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Haematologica 2019 Volume 104(11):2200-2205
Myeloproliferative Neoplasms
Distinguishing essential thrombocythemia JAK2V617F from polycythemia vera: limitations of erythrocyte values
Richard T. Silver1 and Spencer Krichevsky1
1Richard T. Silver Myeloproliferative Neoplasm Center, Division of Hematology/Medical Oncology, Weill Cornell Medicine, New York, NY, USA
ABSTRACT
Distinguishing essential thrombocythemia JAK2V617F from poly- cythemia vera is difficult because of shared mutation and pheno- typic characteristics. The World Health Organization suggested hemoglobin and hematocrit values to diagnose polycythemia vera (PV), but their sensitivity and specificity were not tested. Moreover, red cell values do not accurately predict red cell mass, which we use to discrim- inate essential thrombocythemia JAK2V617F from PV. Eighty-three PV and 39 essential thrombocythemia JAK2V617F patients were diagnosed based on JAK2V617F positivity, chromium-51 red cell mass, and marrow biopsy findings. Red cell values used to construct a receiver operating characteristic analysis determined optimal thresholds for distinguishing essential thrombocythemia JAK2V617F from PV. Red cell value frequen- cies were plotted determining if overlap existed. Chromium-51 red cell mass separated PV from essential thrombocythemia JAK2V617F, but red cell values overlapped in 25.0-54.7%. Our data indicate that a significant proportion of PV patients may be underdiagnosed by using only red cell values. A bone marrow biopsy was performed in 199 of 410 (48.5%) and a serum erythropoietin value was measured in 225 of 410 (54.9%) of potential PV patients at our institution. Without isotope studies, marrow biopsies and serum erythropoietin values should improve diagnostic accuracy and become mandatory, but clinical data suggest these tests have not been routinely performed. Therefore, the clinical hematologist must be aware of imperfect accuracy when using only red cell values for distinguishing essential thrombocythemia JAK2V617F from PV.
Introduction
The JAK2V617F and exon 12 mutations are critical for the diagnosis of poly- cythemia vera (PV); JAK2V617F is also the molecular marker of 50-60% of patients with essential thrombocythemia (ETJAK2V617F).1 Distinguishing these illness- es in their early stages remains a clinical problem because of their shared mutation and phenotypic characteristics.2,3
In clinical situations when the hematocrit (HCT), hemoglobin (HGB), or red blood cell (RBC) count are relatively increased, we distinguish ETJAK2V617F from PV using chromium-51 (Cr-51) labeled RBC and iodine-135 (I135) to measure red cell mass (RCM) and plasma volume, respectively.4 We include the latter to determine if an elevated HCT is attributed to reduced plasma volume when the Cr-51 deter- mined RCM is normal. The distinction of these diagnoses has clinical significance: if a presumptive ETJAK2V617F patient in fact has PV, a significant risk for thrombosis may incur because therapeutic phlebotomy is not performed. Conversely, if a patient is misdiagnosed with PV, inappropriate phlebotomy treatment may cause significant iron deficiency and other related complications.5 In addition, a misdiag- nosis may also affect prognostic models comparing ETJAK2V617F with PV, ETCALR, or ETMPL.
The majority of hematology centers worldwide do not use isotope techniques but instead rely on arbitrarily defined World Health Organization (WHO) 2016
Correspondence:
RICHARD T. SILVER
rtsilve@med.cornell.edu
SPENCER KRICHEVSKY
spk2002@med.cornell.edu
Received: December 11, 2018. Accepted: April 3, 2019. Pre-published: April 4 2019.
doi:10.3324/haematol.2018.213108
Check the online version for the most updated information on this article, online supplements, and information on authorship & disclosures: www.haematologica.org/content/104/11/2200
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