Transfusion Medicine

Transfusion Medicine Study Notes

Objectives

  • List and describe the different blood components used in transfusion medicine.

  • List common indications for transfusion.

  • List five clinically significant or common types of transfusion reactions, and describe their pathogenesis, clinical features, and treatment.

  • Understand the rationale and/or goals of plasmapheresis therapy.

  • Understand the concept of a “Category I” indication for plasmapheresis, and give examples.

Outline

A. Blood Components

  • Red Blood Cells (RBCs)

  • White Blood Cells (WBCs)

  • Platelets

  • Plasma (and plasma derivatives)

B. Indications for Transfusion
C. Adverse Reactions

  1. Hemolytic

  2. Febrile

  3. Allergic

  4. TACO (Transfusion Associated Circulatory Overload)

  5. TRALI (Transfusion-Related Acute Lung Injury)

D. Plasmapheresis

A. Blood Components

1. Whole Blood

  • Definition: Traditionally the entirety of donated blood which contains all components of blood.

  • Separation: Components can be separated by centrifugation, which separates cellular elements from plasma.

  • Uses:

    • Provides oxygen-carrying capacity, coagulation factor replacement, platelet functionality, and blood volume expansion.

    • Currently used in massive transfusion situations (particularly in trauma).

    • Used in intrauterine/neonatal exchange transfusion.

2. Components Collected by Apheresis

  • Apheresis: Method of separating the donor’s blood into its components using specialized equipment, allowing for higher yield of specific blood elements compared to traditional separation techniques.

  • Results: Specific blood elements are harvested, while the remainder is reinfused back to the donor.

3. Red Blood Cell (RBC) Production and Storage

  • Collection: RBCs are separated from whole blood or via apheresis.

  • Anticoagulant Preservative Solution: Cells are collected into a sterile bag with a solution that allows storage for 35-42 days.

  • Leukoreduction: Nearly all RBCs are leukoreduced shortly after collection; this reduces the formation of antibodies against foreign HLA antigens and minimizes febrile transfusion reactions and infections (like CMV).

  • Storage Conditions: RBC units are stored at 1-6°C and can withstand transport at 1-10°C.

  • Potassium Leak: RBCs leak potassium progressively; at expiration, 75-85% of RBCs are recoverable and functional.

  • Washing: Washing RBCs can remove up to 95% of plasma proteins to avoid severe allergic reactions or IgA deficiency; the shelf life is 24 hours after washing (open system) and 14 days (closed system).

  • Freezing: RBCs can be frozen for over 10 years, useful for rare phenotypes.

4. Platelet Production and Storage

  • Pooling and Apheresis: Platelets collected from whole blood are pooled (4-8 units), while apheresis platelets are single donor units containing a minimum of 3 x 10^11 platelets in ~200 mL plasma.

  • Storage Conditions: Stored on an agitator at 20-24°C for 5 days; post-transfusion platelet count is checked 10-60 minutes later.

  • Goal: Increase platelet count by 15-25,000/mL at 1 hour.

  • Advantages of Apheresis Platelets: Fewer donor exposures, lower risk of bacterial contamination/sepsis, fewer donor RBCs in unit.

5. Plasma Production and Storage

  • Fresh Frozen Plasma (FFP): Separated and frozen within 8 hours post-collection; sizes from whole blood (250-300 mL) and apheresis (300-500 mL).

  • Common Indications: Coagulation factor replacement in massive transfusion, DIC, liver disease, plasma exchange in TTP, and to supply deficient factors when no concentrates are available.

  • Storage Conditions: FFP can be stored at ≤ -18°C for up to one year.

    • After thawing: Keep at 1-6°C for 24 hours or at 20-25°C for 4 hours.

    • Beyond this period, it is termed Thawed Plasma, with concern about factor activity degradation.

6. Cryoprecipitate Production and Storage

  • Definition: Created by slowly thawing FFP; contains factors VIII, XIII, fibrinogen, and vWF.

  • Storage Conditions: Must be kept frozen until ordered, used within 6 hours after thawing.

  • Concentration Levels: Each unit contains ≥ 150 mg of fibrinogen and is expected to raise fibrinogen levels by approximately 80 mg/dL in non-bleeding patients.

B. Indications for Transfusion

  • Whole Blood: For actively-bleeding trauma patients with expected blood loss >15%.

  • Red Blood Cells: For symptomatic anemia requiring an increase in oxygen-carrying capacity.

  • Platelets: For bleeding due to thrombocytopenia (usually <50k/uL), defective platelets, or prophylaxis against bleeding.

