28 Transfusion Medicine
- Platelet threshold: prophylactic ≤10K/μL; ↑ to 20K w/ fever/sepsis/alloimmunization; <50K preop
- Refractoriness (CCI <5K): HLA/HPA alloimmunization → HLA-matched/crossmatched products
- RBC transfusion: ABO-compatible; RhD status determines donor; SCD/cold agglutinins need special matching
- Plasma & cryo: FFP 200–250 mL/unit (↑ factors II/V/VII/IX/X by ~3%); cryo ↑ fibrinogen, vWF, FXIII
- Transfusion reactions: AHTR (fever, back pain, hemoglobinuria → STOP) | TACO (HTN, ↑ BNP) | TRALI (bilateral infiltrates, <6h) | FNHTR (fever only) | TA-GVHD (rare, irradiate to prevent)
- Infectious risk: HIV 1/4.6M | HCV/HBV rare w/ NAT | bacterial 1/10K | WNV/Zika seasonal screening
- Special populations: HSCT (CMV-matched/seroneg, irradiated) | SCD (simple/exchange transfusion) | HDFN (IUT/phototherapy)
- Bloodless medicine: cell salvage, ANH, desmopressin, recombinant factors
28.1 Clinical Transfusion of Platelets
- Prophylactic threshold: ≤10K/μL (standard)
- ↑ to 20K: fever, sepsis, splenomegaly, alloimmunization
- <50K: preop; <100K: neurosurgery/intracranial
- Dose: 1 apheresis unit ↑ 30–60K/μL; ↓ by 5–10K/μL per unit w/ fever/splenomegaly
- Refractoriness: CCI <5K after ≥2 transfusions (10–90% prevalence by cause)
28.1.1 Platelet Refractoriness
Diagnosis - Check plt count ≤1h post-transfusion; CCI = (Δ plt count × BSA) ÷ plt transfused - CCI <5–10K indicates refractoriness
Immune causes (HLA/HPA alloimmunization) - HLA alloimmunization: most common; ↑ risk prior transfusions/pregnancy - Check HLA antibodies & recipient HLA type - Select HLA-matched or crossmatched products - ABO-matched if HLA-incompatible unavailable - HPA alloimmunization: HPA-1a/1b most common; NAIT in neonates
Non-immune causes - Fever, active bleed, sepsis, BM involvement, meds, splenomegaly, coagulopathy - RhD immunization (prevent w/ anti-D) - Hypervolemia, hypoxia, DIC
Clinical Pearls
- HLA-matched platelets ↓ DTCs & infection risk in HSCT
- Leukoreduction minimizes immune priming
28.2 Granulocyte Transfusion
- Rare: severe fungal/bacterial infection w/ inadequate recovery & documented source control
- Yield: G-CSF + dexamethasone ↑ yield
- ABO-compatible: short lifespan (4–8h optimal)
- Indications: infection despite abx; ANC <500 unresponsive; anticipated granulocytopenia; bacteremia/fungemia
- Risks: allergic Rxn, TRALI, HLA/HPA alloimmunization
28.3 Plasma Products
Plasma (FFP) - Storage: –18°C; 1-year lifespan - Dose: 10–15 mL/kg (~3% factor increment per unit) - Use: coagulation factors, bleeding, DIC, massive transfusion, vit K-deficiency - Viral inactivation available (solvent detergent, UV)
Cryoprecipitate - Components: fibrinogen 80–100 mg/unit, FVIII, vWF, FXIII, fibronectin - Dose: 1 unit/10 kg (↑ fibrinogen ~10 mg/dL) - Indications: hypofibrinogenemia, post-massive transfusion, vWD - Fibrinogen concentrate alternative (ABO-compatible not required)
Recombinant factors - rFVII: ↓ bleeding hemophilia A/B, thrombocytopenia - rFVIII: hemophilia A - rFIX: hemophilia B
28.4 Whole Blood
- Interest: military/trauma resuscitation
- Advantage: balanced ratios (RBC, plt, factors); ↓ donor exposure vs component therapy
