Masked PV Case Highlights Challenge of Diagnosis in Younger Women

Polycythemia vera (PV) can be hard to identify due to its status as a rare disease, but a new case report shows why the condition can be particularly difficult to diagnose in a particular patient population: women of childbearing age.

The case report appeared in Cureus.

PV is a rare blood disorder marked by expansion of red blood cell (RBC) mass. Yet, the study authors said because the assay used to assess RBC mass is not commonly used in clinical practice, the first signal that something is wrong is often irregular hemoglobin and hematocrit levels. Other factors that can be used to diagnose PV include certain bone marrow biopsy features, the discovery of a particular Janus kinase 2 mutation, and decreased serum erythropoietin.

Iron metabolism is often dysregulated in patients with PV, the investigators said, and women of childbearing age with the condition often experience iron deficiency that can complicate diagnosis because chronic blood loss and iron depletion can limit RBC expansion.

“This has diagnostic implications, as hemoglobin and hematocrit levels cannot reach the defined PV diagnostic threshold, blurring the clinical picture and delaying a targeted investigation,” they wrote.

Such cases are referred to as “masked” PV.

In the case report, the investigators outlined one such case. A 41-year-old woman sought emergency care after experiencing headaches and dizziness. The patient had a history of anxiety disorder and menometrorrhagia-associated anemia, and had recently received a diagnosis of arterial hypertension. The only medications she had been taking were an oral contraceptive and lisinopril (Zestril).

The patient was given captopril and metamizole to treat her symptoms, and referred for a follow-up outpatient appointment. During the appointment, the patient referred to gradually worsening symptoms that included fatigue, nausea, holocranial pulsating headache, and paraesthesia of the wrists and hands. Clinicians noted high blood pressure and a palpable spleen. When they ordered laboratory tests, the patient’s RBC count was high and she had thrombocytosis, but her hemoglobin and hematocrit were normal, the authors said.

“Profound microcytosis and hypochromia were confirmed in peripheral blood smear, and iron studies showed low levels of ferritin, serum iron, and transferrin saturation,” they wrote.

The patient was given an iron supplement and switched to a new antihypertensive therapy.

Iron supplementation led to a fleeting improvement in her fatigue symptoms, but her iron and serum erythropoietin levels remained low. As physicians sought to confirm or exclude other causes, they performed an abdominal ultrasound and confirmed splenomegaly.

They next used a polymerase chain reaction test to look for JAK2 mutations, and found the V617F mutation, which is associated with PV. A bone marrow biopsy was also performed, and it revealed hypercellular medulla with mature trilineage growth, erythroid hyperplasia, and other features suggestive of PV. The patient was given acetylsalicylic acid and referred to a hematologist, who initiated cytoreductive therapy with hydroxyurea. A year later, the patient was clinically asymptomatic and had a controlled blood count.

The study authors said most patients with PV receive their diagnosis in their sixth decade of life, while adding that younger females with PV are at a higher risk of misdiagnosis or delayed diagnosis because their symptoms can often be explained by iron depletion or arterial hypertension.

“The assessment of spleen enlargement is a key point of the physical examination, which should be confirmed by abdominal ultrasound,” they said.

They also said the case shows why serum erythropoietin and RBC count are important parameters to assess when PV is suspected and severe iron deficiency is present.

“These tests are widely available and can provide additional evidence to support PV investigation,” they wrote.

Reference

Almeida LR, Faustino D, Gameiro R, Salvado V, Dias L. Masked polycythemia vera and iron deficiency in a fertile-age woman. Cureus. Published online January 9, 2023. doi:10.7759/cureus.33545