9.4 HLA, Platelet-Specific, and Granulocyte-Specific Antigens

9.4 HLA, Platelet-Specific, and Granulocyte-Specific Antigens

Quick Answer: HLA Class I (A, B, C) is on platelets and leukocytes. HLA antibodies cause platelet refractoriness, TRALI (when they are in the donor), and febrile nonhemolytic reactions. Immune refractoriness is managed with a PRA and HLA-matched or crossmatched platelets. HPA-1a (PlA1) on GPIIIa is the classic NAIT and post-transfusion purpura antigen. HNA antibodies cause TRALI (especially HNA-3a) and neonatal alloimmune neutropenia. Do not work a platelet problem on a red-cell panel.

The June 9, 2026 outline gives these three families their own lines — II.B.14 HLA, II.B.15 platelet-specific, II.B.16 granulocyte-specific — because the serology is not RBC serology. The antigens live on different cells, the syndromes are different, and the product you issue is different.

HLA Class I is the platelet antigen that is not HPA

HLA genes sit in the MHC on chromosome 6. Class I (HLA-A, -B, -C) is on all nucleated cells and on platelets. Class II (HLA-DR, -DQ, -DP) is on antigen-presenting cells and activated lymphocytes, not on resting platelets. That distribution is why immune platelet refractoriness is a Class I problem (mostly A and B; C is weakly expressed and less often the matching target) and why TRALI can be Class I or Class II (donor antibody meeting recipient leukocytes).

Panel-reactive antibody (PRA) is the percent of a cell or bead panel that the patient’s HLA antibody hits. A PRA of 80% means random apheresis platelets will fail most of the time. HLA-matched platelets are matched at A and B (older grades A / BU / B2U still appear in stems). Crossmatched platelets test patient serum against donor platelets when a full match is unavailable. Neither product fixes nonimmune refractoriness.

Corrected count increment (CCI) separates the two. A 1-hour CCI < 5,000–7,500 on two sequential, ABO-compatible, properly stored platelets, in a patient without fever, sepsis, DIC, splenomegaly, bleeding, or amphotericin, is immune refractoriness. Check HLA antibodies first; they are far more common than HPA antibodies in multiply transfused adults. Leukoreduction of cellular products prevents many HLA alloimmunizations and FNHTR (recipient antibody versus donor leukocytes). It does not erase antibody that is already there and it does not prevent HPA-mediated NAIT.

TRALI, FNHTR, and who owns the antibody

TRALI is acute noncardiogenic pulmonary edema during or within six hours of transfusion. The classic immune mechanism is donor leukocyte antibody — anti-HLA Class I, anti-HLA Class II, or anti-HNA — in a plasma-rich product (plasma, apheresis platelets) attacking recipient neutrophils in the lung. Anti-HNA-3a is notorious for severe TRALI. Multiparous female donors are the historic high-risk source; male-only or never-pregnant-female plasma is a mitigation, not a guarantee. Implicated donors are deferred from plasma-rich donation. TRALI is not TACO (volume overload), not TA-GVHD (prevented by irradiation), and not platelet refractoriness.

FNHTR is fever and chills without hemolysis. Two mechanisms appear on BB items: recipient anti-HLA / anti-HNA versus donor leukocytes, and biologic response modifiers that accumulate in stored platelets. Leukoreduction prevents the antibody-versus-leukocyte form. Antipyretics treat symptoms; they do not identify the antibody.

Directionality is the exam hinge. Recipient HLA antibody → refractoriness and FNHTR. Donor HLA/HNA antibody → TRALI. Swapping donor and recipient fails the item.

HPA-1a: NAIT and PTP

Human platelet antigens (HPA) are polymorphisms on platelet glycoproteins, not HLA. HPA-1a (PlA1) is on GPIIIa (integrin β3). About 98% of people of European ancestry are HPA-1a-positive. The 2% who are HPA-1a-negative can make anti-HPA-1a, the most important platelet-specific antibody in U.S. stems.