- Contraindication: ABO incompatibility (requires crossmatch)
- Logistics: special processing; limited availability civilian US
28.5 Special Transfusion Settings
28.5.1 HSCT
Challenges - Alloimmunization, HLA sensitization, prior transfusions - Directed-donor → minor histocompatibility antigen alloimmunization → ↑ graft rejection
Management - CMV-matched/seroneg: CMV-mismatch (pos donor → neg recip) - Irradiated: RBC, plt → prevent TA-GVHD - Leukoreduced: ↓ CMV transmission (all transfusions) - Lower plt trigger: ↑ bleed risk post-HSCT; monitor PT/PTT, fibrinogen - HLA-matched/crossmatched: if plt refractoriness develops - ABO-incompatible: forward (donor anti-recip) ↑ hemolysis; reverse ↑ infection - Non-ABO: recipient antibodies → delayed hemolysis; crossmatch before transfusion
28.5.2 Sickle Cell Disease
- Simple transfusion: acute crisis/chest syndrome/stroke; goal Hb 10, HbS <30%
- Exchange transfusion: 1 L RBC in 2–4h (automated apheresis option)
- Indications: acute stroke, chest syndrome, priapism, pain, splenic sequestration
- Alloimmunization: 10–20% transfused pts; HLA/RBC alloimmunization → refractoriness
- Extended matching: Kell, Kidd, M/N, S/s → ↓ alloimmunization; incompatibility screening essential
28.5.3 Hemolytic Disease Fetus/Newborn (HDFN)
- Maternal alloimmunization: ABO/Rh/Kell → passive hemolysis in fetus
- Intrauterine transfusion (IUT): US-guided PUBS; fetal Hb threshold ~25%
- Phototherapy-only strategy; exchange if bili exceeds threshold
- IUT: severe hemolysis ± hydrops; group O, low-titer, crossmatched RBCs
- Neonatal alloimmune thrombocytopenia (NAIT)
- Maternal anti-HPA antibodies (HPA-1a most common)
- Tx: IVIG, steroids, HPA-neg plt if urgent
28.5.4 Pediatric
- RBC: 15 mL/kg → ↑ Hb ~3 (CMV-seropos ↓ infection if ≤2 units)
- Neonatal RBC: 15 mL/kg; restrictive (Hb 7 if stable); ≤2 units = CMV-seropos ok
- Platelet: prophylactic ≤10K (neonates <25K); small volumes → avoid overload
- FFP/cryo: limited efficacy data; weight-based dosing
- CMV-seropos & irradiated: preterm <1.2 kg, ≤1mo old → prevent TA-GVHD
- NAIT: maternal anti-HPA → restrictive (20–25K in hemorrhage); CMV-seropos if avail
- Hemolysis: phototherapy thresholds; exchange if severe bili (kernicterus risk)
28.6 Transfusion Reactions
| Reaction | Symptom | Primary Differential | Prevalence per 100,000 Units |
|---|---|---|---|
| AHTR | Fever, rigors, chills | Bacterial contamination, endotoxin | 1,000-3,000 (varies by component) |
| Dyspnea | TRALI | 0.4-1.0 (w/ mitigation strategies) | |
| TACO | 10.9 | ||
| TAD | Unknown | ||
| BACON | 0.03-3.3 (septic reaction; varies by component) | ||
| Urticaria | Anaphylactic | 8 | |
| Allergic | 112.2 | ||
| Anaphylactic | 8 | ||
| Hypotension | AHTR | 2.5-7.9 | |
| BACON | 0.03-3.3 (septic reaction; varies by component) | ||
| Bradykinin | Unknown | ||
| Anaphylactic | 8 | ||
| Fever | FNHTR | 1,000-3,000 (varies by component) | |
| AHTR | 2.5-7.9 | ||
| BACON | 0.03-3.3 (septic reaction; varies by component) | ||
| DHTR | 1:25,000 to 1:25,000 | ||
| Cytopenia | PTP | 1.8 | |
| DHTR | 40 | ||
| TA-GVHD | Extremely rare |
| Abbreviation | Event |
