Testing for Polycythemia Vera

Srdan Verstovsek, MD:The patient case that we are describing is a case of apparent erythrocytosis. The patient presents with very, very high levels of hematocrit and hemoglobin, which is associated with an increase in blood pressure. In this case, the patient was recently diagnosed with hypertension. This is also associated with an increase in the size of the spleen. The spleen is the filter of the blood. If you have too many blood cells going around in circulation, the spleen will commonly be enlarged as well.

So this was highly suggestive of a condition called polycythemia vera. One would need to do additional testing, including molecular testing for theJAK2V617F mutation, which is present in about 96% of patients and in this particular patient, and a bone marrow biopsy to make sure that this is really being caused by the disease. In this case, this is apparent. The question is, Is the bone marrow biopsy necessary or not?

In the community setting, many people ask whether bone marrow is absolutely necessary as part of the diagnostic process in polycythemia vera. This comes from the recent modification in 2016 regarding the diagnostic process. The guideline that was published a couple of years ago says that a bone marrow biopsy should be done, but in the community setting, is this absolutely necessary? I would say that this is absolutely not necessary. Just like in our particular case, if there is apparent erythrocytosis and you have aJAK2V617F mutation, iron deficiency, and low erythropoietin, what else can it be? So, in cases like this, with apparent erythrocytosis explained by all the other supportive factors, perhaps bone marrow is not necessary.

In a patient with apparent erythrocytosis, you would think that there might be a possibility for having disease in the bone marrow, which makes these red blood cells grow without control. There are other findings that would be suggestive of the disease. That would be an increase in the spleen, which is a filter of the blood. That would catch all these red blood cells that grow around the circulation. Then the symptoms—the patient has symptoms from an enlarged spleen, as well as symptoms of a general nature like headache and fatigue. Once the circulation is impaired, there is a problem with getting oxygen to tissue around the body and patients have these systemic symptoms.

Many times, although not in this particular case, patients would also have an increase in the white cells, or platelets. About 40% to 60% of patients with polycythemia vera would have those findings as well. Other silent findings in the blood may include microcytosis. Here the small size of the red blood cells (MCV [mean corpuscular volume]) that is automatically obtained when you do the complete blood count would indicate iron deficiency. One can then extend the testing in the blood into iron deficiency by measuring the iron ferritin, which is typically low. More specifically, in polycythemia vera, you can test for theJAK2V617F mutation, which is seen in about 97% to 98% of patients with polycythemia vera.

In addition, one can also measure erythropoietin to see whether these red blood cells grow without control. This is a growth factor that boosts the production of red blood cells. In polycythemia vera, it’s not necessary. The body shuts down the production of erythropoietin because red blood cells grow on their own. So, erythropoietin is a blood test that can also be done.

The combination of very high red blood cells, enlargement of the spleen, and symptoms that are often associated with the enlargement or increasing cell counts of platelets, iron deficiency, and low erythropoietin would help conclude polycythemia vera. In this case, the red blood cell count is so high that there is no other real possibility, once you have documented aJAK2V617F mutation, that there is anything else causing that increase in red blood cells. It is polycythemia vera, even without the bone marrow biopsy.

Transcript edited for clarity.

June 2016

• A 49-year old male presents with headache, fatigue, and pain under his left ribs
• PMH includes depression and newly diagnosed hypertension
• Physical exam: BP, 160/90; abdominal exam reveals splenomegaly — spleen palpable 6 cm below costal margin
• Laboratory values:
  • Hb=20.7 g/L
  • HCT= 59.4%
  • WBC=10.2x10⁹/L
  • Platelets= 325 x10⁹/L
• Bone marrow biopsy:
  • MF-1 fibrosis and megakaryocytic hyperplasia with atypia
  • JAK2-positive
• Patient was started on phlebotomy as needed and aspirin 81 mg

October 2016

• Patient returns 4 months later with continued headache and dizziness
• He has had 3 phlebotomies in the past 3 months
• Patient was started on hydroxyurea 1000 mg/day

January 2017

• Patient returns 3 months later with abdominal fullness, continued fatigue, difficulty concentrating, fever, and leg ulcer
• Laboratory values:
  • Hb= 22.4 g/L
  • HCT= 65.3%
  • WBC=13.3x10⁹/L
  • Platelets=153x10⁹/L
• Patient is started on ruxolitinib