surgical bleeding. The PBAC was performed on 4/10 participants in reference to their last period with a median score of 36 and range of 0-112 (>150 is abnormal). The majority (3/4) of participants filling out the PBAC received VWF concentrate prophylaxis for HMB. The majority (23 participants, 66%) utilized factor concentrates for prophylaxis or on-demand treatment; six patients (17%) were on continuous prophylaxis, while 12 (34%) were on event-based or HMB prophylaxis while the remainder received episodic treatment. Participants most commonly used plasma derived VWF concentrate (93.9%) with the remainder using recombinant VWF. Discussion: Initial evaluation of 35 participants with clinically severe VWD demonstrated a predominance of mucosal bleeding with a minority of participants endorsing joint bleeds at enrollment. Despite abnormal ISTH BAT scores in all participants, PBAC scores were within normal range, likely reflecting appropriate management of HMB with most participants receiving VWF concentrate for HMB prophylaxis. In contrast to patients with mild disease where antifibrinolytics and desmopressin are frequently used, factor replacement was the most common treatment modality. Future analysis will focus on laboratory evaluation, bleeding phenotype, response to factor replacement therapy and quality of life. Disclosures Weyand: Shire: Membership on an entity's Board of Directors or advisory committees; Kedrion: Membership on an entity's Board of Directors or advisory committees; Aptevo: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees. Friedman:Alexion: Speakers Bureau; Bayer: Consultancy; Instrumentation Laboratories: Consultancy; Alexion: Consultancy. Haley:ATHN: Research Funding. Roberts:Sanofi: Consultancy, Speakers Bureau; Novo Nordisk: Consultancy, Speakers Bureau; Pfizer: Consultancy; Takeda: Consultancy, Research Funding, Speakers Bureau; uniQure: Consultancy; Octapharma: Consultancy, Speakers Bureau. Sidonio:Genentech: Membership on an entity's Board of Directors or advisory committees; Sanofi/Bioverativ: Membership on an entity's Board of Directors or advisory committees; Octapharma: Membership on an entity's Board of Directors or advisory committees; Bayer: Membership on an entity's Board of Directors or advisory committees; Novo Nordisk: Membership on an entity's Board of Directors or advisory committees; Uniqure: Membership on an entity's Board of Directors or advisory committees; Biomarin: Membership on an entity's Board of Directors or advisory committees; Catalyst Sciences: Membership on an entity's Board of Directors or advisory committees; Emergent Solutions: Membership on an entity's Board of Directors or advisory committees; Takeda: Membership on an entity's Board of Directors or advisory committees; Pfizer: Membership on an entity's Board of Directors or advisory committees; Kedrion: Membership on an entity's Board of Directors or advisory committees; Takeda: Research Funding; Genentech: Membership on an entity's Board of Directors or advisory committees; Octapharma: Research Funding; Grifols: Research Funding; Grifols: Membership on an entity's Board of Directors or advisory committees. OffLabel Disclosure: VWF concentrates used for heavy menstrual bleeding

Type 3 Von Willebrand Disease with Alloantibodies and Its Challenging Management During Episode of Bleeding

Blood ◽  
2010 ◽  
Vol 116 (21) ◽  
pp. 1405-1405
Author(s):  
Anupam Verma ◽  
Hassan Yaish ◽  
George M. Rodgers
Keyword(s):  
Factor Viii ◽  
Clinical Course ◽  
Conflicts Of Interest ◽  
Von Willebrand Disease ◽  
Recombinant Factor Viii ◽  
Severe Bleeding ◽  
Post Infusion ◽  
Life Threatening ◽  
Type 3 ◽  
Von Willebrand

