The Relationship of Oxygen Transport and Cardiac Index for the Prevention of Sickle Cell Crises

Abstract

The formation of deoxyhemoglobin S (deoxy-Hb S) polymers is the key triggering event for the complex pathophysiologic manifestations of sickle cell anemia (SCA). This polymer formation is associated with a marked right-shifted oxyhemoglobin dissociation curve (decreased affinity, increased P50), which results in a decrease in arterial oxygen saturation (SaO2). There is a delay period (“delay time”) from the formation of deoxy-Hb S to polymerization that is markedly sensitive (to the power of 30–40) to the concentration and solubility changes of deoxy-Hb S. Deoxy-Hb S polymer formation leads to sickle cell vaso-occlusion, a unique characteristic of SCA. This theoretical study, which views SCA as a disease of oxygen transport, provides a novel framework to suggest that a small to modest increase in cardiac index (by decreasing the P50 and thus increasing the SaO2) could change the distribution of the delay times (sec) such that the balance between occlusion and opening of microcirculatory vessels is shifted favoring the opening of these vessels, therefore disfavoring vaso-occlusion. Our approach integrates a mathematical model of oxygen transport in SCA with: (1) the expression relating the solubility of deoxy-Hb S to SaO2, and (2) the kinetic expression relating the delay time to the solubility of deoxy-Hb S.

CE: Understanding the Complications of Sickle Cell Disease

“…Most of those affected are of African ancestry or self-identify as Black; a minority are of Hispanic or southern European, Middle Eastern, or Asian Indian descent. 13 It is estimated that between 70,000 and 100,000 Americans have SCD. Although SCD is associated with major morbidity, currently more than 90 percent of children with SCD in the United States and the United Kingdom survive into adulthood.…”

Modifying priming techniques in cardiopulmonary bypass circuit in known case of sickle-cell trait undergoing open heart surgery

“…1 In the presence of HbS or HbSS, the red blood cells (RBCs) tend to become stiff, sticky, and sickle shaped losing their functional properties when exposed to triggers like low oxygen environment, hypothermia, hypotension, stress, anxiety, acidosis, vasoconstriction, dehydration, and venous stasis. [2][3][4][5][6] They cause inflammation of the vessel wall and activate selectins. Selectin is the responsible sticky factor which leads to blood cells sticking to vessel wall and promotes sickling.…”

Sickle cell disease: Classification of clinical complications and approaches to preventive and therapeutic management

“…Most of those affected are of African ancestry or self-identify as Black; a minority are of Hispanic or southern European, Middle Eastern, or Asian Indian descent [4]. It is estimated that between 70,000 and 100,000 African Americans have SCD.…”