5-(Hydroxymethyl)furfural restores low-oxygen rheology of sickle trait blood in vitro

Scott Hansen, David K. Wood, John M. Higgins

Research output: Contribution to journalArticlepeer-review

12 Scopus citations


Sickle cell trait (SCT) is the benign heterozygous carrier state for the sickle variant of the HBB gene. Most of the ~300 million people with SCT worldwide will not experience any significant complications. However, accumulating evidence finds SCT associated with increased risk for the common conditions of chronic kidney disease and venous thromboembolism, and severe but rare renal medullary carcinoma and exercise-induced rhabdomyolysis. The mechanism is uncertain, but probably involves pathological rheology of SCT blood in regions of low oxygen tension, resulting from sickle haemoglobin polymerization in SCT red cells and leading to reduced blood flow and further tissue hypoxia and damage. Here, we used an in vitro microfluidic flow system to study the oxygen-dependent rheology of SCT blood and show that 5-(hydroxymethyl)furfural, a natural breakdown product of glucose and fructose-containing foods, such as fruit juices, can reduce the effects of hypoxia on SCT blood rheology in vitro, restoring near-normal flow velocities at very low oxygen. While opinions regarding the clinical significance of the risks associated with SCT are still evolving, these results suggest that a compound present in some food may provide a potential approach for managing risks that may be associated with SCT.

Original languageEnglish (US)
Pages (from-to)985-993
Number of pages9
JournalBritish journal of haematology
Issue number6
StatePublished - Mar 1 2020

Bibliographical note

Funding Information:
The authors were supported by NHLBI grant R01HL132906 to DKW. The authors thank Chhaya Patel and Hasmukh Patel for help processing clinical specimens and Akito Nakagawa for experimental expertise. The authors are grateful for helpful suggestions and thoughtful feedback provided by two anonymous reviewers, Robert Molokie, Jonathan Carlson, and multiple colleagues.

Publisher Copyright:
© 2019 British Society for Haematology and John Wiley & Sons Ltd


  • 5HMF
  • blood flow
  • microfluidics
  • rheology
  • sickle cell trait


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