Abstract Abstract 1405 Type 3 Von Willebrand Disease (VWD) is the most severe and least common of the three VWD types. The incidence varies by ethnicity ranging from 0.1–5.3 cases/million. 8.5% of patients develop alloantibodies to Von Willebrand Factor (VWF), becoming non-responsive to treatment or prone to life threatening reactions. Predisposing factors include extent of previous exposure to VWF and mutations causing a null-allele gene. Variability of the clinical course is attributed to different antigenic specificities and potency of the antibodies. Management of these patients during events of bleeding is challenging. We report 2 cases of girls with type 3 VWD. The first was diagnosed at birth and had her initial VWF transfusion as a neonate. The second was diagnosed at 4 years of age. Both were frequently treated with VWF and developed alloantibodies. The clinical course, severity and circumstances leading to the diagnosis were different in both cases. Life threatening anaphylactic reactions like hypotension, bronchospasm and tongue edema was noticed in the first. The second showed poor factor recovery and response to treatment with urticaria. She continued to tolerate therapy but failed tolerance induction. Peak antibody level was 84 BU compared to 3 BU in the first. Novel VWF gene mutations were detected in both. Recently the first patient was managed for profuse bleeding post extensive dental procedure. Recombinant Factor VIII infusion was administered every 3 hours with monitoring of aPTT and Factor VIII levels. Based on peak and post 3 hour levels of Factor VIII, we concluded the half life of Factor VIII could be as short as 2 hours in patients with type 3 VWD. Post infusion peak level might approach 200% in some instances. Due to persistent bleeding despite adequate correction of Factor VIII and aPTT, platelet transfusion was cautiously administered which proved to be not only effective in controlling bleed but was also safe and not associated with any anaphylactic reaction. In conclusion, patients with type 3 VWD and alloantibodies can be successfully managed with aggressive frequent therapy with recombinant Factor VIII infusions. Platelet transfusions during episodes of severe bleeding can also be safe and effective.Administration of Factor VIII by continuous infusion could be an option if high post infusion peaks are to be avoided. Disclosures: No relevant conflicts of interest to declare.

scholarly journals Successful Aortic Aneurysm Repair in a Woman with Severe von Willebrand (Type 3) Disease

2015 ◽  
Vol 2015 ◽  
pp. 1-8
Author(s):  
Victoria Campbell ◽  
Kevin Marriott ◽  
Rex Stanbridge ◽  
Abdul Shlebak
Keyword(s):  
Aortic Aneurysm ◽  
Severe Form ◽  
Von Willebrand Disease ◽  
Severe Bleeding ◽  
Recessive Trait ◽  
Aneurysm Repair ◽  
Factor Concentrate ◽  
Type 3 ◽  
Von Willebrand ◽  
Aortic Aneurysm Repair

von Willebrand disease type 3 (VWD3) is a rare but the most severe form of von Willebrand disease; it is due to almost complete lack of von Willebrand factor activity (VWF:RCo). It is inherited as autosomal recessive trait; whilst heterozygote carriers have mild, or no symptoms, patients with VWD3 show severe bleeding symptoms. In the laboratory, this is characterised by undetectable VWF:Ag, VWF:RCo, and reduced levels of factor VIII < 0.02 IU/dL. The bleeding is managed with von Willebrand/FVIII factor concentrate replacement therapy. In this rare but challenging case we report on the successful excision and repair of an ascending aortic aneurysm following adequate VWF/FVIII factor concentrate replacement using Haemate-P.

scholarly journals Genotypes of European and Iranian patients with type 3 von Willebrand disease enrolled in 3WINTERS-IPS

2021 ◽  
Vol 5 (15) ◽  
pp. 2987-3001
Author(s):  
Luciano Baronciani ◽  
Ian Peake ◽  
Reinhard Schneppenheim ◽  
Anne Goodeve ◽  
Minoo Ahmadinejad ◽  
...  
Keyword(s):  
Missense Variant ◽  
European Population ◽  
Von Willebrand Disease ◽  
Null Alleles ◽  
Severe Bleeding ◽  
Compound Heterozygous ◽  
Large Deletions ◽  
Type 3 ◽  
Von Willebrand ◽  
Iranian Patients

