Elsevier

Medical Hypotheses

Volume 72, Issue 5, May 2009, Pages 578-580
Medical Hypotheses

Pathophysiologic considerations for the interactions between obstructive sleep apnea and sickle hemoglobinopathies

https://doi.org/10.1016/j.mehy.2008.12.012Get rights and content

Summary

There are contradictory reports about the effects of obstructive sleep apnea (OSA) on clinical vaso-occlusive events in sickle hemoglobinopathies. The discourse has focused on the possible effects of OSA-associated hypoxemia on hemoglobin S (HbS) polymerization. Advances in understanding the pathogenesis of sickle vaso-occlusion and the physiologic consequences of OSA suggest that the potential for interaction exceeds simple hypoxemia. HbS polymerization, red cell–endothelial cell interactions, hypercoagulability, neutrophil activation and vasoactive factors constitute the multi-pathway model of sickle cell vaso-occlusion. These processes are abnormal in OSA and theoretically these abnormalities may initiate or potentiate vaso-occlusion. If this hypothesis is correct, OSA may convert the clinically benign genetic carrier state of sickle cell trait to a clinically overt disease. Reported clinical events in sickle cell trait are usually related to exposure to relative hypoxia, and are limited to the spleen and renal medulla. Studies to compare the prevalence of events (splenic infarction and hematuria) in sickle cell trait with and without OSA, as well as their relationship to exposure to environmental hypoxia will be a first step in verifying this hypothesis.

Section snippets

Background

Sickle cell trait is a benign genetic carrier state without hematological manifestations. In the United States, sickle cell trait occurs in 7–10% of the black population [1]. Obstructive sleep apnea is an increasingly common disorder affecting 4% of middle-aged adults [2] and African-Americans may have a higher prevalence than Caucasian-Americans [3]. Therefore, co-existent sickle cell trait and OSA would not be expected to be rare.

Normal hemoglobin (HbA) consists of two alpha and two beta

Hypothesis

Vaso-occlusion in sickle hemoglobinopathies involves multiple pathways that include polymerization, sickle cell–endothelial cell interactions, vascular reactivity, leucocyte activation and hypercoagulability. Since OSA adversely affects these processes it can convert sickle cell trait to a condition with overt vaso-occlusive episodes.

Polymerization

The most important determinant in the occurrence of polymerization is deoxygenation. The degree of hypoxia required to initiate polymerization varies with the quantity of HbS in the erythrocyte. In HbAS erythrocytes, polymerization begins at oxygen saturation of 60% [14]. This degree of hypoxia is unlikely to be simply secondary to OSA but other conditions that promote hemoglobin deoxygenation exist in OSA.

Respiratory acidosis is common in obstructive sleep apnea. Hydrogen ions shift the

Conclusion

There seems to be enough preliminary evidence to justify investigating a possible interaction between OSA and sickling hemoglobinopathies. The preceding discussion does not exhaust the current state of knowledge on pathophysiologic processes in these diseases but highlights areas where experimental evidence exists for perturbations of similar processes in both conditions. It is important to point out that the existence of hemostatic activation, for example, in both conditions does not establish

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