Treatment Of Von Willebrand Disease Research Articles

A Systematic Review of Efficacy and Safety of Plasma-Derived von Willebrand Factor/Factor VIII Concentrate (Voncento) in von Willebrand Disease.

For the treatment of von Willebrand disease (VWD), von Willebrand factor (VWF) concentrates can be used in on-demand, long-term prophylaxis, and surgical prophylaxis regimens. This systematic literature review was conducted to evaluate the efficacy, consumption, and safety of plasma-derived human coagulation FVIII/human VWF (pdVWF/FVIII; Voncento/Biostate) for the treatment of patients with any inherited VWD type. An electronic search was conducted in MEDLINE and Cochrane Library databases on VWD therapies. All retrieved publications were assessed against predefined inclusion/exclusion criteria following the Cochrane group recommendations. Associated pharmacovigilance data were collected across the same time period. Eleven publications from eight study cohorts were identified for data retrieval. All were from multicenter studies and included both pediatric and adult patients. Eight publications included evaluations of the efficacy of pdVWF/FVIII for on-demand treatment, eight included long-term prophylactic treatment, and eight included surgical prophylaxis. Treatment protocols and VWF administration methods differed between studies, as did safety evaluations. The clinical response was rated as excellent/good for on-demand treatment in 66 to 100% of nonsurgical bleeds, 89 to 100% in the treatment of breakthrough bleeds during long-term prophylaxis treatment, and hemostatic efficacy in surgical procedures was 75 to 100%. Pharmacovigilance data confirmed a low incidence of adverse events in treated patients. This review provides a comprehensive summary of studies that evaluated the use of pdVWF/FVIII in VWD demonstrating the long-term effectiveness and safety of this pdVWF/FVIII across all ages, types of VWD, and treatment settings.

Hemostatic potential of recombinant von Willebrand factor and standard or pegylated extended half-life recombinant factor VIII on thrombus formation under high shear flow

BackgroundVon Willebrand factor (VWF) and factor VIII (FVIII) complex play a pivotal role in hemostasis. A deficiency or defect of VWF causes von Willebrand disease (VWD). Recombinant (r)VWF product has proved to be effective for hemostatic treatment of VWD, but limited information is available on their role in moderating thrombus formation under flow condition. We aimed to assess thrombus formation in the presence of rVWF combined with rFVIII or pegylated-extended half-life rFVIII (peg-EHL-rFVIII) in VWD whole blood under high shear flow.MethodsPerfusion chamber experiments under high shear (2,500 s− 1) combined with immunostaining were performed using patient’s whole blood with type 1 VWD, mixed with rVWF (Vonvendi®; 1.6 IU/mL), rFVIII or peg-EHL-rFVIII (Advate® or Adynovate®; 1.0 IU/mL), or both. Similar experiments were also conducted with clinical medical devices (T-TAS®).ResultsThe addition of rFVIII did not augment thrombus formation assessed by surface coverage (SC) and thrombus height (TH), whereas rVWF enhanced these parameters (SC 19.1 ± 1.1% vs. 30.1 ± 4.1%, TH 2.2 ± 0.14 μm vs. 3.6 ± 0.40 μm, respectively). The co-presence of rVWF/rFVIII was comparable to plasma-derived VWF/FVIII (Confact®, VWF:FVIII ratio = 1.6:1.0) for increasing thrombogenicity in SC (32.5 ± 4.3% vs. 38.7 ± 5.5%) and in TH (5.0 ± 0.60 μm vs. 5.5 ± 0.64 μm), respectively. The pre-incubation time with rVWF and rFVIII appeared to have a little effect on the size of thrombus. Peg-EHL-rFVIII mediated thrombus formation to similar extent as rFVIII in the co-presence of rVWF. Similar results were obtained even with T-TAS. Immunostaining demonstrated that rFVIII and peg-EHL-rFVIII were similarly co-localized with rVWF in formed thrombi, indicating that pegylation did not interfere with molecular complexes.ConclusionThe effects of high-level rVWF and peg-EHL-rFVIII on thrombus formation were comparable to conventional therapeutic products in a patient’s whole blood with VWD under high shear flow.

