Use of Serum Antiopoietin-2 Assay for Therapeutic Decision-Making in Patients with Vascular Anomalies

Vascular anomalies (VA), comprised of tumors and malformations, are a spectrum of disorders including benign and malignant lesions characterized by abnormal growth or development of vascular and/or lymphatic vessels that can affect any organ. If left untreated VA can be associated with substantial morbidity and mortality through disfiguration, organ dysfunction, hemorrhage, infection, and/or thrombosis. Correct diagnosis is critical to provide optimal management recommendations but is often challenging due to the phenotypic heterogeneity of these lesions. The biomarker angiopoietin-2 (ang-2), a member of a family of growth factors that regulate blood vessel growth and development, has previously been reported to be elevated in certain VA associated with coagulopathy, including Kaposiform hemangioendotheliomas (KHE) and Kaposiform lymphangiomatosis (KLA) (Le Cras TD, Angiogenesis 2017). Ang-2 levels have been reported to decrease in some patients in response to treatment with sirolimus (Le Cras TD, Angiogenesis 2017; Crane J, Pediatr Blood Cancer 2020). Based upon the published methodology, a clinical serum ang-2 assay was developed that employs a quantitative sandwich enzyme immunoassay technique using a monoclonal antibody specific for human ang-2. Age specific normal ranges for serum ang-2 were determined and were congruent with those first reported for the research assay (range: 1,434-4,141 pg/mL). Here we describe two VA cases in which the clinical ang-2 assay was utilized to aid diagnosis and to detect treatment response, replacing or limiting more invasive, expensive, and high-risk evaluations such as sedated imaging or surgical biopsy.