Polycythemia rubra vera: An unlikely cause of severe pulmonary embolism

Rami N. Khouzam, MD, FACC, FACP, FASNC, Mary Jane Gallahan, PA-C, PhD?

May 30, 2011

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Polycythemia rubra vera: An unlikely cause of severe pulmonary embolism

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CASE 

An 80-year-old female presented with mild pain in the left leg followed a month later by slight shortness of breath without chest pain. The patient had a known history of polycythemia rubra vera (PRV) for at least 3 years, hypertension, and coronary artery disease. She had been followed by a hematologist and was having occasional phlebotomies as needed. On presentation, vital signs were stable including an arterial oxygen saturation of 96%. All laboratory values were unremarkable with the exception of elevated levels of hemoglobin at 19.8 g/dL (normal range: 12-15 g/dL), hematocrit at 69.7% (normal range: 36-48%), and total RBC mass at 38 mL/kg (normal range in females: 21-27 mL/kg). WBC count was slightly high at 14.3×10⁹ (normal range: 4.8-10.8×10⁹/L). Serum vitamin B12 concentration was elevated at 993 pg/mL (normal range: 200-900 pg/mL). Erythropoietin level was low at 1.3 IU/mL (normal range: 4.1-19.5 IU/mL). JAK2V^617F mutation was tested and the result was positive.  

A full workup for hypercoagulable tendency (by the patient's hematologist) was unremarkable for all of the following: factor V Leiden (R506Q) mutation, factor II (prothrombin), protein C and S, antithrombin III, lupus anticoagulant, and anticardiolipin. CT of the chest with contrast was ordered. The scan showed a filling defect (arrows, right and left panels) representing pulmonary embolism with thrombus shown in the distal right main pulmonary artery. Mild splenomegaly was noted on examination and CT findings. Left leg deep venous thrombosis (DVT) was diagnosed, followed a month later by right arm DVT and a pulmonary embolism with thrombus in the distal right main pulmonary artery. 

DISCUSSION

Polycythemia rubra vera is a rare myeloproliferative disorder that can be associated with severe organ damage and high mortality (Figure 1).¹ It occurs in about 2 of every 100,000 people. The average age at which PRV is diagnosed is 60 years, and the disorder rarely occurs in people younger than 20 years. More men than women develop PRV. Symptoms and signs usually include headache, breathlessness, disturbed vision, weakness, dizziness, general itching, flushing, facial redness, red eyes, and enlarged spleen or liver. Occasionally, patients with PRV have no symptoms. 

Diagnosis Until recently, diagnostic criteria for polycythemia rubra vera were based on the Polycythemia Vera Study Group Diagnostic Criteria, which relied on RBC mass, arterial oxygen saturation, splenomegaly, thrombocytosis, leukocytosis, leukocyte alkaline phosphatase activity, and vitamin B₁₂ binding capacity.² The diagnosis of PRV is now made based on the 2008 World Health Organization (WHO) criteria, which integrate molecular diagnostics into evaluation and screening.³ PRV is diagnosed when both major and one minor criterion are present or when the first major criterion is present with any two minor criteria. The major criteria include  

Hemoglobin level greater than than 18.5 g/dL in men (greater than 16.5 g/dL in women) or other evidence of increased red cell volume, (or) hemoglobin or hematocrit level higher than 99th percentile of method-specific reference range for age, sex, altitude of residence, (or) hemoglobin level greater than 17 g/dL in men (greater than 15 g/dL in women) if associated with a documented and sustained increase of at least 2 g/dL from an individual's baseline value that cannot be attributed to correction of iron deficiency, (or) elevated red cell mass greater than 25% above mean normal predicted value. 
Presence of JAK2V^617F or similar mutation (eg, JAK2 exon 12 mutation).

The minor criteria include 