Abstract

Von Willebrand disease (VWD) is the most common congenital bleeding disorder, affecting up to 1% of the population. In type 1 VWD, which accounts for 65% of the disease, bleeding may be mild and up to 50% may have a normal screening APTT. Thus, in many the diagnosis may be missed and excess bleeding may occur postoperatively, which could potentially be prevented if reliable preoperative predictors existed. In order to assess possible predictors of postoperative bleeding and determine a cost-effective strategy to predict postoperative bleeding in patients with type 1 VWD, we constructed a decision tree model to test various screening strategies, including bleeding severity score (BSS), VWD assays (VWF:RCo; VWF:Ag, VIII:C), platelet function (PFA-100), and family bleeding history (Fam Hx), alone and in combination, in various sequence. For the model, sensitivity and specificity of coagulation tests, BSS, and family bleeding history were determined on 129 subjects with type 1 VWD, including 74 experiencing postoperative bleeding prior to diagnosis and 55 experiencing no postoperative bleeding prior to diagnosis. BSS was determined for each subject at the time of diagnosis (but prior to surgical bleeding), based on abstracted outpatient medical records. Testing, transfusion, and hospitalization costs were based on local costs, and DDAVP cost was based on average wholesale price. Outcomes were testing strategy cost and strategy effectiveness, as measured by postoperative bleeding risk. It was assumed that all patents testing positive, based on a given strategy, would receive preoperative DDAVP and be 100% protected from bleeding; and that those who developed postoperative bleeding would require three days of hospitalization and receive a transfusion. In the base case analysis, with VWD prevalence of 1%, BSS 3 3 and the Test Series (any of VWF:RCo VWF:Ag, F.VIII) dominates over all other strategies, based on having the highest sensitivity. When prevalence is varied 0–1%, the strategy of BSS 3 3 and the Test Series seems a reasonable choice if prevalence is 3 1%. At 1% prevalence, the incremental cost-effectiveness ratio (ICER) is about $103,000 which is at the edge of what may be considered economically reasonable. However, the ICER, for this strategy falls fairly rapidly, and is < $100,000 when prevalence is 3 1.03%. We also varied the proportion requiring hospitalization or transfusion to 5% and 1%, respectively, but these did not significantly affect the results. In conclusion, in individuals with BSS 3 3, proceeding with the Test Series (VWF:RCo, VWF:Ag, F.VIII) is a clinically and economically reasonable strategy for those in whom DDAVP should be given to prevent surgical bleeding, when the bleeding risk is 3 1%.

Strategy Cost Incremental Cost Effectiveness Incremental Effectiveness ICER 
BSS ≥ 3 & Test Series $1,296.10  0.055   
Fam Hx $1,703.90 $407.70 0.087 −0.032 (Dominated) 
Fam Hx & Test Series $2,187.50 $891.40 0.111 −0.056 (Dominated) 
Fam Hx or BSS ≥ 3 & Test Series $2.435.40 $1,139.30 0.127 −0.072 (Dominated) 
Test Series $2,508.60 $1,212.50 0.132 −0.077 (Dominated) 
BSS ≥ 3 $2.974.30 $1,678.10 0.171 −0.116 (Dominated) 
BSS ≥ 5 $5,966.10 $4.669.90 0.364 −0.309 (Dominated) 
No Testing or Rx $9,238.30 $7.942.20 0.574 −0.519 (Dominated) 
Strategy Cost Incremental Cost Effectiveness Incremental Effectiveness ICER 
BSS ≥ 3 & Test Series $1,296.10  0.055   
Fam Hx $1,703.90 $407.70 0.087 −0.032 (Dominated) 
Fam Hx & Test Series $2,187.50 $891.40 0.111 −0.056 (Dominated) 
Fam Hx or BSS ≥ 3 & Test Series $2.435.40 $1,139.30 0.127 −0.072 (Dominated) 
Test Series $2,508.60 $1,212.50 0.132 −0.077 (Dominated) 
BSS ≥ 3 $2.974.30 $1,678.10 0.171 −0.116 (Dominated) 
BSS ≥ 5 $5,966.10 $4.669.90 0.364 −0.309 (Dominated) 
No Testing or Rx $9,238.30 $7.942.20 0.574 −0.519 (Dominated) 

Disclosures: Ragni:Wyeth: Provision study drug, Research Funding; Baxter Bioscience: Research Funding; Chiron Corporation: Research Funding; Manchester Hospital NHS Trust: Research Funding; Archemix Corporation: Consultancy, Research Funding; Bayer: Consultancy, Research Funding; Novo-Nordisk: Consultancy, Research Funding.

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