EE722 Cost-Utility Analysis for Haemate-P in the Treatment of Von Willebrand Disease

EE722 Cost-Utility Analysis for Haemate-P in the Treatment of Von Willebrand Disease

Ralb and Exocyst Regulate Endothelial Cell Von Willebrand Factor Release

Background: Identification of novel therapeutic targets for pharmacologic modulation of circulating von Willebrand factor (vWF) would be invaluable in treatment of von Willebrand disease, but also in other pathophysiologic processes where vWF plays a vital role. These include cardiovascular disease, cancer metastasis, angiogenesis, and smooth muscle proliferation. vWF is almost exclusively produced by the endothelial cells and stored in specialized secretory granules, Weibel Palade bodies (WPBs). We have previously shown that loss of the exocyst complex, an essential multi-subunit trafficking protein, which physically tethers secretory granules to the plasma membrane in yeast, increases vWF release. Small GTPases act as regulatable molecular switches. Cycling between GTP-bound ('on') and GDP-bound ('off') states, they control all essential cellular processes. Among these, Ral GTPase has previously been shown to be important in WPB secretion and vWF release. Since Ral specifically regulates exocyst in other cellular functions, we hypothesized that exocyst is also under direct control of Ral in vWF release. Methods: All experiments were performed on human umbilical vein endothelial cells (HUVECs). RalA/B and exocyst depletion were performed via targeted siRNAs. vWF antigen was estimated using ELISA. RalB activation was determined by a commercial pulldown assay specific for the activated form of RalB. Expression of FLAG-tagged RalB was performed by lentiviral transduction. RalB mutants were generated using site-directed mutagenesis of FLAG-RalB (WT). Spinning disc confocal microscope was used for immunofluorescence (IF). Immuno-electron microscopy was performed using immune-gold labeling. FLAG-pulldown and immunoprecipitation (IP) was performed on cell lysates using antibody-labeled magnetic beads. Results: RalB but not RalA depletion, or degradation with the RalB-selective inhibitor dihydroartemisinin, significantly impaired thrombin-induced vWF exocytosis (55±7% decrease). RalB was activated (GTP-bound) and phosphorylated upon thrombin stimulation of HUVECs. Correspondingly, expression of constitutively active RalB-G23V mutant, which stays in a GTP-bound state, significantly increased vWF exocytosis compared to RalB-WT (69±4.6% increase). IF and EM confirmed co-localization of RalB and exocyst on WPBs. Unexpectedly, FLAG pulldown and protein identification by mass spectrometry demonstrated that RalB-WT (GDP-bound;“off”) but not RalB-G23V (GTP-bound;“on”) interacts with exocyst, confirmed by immunoblotting. IP of resting and thrombin-stimulated native HUVEC lysates with RalB antibodies, as well as reverse-IP with exocyst antibodies confirmed this differential binding. Exocyst binding site mutation (RalB-WTD49E) and transduction of these mutants in HUVECs resulted in significantly augmented vWF exocytosis (40±3% increase), like constitutively active RalB-G23V mutant. Moreover, IF showed uniform cytoplasmic distribution of WPB cigars in RalB-WT HUVECs, whereas in RalB-WTD49E mutants WPBs were found at the plasma membrane, like RalB-G23V. This confirms that RalB-free exocyst tethers WPB to the plasma membrane ( Figure 1). Serine phosphorylation site mutation (RalB-WTS198A), previously shown to regulate GTPase activity of RalB, hence GTP-GDP cycling, also significantly decreased RalB exocyst binding, in turn increasing vWF release. This shows that post-translational phosphorylation of RalB at serine 192, which is also accelerated by thrombin activation of endothelial cells, regulates RalB-exocyst interaction, hence vWF release. Conclusions: We have identified an important regulatory role of RalB in exocyst-dependent WPB secretion and vWF release. WPB localized exocyst is associated with RalB in resting endothelium. Endothelial cell activation switches RalB ‘on’, and exocyst, now uncoupled from GTP-bound RalB, is free to tether WPBs to the plasma membrane and facilitate vWF release.

