How is platelet refractoriness best managed?

Management of Platelet Refractoriness

Patients with confirmed alloimmune platelet refractoriness should receive HLA-A and HLA-B matched platelets as first-line therapy, with platelet cross-matching reserved for those who fail HLA-matched products or cannot be HLA-typed. 1

Step 1: Confirm True Platelet Refractoriness

Before pursuing specialized platelet products, you must document genuine refractoriness:

• Require at least two consecutive ABO-compatible platelet transfusions (stored <72 hours) that both produce poor increments 1
• Measure platelet counts 1 hour (or 10 minutes) post-transfusion to calculate the corrected count increment (CCI) 1
• Define poor response as CCI <5,000 or absolute increment <2,000/unit of pooled platelets (or <10,000 for apheresis platelets) 1

Critical pitfall: Never diagnose refractoriness based on ABO-incompatible transfusions, as ABO mismatch alone can compromise increments 2, 3. This is the most common diagnostic error.

Step 2: Distinguish Immune from Non-Immune Causes

Once refractoriness is confirmed, immediately test for HLA antibodies:

• Order HLA class I antibody testing on all refractory patients to confirm alloimmunization 1
• Approximately 90% of alloimmunized patients have anti-HLA antibodies detectable by standard assays 1

Non-immune causes that mimic refractoriness include: 1

• Sepsis or active infection
• Splenomegaly or hypersplenism
• Disseminated intravascular coagulation (DIC)
• Active hemorrhage
• Drug-induced antibodies

Key distinction: Patients refractory due to non-immune factors should NOT receive HLA-matched or cross-matched platelets, as these expensive products provide no benefit 1

Step 3: Management Algorithm for Confirmed Alloimmune Refractoriness

First-Line: HLA-Matched Platelets

Provide HLA-A and HLA-B matched platelets from typed donor registries 1

• Success rate: 50-60% of transfusion events produce adequate increments 1
• Blood suppliers maintain computerized registries of HLA-typed apheresis donors 1
• Single-antigen mismatches (particularly HLA-B44 or B45) may still produce satisfactory increments in 75% of cases 1

Second-Line: Platelet Cross-Matching

For patients who fail HLA-matched platelets, use platelet cross-matching techniques to identify compatible donors: 1

This applies to three specific scenarios:

1. HLA type cannot be determined (e.g., severe leukopenia preventing lymphocyte typing) 1
2. Uncommon HLA phenotypes with no available matched donors in registries 1
3. Persistent poor increments despite HLA-matched products (occurs in 40-50% of cases) 1

These two techniques are complementary—cross-matching may identify compatible donors not predicted by HLA matching alone, possibly due to platelet-specific antigens (HPA antibodies) 1, 4

Additional Considerations for HPA Antibodies

• Test for human platelet antigen (HPA) antibodies in patients refractory to both HLA-matched and cross-matched platelets 1, 4
• HPA antibodies are rare but require HPA-selected or cross-match-selected products 1

Step 4: Transfusion Strategy for Refractory Patients

Transfuse alloimmunized patients ONLY for active bleeding, not prophylactically 1

• There is no evidence that prophylactic transfusions producing poor increments benefit alloimmunized patients 1
• Reserve limited HLA-matched/cross-matched inventory for therapeutic (not prophylactic) indications 1

Common Pitfalls to Avoid

1. Diagnosing refractoriness after a single failed transfusion—always require two documented failures 1
2. Using ABO-incompatible products when assessing refractoriness—this confounds the diagnosis 2, 3
3. Providing HLA-matched products to patients with non-immune refractoriness—this wastes expensive resources without clinical benefit 1
4. Continuing prophylactic transfusions in alloimmunized patients with persistent poor increments—switch to therapeutic-only strategy 1
5. Failing to check platelet storage time—products stored >72 hours may produce poor increments regardless of immune status 1

Prevention Considerations

While not directly addressing management of established refractoriness, leukoreduction of blood products reduces HLA alloimmunization rates from 50% to 3-4% in at-risk populations 5, 6, 7. This represents the most effective preventive strategy but does not reverse established alloimmunization.