Assessment of Immature Platelet Fraction in the Diagnosis of Wiskott-Aldrich Syndrome.

Fabio Candotti,Robert Sokolic,Neal Oden

doi:10.3389/fped.2015.00049

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.

Highlights

Immune thrombocytopenia (ITP) is the most common cause of newly discovered isolated thrombocytopenia in childhood [1], with an incidence of 1.9–6.4 in 100,000 children per year, and a prevalence of 9.3 in 100,000 boys [2]
In both subjects with a diagnosis of immune thrombocytopenia (ITP) and subjects with Wiskott–Aldrich syndrome (WAS), as well as in both groups together, the platelet counts were lower in CBCs that did not report an Mean platelet volume (MPV) as compared with CBCs that did report an MPV (Table 1)
Complete data, including a reported platelet count, MPV, and immature platelet fraction (IPF) percentage, were available for 160 blood draws from 38 subjects with a diagnosis of ITP and 27 blood draws from 18 subjects

Summary

Introduction

Immune thrombocytopenia (ITP) is the most common cause of newly discovered isolated thrombocytopenia in childhood [1], with an incidence of 1.9–6.4 in 100,000 children per year, and a prevalence of 9.3 in 100,000 boys [2]. In order to diagnose the most common cause of newly recognized thrombocytopenia in children, IPF in Wiskott–Aldrich syndrome all less common causes must first be ruled out. This leads to a situation wherein the need for parsimonious use of diagnostic resources conflicts with the imperative to make a diagnosis by ruling out other diagnoses, potentially leading to premature closure in the diagnosis of boys newly found to be thrombocytopenic. A known source of diagnostic error [4], can lead to two potential adverse consequences – treatment for a disease that is felt to be present but, is not, and delay of diagnosis and treatment of the disease that is present. Extensive resources have been invested by the American Society of Hematology in developing guidelines to diagnose ITP expeditiously, attempting to minimize both misdiagnosis of less common forms of thrombocytopenia and potentially costly, lowyield, and/or invasive investigations [3]

Methods

Results

Conclusion