Cardiovascular risks of anemia correction with erythrocyte stimulating agents: should blood viscosity be monitored for risk assessment?

Jeong et al. review the concept that elevated and elevation of blood viscosity is associated
with increased health risk of all forms. As a corollary it is proposed that patient blood viscosity
should be assessed as a mean for understanding and quantifying this risk. The perception that
increased blood viscosity is deleterious is embedded in medicine since antiquity, and it is certainly
validated by the extensive and comprehensive review of Jeong et al. Nevertheless, current findings
demonstrate instances where increasing blood viscosity is beneficial.

This divergence is a function of
the condition of the circulation. In a system of inert vessels an increase in blood viscosity is per force
associated with the increase in viscous losses and therefore the energy expended by the heart in
propelling blood through the circulation. However, blood vessels are compliant and the increase in
blood viscosity usually leads to the increase in vessel wall shear stress, to which the vascular
endothelium responds by producing nitric oxide, the potent dilator of smooth muscle. As a
consequence, the increase in blood viscosity which in principle increases the contribution to peripheral
vascular resistance due to the fluid properties of blood is compensated by the change in the
anatomical component of vascular resistance determined by vessel diameter.

Martini et al.¹ demonstrated the significant circulatory benefit derived from increasing blood viscosity by increasing
hematocrit by 10% and Salazar et al.² showed the deleterious effect caused by 10% hemodilution.
Clearly, these effects occur in the presence of a healthy, normally functioning endothelium and are
dependent on the magnitude of the change, since the dilatory response due to viscosity related
increase in shear stress is eventually overcome by the actual increase in blood viscosity.

In conditions
of acute anemia due to haemorrhage, blood viscosity is too low to maintain functional capillary
density, a problem that can be treated by incersaing plasma viscosity as shown by Cabrales et al.³ The intensive treatment of type 2 diabetes has shown to increase hematocrit and lower blood pressure.⁴

In summary, our commentary is presented to highlight the potential dual outcome from changing blood viscosity, and to support the contention that useful diagnostic information could be derived from a reliable and convenient method for measuring blood viscosity.

– C. Makena Hightower and Marcos Intaglietta

References

1. Martini J, Tsai AG, Cabrales P, Johnson PC, Intaglietta M. Increased cardiac output and
microvascular blood flow during mild hemoconcentration in hamster window model. Am J Physiol
Heart Circ Physiol 2006;291:H310-7.

2. Salazar Vzquez BY, Martini J, Tsai AG, Johnson PC, Cabrales, P, Intaglietta M. The variability
of blood pressure due to small changes of hematocrit. Am J Physio Heart Circ Physiol 2010; 299(3):H863-7.

3. Cabrales P, Tsai AG, Intaglietta M. Increased plasma viscosity prolongs microhemodynamic
conditions during small volume resuscitation from hemorrhagic shock. Resuscitation 2008;77:379-86.

4. Salazar Vzquez BY, Martini J, Chvez Negrete A, Tsai AG, Forconi S, Cabrales P, Johnson PC,
Intaglietta M. Cardiovascular benefits in moderate increases of blood and plasma viscosity surpass
those associated with lowering viscosity: Experimental and clinical evidence. Clin Hemorheol
Microcirc 2010;44:75-85.