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 32-year old pregnant woman refers to the Emergency Unit for abdominal pain. Sonography reveals SVT of the splenic-portal axis and blood tests disclose anemia (Hb = 10.5 g/dL; Hct = 32%), leukocytosis (WBC = 18.2 × 109/L), and thrombocytosis (Plt = 596 × 109/L) with low Epo levels (3.3 mU/mL [4.3–29]), and JAK2 mutation. A BM biopsy (a–c) discloses PV changes with hypercellularity, expansion of the three hematopoietic lineages, clustering of polymorphic megakaryocytes, and no fibrosis. Despite this, the lack of the first major criterion hampers a formal diagnosis of PV.\nThe present case depicts the prototypic features of “masked PV”, presenting with SVT. A further bias is the concurrent pregnancy, which itself favors deep vein thrombosis. Such a clinical event may occur in any subtype of MPN, either at diagnosis or during the course of the disease. A higher thrombotic risk is related to a hyperinflammatory state and neutrophilia, which are more commonly experienced in PV []. Besides the diagnostic issues, it should be stressed that thrombotic events pose the highest threat for patients with early phase MPN. Despite the risk factors for vascular events are only partially defined, major determinants include JAK2 status, age, neutrophil count, and a positive history of thrombosis [,,].