Blood & Blood Transfusion - Comprehensive Guide

1. COMPOSITION OF BLOOD

• Plasma (~55%): water, proteins (albumin, globulins, fibrinogen, clotting factors), electrolytes, hormones, nutrients, waste products
• Formed elements (~45%):
  • Red blood cells (RBCs/erythrocytes): oxygen transport via hemoglobin
  • White blood cells (leukocytes): immunity and defense
  • Platelets (thrombocytes): hemostasis

2. BLOOD GROUPS

ABO System

Rh System

• ~45 RBC blood group systems are recognized; ~390 antigens described
• Five systems routinely investigated due to clinical significance of their antibodies: Rh, Kell, Duffy, Kidd, and MNS - testing all five achieves ~95% routine transfusion compatibility
• Warm autoantibodies (IgG, active at 37°C): most often directed against Rh antigens - cause warm autoimmune hemolytic anemia
• Cold autoantibodies (IgM, active at 4°C): directed against ABO, HI, I, P antigens

Alloimmunization

• Anti-RBC antibodies (risk of hemolysis)
• Anti-HLA antibodies (platelet refractoriness, TRALI)
• Anti-HPA (human platelet antigen) antibodies
• Anti-HNA (human neutrophil antigen) antibodies

3. BLOOD COMPONENTS AND COLLECTION

Collection and Manufacturing

Blood Components

• Hematocrit: 70-80%
• Shelf life: 35-42 days at 2-6°C
• 1 unit raises adult hemoglobin by ~1 g/dL or hematocrit by ~3%
• In children: 10 mL/kg raises Hb ~1 g/dL
• Transfusion time: 60-90 min per unit; must not exceed 4 hours (bacterial growth risk)
• Indication: Improve oxygen delivery to tissues

• Contains all coagulation factors (1 unit of activity per mL)
• Indications: Coagulopathy reversal, massive transfusion, liver disease
• Dosing: 10-30 mL/kg (variable clinical response)
• Note: PCC (prothrombin complex concentrate) preferred over FFP for vitamin K antagonist reversal in life-threatening hemorrhage

• Stored at room temperature (22°C) with gentle agitation
• Shelf life: 5-7 days
• Transfusion triggers:
  • Prophylactic: count <10,000/μL (stable adult)
  • Central venous catheter placement: <20,000/μL
  • Lumbar puncture / non-neuroaxial surgery: <50,000/μL
• Dose: 6 units (pooled "six-pack") or 1 apheresis unit → raises platelet count ~40,000-60,000/μL
• Apheresis platelets expose recipient to plasma proteins of only one donor (lower allergic reaction risk)

• Derived from plasma; rich in fibrinogen, Factor VIII, Factor XIII, vWF, fibronectin
• Indicated for significant hypofibrinogenemia (<100 mg/dL)
• Dose: ~10 bags raises fibrinogen by ~1 g/L (100 mg/dL)

• Shelf life shorter than components but can be cost-effective
• Low-titer O whole blood (LTOWB) is safe and effective, especially in hemorrhagic resuscitation
• Advantages over component therapy: physiologic balance, higher hemostatic factors, more fibrinogen delivery, fewer donor exposures
• Risk: Rh isoimmunization in premenopausal women receiving LTOWB (consider Rh immunoglobulin)

• Used rarely in severe neutropenia with refractory infection; not leukoreduced

Leukoreduction (Leukocyte Reduction)

• Febrile non-hemolytic transfusion reactions (FNHTRs)
• CMV transmission risk
• Alloimmunization
• Immunomodulation

Additional Processing

Storage Lesion

• Loss of RBC deformability
• Potassium leakage
• Irreversible membrane changes
• Impaired oxygen unloading in microcirculation

4. BLOOD TYPING AND COMPATIBILITY TESTING

• Blood type: identify ABO group and Rh factor
• Antibody screen: detect unexpected alloantibodies

• Confirms compatibility between donor RBCs and recipient serum
• Electronic crossmatch acceptable if no alloantibodies detected

