title: Assessment of Immature Platelet Fraction in the Diagnosis of Wiskott-Aldrich Syndrome.
abstract: Children with Wiskott-Aldrich syndrome (WAS) are often first diagnosed with immune thrombocytopenia (ITP), potentially leading to both inappropriate treatment and the delay of life-saving definitive therapy. WAS is traditionally differentiated from ITP based on the small size of WAS platelets. In practice, microthrombocytopenia is often not present or not appreciated in children with WAS. To develop an alternative method of differentiating WAS from ITP, we retrospectively reviewed all complete blood counts and measurements of immature platelet fraction (IPF) in 18 subjects with WAS and 38 subjects with a diagnosis of ITP treated at our hospital. Examination of peripheral blood smears revealed a wide range of platelet sizes in subjects with WAS. Mean platelet volume (MPV) was not reported in 26% of subjects, and subjects in whom MPV was not reported had lower platelet counts than did subjects in whom MPV was reported. Subjects with WAS had a lower IPF than would be expected for their level of thrombocytopenia, and the IPF in subjects with WAS was significantly lower than in subjects with a diagnosis of ITP. Using logistic regression, we developed and validated a rule based on platelet count and IPF that was more sensitive for the diagnosis of WAS than was the MPV, and was applicable regardless of the level of platelets or the availability of the MPV. Our observations demonstrate that MPV is often not available in severely thrombocytopenic subjects, which may hinder the diagnosis of WAS. In addition, subjects with WAS have a low IPF, which is consistent with the notion that a platelet production defect contributes to the thrombocytopenia of WAS. Knowledge of this detail of WAS pathophysiology allows to differentiate WAS from ITP with increased sensitivity, thereby allowing a physician to spare children with WAS from inappropriate treatment, and make definitive therapy available in a timely manner.
authors.affiliation: Office of Cellular, Tissue and Gene Therapies, Center for Biologics Evaluation and Research, Food and Drug Administration , Silver Spring, MD , USA.
authors.forename: Robert
authors.initials: R
authors.lastname: Sokolic
authors.affiliation: Emmes Corporation , Rockville, MD , USA.
authors.forename: Neal
authors.initials: N
authors.lastname: Oden
authors.affiliation: Disorders of Immunity Section, Genetics and Molecular Biology Branch, National Human Genome Research Institute, National Institutes of Health , Bethesda, MD , USA ; Division of Immunology and Allergy, Centre Hospitalier Universitaire Vaudois , Lausanne , Switzerland.
authors.forename: Fabio
authors.initials: F
authors.lastname: Candotti
keywords: Wiskott–Aldrich syndrome; differential diagnosis; immature platelet fraction; immune thrombocytopenic purpura; thrombocytopenia