Response to desmopressin is influenced by the genotype and phenotype in type 1 von Willebrand disease (VWD): results from the European Study MCMDM-1VWD

Castaman, Giancarlo; Lethagen, Stefan; Federici, Augusto B.; Tosetto, Alberto; Goodeve, Anne; Budde, Ulrich; Batlle, J.; Meyer, Dominique; Mazurier, Claudine; Fressinaud, Édith; Goudemand, Jenny; Eikenboom, Jeroen; Schneppenheim, Reinhard; Ingerslev, Jørgen; Vorlová, Z; Hui‐Kang, David; Holmberg, Lars; Pasi, John; Hill, F. G. H.; Peake, I. R.; Rodeghiero, Francesco

doi:10.1182/blood-2007-08-109231

Cited by 186 publications

(207 citation statements)

References 25 publications

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“…DDAVP is used to treat type 1 VWD, with a 2‐4–fold increase in VWF and a 3‐6–fold increase in FVIII within 30‐60 minutes 47, 48. Since patients with type 2 VWD do not have functional VWF, treatment with DDAVP is not usually adequate to alleviate bleeding symptoms as it only increases the concentration of dysfunctional VWF in the blood.…”

Section: Treatment Of Vwdmentioning

confidence: 99%

Current issues in diagnosis and treatment of von Willebrand disease

Keesler

Flood

2018

Research and Practice in Thrombosis and Haemostasis

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Essentials Classification of VWD includes quantitative (types 1 and 3) and qualitative (type 2) variants.New assays of VWF‐platelet binding may improve accuracy in diagnosis.Collagen binding represents an additional function of VWF not measured by current tests.Treatment options for VWD include desmopressin, plasma‐derived, and recombinant VWF. Clinically, von Willebrand disease (VWD) presents as mucosal bleeding caused by a decreased quantity or quality of von Willebrand factor (VWF). Diagnosis of VWD requires careful consideration of patient specific factors, bleeding symptoms, and laboratory results. Patients with borderline low VWF levels remain challenging, given that low VWF is not necessarily a guarantee of bleeding, but is present in many patients with symptoms, and treatment of low VWF may improve bleeding. Laboratory diagnosis of VWD is complex and no single test can determine the presence or absence of functional VWF. Historically, VWF binding to platelet GPIbα was measured by the ristocetin cofactor assay (VWF:RCo); a new assay using platelet GPIbα in the absence of ristocetin (VWF:GPIbM) is gradually replacing the VWF:RCo due to improved accuracy in diagnosis. VWF binding to collagen is a separate function, and requires specific testing to determine if a collagen binding defect is present. Regardless of these laboratory complexities, clinicians can empirically treat VWD to alleviate bleeding symptoms by raising VWF levels through desmopressin or VWF concentrate. Recombinant VWF is now available, but clinicians may need to add an initial dose of FVIII when treating emergency bleeds.

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Section: Treatment Of Vwdmentioning

confidence: 99%

Current issues in diagnosis and treatment of von Willebrand disease

Keesler

Flood

2018

Research and Practice in Thrombosis and Haemostasis

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“…44,[47][48][49] Desmopressin induces a significant increase of plasma FVIII and VWF levels after administration by triggering their release from endothelial cells and represents the first-choice option for patients with type 1 VWD, in whom cellular VWF is usually normal. Type 2 VWD patients have a highly variable pattern of response to DDAVP, although it is better in type 2M than in type 2A.…”

