Reduced global cerebral oxygen metabolic rate in sickle cell disease and chronic anemias

Abstract

Anemia is the most common blood disorder in the world. In patients with chronic anemia, such as sickle cell disease or major thalassemia, cerebral blood flow increases to compensate for decreased oxygen content. However, the effects of chronic anemia on oxygen extraction fraction (OEF) and cerebral metabolic rate of oxygen (CMRO₂ ) are less well understood. In this study, we examined 47 sickle-cell anemia subjects (age 21.7 ± 7.1, female 45%), 27 non-sickle anemic subjects (age 25.0 ± 10.4, female 52%) and 44 healthy controls (age 26.4 ± 10.6, female 71%) using MRI metrics of brain oxygenation and flow. Phase contrast MRI was used to measure resting cerebral blood flow, while T₂ -relaxation-under-spin-tagging (TRUST) MRI with disease appropriate calibrations were used to measure OEF and CMRO₂ . We observed that patients with sickle cell disease and other chronic anemias have decreased OEF and CMRO₂ (respectively 27.4 ± 4.1% and 3.39 ± 0.71 ml O₂ /100 g/min in sickle cell disease, 30.8 ± 5.2% and 3.53 ± 0.64 ml O₂ /100 g/min in other anemias) compared to controls (36.7 ± 6.0% and 4.00 ± 0.65 ml O₂ /100 g/min). Impaired CMRO₂ was proportional to the degree of anemia severity. We further demonstrate striking concordance of the present work with pooled historical data from patients having broad etiologies for their anemia. The reduced cerebral oxygen extraction and metabolism are consistent with emerging data demonstrating increased non-nutritive flow, or physiological shunting, in sickle cell disease patients.

Figure 1.

Boxplot and linear correlations of oxygen supply and utilization values. Chronically anemic subjects demonstrated (A) increased CBF, (B) similar oxygen delivery but (C) lower OEF and (D) lower CMRO₂ compared to healthy controls. Linear correlation (E) between CMRO₂ and hemoglobin and (F) between cerebral OEF and brachial OEF in the cohort in this study. * denoted statistical significance p<0.05; NS denoted no significant difference.

Figure 2.

Relationship between CMRO₂, age and anemia severity in historical references. (A) Linear correlation between CMRO₂ and age. (B) Linear correlation between age-adjusted CMRO₂ and hemoglobin. (C) Lower CMRO₂ in different anemia types compared to controls.

Figure 3.

Relationship between CMRO₂ and anemia severity when pooling the data from this current study (blue) with historical references (red). (A) Linear correlation between CMRO₂ and hemoglobin. (B) Lower CMRO₂ in different anemia types compared to controls.