Neonatal alloimmune thrombocytopenia (NAIT) is the platelet version of HDFN: a mother who lacks HPA-1a is immunized (often in a first pregnancy — unlike anti-D), IgG crosses the placenta, and the HPA-1a-positive fetus is thrombocytopenic. Intracranial hemorrhage is the feared complication. Maternal platelet count is normal. Diagnosis is maternal antibody that reacts with paternal (or HPA-1a-positive) platelets and not with HPA-1a-negative platelets. Treatment of the bleeding neonate is HPA-1a-negative platelets or IVIG; washed maternal platelets are an emergency source because the mother lacks the target antigen. Random platelets may be consumed. Anti-HPA-5b is the second most common NAIT specificity in Europeans; anti-HPA-4 is more important in some Asian populations. Do not force every NAIT stem into HPA-1a if the stem gives a different typed specificity.

Post-transfusion purpura (PTP) is abrupt, severe thrombocytopenia 5–10 days after transfusion in a previously immunized patient — classically a multiparous HPA-1a-negative woman. Anti-HPA-1a destroys transfused and autologous platelets (autologous destruction is the conceptual trap). Treat with IVIG. Further platelets, if unavoidable, should be antigen-negative; random platelets can worsen the count. PTP is not HIT (heparin, PF4), not ITP, and not NAIT in the adult patient.

HNA: TRALI and neonatal neutropenia

Human neutrophil antigens (HNA) live on granulocytes. Names you need: HNA-1 (FcγRIIIb / CD16b), HNA-2 (CD177), HNA-3 (CTL2 / SLC44A2). Donor anti-HNA, especially anti-HNA-3a, is a premier TRALI antibody. Neonatal alloimmune neutropenia (NAIN) is maternal anti-HNA attacking fetal neutrophils — the neutrophil counterpart of NAIT. The neonate has isolated neutropenia and infection risk; the mother has a normal neutrophil count. Granulocyte transfusion is a separate product decision (irradiated, CMV-safe, ABO-compatible) and is not the first-line NAIN therapy.

HLA versus HPA versus RBC — do not mix the benches

A red-cell antibody screen does not detect anti-HLA, anti-HPA-1a, or anti-HNA. A platelet crossmatch does not rule out anti-K. If the stem is isolated neonatal thrombocytopenia with a negative RBC antibody screen, you are in HPA, not Kell, unless the stem also gives HDFN-range anemia.

Molecular HLA versus serology at BB depth

Serologic HLA (CDC cytotoxicity, ELISA, flow PRA, Luminex single-antigen beads) asks “which antigens does this serum hit?” That is the language of PRA and platelet matching. Molecular HLA (SSP, SSO, NGS) asks “which alleles does this person carry?” at low resolution (two-digit, antigen-equivalent) or high resolution (four-digit allele). Hematopoietic transplant needs high-resolution A, B, C, DRB1 (and often DQB1/DPB1). Platelet matching is usually low-resolution HLA-A and -B. Do not order NGS allele-level typing as the first step in refractoriness, and do not issue transplant-grade allele-matched platelets when a serologic A/B match or a platelet crossmatch would suffice. Molecular typing also assigns HPA and HNA genotypes when serologic reagents are scarce — the same logic as HEA arrays for red cells, not a replacement for an antibody identification when the antibody is already in the serum.

Exam traps

• Treating platelet refractoriness with HPA-1a-negative platelets before HLA workup in a multiply transfused adult.
• Treating NAIT with HLA-matched platelets that are still HPA-1a-positive.
• Assigning TRALI to recipient HLA antibody (that is refractoriness/FNHTR) instead of donor leukocyte antibody.
• Using irradiation (TA-GVHD) or washing (allergic/potassium) as TRALI prevention.
• Calling PTP “HIT” because both drop the platelet count after an exposure.
• Expecting a red-cell panel to detect anti-HPA-1a or anti-HNA-3a.