Why is plasma from female donors sometimes discarded during blood transfusion?

Why Plasma from Female Donors is Preferentially Excluded from Transfusion

Plasma from female donors, particularly those with a history of pregnancy, is preferentially excluded or discarded from blood transfusion because these donors have a significantly higher frequency of anti-HLA (Human Leukocyte Antigen) and anti-HNA (Human Neutrophil Antigen) antibodies that cause Transfusion-Related Acute Lung Injury (TRALI), a leading cause of transfusion-related mortality. 1

The TRALI Problem and Female Donor Risk

Why Female Donors Are High-Risk

• Multiparous women develop leukocyte antibodies during pregnancy when exposed to fetal antigens, making their plasma particularly dangerous for transfusion recipients 1, 2
• Anti-HLA Class I, Class II, and granulocyte-specific antibodies in donor plasma interact with recipient neutrophils, causing severe pulmonary complications 3, 2
• Fresh frozen plasma (FFP) and platelet concentrates are the blood products most frequently implicated in TRALI, as they contain the highest plasma volumes that harbor these antibodies 3, 4

The Clinical Impact of TRALI

• TRALI presents with acute respiratory distress, hypoxemia, bilateral pulmonary infiltrates, and non-cardiogenic pulmonary edema occurring within 1-6 hours of transfusion 3, 2
• TRALI has a mortality rate between 5-25% and was historically the leading cause of transfusion-related death 4, 5
• The syndrome is often underdiagnosed and underreported despite its severity 3, 4

The Male-Only Plasma Strategy

Implementation and Effectiveness

• The UK implemented male-only plasma for component therapy beginning in 2003, which dramatically reduced TRALI incidence 1
• A large retrospective analysis showed that conversion to low-TRALI-risk plasma (all-male donor plasma, male-predominant plasma, nulliparous female plasma, or HLA antibody-tested plasma) reduced the incidence of TRALI reactions in plasma recipients from 0.0084% to zero (p = 0.052) 6
• Since Germany implemented male-only plasma policies in 2009, no TRALI-related deaths have been registered 2

Current International Standards

• The AABB (American Association of Blood Banks) requires that all plasma-containing components and whole blood for transfusion must be collected from men, women who have never been pregnant, or women who have tested negative for HLA antibodies 5
• This mitigation strategy has been adopted worldwide across the United States, Canada, and European countries 5

Important Clinical Caveats

Not All Female Plasma is Discarded

• Nulliparous (never pregnant) female donors can still donate plasma if they test negative for leukocyte antibodies 2, 5
• Women with a history of pregnancy can donate if they test negative for anti-HLA antibodies, though many blood banks preferentially use male donors to simplify screening 5

Red Blood Cells Also Carry Risk

• RBCs now account for approximately 50% of TRALI fatalities, as they contain residual plasma (38-66 mL depending on processing method) 7
• RBCs from female donors with high-strength anti-HLA Class II antibodies have been implicated in severe and fatal TRALI cases 7
• The combination of high-strength antibodies and large residual plasma volume in RBC units can explain severe RBC-associated TRALI 7

Ongoing Challenges

• Despite mitigation strategies, TRALI remains the most common cause of transfusion-associated death in the United States 5
• The risk has not been completely eliminated, emphasizing the need for continued vigilance and reporting 5

Practical Implications for Transfusion Practice

• Blood banks prioritize male donors for plasma and platelet products to minimize TRALI risk 1
• When group AB plasma is needed for emergency transfusion (unknown blood type), male-only sources are preferred 1
• Clinicians should maintain high suspicion for TRALI when patients develop acute respiratory distress within hours of any blood product transfusion, not just plasma 3, 2
• Treatment of TRALI requires immediate cessation of transfusion, oxygen therapy, and critical care supportive measures—diuretics should be avoided as this is non-cardiogenic pulmonary edema 3, 2