Table 3: Inferences drawn from and the quality of evidence graded by 2 observers
Inference	Quality of evidence
Oxyhemoglobin dissociation curve
Anemia shifts the oxyhemoglobin curve to the right because of increased 2,3­DPG levels	Ci
Anemia causes clinically significant rightward shifts in the oxyhemoglobin curve because of the Bohr effect	Civ
The shift in the oxyhemoglobin curve has been clearly established in many forms of anemia (excluding hemoglobinopathies)	Cii
The shift in the oxyhemoglobin curve has been clearly established in a number of human diseases	Civ
Cardiac output
Cardiac output increases with increasing degrees of normovolemic anemia provided that blood volume is adequate	Ci
Increased cardiac output in normovolemic anemia is a result of increased stroke volume	Ci
The contribution of increased heart rate to the increase in cardiac output following normovolemic anemia is variable	Ci
Other hemodynamic alteration
Changes in blood viscosity result in many of the hemodynamic changes in normovolemic anemia	Ci
Normovolemic anemia is accompanied by increased sympathetic activity	Ci
Normovolemic anemia causes increased myocardial contractility	Cii
Normovolemic anemia causes a decrease in systemic vascular resistance	Ci
Normovolemic anemia results in a redistribution of cardiac output toward the heart and brain and away from the splanchnic circulation	Ci
Maximum global O2 delivery occurs at hemoglobin concentrations ([Hb]) of 100-110 g/L	Ciii
Global O2 delivery declines above and below [Hb] of 100-160 g/L	Ci
Coronary and cerebral blood flow
Coronary blood flow is increased during anemia	Ci
Cerebral blood flow is increased during anemia	Ci
Coronary artery disease in the presence of moderate degrees of anemia ([Hb] below 90 g/L) results in impaired left ventricle contractility or ischemia	Ci
Moderate anemia does not aggravate cerebral ischemia in patients with cerebrovascular disease	Ci
Note: 2,3­DPG = 2,3­diphosphoglycerate.

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