New and emerging therapies for women, girls, and people with the potential to menstruate with VWD

AbstractInnovation in therapies for patients with von Willebrand disease (VWD) has lagged far behind that for hemophilia, creating inequity in the bleeding disorder community. Although currently existing treatments of antifibrinolytics, desmopressin, and plasma-derived von Willebrand factor replacement are considered effective, multiple studies report poor quality of life in patients with VWD, especially those with heavy menstrual bleeding (HMB). This disconnect underscores the need for novel therapies that are safe and effective and that consider a patient’s specific contraceptive and reproductive needs. Recombinant von Willebrand factor is the most recent new therapy for VWD; the data specific to women are reviewed. We also present emerging data on emicizumab for the treatment of VWD, BT200 (rondoraptivon pegol), generalized hemostatic therapies (VGA039 and HMB-011), as well as treatments based on nanotechnology (platelet-inspired nanoparticles and KB-V13A12). We are optimistic as we move toward pivotal clinical trials for these elegant and innovative treatments.

An evaluation of von Willebrand factor (recombinant) therapy for adult patients living with severe type 3 von Willebrand disease

ABSTRACT Introduction Von Willebrand Factor (VWF) containing concentrates have been used for the treatment of von Willebrand Disease (VWD) for many years. Recently, however, a novel recombinant VWF (rVWF or vonicog alpha, VONVENDI [US], VEYVONDI [Europe]) has arrived to the market for the treatment of VWD. Initially, rVWF was approved by the U.S. Food and Drug Administration (FDA) for the on-demand treatment and control of bleeding episodes and for the perioperative management of bleeding for patients with VWD. More recently, however, the FDA has approved rVWF for routine prophylaxis to prevent bleeding episodes for those patients with severe type 3 VWD receiving on-demand therapy. Areas Covered This review will focus on recent phase III trial results from NCT02973087 regarding the use of long-term routine twice weekly prophylaxis with rVWF for the prevention of bleed events in patients with severe type 3 VWD. Expert Opinion A novel rVWF concentrate may have greater hemostatic potential over prior plasma-derived VWF concentrates and is now FDA approved for use in routine prophylaxis for patients with severe type 3 VWD in the United States. This greater hemostatic potential may be due to the presence of ultra-large VWF multimers and a more favorable high-molecular-weight multimer pattern compared to prior pdVWF concentrates.

Type 2M VWD Laboratory Defects More Consistent Than Bleeding Symptoms across Family Members

