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The following is a summary of “Pyruvate Kinase Function Correlates With Red Blood Cell Properties and Clinical Manifestations in Sickle Cell Disease,” published in the February 2025 issue of American Journal of Hematology by Traets et al. 

Pyruvate kinase (PK) is essential for ATP production. Reduced PK activity and thermostability are key features of sickle cell disease (SCD). 

Researchers conducted a retrospective study to assess the link between impaired PK function, sickle RBC properties, and SCD complications.  

They included 97 non-transfused patients with SCD (88 HbSS, 9 HbS/β0 thalassemia) and analyzed PK thermostability correlations with RBC parameters, sickle RBC properties, and clinical manifestations. They used multivariate Poisson regression to assess the association between PK function and SCD complications. 

The results showed PK thermostability correlated with reticulocyte count (r = −0.402, P < 0.0001), hemoglobin F (r = 0.394, P < 0.0001), point of sickling (r = −0.417, P < 0.0001), oxygen affinity (r = 0.408, P < 0.001), and RBC adhesion to laminin (r = −0.322, P = 0.024). A low PK/HK ratio correlated with decreased PK thermostability (r = 0.308, P = 0.002), RBC deformability (r = 0.268, P = 0.009), and elevated 2,3-diphosphoglycerate (r = −0.244, P = 0.016). Every 10-unit decrease in PK thermostability and 1-unit decrease in PK/HK ratio increased SCD complications by 11% (P = 0.012) and 10% (P = 0.019), respectively. 

Investigators found that impaired PK function was linked to compromised sickle RBC properties and increased SCD complications, supporting the potential of PK activation therapy. 

Source: onlinelibrary.wiley.com/doi/full/10.1002/ajh.27644