What is the role of locus-specific antibody assessment in diagnosing the cause of platelet refractoriness?

Role of Locus-Specific Antibody Assessment in Diagnosing Platelet Refractoriness

Locus-specific antibody assessment is essential for diagnosing immune-mediated platelet refractoriness, with HLA antibody testing being the primary diagnostic tool since approximately 90% of alloimmunized patients will have antibodies against HLA antigens. 1

Diagnosing Platelet Refractoriness

Definition and Criteria

• Platelet refractoriness is defined as inadequate platelet count increment after transfusion
• Diagnosis requires at least two consecutive ABO-compatible platelet transfusions (stored <72 hours) resulting in poor increments 1, 2
• Poor increment is defined as Corrected Count Increment (CCI) <5,000 1
• CCI calculation: (absolute increment × body surface area [m²]) / (number of platelets transfused × 10¹¹) 2

Post-Transfusion Monitoring

• Platelet counts should be performed 10-60 minutes after transfusion 1
• For practical purposes without platelet counts of infused products:
  • Adults: Expect ~2,000/unit of platelet concentrate or ~10,000/transfusion of apheresis platelets
  • Children: Expect ~3,500/m²/unit 2

Role of Antibody Assessment in Diagnosis

Immune vs. Non-Immune Causes

• When refractoriness is confirmed, determining the cause is critical as management differs significantly 1
• Non-immune causes include:
  • Hypersplenism
  • Disseminated intravascular coagulation
  • Shock
  • Massive hemorrhage
  • Drug-related antibodies 1

Locus-Specific Antibody Testing

1. HLA Antibody Testing:

   • Primary test as 90% of alloimmunized patients have HLA antibodies 1, 3
   • Focus on Class I HLA molecules (A and B alleles) 4
   • Modern methods like LUMINEX® technology provide improved sensitivity and specificity 5

2. Human Platelet Antigen (HPA) Testing:

   • Secondary test when HLA antibodies are negative or patient remains refractory despite HLA-matched platelets 5
   • Less common cause of immune refractoriness but important to identify 3

Management Based on Antibody Assessment Results

HLA Antibody Positive Patients

• Provide HLA-A and HLA-B matched platelet transfusions 1, 2
• If perfect HLA matching is not possible, use antibody specificity prediction method to identify compatible units lacking antigens recognized by patient's antibodies 4

HPA Antibody Positive Patients

• Provide HPA-selected or crossmatch-selected platelet transfusion 1
• Consider platelet crossmatching techniques to identify compatible donors 6

Combined Approach

• For patients who don't respond to HLA-matched platelets:
  • Perform platelet crossmatching to identify compatible donors 1
  • These techniques are often complementary 2

Non-Immune Refractoriness

• Patients with refractoriness due solely to non-immune factors should not receive HLA-selected or crossmatch-selected platelets 1
• Address underlying cause (e.g., treat DIC, septicemia) 7

Common Pitfalls in Antibody Assessment

• Using ABO-incompatible platelets for assessment can compromise post-transfusion increments 2
• Diagnosing refractoriness based on a single poor increment can lead to misdiagnosis 2
• Delayed assessment may miss peak platelet increment 2
• Failure to calculate CCI can lead to misinterpretation of transfusion adequacy 2
• Not testing for both HLA and HPA antibodies when indicated 5

By systematically assessing for locus-specific antibodies, clinicians can accurately diagnose the cause of platelet refractoriness and implement appropriate management strategies, ultimately improving patient outcomes by reducing bleeding risk in these vulnerable patients.