Effects of total hemoglobin and hemoglobin S concentration on cerebral blood flow during transfusion therapy to prevent stroke in sickle cell disease.

Abstract

The standard treatment of stroke in sickle cell disease is chronic transfusion to maintain the fraction of abnormal hemoglobin (hemoglobin S [HbS]) below 20%. Risks associated with such transfusion can be reduced by allowing higher HbS levels, but the physiological consequences of this modification are unknown. Cerebral blood flow is elevated in sickle cell disease proportionate to the degree of anemia and is reduced by transfusion. We tested the effects of various HbS levels on cerebral blood flow during the course of transfusion therapy. We monitored cerebral blood flow (by the 133Xe inhalation method) in three patients whose chronic transfusion program was changed from a traditional regimen (HbS < 20%) to a moderate one, allowing HbS to rise to 45% to 50% between treatments. As expected, cerebral blood flow was higher with lower hemoglobin and higher HbS concentration. However, the HbS fraction appeared to exert a separate influence on the hyperemia, independent of total hemoglobin concentration. Furthermore, cerebral blood flow was higher during the modified regimen, despite equivalent anemia. These results suggest caution in adapting the modified transfusion regimen. Although HbS concentrations of 50% did not cause any frank neurological sequelae, the possible consequences of the associated hyperemia over time are unknown. We conclude that larger clinical and physiological studies of moderate transfusion regimens (allowing higher concentration of HbS) are necessary before it can become standard therapy.

Hemodynamic Etiology of Elevated Flow Velocity and Stroke in Sickle-Cell Disease

“…Of the nontransfused group, 25 patients remained stroke free and 14 did develop stroke: the only difference between these two groups was TCD velocities, higher in the stroke group. Finally, we have shown by serial observations that cerebral perfusion and TCD velocities are strongly and negatively correlated with Hct in each individual patient, and can rise or fall very quickly, within months on changing transfusion regimens (Hurlet-Jensen et al, 1994) or even within minutes during transfusion (Venketasubramanian et al, 1994). These rapid changes are inconsistent with the relatively slow rate of development of stenotic disease, but compatible with a hemodynamic etiology.…”

How I treat and manage strokes in sickle cell disease

“…Based on the established benefits of initial blood transfusion therapy in SCD, increasing Hb levels with increased oxygen delivery while simultaneously decreasing the HbS levels 46 (both of which are associated with improvement of blood flow to the brain), our strategy is to perform an initial exchange transfusion. 47 Additional indirect evidence is based on the observation that at the vast majority of hematology centers, an initial exchange transfusion with a prior simple transfusion or with an exchange alone is preferred over simple transfusion for children presenting with acute strokes.…”

Stroke in children with sickle cell disease

“…The presumed cause of ischemic cerebral infarct is a regional mismatch between energy demand and supply. Cerebral hemodynamic studies in patients with SCD indicate that oxygen delivery to the brain can be increased by increasing the hemoglobin concentration [106,Class II]. In patients with SCD at rest, an increase in hemoglobin concentration results in a decrease in the mean velocity of blood in the middle cerebral artery [107].…”