Periinterventional Management of Edoxaban in Major Procedures: Results from the DRESDEN NOAC REGISTRY

Background Edoxaban is a non-vitamin K dependent oral anticoagulant (NOAC) licensed for venous thromboembolism (VTE) treatment or stroke prevention in atrial fibrillation. Major surgical procedures are not uncommon in anticoagulated patients but data on perioperative edoxaban management are scarce

Rat tissue kallikrein releases a kallidin-like peptide from rat low-molecular-weight kininogen

1. The kallikrein–kinin system is subdivided into the plasma and tissue–kallikrein–kinin system, with bradykinin (BK) and kallidin (KAL) (Lys(0)-bradykinin) as functional peptides. This occurs in both humans and other mammals. Both peptides are released by plasma and tissue–kallikrein. BK, but not KAL, has been detected in rats until now. One can explain this observation by the structural differences found in the sequence of rat high- and low-molecular kininogen containing an Arg-residue instead of a Lys-residue in front of the N-terminus of the BK sequence. Nevertheless, we were able to measure a kallidin-like peptide (KLP), in rat plasma and urine, using a specific KAL antiserum. 2. In order to confirm our data, we isolated low-molecular-weight kininogen from rat plasma and incubated it with purified rat glandular kallikrein. The generated peptide was retained on a high-pressure liquid chromatography column and displaced by an excess of angiotensin I. The KLP-containing fraction was identified with the KLP radioimmunoassay. A specific ion signal with a mass to charge ratio (m/z) of 1216.73 was detected with matrix-assited laser desorption/ionization mass spectrometry. 3. As proposed earlier, the structure of this peptide is Arg(1)-KAL, instead of Lys(1)-KAL. The structural similarity between the Lys- and the Arg-residue explains the high crossreactivity (80%) of KLP with the specific KAL antibody. 4. The incubation of KLP with angiotensin-converting enzyme yields two molecules with masses of 913.4 and 729.3 containing the sequence H–Arg–Arg–Pro–Pro–Gly–Phe–Ser–Pro–OH and H–Arg–Arg–Pro–Pro–Gly–Phe–OH. The enzymatic cleavage could be inhibited by captopril. 5. The data suggest that in rats, as in other mammals, the tissue kallikrein–kinin system mediates its physiological effects via a kallidin-like peptide, which is Arg(1)-kallidin (Arg(0)-bradykinin)