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Abstract: We evaluated the cost-effectiveness of prophylaxis with recombinant von Willebrand factor (rVWF) vs with plasma-derived von Willebrand factor (pdVWF) for patients with severe Von Willebrand disease. We found that rVWF is a cost-saving factor replacement compared with pdVWF across all willingness-to-pay thresholds in the United States., (© 2024 American Society of Hematology. Published by Elsevier Inc. All rights are reserved, including those for text and data mining, AI training, and similar technologies.)

BACKGROUND: von Willebrand disease (VWD) can lead to serious, life-threatening bleeding events associated with substantial clinical and economic burden. OBJECTIVE: To estimate the prevalence, health care resource utilization (HCRU), and costs associated with major bleeding events in patients with VWD. METHODS: This was a retrospective analysis of the IBM MarketScan database (2008-2016). Selected patients had ≥ 2 VWD diagnoses, no diagnosis of acquired coagulation factor deficiency, and continuous health care plan enrollment for ≥ 12 months from eligibility start date. Prevalence was calculated as the proportion of eligible patients with ≥ 1 major bleeding event during the observation period (start to end of continuous eligibility). HCRU and costs in the 12-month continuous enrollment period following the first major bleeding event were compared with those from a comparable 12-month period for patients without major bleeding events. RESULTS: Of the 19,785 patients with VWD, 15% experienced ≥ 1 major bleeding event during a median follow-up of 4 years; 89% of these events were gastrointestinal bleeds. For the economic analysis, 773 patients with ≥ 1 major bleeding event and 4,285 patients without major bleeding events met the selection criteria. Controlling for baseline covariates, patients with major bleeding events had significantly ( P < 0.0001) more inpatient admissions (incidence rate ratio [IRR] = 3.2; 95% CI = 2.78-3.77), longer inpatient stays (IRR = 3.9; 95% CI = 3.12-4.93), and more emergency department visits (IRR = 2.0; 95% CI = 1.77-2.27) and outpatient visits (IRR = 1.3; 95% CI = 1.19-1.34) than patients without major bleeding events. Annual health care costs were significantly higher ( P < 0.01) for patients with major bleeding events than those without them (predicted mean cost differences: total = $20,890, pharmacy = $2,593, and medical = $18,293). CONCLUSIONS: Major bleeding events were associated with increased HCRU and costs, mostly inpatient costs. Therefore, optimizing therapy to prevent or reduce major bleeding events has the potential to reduce health care use and costs in patients with VWD. DISCLOSURES: This study was funded by Baxalta U.S. Inc., a Takeda company (Lexington, MA). The study sponsor was involved with the study design, analysis, and interpretation of data; writing of the manuscript; and the decision to publish the article. Lu, Wu, and Ewenstein are employees of Baxalta U.S. Inc., a Takeda company, and are Takeda stock owners. Farahbakhshian is an employee of Shire U.S. Inc., a Takeda company, and is a Takeda stock owner. Oladapo was an employee of Baxalta U.S. Inc., a Takeda company, at the time the analysis was completed and the manuscript developed, and is a Takeda stock owner.

Competing Interests: Disclosure The authors report no conflicts of interest in this work.

Patients with von Willebrand disease (VWD) often require treatment with supplemental von Willebrand factor (VWF) prior to procedures or to treat bleeding. Commercial VWF concentrates and more recently recombinant human VWF (rVWF) have replaced cryoprecipitate as the mainstay of therapy. In comparison with cryoprecipitate, the VWF content and multimer distribution under current manufacturing processes of these commercial products has not been reported. We measured the factor VIII (FVIII:C), VWF antigen (VWF:Ag), VWF collagen-binding activity (VWF:CB), VWF platelet-binding activity by GPIbM enzyme-linked immunosorbent assay (VWF:GPIbM), and percentage of high-molecular-weight (HMWM) VWF in 3 pools of group A and O cryoprecipitate, 3 vials of VWF concentrate (Humate-P), and 1 lot of rVWF (Vonvendi). We found that both group O and group A cryoprecipitate have significantly higher ratios of VWF:GPIbM activity and FVIII:C activity relative to VWF:Ag and have better preservation of HMWM than Humate-P. Although not compared statistically, rVWF appears to have more HMWM VWF and a higher ratio of VWF:GPIbM to VWF:Ag than Humate-P and cryoprecipitate. The estimated acquisition cost for our hospital for treating one major bleeding episode was more than 4-fold higher with Humate-P and 7- to 10-fold higher with rVWF than with cryoprecipitate.

Purpose: A multidisciplinary initiative to promote more cost-effective use of blood factor derivatives and increase pharmacist involvement in associated order verification, dispensing, and monitoring activities is described., Summary: After an evaluation of a hospital's procedures for the use of blood factor derivatives identified inconsistencies and opportunities for cost savings, a revised medication-use process promoting continuous infusion of selected products (factors VIII, IX, and VIII/von Willebrand factor) was developed by pharmacy staff with input from physicians and nurse educators. The implementation of the enhanced medication-use procedures included (1) the publication of a compendium of key information on commonly used blood factors, including specific guidance on dosing and administration, (2) the use of Web-based educational modules targeting pharmacists and nurses, (3) greater involvement by pharmacists in blood factor order justification and verification, (4) routine pharmacist assessment of pertinent laboratory values and other determinants of optimal dosing, and (5) refined procedures for changing i.v. tubing. Surveys of pharmacists conducted before and after the practice changes indicated a significant increase in their knowledge of blood factor products and evidence-based best practices for the management of hemophilia., Conclusion: Through a multidisciplinary initiative involving pharmacists, physicians, and nurses, new procedures to promote continuous infusion of selected blood factor products were implemented. Results of a postimplementation survey indicated that educational tools were effective in increasing pharmacists' knowledge of blood factor derivatives and hemophilia management.

