PubMed: 29603246

Title
Elevated free hemoglobin and decreased haptoglobin levels are associated with adverse clinical outcomes, unfavorable physiologic measures, and altered inflammatory markers in pediatric cardiac surgery patients.
Journal
Transfusion
Volume
58
Issue
None
Pages
1631-1639
Date
2018-07-01
Authors
Cholette JM | Blumberg N | Alfieris GM | Eaton MP | Gensini F | Henrichs KF | Phipps R | Pietropaoli AP | Powers KS | Refaai MA | Rubenstein JS | Spinelli SL | Sweeney D

Evidence afb8f8db66

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.

Evidence 8602384869

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).

Evidence 4cab2c18ab

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.

Evidence ffe6f2fcf8

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).

Evidence ee4f12121a

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

Evidence c615e55f15

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.

Evidence 25955b8868

Lower haptoglobin levels are associated with poor outcomes, immunomodulation, and unfavorable changes in physiologic measures.12,13,26,27

Evidence b3cf4de2ab

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).

Evidence 4dfe8dc0e5

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).

Evidence 3f8b37a0f6

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).

Evidence 8532c6ebe4

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).

Evidence f1592f95af

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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