What effect does plasmapheresis (plasma exchange) have on ionized calcium levels?

Effect of Plasmapheresis on Ionized Calcium

Plasmapheresis causes hypocalcemia by depleting ionized calcium through two mechanisms: direct removal of calcium-containing plasma and citrate-mediated chelation of calcium ions from the anticoagulant used during the procedure. 1, 2

Mechanisms of Calcium Depletion

Direct Depletion

• Replacement fluids (typically 4.5-5% human albumin solution) contain no calcium or magnesium, so exchanging patient plasma with these fluids directly depletes these ions from circulation 1
• The removal of calcium-containing plasma without replacement creates an immediate deficit 1

Citrate-Mediated Chelation

• Anticoagulant citrate dextrose solution (ACD-A) used during plasmapheresis chelates divalent cations, particularly ionized calcium, converting it to an inactive, anion-bound form 1, 2
• Studies demonstrate a net shift of serum calcium from the ionized and protein-bound fractions to the anion-bound fraction during citrate exposure 2
• When fresh frozen plasma (FFP) is used as replacement fluid at the end of the procedure, its citrate content further reduces the proportion of calcium that remains ionized 1

Clinical Impact on Calcium Levels

• Ionized calcium levels fall by 5-8% during plasmapheresis when prophylactic calcium supplementation is not provided 3, 4
• Without calcium supplementation, ionized calcium can drop to 0.78 mmol/L (below the critical threshold of 0.9 mmol/L) 1
• The fall in ionized calcium typically occurs after 40-60 minutes of the procedure 4

Clinical Consequences

• Hypocalcemic tetany is a known complication of plasmapheresis due to these calcium changes 1
• Symptomatic hypocalcemia occurs in 14% of procedures without adequate calcium supplementation 5
• Protein-bound calcium appears relatively labile and may shift to help maintain ionized calcium levels, but this compensatory mechanism is insufficient to prevent hypocalcemia 2

Prevention Strategies

Prophylactic calcium supplementation is essential to prevent symptomatic hypocalcemia during plasmapheresis:

• Adding calcium gluconate to replacement fluid (18.6 mg elemental calcium/100 mL of 5% albumin) maintains ionized calcium levels throughout the procedure and reduces symptomatic hypocalcemia to 2% 5
• Direct IV infusion of calcium gluconate at 1.6 g/h stabilizes plasma ionized calcium and prevents hypocalcemic reactions 4
• Supplementing albumin with 2 mmol/L calcium chloride and 0.8 mmol/L magnesium sulfate prevents the falls in ionized calcium that would otherwise reach critically low levels 1