Can Immature Platelet Fraction (IPF) be Used to Assess Bleeding Risk in Pediatric Immune Thrombocytopenia (ITP) and to Differentiate ITP from Bone Marrow Failure/Aplastic Anemia? A Retrospective Analysis

Immune Thrombocytopenia (ITP) usually presents with isolated, severe thrombocytopenia with very low platelet count (generally less than <30 x 10⁹/L) in the absence of other hematologic abnormalities. However, ITP is a diagnosis of exclusion without any definite diagnostic test that can confirm the diagnosis at the time of presentation and clinicians occasionally worry at the time of presentation about other bone marrow processes that may present with thrombocytopenia, which would require considerably different therapy. In light of current guidelines suggesting that observation is likely to be safe in pediatric patients with low platelet counts without significant bleeding, identifying patients at risk for severe hemorrhage is even more important to help guide therapy. In addition, appropriately differentiating ITP from other diagnoses may also prevent inappropriate administration of ineffective therapies. The immature platelet fraction (IPF) is a measure of platelet turnover measuring RNA containing, large platelets by fluorescently labeling the platelets and utilizing flow cytometric gates programmed into the Sysmex XN-3000 hematology analyzer.  We examined the medical laboratory records of 134 patients who had an IPF performed over the past 4 months for correlation between IPF and bleeding manifestations. In ITP patients who presented with significant bleeding symptoms (defined as epistaxis which was more than brief, oral bleeding more than palatal petechiae or GI or intracranial hemorrhage), the IPF was significantly lower than in those who presented with no bleeding or cutaneous bleeding only (bruising and petechiae): IPF=4.3%±1.6 SEM in bleeding patients versus 21.8%±1.8 SEM in not bleeding patients; p<0.0001. In two patients with life threatening hemorrhage and ITP (GI bleeding with drop in hemoglobin requiring both PRBC transfusion and treatment to raise the platelet count; ICH resulting in mortality), the IPF was low at the time of initial hemorrhage, but increased after ITP therapy (GI Bleed: plt 1K, IPF 5.3% increased to 20.3% after IVIG; ICH plt 6K, IPF 1.8% increased to 12.8% after IVIG and prednisone). We also examined first platelet count and IPF in 127 patients with ITP and 21 patients with BMF/AA who presented to our institution since October 2013. In this cohort of patients, the IPF in patients with ITP was significantly higher than in the BMF/AA patients and an IPF of >5.3 was associated with a negative predictive value of 80% for BMF/AA (IPF 16.6%±1.2 SEM in ITP vs. 2.9%±1.4 SEM in BMF/AA).  In summary, we demonstrate that the IPF is a useful and simple adjunct in diagnosis of ITP which can help differentiate the patients most likely to have ITP from those who may need further diagnostic evaluation and require treatment to prevent bleeding complications. Further studies will focus on the ability of the IPF to prospectively predict the bleeding risk of patients and categorize patients.