Diagnosis of Polycythemia Vera

Jamile M. Shammo, MD:So, we’re talking about a patient who’s 67 years old and who presented to the hematologist with complaints of fatigue. She was found to have a high hematocrit and was diagnosed with polycythemia vera after determining that she was JAK2-positive. Her physical exam at that time was unremarkable, basically. Her CDC was consistent with high hematocrit. So, her CDC was remarkable for a high hematocrit at about 48%. Also, she has some leukocytosis, 1200 white cells and mild thrombocytosis in the 600,000 range. She was testedJAK2-positive; hence the diagnosis of polycythemia was made with some certainty—although, we can talk about the most recent guidelines or the WHO 2016 guidelines for making the diagnosis of PV.

Nonetheless, her physician determined that she had acquired cytoreduction, and initiated Hydrea (hydroxyurea) at 500 mg/day, which is 1 tablet, in addition to adding in a low-dose aspirin. And the patient, after 3 months, actually had resolution of some of her symptomatology, which we’d mentioned, and her hematocrit was optimized. Pruritus went away. However, about a year and- a half later, she had returned to the clinic and now she has some left upper quadrant pain. Her hematocrit had risen to about 48% again, like how she presented initially. And then, the treating hematologist opted to increase her dose of Hydrea to 1000 mg/day, which is 2 tablets. So, obviously, this needs to be assessed later, which was done. The patient, even though her spleen got somewhat smaller, she continues to have high hematocrit and has required multiple phlebotomies a few months after dose escalation of Hydrea.

I think the issue in suspecting polycythemia vera is something that primary care physicians have to be made aware of. Because, obviously, they’re the first physician to assess a given patient, and unless you have abnormalities on a blood count, those patients will not be referred to hematology. So, if a primary care physician sees a patient who complained of symptoms of splenomegaly, felt a spleen on exam, or did the CDC and noticed high white blood cell count, high platelet count, or high hematocrit, then this patient deserves to be referred to hematology, particularly because those abnormalities do not resolve. You ruled out other causes, let’s say infection or any kind of a reactive condition. Those patients need to be evaluated by hematology for sustained rise in their abnormalities on their CDC.

The issue with the high hematocrit is a sticky one because sometimes patients may be iron deficient, particularly those who have polycythemia, and hence their parameters may not necessarily be as high as might trigger the primary care physician to send them to hematology. So, I think that was taken into consideration when the new WHO 2016 criteria were put together, which brought down the level beyond that a hematocrit is considered abnormal for men and women. In essence, from 18.5 g/dL to 16.5 g/dL for men and from 18 g/dL to 16 g/dL in women.

But I think, again, we have to educate primary care doctors so that they know that this is the new number now that they have to be concerned about if a patient of theirs had higher hemoglobin or hematocrit beyond those points. And, again, once this is done and taken care of, the hematology evaluation could take place. Now with the advent of the ability to orderJAK2testing, and it’s being 95% positive in PV patients, the diagnosis has gotten somewhat easier in the clinic.

Transcript edited for clarity.

August 2014

• A 67-year-old female is diagnosed PV after complaining of fatigue
• Physical Exam was unremarkable
• CBC:
  • HCT, 48%
  • WBC, 12,100/μL
  • Platelets, 603,000/μL
• Mutation testing: JAK2 V617F-positive
• The patient was started on treatment with low-dose aspirin and hydroxyurea 500 mg/day
• Her symptoms resolved within 3 months

February 2016

• She now complains of left upper quadrant pain
• For 1.5 years, the patient was maintained on treatment; however, for the past 9 months her hematocrit has risen to 48% and she has required 4 phlebotomies in last 6 months
• Hydroxyurea was increased from 500 mg to 1,000 mg daily
• Physical Exam: remarkable for splenomegaly

August 2016

• Physical Exam: still remarkable for splenomegaly, slightly smaller
• HCT 47.5%