High-Dose Platelet-Rich Plasma and Systemic Citrate Exposure: Implications for Calcium Homeostasis and Procedural Safety

Background: Platelet-rich plasma (PRP) has evolved from smallvolume
orthopaedic use to increasingly high-dose, high-volume
protocols across musculoskeletal, spinal, aesthetic, hair restoration,
and emerging systemic applications. Efforts to optimise platelet dose
have led to larger whole-blood collections and expanded reliance
on citrate-based anticoagulants. Although citrate anticoagulation is
well established in transfusion and apheresis medicine, its systemic
physiological implications have received comparatively limited
attention within regenerative practice.

Discussion: Citrate chelates ionised calcium and may acutely
reduce the biologically active calcium fraction, particularly when
delivery rate exceeds metabolic clearance or when compounded
by alkalosis or reduced buffering capacity. In transfusion medicine,
citrate-associated hypocalcaemia is anticipated and mitigated
through structured procedural safeguards. In contrast, regenerative
procedures are often performed outside haematology or apheresis
frameworks, and safety protocols may not consistently reflect
extracorporeal medicine standards.

Conclusion: Citrate anticoagulation remains appropriate and
safe in PRP preparation. However, as platelet dose and systemic
exposure increase - particularly with hybrid intravenous or
neuroaxial models - predictable electrolyte perturbations warrant
structured consideration. Proactive adoption of proportionate safety
measures, analogous to apheresis practice, represents a prudent
strategy for an evolving field.