Diagnosis of pyruvate kinase (PK) deficiency remains challenging in clinical practice. To avoid the influence of reticulocytosis when measuring PK activity, was proposed to measure PK:hexokinase (HK) enzyme activity ratio. However, decreased PK activity and PK:HK ratio were observed in patients with other anemias, so use of this ratio in differential diagnostics remains questionable. Here, we assessed the specificity and sensitivity of this ratio in the differential diagnosis of PK deficiency (PKD) and other anemias. Under these conditions, the specificity of the ratio was 73% while the specificity of PK activity was 95%. In a cohort of PKD (n=41) and other anemias (n=62) patients with molecularly confirmed anemias, we demonstrated the absence of PK activity dependence on reticulocytosis in PKD patients and showed the reason for this absence: PK activity is already significantly (23-fold) reduced in reticulocytes in these patients. A decrease in PK activity in both reticulocytes and erythrocytes was also found in patients with other anemias, but to a much lesser extent. Transfusions contribute more to the false-normal result of PK activity than reticulocytosis and we suggested measuring specific PK activity in reticulocytes during regular transfusions, since after the transfusion the patients blood contains only his own reticulocytes.
Koleva et al. (Thu,) studied this question.