27.1 Transfusion Medicine: Products, Thresholds, Reactions & Apheresis
Key Takeaways
The TRICC and TRISS trials support a hemoglobin transfusion threshold near 7 g/dL in critically ill and septic shock patients, with TRICS III supporting 7.5 g/dL in cardiac surgery.
Transfusion-related acute lung injury presents within 6 hours with hypoxemia and bilateral infiltrates and normal filling pressures, whereas TACO features hypertension, elevated filling pressures, and a diuretic response.
Acute hemolytic transfusion reaction from ABO incompatibility causes fever, flank pain, hemoglobinuria, and disseminated intravascular coagulation; the first step is stopping the transfusion and supporting renal perfusion.
Anaphylactic reaction to plasma-containing products in a patient with IgA deficiency requires washed cellular products and IgA-deficient plasma.
Therapeutic plasma exchange is first-line therapy for TTP, Guillain-Barre syndrome, myasthenic crisis, anti-GBM disease, and symptomatic hyperviscosity.
Products and When to Use Them
| Product | Content and effect | Typical ICU use |
|---|---|---|
| Packed red cells | One unit raises hemoglobin by about 1 g/dL | Anemia with impaired oxygen delivery; see thresholds below |
| Platelets | One apheresis unit raises the count by about 30,000 to 50,000/µL | Bleeding with a count below 50,000/µL (below 100,000/µL for CNS or ophthalmic bleeding), prophylaxis below 10,000/µL, or before procedures |
| Plasma | All coagulation factors, about 10 to 15 mL/kg to raise factor levels meaningfully | Bleeding with multifactor deficiency; not for isolated INR correction before low-risk procedures |
| Cryoprecipitate | Fibrinogen, factor VIII, von Willebrand factor, factor XIII, fibronectin | Fibrinogen below about 150 mg/dL with bleeding; disseminated intravascular coagulation; postpartum hemorrhage |
| Prothrombin complex concentrate (4-factor) | Factors II, VII, IX, X with low volume | Warfarin reversal with major bleeding; factor Xa inhibitor-associated bleeding |
| Fibrinogen concentrate | Standardized fibrinogen dose | Hypofibrinogenemia, especially in cardiac surgery and obstetrics |
| Albumin | Colloid; 25% for paracentesis and hepatorenal syndrome | Large-volume paracentesis, spontaneous bacterial peritonitis, hepatorenal syndrome; not routine resuscitation, and avoided in traumatic brain injury |
| Modified products | Irradiation prevents transfusion-associated graft-versus-host disease (for hematopoietic cell transplant recipients, those receiving purine analogues, and directed donations from relatives); leukoreduction reduces febrile reactions, CMV transmission, and alloimmunization; washing removes plasma proteins for IgA deficiency or repeated severe allergic reactions | Match the modification to the mechanism |
Transfusion Thresholds
| Population | Threshold |
|---|---|
| General critically ill (TRICC) | 7 g/dL |
| Septic shock (TRISS) | 7 g/dL |
| Upper gastrointestinal bleeding | 7 g/dL (restrictive strategy improved survival in cirrhosis) |
| Cardiac surgery (TRICS III) | 7.5 g/dL |
| Myocardial infarction (MINT) | A liberal strategy near 10 g/dL may be preferred; evidence is less definitive, and 8 to 10 g/dL is commonly used |
| Hip fracture and cardiovascular disease (FOCUS) | 8 g/dL or symptoms |
| Active major hemorrhage | Balanced ratios rather than a hemoglobin threshold |
Transfuse one unit at a time and reassess, except in active hemorrhage.
Acute Reactions: Recognizing Them by Pattern
| Reaction | Timing and features | Management |
|---|---|---|
| Acute hemolytic (ABO incompatibility) | Minutes: fever, chills, flank or back pain, hemoglobinuria, hypotension, disseminated intravascular coagulation; in an anesthetized patient, bleeding and hypotension may be the only clues | Stop the transfusion, maintain intravascular volume and urine output, send the unit and samples for investigation, support with products as needed |
| Febrile nonhemolytic | A rise of 1 °C or more with chills, from cytokines or recipient antibodies to donor leukocytes | Stop, exclude hemolysis and sepsis, give an antipyretic; leukoreduced products thereafter |
| Allergic (urticarial) | Hives without systemic features | Pause, give an antihistamine, resume cautiously |
| Anaphylaxis | Minutes: bronchospasm, angioedema, shock; classically in IgA deficiency with anti-IgA antibodies, or haptoglobin deficiency | Stop, give epinephrine and supportive care; future transfusions use washed cellular products and IgA-deficient plasma |
| TRALI | Within 6 hours: hypoxemia with bilateral infiltrates, no evidence of volume overload (normal filling pressures), often fever and transient leukopenia; from donor antibodies or bioactive lipids priming neutrophils | Supportive: lung-protective ventilation; diuretics do not help; report to the blood bank so donors can be evaluated |
| TACO | Within 6 to 12 hours: dyspnea, hypertension, elevated filling pressures and BNP, responds to diuresis | Slow or stop the transfusion, upright positioning, diuretics, oxygen; prevent by transfusing slowly in patients at risk |
| Bacterial contamination | High fever, rigors, shock within minutes to hours; platelets are the highest-risk product because of room-temperature storage | Stop, culture the patient and the unit, broad-spectrum antibiotics |
| Hypotensive reaction | Isolated hypotension, associated with ACE inhibitors and bradykinin generation | Stop; usually self-limited |
| Citrate toxicity | Massive or rapid transfusion, or apheresis: ionized hypocalcemia with paresthesias, QT prolongation, and reduced contractility | Calcium chloride or gluconate, with ionized calcium monitoring |
Delayed reactions: delayed hemolysis (3 to 14 days, with a falling hemoglobin and a new antibody), alloimmunization, post-transfusion purpura, iron overload, and transfusion-associated graft-versus-host disease (rash, diarrhea, pancytopenia, and liver dysfunction 1 to 6 weeks later in susceptible patients, which is nearly always fatal and is prevented by irradiation).
