Biologic response to desmopressin in patients with severe Type 1 and Type 2 von Willebrand disease: results of a multicenter European study

University of Milan, Milano, Lombardy, Italy
Blood (Impact Factor: 10.45). 04/2004; 103(6):2032-8. DOI: 10.1182/blood-2003-06-2072
Source: PubMed


This study prospectively evaluated the rate of biologic response to desmopressin (DDAVP) in 66 patients with type 1 or 2 von Willebrand disease (VWD), each of whom had, on the basis of available records, a clinically significant bleeding history and at least one of the following laboratory abnormalities: bleeding time (BT) longer than 15 minutes, ristocetin cofactor activity (VWF:RCo) less than 10 IU/dL, factor VIII coagulant activity (FVIII:C) less than 20 IU/dL (severe VWD). Before the study, responsive patients were defined as those who, 2 hours after infusion of 0.3 microg/kg DDAVP, had increased baseline values of VWF:RCo and FVIII:C by at least 3-fold and achieved levels of at least 30 IU/dL for both and a BT of 12 minutes or less. The rate of biologic response varied according to VWD types and was higher in type 1 (7 of 26, 27%) than in type 2 (7 of 40, 18%) (type 2A [1 of 15, 7%], type 2M [3 of 21, 14%], type 2N [3 of 4, 75%]). Mutations in the VWF gene were previously known or newly identified in most patients with types 2A (n = 15 of 15), 2M (n = 15 of 21), and 2N (n = 4 of 4), but in none of those with type 1 VWD. Genotype provided more information than phenotype in predicting individual responses to DDAVP only in patients with 2A and 2N VWD. This prospective study showed that the rate of biologic response to DDAVP is relatively low not only in type 2 but also in type 1 VWD when uniform and stringent criteria for patient selection and responsiveness are applied.

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    • "The data on response to DDAVP infusion in patients heterozygous for this mutation are conflicting (Federici et al, 2004; Castaman et al, 2008). One out of four patients responded to DDAVP in a study by Federici et al (2004); we have previously shown a good response to DDAVP, raising VWF:Ag levels more than three-fold in three family members with this mutation (Castaman et al, 1995), while in the MCMDM- 1VWD study the patient did not respond (Table II). Such a variation in response among patients carrying the same "
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    ABSTRACT: Von Willebrand disease (VWD) is a bleeding disorder characterized by reduced plasma von Willebrand factor (VWF) levels or functionally abnormal VWF. Low VWF plasma levels in VWD patients are the result of mutations in the VWF gene that lead to decreased synthesis, impaired secretion, increased clearance or a combination thereof. However, expression studies of variants located in the A domains of VWF are limited. We therefore characterized the biosynthesis of VWF mutations, located in the VWF A1–A3 domains, that were found in families diagnosed with VWD. Human Embryonic Kidney 293 (HEK293) cells were transiently transfected with plasmids encoding full-length wild-type VWF or mutant VWF. Six mutations in the A1–A3 domains were expressed. We found that all mutants, except one, showed impaired formation of elongated pseudo-Weibel-Palade bodies (WPB). In addition, two mutations also showed reduced numbers of pseudo-WPB, even in the heterozygous state, and increased endoplasmic reticulum retention, which is in accordance with the impaired regulated secretion seen in patients. Regulated secretion upon stimulation of transfected cells reproduced the in vivo situation, indicating that HEK293 cells expressing VWF variants found in patients with VWD can be used to properly assess defects in regulated secretion.
    Full-text · Article · Aug 2014 · British Journal of Haematology
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    • "c o m / l o c a t e / b l r e 2. Haemophilia and von Willebrand disease (VWD) 2.1. Effects of desmopressin in patients not undergoing surgery Most patients with Type 1 VWD and FVIII/VWF levels N10 IU/mL do respond to DDAVP [23] whereas Type 2 has a more variable response pattern [24]. The use in most cases of Type 2B is contraindicated due to the risk of platelet aggregation and thrombocytopenia and Type 3 VWD is nonresponsive. "
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    ABSTRACT: Stimulation with the vasopressin analogue desmopressin (DDAVP) of extrarenal arginine vasopressin (AVP) V2-receptors in endothelial cells and possible in platelets increases the circulating levels of coagulation factor VIII (FVIII), von Willebrand factor (VWF) and tissue plasminogen activator (t-PA). The purpose of this paper is to provide an updated review of current information on the efficacy and safety of DDAVP in the treatment of haemophilia, von Willebrand Disease (VWD), Uremia, Liver Cirrhosis, and in Congenital or Drug-Induced Platelet Dysfunction – under surgical or non-surgical conditions. In summary, desmopressin is an effective hemostatic drug that when administered iv, sc or intranasally increases plasma levels of FVIII and VWF 2–6 times and improves platelet function. It has a proven hemostatic efficacy in mild hemophilia A and VWD as well as in uremia, liver chirrosis and in congenital and acquired, drug induced platelet dysfunction. Desmopressin has few side effects but observation is advised in small children and elderly.
    Full-text · Article · May 2014 · Blood reviews
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    • "Treatment can be repeated every 12–24 hours depending on the type or severity of the bleed. Plasma vWF:FVIII levels are increased to 2–4 times above the baseline within 30 minutes and in general high levels last in the plasma for 6–8 hours.11,12 "
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    ABSTRACT: Von Willebrand disease (vWD) is the most common hereditary bleeding disorder. The aim of therapy is to correct the dual hemostatic defect, due to defective platelet adhesion-aggregation and abnormal coagulation due to Factor VIII (FVIII) deficiency. The choice of treatment depends on a number of factors, including the severity of the bleed, the procedure planned, the subtype and severity of the disease and the age and morbidity of the patient. Desmopressin (DDAVP) is the treatment of choice for type 1 vWD as it increases endogenous release of FVIII and von Willebrand factor (vWF) and is also used in some subtypes of type 2 vWD. In those patients in whom DDAVP is ineffective or contraindicated, levels can be restored by infusing vWF:FVIII concentrates. The role of antifibrinolytic treatment is an important adjunct to replacement therapy during minor or major surgery involving mucosal surfaces. The dosing and timing of vWF:FVIII concentrates is important depending on the nature of the surgical procedure. The role of secondary prophylaxis needs to be further defined.
    Full-text · Article · Apr 2011 · Hematology Research and Reviews
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