• Untyped blood: Group O Rh-negative PRBCs (universal donor for RBCs)
• Type-specific blood: Can be issued within minutes once type is known

5. TRANSFUSION INDICATIONS AND THRESHOLDS

Red Cell Transfusion (AABB 2016 Guidelines)

6. MASSIVE TRANSFUSION PROTOCOL (MTP)

Complications of Massive Transfusion ("Lethal Triad")

7. TRANSFUSION REACTIONS

Acute Reactions

• Most common reaction: ~1 in 100-200 transfusions
• Mechanism: Cytokines from donor leukocytes
• Presentation: Temperature rise ≥1°C (2°F), no hemolysis
• Treatment: Antipyretics; leukoreduced products reduce incidence

• Second most common: ~1 in 300 transfusions
• Range: urticaria/pruritus → anaphylaxis
• Mechanism: IgE-mediated reaction to donor plasma proteins; IgA-deficient recipients may have anti-IgA antibodies
• IgA deficiency: affects 1 in 700, but severe reactions in minority
• Treatment:
  • Mild (localized): antihistamines; transfusion may be restarted
  • Severe/recurrent: steroids 2-3 hours pre-transfusion
  • Anaphylaxis: epinephrine; give IgA-deficient units or washed units

• Incidence: 1 in 6,000-30,000 transfusions; fatal: 1 in 100,000-600,000
• Mechanism: Usually ABO incompatibility (most from clerical error); complement activation → intravascular hemolysis
• Presentation: Abrupt fever, chills, back/flank pain, hypotension, DIC, hemoglobinuria, renal failure, sense of "impending doom," burning at infusion site
• Lab: Positive DAT, pink serum, hemoglobinuria, elevated bilirubin, schistocytes, coagulopathy
• Treatment: STOP transfusion immediately → IV fluids, monitor renal function, treat DIC
• Fatal reactions must be reported to the FDA within 7 days

• Leading cause of transfusion-related mortality
• Incidence: 1 in 5,000-190,000 transfusions
• Mechanism: Donor anti-HLA or anti-HNA antibodies react with recipient neutrophils → massive pulmonary neutrophil activation → non-cardiogenic pulmonary edema
• Presentation: Acute respiratory distress within 6 hours of transfusion; bilateral pulmonary infiltrates; NO evidence of fluid overload
• Treatment: Stop transfusion; supportive respiratory care (NIPPV or intubation/mechanical ventilation)

• Presentation: Dyspnea, elevated BNP, hypertension, bilateral pulmonary infiltrates
• Distinguish from TRALI: TACO shows elevated filling pressures

Delayed Reactions

• Incidence: ~1 in 1,500 transfusions
• Timing: 5-14 days after transfusion (anamnestic antibody response)
• Most commonly implicated antigens: Kidd (most severe - intravascular hemolysis), E, c, Kell, Duffy
• Findings: Positive DAT (mixed field), hyperbilirubinemia, microspherocytes
• Treatment: Identify responsible antibody; avoid further exposure; usually no acute treatment needed

• Donor T-lymphocytes attack immunocompromised recipient
• Prevention: Irradiation of cellular blood products in at-risk patients

Infectious Risks (Current Estimated Rates)

• Most common transfusion-transmitted infection; mortality 25% (platelets), 70% (RBCs)
• Platelet-related: Staphylococcal species (stored at room temperature)
• RBC-related: Psychrophilic Gram-negative bacilli - Yersinia enterocolitica (most common), Serratia, Citrobacter, Pseudomonas
• Treatment: Stop transfusion, Gram stain the unit, broad-spectrum antibiotics, hemodynamic support

8. SPECIAL TOPICS

Autologous Blood Transfusion

• Patient donates own blood before elective surgery
• Now used rarely due to little advantage over allogeneic (with modern blood safety)
• Still useful for patients with rare blood group phenotypes

Autotransfusion (Intraoperative Cell Salvage)

• Blood collected from uncontaminated bleeding sites (e.g., thoracic trauma) and returned to patient
• Advantages: immediate availability, perfect compatibility, no disease transmission risk, acceptable to Jehovah's Witnesses

