Thrombin activatable fibrinolysis inhibitor and its relationship to fibrinolysis and inflammation during the acute and convalescent phase of ischemic stroke

Abstract

To investigate thrombin activatable fibrinolysis inhibitor (TAFI) in ischemic stroke and its relationship to fibrinolysis and inflammation, we investigated 32 patients with ischemic stroke during the acute phase and after 60 days. TAFI antigen levels, global markers of hemostasis (coagulation and fibrinolysis) and inflammatory markers were measured in plasma. TAFI antigen levels were significantly elevated at admission (128%; 109-151%) and at day 1 (129%; 109-152%) compared with day 60 (108%; 91-127%; both P < 0.01) and with healthy control individuals (99%; 76-122%; P < 0.05). In parallel, fibrinolysis assessed as the overall fibrinolysis potential (OFP), part of the overall hemostatic potential assay (OHP), was decreased at all time points compared with control individuals (P < 0.01 for all) and was found to be inversely related to TAFI (r = -0.40; P = 0.0008; n = 20). The OFP and the overall coagulation potential (another part of the OHP assay), and to a lesser degree TAFI, showed significant relationships to C-reactive protein and fibrinogen. In conclusion, elevated TAFI antigen levels may be a consequence of an acute phase reaction, and together with a depressed OFP suggest impaired fibrinolysis in patients with acute ischemic stroke. The OHP method may be useful as a complement to standard hemostatic variables in evaluating hemostasis in stroke patients.

The decrease in procarboxypeptidase U (TAFI) concentration in acute ischemic stroke correlates with stroke severity, evolution and outcome

“…Previous studies on proCPU plasma concentration in an acute ischemic stroke population reported higher proCPU levels in stroke patients in comparison with controls [24,25]. In our present study, mean proCPU levels at admission of the total stroke population amounted to 966 ± 179 U L )1 .…”

“…Several epidemiological studies demonstrated that plasma proCPU concentrations are related to thrombotic tendency [19,20]. Association between plasma proCPU levels and the occurrence of ischemic stroke was reported in a number of clinical studies [21][22][23][24][25]. Recently, we demonstrated in patients with ischemic stroke receiving thrombolytic therapy, that activation of the proCPU system takes place and results in measurable amounts of CPU in the circulation [4].…”

Innovative thrombolytic strategy using a heterodimer diabody against TAFI and PAI-1 in mouse models of thrombosis and stroke

“…In line with this observation, TAFI and PAI-1 levels are increased in patients suffering from ischemic stroke, often correlating with stroke severity, suggesting a negative impact of these antifibrinolytic molecules in stroke development. 8,[44][45][46][47][48][49][50] Interestingly, whereas the diabody ameliorated the outcome in this model, tPA has a controversial effect, potentially through aggravating neuronal damage after focal cerebral ischemia. 51 As a control, an in vitro neurotoxicity assay was performed with or without N-methyl-D-aspartate and demonstrated the absence of any neurotoxicity associated with the diabody (supplemental Figure 4).…”

Increased thrombin-activatable fibrinolysis inhibitor and decreased tissue factor pathway inhibitor in patients with hyperthyroidism

“…The thrombin-activatable fibrinolysis inhibitor (TAFI), an enzyme that may act as a link between coagulation and fibrinolysis, inhibits fibrinolysis by removing carboxyterminal residues from partially degraded fibrin, thus decreasing plasminogen binding on the surface of fibrin [15,16]. Increased TAFI levels have been associated with several thrombotic conditions like venous thromboembolism [17,18] and ischemic stroke [19,20].…”