Polycythemia vera (PV), a clonal hematopoietic stem cell disorder, is the most common myeloproliferative neoplasm (MPN) and is characterized by an overproduction of morphologically and functionally normal blood cells. Mutations of the Janus kinase 2 (JAK2), a member of the tyrosine kinase family of enzymes that is involved in signal transduction for erythropoietin, thrombopoietin, and granulocyte colony-stimulating factor (G-CSF), underlie a high proportion of cases of PV.

PV was initially believed to follow a progression from erythrocytosis to myelofibrosis and leukemic transformation, but it is now known that PV is not a homogenous disorder. Instead, its presentation and progression are related to host factors including genetic variations, age, and gender. For example, women deregulate fewer genes, and the clinical course of the disease is different in them compared with men. Some patients with PV are genetically predisposed to an aggressive clinical course while for others, the disease is more indolent.

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First recognized in 1892, PV has been studied for more than 125 years; since 2014 alone, there have been 589 publications about diagnosing PV and 655 about managing it. But despite the large body of literature, there remains no consensus on how to diagnose PV, how to manage it proactively as opposed to supportively, or whether it is even a separate entity from essential thrombocytosis (even though they are genetically distinct disorders).

Jerry L Spivak, MD, from the hematology division at the Johns Hopkins University School of Medicine in Baltimore, Maryland, recently authored a review article published in Blood outlining his strategies for diagnosis and management of PV in an evidence-based manner, as well as the associated challenges.

“From my perspective, you have a difficult task because the MPN field is not like other fields in medicine,” Dr Spivak said in an interview with Hematology Advisor. “It is rife with fake news and lack of rigorous scientific and clinical insight even though the basic concepts are not hard to comprehend.”

For example, he pointed out, some MPN experts have said that blood volumes in women are comparable with those in men even though men produce 10 times more androgen than women. This idea can negatively affect recommendations for the target hematocrit of phlebotomy therapy in PV.