Background Von Willebrand disease (VWD) is an inherited bleeding disorder characterized by a defect or decrease of von Willebrand factor (VWF). Type 2 VWD results from qualitative defects in VWF. Type 2M VWD is defined by defective platelet binding to GPIb and/or collagen. While the inheritance of type 2M VWD is autosomal dominant, the extent of symptoms across family members has not been well characterized. Methods Subjects included index cases with type 2M VWD and all enrolled family members from a large US study of VWD (Zimmerman Program). Index cases were enrolled due to a prior diagnosis of VWD. All available family members were enrolled if willing. VWF testing performed included VWF antigen (VWF:Ag), VWF platelet binding by either VWF ristocetin cofactor activity (VWF:RCo) or VWF:GPIbM, collagen binding with types I, III or IV collagen (VWF:CB1, VWF:CB3, VWF:CB4) and VWF multimer distribution. Bleeding scores were calculated using the ISTH bleeding assessment tool (BAT). DNA sequencing was performed for the full length VWF gene. Statistics were calculated using GraphPad Prism with a p value of <0.05 considered significant. Family members were defined as affected if they had VWF activity levels consistent with type 2M VWD and presence of genetic variant if identified. Results 24 index cases, 51 affected family members and 40 unaffected family members were available for analysis. The mean VWF:RCo/VWF:Ag ratio for index cases was 0.5 and the mean VWF:CB/VWF:Ag ratio was 1.05. The VWF:RCo/VWF:Ag ratio was similar in affected family members (0.44, p=NS) but higher as expected in unaffected members (0.89, p<0.001 for index case vs. unaffected, p<0.001 for affected vs. unaffected). In contrast, there was no difference in VWF:CB/VWF:Ag ratios between index cases and affected family members (0.94, p=NS). Data for VWF:GPIbM, collagens I and IV were available only on index cases, and showed low VWF:GPIbM/VWF:Ag (mean 0.79), higher VWF:CBI/VWF:Ag (mean 1.31) and lower VWF:CBIV/VWF:Ag (mean 0.85). There was a negative correlation between VWF:GPIbM and VWF:CBIV, with subjects having either low VWF:GPIbM and normal VWF:CBIV or low VWF:CBIV and normal VWF:GPIbM. Similar results were seen for VWF:CB1 although only 1 subject was diagnosed with type 2M VWD and low VWF:CB1. Median bleeding scores were highest in index cases (7.5), intermediate in affected family members (3) and normal in unaffected family members (1). There was a significant difference between index cases and affected family members (<0.015), and between index cases and unaffected family members (p<0.001). One subject had a genetic variant in the VWF A3 domain, one in the VWF D3 domain and the remainder of index cases had a defect in the VWF A1 domain. Conclusions These findings suggest that decreases in platelet and collagen binding activity increase bleeding risk in families with type 2M VWD. Index cases had higher bleeding scores as compared to affected family members, suggesting that diagnosis of family members may require more attention. Precise understanding of these defects may assist in better diagnosis and treatment of von Willebrand disease.

Sixth Åland Island Conference on von Willebrand disease.

IntroductionThe sixth Åland Islands Conference on von Willebrand disease (VWD) on the Åland Islands, Finland, was held from 20 to 22 September 2018.AimThe meeting brought together experts in the field of VWD from around the world to share the latest advances and knowledge in VWD.Results and discussionThe topics covered both clinical aspects of disease management, and biochemical and laboratory insights into the disease. The clinical topics discussed included epidemiology, diagnosis and treatment of VWD in different countries, management of children with VWD, bleeding control during surgery, specific considerations for the management of type 3 VWD and bleeding control in women with VWD. Current approaches to the management of acquired von Willebrand syndrome were also discussed. Despite significant advances in the understanding and therapeutic options for VWD, there remain many challenges to be overcome in order to optimise patient care. In comparison with haemophilia A, there are very few registries of VWD patients, which would be a valuable source of data on the condition and its management. VWD is still underdiagnosed, and many patients suffer recurrent or severe bleeding that could be prevented. Awareness of VWD among healthcare practitioners, including non‐haematologists, should be improved to allow timely diagnosis and intervention. Diagnosis remains challenging, and the development of fast, simple assays may help to facilitate accurate and rapid diagnosis of VWD.

Management of von Willebrand disease. Recommendations of the Hemostasis Group of the Polish Society of Hematology and Transfusiology (2022)

Recommendations of the Group on Hemostasis of the Polish Society of Hematology and Transfusiology are an update of the guidelines issued in 2008 [1]. In the absence of adequately designed randomized clinical trials for the diagnosis and treatment of von Willebrand disease, these recommendations are largely based on retrospective studies, expert opinions, series of case reports as well as guidelines published in other countries. In questionable cases, most conclusive for the final diagnosis of von Willebrand disease (VWD) is the physician’s experience and his assessment of the patient’s clinical picture.