  • FFP: For bleeding and prophylaxis in patients with factor deficiencies.

  • Cryoprecipitate: For fibrinogen deficiency.

Appendix A: Automatic Approval for Component Orders (UH-TMC policy)

  • FFP-Thawed Plasma Confirmation levels (e.g., INR, ROTEM criteria)

  • Platelet Apheresis Orders: Specific counts and conditions leading to transfusion.

  • Liquid Plasma: Restrictions and emergency guidelines.

  • Cryoprecipitate indications (fibrinogen levels and conditions).

C. Transfusion Reactions

1. Definitions and General Considerations

  • Acute Transfusion Reactions: Defined as reactions occurring during or within 24 hours of transfusion; symptoms can include dyspnea, fever, hypotension, urticaria, and pain.

  • Clinical History: Important factors include:

    • Patient’s medical history (e.g., fever, previous transfusions, IgA deficiency).

    • Identification of blood component being transfused and its leukoreduction status.

    • Volume of the blood component can influence reactions.

2. Types of Transfusion Reactions

  • Hemolytic Reactions: Can be acute or delayed.

  • Febrile Non-Hemolytic Transfusion Reactions (FNHTR): CDC defines as ≥ 1°C rise in temperature.

  • Allergic Reactions: Defined by the NHSN protocol based on specific symptoms arising during or after the transfusion.

  • Circulatory Overload (TACO): New or worsening respiratory symptoms and other diagnostic criteria.

  • Acute Lung Injury (TRALI): Acute respiratory distress occurring within 6 hours after transfusion.

3. Hemolytic Transfusion Reactions

  • Definition: Accelerated destruction of transfused RBCs due to antibody-mediated incompatibility.

  • Acute: Occurs within 24 hours; can present with fever, pain, hemoglobinuria, and shock.

  • Delayed: Often appears compatible at initial check; anamnestic response occurs in previously sensitized patients.

  • Common Antibodies: Anti-Jka, anti-Jkb, anti-K, Rh, and Duffy.

4. Febrile Non-Hemolytic Reactions (FNHTR)

  • Cause: Antibody mechanism reacting with donor leukocytes causing cytokine release.

  • Symptoms: Fever, malaise, headache, and nausea.

  • Management: Exclude other causes; usually mild and requires symptomatic treatment.

5. Allergic Reactions

  • Classification: Localized (like hives) vs systemic (anaphylaxis).

  • Symptoms: Includes conjunctival edema, tongue edema, flushing, and respiratory distress.

  • Management: Mild allergic reactions treated with antihistamines; severe reactions require epinephrine and corticosteroids. Bleeding reactions and anaphylaxis require intervention prioritizing patient safety.

6. TACO – Transfusion Associated Circulatory Overload

  • Definition: Diagnosed with new/worsening respiratory distress or edema within 12 hours of transfusion.

  • Incidence: Most common cause of major morbidity/mortality associated with transfusion; mortality near 10%.

  • Pathophysiology: Volume overload leading to elevated left arterial pressure and pulmonary edema.

7. TRALI – Transfusion-Related Acute Lung Injury

  • Definition: Acute respiratory distress occurring during/within 6 hours post-transfusion; characterized by pulmonary infiltrates without evidence of fluid overload.

  • Incidence and Mortality: Up to 15% in critically ill patients; mortality estimated at 10-15%.

  • Differential Diagnosis: Distinguish from TACO, anaphylaxis, and bacterial contamination.

D. Plasmapheresis

1. Overview

  • Definition: Removal of plasma from patient's blood to eliminate harmful substances or replace deficient substances.

  • Applications: Indicated for conditions involving pathogenic immunoglobulins, immune complexes, or cytokines.

  • Therapeutic Plasma Exchange (TPE): To remove life-threatening substances or replenish deficient components.

2. Mechanisms of TPE

  • Substance Removal: Effectiveness based on molecular weight, distribution, and half-life of substances.

  • Monitoring: Requires patient vigilance to assess biochemical status and relevant laboratory tests during TPE.

  • Adjustment: Anticipatory planning for drug levels and maintaining plasma volume.

3. Category Indications for Apheresis

  • Category I Indications: Conditions where apheresis is first-line therapy (e.g., Guillain-Barre syndrome, TTP).

  • Category II and III Indications: Second-line therapy and less established conditions.

  • Rescue Indications: Use of TPE in critical settings without strong evidence of efficacy.

4. Future Prospects for TPE

  • Potential Uses: In septic shock, severe COVID-19, and Alzheimer's disease studies are investigating TPE's role in managing these conditions.