Unexpected citrate toxicity and severe hypocalcemia during apheresis

The citrate anticoagulant used during apheresis procedures is considered a safe medication because it is rapidly metabolized by the donor. However, acute, life-threatening hypocalcemia is possible if the infusion rate of citrate is increased.

A 54-year-old woman with metastatic breast cancer, but otherwise in good health, had just begun a fifth collection of hematopoietic peripheral blood progenitor cells by leukapheresis. The instrument's self-loading apheresis kit was primed uneventfully. Seven minutes into the procedure, the patient developed signs and symptoms suggesting severe hypocalcemia, including muscle spasms, chest pain, and hypotension. The citrate bag was discovered to have emptied, and a section of the anticoagulant tubing was protruding outside of the rotary pump. The patient's ionized calcium level was 0.64 mmol per L (normal range, 1.18-1.38 mmol/L). In subsequent experiments where the anticoagulant tubing was either improperly loaded at the outset or partially pulled out of the rotary pump, no instrument alarms sounded.

Citrate toxicity and life-threatening hypocalcemia can occur if the anticoagulant line of an apheresis instrument is not properly housed in its rotary pump or becomes disengaged during the procedure. Instrument manufacturers are encouraged to consider designs that allow the direct measurement of the volume of citrate delivered. In the interim, periodic visual and tactile confirmation of tubing placement during apheresis procedures is prudent.