Massive transfusion complications: hypothermia, dilutional coagulopathy, hyperkalemia from stored cells, hypocalcemia from citrate, metabolic alkalosis as citrate is metabolized, and acidosis from hypoperfusion.
Special Transfusion Situations
- Sickle cell disease: use phenotypically matched units to limit alloimmunization; exchange transfusion for acute chest syndrome, stroke, and preoperative preparation in selected cases. Suspect hyperhemolysis syndrome if the hemoglobin falls after transfusion with reticulocytopenia.
- Warm autoimmune hemolytic anemia: transfusion is not contraindicated in severe anemia, although crossmatching is difficult; give the "least incompatible" unit while treating with steroids.
- Cold agglutinin disease: warm the patient and use a blood warmer.
- Jehovah's Witness patients: establish which products and techniques are acceptable in advance; use erythropoietin, intravenous iron, cell salvage, tranexamic acid, and meticulous blood conservation.
- Platelet refractoriness: suspect alloimmunization (HLA antibodies) when counts fail to rise; use HLA-matched platelets. Avoid platelet transfusion in TTP and HIT unless there is life-threatening bleeding.
Apheresis and Plasma Exchange
Therapeutic plasma exchange removes plasma (with its pathogenic antibodies, immune complexes, or paraproteins) and replaces it with albumin or plasma. Replacement with plasma is needed in TTP (to supply ADAMTS13) and when there is coagulopathy.
| First-line (Category I) indications relevant to the ICU | Notes |
|---|---|
| TTP | Daily exchange with plasma replacement, plus steroids and caplacizumab |
| Guillain-Barré syndrome | Equivalent to IVIG; do not combine |
| Myasthenic crisis | May act faster than IVIG |
| Anti-GBM disease (Goodpasture) | With steroids and cyclophosphamide |
| ANCA vasculitis with severe disease | PEXIVAS showed no benefit for death or end-stage kidney disease; use is individualized |
| Hyperviscosity syndrome (Waldenström macroglobulinemia, myeloma) | Rapid symptom relief |
| Severe hypertriglyceridemia with pancreatitis | When insulin and supportive therapy fail |
| Acute liver failure | High-volume plasma exchange improved transplant-free survival in a randomized trial |
| Transplant desensitization and antibody-mediated rejection | With IVIG and rituximab |
Leukapheresis is used for symptomatic hyperleukocytosis (leukostasis), and red cell exchange for acute chest syndrome, stroke in sickle cell disease, and severe babesiosis or malaria in selected cases.
Complications of apheresis: citrate-induced hypocalcemia, hypotension, catheter complications, coagulation factor depletion (with albumin replacement), and removal of therapeutic drugs and antibodies, so timing with medication dosing matters.
A 58-year-old woman receives 2 units of packed red cells for anemia after surgery. Three hours into the second unit she develops dyspnea, an oxygen saturation of 86%, bilateral infiltrates on chest radiograph, a temperature of 38.4 °C, and a blood pressure of 104/62 mmHg. Central venous pressure is 6 mmHg, BNP is normal, and echocardiography shows normal biventricular function. What is the most likely diagnosis and appropriate management?
Transfusion-associated circulatory overload, managed with intravenous furosemide
Transfusion-related acute lung injury, managed with supportive lung-protective ventilation and blood bank notification
Acute hemolytic transfusion reaction, managed with alkaline diuresis
Anaphylactic transfusion reaction, managed with epinephrine and washed products
A 44-year-old man with a hematologic malignancy requires platelet transfusion. He has a history of severe anaphylaxis during two previous plasma-containing transfusions, and serum IgA is undetectable. Which approach is most appropriate for future transfusions?
Premedicate with diphenhydramine and transfuse standard products
Use irradiated products to prevent graft-versus-host disease
Use washed cellular products and IgA-deficient plasma
Use leukoreduced products to prevent febrile reactions
A 69-year-old man in the ICU with septic shock from pneumonia has a hemoglobin of 7.4 g/dL. He is on norepinephrine at 0.1 mcg/kg/min, has a lactate of 1.8 mmol/L, no bleeding, and no acute coronary syndrome. Which transfusion decision is best supported by randomized evidence?
Transfuse 1 unit now, targeting a hemoglobin of 9 to 10 g/dL for better oxygen delivery
Withhold transfusion unless the hemoglobin falls below 7 g/dL or he bleeds or becomes ischemic
Transfuse 2 units now because he requires vasopressors
Transfuse only after measuring central venous oxygen saturation below 70%
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