Evolving Risk Assessment Beyond Traditional Binary Classification

Dr. Pankit Vachhani from the University of Alabama at Birmingham and Dr. Firas El Chaer from Miami Cancer Institute introduce their discussion on optimizing care for patients with polycythemia vera (PV). They present the first case scenario involving a 54-year-old man with a two-year history of JAK2V617F-mutated PV, initially categorized as low-risk with no prior thrombotic events. His medical history includes well-controlled hypertension and family history of ischemic strokes, while working full-time with frequent travel demands.

Despite initial management with low-dose aspirin and intermittent phlebotomies, followed by hydroxyurea titrated to maximum tolerated dose, his hematocrit remained inadequately controlled. Over the past 12 months, he required phlebotomies approximately every 6-8 weeks to maintain hematocrit below 45%. Recent laboratory studies revealed white blood cell counts ranging 13,000-15,000, stable platelet counts, and iron deficiency evidence. Review of systems demonstrated worsening fatigue, reduced exercise tolerance, and intermittent pruritus.

Dr. El Chaer emphasizes that although this patient was appropriately categorized as low-risk initially under classical binary framework (age below 60 years, no thrombotic history), his risk profile has changed over 2 years, warranting explicit reassessment rather than relying on original categorization. Key concerning factors include persistent leukocytosis (13,000-15,000 range) representing independent predictor risk factor supported by multiple retrospective analyses, including major 2024 publication by Aaron Gerds reinforcing associations between elevated white blood cell count and both arterial and venous thrombosis in PV. Additionally, inadequate hematocrit control despite maximally titrated hydroxyurea means significant time spent above target thresholds between phlebotomies, precisely the exposure period associated with thrombosis risk.

Dr. Vachhani contextualizes the historical evolution of PV management, noting decades-long focus purely on thrombotic risk assessment. Current approaches now extend beyond thrombotic risk considerations, incorporating symptom management, iron deficiency prevention, myelofibrosis progression prevention, and bleeding event prevention. This evolution reflects accumulated data from the past 10-15 years and availability of newer treatment options that modify underlying disease course, transforming purely clinically driven thrombotic risk reduction approaches into comprehensive disease management strategies addressing symptoms, iron deficiency, and disease progression prevention.