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The Physical Foundation of Vasoocclusion in Sickle Cell Disease
Journal article   Open access   Peer reviewed

The Physical Foundation of Vasoocclusion in Sickle Cell Disease

Alexey Aprelev, William Stephenson, Hongseok (Moses) Noh, Maureen Meier and Frank A Ferrone
Biophysical journal, v 103(8), pp L38-L40
17 Oct 2012
PMID: 23083726
url
https://doi.org/10.1016/j.bpj.2012.09.003View
Published, Version of Record (VoR) Open

Abstract

Biophysical Letter
The pathology of sickle cell disease arises from the occlusion of small blood vessels because of polymerization of the sickle hemoglobin within the red cells. We present measurements using a microfluidic method we have developed to determine the pressure required to eject individual red cells from a capillary-sized channel after the cell has sickled. We find that the maximum pressure is only ∼100 Pa, much smaller than typically found in the microcirculation. This explains why experiments using animal models have not observed occlusion beginning in capillaries. The magnitude of the pressure and its dependence on intracellular concentration are both well described as consequences of sickle hemoglobin polymerization acting as a Brownian ratchet. Given the recently determined stiffness of sickle hemoglobin gels, the observed obstruction seen in sickle cell disease as mediated by adherent cells can now be rationalized, and surprisingly suggests a window of maximum vulnerability during circulation of sickle cells.

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Web of Science research areas
Biophysics
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