Discuss blood component therapy. For 20 marks
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Blood Component Therapy
Introduction
Blood component therapy is founded on the principle that patients should receive only the specific fraction of blood they lack, rather than whole blood. This targeted approach conserves precious blood resources, minimizes the risk of adverse reactions, and allows each donation to benefit multiple patients. Patient Blood Management (PBM) programs have institutionalized this philosophy, combining appropriate component use with non-transfusion modalities (such as iron repletion for iron-deficiency anemia) to improve outcomes and reduce costs.
- Henry's Clinical Diagnosis and Management by Laboratory Methods, p. 879
1. Packed Red Blood Cells (PRBCs)
Preparation and Characteristics
PRBCs are prepared by removing most plasma from whole blood. The hematocrit (Hct) is approximately 57-60%, and they contain the same hemoglobin (Hb) mass as whole blood. Key metabolic characteristics include a pH of ~6.79, elevated potassium (~20.5 mmol/L), and lactic acid ~9.4 mmol/L.
Indication and Transfusion Triggers
- PRBCs are given to increase oxygen (O2) carrying capacity, not simply to expand volume.
- The Hb value alone is insufficient - the overall clinical picture (hemodynamics, organ perfusion, O2 delivery, anticipated losses) must guide decisions.
- Transfusion is rarely indicated when Hb > 10 g/dL; almost always indicated when Hb < 6 g/dL, especially in acute anemia.
- A restrictive strategy (Hb trigger < 7-8 g/dL) is now standard for most patients based on the landmark TRICC trial (838 critically ill patients), which showed no mortality benefit of liberal transfusion (trigger 10 g/dL) over restrictive (trigger 7 g/dL), with fewer cardiac events (pulmonary edema, MI) in the restrictive group (13.2% vs. 21.0%, p < 0.001).
- Symptomatic anemia (fatigue, tachycardia, tachypnea, dyspnea, postural hypotension, impaired mentation) is an indication regardless of Hb level.
- Acute blood loss > 15% of blood volume may warrant transfusion.
Special Situations
- Sickle cell disease (SCD): Hb < 5 g/dL or acute drop of 20% from baseline; target post-transfusion Hct ~30%. Exchange transfusion preferred to keep HbS < 30% and prevent stroke.
- Cardiac patients: threshold may be higher (Hb < 8-10 g/dL) given limited tolerance for anemia.
- Critically ill patients on ICU ventilators: Hb < 7 g/dL is a generally accepted trigger.
Carrier Solutions
- Recommended diluents: 0.9% saline, 5% dextrose in 0.9% saline, Normosol-R (pH 7.4).
- Lactated Ringer's is contraindicated as a carrier: its calcium content can reverse citrate anticoagulation and trigger clotting in the tubing.
- Hypotonic solutions cause RBC swelling and lysis - must be avoided.
- Miller's Anesthesia, 10e, p. 6581-6585
2. Platelet Concentrates
Preparation
Platelets are obtained by:
- Pooled concentrates: from 4-6 whole blood donations.
- Apheresis (single-donor) concentrates: from one donor via automated collection; preferred to reduce alloimmunization.
- Storage: room temperature with constant gentle agitation for up to 7 days (risk of bacterial contamination increases with longer storage).
Indications
| Clinical Setting | Platelet Threshold |
|---|---|
| Active bleeding | < 50,000/μL |
| Before surgery/invasive procedure | < 50,000-100,000/μL |
| Prophylaxis in bone marrow failure (stable) | < 10,000-20,000/μL |
| Premature neonate (unstable) | < 100,000/μL |
| Massive transfusion with bleeding | < 50,000-100,000/μL |
Efficacy Monitoring
Each platelet concentrate increases platelet count by ~7-10 × 10⁹/L per unit at 1 hour in a 70-kg adult. Ten units are needed to raise count by ~100 × 10⁹/L. Efficacy is reduced by splenomegaly, fever, sepsis, active bleeding, or prior sensitization (alloimmunization).
Bacterial Contamination Risk
Bacterial contamination of platelets is the third leading cause of transfusion-related death. Contamination rate ~1 per 2500 units by active surveillance; septic reactions were historically under-reported (reported at 1 per 100,000 units in passive systems).
