18.1 Immunologic Transfusion Reactions

18.1 Immunologic Transfusion Reactions

Quick Answer: For any suspected reaction, stop the transfusion first, keep the line open with 0.9% NaCl, and do a bedside clerical check. Acute hemolytic reactions are classically ABO, intravascular, and present with fever, back or flank pain, hemoglobinuria, DIC, and shock; the DAT may be positive or mixed-field, or even negative if donor cells are already gone. Delayed HTR is anamnestic; Kidd is the classic specificity; the picture is a falling hemoglobin, spherocytes, a new antibody, and a positive DAT. FNHTR is cytokine- or leukocyte-driven. Allergic and anaphylactic reactions implicate plasma proteins, especially IgA and haptoglobin deficiency. TRALI is donor HLA/HNA antibody, acute hypoxemia, and noncardiogenic edema within 6 hours, mitigated with male or never-pregnant plasma. TA-GVHD, PTP, and alloimmunization finish the list. The workup is clerical, visual hemolysis, DAT, ABO/Rh repeat, crossmatch, antibody screen, eluate when needed, and cultures if there is fever.

This is V.C.1 on the June 9, 2026 BB outline. Chapter 17 told you when to issue a unit. This section tells you what to do when that unit hurts the patient. The exam will not forgive a candidate who starts an eluate before stopping the bag, who calls TACO a TRALI, or who irradiates a unit to prevent FNHTR.

Stop first, then split clerical from serologic

Every suspected reaction starts the same way at the bedside:

1. Stop the transfusion. Clamp the set. Do not finish the bag “because only 20 mL is left.”
2. Keep intravenous access with 0.9% sodium chloride through a new or flushed line. Do not push the remaining unit in with saline.
3. Check the patient’s identity against the unit tag and the transfusion record — the clerical check.
4. Notify the responsible clinician and the transfusion service.
5. Return the bag, the attached set, and a post-transfusion specimen to the blood bank.

Restarting is allowed only after the blood bank and the clinician agree the event is a mild isolated allergic reaction and a written protocol permits it. Isolated hives after an antihistamine is a later decision, not a reason to keep dripping an unidentified reaction.

Clerical versus serologic is the next split. Most fatal acute hemolytic events in modern inventories are wrong unit to the wrong patient or wrong sample under the right label — a clerical disaster. The serologic workup asks whether the unit was actually incompatible. A clean DAT and a matching ABO do not excuse a wristband mismatch. A mixed-field DAT does not invent a clerical error that is not there. Do both checks. Report both.

Acute hemolytic transfusion reaction

AHTR is immune destruction of transfused red cells, usually during or within 24 hours. The prototype is ABO incompatibility: recipient anti-A or anti-B binds donor A or B antigen, fixes complement, and opens the membrane. That is intravascular hemolysis. Free hemoglobin appears in plasma and urine. Complement and cytokine storm produce fever, hypotension, and DIC. Hemoglobin pigment plus hypotension injure the kidney.

The bedside postcard is fever, back or flank pain, chest or infusion-site pain, hemoglobinuria, hemoglobinemia (pink or red plasma), shock, and oozing from lines. Anesthetized patients may show only hypotension, hemoglobinuria, or unexplained bleeding.

The DAT is often positive, classically mixed-field if some donor cells remain. It can be negative if every incompatible cell has already lysed. Do not use a negative DAT to rule out AHTR when the plasma is red, the clerical check fails, and the patient is in shock. Inspect the post-transfusion specimen. Repeat ABO/Rh on the unit, the pre-transfusion sample, and the post-transfusion sample. Recrossmatch. The unit’s segments are the legal red cells.

Non-ABO AHTR exists — Kidd, Kell, Duffy, and some others can fix complement — but ABO remains the exam’s intravascular story. Physical hemolysis (18.2) mimics pink plasma without an antibody.

Worked scenario. A group O patient is issued a group A unit after a sample drawn from the roommate. Ten minutes in: fever, back pain, red urine. Stop. The wristband does not match the tag. Plasma is pink. DAT is mixed-field. That is AHTR until proven otherwise. Support blood pressure and DIC; do not wait on an eluate before calling the clinician.

Delayed hemolytic transfusion reaction

DHTR is usually extravascular hemolysis 3–14 days after transfusion (the useful exam window; outliers exist). The patient was previously immunized. The current antibody screen was negative because the titer had fallen below detection. Antigen-positive cells restimulate a secondary (anamnestic) IgG response that coats remaining donor cells.