Сompliance with therapy in patients with von Willebrand's disease

Von Willebrand's disease (VWD) bleeding is less likely to endanger life, unlike hemophilia. The lack of a significant decrease the quality of life leads to decrease in the compliance of patients with VWD. To improve the situation, the staff of the Department of Hemostasis Disorders, Russian National Research Center for Hematology conducted this program in Moscow and the Moscow region. Determine the patients' compliance to therapy, as well as the difficulties and wishes associated with the treatment of VWD. Survey of patients with VWD on a visit to a hematologist or via phone calls. Questions included information on diagnosis, safety, efficacy, and convenience of replacement therapy, communication, bleeding control, and social standing. The study was approved by the Independent Ethics Committee and the Scientific Council of the National Medical Research Centre for Hematology of the Ministry of Healthcare of the Russian Federation. 41 patients took a part in it: 17 male and 24 female. The majority of initial visits to a specialist are associated with bleeding from the nose and gums (26%), with hematomas (20%), dental operations (13%) and injuries (11%). Most often, the diagnosis was installed by a pediatrician (47%), less often by a surgeon (14%) or genetic inheritance (14%), gynecologists (9%), dentists (7%), otorhinolaryngologists (2%) and doctors of other specialties (7%). Completely satisfied with the therapy are 76% of the respondents. However, one patient considers the therapy ineffective. VWD is the most common coagulopathy, which can be encountered by a doctor of any specialty. Our survey identified a need to educate patients about intravenous injections. The communication between patient and doctor and the therapy correction on time could be improve compliance and reduce the cost of the state for the treatment of complications associated with non-compliance of patients.

Efficacy of emicizumab in von Willebrand disease (VWD) patients with and without alloantibodies to von Willebrand factor (VWF): Report of two cases and review of literature

von Willebrand disease (VWD) is the common bleeding disorder with a clinically relevant bleeding prevalence of 1:10,000. von Willebrand disease patients lack both von Willebrand factor (VWF) and factor VIII (FVIII), which are critical for normal haemostasis. The conventional treatment for VWD includes desmopressin and replacement therapy with plasma derived FVIII with VWF concentrates or recombinant VWF. Development of alloantibodies is a rare occurrence, there is a paucity in the literature of treatment modalities in these patients. Not many reports are available in literature on the efficacy of emicizumab in VWD patients with or without alloantibodies to VWF. To do systematic review of literature on emicizumab in VWD and report our experience of emicizumab in two patients of VWD METHODS: We used electronic search engines till May 2021 in 'Google scholar' and 'PubMed', to collect the case reports or case series on use of emicizumab for management of VWD. Two of our severe VWD patients were successfully treated with emicizumab. A systematic review was performed and the results discussed. The electronic search revealed six case reports using emicizumab for treatment of VWD. Two were in vitro studies and four in patients with VWD type 3 disease. In vitro studies and in VWD patients on emicizumab, showed improvement in thrombin generation and fibrin formation. Among four patients, three had alloantibodies to VWD and one was negative. All these patients were treated with emicizumab for 6-12m. After starting emicizumab, none of them had spontaneous bleeding requiring treatment. During treatment with emicizumab, one patient had trauma-associated soft tissue hematoma, which was treated with rFVIIa and another patient had bleeding following dental exfoliation treated with Humate P. We treated two of our VWD patients one with and one without inhibitors with emicizumab after failure of other therapies. Both the patients showed marked improvement and continued to remain well and free of bleeding episodes. None of the patients had any thrombosis or thrombotic microangiopathy (TMA) during treatment with emicizumab. In conclusion, this review supports the safety and efficacy of emicizumab in type 3 VWD patients with or without alloantibodies. Further large studies are required to confirm the safety and efficacy of emicizumab in VWD.

Von Willebrand disease - detection, diagnostics and treatment

von Willebrand disease is the most common inherited bleeding disorder, with mucocutaneous bleeding and menorrhagia as leading clinical manifestations. Cause of the bleeding diathesis is deficit or dysfunction of the vonWillebrand factor, plasma protein with important roles in adhesion of platelets to the site of vascular injury and transport and protection of coagulation factor VIII. Prevalance of the disease, according to different registries, is between 1 von Willebrand disease on 100 persons to 1 von Willebrand disease on 10000 persons. These data shows that detection of the disorder is not easy and that many cases are undiagnosed. That why bleeding assessment tools are developed and they are widely used for many years. Confirmation of the diagnosis is through laboratory testing. Some of tests are not easily accessible. Therapy of the disorder depends on goals of the treatment (stopping bleeding, prophylaxis or preoperative management). Last year, new guideline for diagnostics and treatment of von Willebrand disease was published by experts of World Federation of Haemophilia, International Society of Thrombosis and Haemostasis, American Society of Hematology and National Hemophilia Foundation. In this paper, new recommendations for detection, diagnostics and treatment of the von Willebrand disease, are presented.