|---|---|
| AHTR | Acute hemolytic transfusion reaction |
| DHTR | Delayed hemolytic transfusion reaction |
| FNHTR | Febrile nonhemolytic transfusion reaction |
| TACO | Transfusion-associated circulatory overload |
| TRALI | Transfusion-related acute lung injury |
| TAD | Transfusion-associated dyspnea |
| PTP | Posttransfusion purpura |
| BACON | Bacterial contamination |
| HTRV | Human T-cell lymphotropic virus |
| TA-GVHD | Transfusion-associated graft-versus-host disease |
28.6.1 Acute Hemolytic (AHTR)
- Mechanism: ABO/RBC antigen mismatch → IgM/IgG → complement → lysis
- Presentation: fever, chills, back/chest/flank pain, dark urine, ↓ BP, DIC
- Cause: patient misidentification & specimen mismatch (use bedside verification, barcode)
- Mgmt: STAT STOP transfusion
- IV access, fluids, vasopressors if hypotensive
- Type & screen, DAT, Hb/Hct, BUN/Cr, PT/PTT, fibrinogen
- Urine output >200 mL/h (IV fluids ± diuretics if oliguric)
- Contact blood bank
- Consider exchange if massive hemolysis
Pearl: Recognition & cessation of transfusion essential for survival. Bedside verification & computerized ID reduce errors.
28.6.2 TACO (Circulatory Overload)
- Mechanism: volume expansion → pulmonary edema
- Presentation: dyspnea, orthopnea, ↑ JVP, crackles, ↑ BP, pulm edema on CXR
- Risk: age >60, cardiac dz, renal fail, massive transfusion
- Prevention: slow infusion (3.5–4h/RBC unit)
- Mgmt: STOP, furosemide, O₂, vasodilators if HTN
28.6.3 TRALI (Acute Lung Injury)
- Mechanism: immune/non-immune; donor HLA/HPA antibodies ± neutrophil priming → ↑ vascular permeability
- Presentation: fever, dyspnea, hypoxia, bilateral infiltrates <6h post-transfusion
- Diagnosis: acute distress, bilateral CXR infiltrates, PaO₂ drop (P/F <300), PCWP <18
- Incidence: 1/5K transfusions (FNHTR more common)
- Prevention: leukoreduction, donor HLA/HPA screening
- Mgmt: O₂, mechanical vent if needed; recovery 48–96h (steroids not routine, diuretics if overload)
28.6.4 Delayed Hemolytic (DHTR)
- Mechanism: anamnestic immune response to prior RBC antigen → IgG extravascular lysis (splenic)
- Presentation: anemia, jaundice, ↑ bili, ↑ LDH, ↓ hapto (may be asymptomatic)
- Diagnosis: DAT(+) IgG, new alloantibody on repeat type & screen, RBC panel specificity
- Mgmt: supportive; crossmatched RBC if urgent; monitor bili & Hb (further transfusions may worsen)
28.6.5 Allergic Reactions
- Urticaria: IgE-mediated to plasma proteins; minor common, mild
- Anaphylaxis: rare; severe in IgA deficiency (anti-IgA antibodies)
- Mgmt:
- Minor: antihistamine, continue transfusion
- Severe: STOP, epinephrine 0.3–0.5 mL 1:1000 IM/SQ, supportive care
- Recurrent: washed products (↓ plasma); IgA-deficient pts → IgA-deficient plasma
28.6.6 FNHTR (Febrile Nonhemolytic)
- Definition: ≥1°C rise w/ chills <4h; no hemolysis/sepsis
- Prevalence: 1–3K/100K units
- Prevention: leukoreduction (prestorage, not bedside)
- Mgmt: acetaminophen/NSAID pre-transfusion; rule out hemolysis/infection
28.6.7 PTP (Posttransfusion Purpura)
- Mechanism: HPA alloimmunization (usually HPA-1a) 5–10d post-transfusion → <20K
- Diagnosis: HPA alloantibodies; self-limited (resolves 1–2w)
