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 44-year old female with unremarkable past clinical history refers to the Hematology Clinic for persistent thrombocytosis (Hb = 15.2 g/dL; Hct = 44.8%; WBC = 12.65 × 109/L [N = 9.58 × 109/L]; Plt = 742 × 109/L). Epo levels are close to the lower limit of normal (4.29 mU/mL; range: 4.3–29), LDH is not increased (206 U/L, range: 135–214) and JAK2 mutation is detected (VAF = 5.5%). Splenomegaly is not documented at clinical examination and sonography. BM biopsy (d–f) discloses a hypercellular marrow with features of panmyelosis, maturing erythroid and myeloid lineages and polymorphous, and loosely clustering megakaryocytes with frequent giant hyperlobated forms. A minor increase in reticulin fibers is observed, consistent with MF-1 according to WHO criteria. This case displays borderline features between a pre-polycythemic phase of PV (highly supported by the very typical morphologic pattern) and pre-fibrotic PMF.\nA diagnosis of ET is ruled out by BM histology. In contrast to case 1, the still low JAK2 allele burden could be responsible for the blood count, which is not fully consistent with PV. In similar cases, concurrent hematopoiesis-modifying factors (e.g., thalassemic trait, vitamin deficiencies, malabsorption, etc.) should be investigated. In addition, a minor increase in fibrosis should warrant closer monitoring.