Sickle Cell Anemia as a Disease of Oxygen Transport: Possible Implications for the Prevention of Sickle Cell Crises.
Authors: Farrell Kevin , Dent Leon , Buchowski Maciej , Aguinaga Maria del Pilar 
Published: October 2019

Abstract 4617

Introduction

The formation of deoxy-sickle hemoglobin polymers is the key triggering event for the pathophysiological manifestations of Sickle Cell Anemia (SCA). The formation of deoxy-sickle hemoglobin polymers is directly related to the degree of oxygen desaturation (Sa02) which is a known component of SCA [Prior studies have demonstrated SaO2's in the 78 – 90% range]. This decrease in Sa02 in SCA results from the marked shift to the right of the oxyhemoglobin dissociation curve that commonly occurs in SCA. Prior attempts to have this corrected have focused directly on the right shifted curve itself, rather than the underlying physiologic reasons for the shift. A right-shifted curve results in a decreased affinity between oxygen and hemoglobin which at bottom is a defense mechanism to improve oxygen delivery to the tissues in the presence of anemia.

Our hypothesis is that a modest increase in cardiac output under certain conditions of hemoglobin concentration [Hb], oxygen consumption [VO2], cardiac output [Q], and oxygen tension at 50% saturation [P50] (while breathing room air) can decrease the extent of a rightward shift of the oxyhemoglobin dissociation curve (ie. resulting in a decreased torr value for the P50). Since a decrease in the P50 will result in an increase in the SaO2 which is directly related to the degree of polymer formation, an increase in Q can potentially decrease the deoxy-sickle hemoglobin polymer fraction.

Methods

The approach and theoretical data presented below is based on the method of oxygen transport calculations (J. Surg Research 2009;155; 201-209) and the quantitative relationship between deoxy-sickle hemoglobin and SaO2 as determined by magnetic double resonance spectroscopy (Proc. Natl Acad Sci 1980: 77; 5487-5491).

Results

The theoretical data below are cardiac outputs (L/min/m2) at various hemoglobin concentrations and P50 levels as shown below for a VO2 fixed at 150 ml/min/m2 and a mixed venous PO2 [PvO2] fixed at 40 torr and an FiO2 of 0.21 (room air)

Discussion

The elevated P50's remain an inviting target for future therapeutic modalities in sickle cell disease. The theoretical oxygen transport data presented support the concept that elevation of the cardiac output could potentially decrease the rightward shift of the oxyhemoglobin dissociation curve. This should result in a decrease of the deoxy-sickle hemoglobin polymer fraction leading, potentially, to a decreased incidence of sickle cell crises. For a given increase in Q, a higher P50, a lower Hb, and a lower VO2 (data not shown) will result in a greater decrease in P50. Based on the above data the ideal range of oxygen transport parameters where a modest increase in Q (approximately 0.5 L/min/m2) would be most effective, would be for P50's from 42 to 50 torr with a Hb range of 7 – 9 gms.%. It remains unknown the degree to which the increase in P50 in Sickle Cell Anemia is responsive to increased tissue oxygen delivery. This is a question that potentially can be answered in the experimental laboratory.

Disclosures:

No relevant conflicts of interest to declare.