Patient With Polycythemia Vera Develops Multiple Pulmonary Emboli in the Setting of Uncontrolled Disease

Presentation

Mrs. L is a 77-year-old woman who was initially referred to hematology in 2019 with elevated red blood cells (RBCs) and white blood cells (WBCs). Peripheral blood workup performed 2 years later in 2021 identified the presence of the JAK2 V617F mutation, and she was diagnosed with polycythemia vera (PV); the presence of the JAK2 mutation, which occurs in 95% of patients with PV, and a hematocrit >48%¹supported this diagnosis. Mrs. L initiated intermittent phlebotomies, noting a frequency of every month. She was seeking a second opinion due to persistent erythrocytosis and leukocytosis and significant fatigue. 

Comprehensive Assessment

At the time of referral, review of blood counts over the past year revealed the following: 

Additional workup in our office included a platelet count of 361 x 10⁹/L, serum iron 14.0 mcg/dL, total iron binding capacity 442.0 mcg/dL, iron saturation 3.2%, and ferritin 6.8 ng/mL.  

Bone marrow aspiration and biopsy demonstrated the following:  

• Hypercellular marrow (95%) with trilineage hematopoiesis and atypical megakaryocytic hyperplasia. Decreased marrow iron stores. Mildly increased reticulin fibrosis (MF-1). Moderate leukocytosis with neutrophilia, eosinophilia, and basophilia.  
• Normal karyotype 46,XX[20] 
• A molecular panel demonstrated JAK2 V617F mutation 

Mrs. L was started on hydroxyurea in an attempt to control the significant erythrocytosis and leukocytosis and to eliminate the need for phlebotomy in the setting of severe iron deficiency, likely contributing to her fatigue.   

Hospitalization

Unfortunately, Mrs. L was hospitalized shortly after her initial visit to our office due to the development of significant dyspnea and subsequent respiratory failure. Workup in the hospital identified pulmonary emboli and progressive infarction of most of the lower lobe in addition to significant leukocytosis with a WBC count of 76 x 10⁹/L. She was started on heparin and transitioned to oral anticoagulation at time of discharge. Mrs. L was also discharged on supplemental oxygen and referred to pulmonology due to an abnormal echocardiogram noting bordering pulmonary hypertension. Of note, no deep-vein thromboses were found in the lower extremities.  

Post-Discharge Follow-Up

Mrs. L presented for frequent follow-up after this event for close monitoring. She continued to improve clinically and started to have improvement in her blood counts. Hydroxyurea was required at a high dose to control leukocytosis and erythrocytosis, and Mrs. L then developed thrombocytopenia. Her AP suggested that she start ruxolitinib as second-line therapy and she agreed. Hydroxyurea was tapered after starting ruxolitinib and eventually was discontinued.   

Discussion

Mrs. L’s case represents one in which the lack of disease control contributed to the development of a significant and potentially life-threatening thrombotic event. The National Comprehensive Cancer Network guidelines recommend starting cytoreductive therapy for patients with PV who are older than age 60 and/or for those who have had a prior thrombotic event.² If Mrs. L had started cytoreduction earlier, this event may have been preventable. It is important to understand how to assess risk in patients with PV and to initiate treatment when indicated. Mrs. L had a thrombotic event while on hydroxyurea, which would be an indication to pursue alternative cytoreduction therapy, perhaps ruxolitinib. Although she was not exposed to hydroxyurea very long prior to the event, the development of thrombocytopenia at the dose needed to control her WBC and RBC should prompt one to consider an alternative therapy. Mrs. L is now nearly 1 year post these events; she is off oxygen, feeling well on ruxolitinib, and traveling.  

References

1. Tefferi A, Barbui T. Polycythemia vera: 2024 update on diagnosis, risk-stratification, and management. Am J Hematol. 2023;98:1465-1487.
2. National Comprehensive Cancer Network. NCCN Clinical Practice Guidelines in Oncology: Myeloproliferative Neoplasms. Version 3.2023. Accessed October 25, 2023. https://www.nccn.org/professionals/physician_gls/pdf/mpn.pdf