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Blood Bank

Anticoagulants/Additives

Anticoagulant-preservative and additive solutions are essential cocktails designed to prevent clotting and provide the necessary fuel and environment for red blood cells to survive storage. The evolution from simple citrate solutions to complex Additive Solutions like AS-1 or AS-3 has dramatically increased the shelf life of RBCs (from 21 to 42 days), improving blood inventory management and availability. Understanding the role of each ingredient helps appreciate why these solutions are critical for transfusion medicine

Without anticoagulants and additives, whole blood would clot almost immediately, and red blood cells wouldn’t survive long enough outside the body to be useful for transfusion. These solutions are carefully formulated liquids present in the blood collection bags. Their primary goals are twofold:

  1. Prevent Clotting (Anticoagulation) To stop the coagulation cascade from activating the moment blood leaves the vein
  2. Maintain Cell Viability and Function (Preservation/Addition) To provide nutrients and a suitable chemical environment so that red blood cells, in particular, remain alive and functional during storage

Key Components and Their Roles

Let’s break down the common ingredients found in these solutions and why they are included:

  • Citrate (Sodium Citrate / Citric Acid)
    • Function: The primary anticoagulant
    • Mechanism: It works by chelating (binding) ionized calcium (Ca++). Calcium is essential for multiple steps in the coagulation cascade. By binding it up, citrate effectively stops clotting before it can start within the collection bag. Citric acid also helps lower the initial pH
  • Dextrose (Glucose)
    • Function: The primary energy source for red blood cells
    • Mechanism: RBCs rely on anaerobic glycolysis to produce ATP (adenosine triphosphate), the energy currency they need to maintain membrane integrity, ion pumps, and shape. Dextrose fuels this process throughout storage
  • Adenine * Function: A substrate for ATP synthesis * Mechanism: As RBCs consume ATP during storage, adenine provides a necessary building block for the cells to synthesize new ATP, helping to maintain energy levels for longer periods. This was a key addition that significantly extended RBC shelf life
  1. Phosphate (Sodium Biphosphate / Monobasic Sodium Phosphate)
    • Function: Acts as a buffer and supports ATP/2,3-DPG levels
    • Mechanism: Helps maintain a more optimal pH within the stored unit as acidic metabolic byproducts accumulate. Phosphate is also crucial for glycolysis and the synthesis of 2,3-diphosphoglycerate (2,3-DPG), a molecule important for oxygen release from hemoglobin (though 2,3-DPG levels inevitably fall during storage)
  • Mannitol (Found only in some Additive Solutions, e.g., AS-1, AS-5)
    • Function: Protects against storage-related hemolysis
    • Mechanism: Thought to act as an osmotic stabilizer, helping to strengthen the red blood cell membrane and reduce the amount of cell lysis (bursting) that occurs during storage
  • Saline (Sodium Chloride - Found only in Additive Solutions)
    • Function: Provides volume and appropriate osmolarity for the additive solution

Common Formulations and Their Impact on Storage

The specific combination and concentration of these ingredients determine the approved storage duration (shelf life) for Red Blood Cells. Here’s the evolution:

  • ACD (Acid-Citrate-Dextrose)
    • An older formulation
    • Components: Citrate, Citric Acid, Dextrose
    • RBC Shelf Life: 21 days at 1-6°C
  • CPD (Citrate-Phosphate-Dextrose)
    • Improvement over ACD by adding Phosphate
    • Components: Citrate, Citric Acid, Dextrose, Monobasic Sodium Phosphate
    • RBC Shelf Life: 21 days at 1-6°C. (Better maintenance of 2,3-DPG initially compared to ACD)
  • CP2D (Citrate-Phosphate-Double Dextrose)
    • Same as CPD but with twice the dextrose
    • Components: Citrate, Citric Acid, more Dextrose, Monobasic Sodium Phosphate
    • RBC Shelf Life: 21 days at 1-6°C. (Provides more fuel, but doesn’t extend maximum storage time)
  • CPDA-1 (Citrate-Phosphate-Dextrose-Adenine)
    • The major breakthrough adding Adenine
    • Components: Citrate, Citric Acid, Dextrose, Monobasic Sodium Phosphate, Adenine
    • RBC Shelf Life: 35 days at 1-6°C. (The adenine allows better ATP regeneration, significantly extending viability)
  • Additive Solutions (AS) - e.g., AS-1 (Adsol), AS-3 (Nutricel), AS-5 (Optisol), AS-7 (SOLX)
    • Concept: This is the current standard for most Red Blood Cell units. Whole blood is collected into a primary bag containing a minimal amount of anticoagulant-preservative (usually CPD). Soon after collection, most of the plasma is expressed off (to make FFP or other plasma components), and then ~100-110 mL of the Additive Solution from an attached satellite bag is added directly to the packed red cells
    • AS Components: Typically contain Saline, Adenine, Dextrose, and sometimes Mannitol (AS-1, AS-5) or extra Citrate and Phosphate (AS-3)
    • RBC Shelf Life: 42 days at 1-6°C
    • Advantages
      • Extends shelf life to 6 weeks
      • Results in RBCs with a lower viscosity (hematocrit usually 55-65%) which may improve transfusion flow
      • Allows for harvesting of more plasma from the original whole blood donation

Impact on Stored Components

  • Red Blood Cells: The primary focus of these solutions. They aim to minimize the “storage lesion” – the collection of biochemical and morphological changes occurring during storage (decreased ATP & 2,3-DPG, pH drop, potassium leakage, cell shape changes). Additives slow these changes but don’t eliminate them
  • Platelets: Collected with citrate anticoagulants (usually ACD or CPD). Platelet storage requires different conditions (room temperature with agitation) and specific Platelet Additive Solutions (PAS) are now often used to replace a portion of the plasma for storage, but the initial anticoagulant is still citrate-based
  • Plasma (FFP, PF24, etc.): The anticoagulant (CPD, CPDA-1, ACD) collected with the whole blood remains in the plasma component. The primary storage method is freezing, which halts biochemical degradation and preserves coagulation factor activity

Key Terms

  • Anticoagulant: A substance that prevents blood from clotting (e.g., Citrate)
  • Preservative: A substance that helps maintain the viability and function of cells during storage (e.g., Dextrose, Adenine, Phosphate)
  • Additive Solution (AS): A solution added to packed red blood cells after plasma removal, designed to optimize RBC survival during 42-day storage (contains Saline, Adenine, Dextrose +/- Mannitol)
  • Citrate: The primary anticoagulant used in blood collection, works by binding calcium
  • Dextrose: Glucose; the main energy source for stored RBCs
  • Adenine: A component necessary for RBCs to synthesize ATP, extending storage life
  • Phosphate: A buffer that helps maintain pH and supports ATP/2,3-DPG levels
  • Mannitol: An additive in some AS solutions that helps protect RBC membranes
  • Shelf Life: The maximum allowable time a blood component can be stored before expiration (e.g., 42 days for AS-preserved RBCs at 1-6°C)
  • Storage Lesion: The sum of biochemical and morphological changes that occur in red blood cells during storage