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

Mannucci, Pier Mannuccio; Chediak, Juan; Hanna, Wahid T.; Byrnes, John; Ledford, Marlies; Ewenstein, Bruce M.; Retzios, Anastassios D.; Kapelan, Barbara; Schwartz, Richard S.; Kessler, Craig M.

doi:10.1182/blood.v99.2.450

Cited by 174 publications

(177 citation statements)

References 24 publications

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“…24 In vWD patients, however, the need for platelet concentrates to prevent or stop bleeding is very rare. 28,29 It is nevertheless important to note that measurement of the bleeding time may not always have a good predictive value for the risk of severe clinical bleeding. 30 Despite no or partial correction of bleeding time after infusion of vWF concentrates in vWD patients, major surgical procedures are carried out successfully and spontaneous bleeding episodes are controlled.…”

Section: Discussionmentioning

confidence: 99%

Restoration of Plasma von Willebrand Factor Deficiency Is Sufficient to Correct Thrombus Formation After Gene Therapy for Severe von Willebrand Disease

Meyer

Vandeputte

Pareyn

et al. 2008

ATVB

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Objective-Gene therapy for severe von Willebrand disease (vWD) seems an interesting treatment alternative with long-term therapeutic potential. We investigated the feasibility of targeting the liver for ectopic expression of physiologically active von Willebrand factor (vWF). Methods and Results-The capacity of transgene-encoded murine vWF to restore vWF function was studied in a mouse model of severe vWD after liver-specific gene transfer by hydrodynamic injection. By using a hepatocyte-specific ␣1 antitrypsin promoter, a considerably higher and longer-lasting vWF expression was obtained when compared with a cytomegalovirus promoter, reaching maximum vWF plasma levels that are 10Ϯ1 times higher than the wild-type level. Liver-expressed vWF showed the full range of multimers, including the high molecular weight multimers, and restored factor VIII plasma levels, consistent with correction of the bleeding time 3 but not 7 days after gene transfer.

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Section: Discussionmentioning

confidence: 99%

Restoration of Plasma von Willebrand Factor Deficiency Is Sufficient to Correct Thrombus Formation After Gene Therapy for Severe von Willebrand Disease

Meyer

Vandeputte

Pareyn

et al. 2008

ATVB

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“…10,11 Cryoprecipitate has previously been used to replenish vWF levels but is no longer considered because of the potential risk of transfusion-associated infection.…”

Section: Typementioning

confidence: 99%

Von Willebrand disease

Wilde

2007

Clinical Medicine

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“…A good clinical response was observed in 86% of the spontaneous bleeding episodes and in 71% of the surgical or invasive procedures. 32 Two retrospective studies and one prospective study have also been performed using Fandhi ® , a concentrate manufactured using a process very similar to that of Alphanate. [33][34][35] Haemate-P ® or Humate-P ® , an intermediate-purity VWF/FVIII concentrate, has been widely used in VWD.…”

Section: Current Management Of Von Willebrand Diseasementioning

confidence: 99%

“…32 This study included 53 patients receiving treatment with a double virus-inactivated VWF/FVIII concentrate (Alphanate ® ) for 87 bleeding episodes and in 39 patients receiving treatment prior to 71 surgical or invasive diagnostic procedures. A good clinical response was observed in 86% of the spontaneous bleeding episodes and in 71% of the surgical or invasive procedures.…”

Section: Current Management Of Von Willebrand Diseasementioning

confidence: 99%

Current Management of von Willebrand Disease

Federici¹

2008

European Oncology &Amp; Haematology

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Table 1 shows the relative frequency of bleeding symptoms in three large series of patients diagnosed at specialised centres. Several attempts were recently made to evaluate the sensitivity and specificity of bleeding symptoms, especially in the mild cases with VWD1 and VWF: RCo (>20U/dl). In a multicentre study carried out in obligatory carriers of VWD1, menorrhagia and epistaxis were poor predictors of the disease, while cutaneous bleeding and bleeding after dental extractions were more sensitive symptoms for diagnosis. 9 A bleeding severity score (BSS) has been analysed in affected and non-affected members of 154 families enrolled prospectively in a large European study on VWD1. 10 Despite the fact that this BSS was investigated prospectively in VWD1, this approach can be useful in all VWD, as was recently proposed in a prospective study. 11The diagnosis of VWD, particularly VWD1, may require several laboratory tests to be repeated on different occasions. These tests are usually applied for patients with suspected bleeding disorders. Table 2 summarises the different steps for VWD diagnosis. The bleeding time (BT), an original hallmark of the disease, is not always prolonged and may be normal in patients with mild forms of VWD, such as those with VWD1 and normal platelet VWF content. 4 It is therefore not particularly useful for diagnosis. Evaluation of closure time (CT) with the platelet function analyser (PFA-100) gives a rapid and simple measure of VWF-dependent platelet function at high shear stress. It can be performed in whole blood and can be employed instead of the BT in children or when the BT is not feasible. This system is sensitive and reproducible for VWD screening. The computerised axial tomography (CT) scan is normal in VWD2N and cannot be modified in VWD3 after the administration of VWF/FVIII concentrates. 12 Based on these observations, BT and CT were not introduced in the flow chart to be used in the differential diagnosis of VWD types (see Figure 2). Molecular and pre-natal diagnoses of VWD have been in use since the early 1990s. The first mutations were found within exon-28 of the VWF gene that is responsible for domains A1, A2 and A3. Most VWD2A cases are due to missense mutations in the A1 domain, with

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

Cited by 174 publications

References 24 publications

Restoration of Plasma von Willebrand Factor Deficiency Is Sufficient to Correct Thrombus Formation After Gene Therapy for Severe von Willebrand Disease

Restoration of Plasma von Willebrand Factor Deficiency Is Sufficient to Correct Thrombus Formation After Gene Therapy for Severe von Willebrand Disease

Von Willebrand disease

Current Management of von Willebrand Disease

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