Answer to Brain Teaser

Hydroxyurea (HU) typically causes macrocytosis. Normally, an elevated mean cell volume (MCV) will result in a reduced RBC count to maintain a constant Hct (optimal Hct is evolutionarily selected for; Hct = RBC count x MCV).

However, in polycythemia vera (P. vera) the RBCs are marching to their own tune. They don’t care/recognize that the MCV is elevated, so in the absence of a compensatory decrease, the Hct will increase (before and unless cytoreductive effects of HU kick in).

HU-mediated elevation in MCV and Hct will increase blood viscosity and total peripheral resistance, and thus impair cardiac output. … over time, HU-mediated cytoreduction may offset the early effect of HU on Hct.