Citrate as an Anticoagulant in Blood Products
Citrate is used as the anticoagulant in all standard blood components, including whole blood, packed red blood cells (PRBCs), fresh frozen plasma (FFP), and platelets. 1
Blood Products Containing Citrate
All Major Blood Components
- Whole blood is collected and stored with citrate-based anticoagulants 2
- Packed red blood cells (PRBCs) contain citrate in the preservative solution, with each standard unit (300-400 mL) containing up to 3 grams of citrate 3
- Fresh frozen plasma (FFP) and related plasma products (PF24, thawed plasma) contain particularly high citrate concentrations 3
- Platelets are collected and stored with citrate anticoagulants, with citrate present in significant amounts 1
Specific Citrate Formulations Used
The blood banking industry employs several citrate-based anticoagulant formulations 4:
- Citrate-phosphate-dextrose-adenine (CPDA) is used in a 1:8 ratio for whole blood collection 4
- Acid-citrate-dextrose formula A (ACD-A) and formula B (ACD-B) are commonly used during automated plasmapheresis in 1:12 or 1:15 ratios 4
- Citrate-phosphate-dextrose (CPD) and its variants (CPD-A) are effective anticoagulants for blood component preparation 1, 2
- Trisodium citrate at 0.109 M final concentration is the most commonly used anticoagulant 1
Mechanism of Action
Citrate functions as an anticoagulant by chelating ionized calcium in the blood, thereby preventing the calcium-dependent steps in the coagulation cascade 5. Calcium ions are essential cofactors for activating multiple coagulation factors (II, VII, IX, X) and are necessary for fibrin polymerization and platelet adhesion 5.
Critical Clinical Implications
Citrate Toxicity During Transfusion
When large volumes of blood products are transfused rapidly, citrate metabolism can be overwhelmed, leading to hypocalcemia 1:
- Hypocalcemia occurs in approximately 70% of patients receiving large volume transfusions 3
- Cardiac manifestations include dysrhythmias and impaired myocardial contractility 1, 3
- Coagulopathy develops with platelet dysfunction and decreased clot strength 3
High-Risk Scenarios
Citrate toxicity is exacerbated by 1, 3:
- Liver dysfunction (impaired citrate metabolism)
- Hypothermia (reduced metabolic clearance)
- Hypoperfusion (decreased hepatic metabolism)
- Renal insufficiency (impaired citrate clearance) 3
Monitoring and Management
- Monitor ionized calcium every 1-4 hours during massive transfusion protocols 3
- Target ionized calcium >0.9 mmol/L to support cardiovascular function and coagulation (normal range: 1.1-1.3 mmol/L) 3
- Administer calcium chloride (preferred over gluconate): 1 gram per liter of citrated blood products transfused, as calcium chloride 10% provides 270 mg elemental calcium per 10 mL versus only 90 mg in calcium gluconate 3
Product-Specific Considerations
FFP and platelets warrant particular vigilance as they contain the highest citrate concentrations among blood products 3. Standard coagulation laboratory tests may not reflect the true impact of hypocalcemia on coagulation, as blood samples are citrated then recalcified before analysis 3.