Secondary causes of elevated hemoglobin in patients undergoing molecular testing for suspected polycythemia vera in southwestern Ontario: a chart review

Abstract

rythrocytosis is defined as a concentration of red blood cells higher than age-and sex-specific reference ranges, most commonly measured as an increase in the hemoglobin level or hematocrit. Since the identification of the JAK2 V617F mutation in patients with polycythemia vera in 2005, 1 molecular testing of the JAK2 gene has become part of the standard diagnostic workup for patients presenting with erythrocytosis. The increasing availability of molecular diagnostics and a decrease in hemoglobin thresholds (> 160 g/L for women, > 165 g/L for men) required to diagnose polycythemia vera in the revised 2016 World Health Organization (WHO) classification 2 are 2 potential factors driving increased use of molecular testing in patients with erythrocytosis. 3 Secondary causes of erythrocytosis -such as smoking, hypoxic lung diseases and medications -are more common than polycythemia vera, and current literature supports first excluding these causes by taking a thorough medical history and by focused investigations, including serum erythropoietin levels, before performing molecular testing. 4 Despite these recommendations, in practice, this work-up is often performed concurrently with molecular testing, which can carry substantial health care costs.The primary objective of this study was to characterize practice patterns in the investigation of erythrocytosis at our centre, focusing on the use of molecular testing for JAK2

Sodium‐glucose cotransporter‐2 inhibitor‐associated erythrocytosis: A retrospective cohort study

“…Our results support the previously reported association between SGLT‐2 inhibitor use and JAK2 ‐negative erythrocytosis [2–8], which can lead to potentially unnecessary investigations and treatments. We previously described JAK2 ‐negative SGLT‐2 inhibitor‐associated erythrocytosis in 12.1% of referrals for erythrocytosis to our institution [5]. Normalization or return to baseline of hemoglobin levels was seen in the majority of patients who discontinued or underwent dose reduction of SGLT‐2 inhibitors.…”

“…Our results support the previously reported association between SGLT-2 inhibitor use and JAK2-negative erythrocytosis [2][3][4][5][6][7][8], which can lead to potentially unnecessary investigations and treatments. We previously described JAK2negative SGLT-2 inhibitor-associated erythrocytosis in 12.1% of referrals for erythrocytosis to our institution [5]. Normalization or return to baseline of hemoglobin levels was seen in the majority of patients who discontinued or underwent dose reduction of SGLT-2 inhibitors.…”

“…Exclusion criteria were patients who were JAK2 ‐positive or on concomitant testosterone, as this is a well‐defined cause of drug‐induced erythrocytosis. Methods for JAK2 mutation testing are described previously [5], consisting of quantitative polymerase chain reaction testing, single nucleotide polymorphism allelotyping, or next‐generation sequencing (NGS, Oncomine Myeloid Research Assay) to detect the JAK2 V617F mutation; NGS also detected mutations in exons 12–15. Primary outcomes were median change in hemoglobin from baseline, and secondary outcomes were clinical outcomes including arterial and venous thrombosis.…”

“…Dear Editor, Sodium-glucose cotransporter-2 (SGLT-2) inhi bitor use is an underrecognized cause of elevated hemoglobin (erythrocytosis) [1][2][3][4][5]. The natural history of this condition remains uncertain.…”

Dapagliflozin-Induced Erythrocytosis in Chronic Kidney Disease: A Rare Occurrence

“…In addition to their excellent efficacy, SGLT2i can have certain adverse effects. Erythrocytosis as a side effect of SGLT2i has been reported to range from 2% to 19% [ 2 ]. Although the exact mechanism remains unclear, the putative mechanism includes hemoconcentration, modulation of iron metabolism, and erythrocytosis stimulation by suppression of hypoxia-inducible factor (HIF)-1α and activation of HIF-2α [ 3 ].…”