Red blood cell antibody-induced anemia causes differential degrees of tissue hypoxia in kidney and brain(1)
Even moderate levels of preoperative anemia [hemoglobin (Hb) concentrations between 80 and 100 g/l] have been associated with an increased risk of renal injury {odds ratio (OR): 1.38 [95% confidence interval (CI) 1.18–1.62], P < 0.05}. TER119 is a monoclonal antibody specific to the glycophorin-A complex on the surface of RBC. Intravenous administration of this antibody induces a moderate degree of anemia over a span of days, resulting in subacute anemia. RBC-specific antibody (TER119) was administered to anesthetized mice via tail vein (1 μg/g body weight).
A single injection of RBC-specific antibody induced moderate anemia with a nadir Hb concentration of 89 ± 13 g/l on day 4 compared with a baseline value of 147 ± 7 g/l and a control value of 143 ± 7 g/l. Double-injected mice developed severe anemia, with Hb concentrations being reduced to 54 ± 5 g/l on day 5 compared with single-injected mice with a value of 95 ± 11 g/l. Hb values for mice receiving a single injection and double injection returned to control values by 14 days following injection.
Plasma Hb levels rose to a peak value of 1.2 ± 0.3 g/l at 6-h following RBC-specific antibody injection, which was higher than a control value of 0.3 ± 0.3 g/l. No gross hematuria was observed in any mice. By day 1 following injection, plasma Hb concentrations in the anemia group were reduced to 0.5 ± 0.3 g/l, which was not significantly different from the control value of 0.5 ± 0.3 g/l. Spleen weight increased to a maximum of 0.21 ± 0.04 g by day 4 after RBC-specific antibody injection, more than twofold higher than a control value of 0.09 ± 0.01 g. No difference in liver weight was observed between anemic and control mice.
SpO2 values increased in anemic mice from a baseline value of 97.1 ± 0.6% to a day 3 value of 98.1 ± 0.2 and a day 4 value of 97.8 ± 0.4%.
Further evidence linking renal hypoxia and acute kidney injury has been reviewed recently. For example, renal tissue hypoxia has been measured following experimental models of contrast-induced nephropathy, sepsis-induced kidney injury, and ischemia-reperfusion injury.
Characterization of this model of subacute anemia suggests that the reduction in Hb was secondary to a degree of early acute intravascular hemolysis and subsequent splenic sequestration of RBCs. This was demonstrated by a slight increase in plasma Hb concentrations at 6 h, followed by a marked increase in spleen weight on day 4. Previous studies characterizing the effect of TER119 and other anti-RBC antibodies on RBC hemolysis have demonstrated evidence of gross hematuria utilizing higher doses of anti-RBC antibodies.