Concurrent marked hypocalcemia and hypokalemia are associated with clinically significant citrate toxicity during...

Citrate anticoagulation during peripheral blood stem cell (PBSC) collection decreases ionized calcium and may also reduce potassium. Although hypocalcemia is a well-recognized cause of citrate toxicity, the clinical significance of concurrent hypokalemia remains unclear. We evaluated whether concurrent marked hypocalcemia and marked hypokalemia were associated with citrate toxicity in PBSC donors.

This secondary analysis included healthy PBSC donors from a prospective study. Marked hypocalcemia and marked hypokalemia were defined as minimum ionized calcium ≤ 1.0 mmol/L and potassium ≤ 3.0 mmol/L, respectively. Donors were classified as neither decrease, either decrease alone, or concurrent decreases. The primary outcome was Grade ≥ 2 citrate toxicity. Firth-type modified Poisson regression with an improved robust variance estimator was used to estimate risk ratios (RRs).

Forty-two donors were included. Grade ≥ 2 citrate toxicity occurred in 1/29 donors (3.4%) with neither decrease, 2/8 (25.0%) with either decrease alone, and 2/5 (40.0%) with concurrent marked hypocalcemia and marked hypokalemia. Compared with neither decrease, concurrent decreases were associated with higher Grade ≥ 2 citrate toxicity risk in the primary adjusted Firth-type analysis (RR, 5.472; 95% CI, 1.126-26.590). In the adjusted continuous-exposure sensitivity analysis, RRs per 0.1 mmol/L increase were 0.462 and 1.244 for minimum ionized calcium and potassium, respectively. Categorical estimates had wide confidence intervals, warranting cautious interpretation.

Concurrent marked hypocalcemia and marked hypokalemia were associated with clinically significant citrate toxicity during PBSC collection. Concurrent electrolyte depletion may identify donors at increased risk of clinically significant citrate reactions.