Selective Destruction of Reticulocytes (Retics) in Pyruvate Kinase (PK) Deficiency

Abstract

PK retics lack adequate glycolysis and are peculiarly susceptible to irreversible damage in the spleen because they are dependent upon mitochondrial function for which splenic venous PO₂ is insufficient [Blood 34: 861, 1969]. The fraction and mass of PK deficient retics immediately trapped in the spleen should therefore influence clinical severity. A 22-year-old male (J.P.) with icterus and splenomegaly and with RBC PK 0.25 units (normal > 2.0 units) Hgb. 13.3 g% and retics 7% illustrates this mechanism. Mean RBC life span was approximately 100 days (T 1/2⁵¹Cr = 33 days), but bilirubin turnover (³H bilirubin) was 5 × normal yielding mean RBC life span of only 20 days. ferrokinetics with ⁵⁹Fe showed plasma iron turnover 5 × normal ; rapid marrow ⁵⁹Fe uptake, but low cumulative RBC⁵⁹Fe and immediate splenic sequestration of newly labeled cells. These data provide evidence that the majority of J.P.'s newly formed retics were immediately sequestered in the spleen. The remainder survived normally and these were sufficient in number to provide 13.3 g % hemoglobin. That the low PK level in circulating mature J.P. cells did not limit their survival was additionally supported by therapeutic transfusion of J.P. cells to a severely anemic homozygous PK deficient female (C.D.) with much higher RBc PK (0.9 units) but with marked splenomegaly. Isologous survival of J.P. cells in C.D. was only modestly reduced (T 1/2 ⁵¹Cr RBC = 18 days) whereas the autologous survival of C.D. cells was markedly shortened (T 1/2 = 7 days).

Thus low levels of PK need not limit the survival of mature RBC. Retics are much more vuluerable to the block in glycolysis and become irreversibly sequestered in the hypoxic splenic circulation.

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