Should oxygen-delivery potency matter more than hemoglobin concentration alone?
Hemoglobin concentration tells us how much hemoglobin is present. It does not, by itself, quantify how effectively a specific blood product or hemoglobin formulation loads oxygen, unloads it under tissue conditions, interacts with flow and microcirculation, or ultimately contributes to tissue oxygen delivery.
A functional potency question can now be asked quantitatively.
Rogers and colleagues introduced lung-to-tissue oxygen flux, L-TOF, as an in vitro metric for comparing oxygen-delivery potency across fresh and stored red-cell products and formulations containing hemoglobin-based oxygen carriers.
The authors explicitly note that transfusion dosing is commonly based on hemoglobin levels without accounting for differences in oxygen-delivery potential between products.
Concentration should not be confused with function.
For BHOC development, the central question is not simply how many grams of hemoglobin are administered. The more useful development question is how much reproducible oxygen-delivery function a defined dose provides under relevant physiological conditions.
A functional potency framework could eventually connect formulation attributes, oxygen affinity, dose and oxygen unloading with downstream physiological endpoints. That relationship has to be demonstrated, not assumed.
L-TOF suggests that equal volume or equal hemoglobin does not automatically mean equal modeled oxygen-delivery potency.
From analytical potency to clinically meaningful oxygen delivery.
Chu and colleagues (2026) provide a complementary functional framework for characterizing oxygen-supply efficiency beyond hemoglobin concentration alone. Their parameter system integrates oxygen affinity (P50), cooperativity through the Hill coefficient, Bohr-effect responsiveness through an acid-base sensitivity index, and theoretical oxygen-release capacity under simulated lung and tissue conditions [2]. The study included red blood cells, bovine hemoglobin (bHb) and a dextran-modified bovine hemoglobin conjugate (Dex20-bHb), making the analytical approach directly relevant to research questions around cell-free and modified hemoglobin oxygen carriers.
These analytical properties are only one layer of functional oxygen delivery. Comparative studies of a structurally different natural extracellular hemoglobin provide additional questions for testing. Tsai and colleagues evaluated microvascular response together with nitric-oxide and carbon-monoxide reaction kinetics in preclinical models [3], while Le Gall and colleagues examined biodistribution and the ability of the same extracellular hemoglobin system to reduce hypoxia in poorly vascularized tissue in vivo [4]. These studies do not establish equivalence with BHOC, but they support separating oxygen-binding properties, vascular interaction, microcirculatory behavior and tissue oxygenation when functional potency is evaluated.
References
- Rogers SC, Brummet M, Tobin KV, et al. Defining and quantifying oxygen delivery potency of blood products. Blood Red Cells & Iron. 2026;2(2):100054. doi:10.1016/j.brci.2026.100054. PMID:42453356.
- Chu Z, You G, Li W, et al. Simulated Oxygen Supply Efficiency Assessment to Represent Stored Red Blood Cells Quality. Life. 2026;16(2):205. doi:10.3390/life16020205. PMID:41752843.
- Tsai AG, Intaglietta M, Sakai H, Delpy E, Drieu La Rochelle C, Rousselot M, Zal F. Microcirculation and NO-CO studies of a natural extracellular hemoglobin developed for an oxygen therapeutic carrier. Curr Drug Discov Technol. 2012;9(3):166-172. doi:10.2174/157016312802650814. PMID:22564165.
- Le Gall T, Polard V, Rousselot M, et al. In vivo biodistribution and oxygenation potential of a new generation of oxygen carrier. J Biotechnol. 2014;187:1-9. doi:10.1016/j.jbiotec.2014.07.008. PMID:25034433.