Bradykinin Generation In Clinical Blood Samples: An Index Of Intrinsic Coagulation Activation

Abstract

Fibrinopeptide A (FPA) is frequently elevated in thromboembolism and DIC. As to the question which of the coagulation pathways (intrinsic vs extrinsic) is triggered under these conditions, measurement of FPA alone permits no answer. We measured both kallikrein (reflecting contact activation) and FPA in patients with classical DIC, established deep venous thrombosis (DVT) and pulmonary embolism (PE). Circulating kallikrein was measured as its capacity to generate bradykinin (BK) in whole blood (in the presence of kininase inhibitors) immediately after venipuncture. After incubation for 10 min. at room temp, kallikrein inhibitors were added. The increment of the BK concentration (ΔBK) -measured by radioimmunoassay- was used as marker of circulating kallikrein. The specificity and sensitivity of this method were superior to amidolytic assays for kallikrein.These data indicate the measurement of ΔBK is a potential tool to discriminate between intrinsic and extrinsic coagulation activation. In 2 patients with thromboembolism FPA normalised upon adequate anticogulant therapy, whereas ΔBK remained accerlerated for several weeks. This observation suggests that in these patients anticoagulant therapy was not adequate in eleminating the cause of coagulation activation. It is known that FPA is also frequently elevated in a variety of disorders not primarily associated with thrombosis or DIC. In 36 patients with chronic inflammatory diseases, FPA was elevated in 20 cases, whereas only in 1 patient ΔBK was accelerated (together with elevated FPA). We therefore conclude that the measurement of ΔBK is a more specific marker of intravascular coagulation activation, than the measurement of FPA.