Real-World Data on the Effectiveness and Safety of wilate for the Treatment of von Willebrand Disease.

Background The efficacy and safety of wilate (human von Willebrand factor/coagulation factor VIII) in patients with von Willebrand disease (VWD) has been demonstrated in clinical trials. Here, we present real-world data on the use of wilate for the routine care of patients with VWD. Objectives The objectives of this observational, prospective, phase 4 study were to evaluate the safety, tolerability, and effectiveness of wilate in on-demand treatment of bleeding episodes (BEs), long-term prophylaxis, and surgical prophylaxis among patients with any type of VWD. Methods Patients were enrolled at 31 study centers in 11 countries and followed for up to 2 years. Safety endpoints included adverse drug reactions (ADRs) and drug tolerability. Effectiveness was assessed using annualized bleeding rates (ABRs) during prophylaxis and predefined criteria for the treatment of BEs and surgical prophylaxis. Results A total of 111 patients (76 [68%] female) including 41 (37%) children were treated with wilate. Twenty-five patients received prophylaxis, 29 on-demand treatment, and 62 surgical prophylaxis. Tolerability was rated by patients as “excellent” for 96.2% of 6,497 infusions. No unexpected ADRs or thrombotic events were reported. Median ABR during prophylaxis was 1.9. Effectiveness was assessed as “excellent” or “good” by patients and investigators for 100% of BEs treated on-demand, 98% (patient rating) and 99% (investigator rating) of breakthrough BEs, and 99% of surgical procedures (investigator rating). Conclusion wilate was safe, well tolerated, and effective for the prevention and treatment of bleeding in pediatric and adult VWD patients in a real-world setting.

Quantitative Analysis of Von Willebrand Factor (VWF) Multimers in Von Willebrand Disease (VWD) Patients Recruited through the Zimmerman Program for the Molecular and Clinical Biology of VWD

Quantitative Analysis of Von Willebrand Factor (VWF) Multimers in Von Willebrand Disease (VWD) Patients Recruited through the Zimmerman Program for the Molecular and Clinical Biology of VWD

