There are in vitro and animal model data linking increased free Hb, heme, and iron to inflammation, 6 infection,7 platelet (PLT) activation,8,9 vasculopathy, 10 and thrombosis.
Preoperative adult normal haptoglobin levels, compared with lower preoperative haptoglobin levels, were associated with significantly lower Day 1 peak blood lactate levels and higher nadir mean arterial pressures on day one (Figs. S1 and S2, available as supporting information in the online version of this paper) as well as on the first and second days postoperatively (data not shown).
Children undergoing open heart surgery experience a progressively increasing risk of postoperative infection and thrombosis, increasing need for mechanical ventilation and inotropes, increasing Day 1 through Day 2 peak blood lactate, and decreased nadir mean arterial pressure as the levels of free Hb increase and the levels of haptoglobin decrease.
The postoperative infection rate was significantly higher in children receiving the oldest blood (third tertile, 25-38 days) compared to those receiving the freshest RBCs (first tertile, 7-15 days) (34% vs. 7%; p50.004).
Increased circulating cell-free Hb, heme, and iron and decreased haptoglobin concentrations have been associated with morbidity and mortality in both animal models and patients.4,5
Our findings in the complex setting of critically ill pediatric cardiac surgery patients demonstrate that higher levels of free Hb and lower levels of haptoglobin are associated with serious postoperative clinical complications (infection, thrombosis, death), immunomodulation, and inflammation.
Lower haptoglobin levels are associated with poor outcomes, immunomodulation, and unfavorable changes in physiologic measures.12,13,26,27
The median (and mean—data not shown) free Hb levels preoperatively and at all postoperative time points (immediately and 6 and 12 hr postoperatively) were higher (p50.057) in those who later developed a proven thrombosis (Fig. 3 displays the 12-hr data).
However, patients who died had significantly higher plasma cell-free Hb and lower haptoglobin concentrations at all time points, preoperatively and immediately postoperatively and 6 and 12 hours postoperatively (Fig. 1 shows the 12-hr postoperative data).
Adult normal levels of preoperative haptoglobin were associated with a substantially, but not significantly lower rate of infection than lower levels (Table 1, second row).
Adult normal levels of preoperative haptoglobin were associated with a substantially and significantly lower incidence of thrombosis than lower levels of haptoglobin (Table 1; row 3).
Furthermore, experiments of nature that lead to increased levels of chronic hemolysis, such as sickle cell anemia and paroxysmal nocturnal hemoglobinuria, provide evidence that low levels of hemolysis may be harmful, and contribute to inflammation, thrombosis, vasculopathy, and impaired host defenses against infection.1,11
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If you find BEL Commons useful in your work, please consider citing: Hoyt, C. T., Domingo-Fernández, D., & Hofmann-Apitius, M. (2018). BEL Commons: an environment for exploration and analysis of networks encoded in Biological Expression Language. Database, 2018(3), 1–11.