How is pyruvate kinase deficiency managed?

Management of Pyruvate Kinase Deficiency

Pyruvate kinase deficiency requires supportive care with symptom-directed transfusions, regular monitoring for complications, and consideration of splenectomy in select patients, while avoiding hemoglobin-threshold-based transfusion triggers. 1, 2

Supportive Management Approach

Red Blood Cell Transfusions

• Transfuse based on symptoms (fatigue, exercise intolerance, poor growth in children), NOT based on a specific hemoglobin threshold, as patients tolerate anemia better than expected due to elevated 2,3-DPG causing rightward shift in oxygen dissociation curve 3, 2
• Use irradiated blood components exclusively to prevent transfusion-associated graft-versus-host disease 3
• Wait at least 50 days after transfusion before performing PK enzyme testing, as donor red cells mask deficiency for up to 120 days 4, 5

Iron Overload Management

• Monitor for iron overload even in non-transfused patients, as ineffective erythropoiesis causes iron accumulation independent of transfusions 4, 1
• Initiate chelation therapy when clinically indicated based on ferritin levels and organ iron burden assessment 1, 6

Surgical Interventions

Splenectomy

• Consider splenectomy for patients with severe transfusion-dependent anemia or significant symptoms impacting quality of life 1, 2
• The decision must be individualized based on disease burden, transfusion requirements, and long-term outlook, particularly given emerging targeted therapies 2, 6
• Splenectomy typically reduces transfusion requirements but does not cure the underlying hemolysis 1

Cholecystectomy

• Monitor for bilirubin gallstones, a common complication of chronic hemolysis 3, 1
• Perform cholecystectomy when symptomatic cholelithiasis develops 1, 6

Monitoring Protocol

Regular Hematology Follow-up

• All children and adolescents require hematology visits at least every 6 months regardless of transfusion status 7
• Obtain complete blood count with reticulocyte count at each visit 4, 7
• Monitor markers of hemolysis (LDH, haptoglobin, indirect bilirubin) 4

Complication Surveillance

• Screen for iron overload with ferritin levels and consider MRI for organ iron assessment 1, 7
• Monitor for extramedullary hematopoiesis, particularly paravertebral masses that may cause neurological complications 1, 2
• Assess for pulmonary hypertension and thrombotic complications in severely affected patients 1
• Perform abdominal ultrasound to screen for gallstones 1, 6

Advanced Therapies

Hematopoietic Stem Cell Transplantation

• Reserve for severely affected patients with poor quality of life despite optimal supportive care 2, 6
• Outcomes have been mixed in the small number of reported cases 6

Emerging Disease-Modifying Therapies

• Novel pyruvate kinase activators and gene therapy approaches are in clinical development and may transform management 1, 6, 8
• These therapies aim to decrease chronic hemolysis and avoid complications of current supportive treatments 1

Critical Management Pitfalls

• Never use hemoglobin thresholds alone to guide transfusion decisions—the elevated 2,3-DPG allows patients to function at lower hemoglobin levels than other anemias 3, 2
• Avoid enzyme testing shortly after transfusion, as this causes falsely normal results 4, 5
• Do not overlook iron overload in non-transfused patients, as ineffective erythropoiesis alone causes accumulation 4, 1
• Recognize that degree of enzyme deficiency does not predict clinical severity—management must be symptom-based 9, 2