Objective: To construct a decision analysis model to evaluate the cost utility of von Willebrand disease (VWD) testing in adolescents with menorrhagia., Study Design: A 20-year Markov decision analytic model was constructed to evaluate the cost utility of two strategies: testing or not testing for VWD. The model includes probabilities of remaining well, suffering an acute menorrhagia bleeding event, surgical complications, oral contraceptive pill complications, or dying. Probabilities, costs, and utilities were estimated from published literature. The prevalence of type 1 VWD in adolescent females with menorrhagia was estimated at 13%., Results: The cost of testing adolescents with menorrhagia for VWD was $1790, versus $1251 for not testing for VWD. The effectiveness of not testing in quality-adjusted life-years (QALYs) gained (14.237 QALYs) was similar to the VWD testing strategy (14.246 QALYs). Compared with not testing for VWD, screening for VWD had an incremental cost-effectiveness ratio of $62,791 per QALY, a value typically considered economically reasonable., Conclusions: In adolescents with menorrhagia, testing for VWD before the initiation of oral contraceptives is cost-effective., (Copyright (c) 2010 Mosby, Inc. All rights reserved.)

Molecular diagnosis of von Willebrand Disease (VWD) is particularly complex. The autosomal von Willebrand factor gene (VWF) is large and highly polymorphic, and there is a highly homologous (>96%) partial pseudogene in chromosome 22. Because of these difficulties, application of molecular study of VWD to the clinical routine has been considerably delayed. Recent advances in sequencing technology and bioinformatics could convert direct sequencing of the complete VWF into a routine diagnostic tool for VWD, which is especially desirable in types 1 and 3. This study describes a highly optimized procedure in which all the coding and intronic flanking regions of VWF are amplified under identical thermocycling parameters in a ready-to-use PCR plate format. The entire sequencing procedure, from blood extraction to mutation identification, can be done within 24 hours, resulting in a simple, versatile, cost-effective strategy with little hands-on time requirements. To validate the method, we performed full-length VWF sequencing of 21 index cases including seven of each VWD type. A total of 30 VWF genetic variations were identified. Twelve of these sequence variations are new, including four missense, one nonsense, one insertion, the first insertion-deletion described in VWF, and 5 potential splice site mutations. To our knowledge, this is the fastest and most efficient protocol designed to date for complete sequencing of the VWF coding region in the molecular diagnosis of VWD.

A variety of treatment options are available at present for patients with von Willebrand disease (vWD), some of which are affordable for patients in developing countries. For most patients who have type 1 vWD, desmopressin acetate (DDAVP) is the treatment of first choice, at least for minor bleedings and for prophylaxis. It is advisable, however, to use a test dose first to note the patient's response. DDAVP is safe to use, affordable, and easy to administer. However, most patients with type 2 vWD and all patients with type 3 fail to respond to DDAVP. For these patients, other options are used. Almost all patients with vWD will benefit from fresh frozen plasma and from cryoprecipitate, and these are viable options for developing countries. Both have certain disadvantages, but they can, depending upon the circumstances and facilities, be produced in developing countries. In developed countries, factor VIII/von Willebrand factor concentrates are widely used, especially for major bleedings and for surgeries on these patients. These concentrates are safe and virus inactivated, but costly. Ancillary treatment modalities such as antifibrinolytic agents and certain hormones are usually given in conjunction with other modalities. The treatment of patients with antibodies to vWF is also described, and monitoring needs during therapy are reviewed.

There is limited information on von Willebrand disease (vWD) in developing countries. A questionnaire survey in 1998 showed that overall, less than one third of the expected number of patients with vWD in the population had been detected. Among those registered, the proportion with the severe form of the disease was relatively higher, forming up to 50% of the total, particularly in those countries with high prevalence of consanguineous marriages. Diagnosis was based on von Willebrand factor antigen (vWF:Ag) assays, vWF ristocetin cofactor (vWF:Rco) activity, and ristocetin-induced platelet aggregation (RIPA) at the reporting centers, but vWF multimer analysis was not widely available. Responsiveness to desmopressin acetate (DDAVP), which could be very significant clinically, was not often assessed. An attempt was made to assess accuracy of reporting of the prevalence of vWD by conducting a second survey aimed at normalizing the reported numbers with that of severe hemophilia A in a defined population on the presumption that the latter is less likely to be missed. These data showed that in most countries, the ratio of patients with vWD to severe hemophilia varied between 0.1 to 0.6 with a mean of approximately 0.4, as opposed to an expected ratio of approximately 1 (based on population-based data from Italy), confirming the underdiagnosis of vWD even within the same health-care system. A system for collecting more extensive and detailed data on vWD from developing countries (where 80% of the world's population lives) is required. Efforts are needed to develop national registries and make at least basic services for diagnosis and treatment widely available.

This paper presents the results of a contingent valuation study measuring willingness to pay (WTP) for treatment of patients with von Willebrand's disease. Median WTP for treatment of this disorder was $1,500 or $3,500, depending on how the initial bid was structured. Regression analysis shows that income, education, and a category rating scale for health status were significant in predicting WTP. The adjusted annual WTP was $2,178. WTP surveys may increasingly be useful for health technology assessment. Starting point bias in how the bids are structured must be recognized.