Abstract:
Polycythaemia vera (PV) belongs to the group of myeloproliferative neoplasms with excessive increase in hemoglobin levels. They are clinically characterized by nonspecific symptoms such as fatigability, pruritus, early satiety due to splenomegaly, increased risk of infections, and thrombotic events. JAK2 V617F mutation present in 80-90% of MPNs and JAK2 exon12 mutations are seen in 4%-5% cases of MPNs like PV. Activation of JAK2 by either point mutation or fusion protein causes activation of the JAK-STAT pathway. While mutations in JAK2 are reported in numerous MPN phenotypes, exon 12 mutations specifically result in erythrocytosis due to increased EPO signaling.
Case series
Case 1-A 21-year male presented to the hematology OPD with complains of parasthesias and off and on headache for the past 6 months. He was on multiple symptomatic medications but to no relief. On routine investigations it was seen that he had a persistent hemoglobin level fluctuating between 17.5gm/dl and 18.5 gm/dl. He has iron deficiency for which he is on single oral iron tablet. No definite organomegaly was seen. In hematology OPD he was investigated for polycythemia vera keeping in mind the WHO criterias. His Serum EPO levels are within normal range,JAK2 V617F/exon 12mutation analysis is negative. A bone marrow aspiration and biopsy study done shows Hypoplastic marrow for age with erythroid predominance. In view of his clinical presentation he is being treated with ecosprin, Supplemental iron orally and phlebotomy every 3 months and patient is clinically relieved of his symptoms. His last hemoglobin value is stable at 16.5gm/dl.
Case 3- A 29-year male presented to hematology OPD with paresthesias and weakness for 3 months. A routine CBC investigation showed a high hemoglobin level of 19.7 gm/dl. Mildly raised RBC count was also seen. Rest all parameters were within normal limits. Similar to the previous case no relevant examination findings were there. A low serum EPO levels of <1 mIU/Ml (4.3-29.0 mIU/ML) was seen. JAK 2V617F/exon12 mutation analysis was negative. The patient has been started on ecosprin and phlebotomy every 3 months and is symptomatically relieved.
Conclusion-All three cases that presented to the department had been undiagnosed for 2-3 months before they reached our setup. The unique feature of all these cases was negativity for both JAK2V617F as well as JAK2 exon 12 mutation despite its clinical behavior being that of PV .These cases are being actively managed as low risk polycythemia vera and since the start of the treatment comprising of phlebotomy once very 3 months their hemoglobin and hematocrit concentrations are maintained. No cytoreductive therapy is being given .Such unique presentations need to be reported and discussed extensively.
