Changes of proteins induced by anticoagulants can be more sensitively detected in urine than in plasma.

The most fundamental property of biomarkers is change. But changes are hard to maintain in plasma since it is strictly controlled by homeostatic mechanisms of the body. There is no homeostatic mechanism for urine. Besides, urine is partly a filtration of blood, and systematic information can be reflected in urine. We hypothesize that change of blood can be reflected in urine more sensitively. Here we introduce the interference into the blood by two anticoagulants heparin or argatroban. Plasma and urine proteins were profiled by LC-MS/MS and then validated by Western blot in totally six SD female rats before and after the drug treatments. In argatroban treated group, with exactly the same experimental procedure and the same cutoff value for both plasma and urine proteins, 62 proteins changed in urine, only one of which changed in plasma. In heparin treated group, 27 proteins changed in urine but only three other proteins changed in plasma. Both LC-MS/MS and Western blot analyses demonstrated drug-induced increases in transferrin and hemopexin levels in urine but not in plasma. Our data indicates that urine may serve as a source for more sensitive detection of protein biomarkers than plasma.