REVEAL study

Findings from an important new study for the management of polycythemia (PV) patients have just been released.

Called the REVEAL study*, it shows that leukocytosis (a high white cell count) is a risk factor for thrombosis (blood clots) in patients with PV. The study showed thrombosis to occur in high and low-risk patients, and even in patients in whom hematocrit was adequately controlled.

To date, known risk factors for thrombosis in PV patients included advanced age, previous history of blood clots, and elevated hematocrit >.45. There was insufficient data to include elevated white blood cell (WBC) counts as a known risk factor.

However, in an analysis of 2271 PV patients, the REVEAL study found 142 blood clots in 106 patients.
Specifically. during the study period of just under 4 years, it identified:

• Significant associations with initial blood clot occurrence for hematocrit level >45% and WBCs >11 × 10⁹/L .
• Elevated WBC count was significantly associated with initial thrombosis in both low and high-risk PV patients.
• Even when hematocrit was controlled at 45% or lower, WBC count >12 × 10⁹/L was significantly associated with thrombosis.
• There are different risk factors for arterial and venous thrombosis, an observation that has also been reported in essential thrombocythemia. Both leukocytosis and thrombocytosis (high platelet count), poor hematocrit control, and age were associated with a higher risk of arterial thrombosis, whereas female sex, history of previous thrombosis, and leukocytosis turned out to be the main risk factors for venous thrombosis.

The study’s authors feel that, even without a large study proving that lowering leukocytosis reduces blood clots, there is sufficient evidence to ‘support the inclusion of leukocytosis in the definition of high-risk polycythemia vera’. They also suggest that two elements of clinical practice could be changed:
– ‘low-risk patients with persistent leukocytosis could be elevated to the high-risk category and, therefore, be candidates for cytoreduction’ and
– ‘normalization of leukocytes should be included as an objective of treatment in patients receiving cytoreduction.’

There are two abstracts available discussing the REVEAL study’s findings.

REVEAL puts leukocytes into risk stratification 

Association between elevated white blood cell counts and thrombotic events in polycythemia vera: analysis from REVEAL

* REVEAL is a prospective observational study that enrolled 2510 patients with PV, with median follow-up of 44.7 months (range, 2-59 months). REVEAL stands for The Prospective Observational Study of Patients with Polycythemia Vera in US Clinical Practices.