Koleva Larisa, Dolgikh Ivan A, Kryukova Aleksandra V, Prudinnik Dmitry S, Bovt Elizaveta A, Shakhidzhanov Soslan S, Mann Svetlana G, Smetanina Nataliya S, Ataullakhanov Fazoil I, Sinauridze Elena I
Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 1 Samor Mashel Str., 117198 Moscow, Russia.
Center for the Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences, 30 Srednyaya Kalitnikovskaya Str., 109029 Moscow, Russia.
Int J Mol Sci. 2025 Sep 4;26(17):8606. doi: 10.3390/ijms26178606.
Diagnosis of pyruvate kinase deficiency (PKD) remains challenging in clinical practice. The pyruvate kinase (PK) to hexokinase (HK) activity ratio (PK/HK) was proposed to reduce the confounding effect of reticulocytosis on PK activity measurement. However, decreased PK activity and PK/HK ratios have also been observed in other anemias, raising doubts about their diagnostic value. We assessed the diagnostic accuracy of PK/HK ratio versus PK activity in differentiating PKD from other hereditary anemias. This study included 41 patients with molecularly confirmed PKD and 62 patients with other anemias. We also evaluated the influence of reticulocytosis and transfusions on erythrocyte PK activity. The PK/HK ratio showed 73% specificity, while PK activity alone achieved 95%. In PKD patients, reticulocytosis did not affect PK activity because reticulocyte PK activity was already markedly reduced (23-fold) compared with controls. In other anemias, decreases in PK activity were present in both reticulocytes and erythrocytes, but to a lesser extent. Transfusions contribute more to the false-normal result of PK activity than reticulocytosis. Measuring reticulocyte-specific PK activity during regular transfusions provided reliable results, as only patient-derived reticulocytes are present in the blood. PK activity demonstrates higher specificity than PK/HK ratio in diagnosing PKD. Reticulocytosis is not a confounder, while transfusions remain the main limitation. Reticulocyte-specific PK activity measurement may improve diagnostic accuracy in transfused patients.
在临床实践中，丙酮酸激酶缺乏症（PKD）的诊断仍然具有挑战性。有人提出丙酮酸激酶（PK）与己糖激酶（HK）的活性比（PK/HK）可降低网织红细胞增多对PK活性测量的混杂影响。然而，在其他贫血中也观察到PK活性和PK/HK比值降低，这使其诊断价值受到质疑。我们评估了PK/HK比值与PK活性在鉴别PKD和其他遗传性贫血方面的诊断准确性。本研究纳入了41例经分子确诊的PKD患者和62例其他贫血患者。我们还评估了网织红细胞增多和输血对红细胞PK活性的影响。PK/HK比值的特异性为73%，而仅PK活性的特异性达到95%。在PKD患者中，网织红细胞增多不影响PK活性，因为与对照组相比，网织红细胞PK活性已经显著降低（23倍）。在其他贫血中，网织红细胞和红细胞中的PK活性均有下降，但程度较轻。输血比网织红细胞增多对PK活性假正常结果的影响更大。在定期输血期间测量网织红细胞特异性PK活性可提供可靠结果，因为血液中仅存在患者来源的网织红细胞。在诊断PKD时，PK活性比PK/HK比值具有更高的特异性。网织红细胞增多不是混杂因素，而输血仍然是主要限制因素。测量网织红细胞特异性PK活性可能提高输血患者的诊断准确性。