Abstract Type 3 von Willebrand disease (VWD3) is a rare and severe bleeding disorder characterized by often undetectable von Willebrand factor (VWF) plasma levels, a recessive inheritance pattern, and heterogeneous genotype. The objective of this study was to identify the VWF defects in 265 European and Iranian patients with VWD3 enrolled in 3WINTERS-IPS (Type 3 Von Willebrand International Registries Inhibitor Prospective Study). All analyses were performed in centralized laboratories. The VWF genotype was studied in 231 patients with available DNA (121 [115 families] from Europe [EU], and 110 [91 families] from Iran [IR]). Among 206 unrelated patients, 134 were homozygous (EU/IR = 57/77) and 50 were compound heterozygous (EU/IR = 43/7) for VWF variants. In 22 patients, no or only one variant was found. A total of 154 different VWF variants (EU/IR = 101/58 [5 shared]) were identified among the 379 affected alleles (EU/IR = 210/169), of which 48 (EU/IR = 18/30) were novel. The variants p.Arg1659*, p.Arg1853*, p.Arg2535*, p.Cys275Ser, and delEx1_Ex5 were found in both European and Iranian VWD3 patients. Sixty variants were identified only in a single allele (EU/IR = 50/10), whereas 18 were recurrent (≥3 patients) within 144 affected alleles. Nine large deletions and one large insertion were found. Although most variants predicted null alleles, 21% of patients carried at least 1 missense variant. VWD3 genotype was more heterogeneous in the European population than in the Iranian population, with nearly twice as many different variants. A higher number of novel variants were found in the Iranian VWD3 patients.

A Novel Mutation Glyl672→Arg in Type 2A and a Homozygous Mutation in Type 2B von Willebrand Disease

1996 ◽  
Vol 76 (02) ◽  
pp. 253-257 ◽  
Author(s):  
Takeshi Hagiwara ◽  
Hiroshi Inaba ◽  
Shinichi Yoshida ◽  
Keiko Nagaizumi ◽  
Morio Arai ◽  
...  
Keyword(s):  
Missense Mutation ◽  
Novel Mutation ◽  
Point Mutations ◽  
Japanese Patients ◽  
Von Willebrand Disease ◽  
Homozygous Mutation ◽  
Missense Mutations ◽  
Reaction Products ◽  
Type 3 ◽  
Von Willebrand

SummaryGenetic materials from 16 unrelated Japanese patients with von Willebrand disease (vWD) were analyzed for mutations. Exon 28 of the von Willebrand factor (vWF) gene, where point mutations have been found most frequent, was screened by various restriction-enzyme analyses. Six patients were observed to have abnormal restriction patterns. By sequence analyses of the polymerase chain-reaction products, we identified a homozygous R1308C missense mutation in a patient with type 2B vWD; R1597W, R1597Q, G1609R and G1672R missense mutations in five patients with type 2A; and a G1659ter nonsense mutation in a patient with type 3 vWD. The G1672R was a novel missense mutation of the carboxyl-terminal end of the A2 domain. In addition, we detected an A/C polymorphism at nucleotide 4915 with HaeIII. There was no particular linkage disequilibrium of the A/C polymorphism, either with the G/A polymorphism at nucleotide 4391 detected with Hphl or with the C/T at 4891 detected with BstEll.

Evaluation of the Abnormal Platelet Function in von Willebrand Disease by the Blood Filtration Test

1996 ◽  
Vol 76 (03) ◽  
pp. 460-468 ◽  
Author(s):  
Francesco I Pareti ◽  
Marco Cattaneo ◽  
Luca Carpinelli ◽  
Maddalena L Zighetti ◽  
Caterina Bressi ◽  
...  
Keyword(s):  
Platelet Function ◽  
Relevant Information ◽  
Von Willebrand Disease ◽  
Type I ◽  
Cumulative Number ◽  
Primary Hemostasis ◽  
Normal Platelet ◽  
Filter Test ◽  
Type 3 ◽  
Von Willebrand

SummaryWe have evaluated platelet function in different subtypes of von Willebrand disease (vWD) by pushing blood through the capillarysized channels of a glass filter. Patients, including those with type IIB vWD, showed lower than normal platelet retention and increased cumulative number of blood drops passing through the filter as a function of time. In contrast, shear-induced platelet aggregation, measured in the cone-and-plate viscometer, was paradoxically increased in type IIB patients. Treatment with l-desamino-8-D-arginine vasopressin (DDAVP) tended to normalize the filter test in patients with type I-platelet normal and type I-platelet low vWD, but infusion of a factor VUI/von Willebrand factor (vWF) concentrate lacking the largest vWF multimers was without effect in type 3 patients. Experiments with specific monoclonal antibodies demonstrated that the A1 and A3 domains of vWF, as well as the glycoproteins Ibα and Ilb-IIIa on platelets, are required for platelet retention in the filter. Thus, the test may reflect vWF function with regard to both platelet adhesion and aggregation under high shear stress, and provide relevant information on mechanisms involved in primary hemostasis.

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