Haptoglobin or Hemopexin Therapy Prevents Acute Adverse Effects of Resuscitation After Prolonged Storage of Red Cells
Background—Extracellular hemoglobin and cell-free heme are toxic breakdown products of hemolyzed erythrocytes. Mammals synthesize the scavenger proteins haptoglobin and hemopexin, which bind extracellular hemoglobin and heme respectively. Transfusion of packed red blood cells (PRBCs) is a life-saving therapy for patients with hemorrhagic shock. Because erythrocytes undergo progressive deleterious morphological and biochemical changes during storage, transfusion of PRBCs that have been stored for prolonged intervals (SRBCs; stored for 35-40 days in humans or 14 days in mice) increases plasma levels of cell-free hemoglobin and heme. Therefore, in patients with hemorrhagic shock, perfusion-sensitive organs such as the kidneys are challenged not only by hypoperfusion, but also by the high concentrations of plasma hemoglobin and heme that are associated with the transfusion of SRBCs.
Methods—To test whether treatment with exogenous human haptoglobin or hemopexin can ameliorate adverse effects of resuscitation with SRBCs after two hours of hemorrhagic shock, mice receiving SRBCs were given a co-infusion of haptoglobin, hemopexin or albumin.
Results—Treatment with haptoglobin or hemopexin but not albumin improved the survival rate and attenuated SRBC-induced inflammation. Treatment with haptoglobin retained free hemoglobin in the plasma and prevented SRBC-induced hemoglobinuria and kidney injury. In mice resuscitated with fresh PRBCs, treatment with haptoglobin, hemopexin, or albumin did not cause harmful effects.
Conclusions—In mice the adverse effects of transfusion with SRBCs after hemorrhagic shock are ameliorated by treatment with either haptoglobin or hemopexin. Haptoglobin infusion prevents kidney injury associated with high plasma hemoglobin concentrations after resuscitation with SRBCs. Treatment with the naturally occurring human plasma proteins haptoglobin or hemopexin may have beneficial effects in conditions of severe hemolysis following prolonged hypotension.
- extracellular hemoglobin
- stored blood transfusion
- hemoglobin and heme scavengers
- critical care
- Received October 20, 2015.
- Revision received May 28, 2016.
- Accepted June 30, 2016.