A 48-year-old Caucasian lady, an elementary school teacher from Minnesota, was noted to have erythrocytosis while undergoing a kidney donor evaluation. Hgb and Hct were 19.4 g/dl and 57%, respectively, with normal leukocyte and platelet count. The patient had a history of persistent erythrocytosis with Hgb/Hct of 19.3 g/dl/58%, documented two decades prior to her diagnosis. Her medical history was significant for hypertension, optimally controlled with lisinopril; tobacco use, vascular events, or microvascular symptoms were absent in her medical history. Importantly, both her mother and brother were previously noted to have erythrocytosis. Initial laboratory evaluation included EPO (1.1 mIU/mL; normal reference range 2.6–18.5) and peripheral blood JAK2 mutational screen (wild-type for both exons 12 and 14). Based on family history and subnormal EPO, EPOR mutation screen was pursued and revealed a heterozygous c.1316G>A, p.(Trp439*) mutation in exon 8 that caused a premature stop codon and truncated the 70 C-terminal amino acids resulting in a gain of function []; the altered C-terminal increases EPOR stability at the cell surface resulting in pre-activation of both receptor and constitutive JAK2 signaling similar to what is seen in PV []. This EPOR mutation has been shown to be associated with autosomal dominant erythrocytosis [] and also reported as a de novo alteration [, ]. Taken together, this information supported a diagnosis of autosomal dominant hereditary or familial erythrocytosis type 1. Most patients with EPOR mutations are asymptomatic; with isolated cases experiencing cardiovascular complications and deep vein thrombosis []. While phlebotomy may benefit some patients in alleviating symptoms, it does not appear to have a protective effect with regards to cardiovascular events []. In terms of management, optimal hypertension control with lisinopril was emphasized and low-dose aspirin initiated. Since our patient was asymptomatic, routine phlebotomy was not recommended, however, phlebotomy prior to kidney donation was a consideration.
A 79-year old woman with beta-thalassemia minor and IgG+ monoclonal gammopathy of undetermined potential presents with stable Hb levels and a steady increase of platelet count (Hb = 13.2 g/dL; Hct = 43.5%; WBC = 14.2 × 109/L [N 9.67]; Plt = 866 × 109/L; LDH levels within normal ranges, Epo not assessed). JAK2 mutation is detected on peripheral blood (VAF not known). A BM biopsy (g–i) is hypercellular, with erythroid precursor expansion, megaloblastosis, and clustering of megakaryocytes, ranging in morphology from small, hypolobulated forms (including naked nuclei) to giant, hyperlobulated (“staghorn”) cells. No increase in reticulin fibers and CD34+ blasts is observed; the lympho-plasmacytic infiltrate is unremarkable.\nThe global picture strongly favors a diagnosis of MPN, but the differential diagnosis between ET and PV cannot be definitively settled. The former is favored by thrombocytosis and by prominent ET-type megakaryocyte morphology, and the latter is supported by the coexistence of neutrophilia alongside with normal Hb levels (possible effect of the concurrent thalassemic trait) [].