Polycythemia Vera with High Erythropoietin Level : Case Report

C l i n M e d International Library Citation: Nassabein R, al khatib M, Abbas MH, youssef M, Amer D, et al. (2016) Polycythemia Vera with High Erythropoietin Level: Case Report. Int J Blood Res Disord 3:023 Received: June 22, 2016: Accepted: August 27, 2016: Published: August 30, 2016 Copyright: © 2016 Nassabein R, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. Nassabein et al. Int J Blood Res Disord 2016, 3:023


Introduction
In the presence of symptoms, Erythrocytosis, warrants further investigation to distinguish primary causes from secondary.It is well established that high erythropoietin levels exclude primary causes of PV, which requires searching for secondary causes.In place this leads us to the following: Can high erythropoietin level be present in PV?

Case Report
A married male of 49-years-old, with maternal family history of hypertension and dyslipidemia, was presented to our hospital.He complained of a one week duration severe headache, with no focal deficit on neurological exam.Brain CT without contrast was done, to show no evidence of intracranial bleed.Labs showed Hemoglobin of 18 g\dl, platelet count of 156 and WBC of 12300/mm 3 .Due to the above results, the patient was admitted for further investigation.
Evaluation of secondary causes of erythrocytosis was started.Erythropoietin level was 161.8 mIU/ml (NL: 2.6-18.5 mIU/ml).Brain magnetic resonance imaging/arteriography and venography revealed no thrombosis or brain tumor.The patient is a non-smoker, with no evidence of hypoxia by ABG's and lives at sea level.CT scan of the abdomen and pelvis was done for the developing jaundice.However, no evidence of renal vessel narrowing, nor kidney or liver mass were shown.Alpha fetoprotein level 1.8 ng\ml.

Abstract
Polycythemia Vera (PV) is a myeloproliferative disorder of bone marrow stem cells characterized by erythrocytosis.Elevated erythropoietin level strongly indicates secondary erythrocytosis and excludes PV diagnosis.However, patients with PV who co-present with Budd-Chiari syndrome (BCS) have been documented with elevated serum erythropoietin levels provided that JAK2 mutation is positive.

Discussion
The abnormal proliferation of PV is sustained by oncogenic mutations in JAK-STAT pathway (signal transducers and activators of transcription).These mutations are the V617F mutation within exon 14 (95% of PV) and other different mutations within exon 12 (4% of PV) of the JAK2 gene [1].
Low erythropoietin is used in the diagnosis of PV, as it is the minor diagnostic criteria according to WHO classification 2016 [2].In the presence of elevated serum erythropoietin levels, searching for secondary causes of polycythemia is attempted [3].
PV is one of the most frequent condition causing BCS (10-40% of cases).In patients with polycythemia co-presenting with BCS, it has been described in few reports to have high serum Erythropoietin levels (4, 5, and 6).Thumures, et al. [4]; described four patients that were presented with BCS, with elevated red cell mass, and founded to have elevated serum erythropoietin level where polycythemia was confirmed with JAK2 mutation assay and bone marrow biopsy examination [5].Jones C, et al. [6] also described a patient that was presented with acute Budd-Chiari syndrome, and found to have elevated hemoglobin level, high serum erythropoietin level, and positive JAK2 mutation which was treated with rivaroxaban (xarelto).
It was hypothesized that Erythropoietin production is regulated in an oxygen-dependent manner, and driven via hypoxia-inducible transcription factors (HIF)-1 and (HIF)-2, that are believed to be upregulated in patients with BCS having hypoxic liver injury and hepatocyte necrosis [7].
Our patient was presented with severe headache, elevated HB level, hepatosplenomegaly, ascites, and found to have Budd-Chiari syndrome.Erythropoietin level was high, although bone marrow aspirate and biopsy where suggestive of PV.In addition to the two major principles of WHO criteria of diagnosis: JAK-2 mutation and elevated HB level.This can be explained by the postulated hypothesis that BCS caused hypoxia of the liver in the absence of clinical hypoxia, and lead to high erythropoietin levels.In such patient the identification of JAK 2 V617F mutation confirm the diagnosis of PV.

Conclusion
PV in the presence of Budd-Chiari syndrome can have elevated erythropoietin levels; hence, diagnosis is reached by identification of the JAK-2 mutation.