Managing acute vascular events in patients with myeloproliferative neoplasms

Case 1 A 62-year-old man is referred to hematology clinic for a new diagnosis of polycythemia vera (PV). His older brother was diagnosed with PV 6 months ago after presenting to an emergency room with a submassive pulmonary embolism and the patient wants to know what his risk is for developing thrombosis and how he can reduce it. His past medical history is notable for hyperlipidemia and hypertension. He has no personal history of thrombosis and is otherwise asymptomatic. His only medications are simvastatin and hydrochlorothiazide. Initial evaluation is notable for a hematocrit of 52% and a platelet count of 620,000/μL. Epidemiology of thrombosis in myeloproliferative neoplasms Thrombosis rates are roughly similar among PV, essential thrombocythemia (ET) and primary myelofibrosis (PMF) patients, averaging 4.9% per year in PV, 1.4% per year in ET, and 1.75% per year in PMF (see Table 18.1 for arterial and venous rates). The remainder of myeloproliferative neoplasms (MPNs) are less well studied (chronic eosinophilic leukemia/hypereosinophilic syndrome, systemic mastocytosis) or known to have a distinct molecular biology (chronic myeloid leukemia). In this chapter, we will focus primarily on thrombosis in ET and PV as the two most common and pathophysiologically similar MPNs. Risk stratification Individual thrombosis risk stratification often directs treatment plan in patients with MPNs, including initiation of cytoreductive agents. Current risk stratification is largely based on age and history of thrombosis, as the combination of age >60 years and previous history of thrombosis confers a hazard ratio (HR) of 17.3 for future thrombosis. Patients with neither are considered at low risk, and all others are considered at high risk. A number of other potential risk factors have also been studied in these patients. Cardiovascular risk factors Traditional cardiovascular risk factors, including hypercholesterolemia, male gender, and smoking, are all associated with increased rates of thrombosis, particularly arterial thrombosis, in patients with MPNs. Thrombocytosis While thrombocytosis is a hallmark of ET and is often noted in PV, the degree of platelet elevation does not clearly correlate with thrombosis risk. Further implications and management of thrombocytosis will be addressed later in this chapter. Leukocytosis Several studies have demonstrated that leukocytosis, both at baseline and during cytoreductive therapy, is a marker of increased risk of primary and recurrent thrombosis in patients with MPNs.