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.

Effects of eltrombopag on platelet count and platelet activation in Wiskott-Aldrich syndrome/X-linked thrombocytopenia

“…30 On the other hand, there are several studies demonstrating that platelet production in WAS appears to be impaired. 5,[31][32][33][34][35] In the present study, compared with thrombocytopenic children with ITP also treated with eltrombopag, platelet production was not only decreased in WAS/XLT patients prior to treatment but the increase in AIPF in response to eltrombopag was also far less ( Figure 5). Regardless of the relative roles of accelerated destruction and impaired production, the response to the thrombopoietic agent eltrombopag in 5 out of 8 WAS/XLT patients, and the long-term response in 4 responders ( Figure 4B), provides evidence for a novel treatment of WAS/XLT with relatively high efficacy and good tolerability.…”

MYH9‐macrothrombocytopenia caused by a novel variant (E1421K) initially presenting as apparent neonatal alloimmune thrombocytopenia

“…Similarly, pediatric ITP patients have a median IPF of 12% with no reported levels ≥40% . Though there are limited data, patients with other congenital thrombocytopenias also have IPFs < 40% . Combined, these reports suggest that IPF measurements likely can distinguish MYH9 disorders, including in infancy, from other causes of thrombocytopenia.…”

Wiskott–Aldrich syndrome that was initially diagnosed as immune thrombocytopenic purpura secondary to a cytomegalovirus infection

“…WAS is traditionally differentiated from ITP based on the small size of the PLTs seen in WAS patients. 1 However, the clinical phenotype of WAS itself is very heterogeneous, and some WAS patients have been found to have normal MPV. 1 , 3 The clinical phenotypes of WAS, including PLT size, depend on the mutations present in the WAS gene.…”

“…WAS is sometimes difficult to differentiate from immune thrombocytopenic purpura (ITP). 1 We describe the case of a 2-month-old boy with WAS who was initially diagnosed with ITP secondary to a human cytomegalovirus (HCMV) infection.…”