Management of Pyruvate Kinase Deficiency
Overview of Treatment Approach
Management of pyruvate kinase deficiency is primarily supportive, focusing on symptom-directed red blood cell transfusions, monitoring and treating iron overload, splenectomy in severely affected patients, and managing complications of chronic hemolysis. 1
Transfusion Management
When to Transfuse
Transfuse based on symptoms rather than hemoglobin thresholds, as patients with PKD tolerate anemia surprisingly well due to elevated red cell 2,3-DPG, which shifts the oxygen dissociation curve rightward and improves tissue oxygen delivery. 1
Infants and young children (<5 years) are more likely to require regular transfusions (53% vs. 14% in older children), with transfusion needs typically decreasing with age. 2
Neonatal jaundice requiring phototherapy and/or exchange transfusion is common in the newborn period. 1
Exacerbations requiring occasional transfusion may occur during acute infections or pregnancy. 1
Transfusion Requirements
All blood products for PKD patients must be irradiated to prevent transfusion-associated graft-versus-host disease. 3
Only cellular components (whole blood, red blood cells, platelets, granulocytes) require irradiation. 3
Splenectomy Considerations
Indications and Benefits
Splenectomy should be considered in severely affected patients with high transfusion burden or significantly impaired quality of life, but the diagnosis must be definitively confirmed first and thrombophilic disorders excluded. 1
Splenectomy typically increases hemoglobin by 1-3 g/dL and may reduce or eliminate transfusion requirements, though it does not arrest hemolysis. 1
Most children experience increased hemoglobin and decreased transfusion burden post-splenectomy. 2
Critical Exclusions Before Splenectomy
- Exclude hereditary stomatocytosis and other thrombophilic disorders before performing splenectomy, as splenectomy is contraindicated in stomatocytosis due to thrombotic risk. 1
Risks and Complications
Post-splenectomy complications include infection/sepsis (12% in children) and thrombosis (1.3%), even during childhood. 2
Thromboembolic events occur particularly in splenectomized patients. 1
Splenectomy results in conspicuous rise in reticulocytes even as anemia improves. 1
Iron Overload Management
Monitoring Requirements
Monitor iron burden regularly in all patients regardless of transfusion status, as iron overload occurs in both transfusion-dependent and transfusion-independent patients. 1, 3
Iron overload affects 48% of children with PKD. 2
Pathophysiology
In transfusion-independent patients, iron overload results from ineffective erythropoiesis with inappropriately low hepcidin levels. 1, 3
Coinheritance of hereditary hemochromatosis mutations may contribute to iron accumulation. 1
Treatment
- Initiate chelation therapy when iron overload is documented. 4
Complication Monitoring and Management
Gallstones
Screen for gallstones regularly after the first decade of life, as they occur with increased frequency (20% in children) and may develop even after splenectomy. 1, 2
Coinheritance of UGT1A1 TA promoter polymorphism increases gallstone risk. 1
Other Complications to Monitor
Aplastic crisis following parvovirus B19 infection requires vigilance. 1
Extramedullary hematopoiesis can cause spinal cord compression and requires personalized treatment. 1, 5
Pulmonary hypertension may develop, particularly in splenectomized patients. 1
Perinatal complications occur in 31% of cases. 2
Rare complications include kernicterus, chronic leg ulcers, acute pancreatitis secondary to biliary disease, splenic abscess, and fulminant hepatic failure. 1
Follow-Up Schedule
All children and adolescents with PKD should receive hematology care visits at least every 6 months regardless of transfusion status to monitor for complications and organ dysfunction. 6
Emerging Therapies
Disease-modifying therapies including pyruvate kinase activators and gene therapy are in clinical development and may transform PKD management by decreasing chronic hemolysis symptoms and avoiding complications of current supportive treatments. 4, 6, 7
These novel approaches may change the course of disease in childhood and beyond. 6
Critical Pitfalls to Avoid
Do not perform diagnostic enzyme testing within 50 days of transfusion, as donor red cells can mask PK deficiency for up to 120 days and cause falsely normal results. 3
Do not use hemoglobin thresholds alone to guide transfusion decisions—assess symptoms and quality of life impact. 1, 5
Do not assume iron overload only occurs in transfused patients—monitor all PKD patients. 1, 3
Ensure definitive diagnosis before splenectomy and exclude contraindications like stomatocytosis. 1