The “Hageman” connection: Interrelationships of blood coagulation, fibrino(geno)lysis, kinin generation, and complement activation

Abstract

The activation pathways for the generation of enzymes involved in blood clotting, clot lysis, complement activation, and kinin generation are briefly reviewed. The interrelationship of the four systems is illustrated by the multiple functions of four key enzymes: Factor XIIa, kallikrein, plasmin, and C1 esterase. The pivotal role of Factor XIIa in establishing this connection is elucidated.

Immunoglobulin G and complement immunoreactivity in the cerebral cortex of patients with Rasmussen’s encephalitis

“…MAC capillary staining likely reflects activation of the CЈ cascade by clotting cascade proteases or surgical injury. 26 In contrast to this, sections cut from four of seven RE patients (two of five active cases, two of two chronic cases) and all CPE samples failed to demonstrate robust, repeatable cell labeling with anti-IgG, C4, C8, or MAC antibodies. In one CPE patient (Patient 9), labeling of neurons was detected in some sections stained with the anti-MAC antibody.…”

Livedoid Vasculopathy

“…Individuals with LA are at increased risk of thrombosis 39 ; antiphospholipid antibodies with an inhibitory effect on the activated protein C-protein S complex have been identified. 40 Cutaneous ulceration and necrosis have been described in association with circulating LA, 41 and LA and ACAs have been reported in patients with livedoid vasculopathy. 4,42,43 The prevalence of LA in our study group is higher than that in the healthy population (8%).…”

“…8 Complement deposition may be a consequence of activation of the coagulation pathway. 41 A few reports have also considered complement activation as a mediator of antiphospholipid antibodyinduced thrombosis and fetal loss. 49,50 Anticardiolipin antibodies were detected in 8 of our patients, with 5 of 7 specimens studied at immunofluorescence testing having complement in vessel walls.…”

Activated factor XII type A and B-type natriuretic peptide are complementary and incremental predictors of mortality in patients following admission with acute coronary syndrome

“…In vitro, aXIIa activates factor XI to factor XIa [2], which initiates a coagulation cascade containing factor IX (with factor VIII as a cofactor), factor X (with factor Va as a cofactor) and prothrombin, and finally results in the formation of active thrombin and fibrin polymers. XIIa also converts prekallikrein to kallikrein [3], which can result in the release of the vasoactive peptide bradykinin from high molecular weight kininogen (HMWK) [4], neutrophil activation [5] and interaction with the fibrinolytic system via conversion of plasminogen to plasmin [6,7]. Kallikrein is also capable of converting FXII to XIIa in two steps.…”