{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,4,14]],"date-time":"2026-04-14T23:57:18Z","timestamp":1776211038017,"version":"3.50.1"},"reference-count":32,"publisher":"MDPI AG","issue":"17","license":[{"start":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T00:00:00Z","timestamp":1756944000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100006769","name":"Russian Science Foundation","doi-asserted-by":"publisher","award":["25-25-00445"],"award-info":[{"award-number":["25-25-00445"]}],"id":[{"id":"10.13039\/501100006769","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["IJMS"],"abstract":"<jats:p>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.<\/jats:p>","DOI":"10.3390\/ijms26178606","type":"journal-article","created":{"date-parts":[[2025,9,4]],"date-time":"2025-09-04T10:55:37Z","timestamp":1756983337000},"page":"8606","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":2,"title":["Pyruvate Kinase Deficiency: Markedly Decreased Reticulocyte PK Activity and Limited Specificity of the PK\/HK Ratio"],"prefix":"10.3390","volume":"26","author":[{"given":"Larisa","family":"Koleva","sequence":"first","affiliation":[{"name":"Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 1 Samor Mashel Str., 117198 Moscow, Russia"},{"name":"Center for the Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences, 30 Srednyaya Kalitnikovskaya Str., 109029 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ivan A.","family":"Dolgikh","sequence":"additional","affiliation":[{"name":"Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 1 Samor Mashel Str., 117198 Moscow, Russia"},{"name":"Center for the Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences, 30 Srednyaya Kalitnikovskaya Str., 109029 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0009-0000-0790-8466","authenticated-orcid":false,"given":"Aleksandra V.","family":"Kryukova","sequence":"additional","affiliation":[{"name":"Faculty of Fundamental Physical and Chemical Engineering, M.V. Lomonosov Moscow State University, 1 Leninskie Gory Str., 119991 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5995-7702","authenticated-orcid":false,"given":"Dmitry S.","family":"Prudinnik","sequence":"additional","affiliation":[{"name":"Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 1 Samor Mashel Str., 117198 Moscow, Russia"},{"name":"Center for the Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences, 30 Srednyaya Kalitnikovskaya Str., 109029 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elizaveta A.","family":"Bovt","sequence":"additional","affiliation":[{"name":"Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 1 Samor Mashel Str., 117198 Moscow, Russia"},{"name":"Center for the Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences, 30 Srednyaya Kalitnikovskaya Str., 109029 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Soslan S.","family":"Shakhidzhanov","sequence":"additional","affiliation":[{"name":"Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 1 Samor Mashel Str., 117198 Moscow, Russia"},{"name":"Center for the Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences, 30 Srednyaya Kalitnikovskaya Str., 109029 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Svetlana G.","family":"Mann","sequence":"additional","affiliation":[{"name":"Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 1 Samor Mashel Str., 117198 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8805-1499","authenticated-orcid":false,"given":"Nataliya S.","family":"Smetanina","sequence":"additional","affiliation":[{"name":"Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 1 Samor Mashel Str., 117198 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Fazoil I.","family":"Ataullakhanov","sequence":"additional","affiliation":[{"name":"Center for the Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences, 30 Srednyaya Kalitnikovskaya Str., 109029 Moscow, Russia"},{"name":"Department of Physiology, Perelman School of Medicine, University of Pennsylvania, 3400 Civic Center Blvd, Philadelphia, PA 19104, USA"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Elena I.","family":"Sinauridze","sequence":"additional","affiliation":[{"name":"Dmitry Rogachev National Medical Research Center of Pediatric Hematology, Oncology and Immunology, 1 Samor Mashel Str., 117198 Moscow, Russia"},{"name":"Center for the Theoretical Problems of Physico-Chemical Pharmacology, Russian Academy of Sciences, 30 Srednyaya Kalitnikovskaya Str., 109029 Moscow, Russia"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2025,9,4]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"173","DOI":"10.1111\/ejh.13424","article-title":"Prevalence of Pyruvate Kinase Deficiency: A Systematic Literature Review","volume":"105","author":"Secrest","year":"2020","journal-title":"Eur. 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