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

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.

Erythrocytosis, thrombocytosis, and rate of recurrent thromboembolic event—A population based cohort study

“…When including older participants from the same survey (age 70-79 and age over 80) the prevalence of unexplained erythrocytosis increased from 35.1 per 100 000 population to 47.9 and 53.5 per 100 000, respectively. Recent publications 11,13 have shown that unexplained erythrocytosis is more common in men than in women, which is consistent with our findings.…”

“…Regarding elevated Hb/HCT, our results with one fourth of all patients with elevated Hb/HCT classified as SE is consistent with earlier studies 11,12 . In our study the participants were relatively old (median age 73.5) and the frequency of elevated Hb/HCT were 13.2%, out of these 71.6% were categorized as unexplained erythrocytosis.…”

“…In our study the participants were relatively old (median age 73.5) and the frequency of elevated Hb/HCT were 13.2%, out of these 71.6% were categorized as unexplained erythrocytosis. These results are similar to those in a study from Slovenia where 57.8% of the patients with erythrocytosis were unexplained 11 . In a recently published study from the NHANES survey where the participants were younger (20–69 years) and using a higher cut off value for Hb (>18.5 g/dL in men and >16.5 g/dL in women) and HCT (>55.5% in men and > 49.5% in women) they found that 25% of patients with erythrocytosis were unexplained.…”

“…In this "real-world" cohort of 3931 patients with thromboembolic event approximately one third had elevated Hb/HCT or platelet at Regarding elevated Hb/HCT, our results with one fourth of all patients with elevated Hb/HCT classified as SE is consistent with earlier studies. 11,12 In our study the participants were relatively old (median age 73.5) and the frequency of elevated Hb/HCT were 13.2%, out of these 71.6% were categorized as unexplained erythrocytosis. These results are similar to those in a study from Slovenia where 57.8% of the patients with erythrocytosis were unexplained.…”

JAK2 Unmutated Polycythaemia—Real-World Data of 10 Years from a Tertiary Reference Hospital

“…However, since the discovery of JAK2 V617F in 2005, the vast majority of them are reviews based on expert suggestions, not on original research work. There are only singular studies that systematically analysed causes, diagnostic steps and outcomes, including thrombotic events in patients with JAK2 unmutated polycythaemia [ 4 , 5 ].…”