The Clinical Utility of the 1-Deamino-8-D-Arginine Vasopressin (DDAVP) Trial in the Management of Patients with Von Willebrand Disease: A Retrospective Study.

DDAVP has been shown to be effective in securing hemostasis in certain patients with mild and moderate von Willebrand disease (vWD) undergoing hemostatic challenge. However as the response to this agent is heterogeneous, it is currently recommended that patients with vWD undergo a therapeutic trial of this agent prior to any elective invasive procedures. We performed a retrospective review of DDAVP response in patients with vWD in order to determine which patient groups most benefit from a DDAVP trial, and the optimum testing protocol, particularly examining the need to recall the patient for testing at 24 hours.

Between 1990–2006 we identified 129 patients undergoing DDAVP trial for a historical diagnosis of vWD based on a previous low von Willebrand factor antigen (vWF:Ag), ristocetin cofactor activity (vWF:RiCoF) or collagen-binding activity (vWF:CBA), and a bleeding history. Twenty-one patients were excluded from analysis having normal vWD parameters prior to DDAVP infusion. The median age of patients was 25 years, (range 4–64), with 60% being female. The distribution of vWD subtypes was as follows: 94 type 1, eight type 2A, and six with a bleeding phenotype and no abnormality other than mildly reduced vWF:RiCoF. DDAVP was administered by IV infusion with samples taken for testing pre-infusion and between 1–2 hours post infusion. Additional testing at 24 hours was performed in the majority after 2003. A complete response (CR) was defined as an increase in all vWD parameters to within the normal range (vWF:Ag [50–200%], vWF:RiCoF [50–150%], vWF:CBA [50–200%]); a partial response (PR), an increase to between 30% and lower limit of normal.

Results: In the type 1 vWD cohort, at one hour post infusion 75/94 experienced CR, 15/94 PR and 4/94 no response (NR). All patients with baseline vWF:Ag >15% and vWF:CBA >9% responded. Virtually all patients with a baseline vWF:Ag >25%, vWF:RiCoF >25% and a vWF:CBA >27% had a CR at one hour. Factor VIII levels reached normal levels in all cases regardless of vWF responses. No patient with type 2A responded, and all patients with mildly reduced RiCoF in isolation achieved CR. Nineteen patients with type 1 disease underwent testing at 24 hours. 13/15 with type 1 and a CR at one hour had adequate (>30%) levels at 24 hours. None of four patients with a PR at one hour had adequate levels at 24 hours. Median vWF:Ag and vWF:CBA levels were approximately 20% above initial levels at 24 hours in the responders.

Conclusions: Patients with type 2A, and type 1 vWD with baseline vWF:Ag ≤15% and vWF:CBA ≤9% should not undergo DDAVP trial as they are unlikely to respond. Patients with type 1 vWD and baseline vWF:Ag >25%, vWF:RiCoF >25% and vWF:CBA >27%, or others with isolated low vWF:RiCoF and bleeding phenotype, need not undergo a DDAVP trial to establish efficacy. However, these patients may still require a DDAVP trial for assessment of safety and tolerability. It is not essential to measure factor VIII levels in patients who are undergoing a DDAVP trial. All patients with vWD parameters in the normal range one hour following DDAVP should be considered for further testing at 24 hours to identify the occasional suboptimal responder. Implementation of this testing strategy would reduce the requirement for DDAVP trials by approximately 35%, based upon our series.