- Miller's Anesthesia, 10e, p. 6595-6601
3. Fresh Frozen Plasma (FFP)
Preparation
FFP is separated from whole blood and frozen within 8 hours (or 24 hours as PF24) to preserve all clotting factors, particularly the labile factors V and VIII. Thawed plasma may be stored at 1-6°C for up to 5 days. PF24 has ~25% reduction in factor VIII compared to standard FFP.
Indications (ASA 2015 Guidelines)
- Coagulopathy with INR > 2 (in absence of heparin).
- Coagulopathy after massive transfusion (> 1 blood volume, ~70 mL/kg) when coagulation tests unavailable.
- Known factor deficiency with bleeding or DIC when specific concentrates unavailable.
- Warfarin reversal with severe bleeding (when 4-factor PCC is unavailable).
- Thrombotic thrombocytopenic purpura (TTP) - provides ADAMTS-13 (vWF-cleaving protease).
Dosing and Notes
- Dose: 15-30 mL/kg to achieve hemostatic effect.
- Repeat dosing every 3-4 hours may be needed in actively bleeding patients.
- Standard coagulation tests (PT, aPTT) are poorly predictive of bleeding risk; no benefit from FFP when INR < 1.8-2.0 in non-bleeding patients.
- 4-factor PCC provides faster and more complete warfarin reversal than FFP.
- Risks: TRALI, TACO, allergic/anaphylactic reactions.
- Miller's Anesthesia, 10e, p. 6602; Henry's Clinical Diagnosis, p. 881
4. Cryoprecipitate
Preparation and Contents
Cryoprecipitate is the cold-insoluble precipitate formed when FFP is thawed at 1-6°C. One unit contains:
- Fibrinogen (~250 mg per bag) - the primary indication
- Factor VIII (80-100 IU)
- von Willebrand factor (vWF)
- Factor XIII
- Fibronectin
Indications
| Indication | Notes |
|---|---|
| Hypofibrinogenemia (fibrinogen < 100 mg/dL) with bleeding | Primary use |
| DIC with bleeding | Fibrinogen replacement |
| Postpartum hemorrhage with coagulopathy | Fibrinogen + FXIII |
| Factor XIII deficiency | With bleeding/pre-surgery |
| Uremic bleeding | If DDAVP ineffective (DDAVP preferred) |
| Topical fibrin sealant | Mixed with calcium + thrombin |
Dosing
In adults, 1 unit per 10 kg body weight (typically 10 bags pooled) raises fibrinogen by ~50-70 mg/dL. Direct comparison between cryoprecipitate and fibrinogen concentrate shows no consistent difference in outcomes in bleeding patients.
- Henry's Clinical Diagnosis and Management, p. 882
5. Whole Blood
Whole blood contains RBCs, plasma, and platelets but the platelets are non-functional after 24 hours of storage. It is rarely available outside trauma centers. In massive hemorrhage, the concept of "balanced resuscitation" with fixed ratios (1:1:1 - PRBCs: FFP: platelets) mimics whole blood and is now preferred in damage control resuscitation.
6. Special Considerations
Massive Transfusion
- Defined as replacement of ≥ 1 blood volume (>10 units PRBCs) within 24 hours.
- Complications include:
- Dilutional thrombocytopenia - most common cause of nonsurgical bleeding
- Dilutional coagulopathy
- Citrate toxicity (hypocalcemia)
- Hyperkalemia
- Hypothermia (use blood warmers)
- Metabolic acidosis
- Massive transfusion protocol (MTP): ratio of 1:1:1 (PRBCs: FFP: platelets) reduces mortality.
Leukoreduction
- Removal of donor white blood cells from blood products.
- Reduces febrile non-hemolytic reactions, CMV transmission, and HLA alloimmunization.
- All immunocompromised patients (organ transplant recipients, premature infants, cancer patients) should receive leukoreduced, CMV-negative products.
Irradiation
- Used to prevent transfusion-associated graft-versus-host disease (TA-GvHD) in immunocompromised patients by rendering donor lymphocytes unable to proliferate.
