A retrospective study of the utility of desmopressin (1‐deamino‐8‐D‐arginine vasopressin) trials in the management of patients with von Willebrand disorder

Sir, desmopressin (1-deamino-8-d-arginine vasopressin; DDAVP) is effective in securing haemostasis in selected patients with von Willebrand disorder (VWD) undergoing haemostatic challenge (Mannucci, 2004). Because of the heterogenous response to DDAVP, it is currently recommended that patients with VWD undergo a therapeutic trial prior to elective surgical procedures. 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. Between 1990 and 2006, we identified 129 patients who underwent a DDAVP trial with a bleeding history and a prior diagnosis of VWD. During this period, patients known to have type 2B or type 3 VWD did not undergo DDAVP trials, according to unit protocol. Review of results obtained immediately prior to DDAVP administration confirmed 104 of these patents to have VWD with sufficient laboratory testing for definitive classification; of the remaining patients, six had no abnormality other than mildly reduced ristocetin cofactor assay [von Willebrand factor (VWF):RCo] activity and 19 had normal VWF parameters (the latter were excluded from subsequent analysis). Classification was performed according to standard criteria (Sadler et al., 2006) on the basis of factor VIII (FVIII) levels, von Willebrand factor antigen (VWF:Ag), VWF:RCo, collagen binding assay (VWF:CB); multimer analysis and ristocetin-induced platelet aggregation were available in selected cases. Type 2A was distinguished from type 1 VWD by a function (VWF:CB and/or VWF:RCo) to antigen ratio of <0.7 and multimer analysis which was performed in all cases where VWF parameters were <20%. The majority of patients were adults (median age 25 years, range 4–64 years; 60% female) with type 1 VWD (94/104) or type 2A VWD (8/104). Two patients had type 2N VWD. Six patients had isolated low VWF:RCo activity (in the context of normal VWF:Ag and VWF:CB). The majority (5/6) of this subgroup had a function (VWF:RCo) to VWF:Ag ratio <0.7, consistent with a type 2 defect, but as results of multimer analysis were unavailable they could not be definitively classified as type 2M. DDAVP (0.3 lg/kg) was administered by slow intravenous infusion over 45 min. Blood samples were collected at baseline and approximately 1 h post administration, with additional testing performed at 24 h where possible. Although there is theoretical benefit to additional testing at 2 and 4 h post-DDAVP, this was not performed in the majority of our cases because of practical limitations of serial phlebotomy in the ambulatory setting. A complete response (CR) at either time-point post-DDAVP was defined as an increase in all VWD parameters to greater than the lower limit of normal (50% activity of normal pooled plasma for FVIII, VWF:Ag, VWF:RCo and VWF:CB, respectively); a partial response (PR) was defined as an increase to between 30% and lower limit of normal. The latter response criterion was chosen as this was deemed to be the lowest acceptable level for VWF parameters to obtain adequate haemostasis in minor bleeding challenges. Our results are summarised in Table 1. In the type 1 cohort at 1-h post-infusion, 75 of 94 patients experienced a CR, 14 a PR, and five had no clinically significant response. All patients with baseline VWF:Ag >15% and VWF:CB >9% responded with at least a PR, but only 2/6 with either of these parameters <10% responded. Virtually all patients (55 of 57) with a baseline VWF:Ag, VWF:RCo and VWF:CB >20% had a CR at 1 h. Factor VIII levels reached normal levels in all cases regardless of VWF responses. No patient with type 2A responded adequately. All patients with mildly reduced VWF:RCo in isolation and both patients with type 2N VWD achieved a CR. LETTER TO THE EDITOR INTERNATIONAL JOURNAL OF LABORATORY HEMATOLOGY