Platelets are tiny, colorless cell fragments circulating in the blood that are necessary for clotting and stopping bleeding after injury or surgery. Patients undergoing cancer therapy, major surgery, or organ transplantation often require platelet transfusions to prevent hemorrhage. Platelet donation, known as apheresis, involves drawing whole blood, separating the platelets using a specialized machine, and returning the remaining components to the donor. While the process is safe, blood centers impose specific restrictions on some female donors due to a biological risk: the presence of specific antibodies that can develop after pregnancy.
Understanding the TRALI Risk
The concern leading to the deferral of certain female platelet donors is the risk of Transfusion-Related Acute Lung Injury (TRALI). TRALI is a complication of blood transfusions that causes sudden respiratory distress and pulmonary edema in the recipient, usually within six hours of the transfusion. It is currently the leading reported cause of transfusion-related mortality in many countries.
The syndrome is triggered by antibodies in the donor’s plasma that react with the recipient’s white blood cells (neutrophils or leukocytes). These antibodies cause the recipient’s white blood cells to clump and activate within the lungs, leading to inflammation and fluid accumulation. The most common antibodies responsible are those directed against Human Leukocyte Antigens (HLA) and, less frequently, Human Neutrophil Antigens (HNA).
Apheresis platelet products contain a significant volume of plasma, making them a high-plasma-volume component. This increases the TRALI risk if these specific antibodies are present. Although HLA antibodies can be found in some male donors, they are most frequent and at higher concentrations in women who have been pregnant, necessitating strategies to mitigate this risk.
How Pregnancy Leads to Sensitization
The presence of HLA antibodies in previously pregnant women results from a natural immune process called alloimmunization. During pregnancy, the woman’s immune system is exposed to foreign antigens inherited from the father and present on the developing fetus. These paternal Human Leukocyte Antigens (HLA) can enter the mother’s circulation, primarily during childbirth or through fetomaternal hemorrhage earlier in gestation.
The mother’s body recognizes these paternal HLA markers as non-self and mounts an immune response, producing alloantibodies (HLA antibodies). This sensitization can occur regardless of the pregnancy’s outcome, including after a live birth, miscarriage, or stillbirth. The prevalence of HLA antibodies increases significantly with the number of pregnancies a woman has experienced.
These antibodies can persist in the mother’s blood for many years after the pregnancy has concluded. The persistent presence of these antibodies in the plasma classifies a previously pregnant woman as a potential risk factor for TRALI in a transfusion recipient.
Testing and Donor Eligibility Screening
To maintain the safety of the blood supply, blood collection organizations have established screening protocols to identify donors at high risk of causing TRALI. The first step is a screening questionnaire where all female donors are asked about any history of pregnancy. A woman who has never been pregnant is considered low risk for HLA sensitization and is typically eligible to donate platelets, similar to most male donors.
For women who report a history of pregnancy, blood centers perform laboratory testing to check for high levels of HLA or HNA antibodies in their plasma. This testing accurately detects and measures the concentration of these specific antibodies. If a woman tests negative or has antibody levels below the safe threshold, she may remain eligible to donate apheresis platelets.
If the screening reveals a high concentration of HLA or HNA antibodies, the donor is permanently deferred from donating platelet products that contain plasma. This deferral is a public health measure to reduce the risk of a severe adverse reaction in the recipient. The policy ensures that the potential benefit of the donation is not outweighed by the danger of TRALI.
Alternative Ways to Help
For women deferred from donating apheresis platelets due to pregnancy history and positive antibody screening, alternative donation options remain available. These women are typically still eligible to donate whole blood, the most common type of donation. Whole blood is processed to separate its components, and the plasma containing high-risk antibodies can be safely diverted or used for manufacturing non-transfusable plasma derivatives.
Donating red blood cells is another option, either through a whole blood donation or a specialized apheresis procedure. Red blood cell products contain very little residual plasma, significantly lowering the TRALI risk compared to platelet products. By donating these components, women who cannot donate platelets still provide a life-saving resource for patients needing transfusions for anemia, trauma, or surgery.