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Manifestations of disease in PKD
sent for additional genetic analyses including non-coding intronic region sequencing and copy number variation analyses.
Impact of disease manifestations on treatment decisions
Splenectomy and hematopoietic stem cell transplantation in pyruvate kinase deficiency
CASE: A 6-year old boy with genetically confirmed PKD pres- ents to the hematology clinic for a discussion regarding his man- agement, particularly for consideration of splenectomy. This is prompted by the complications of his disease thus far. In his life- time he has received a total of ten red blood cell transfusions dur- ing episodes of symptomatic anemia in the setting of increased hemolysis with viral infections.
Supportive care for PKD is focused on transfusions and/or splenectomy. Approximately 60% of PKD patients are splenectomized, with a median hemoglobin rise of 1.6 g/dL.11 Splenectomy is often performed in patients with significant anemia, transfusion burden, and/or massive splenomegaly. The potential benefits and risks of splenec-
tomy must be weighed against those of continued anemia and/or red blood cell transfusions. The risks of splenecto- my, including post-splenectomy infections and thrombot- ic complications, have been extensively reviewed else- where.40-43 The rate of venous thrombosis in PKD is 10%, which is similar to the rate in other hemolytic disorders, while the reported rate of post-splenectomy sepsis may be as high as 7%, which is higher than that reported in other cohorts of splenectomized individuals.36 The risk of sepsis is highest in the first year after surgery and in young chil- dren but is life-long. The decision to proceed with splenec- tomy should be delayed until after the age of 5 years, but this timing and the risk of post-splenectomy sepsis must be weighed against the risks of iron loading in patients treated with regular transfusions. Early referral to hema- tology and surgery for evaluation is advised to assess the pros and cons of splenectomy.
The majority of patients with PKD will experience an improvement in hemolysis with both an increased hemo- globin and decreased transfusion burden after splenecto- my; however, patients have continued compensated hemolysis with an ongoing risk of severe anemia due to increased hemolysis with infections, aplastic crises associ- ated with parvovirus, and bilirubin-related gallbladder dis-
Figure 4. The glycolytic pathway. Deficiency of pyruvate kinase results in diminished ATP production as well as buildup of pathway intermediates proximal to pyruvate kinase, most notably 2,3-diphosphoglycerate. Modified with permission from Grace and Glader.57 Glucose-6-P: glucose-6-phosphate; Fructose-6-P: fructose-6-phos- phate; Fructose 1,6-DP: fructose 1,6-diphosphate; DHAP, dihydroxyacetone phosphate; G3P: glucose-3-phosphate; 1,3-DPG: 1,3-diphosphoglycerate; 2,3-DPG, 2,3- diphosphoglycerate; 3-PG: 3-phosphoglycerate; PEP: phosphoenolpyruvate. Blue: enzymes in glycolytic pathway that correlate with the more common glycolytic enzy- mopathies.
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