Pyruvate Kinase, Erythrocytes
Clinical Information Discusses physiology, pathophysiology, and general clinical aspects, as they relate to a laboratory test
Deficiencies of most of the enzymes of the Embden-Meyerhof (glycolytic) pathway, including pyruvate kinase (PK), have been reported. PK deficiency, although relatively rare, is the erythrocyte enzyme deficiency most frequently found to be a cause of chronic nonspherocytic hemolytic anemia (CNSHA). It is an autosomal recessive disorder and parents of affected patients are typically carriers. It is possible the mutation arose as partial protection against malaria.PK deficiency is the most easily masked of the RBC enzyme disorders and is therefore difficult to classify without complete information which may require correlation with results of PKLR gene molecular testing (PKLRG / Pyruvate Kinase Liver and Red Blood Cell (PKLR) Full Gene Sequencing and Large Deletion Detection). Most hemolytic anemias due to PK deficiency are associated with activity levels less than 40% of mean normal. However, some patients with clinically significant hemolysis can have normal or only mildly decreased PK enzyme activity, which paradoxically may occur in individuals with the most severe symptoms. Carriers (heterozygotes) may show mildly decreased activity and are hematologically normal. Some PK carrier states can exacerbate other RBC disorders (ie coincident glucose-6-phosphate dehydrogenase: G6PD deficiency or hemoglobin S trait).
Clinically significant PK deficiency manifests in widely variable severity ranging from incidental compensated mild normocytic anemia to severe neonatal anemia. Other symptoms include jaundice, early gallstones, splenomegaly and iron overload even in the absence of frequent transfusions. Rare severe forms are associated with hydrops fetalis/fetal demise. Rarely, acquired PK deficiency can arise secondary to myeloid neoplasms.
Evaluation of nonspherocytic hemolytic anemia
Evaluation of neonatal anemia
Evaluation of unusually severe hemoglobin S trait
Evaluation of unusually severe glucose-6-phosphate dehydrogenase deficiency
Investigating families with pyruvate kinase deficiency to determine inheritance pattern and for genetic counseling
Most hemolytic anemias due to pyruvate kinase (PK) deficiency are associated with activity levels less than 40% of mean normal. However, some patients with clinically significant hemolysis can have normal or only mildly decreased PK enzyme activity, which paradoxically may occur in individuals with the most severe symptoms. Carriers (heterozygotes) may show mildly decreased activity and are hematologically normal.
Elevated PK concentrations can be found in those patients with younger erythrocyte population. This may be due to the patient being a newborn or young red cells are being produced in response to the anemia (reticulocytosis).
Cautions Discusses conditions that may cause diagnostic confusion, including improper specimen collection and handling, inappropriate test selection, and interfering substances
Because leukocytes also contain pyruvate kinase (PK) that is not diminished in hereditary erythrocytic PK deficiency, freeing the blood of white blood cells is always critical to this test. If the WBC count is very high, false-negative results may occur due to inability to adequately remove WBCs from the assay.
Reference Values Describes reference intervals and additional information for interpretation of test results. May include intervals based on age and sex when appropriate. Intervals are Mayo-derived, unless otherwise designated. If an interpretive report is provided, the reference value field will state this.
> or =12 months: 6.7-14.3 U/g Hb
Reference values have not been established for patients who are <12 months of age.
Clinical References Provides recommendations for further in-depth reading of a clinical nature
1. Grace RF, Zanella A, Neufeld EJ, et al: Erythrocyte pyruvate kinase deficiency: 2015 status report. Am J Hematol 2015 Sep;90(9):825-830
2. Pissard S, Max-Audit I, Skopinski L, et al: Pyruvate kinase deficiency in France: a 3-year study
reveals 27 new mutations. Br J Haematol 2006 Jun;133(6):683-689
3. Zanella A, Fermo E, Bianchi P, et sl: Pyruvate kinase deficiency: the genotype-phenotype association. Blood Rev 2007 Jul;21(4):217-231
4. Beutler E: Hereditary nonspherocytic hemolytic anemia: pyruvate kinase deficiency and other abnormalities. In Hematology. Fourth edition. Edited by WJ Williams, E Beutler, AJ Erslev, MA Lichtman. New York, McGraw-Hill Information Services Company, Health Professions Division, 1990, pp 606-612