Perioperative Management of Von Willebrand Disease: An Institutional Experience

Introduction: Von Willebrand disease (VWD) is the most common inherited bleeding disorder affecting as many as 1% of the population. Mucocutaneous symptoms predominate, and include ecchymosis, menorrhagia, and epistaxis. In addition, perioperative bleeding is common, and often prompts diagnosis; therefore, affected patients require perioperative VWD-specific therapy to prevent surgical related bleeding. VWF-specific therapy includes DDAVP, intravenous and nasal, and VWF concentrates, plasma derived, and more recently, recombinant. Unfortunately, few standard evidence-based guidelines are in place concerning the perioperative management of VWD, in part due to a limited number of high quality clinical research studies addressing the topic. Because of this, treatments vary widely, often based on local practice and physician experience. To evaluate the efficacy and safety of perioperative VWD-specific therapy, we aimed to describe our experience managing VWD patients undergoing surgery. Methods: We performed a retrospective chart review of patients with VWD receiving care at the Hemophilia Center of Western Pennsylvania (HCWP) who underwent surgery at a University of Pittsburgh Medical Center (UPMC) affiliated hospital between January 1, 2015, and May 31, 2017. Surgery was defined as any invasive procedure, including childbirth. Data collected included demographics; VWD subtype; VWD-specific therapy, including type, dose, frequency, and duration; estimate blood loss during surgery; presence of postoperative bleeding; and whether or not thrombosis occurred. Results: A total of64 patients with VWD receiving care at HCWP underwent surgery at an UPMC-affiliated hospital during the time period. The mean age of participants was 32.9 ± 17.5 years (median 33, range 2 to 89). Of these, 86% of patients were female. By type, 80% were type 1 VWD; 17% were type 2 VWD (2A, n=1; 2B, n=5; 2M, n=3; and 2N, n=2); and 2 were type 3 VWD (Table 1). The most common surgeries performed included vaginal delivery, n=7; cesarean section, n=6; dental extraction, n=4; colonoscopy with biopsy, n=3; and breast biopsy, n=3 (Table 1). 83% of patients received VWF concentrates, and the remaining patients received DDAVP (Table 1). Reasons for VWF concentrate use included DDAVP allergy, poor response to DDAVP, type of VWD, and type of surgery. Dosing, frequency, and duration of VWD-specific therapy differed considerably. Estimated blood loss (EBL), intraoperatively, was minimal (defined as less than 100 mL) in all but 12 surgeries, 11 of which involved childbirth with EBL 1000 mL or less in all. The other surgery was a dental extraction of 23 teeth with EBL 270 mL. Postoperative bleeding occurred in 3 patients, and included minor epistaxis following adenoidectomy and minor oral mucosa bleeding following a single dental extraction. 1 patient experienced a large breast hematoma following bilateral breast reduction requiring operative evacuation. No thromboses occurred. Discussion: We describe the perioperative management of 64 patients with VWD at our institution. VWD-specific therapy was both safe and effective, evidenced by minimal bleeding and no adverse events. A large number of patients were pregnant. It is our practice to utilize VWF concentrates in most pregnant VWD patients during childbirth due to the risk of DDAVP induced fluid retention and hyponatremia in the peripartum period. Our findings are indicative of its efficacy and safety in this particular situation. Despite these findings, there were considerable differences in dosing, frequency, and duration of VWD-specific therapy. This parallels the known variation in treatment of VWD among practitioners, in large part, due to the lack of evidence-based guidelines available to help standardize therapy. In conclusion, we describe the safe and effective perioperative management of VWD while acknowledging differences in treatment, which further underscores the need for high quality clinical research studies and evidence-based guidelines to standardize the perioperative management of VWD. Download : Download high-res image (308KB) Download : Download full-size image Disclosures Ragni: Alnylam, CSL Behring, Dimensions, Genetech/Roche,Pfizer, Shire, SPARK: Research Funding; A Anylam,Biomarin,Tecere, Benitec: Honoraria.

Diagnosis and management of von Willebrand disease: A community-wide effort to deliver evidence-based clinical practice guidelines.

Diagnosis and management of von Willebrand disease: A community-wide effort to deliver evidence-based clinical practice guidelines.

Correcting dominant‐negative von Willebrand disease

Correcting dominant‐negative von Willebrand disease

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)

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)

Healthcare Utilization and Health Related Quality of Life in Persons with Von Willebrand Disease

Healthcare Utilization and Health Related Quality of Life in Persons with Von Willebrand Disease

Клинические примеры применения фактора VIII свертывания крови с фактором Виллебранда у рожениц с III типом болезни Виллебранда

Болезнь Виллебранда (БВ) может представлять определенные трудности у рожениц с данной патологией. Приведены 2 клинических примера использования у женщин с БВ фактора VIII свертывания крови с фактором Виллебранда, показана эффективность и безопасность их применения. У одной пациентки было также показано использование фактора свертывания крови VIII с фактором Виллебранда во время экстракорпорального оплодотворения. Von Willebrand disease presents a certain hemostatic problem among parturients. This article shows the effectiveness and safety of using coagulation factor VIII with von Willebrand factor for the prevention of bleeding in childbirth in 2 patients with type 3 von Willebrand disease. In one patient, the use of coagulation factor VIII with von Willebrand factor during in vitro fertilization was also shown.