Is the plasma kallikrein-kinin system antithrombotic?
Robert W. Colman TEMPLE UNIVERSITY SCHOOL OF MEDICINE In this issue, Shariat-Madar and colleagues provide evidence that BK B2 receptor knockout (BKB2R-/-) mice have a long bleeding time and delayed thrombosis that depends in part on nitric oxide and prostacyclin elevation produced by angiotensin II binding to an overexpressed receptor. In vitro, there was a markedly decreased concentration of a component of the plasma kallikrein-kinin system (KKS) that appeared to result in defective coagulation, which was shown by the prolonged aPTT in patients and experimental animals with low plasma levels of factor XII, prekallikrein, or high-molecular-weight kininogen (HK). However, hereditary deficiency of any of these proteins is not associated with excessive or spontaneous bleeding. Plasma kallikrein is a kinetically favorable activator of prourokinase to urokinase.1 Urokinase binds to its receptor, uPAR, on the endothelial-cell surface. Since prekallikrein binds to HK, which associates with th
