RESULTS
From 2000 to 2020, 40 patients were diagnosed with erythrocytosis at the center, in a male-to-female ratio of 7 to 1. Their mean age was 15.31 ± 2.49 years (8.34–17.92) years at diagnosis and 17.92 ± 2.96 years (11.43–27.17) at data collection, and the median follow-up time was 9 months, ranging from 6 months to 13.80 years. Thirty-two (80.0%) patients had been referred in the past 24 months due to full-blood count screening performed in schools. In terms of family relatedness, two of the patients were siblings. Table 1 summarizes the demographic and laboratory characteristics of the patients.
The medical histories of the patients involved no other diseases, and patients generally seemed to be healthy. Seventeen families (43.58%) had relatives with erythrocytosis, or relatives who regularly received phlebotomies, and in seven and five families, fathers and siblings were also affected, respectively. In 11 families (28.20%), 15–48-year-old relatives had experienced myocardial infarction, stroke, and/or sudden death.
Physical examination revealed that 14 (35.0%) patients had plethora, while none had splenomegaly or any other pathological findings. The Hgb levels, age, and sex of the patients at diagnosis appear in Figure 1; mean Hgb at diagnosis was 17.40 ± 1.34 g/dL (14.63–23.0 g/dL). All patients’ leukocyte counts, platelet counts, venous blood gas levels, capillary oxygen saturation levels (>95%), and results of Hgb electrophoresis (i.e., with high-performance liquid chromatography) were within normal limits. To analyze EPOR mutations, the blood samples of the first seven patients had been sent to Portugal, but results revealed only a previously identified heterozygous EPOR nonsense mutation c.1316G>A (p.Trp439Term) in two siblings.13 No patient exhibited a JAK2mutation or splenomegaly, thrombocytosis and/or leukocytosis which are characteristic findings of myeloproliferative disease.
Recurrent phlebotomies (i.e., 1–12 times/year) had been performed on demand in all patients in the presence of symptoms of hyperviscosity, and all patients had reported symptom relief after the procedure (Table 1). Many patients had been prescribed acetylsalicylic acid as an antiaggregant but had demonstrated poor compliance. All patients had been informed about potential bleeding and thrombosis at diagnosis, and good hydration, an active lifestyle, and abstinence from smoking, mountain climbing, and scuba diving had been recommended. No thrombotic episodes had occurred in any patients during follow-up.
Symptoms and signs of CE detected in the patients are listed in Table 2. The most common presenting symptoms were headache (80.0%), numbness and tingling in the hands and feet (45.0%), and pruritus (37.5%). At least one gastrointestinal symptom (e.g., nausea, vomiting, abdominal pain, and rectal bleeding) was reported in 40.0% of patients. Gastrointestinal symptoms were prominent, and patients reported visiting numerous pediatricians for years in search of a diagnosis. Six cases of CE (15.0%), despite being asymptomatic at diagnosis, were detected during routine whole blood screening.