7. Transfusion Reactions
Acute Reactions
| Reaction | Mechanism | Features | Management |
|---|---|---|---|
| Acute Hemolytic (AHTR) | ABO incompatibility; complement activation; intravascular hemolysis | Fever, chills, hypotension, hemoglobinuria, flank pain; in anesthetized patients: unexplained tachycardia, diffuse oozing, hemoglobinuria | Stop transfusion immediately; IV fluids; maintain urine output; treat DIC |
| Febrile Non-Hemolytic (FNHTR) | Cytokine accumulation or HLA antibodies against donor WBCs | Temperature rise ≥ 1°C, chills/rigors within 1 h | Antipyretics (acetaminophen 325-500 mg); rule out AHTR; consider leukoreduction for future |
| Allergic/Urticarial | IgE-mediated to donor plasma proteins | Urticaria, pruritus (no fever) | Antihistamine (diphenhydramine 25-50 mg); may continue transfusion |
| Anaphylaxis | IgA deficiency with anti-IgA antibodies | Severe bronchospasm, hypotension, angioedema | Stop transfusion; epinephrine; IgA-deficient products in future |
| TRALI (Transfusion-Related Acute Lung Injury) | Donor anti-HLA or anti-HNA antibodies activate recipient neutrophils in pulmonary capillaries | Acute hypoxia, bilateral pulmonary infiltrates within 6 h of transfusion, no cardiac cause | Stop transfusion; supportive care; O2/mechanical ventilation; usually resolves in 48-96 h |
| TACO (Transfusion-Associated Circulatory Overload) | Volume overload | Acute pulmonary edema, hypertension, elevated BNP | Diuretics; slow/stop transfusion |
| Septic Reaction | Bacterial contamination (especially in platelets) | High fever, rigors, hypotension, shock | Stop transfusion; blood cultures; IV antibiotics; vasopressors |
Delayed Reactions
- Delayed hemolytic reaction (DHTR): 3-10 days post-transfusion; due to anamnestic antibody response to minor RBC antigens; mild hemolysis, falling Hb, positive DAT.
- Post-transfusion purpura (PTP): thrombocytopenia 5-10 days post-transfusion due to anti-HPA-1a antibodies; treat with IVIG.
- Transfusion-transmitted infections: HIV, HCV, HBV, CMV, bacterial sepsis. Risk dramatically reduced by nucleic acid testing (NAT).
- Henry's Clinical Diagnosis and Management, p. 879-884; Miller's Anesthesia, 10e, p. 6600-6605
8. Patient Blood Management (PBM) Principles
PBM is a multidisciplinary approach that encompasses:
- Pre-operative anemia optimization - treat iron deficiency, use erythropoiesis-stimulating agents (ESAs).
- Minimizing surgical blood loss - deliberate hypotension, meticulous hemostasis, antifibrinolytics (tranexamic acid).
- Tolerance of physiological anemia - restrictive transfusion thresholds, ANH (acute normovolemic hemodilution), intraoperative cell salvage.
- Appropriate component use - matching the component to the specific deficit.
PBM programs have demonstrated improved patient outcomes and reduced healthcare costs.
Summary Table of Blood Components
| Component | Contents | Storage | Indication | Dose |
|---|---|---|---|---|
| PRBCs | RBCs, Hct ~57-60% | 4°C, 42 days | Anemia, hemorrhage | 1 unit raises Hb ~1 g/dL |
| Platelets (pooled) | Platelets, plasma | 22°C, 5-7 days (agitation) | Thrombocytopenia, platelet dysfunction | 1 pooled unit (4-6 bags) |
| FFP/PF24 | All clotting factors, plasma proteins | -18°C; thawed: 4°C/5 days | Coagulopathy, TTP, warfarin reversal | 15-30 mL/kg |
| Cryoprecipitate | Fibrinogen, F-VIII, vWF, F-XIII | -18°C | Hypofibrinogenemia, DIC, postpartum hemorrhage | 1 unit/10 kg |
| Whole blood | All components | 4°C, 35 days | Massive hemorrhage (limited availability) | As needed |
Sources:
- Miller's Anesthesia, 10e - Blood Component Therapy: Indications for Transfusion (pp. 6581-6610)
- Henry's Clinical Diagnosis and Management by Laboratory Methods - Blood Component Therapy, Transfusion Reactions (pp. 879-884)
- Morgan and Mikhail's Clinical Anesthesiology, 7e - Fluid Management and Blood Component Therapy (p. 2247+)
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