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同種免疫致敏
Alloimmunization (RBC + HLA + Platelet)
概覽
Buzzwords → Dx
| Buzzword | Diagnosis / Clue |
|---|---|
| Falling Hb 3-14 d post-transfusion + jaundice + positive DAT | DHTR — alloantibody (Kidd, Duffy, Kell, Rh) |
| Anti-K alloimmunization | Common in chronic-transfusion SCD; severe HDFN |
| Anti-D in Rh- pregnant | HDFN — prevented by RhoGAM at 28 wk + within 72 h of delivery / fetomaternal hemorrhage |
| Kleihauer-Betke test | Quantifies fetomaternal hemorrhage; calculates RhoGAM dose |
| Anti-D titer ≥1:16 in pregnancy | High HDFN risk — fetal monitoring (MCA Doppler) + intrauterine transfusion |
| HDFN with hydrops, anemia, kernicterus | Severe HDFN |
| Platelet refractoriness | <30-50 × 10⁹/L rise post-transfusion + immune mechanism (anti-HLA, anti-HPA) |
| HLA-matched / HPA-matched platelets | For HLA-alloimmunized patient |
| Lewis antigen antibodies | Cold reactivity, usually clinically insignificant |
| Anti-Jk^a (anti-Kidd a) | Classic delayed HTR with intravascular hemolysis (titer drops between exposures, anamnestic response) |
| Antigen-matched RBC for SCD | Reduces alloimmunization by ~50 % (Rh + Kell match) |
分類與診斷
Diagnostic Criteria
- DHTR: delayed Hb fall + positive DAT + alloantibody identified on screen.
- HDFN: maternal alloantibody + fetal/neonatal hemolysis (anemia, jaundice, hydrops).
- Platelet refractoriness: post-transfusion increment <2.5 × 10⁹/L per m² within 1 h, on ≥2 occasions.
- HLA antibody screen (panel reactive antibody, PRA): % reactivity to HLA panel.
Workup
- CBC + smear + retic + DAT.
- Antibody screen + identification (which RBC antigen?).
- Hemolysis labs (LDH, haptoglobin, indirect bili).
- Direct observation: schistocytes (microangiopathic), spherocytes (extravascular).
- Maternal anti-D titer (≥1:16 high-risk in pregnancy).
- Kleihauer-Betke or fetal cell flow for fetomaternal hemorrhage.
- MCA Doppler for fetal anemia surveillance.
- HLA antibody panel for platelet refractoriness investigation.
治療
Treatment Algorithm
flowchart TD
A[Suspected alloimmunization] --> B[Antibody screen + identification]
B --> C{Type}
C -- RBC alloantibody --> D[Identify antigen<br>antigen-negative units for future transfusions<br>life-long records]
C -- anti-D in Rh-neg pregnant --> E[RhoGAM 28 wk + within 72 h delivery<br>+ extra dose if Kleihauer + or amnio / abruption]
C -- DHTR active --> F[Supportive — monitor renal + hemolysis<br>future antigen-negative units]
C -- HDFN risk in pregnancy --> G[MCA Doppler + intrauterine transfusion if severe<br>postnatal: phototherapy + exchange transfusion if needed]
C -- platelet refractoriness immune --> H[HLA-matched or HPA-matched platelets<br>or rh ig if Rh+ donor / Rh- recipient]
C -- platelet refractoriness non-immune --> I[Treat cause — DIC, sepsis, splenomegaly, drug-induced; ABO-matched]
陷阱與考點
Pearls / Pitfalls
- Anti-D HDFN prevention is RhoGAM at 28 wk gestation + within 72 h delivery (or after any sensitizing event: amnio, miscarriage, abruption, trauma, transfusion). Kleihauer-Betke quantifies fetomaternal hemorrhage to determine extra RhoGAM dose.
- Kidd antibodies (anti-Jk^a, anti-Jk^b) classic for delayed HTR — titer drops below detection between exposures, then anamnestic response. Cause severe intravascular hemolysis 7–14 days after transfusion.
- Antigen-matched RBCs in SCD (minimum Rh + Kell, ideally also Jk, Fy, S/s) reduce alloimmunization rate from ~30 % to <5 %.
- Platelet refractoriness algorithm:
- Confirm with corrected count increment (CCI) <2.5–7.5 at 1 h.
- Rule out non-immune causes: DIC, sepsis, splenomegaly, drug, fever, bleeding.
- If immune: test for HLA antibodies (PRA) → HLA-matched platelets; or anti-HPA → HPA-matched.
- HLA Class I antibodies (more common in alloimmunization) → use HLA-A and -B matched platelets.
- Anti-HPA (human platelet antigen) antibodies: cause neonatal alloimmune thrombocytopenia (NAIT) and post-transfusion purpura (PTP). NAIT prevention: matched maternal-paternal HPA antigens; treat with IVIG ± maternal corticosteroids antenatal.
- Daratumumab interferes with antibody screen — DTT-treated panel cells.
- Anti-Lewis antibodies are typically cold-reactive and clinically insignificant — don't need antigen-matched units.
- Lifetime medical alert for clinically significant alloantibodies — tell future transfusion sites; antibody titers may decline below detection but can re-emerge.
- Polyagglutination (T or Tn antigen exposure post-bacterial enzyme cleavage) — pneumococcal HUS in children → use washed RBCs (avoid plasma containing anti-T-antigen).
- Anti-CD38 (daratumumab): panagglutination on screen — DTT mitigation; document T&S BEFORE first dose.
- HLA-matched HCT reduces (but does not eliminate) GVHD; HLA antibodies in recipient pre-HCT can cause graft rejection (DSA — donor-specific antibodies).
延伸
Cross-references
- Transfusion Reactions
- Blood Groups + crossmatch
- SCD chronic transfusion
- Allo-HCT — DSA donor-specific antibodies
- Daratumumab T&S interference
- Lab Values — DAT, IAT, anti-D titer
相關題目
- Q-172 — DHTR — Kidd antibody anamnestic response
- Q-173 — Platelet refractoriness — HLA matching
- Q-174 — SCD — antigen-matched RBC transfusion
來源
Sources
Footnotes
-
AABB Technical Manual, 21st Edition, 2024. AABB Press. ↩