In the care of patients with cyanotic congenital heart disease, the definition of anemia is difficult, as the physiologic adaptation to hypoxemia involves erythrocytosis, right-shifting of the hemoglobin dissociation curve, and changing cardiac index[1, 2]. The erythrocytic response to chronic hypoxemia is important for maintenance of systemic oxygen transport[2]. Patients can either suffer from too little of a response, resulting in a relative anemia, or too brisk of a response resulting in hyperviscosity[3]. Thus, a tool to predict the expected values of hemoglobin for a given oxygen saturation would be useful. A relationship for children and adolescents with cyanotic heart disease has been explored by Gidding et al, after exclusion of factors that could destabilize systemic oxygen transport, such as diminished iron stores[3]. A less steep relationship between hemoglobin and oxygen saturation has previously been reported for iron replete patients with Eisenmenger syndrome[4].

This descriptive cross-sectional study prospectively sought to include adults with congenital heart disease with right-to-left shunts. Patients exhibited a wide range of oxygen saturations. The primary objective of this study was to establish the optimal hemoglobin for adults with cyanotic congenital heart disease, employing stringent criteria to exclude patients with evidence of inadequate erythropoeisis. The exclusion criteria were the presence of any of the following criteria: evidence of iron deficiency, vitamin B12 or folate deficiency, elevated serum erythropoietin, reticulocytosis, hypochromia, or a significant rightward shift of the oxygen-hemoglobin dissociation curve. In addition, patients with recent acute hospitalization, therapeutic phlebotomy, differential cyanosis, and use of supplemental oxygen were excluded. The authors were able to show a strong linear correlation between the optimal hemoglobin and oxygen saturation with the regression equation showing the optimal hemoglobin equal to 57.5 – (0.444 x oxygen saturation). For example, a patient with an oxygen saturation of 85% would be expected to have a hemoglobin of 19.7. Because of the rigorous exclusion criteria employed in this study, the slope of this relationship was steeper and demonstrated a better linear relationship than in prior studies[3, 5]. The authors also went on to provide a functional context by taking those patients at an optimal hemoglobin and performing a 6-minute walk test. The 6-minute walk test results of the optimal group were then compared to the non-optimal group. The greater the deviation was from the optimal hemoglobin, the poorer the performance on the 6-minute walk test [5].

This study provides a significant contribution to the care of cyanotic adult congenital patients, providing the clinician with a tool for assessing the adequacy of physiologic compensation given an oxygen saturation. This is particularly useful for patients in a balanced state of erythropoiesis. Not surprisingly, patients with an oxygen saturation less than 75% had non-optimal hemoglobin values. Previous studies have shown these patients to have elevated erythropoietin titers, suggesting the presence of a threshold saturation level below which many patients cannot mount an adequate erythrocytic response[3, 6]. Thus, while it was not possible predict the optimal hemoglobin for these sicker patients, it may be enough to recognize their likely state of unbalanced erythropoeisis[5]. Through its stringent exclusion criteria, the study also alerts the clinician to previously established factors that alter the expected relationship between hemoglobin and oxygen saturation. Knowledge of these criteria aids in identifying factors that may be limiting erythrocytic compensation. Future studies may address ways to bring patients at non-optimal hemoglobin values into the optimal range[7].

REFERENCES:

1. Gidding SS, Stockman JA, 3rd: Effect of iron deficiency on tissue oxygen delivery in cyanotic congenital heart disease. Am J Cardiol 1988;61:605-607. Link
2. Berman W, Jr., Wood SC, Yabek SM, Dillon T, Fripp RR, Burstein R: Systemic oxygen transport in patients with congenital heart disease. Circulation 1987;75:360-368. Link
3. Gidding SS, Bessel M, Liao YL: Determinants of hemoglobin concentration in cyanotic heart disease. Pediatr Cardiol 1990;11:121-125. Link
4. Diller GP, Dimopoulos K, Broberg CS, Kaya MG, Naghotra US, Uebing A, Harries C, Goktekin O, Gibbs JS, Gatzoulis MA: Presentation, survival prospects, and predictors of death in eisenmenger syndrome: A combined retrospective and case-control study. Eur Heart J 2006;27:1737-1742. Link
5. Broberg CS, Jayaweera AR, Diller GP, Prasad SK, Thein SL, Bax BE, Burman J, Gatzoulis MA: Seeking optimal relation between oxygen saturation and hemoglobin concentration in adults with cyanosis from congenital heart disease. Am J Cardiol 2011;107:595-599. Link
6. Tyndall MR, Teitel DF, Lutin WA, Clemons GK, Dallman PR: Serum erythropoietin levels in patients with congenital heart disease. J Pediatr 1987;110:538-544. Link
7. Tay EL, Peset A, Papaphylactou M, Inuzuka R, Alonso-Gonzalez R, Giannakoulas G, Tzifa A, Goletto S, Broberg C, Dimopoulos K, Gatzoulis MA: Replacement therapy for iron deficiency improves exercise capacity and quality of life in patients with cyanotic congenital heart disease and/or the eisenmenger syndrome. Int J Cardiol Link