Prevalence of Unexplained Erythrocytosis and Thrombocytosis - an Nhanes Analysis
Authors: Tremblay Douglas , Alpert Naomi , Taioli Emanuela , Mascarenhas John 
Published: February 2021

Introduction
Polycythemia vera (PV) and essential thrombocythemia (ET) are myeloproliferative neoplasms characterized by erythrocytosis and thrombocytosis, with an estimated prevalence of 22 and 24 per 100,000, respectively in the United States (Ma X et al AJH 2008). However, the prevalence of undiagnosed disease is unknown. We examined the National Health and Nutritional Examination Survey (NHANES) database for unexplained erythrocytosis (UE) and thrombocytosis (UT).
Methods
NHANES is a cross-sectional, nationally representative, population-based survey administered by the Centers for Disease Control and Prevention that utilizes a combination of interviews, physical examinations, and laboratory testing. In the UE group, participants were included if they had a hemoglobin &gt;18.5 g/dL in men or &gt;16.5 g/dL in women or a hematocrit &gt;55.5% in men and &gt;49.5% in women. Participants were excluded if they required oxygen supplementation, had a reported history or pulmonary function test evidence of obstructive lung disease, were receiving exogenous steroids or smoked cigarettes, or had a history of blood, kidney, liver, or uterine cancer. The UT group included participants with a platelet count greater than 450 x 10^9/L, and excluded those with laboratory evidence of iron deficiency, an elevated LDH suggesting inflammation, or reported a current infection, history of cancer, or rheumatologic conditions. Given the availability of necessary eligibility data, NHANES was queried from 2007-2008 for the UE group and 1999-2002 for the UT group. Weighted statistics are presented.
Results
Of the 3348 participants evaluable for UE, 16 (0.38%; 383.0 per 100,000 population) had erythrocytosis of which 4 were unexplained (0.04% of the overall population; 40.8 per 100,000 population). Reasons for erythrocytosis are noted in Table 1. UE participants had a mean hemoglobin of 18.1g/dL (standard error [SE] 0.6) and hematocrit of 50.7% (SE 1.5). Table 2 shows the estimated prevalence of UE by age, gender, and race. The average age was 58.8 years (SE 2.8), which was significantly older than the general population without erythrocytosis (42.8 years [SE 0.5], p&lt;0.0001). All UE participants in the sample were United States (US) born and had an educational level below a college degree. The mean family poverty income ratio was 2.4 (SE 0.6), which was lower, although not significantly different than the NHANES population without erythrocytosis (mean 3.2 [SE 0.1], p=0.2113).
Of the 7403 participants evaluable for thrombocytosis, 108 participants (1.47%; 1,474.6 per 100,000 population) had thrombocytosis of which 33 (0.49% of the overall population; 494.2 per 100,000) were UT. Reasons for thrombocytosis are shown in Table 1. The mean platelet count of the UT group was 494.5 x 10^9/L (SE 9.1). The average age was 42.6 years (SE 3.5) which was not significantly different than the general population without thrombocytosis (45.1 years [SE 0.3], p=0.4582), but those with UT were significantly more likely to be female (76.4% vs. 50.5%, p=0.0117). Table 2 shows the estimated prevalence of UT by age, gender, and race group. The weighted percentage of US born was 86.7% in the UT group, with 63.1% having an educational level below a college degree. The mean family poverty income ratio was 3.1 (SE 0.4), which was not significantly different than the NHANES population without thrombocytosis (mean 3.0 [SE 0.1], p=0.8974).
Conclusions
Although this study is limited by inability to determine World Health Organization (WHO) diagnosis of ET and PV, this NHANES analysis suggests that the prevalence of UE and UT may be higher than commonly appreciated, with an estimated prevalence of 40.8 and 494.2 per 100,000, respectively. This is almost certainly an overestimate as a result of methodologic limitations of an NHANES analysis, including the fact that estimates are based on a small number of participants with UE or UT obtained at a static time point. It is also important to note that not all patients UE and UT fulfill WHO criteria for PV and ET. However, our data do suggest that PV and ET may be under-evaluated in the general population. While it is possible that certain factors may predispose some patients to having undiagnosed disease, the number of participants with unexplained conditions were too small to analyze this in more detail.

Disclosures
Mascarenhas: Celgene, Prelude, Galecto, Promedior, Geron, Constellation, and Incyte: Consultancy; Incyte, Kartos, Roche, Promedior, Merck, Merus, Arog, CTI Biopharma, Janssen, and PharmaEssentia: Other: Research funding (institution).