Management of JAK2 Exon 12-Mutated Patient with Stable Borderline Hemoglobin
This patient requires observation with phlebotomy to maintain hematocrit <45% and low-dose aspirin, without cytoreductive therapy, because they meet low-risk criteria for polycythemia vera (age <60 years, no prior thrombosis) despite the JAK2 exon 12 mutation. 1
Diagnostic Confirmation
Your patient has a confirmed JAK2 exon 12 mutation, which is found exclusively in 2-4% of polycythemia vera cases and establishes the diagnosis of a myeloproliferative neoplasm. 2 The hemoglobin values of 15.8-17 g/dL fall just below the WHO major diagnostic threshold for PV (>18.5 g/dL in men, >16.5 g/dL in women), but this presentation is characteristic of JAK2 exon 12-mutated disease. 1, 3
A critical diagnostic pitfall to recognize: The stable borderline hemoglobin may reflect co-existing iron deficiency masking the true degree of erythrocytosis. 1 Check the red blood cell count and mean corpuscular volume—if the RBC count is elevated with microcytosis (MCV 56-60 fL), this confirms PV despite "borderline" hemoglobin. 1, 3 Iron deficiency can lower measured hemoglobin below diagnostic thresholds while red cell mass remains pathologically elevated. 1
Risk Stratification
The WHO risk stratification applies identically to JAK2 exon 12-mutated PV as to JAK2 V617F-positive disease. 1 Risk is determined by only two variables:
Your patient appears to be low-risk (assuming age <60 and no thrombosis history), based on the 8-year stable course without complications. 1
Treatment Algorithm
Low-Risk Management (Your Patient)
Phlebotomy is the cornerstone: Target hematocrit <45% regardless of mutation type. 1 Even though the hemoglobin has been stable, the JAK2 exon 12 mutation drives progressive erythropoiesis, and without intervention, erythrocytosis tends to increase over time. 1
Low-dose aspirin should be initiated for thrombosis prophylaxis, following the same protocol as JAK2 V617F-positive PV. 1 The absence of extreme thrombocytosis (platelets >1500 × 10⁹/L) in your patient makes aspirin safe—extreme thrombocytosis is uncommon in exon 12-mutated PV and would be the only contraindication due to acquired von Willebrand disease risk. 1
Cytoreductive therapy is NOT indicated for low-risk patients managed adequately with phlebotomy. 1
When to Escalate to Cytoreductive Therapy
Add hydroxyurea or interferon if any of the following develop: 1
- Progression to high-risk status (age >60 or thrombotic event)
- Intolerance to phlebotomy or inadequate hematocrit control
- Symptomatic splenomegaly
- Progressive leukocytosis or thrombocytosis
Monitoring Protocol
Schedule follow-up every 3-6 months with: 1
- Complete blood count (assess all three cell lines)
- Clinical evaluation for thrombotic or hemorrhagic complications
- Spleen size assessment by palpation
Do not monitor JAK2 mutation burden serially—this is not recommended during routine follow-up and does not guide treatment decisions outside of allogeneic stem cell transplantation or interferon therapy contexts. 2
Key Clinical Considerations
The 8-year stability is reassuring but does not change management. JAK2 exon 12-mutated PV has similar long-term outcomes to JAK2 V617F-positive disease, including similar rates of thrombosis, myelofibrosis transformation, leukemic transformation, and mortality. 4 The isolated erythrocytosis phenotype (normal WBC and platelets) is typical of exon 12 mutations but does not confer different prognosis. 4, 5
The absence of symptoms (no night sweats, no pruritus) does not eliminate the need for treatment. These constitutional symptoms are not required for diagnosis or treatment decisions in PV—thrombotic risk drives management, not symptom burden. 2
Bone marrow biopsy findings in exon 12-mutated PV typically show isolated erythroid hyperplasia without the panmyelosis seen in V617F-positive disease, which explains the normal WBC and platelet counts. 1 If bone marrow was not previously evaluated, it may help confirm the diagnosis, particularly if hemoglobin remains borderline.