Diagnosis and management of non-clonal erythrocytosis remains challenging: a single centre clinical experience

Saša Anžej Doma,Nataša Debeljak,Matjaž Sever,Irena Preložnik Zupan,Martina Fink,Aleša Kristan,Tanja Belčič Mikič,Helena Podgornik,Eva Drnovšek

doi:10.1007/s00277-021-04546-4

Saša Anžej Doma, Nataša Debeljak + Show 7 more

Open Access

https://doi.org/10.1007/s00277-021-04546-4

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Abstract

Erythrocytosis has a diverse background. While polycythaemia vera has well defined criteria, the diagnostic approach and management of other types of erythrocytosis are more challenging. The aim of study was to retrospectively analyse the aetiology and management of non-clonal erythrocytosis patients referred to a haematology outpatient clinic in an 8-year period using a 3-step algorithm. The first step was inclusion of patients with Hb > 185 g/L and/or Hct > 0.52 in men and Hb > 165 g/L and/or Hct > 0.48 in women on two visits ≥ two months apart, thus confirming true erythrocytosis. Secondly, polycythaemia vera was excluded and secondary causes of erythrocytosis (SE) identified. Thirdly, idiopathic erythrocytosis patients (IE) were referred to next-generation sequencing for possible genetic background evaluation. Of the 116 patients, 75 (65%) are men and 41 (35%) women, with non-clonal erythrocytosis 34/116 (29%) had SE, 15/116 (13%) IE and 67/116 (58%) stayed incompletely characterized (ICE). Patients with SE were significantly older and had significantly higher Hb and Hct compared to patients with IE. Most frequently, SE was attributed to obstructive sleep apnoea and smoking. Phlebotomies were performed in 56, 53 and 40% of patients in the SE, IE, and ICE group, respectively. Approx. 70% of patients in each group received aspirin. Thrombotic events were registered in 12, 20 and 15% of SE, IE and ICE patients, respectively. Congenital erythrocytosis type 4 (ECYT4) was diagnosed in one patient. The study demonstrates real-life management of non-clonal erythrocytosis which could be optimized using a 3-step diagnostic algorithm.

Highlights

Erythrocytosis is a condition of a true increase in red cell mass (RCM), manifested by high haemoglobin (Hb) concentration (> 165 g/L in men and > 160 g/L in women) and/The causal diversity of erythrocytosis is wide and requires complex diagnostic algorithms
We identified idiopathic erythrocytosis (IE) patients
A total of 126,284 complete blood count (CBC) were performed in adult patients at Haematology outpatient clinic, University Medical Centre (UMC) Ljubljana, After a complete review of the patients’ medical records in 34/116 (29%) patients a secondary erythrocytosis (SE) was determined, in 15/116 (13%) erythrocytosis remained idiopathic (IE) despite all relevant investigations performed, but 67/116 (58%) patients stayed incompletely characterized (ICE) as their condition did not seem clinically relevant for the treating haematologists to Investigations performed/ habits inquired

Summary

Introduction

The causal diversity of erythrocytosis is wide and requires complex diagnostic algorithms. It can have a primary or secondary cause, and both can have either congenital or acquired origin [2,3,4]. Several mutations in nine different genes lead to eight types of congenital (familial) erythrocytosis (ECYT1-8). Mutations in the erythropoietin receptor (EPOR) are indicative of congenital erythrocytosis type 1 (ECYT1). Mutations in genes involved in oxygen sensing (VHL, EGLN1, EPAS1, EPO) cause ECYT 2, 3, 4, and 5, respectively [7]. Mutations in genes that affect Hb oxygen affinity (HBB, HBA1, and HBA2, BPGM) cause ECYT 6, 7 and 8, respectively [7, 8]. If no cause is found, the patient is diagnosed with idiopathic erythrocytosis (IE) [10]

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