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LETTER TO EDITOR
Absence of Polycythemia Vera in Postrenal Transplant Erythrocytosis

Dear Editor:

Posttransplant erythrocytosis is a well-recognized phenomenon occurring in 10% to 15% of renal allograft recipients; however, the pathogenesis remains unclear. Possible causes include disruption of erythropoietin regulation, a mitogeneic effect of the renin-angiotensin system on the erythroid lineage, insulin-like growth factor, and androgenic stimulation.1,2 Posttransplant erythrocytosis usually occurs within 8 to 24 months after kidney transplant, with risk factors that include smoking, renal artery stenosis, and a rejection-free posttransplant course. However, this phenomenon correlates with improved graft function and recipient survival.3

Although erythrocytosis is a relatively common hematologic abnormality with many underlying pathologies, acquired myeloproliferative neoplasm of polycythemia vera is a relatively infrequent cause.4 The diagnosis of polycythemia vera is multidis-ciplinary and requires confirmatory clinical, hema-tologic, and bone marrow morphologic features, a subnormal serum erythropoietin level, and the presence of acquired mutations of the JAK2 gene. Of note, the specific JAK2 V617F is present in more than 95% of patients with polycythemia vera.5 Nonetheless, posttransplant erythrocytosis in the absence of other clinical or laboratory features of polycythemia vera has become a recurrent, if sporadic, prompt for having molecular testing for the JAK2 V617F mutation.

To address the clinical value and laboratory impact of such requests, a retrospective audit was performed on all JAK2 V617F requests received at a molecular diagnostics center for hematologic malignancies. From January 2006 to September 2018 inclusive, the molecular diagnostics center received 17 332 diagnostic requests for JAK2 V617F mutation analyses. Patient consent was required by the referring center. Of total requests for investigation, 34 (0.2%) were received with the sole clinical details provided of posttransplant erythrocytosis. The median age of this group was 53 years and comprised 19 male and 15 female patients. Relationships between living donors and recipients, time from renal transplant to post-transplant erythrocytosis, and serum erythropoietin levels were not provided to this independent molecular testing center. A standardized allele-specific polymerase chain reaction assay (unchanged throughout the audit period) did not detect the JAK2 V617F mutation in any of the 34 patients with posttransplant erythrocytosis.

From a hematologic malignancy and molecular diagnostics perspective, the decision to screen patients for JAK2 V617F and other myeloproliferative neoplasm-associated rearrangements and mutations requires careful consideration to optimize laboratory resources.6 Although the number of requests did not affect the overall workload in the laboratory and although a diagnosis of a JAK2 V617F-positive myeloproliferative neoplasm after renal transplant is possible but exceedingly rare,7 routine screening for the JAK2 V617F mutation in patients with post-transplant erythrocytosis with no clinical or hematologic evidence of polycythemia vera (including a subnormal serum erythropoietin level) appears unjustified.


References:

  1. Vlahakos DV, Marathias KP, Agroyannis B, Madias NE. Posttransplant erythrocytosis. Kidney Int. 2003;63(4):1187-1194.
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  2. Vishnu P, Moreno Vanegas Y, Wadei HM, Rivera CE. Post-transplant erythrocytosis refractory to ACE inhibitors and angiotensin receptor blockers. BMJ Case Rep. 2018;bcr-2018-224622.
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  3. Abouelenein RK, Refaie AF, Alhendy YA, et al. Posttransplant erythrocytosis among Egyptian living-donor kidney transplant recipients. Exp Clin Transplant. 28 Nov 2018. Epub ahead of print. doi: 10.6002/ect.2017.0301
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  4. Lee G, Arcasoy MO. The clinical and laboratory evaluation of patients with erythrocytosis. Eur J Intern Med. 2015;26(5):297-302.
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  5. Helbig G. Classical Philadelphia-negative myeloproliferative neoplasms: focus on mutations and JAK2 inhibitors. Med Oncol. 2018:35(9):119.
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  6. Tefferi A, Noel P, Hanson CA. Uses and abuses of JAK2 and MPL mutation tests in myeloproliferative neoplasms. J Mol Diagn. 2011;13(5):461-466.
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  7. Tatar E, Uslu A, Aykas A, Tasli F, Oztekin O, Cagliyan GA. Splanchnic vein thrombosis following renal transplantation: a case report. BMC Nephrol. 2013;14:161.
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DOI : 10.6002/ect.2019.0117


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From the Cancer Molecular Diagnostics Program, St. James’s Hospital, Dublin, Ireland
Acknowledgements: The author has no sources of funding for this study and no conflicts of interest to declare.
Corresponding author: Stephen E. Langabeer, Cancer Molecular Diagnostics, Central Pathology Laboratory, St. James’s Hospital, Dublin D08 RX0X, Ireland
Phone: +353 1 4103576
E-mail: slangabeer@stjames.ie