What is the management of pyruvate kinase deficiency?

Management of Pyruvate Kinase Deficiency

The management of pyruvate kinase deficiency (PKD) requires a supportive care approach focused on transfusions, splenectomy, and monitoring for complications, with regular follow-up at specialized centers to improve patient outcomes and quality of life. 1

Diagnostic Confirmation

Before initiating management, proper diagnosis is essential:

• Diagnosis requires both PK enzyme activity measurement and PKLR gene analysis 2
• Enzyme testing can yield false normal results due to:
  • Elevated reticulocyte counts
  • Recent transfusions
  • Incomplete removal of platelets/leukocytes
  • Kinetically abnormal mutant PKs 2

Treatment Algorithm

Supportive Care

1. Transfusion Management:

   • Regular or intermittent red cell transfusions based on hemoglobin levels and symptoms
   • Consider chronic transfusion program for severe cases with growth failure or poor quality of life 1
   • Transfusion decisions must account for individual patient symptoms rather than hemoglobin thresholds alone 3

2. Splenectomy:

   • Consider for transfusion-dependent patients or those with severe anemia symptoms
   • Benefits include reduced transfusion requirements and improved hemoglobin levels
   • Timing is critical - typically after age 5 to minimize infection risks 1, 3
   • Requires appropriate pre-splenectomy vaccinations and post-splenectomy antibiotic prophylaxis

3. Iron Overload Management:

   • Monitor iron status regularly even in non-transfused patients due to increased intestinal absorption
   • Initiate chelation therapy when evidence of iron overload appears 1
   • Regular monitoring of ferritin levels, liver and cardiac iron by MRI

Complication Monitoring and Management

1. Gallstones:

   • Regular ultrasound screening
   • Consider prophylactic cholecystectomy at time of splenectomy 3

2. Extramedullary Hematopoiesis:

   • Monitor for masses, particularly in splenectomized patients
   • Consider imaging when clinically indicated 1

3. Pulmonary Hypertension:

   • Echocardiographic screening, especially in adults with chronic hemolysis 1

4. Thrombotic Risk:

   • Higher risk post-splenectomy
   • Consider thromboprophylaxis during high-risk periods 3

Follow-up Protocol

• Children and adolescents: Hematology visits at least every 6 months regardless of transfusion status 4
• Adults: Regular monitoring based on disease severity and complications
• Comprehensive assessment should include:
  • Complete blood count
  • Reticulocyte count
  • Bilirubin levels
  • Iron studies
  • Organ function tests 4

Special Considerations

Neonatal Period

• Severe hemolysis may require exchange transfusion and/or phototherapy 5
• Close monitoring for hydrops fetalis in severe cases 1

Pregnancy

• Increased transfusion requirements often observed
• Close monitoring for fetal complications 3

Future Therapeutic Directions

Disease-modifying therapies in clinical development may:

• Decrease symptoms associated with chronic hemolysis
• Avoid complications of current treatment approaches
• Potentially change the course of disease progression 1, 4

Pitfalls and Caveats

• Reticulocyte counts may be falsely low due to splenic sequestration, masking the true degree of bone marrow compensation 6
• Iron overload can occur even in non-transfused patients due to increased intestinal absorption
• Post-splenectomy patients require lifelong vigilance for overwhelming infections and thrombotic events
• Regular monitoring is essential even in patients with seemingly mild disease, as complications can develop over time 3