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: 10.43). 04/2004; 103(6):2032-8. DOI: 10.1182/blood-2003-06-2072
Source: PubMed

ABSTRACT 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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    • "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.
    Blood reviews 05/2014; DOI:10.1016/j.blre.2014.03.001 · 5.45 Impact Factor
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    • "Apart from exclusion of patients with type 3 VWD (where DDAVP is ineffective) and type 2B VWD (where DDAVP is relatively contraindicated), criteria for selection of appropriate candidates for DDAVP trials are unclear. Predictors of response include the type, severity and genotype of VWD; however, reported response rates vary significantly in the literature (Revel-Vilk et al., 2003; Federici et al., 2004; Mannucci, 2004; Castaman et al., 2008). To determine the patient groups that would most benefit from a DDAVP trial, and the optimum testing protocol, we performed a retrospective analysis of all DDAVP trials for VWD at our institution. "
    International journal of laboratory hematology 11/2008; 32(1 Pt 1):e181-3. DOI:10.1111/j.1751-553X.2008.01117.x · 1.87 Impact Factor
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    • "The DDAVP (0AE3 lg/kg) was administered intravenously (n ¼ 16) or sub-cutaneously (n ¼ 17). The 16 patients who received DDAVP intravenously were enrolled in an European Union (EU) sponsored multicentre study (Biomed 2 European Project on Optimizing Therapy in Severe Forms of VWD), which had local ethics committee approval (Federici et al, 2000). The inclusion criteria for this multicentre study were type 1 or 2 VWD with severe bleeding history (more than one episode of severe blood loss) and one of the following laboratory parameters [bleeding time >15 min; VWF:Ag or VWF ristocetin cofactor activity (VWF:RCo) <10 IU/dl; or FVIII:C <20 IU/dl]. "
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    ABSTRACT: Desmopressin [1-deamino-8-d-arginine vasopressin (DDAVP)] has been successfully used in the treatment of type 1 von Willebrand disease (VWD) and mild haemophilia A (MHA). Data suggest that DDAVP can increase factor XI (FXI) plasma levels and may represent an effective treatment for mild FXI deficiency. We assessed the DDAVP response of FXI coagulant activity (FXI:C), FXI antigen (FXI:Ag), factor V coagulant activity (FV:C), and factor X coagulant activity (FX:C) in 33 individuals with VWD or MHA. DDAVP did not produce a clinically significant increase in FXI:C, FXI:Ag, FX:C or FV:C in any patient. The mean +/- SD FXI:C pre-DDAVP (time 0) and at 1 h post-DDAVP was 90.7 (+/-22.9) U/dl and 92.1 (+/-20.9) U/dl, respectively. The mean (+/-SD) FXI:Ag at time 0 and 1 h was 92.2 (+/-20.1) U/dl and 89.9 (+/-21.3) U/dl, respectively. There was a small reduction at 1 h post-DDAVP in both FV:C, from 101.8 (+/-20.9) U/dl to 97.2 (+/-21.4) U/dl (P < 0.001), and FX:C from 103 (+/-19.5) U/dl to 98.8 (+/-18.7) U/dl (P < 0.001). No significant increase in FXI:C, FXI:Ag, FV:C or FX:C levels was seen at 4 h post-DDAVP. This study failed to demonstrate a clinically significant increase in the levels of FXI, FX or FV following administration of DDAVP.
    British Journal of Haematology 07/2004; 126(1):100-4. DOI:10.1111/j.1365-2141.2004.04988.x · 4.96 Impact Factor
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