Non-Immune Causes of Platelet Refractoriness
Non-immune factors account for the majority of platelet refractoriness cases and must be systematically excluded before diagnosing alloimmune refractoriness. 1, 2, 3
Comparative Table of Non-Immune Causes
| Non-Immune Cause | Mechanism | Clinical Context | Management Approach |
|---|---|---|---|
| Sepsis/Infection [4,3,5] | Increased platelet consumption and activation; endothelial damage | Fever, positive cultures, systemic inflammatory response | Treat underlying infection; platelets consumed regardless of compatibility |
| Splenomegaly/Hypersplenism [1,2,5] | Sequestration of transfused platelets in enlarged spleen | Palpable spleen, cirrhosis, portal hypertension, lymphoma | Consider splenectomy in refractory cases; higher platelet doses may be needed |
| Disseminated Intravascular Coagulation (DIC) [1,2,5] | Consumptive coagulopathy with rapid platelet destruction | Elevated D-dimer, low fibrinogen, prolonged PT/PTT, microangiopathic hemolytic anemia | Treat underlying cause; transfuse for active bleeding only |
| Active Hemorrhage [1,2,5] | Physical loss of transfused platelets through bleeding | Visible bleeding, hemodynamic instability, dropping hemoglobin | Control bleeding source; may require massive transfusion protocol |
| Drug-Induced Antibodies [1,2] | Non-HLA antibodies triggered by medications (e.g., heparin, vancomycin, quinidine) | Recent medication exposure, temporal relationship to drug administration | Discontinue offending agent; antibodies typically non-HLA |
| ABO Incompatibility [1,6] | Suboptimal platelet survival when ABO-mismatched products used | Any transfusion scenario where ABO-compatible products unavailable | Use ABO-compatible platelets for refractoriness assessment; incompatibility can compromise increments |
| Massive Transfusion [7] | Dilutional effect and consumption during resuscitation | Trauma, major surgery, obstetric hemorrhage | Maintain platelet:RBC ratio of 1:2 in massive transfusion |
Critical Diagnostic Approach
Before diagnosing immune-mediated refractoriness, you must document at least two consecutive poor increments (CCI <5,000) with ABO-compatible platelets stored <72 hours, AND exclude all non-immune causes listed above. 1, 2, 6
Key Diagnostic Steps:
- Calculate CCI at 1 hour post-transfusion: CCI = (absolute increment × body surface area in m²) / (platelets transfused × 10¹¹) 1
- Define poor response: CCI <5,000 or absolute increment <2,000/unit pooled platelets (or <10,000 for apheresis) 1, 2
- Order HLA class I antibody testing only after confirming two poor increments with ABO-compatible products and excluding non-immune causes 1, 2
Common Pitfalls to Avoid
- Do not diagnose refractoriness based on ABO-incompatible transfusions, as this alone can cause poor increments 1, 6
- Do not order HLA antibody testing after a single poor increment—requires at least two documented failures 1, 2
- Do not assume immune refractoriness in septic patients—sepsis is the most common non-immune cause and will cause poor increments regardless of HLA matching 4, 3, 5
- Do not provide HLA-matched platelets to patients with purely non-immune refractoriness—this wastes limited donor resources without benefit 1, 2
Management Algorithm for Non-Immune Refractoriness
Patients refractory due solely to non-immune factors should NOT receive HLA-selected or crossmatch-selected platelets. 1
Treatment priorities:
- Address the underlying cause (treat sepsis, manage DIC, control bleeding, remove offending drugs) 4, 3, 5
- Transfuse therapeutically for active bleeding only—not prophylactically—in patients with persistent non-immune consumption 2, 7
- Consider higher platelet doses in patients with splenomegaly, as sequestration is dose-dependent 5