- Mgmt: supportive; IVIG 2 g/kg or steroids if severe bleeding; avoid HPA-incompatible plt unless life-threatening
28.6.8 TA-GVHD (Transfusion-Associated GVHD)
- Mechanism: donor T cells recognize recipient HLA foreign → attack tissues (skin, GI, liver, BM)
- Risk: severe immunosuppression, HLA homozygosity, close relative transfusion
- Presentation: fever, erythematous rash, diarrhea, ↑ LFTs, thrombocytopenia, donor engraftment
- Prevention: irradiate products (1.5–2.5 Gy) in HSCT, severe immunosuppression, IUT
- Prognosis: mortality 80–90%
28.6.9 Infectious Complications
Bacteria & parasites - Bacterial: ↑ plt storage (room temp); rare (1/100K transfusions) - Prevention: aseptic technique, culture/rapid pathogen detection, pathogen reduction - Parasites: malaria, Chagas, babesiosis; geographic variable; rare developed countries
Viruses
| Infectious Agent | Residual Risk per Unit |
|---|---|
| Hepatitis B | 1:1.5 million |
| Hepatitis C | 1:2.3 million |
| HIV | 1:4.6 million |
| HTLV-1, HTLV-2 | 1:3.4 million |
- HIV: 1/4.6M; NAT window <11d
- HCV/HBV: 1/2–1.5M; rare w/ NAT; dual NAT, anti-HCV, anti-HBs, HBsAg
- HTLV-1/2: 1/3.4M; endemic Caribbean/Central America/Japan; rare developed countries
- WNV/Zika: seasonal screening; NAT window 7–10d
28.6.10 Other Complications
Transfusion-associated sepsis - Bacterial risk ↑ room-temp plt; fever, hypotension, shock during/shortly after - Mgmt: STAT STOP, cultures, broad-spectrum abx, supportive care
Avoiding unnecessary transfusion - Iatrogenic anemia: optimize phlebotomy volume - Cell salvage: perioperative RBC recovery; ANH pre-op, post-op salvage - Pharmacologic: desmopressin ↓ bleed (vWD, thrombocytopenia); recombinant factors (rFVIIa, rFVIII, rFIX); tranexamic acid - Restrictive strategy: target Hb 7–8 g/dL most pts (↑ Hb threshold in acute bleed/cardiac dz)
28.7 Blood Component Compatibility
| Recipient Blood Group | Donor Blood Type | RBC Transfusion | Platelet/Plasma Transfusion |
|---|---|---|---|
| O | O | O | O or AB |
| A | A, O | A or O | AB |
| B | B, O | B or O | AB |
| AB | A, B, O, AB | A, B, O, AB | AB |
| Rh neg. | Rh neg. | Rh neg. | Rh pos or Rh neg |
| Rh pos. | Rh pos. | Rh pos. | Rh pos or Rh neg |
Abbreviations: org. = organism; pos. = positive; neg. = negative
28.8 Bloodless Medicine
- Rationale: religious preference, autonomy, ↓ infection/immune complications
- Cell salvage: intraop/postop RBC recovery, wash, concentrate, reinfuse
- ANH (acute normovolemic hemodilution): 1–3 units pre-op → crystalloid/colloid → retransfuse intraop
- Pharmacologic: desmopressin (↑ vWF/FVIII), tranexamic acid, recombinant factors
- Operative: meticulous hemostasis, cautery, avoid hypothermia
- Outcomes: supportive data; select elective, anticipated loss <20% EBV, stable hemodynamics
28.9 Patient Blood Management
Preop optimization - Treat anemia (iron ± ESA); B₁₂/folate; manage coagulopathy (warfarin, antiplatelets)
Intraop - ANH, cell salvage, meticulous hemostasis, ↓ phlebotomy
Postop - Avoid unnecessary phlebotomy; transfuse Hb <7 (higher threshold acute bleed/cardiac)
Restrictive strategy: target Hb 7–8 vs liberal 10–12 → ↓ complications & mortality