Research ArticleSickle Cell Diagnostics

A Biophysical Indicator of Vaso-occlusive Risk in Sickle Cell Disease

Science Translational Medicine  29 Feb 2012:
Vol. 4, Issue 123, pp. 123ra26
DOI: 10.1126/scitranslmed.3002738

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Going with the Flow … or Not

In healthy people, blood flows freely throughout the body, delivering oxygen to tissues via the molecule hemoglobin. For those with sickle cell disease, red blood cells carry a mutated form of hemoglobin, called hemoglobin S, that changes cells into a rigid sickle, or crescent, shape and causes blood flow to slow markedly. Although sickle cell disease can be detected through genetic and molecular tests, there is no objective biomarker of clinical outcome. Wood et al. therefore devised a microfluidic device that can mimic this vaso-occlusive event, allowing them to detect biophysical changes in blood—a new type of marker that could stratify sickle cell patients on the basis of disease severity.

Wood et al. collected blood from 29 patients: 23 of which were classified as having “severe” disease, and 6 of which were “benign.” The blood was flowed through a microfluidic device consisting of a channel coupled to an oxygen reservoir. As sickle cells become deoxygenated, they adopt their stiff, sickle shape. In their device, such deoxygenation would result in a drop in flow velocity, which could be measured as a change in conductance. This biophysical marker helped the authors to successfully identify benign versus severe samples, without using less reliable markers like white blood cell count and hemoglobin S fraction. Wood and colleagues could also predict a patient’s response to therapy, such as a blood transfusion or small-molecule drugs.

It may never be possible to predict the exact timing of vaso-occlusion, but the ex vivo biophysical test proposed by Wood et al. can objectively identify patients who are not responding well to treatment or transfusion. Conversely, the test could pinpoint those who may benefit from such therapies, putting more patients on treatment regimens that make their red blood cells just go with the flow.