According to findings from an analysis published recently in the journal Plasmatology, collective understanding of the disease components involved in the development of fetal and neonatal alloimmune thrombocytopenia (FNAIT) may be enhanced by additional data on the mechanisms involved in platelet transfusion refractoriness (PTR), also known as platelet transfusion failure.
PTR is a disorder in which a person’s platelet counts fail to increase sufficiently after undergoing several transfusions. Frequently reported in those with blood disorders and/or malignancies, PTR can be associated with a life-threatening risk among patients, especially in situations in which platelet counts are very low and a transfusion is needed to survive.
PTR can be divided into immune causes and nonimmune causes of the disease. Although nonimmune causes of PTR are more common (they are reported in around two-thirds of all cases), immune factors such as anti–human leukocyte antigen (HLA) antibodies may play a key role as well.
Diagnostic methods for PTR and FNAIT
It is critical to learn whether PTR is being caused by a nonimmune or an immune factor, because treatments for both forms of the disorder vary. This is particularly true with respect to the need for matching platelets, which are known as HLA-compatible platelets, in individuals with immune-associated PTR.
Read more about FNAIT prognosis
The human platelet antigen (HPA) plays a critical role in patients with FNAIT; the same can be said for HLA among those with PTR. In fact, HPA, especially HPA-1a, is often implicated in patients with FNAIT, whereas HLA is the most commonly reported cause of PTR.
Both PTR and FNAIT share common pathways of alloimmunization. The two disorders involve immune-mediated mechanisms that target platelet antigens. Antigens implicated in FNAIT and PTR can trigger immune responses that result in the destruction of platelets—either transfused platelets (in PTR) or fetal/neonatal platelets (in FNAIT).
Recognizing that a lack of agreement exists with respect to diagnostic approaches and treatment methods for patients with PTR, the researchers sought to examine the reasons for occurrence of the condition, the ways in which to diagnose the disorder and the management strategies for those with PTR.
PTR typically is reported when antibodies develop after a patient receives a platelet transfusion from a donor. This event, in turn, results in the clearance of donor platelets from a patient’s circulation. Various antigens may be involved in this reaction, including HLA, HPA, and ABO blood group antigens.
The occurrence of alloimmunization is via one of two different pathways: direct allorecognition or indirect allorecognition. In the former process, recipient CD4+ T cells, which are derived primarily from foreign HLA antigens, are able to identify donor class II HLA antigens on donor antigen-presenting cells (APCs). In contrast, in the latter process, recipient APCs process donor antigens in order to activate T cells.
PTR diagnosis includes verifying whether a particular patient is refractory and then establishing if the refractoriness is due to immune or nonimmune issues. There are three formulas usually employed to measure PTR: post-transfusion increment (PPI), corrected count increment (CCI), and percentage platelet recovery (PPR).
CCI and PPR are considered to be the most reliable methods, because they make adjustments based on a person’s body surface area (BSA) and the number of platelets transfused. PTI is frequently utilized in daily practice, however, because it is an easier approach that does not depend on a person’s BSA or exact number of transfused platelets.
Additional research needed for FNAIT and PTR
Among patients with the immune type of PTR, the use of HLA-matched vs HPA-matched platelets can lead to improved transfusion outcomes. Transfusing alloimmunized individuals involves the matching of donor-recipient HLA antigens and cross-matching of the platelets being transfused.
Individuals with both FNAIT and PTR face considerable challenges in managing their respective disorders, with the risk for bleeding complications and severe thrombocytopenia possible in either situation. Careful consideration of platelet matching is key to the treatment of both conditions.
“Ongoing research in the field of . . . [PTR] is exploring new ways to manage and prevent this condition,” the authors concluded. This will hopefully be able to shed more light on factors involved in the development of FNAIT as well.
