The most common cause of febrile non-hemolytic transfusion reactions (FNHTRs) is recipient anti-leukocyte antibodies.

- FNHTRs typically occur within 1-6 hours after the transfusion and present with a fever and chills without evidence of hemolysis.
- These reactions are primarily caused by the recipient’s immune system recognizing and reacting against donor leukocytes (white blood cells) present in the transfused blood product.
- Specifically, recipient anti-leukocyte antibodies target donor leukocytes, leading to the release of cytokines such as interleukins and tumor necrosis factor, which induce fever.

Other options:
- Bacterial contamination of blood products is associated with a more severe, often rapid-onset septic transfusion reaction characterized by high fever, chills, and hypotension, but it is not the most common cause of FNHTRs.
- ABO incompatibility leads to acute hemolytic transfusion reactions, a different and more severe clinical syndrome involving hemolysis and possible renal failure.
- Citrate toxicity is related to the anticoagulant used in blood products and manifests as hypocalcemia symptoms, not febrile reactions.

Therefore, the presence of recipient anti-leukocyte antibodies reacting against donor leukocytes is the most common mechanism underlying FNHTRs.

Reference: Hoffbrand's Essential Hematology, 7th Edition, Chapter 10: Transfusion Medicine, pp. 229-231