Transfusion Medicine

ABO and Rh(D) compatibility

• Core principle: the ABO hemolytic reaction is between the recipient's plasma antibodies and the donor's RBC antigens. Naturally occurring ABO isohemagglutinins are predominantly IgM (group O also has a substantial IgG component, hence ABO HDN mainly in group O mothers).
• Universal RBC donor: O Rh-negative. Universal RBC recipient: AB Rh-positive.
• Forward typing: patient RBCs tested against known anti-A and anti-B reagent antisera. Reverse typing: patient plasma tested against known A1 cells and B cells. The two must agree.
• IgG crosses the placenta (hemolytic disease of the newborn); IgM does not cross the placenta but activates the complement system (intravascular hemolysis).

• Rh(D): RhD-positive patients tolerate RhD-positive or RhD-negative units. RhD-negative patients can form IgG anti-D after exposure; give RhD-negative units, especially to females of childbearing potential (avoid alloimmunization affecting future pregnancies and HDN).

Minor RBC antigens, platelet and HLA/HPA systems

• Kell: K antigen ~9% in White populations (k is high-frequency, >99%); K is the most immunogenic antigen after RhD, can cause HDN.
• Kidd (Jka, Jkb): antibodies disappear quickly but show a brisk anamnestic response (classic cause of delayed hemolytic transfusion reaction).
• Duffy (Fya, Fyb): used as an entry receptor by malaria, so ~68% of Black/African-American populations are Duffy-null (Fy(a-b-)); the phenotype approaches 100% in parts of West/Central Africa.
• MNS (M, N, S, s): can also cause hemolytic disease of the newborn.
• Platelets carry the ABO system too, but ABO compatibility is not absolutely required for platelet transfusion.
• HLA system: alloimmunization to HLA (antibodies to class I antigens at the HLA-A and HLA-B loci) is a major cause of platelet transfusion refractoriness.
• Human platelet antigens (HPA): the HPA-1a/1b glycoprotein system underlies neonatal alloimmune thrombocytopenia (NAIT) and post-transfusion purpura (PTP), the latter occurring 7 to 10 days after transfusion.

Blood components: overview

• Packed RBCs (pRBC): 1 unit ~250 to 300 mL, Hct ~55 to 65%; raises Hb ~1 g/dL in a 70-kg adult. Storage 4°C for 42 d (additive solution, AS-1/AS-3/AS-5) or 35 d (CPDA-1). Each unit ~250 mg iron.
• Platelets: 1 apheresis unit (single donor) is roughly equal to 6 random-donor units; raises platelets ~30 to 50K. Stored at room temperature for 5 to 7 d (highest bacterial contamination risk).
• Fresh frozen plasma (FFP): contains all coagulation factors. Dose 10 to 15 mL/kg; raises factor levels ~20 to 25%. Use for warfarin reversal (4F-PCC preferred), TTP plasma exchange, factor deficiency without a specific concentrate, and DIC. Storage frozen for 1 yr.
• Cryoprecipitate: cold-precipitated FFP fraction rich in fibrinogen, FVIII, vWF, FXIII, and fibronectin. 10 units raise fibrinogen ~50 mg/dL. Use for hypofibrinogenemia, factor XIII deficiency, dysfibrinogenemia, and DIC; rarely for vWD or hemophilia A (specific concentrates preferred).
• Granulocyte concentrate: rare; severe neutropenic infections refractory to antibiotics.
• Albumin (5%, 25%): volume expander; large-volume paracentesis, hepatorenal syndrome, spontaneous bacterial peritonitis.
• IVIG: pooled donor immunoglobulin; 0.4 to 1 g/kg dosing; for ITP, GBS, CIDP, primary immunodeficiency, post-transplant CMV.
• Specific factor concentrates: rFVIII/FIX (hemophilia), 4F-PCC (warfarin reversal), antithrombin concentrate (heparin resistance).

Pre-transfusion testing

• Type and screen (T&S): ABO + Rh + indirect antibody screen. Valid 3 days if transfused or pregnant in the prior 3 months (or history uncertain); otherwise per local policy. Workflow is ABO/Rh typing, then RBC antibody screen, then crossmatch.
• Crossmatch: verifies compatibility between the donor unit and recipient (immediate spin or full antiglobulin).
• Type O Rh-negative: universal donor for emergencies (use until type-specific units available).
• AB Rh-positive: universal recipient.

Restrictive vs liberal transfusion

• TRICC (1999): restrictive (Hb <7) non-inferior to liberal (Hb <10) in the ICU.
• FOCUS (2011): restrictive non-inferior in elderly with hip fracture.
• TRISS (2014): restrictive non-inferior in septic shock.
• TITRe2 (2015): primary infection/ischemia composite no different, but 90-day mortality higher with restrictive (4.2% vs 2.6%, HR 1.64, 95% CI 1.00 to 2.67). TRICS III (2017) gave formal noninferiority for restrictive in cardiac surgery.
• REALITY (2021): restrictive non-inferior in acute MI.
• MINT (2023): liberal (Hb <10) vs restrictive (Hb <7 to 8) in acute MI with anemia; primary endpoint (30-day death or MI) not significant (RR 1.15, 95% CI 0.99 to 1.34) but favored liberal. The 2025 ACC/AHA ACS guideline (Class 2b) and 2025 AABB guideline now favor transfusing to Hb ≥10 in acute MI.
• TRACS / TRICS (cardiac surgery): restrictive acceptable in stable cardiac patients.
• Practical: Hb <7 trigger for most patients; <8 in cardiac or orthopedic surgery; <10 in acute MI (AABB 2025, ACC/AHA 2025); symptoms drive transfusion in chronic anemia.