Section: Treatment Of Type 2 Vwd: a Case-based Approachmentioning

confidence: 99%

How I treat type 2 variant forms of von Willebrand disease

Tosetto

Castaman²

2015

Blood

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Type 2 von Willebrand disease (VWD) includes a wide range of qualitative abnormalities of von Willebrand factor structure and function resulting in a variable bleeding tendency. According to the current classification, 4 different subtypes can be identified, each with distinctive phenotypic and therapeutic characteristics. Current available laboratory methods allow a straightforward approach to VWD subtyping, and although the precise molecular characterization remains complex, it is not required for appropriate treatment of the vast majority of cases. Desmopressin can be useful only in a few type 2 cases compared with patients with actual quantitative deficiency (type 1), most often in variants with a nearly normal multimeric pattern (type 2M). However, since no laboratory test accurately predicts response to desmopressin, a trial test should always be performed in all type 2 VWD patients, with the exception of type 2B ones. Replacement therapy with plasma-derived von Willebrand factor-factor VIII concentrates represents the safe mainstay of treatment of all patients, particularly those not responding to desmopressin or requiring a sustained hemostatic correction because of major surgery or bleeding. A significant patient bleeding history correlates with increased bleeding risk and should be considered in tailoring the optimal antihemorrhagic prophylaxis in the individual patient.

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“…39 39 Consequently, patients should always be tested with an in vivo trial rather than by other tests. Thus, in our patient and her daughter, we would perform FVIII:C, platelet aggregation to ristocetin at low concentration, and a desmopressin trial infusion, after obtaining informed consent from both persons.…”

Section: Casementioning

confidence: 99%

“…We define patients as "desmopressin responders" when they exhibit a peak level for both VWF:RCo and FVIII:C of more than 50 IU/dL, which is a concentration that may be considered sufficient for effective hemostasis during minor invasive procedures. 39 Assessment at 4 hours from infusion is advised to identify patients with increased clearance who are possible candidates for alternative treatments. 39,[41][42][43] However, patients with VWD Vicenza, which is associated with the R1205H mutation, and who show the shortest half-life of FVIII and VWF after desmopressin, can be effectively treated with desmopressin for most instances, including parturition.…”

Section: Treatment Of Vwd Casementioning

confidence: 99%

“…39 Assessment at 4 hours from infusion is advised to identify patients with increased clearance who are possible candidates for alternative treatments. 39,[41][42][43] However, patients with VWD Vicenza, which is associated with the R1205H mutation, and who show the shortest half-life of FVIII and VWF after desmopressin, can be effectively treated with desmopressin for most instances, including parturition. 43,44 Patients with type 3 VWD are usually unresponsive to desmopressin, although some patients do experience an increase of FVIII:C to effective hemostatic levels, even without a change in the bleeding time (BT).…”

Section: Treatment Of Vwd Casementioning

confidence: 99%

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How I treat von Willebrand disease

Rodeghiero

Castaman

Tosetto

2009

Blood

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Recent multicenter studies have clarified the molecular basis underlying the different von Willebrand disease (VWD) types, all of which are caused by the deficiency and/or abnormality of von Willebrand factor (VWF). These studies have suggested a unifying pathophysiologic concept. The diagnosis of VWD, remains difficult because its clinical and laboratory phenotype is very heterogeneous and may overlap with normal subjects. Stringent criteria are therefore required for a clinically useful diagnosis. In this paper, we delineate a practical approach to the diagnosis and treatment of VWD. Our approach is based on the critical importance of a standardized bleeding history that has been condensed into a final bleeding score and a few widely available laboratory tests, such as VWF ristocetin cofactor activity, VWF antigen and factor VIII. This approach would help identify those subjects who will probably benefit from a diagnosis of VWD. The next step involves performing a trial infusion with desmopressin in all patients who fail to exhibit an enhanced responsiveness to ristocetin. On the basis of these results and through a series of illustrative examples, the clinician will be able to select the best approach for the optimal management of VWD, according to the patient's characteristics and clinical circumstances. (Blood. 2009;114: 1158-1165)

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Response to desmopressin is influenced by the genotype and phenotype in type 1 von Willebrand disease (VWD): results from the European Study MCMDM-1VWD

Cited by 186 publications

References 25 publications

Current issues in diagnosis and treatment of von Willebrand disease

Current issues in diagnosis and treatment of von Willebrand disease

How I treat type 2 variant forms of von Willebrand disease

How I treat von Willebrand disease

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