The EValuation of ERythrocytosis pRospEctive cohort STudy (EVEREST) is a prospective study designed to shed light on these key questions in the diagnosis, management, and clinical outcomes in patients with elevated hemoglobin (erythrocytosis). This longitudinal, prospective study will generate high quality data that can help inform the optimal approach to diagnosis and management in this patient population.

The EVAluation of Erythrocytosis pRospEctive cohort STudy (EVEREST) is a prospective, longitudinal, observational study designed to provide insights into the diagnosis, management, and outcomes of patients with elevated hemoglobin (erythrocytosis). This study aims to address key gaps in understanding the underlying causes, diagnostic approaches, and clinical outcomes of patients presenting with erythrocytosis in real-world clinical settings.

Erythrocytosis, defined as an elevated hemoglobin concentration, is a frequent reason for referral to hematology and presents substantial diagnostic and therapeutic challenges. The condition may arise from primary causes, such as polycythemia vera (PV), or secondary causes, including chronic hypoxia, erythropoietin-secreting tumors, medications, and exogenous testosterone use. Despite advances in diagnostic tools, there remains considerable uncertainty about the most effective ways to evaluate and manage erythrocytosis, particularly in distinguishing secondary from primary causes and in mitigating associated risks such as arterial and venous thrombosis.

EVEREST is designed to address these knowledge gaps by enrolling a diverse cohort of patients referred to hematology for evaluation of erythrocytosis. Participants will undergo comprehensive clinical evaluation and assessment of potential underlying causes. Data will be collected longitudinally to evaluate real-world management practices, such as the use of phlebotomy, cytoreductive therapy, and antithrombotic agents, and to document clinical outcomes, including rates of thrombosis, bleeding, disease progression, and mortality.

The study has four main objectives:

1. To prospectively measure the incidence of various causes of erythrocytosis in patients referred for elevated hemoglobin levels.
2. To prospectively evaluate the diagnostic accuracy of the JAKPOT prediction rule, a simple prediction rule using complete blood count parameters, for identifying JAK2-positive erythrocytosis/polycythemia vera and differentiating it from secondary causes.
3. To evaluate real-world management strategies for patients with erythrocytosis.
4. To document longitudinal clinical outcomes, including thrombosis, bleeding, disease progression, and survival.

EVEREST aims to recruit 1,500 adult patients across participating clinics. Participants will be followed for clinical outcomes, and data will be collected to better characterize therapeutic approaches utilized in routine clinical care. This study seeks to generate evidence that will inform clinical practice and improve patient care for patients with erythrocytosis.

Outcome Measures EVEREST is a prospective observational study which will investigate multiple interrelated aspects of erythrocytosis, encompassing its causes, diagnostic evaluation, management strategies, and clinical outcomes. Two co-primary outcome measures have been selected to reflect the study's main objectives to measure the incidence and causes of erythrocytosis and the diagnostic accuracy of the JAKPOT prediction rule. Additionally, secondary outcome measures will focus on real-world management strategies and longitudinal clinical outcomes, providing further insights to inform patient care.

Inclusion Criteria:

1. Adult patients (>=18 years) referred to hematology clinics at London Health Sciences Centre with hemoglobin levels >=165 g/L in males or >=160 g/L in females.
2. Patients capable of providing informed consent.
3. Age >= 18 years.

Exclusion Criteria:

1. Patients <18 years.
2. Patients without erythrocytosis.
3. Patients incapable of providing informed consent.

EVEREST will recruit adult patients evaluated for erythrocytosis, hemoglobin levels >=165 g/L in males or >=160 g/L in females, in hematology clinics at London Health Sciences Centre.