Massive transfusion protocol (MTP)

• Definition: ≥10 pRBC in 24 hr OR ≥4 pRBC in 1 hr.
• 1:1:1 ratio (PROPPR trial, pRBC : plasma : platelets) preferred over 2:1:1 in severe trauma.
• TXA in trauma: CRASH-2 trial, give within 3 hours of injury for survival benefit.
• Calcium replacement: citrate in stored blood chelates calcium, causing ionized hypocalcemia that leads to coagulopathy and cardiac dysfunction. Replace IV calcium during MTP.
• Watch for: hyperkalemia (especially in renal failure or with old units), hypothermia, and dilutional coagulopathy.

Transfusion reactions

Transfusion reactions: additional features

• Post-transfusion purpura (PTP): severe thrombocytopenia ~1 week post-transfusion; HPA-1a alloimmunization in HPA-1a-negative patients; treat with IVIG.
• Iron overload: chronic transfusion (~250 mg iron/unit); chelate when ferritin >1000 or liver iron concentration >7 mg/g dry weight.
• Citrate toxicity (hypocalcemia): massive transfusion or apheresis; perioral tingling, paresthesias, tetany. Replace IV calcium.
• Hypothermia and electrolyte disturbances (hyperkalemia, hypocalcemia): massive transfusion.

Blood product modifications: indications

• Leukoreduction (filter): reduces FNHTR, HLA alloimmunization, and CMV transmission. Now universal in most centers.
• Irradiation (gamma or X-ray, 25 Gy): prevents TA-GVHD. Indications: HSCT recipients (before, during, after), congenital T-cell immunodeficiency (SCID, DiGeorge), intrauterine transfusion and post-IUT neonatal transfusions (not routine neonatal top-ups); Hodgkin lymphoma at any stage, lifelong, regardless of active therapy; purine analogues (fludarabine, cladribine), bendamustine, alemtuzumab; and directed donor units. NHL/R-CHOP alone is not a routine indication.
• CMV-seronegative products: for CMV-negative pregnant mothers, fetal/neonatal, HSCT, and severe immunodeficiency. Leukoreduction confers similar "CMV-safe" risk reduction.
• Washed cells: removes plasma proteins. Use in IgA-deficient patients with anti-IgA, severe allergic reactions, and NAIT: use HPA-compatible donor platelets (no routine washing); if maternal platelets are used, wash them (remove maternal anti-HPA) and irradiate.
• Pathogen-reduced products: amotosalen + UVA (INTERCEPT), riboflavin + UV (Mirasol); inactivate many viruses, bacteria, and parasites.
• HLA-matched platelets: for confirmed immune refractoriness. Confirm with corrected count increments after 2 transfusions and exclude nonimmune causes (sepsis, DIC, splenomegaly, bleeding, meds); test for HLA antibodies first. Crossmatch-compatible platelets are an alternative.
• Antigen-matched RBCs: for chronically transfused patients (SCD, thalassemia) to prevent alloimmunization (extended Rh, Kell, Duffy, Kidd matching).

Alloimmunization and special populations

• Sickle cell patients: use Rh (especially C, E), Kell, Duffy, Kidd, and MNS-matched units to reduce alloimmunization. Consider DAT and antibody panel before each transfusion in chronically transfused patients.
• Thalassemia chronic transfusion: similar extended phenotype matching.
• Patients with multiple alloantibodies: require donor compatibility testing and rare blood group registries.
• Hyperhemolysis syndrome (SCD, post-transfusion): severe hemolysis of both native and transfused RBCs, often DAT negative; treat with IVIG + steroids + EPO, sometimes eculizumab; avoid further transfusion if possible.

Transfusion-transmissible infections

• Routine donor screening: HIV (Ab + NAT), HCV (Ab + NAT), HBV (HBsAg + anti-HBc + NAT), HTLV-I/II, syphilis, West Nile virus, T. cruzi (Chagas), and babesia (regional); Zika testing no longer required (FDA 2021).
• CMV: transmissible; mitigate with leukoreduction or CMV-seronegative donors.
• Bacterial contamination: platelets carry the highest risk (room-temp storage); Platelets require an FDA-accepted bacterial risk control strategy: culture-based detection (+/- secondary testing for extended storage), large-volume delayed sampling, or pathogen reduction (which can replace bacterial detection).

High yield (transfusion)

• Hb <7 is the restrictive trigger for most patients; <8 in cardiac or orthopedic surgery.
• 1:1:1 ratio (PROPPR) for massive transfusion; TXA within 3 hours in trauma (CRASH-2).
• TA-GVHD is nearly 100% fatal: prevent with irradiation in immunocompromised recipients.
• IgA deficiency plus anaphylaxis: use washed cells or IgA-deficient products.
• TRALI vs TACO: TRALI is bilateral infiltrates from anti-HLA antibodies (do not diurese); TACO is volume overload (diurese).
• Delayed HTR (anamnestic): 5 to 14 days post-transfusion; falling Hb with a positive DAT; common in chronically transfused patients (SCD, thalassemia). Kidd is the classic culprit.
• PTP: HPA-1a alloimmunization; severe thrombocytopenia ~1 week post-transfusion; treat with IVIG.
• Bacterial contamination is highest in platelets (room-temp storage).
• Kell is the most immunogenic minor RBC antigen after Rh.
• Cryoprecipitate contains fibrinogen, FVIII, vWF, FXIII, and fibronectin.
• IgG crosses the placenta (HDN); IgM activates complement and does not cross the placenta.