ITP can be classified based on the duration of thrombocytopenia. If the thrombocytopenia resolves within 12 months of onset it is classified as acute ITP and if it persists beyond 12 months it is classified as chronic ITP. Acute ITP is the most common cause of pediatric thrombocytopenia, affecting 5/100,000 children annually [1]. ITP is an autoimmune disorder characterized by immunologic destruction of platelets resulting in isolated thrombocytopenia in an otherwise well looking child without lymphadenopathy or hepatosplenomegaly [2]. The median age of presentation with ITP is 69 months [3]. The incidence of ITP peaks between 2 and 5 years of age with a second smaller peak in adolescents [4]. Primary ITP is defined as a platelet count less than 100 × 109 / L in the absence of other causes or disorders that may cause thrombocytopenia [5]. Alternatively ITP may occur secondary to other autoimmune disorders (e.g., systemic lupus erythematosus, anti-phospholipid syndrome, Evans syndrome), viral infections (e.g., cytomegalovirus, hepatitis c, varicella zoster, human immunodeficiency virus) [5] or drugs (e.g., carbamazepine, quinine, and vancomycin) [2, 6].
In children presenting with suspected ITP, leukemia should be considered in the differential diagnosis. Although leukemia is classically associated with hematopoietic abnormalities beyond isolated thrombocytopenia, a bone marrow evaluation was historically performed on all patients with a presumed diagnosed of ITP to rule out leukemia prior to starting therapy. However, a number of retrospective studies called this practice into question [7, 8]. A review of 2239 children enrolled in two Pediatric Oncology Group acute lymphoblastic leukemia clinical trials showed that only 1 child presented with isolated thrombocytopenia, who had no blast cells on the blood smear, hemoglobin > 110 g/L and an absolute neutrophil count > 1.5 × 109 / L. On physical examination, that child had marked hepatosplenomegaly, and thus was unlikely to be misclassified as typical ITP [7]. Subsequently, a review of confirmatory bone marrow analyses performed in 322 children presenting with typical features of acute ITP found zero cases of leukemia [8].
In 2011, the American Society of Hematology (ASH) revised its position statement on ITP, no longer recommending routine bone marrow evaluation in patients suspected of having typical ITP [5]. Both ASH and the American Association of Pediatrics (AAP) advise that in the case of unusual findings on history or physical examination such as fevers, weight loss, fatigue, bone pain, lymphadenopathy or hepatosplenomegaly, or unusual hematologic findings such as abnormal white or red blood cell counts, it is reasonable to perform a bone marrow examination [5, 9]. While ITP is more in children between 2 and 5 years of age and in adolescents, there is no recommendation to alter your diagnostic work-up for children presenting with what appears to be ITP at an atypical age [4].
Our patient had mild hepatomegaly, which may have qualified him for a bone marrow examination even if the peripheral smear was negative. He also had an elevated LDH and urate, which are not listed as criteria for bone marrow evaluation by the ASH or AAP guidelines but were considered as atypical for ITP by the clinical team caring for this patient. Some experts have recommended bone marrow examination if the LDH and urate are elevated in pediatric ITP [9]. However, a literature search did not reveal any primary data assessing these serum markers A recent study in adult patients, showed that urate is commonly elevated in patients with ITP [10]. Further work is needed to understand the significance of a high LDH and urate in pediatric ITP.
The initial management of ITP can include both observation and pharmacologic therapies. Between 80 and 90% of ITP is self-limited, with patients making a full and permanent recovery within 12 months without any treatment [11]. Children over the age of 10 have an increased risk of progressing to chronic ITP with 47.3% having a platelet count < 150 × 109/L 6 months after diagnosis [4]. Patients with platelet counts below 10–20 × 109/L are at increased risk for significant bleeding and this often prompts clinicians to offer pharmacologic interventions to raise the platelet count expeditiously. Initial pharmacologic options include IVIG or a short course of oral corticosteroids [5]. Costs, risk of bleeding and parental preferences factor into decision making [12].
While corticosteroids are one of the first line pharmacologic agents in ITP, they must be reserved for cases where clinicians are confident that the patient does not have leukemia. Steroid administration prior to the diagnosis of leukemia results in delayed diagnosis and may increase the risk of complications and decrease event-free survival [13].
In our case, the patient presented to a quaternary care pediatric hospital with excellent access to laboratory technology and specialists. Recognition of atypical features consisting of mild hepatomegaly, and unexplained elevation of LDH and urate prompted clinicians to recommend IVIG and not corticosteroids as the initial treatment.
This report illustrates the importance of a detailed history and physical exam and careful analysis of presenting hematologic parameters when diagnosing ITP. Even subtle deviations from findings in typical ITP should prompt clinicians to reevaluate the diagnosis. This case also highlights the importance of peripheral smear review by an expert in pediatric hematology/oncology to ensure that blast cells are not missed. In this case, careful review ensured that the patient was fully investigated and did not receive steroids. It is important to emphasize that bone marrow analysis is not required for cases of typical ITP.