Irradiation

• Prevents TA-GVHD in: immunocompromised patients, neonates, intrauterine transfusion recipients, HLA-matched/directed donations, post-stem cell transplant patients

TEG/ROTEM in Massive Transfusion

• Viscoelastic point-of-care tests guide goal-directed transfusion
• Alters transfusion patterns; preliminary data suggest TEG-guided therapy may reduce mortality vs. conventional coagulation parameters, but further study is needed

Sources

• Harrison's Principles of Internal Medicine 22E (2025) - Blood components, blood group antigens
• Rosen's Emergency Medicine - Blood products, transfusion thresholds, massive transfusion, transfusion reactions
• Quick Compendium of Clinical Pathology 5th ed. - Transfusion complications and risk table
• Tietz Textbook of Laboratory Medicine 7th ed. - Blood banking and collection
• Schwartz's Principles of Surgery 11th ed. - Massive transfusion protocol

Blood Collection Tubes - Color, Additive, Mechanism & Use

Complete Reference Table

Key Additive Details

EDTA (Ethylenediaminetetraacetic Acid)

• Mechanism: Chelates (binds) calcium ions - calcium is essential for the clotting cascade
• Forms: K₂EDTA (spray-dried, no sample dilution - preferred) vs K₃EDTA (liquid, dilutes sample ~1-2%)
• Used in: Lavender, Pink, White, Royal Blue, Tan tubes
• Do NOT use for: coagulation tests, chemistry panels requiring ionized calcium, blood cultures

Sodium Citrate

• Mechanism: Chelates calcium (reversible - calcium can be added back)
• Concentration matters: 3.2% for coagulation (light blue), higher ratio for ESR (black)
• Critical note: The light blue tube must be filled to the fill line. Under-filling causes excess citrate relative to plasma volume → falsely prolonged PT/aPTT. In polycythemia (Hct >60%), the same problem occurs because plasma volume is reduced - the citrate volume must be adjusted.

Heparin

• Mechanism: Activates antithrombin III → inhibits thrombin and Factor Xa
• Forms: Sodium heparin, lithium heparin (lithium heparin preferred for most chemistry to avoid sodium or lithium interference)
• Do NOT use for: CBC (causes WBC clumping), coagulation tests, blood bank testing

Sodium Fluoride

• Mechanism: Inhibits enolase enzyme → blocks glycolysis → prevents glucose from being consumed by RBCs
• Preserves glucose for up to 5 days at room temperature
• May cause slight hemolysis if tube is under-filled

Clot Activator (Silica)

• Mechanism: Silica microparticles provide a surface for platelet activation and accelerate the intrinsic clotting pathway
• After collection, tube should be gently inverted 5-10 times, then allowed to clot for 30 minutes before centrifugation

Order of Draw (CLSI Standard)

Why this order? Tissue thromboplastin released during venipuncture can contaminate early tubes. Citrate (blue) must come before additive tubes to prevent EDTA or heparin carryover, which would falsely prolong coagulation times. EDTA drawn before heparin tubes prevents EDTA from chelating calcium and falsely affecting chemistry panels.

Common Mnemonics

• Blood cultures → Sodium citrate (Blue) → Red → Green → Lavender → Grey → Gold

• 🔵 Blue = "Blood clotting tests" (coagulation)
• 🟣 Lavender/Purple = "Lab hematology" (CBC)
• 🟢 Green = "Go chemistry" (plasma chemistry, stat)
• ⬜ Grey = "Glucose guard" (glycolysis inhibitor)
• 🟡 Gold = "General chemistry" (SST serum)
• 🩷 Pink = "Patient blood bank" (type & cross)

Special Notes

• Henry's Clinical Diagnosis and Management by Laboratory Methods - Table 3.4 (Tube Color and Anticoagulant/Additive), p. 2012-2013
• Quick Compendium of Clinical Pathology 5th ed. - Selected blood collection tubes table, p. 192
• BD Vacutainer Tube Guide - manufacturer specifications
• CLSI GP41 Order of Draw Standard