What is alloimmunization with Human Leukocyte Antigen (HLA) antibodies and how does transfusing cross-matched blood samples work?

HLA Alloimmunization and Cross-Matched Platelet Transfusion

Patients with alloimmune refractory thrombocytopenia should be managed with platelet transfusions from donors matched for HLA-A and HLA-B antigens, or through platelet cross-matching techniques when HLA matching is not possible. 1

What is HLA Alloimmunization?

HLA alloimmunization is an immune response where a patient develops antibodies against human leukocyte antigens (HLA) present on donor platelets but absent on their own cells. This process occurs through:

• Mechanism: Exposure to foreign HLA antigens through blood transfusions, pregnancy, or transplantation triggers antibody production
• Prevalence: Approximately 90% of alloimmunized patients develop antibodies specifically against HLA antigens 1
• Clinical Impact: These antibodies destroy transfused platelets, leading to poor post-transfusion platelet count increments and ineffective transfusion support

Diagnosis of Platelet Refractoriness Due to Alloimmunization

Refractoriness to platelet transfusion should only be diagnosed when:

• At least two ABO-compatible platelet transfusions (stored less than 72 hours) result in poor increments 1
• Poor increment defined as corrected count increment (CCI) <5,000 at 10-60 minutes or <2,500 at 24 hours post-transfusion
• Laboratory confirmation of HLA antibodies is essential to differentiate alloimmune causes from non-immune causes 1

Cross-Matched Platelet Transfusion Process

1. HLA Typing: First-line approach involves HLA typing of the patient and identifying donors with matching HLA-A and HLA-B antigens 1

2. Platelet Cross-Matching: Used when:

   • Patient's HLA type cannot be determined
   • Patient has uncommon HLA types with limited donor availability
   • Patient doesn't respond to HLA-matched platelets 1

3. Cross-Matching Technique:

   • Patient's serum is tested against potential donors' platelets
   • Identifies compatible donors regardless of HLA typing
   • Complements HLA matching in many cases 1

4. Effectiveness:

   • HLA-matched platelets provide adequate increments in 50-60% of transfusion events 1
   • Some single-antigen mismatches (e.g., HLA B44 or B45) can still yield satisfactory results in approximately 75% of cases 1

Management Algorithm for Platelet Refractoriness

1. Confirm alloimmunization:

   • Document poor increments with multiple ABO-compatible transfusions
   • Test for HLA antibodies

2. Select appropriate transfusion strategy:

   • First choice: HLA-A and HLA-B matched platelets 1
   • Second choice: Platelet cross-matching when HLA matching is not feasible 1
   • Third choice: For active bleeding only, consider large volume platelet transfusions 1

3. Monitor response:

   • Measure post-transfusion platelet increments
   • Adjust strategy based on clinical response

Important Clinical Considerations

• Leukoreduction: Universal leukodepletion of blood products significantly reduces the risk of HLA alloimmunization 2
• ABO Compatibility: ABO-compatible platelets are preferred as ABO incompatibility can compromise post-transfusion increments 1
• Non-immune factors: Hypersplenism, disseminated intravascular coagulation, shock, and massive hemorrhage can also cause poor platelet increments 1
• Transfusion threshold: For prophylaxis in stable patients, maintain platelets >10×10⁹/L; higher thresholds may be needed for active bleeding or procedures 3

Pitfalls to Avoid

• Don't continue transfusing non-matched platelets to alloimmunized patients for prophylaxis, as they provide no benefit 1
• Don't assume all cases of refractoriness are due to alloimmunization; confirm with antibody testing 1
• Don't overlook that patients with RBC alloantibodies have significantly higher risk of HLA alloimmunization 4
• Don't forget that in transplant recipients, shared HLA antibody specificities between blood and transplant donors can increase risk of allograft failure 5

By following this evidence-based approach to managing HLA alloimmunization and using appropriate cross-matched platelet transfusions, clinicians can significantly improve transfusion outcomes and reduce morbidity in patients requiring platelet support.