Von Willebrand Disease in the elderly: clinical perspectives

Abstract

Von Willebrand disease (VWD) is an inherited bleeding disorder that affects up to 1% of the population. In most cases, VWD results from a mutation in the von Willebrand Factor (VWF) gene, which alters the amount and function of VWF, a key glycoprotein in both primary and secondary hemostasis. A comprehensive analysis of patients with VWD should include VWF activity, antigen levels, platelet function, and a careful bleeding history. Treatment options include antifibrinolytics, desmopressin, and VWF replacement therapy. VWF levels fluctuate due to age, stress, environmental exposures, and pharmacologic treatment. Treatment guidelines exist to treat and prevent bleeding for patients undergoing surgery and medical procedures, but often these must be reevaluated in the setting of age-related comorbidities including cardiovascular events, venous thrombosis, and malignancy. In addition, many age-related complications are associated with a secondary acquired von Willebrand syndrome (AVWS), including malignancies, hypothyroidism, cardiovascular diseases, and cardiac replacement devices. The current literature is limited by a lack of older patients in clinical trials. Larger studies are needed to determine if age-related comorbidities affect VWD patients at different frequencies than the general elderly population. There is also a significant need for registry-based studies to evaluate many age-related comorbidities in VWD patients.

Population Pharmacokinetic Modeling of von Willebrand Factor Activity in von Willebrand Disease Patients after Desmopressin Administration

“…31 Pathophysiologically, desmopressin binds to vasopressin receptors on the endothelial cell surface, ultimately resulting in observed endogenous release of VWF and FVIII. 27,32 Hypothetically, age may influence number or sensitivity of vasopressin receptors, resulting in a higher increase in VWF activity after desmopressin administration. Moreover, although not validated in humans, adult rats have been shown to have more vasopressin receptors than young rats, potentially resulting in a larger increase in VWF activity after desmopressin administration.…”

Acquired Von Willebrand Syndrome (AVWS) in cardiovascular disease: a state of the art review for clinicians

“…Laboratory test results are compatible with type 1 VWD if the levels of both vWF:RCo (ristocetin co-factor) activity and vWF:Ag (antigen) are > 2 SD below the population mean and ABO type adjusted mean on > 2 separate determinations. The plasma vWF multimer distribution is typically normal [33,34].…”

“…Proteolytic cleavage has also been described in patients with pancreatitis, liver cirrhosis and leukemia. In hypothyroidism, AVWS may be the end-result of decreased synthesis of otherwise normal vWF [34,36]. Patients with AVWS have a bleeding phenotype; however, in some instances, a thrombosis phenotype or a concomitant predisposition to both thrombosis and bleeding is observed.…”

Do patients with von Willebrand disease exhibit higher blood loss and revision rates in hip and knee arthroplasty? A case‐control study

“…Patients with this diagnosis have a recognized incidence of haemarthrosis and other bleeding complications. These issues make this cohort of patients impose frequent orthopaedic operations, especially arthroplasty of hip and knee . The presence of a bleeding diathesis potentially increases the risk of perioperative complications include bleeding, a high rate of blood transfusions, wound healing disorders and a high rate of revisions when compared to patients without bleeding disorders …”