An 84-year-old woman presented with a four-week history of dizziness, headaches, and vertigo. Her past medical history included hypercholesterolemia, hypothyroidism, depression and osteopenia, and her regular medication consisted of atorvastatin, levothyroxine, citalopram, calcium, and cholecalciferol. She was a nonsmoker and had no history of cardiac, pulmonary, or renal disease. There was a family history of HBT but no other hematological disorders. The patient was known to have HBT with steady Hb and hematocrit (Hct) values marginally below the lower limit of normal, on yearly check-ups until two years prior to her presentation. A routine complete blood count arranged by her primary care physician nine months prior to presentation had shown Hb 14 g/dL, Hct 45.6%, red cell count (RBC) 6.13 x 1012/L with microcytosis and normal white cell and platelet counts.\nPhysical examination revealed no remarkable findings. Her arterial oxygen saturation was 97%. Abdominal ultrasound examination showed a fatty liver and normal-sized spleen. Computerized brain tomography revealed changes of ischemic leukoencephalopathy. Blood tests showed RBC 7.01 x 1012/L, Hb 15.8 g/dL, Hct 50.4%, mean corpuscular volume (MCV) 69 fL, white cell count 6.76 x 109/L, and platelet count 236 x 109/L. Serum lactate dehydrogenase was 326 U/L (normal range 135-225 U/L), while the rest of her biochemistry profile was unremarkable. Serum levels of iron, ferritin, and vitamin B12 were normal. Hb electrophoresis showed an elevated HbA2 of 3.8% (reference range 1.8-3.2), fetal hemoglobin (HbF) of 0.5% (reference <2%) and no evidence of abnormal Hbs, which was compatible with HBT. Serum Epo levels were low at 3.0 mU/mL (reference range 4.3-29.0 mU/mL). Bone marrow biopsy appearances were compatible with a myeloproliferative neoplasm of the PV type, without excess fibrosis or increased numbers of immature cells. The diagnosis of PV was confirmed by identifying heterozygocity for the JAK2 V617F mutation in peripheral blood white cells, using a real-time polymerase chain reaction assay with hybridization probes and melting curve analysis.\nThe patient showed a good clinical and laboratory response to the administration of low-dose aspirin and hydroxyurea with a target Hct of 42%.
A 17-year-old Caucasian male, a high school student from Missouri was referred for evaluation of unexplained erythrocytosis. He reported a myriad of symptoms including nausea, vomiting, abdominal pain, weight loss, fatigue, headaches, cold hands and feet with numbness and tingling, hyperhidrosis, palpitations, and pruritus. He was a non-smoker without illicit drug or hormone use. Family history was unremarkable. On physical examination, no cutaneous, abdominal or neurological abnormalities were noted. A review of serial blood counts showed a consistent elevation in Hgb >16.5 g/dl, with peak Hgb/Hct of 18.3 g/dl/52.4% and normal leukocyte and platelet counts. PV was excluded with a negative JAK2V617F/exon 12 mutation screen and elevated EPO at 22.6 mIU/mL (normal range; 2.6–18.5 mIU/mL). Bone marrow aspirate/biopsy was without features of a MPN. Hereditary erythrocytosis evaluation did not reveal high-affinity Hgb variants or mutations in 2,3-Bisphosphoglycerate Mutase (BPGM)(exons 1–4), EPOR (exon 8), or oxygen-sensing pathway proteins, including hypoxia-inducible factor 2 α (HIF2A) encoded by endothelial PASS domain protein 1 (EPAS1) (exons 9 and 12), prolyl hydroxylase 2 (PHD2) encoded by egl-9 family hypoxia-inducible factor 1(EGLN1)(exons 1-5), von Hippel Lindau (VHL) (three coding exons and intron/exon boundaries). Chest/abdominal imaging, arterial blood gas, transthoracic echocardiogram with shunt study, urinary catecholamines/metanephrines were unremarkable. Interestingly, MRI brain/spine revealed multiple cerebrovascular malformations; both developmental venous anomalies and cavernous hemangiomas in the frontal and temporal regions. Accordingly, the cerebrovascular malformations were hypothesized to be a plausible link to the patient’s erythrocytosis. Surgical intervention was not feasible due to the presence of multiple anomalies. He was initiated on phlebotomies with marked improvement in symptoms; thereafter, need for periodic phlebotomies was determined by symptoms rather than a target Hct value. This previously published case underscores the importance of a systematic diagnostic approach to JAK2 unmutated erythrocytosis [].