What is Anticoagulant Citrate Dextrose (ACD)?
Anticoagulant citrate dextrose (ACD) is a sterile anticoagulant solution containing citric acid, sodium citrate, and dextrose (glucose) that prevents blood clotting by chelating calcium ions, making it widely used for blood collection, platelet preparation, cell salvage procedures, and therapeutic apheresis.
Composition and Mechanism
ACD exists in two main formulations 1, 2, 3:
- ACD Formula A (ACD-A): Contains 2.2 g sodium citrate dihydrate, 0.73 g anhydrous citric acid, and 2.45 g dextrose monohydrate per 100 mL water for injection
- ACD Formula B (ACD-B): Similar composition but in different concentrations
The anticoagulant works by binding ionized calcium through citrate, which is essential for the coagulation cascade 4, 5. The initial pH of ACD-A is approximately 4.98 6. When metabolized in the body, citrate yields both energy (0.59 kcal/mmol) and bicarbonate (3 mmol per mmol of citrate) 7.
Clinical Applications
Blood Collection and Processing
ACD is extensively used for:
- Platelet-rich plasma (PRP) preparation: ACD-A is one of the most effective anticoagulants for PRP, maintaining platelet integrity and preventing spontaneous activation better than heparin or standard citrate 1, 8
- Therapeutic apheresis: Standard anticoagulant for automated plasmapheresis procedures, typically used in 1:12 or 1:15 blood-to-anticoagulant ratios 9, 6
- Flow cytometry: Preferred for CD4+ T-cell counts and platelet autoantibody testing 10, 3
- Extracellular vesicle research: Efficiently inhibits platelet activation during blood collection 11, 12
Cell Salvage and Dialysis
- Intraoperative cell salvage: Alternative to heparin for anticoagulating salvaged blood, particularly in patients with heparin-induced thrombocytopenia 13
- Regional hemodialysis anticoagulation: ACD-A (0.113 mol/L citrate) produces less metabolic alkalosis compared to hypertonic tri-sodium citrate 14
Advantages Over Other Anticoagulants
ACD demonstrates superior performance in several contexts 1, 8:
- Better maintains platelet structural integrity and function compared to heparin or sodium citrate
- Prevents platelet spontaneous activation more effectively
- Results in higher release of growth factors (TGF-β1) from platelets
- Enhances cell proliferation in regenerative medicine applications
- Avoids heparin-related complications (bleeding, thrombocytopenia)
Important Caveats and Limitations
Metabolic Considerations
When used in large volumes (e.g., during continuous renal replacement therapy or massive transfusion), ACD can contribute significant calories 7:
- Citrate: 218 kcal/day
- Glucose: 295 kcal/day
- Total potential: 513+ kcal/day with certain protocols
Citrate metabolism requires adequate liver function 4, 5. Metabolism is impaired by:
- Hypoperfusion states
- Hypothermia
- Hepatic insufficiency
Calcium and pH Effects
- Hypocalcemia risk: Citrate chelates calcium; ionized calcium levels should be monitored during massive transfusion and maintained >0.9 mmol/L 4, 5
- Acidosis: Residual citrate in red blood cell concentrates can cause marked acidosis (pH <6.30) and hemodynamic instability during rapid transfusion 15
- Calcium restitution required: For regenerative medicine applications, calcium supplementation is necessary to restore normal cellular responses 16
Specific Contraindications
- Not recommended for single-platform absolute CD4+ counting: The liquid form makes accurate volume calculations difficult 10
- Dextrose component concerns: The glucose in ACD-A may confer anti-angiogenic and pro-inflammatory properties in some regenerative medicine applications, with inflammatory papules reported after intradermal injection 16
- Cell salvage in cardiac surgery: Free-flowing retransfusion of ACD-anticoagulated salvaged blood can cause major hemodynamic events from acute hypocalcemia and acidemia 15
Practical Considerations
For short-term catheter use (≤10 days), ACD-A performs similarly to heparin, but heparin appears superior for long-term use (>10 days) 9. When used for cell salvage, acid-citrate dextrose should be clearly labeled, and calcium/pH monitoring is essential during rapid reinfusion 13.