Skip to main content

Blood Bank

Fractionation Products

This section moves beyond the blood components prepared directly in a hospital blood bank (like RBCs, platelets, FFP, Cryo) and delves into highly purified protein products derived from large pools of human plasma through industrial manufacturing processes. These are essentially plasma-derived pharmaceuticals

What are Fractionation Products?

  • Definition: Therapeutic protein concentrates obtained through a large-scale industrial process called plasma fractionation. This process separates and purifies specific proteins from large pools of human plasma collected primarily as Source Plasma (via plasmapheresis) or sometimes Recovered Plasma (plasma from whole blood donations not used for direct transfusion)
  • Process (Simplified): Involves sophisticated biochemical and biophysical techniques, traditionally starting with the Cohn fractionation method (using cold ethanol precipitation) and now often incorporating advanced methods like chromatography (ion exchange, affinity), filtration, and ultrafiltration. A critical part of the manufacturing process includes rigorous steps specifically designed to inactivate or remove viruses (e.g., solvent/detergent treatment, pasteurization, nanofiltration), providing a very high margin of viral safety compared to single-donor plasma components

Key Differences from Standard Blood Components (FFP, Cryo)

Feature Fractionation Products Standard Plasma Components (FFP, Cryo)
Source Large pools (thousands) of plasma donors Single donor (or small pool for Cryo)
Processing Industrial manufacturing (pharmaceutical) Blood bank laboratory separation
Composition Highly purified specific protein(s) Mixture of many plasma proteins
Concentration Standardized, high concentration Variable concentration
Viral Safety Multiple inactivation/removal steps Donor screening & testing only
Storage Often lyophilized (powder), room temp/fridge Frozen (FFP, Cryo)
Shelf Life Long (often years) 1 year (frozen), short post-thaw
Volume Small volume for reconstitution Larger volume (FFP ~250mL)
Regulation As specific pharmaceutical drugs As blood components

Major Plasma Fractionation Products

Here are some of the most important therapeutic products derived from plasma fractionation:

  • Albumin
    • Function: Maintains plasma oncotic pressure (keeps fluid in blood vessels), transports various substances
    • Concentrations: Available typically as 5% (iso-oncotic) and 25% (hyper-oncotic) solutions
    • Indications: Volume expansion (especially 5%), treatment of edema in hypoalbuminemia (e.g., liver disease, nephrotic syndrome), burns, support during plasma exchange
  • Intravenous Immunoglobulin (IVIG)
    • Function: Provides passive immunity (contains a broad spectrum of IgG antibodies), also has complex immunomodulatory effects
    • Indications: Primary immunodeficiency diseases (PIDs), autoimmune disorders (e.g., Immune Thrombocytopenic Purpura - ITP, Guillain-BarrĂ© Syndrome - GBS, Chronic Inflammatory Demyelinating Polyneuropathy - CIDP), Kawasaki disease, prevention/treatment of infections in immunocompromised hosts. (Subcutaneous preparations - SCIG - are also available)
  • Factor VIII Concentrate
    • Function: Essential coagulation factor for the intrinsic pathway
    • Indications: Treatment and prevention of bleeding in Hemophilia A (Factor VIII deficiency). Largely replaced Cryoprecipitate/FFP for this indication due to purity, standardized dosing, and enhanced viral safety. (Recombinant Factor VIII is also widely used)
  • Factor IX Concentrate
    • Function: Essential coagulation factor for the intrinsic pathway
    • Indications: Treatment and prevention of bleeding in Hemophilia B (Factor IX deficiency). (Recombinant Factor IX is also widely used)
  • Prothrombin Complex Concentrates (PCCs)
    • Function: Contains varying combinations of the Vitamin K-dependent coagulation factors: Factor II (Prothrombin), Factor VII, Factor IX, and Factor X. May also contain anticoagulant proteins C and S
    • Types: 3-Factor PCCs (low Factor VII) and 4-Factor PCCs
    • Indications: Urgent reversal of Warfarin (Coumadin) anticoagulation, treatment of bleeding due to deficiency of one or more Vitamin K-dependent factors (e.g., liver disease, specific factor deficiencies if single concentrates unavailable)
  • Fibrinogen Concentrate (Factor I Concentrate)
    • Function: Precursor to fibrin, essential for clot structure
    • Indications: Treatment of bleeding in congenital afibrinogenemia/hypofibrinogenemia or acquired hypofibrinogenemia (e.g., DIC, massive transfusion) when Cryoprecipitate is unavailable or large volumes would be required
  • Alpha-1 Antitrypsin (AAT)
    • Function: Inhibits proteases (like neutrophil elastase) in the lungs
    • Indications: Augmentation therapy for patients with congenital AAT deficiency leading to emphysema
  • Antithrombin (AT) Concentrate (Formerly ATIII)
    • Function: Major inhibitor of thrombin and other coagulation proteases (natural anticoagulant)
    • Indications: Treatment of hereditary AT deficiency, especially during surgery or pregnancy/delivery
  • C1 Esterase Inhibitor (C1-INH) Concentrate
    • Function: Regulates activation of the complement and contact (kallikrein-kinin) systems
    • Indications: Treatment and prevention of attacks in patients with Hereditary Angioedema (HAE)

Advantages of Fractionation Products

  • Targeted Therapy: Allows replacement of only the specific deficient protein
  • Enhanced Viral Safety: Multiple viral inactivation/removal steps significantly reduce the risk of transmitting known viruses
  • Standardized Dosing: Products have defined concentrations and activity levels (often in International Units - IU), allowing for precise dosing
  • Convenience: Many are lyophilized (freeze-dried powder), allowing for room temperature or refrigerated storage and easier transport/reconstitution compared to frozen plasma products
  • Reduced Volume: Provides a therapeutic dose in a much smaller volume than plasma or cryoprecipitate, reducing the risk of circulatory overload

Disadvantages / Considerations

  • Cost: Often significantly more expensive than standard plasma components
  • Source Material: Reliant on a consistent supply of human plasma donations
  • Potential for Reactions: Although highly purified, allergic or anaphylactic reactions can still occur
  • Thrombotic Risk: Particularly associated with PCCs due to the concentration of procoagulant factors
  • Transmission of Novel Pathogens: While current methods are effective against known viruses, the theoretical risk of transmitting new or prion agents (like vCJD) from pooled plasma, although extremely low, cannot be completely eliminated

Key Terms

  • Plasma Fractionation: Industrial process to separate and purify proteins from large pools of plasma
  • Source Plasma: Plasma collected via apheresis specifically for manufacturing into derivatives
  • Recovered Plasma: Plasma separated from whole blood donations, sometimes used for fractionation
  • Cohn Fractionation: Classic method using cold ethanol precipitation
  • Chromatography: Purification technique based on differential binding of proteins to a stationary phase
  • Viral Inactivation/Removal: Mandatory steps in manufacturing (e.g., solvent/detergent, pasteurization, nanofiltration) to enhance safety
  • Lyophilized: Freeze-dried into a powder for stability and reconstitution
  • International Unit (IU): Standardized measure of biological activity for many coagulation factors and other proteins
  • Oncotic Pressure: Pressure exerted by proteins (especially albumin) in plasma that helps hold fluid within blood vessels