Kidd (anti-Jka / anti-Jkb) is the classic specificity because Kidd antibodies vanish between exposures and show dosage. Kell, Duffy, and Rh antibodies do this too. The picture is a hemoglobin that rose and then fell, unexpected transfusion need, spherocytes, mild fever or jaundice, a newly identified alloantibody, and a positive DAT (often mixed-field). An eluate may recover the antibody while the serum is still weak.

Do not call every falling hemoglobin a DHTR. Bleeding and a delayed serologic transfusion reaction (new antibody and DAT+ without clear hemolysis) sit next door. The exam stem that wants DHTR hands you Kidd + falling Hb + spherocytes + new antibody.

Febrile nonhemolytic, allergic, and anaphylactic

FNHTR is a temperature rise, often taught as ≥1 °C, without hemolysis. Two mechanisms: recipient alloantibodies to donor leukocytes, and accumulated cytokines (IL-1, IL-6, TNF) in stored products, especially room-temperature platelets. Prestorage leukoreduction cut the incidence. FNHTR is a diagnosis of exclusion after hemolysis and bacterial contamination are off the table. Treat with an antipyretic. Do not skip the hemolysis workup because “it’s probably just a fever.”

Allergic reactions are recipient IgE against donor plasma proteins: urticaria, pruritus, flushing. Isolated hives without fever, dyspnea, or hypotension may be treated and, under protocol, the same unit continued. That exception is narrow.

Anaphylactic reactions are abrupt bronchospasm, stridor, hypotension, and GI symptoms, often without fever. The two named laboratory associations are IgA deficiency with anti-IgA and haptoglobin deficiency with anti-haptoglobin. Future red cells are washed; plasma-containing products come from IgA-deficient donors when anti-IgA is documented. Do not wash a unit after the fact to treat anaphylaxis already underway — stop, support the airway, and give epinephrine as indicated.

TRALI, TA-GVHD, PTP, and alloimmunization

TRALI is acute hypoxemia and noncardiogenic pulmonary edema during or within 6 hours of transfusion, not explained by another acute lung injury. The dominant mechanism is donor anti-HLA or anti-HNA antibodies (historically multiparous female plasma) that activate recipient neutrophils in the lung. A two-hit model — recipient inflammation plus antibody or bioactive lipids — is the teaching frame. Fever and hypotension are common. BNP is normal or low; diuretics do not seal the leak. Mitigation the exam expects: male, never-pregnant female, or HLA-antibody-tested female plasma (and similar donor selection for apheresis platelets where policy applies). Implicated donors are deferred from plasma-rich products. Contrast TACO in 18.2; do not treat TRALI as volume overload.

TA-GVHD is engraftment of viable donor lymphocytes in a recipient who cannot reject them — congenital T-cell immunodeficiency, intrauterine or neonatal transfusion, Hodgkin lymphoma, purine-analog therapy, and HLA-matched or blood-relative directed units (homozygous donor into a haploidentical recipient). Fever, rash, diarrhea, and pancytopenia appear in days to about a month. Marrow aplasia makes it almost uniformly fatal. Irradiation (25 Gy to the center, ≥15 Gy everywhere) prevents it. Leukoreduction does not. Chapter 4.3 already taught the 28-day irradiated red-cell clock.

Post-transfusion purpura is abrupt, profound thrombocytopenia about 5–10 days after transfusion, classically in a previously pregnant HPA-1a-negative woman with anti-HPA-1a. Autologous and transfused platelets are destroyed. IVIG is first-line treatment.

Alloimmunization is the slow immunologic cost: RBC antibodies (future HTR and HDFN), HLA antibodies (platelet refractoriness), and HPA antibodies. Leukoreduction reduces HLA alloimmunization. Antigen-matched or HLA-selected products are the downstream fix, not a reason to skip today’s reaction workup.

The workup you must be able to list

Exam traps. Stopping is first — not a STAT DAT. A negative DAT does not exclude completed intravascular AHTR. Kidd is delayed, not acute ABO. FNHTR is leftover after hemolysis and bacteria are excluded. TRALI is donor antibody and noncardiogenic edema within 6 hours, not hydrostatic overload. Leukoreduction is not TA-GVHD prophylaxis. Washed cells prevent future severe allergic/IgA reactions; they do not treat AHTR already in progress.