scholarly journals PENGUKURAN DAN APLIKASI KLINIK THROMBIN ACTIVATABLE FIBRINOLYSIS INHIBITOR

2018 ◽  
Vol 16 (1) ◽  
pp. 42
Author(s):  
Mansyur Arif
Keyword(s):  
Blood Loss ◽  
Clinical Application ◽  
Coagulation System ◽  
Fibrin Deposition ◽  
Thrombin Activatable Fibrinolysis Inhibitor ◽  
Fibrinolysis Inhibitor ◽  
Coagulation And Fibrinolysis ◽  
Excessive Blood Loss

Cross regulation of coagulation and fibrinolysis plays an important role in preserving a balanced hemostatic process. These process are exquisitely regulated and protect the organism from excessive blood loss or excessive fibrin deposition. Identification of ThrombinActivatable Fibrinolysis Inhibitor (TAFI) as an inhibitor of fibrinolysis and one of the main intermediates between coagulation andfibrinolysis, greatly improved our understanding of cross regulation of coagulation and fibrinolysis. As TAFI is an enzyme that is activatedby thrombin generated by the coagulation system, its activation is sensitive to the dynamics of the coagulation system. This review willdiscuss the role of TAFI and characterize it with respect to its activation, regulation, and clinical application.

Thrombin-activatable fibrinolysis inhibitor and the risk for recurrent venous thromboembolism

Blood ◽  
2004 ◽  
Vol 103 (10) ◽  
pp. 3773-3776 ◽  
Author(s):  
Sabine Eichinger ◽  
Verena Schönauer ◽  
Ansgar Weltermann ◽  
Erich Minar ◽  
Christine Bialonczyk ◽  
...  
Keyword(s):  
Venous Thromboembolism ◽  
Factor Ix ◽  
Coagulation System ◽  
Thrombin Activatable Fibrinolysis Inhibitor ◽  
Recurrent Venous Thromboembolism ◽  
Fibrinolysis Inhibitor ◽  
Viii And Ix ◽  
Low Levels ◽  
The Impact ◽  
Risk Factor For Recurrence

Abstract The impact of fibrinolysis for predicting the risk for recurrent venous thromboembolism (VTE) is low. We prospectively followed up 600 patients with a first VTE and evaluated the thrombin-activatable fibrinolysis inhibitor (TAFI) as a risk factor for recurrence. A high TAFI level (75th or higher percentile in thrombosis patients) was associated with a 2-fold higher risk for recurrence compared with lower levels. The probability of recurrence 2 years after anticoagulation was 14.5% (95% confidence interval [CI], 8.6-20.4) among patients with high TAFI levels and 6.8% (95% CI, 4.3-9.3) among patients with lower levels (P = .006). Our data also support the concept of a linkage between fibrinolysis and the coagulation system. Patients with high TAFI levels had significantly higher levels of factors XI, VIII, and IX, and a high risk of recurrence was seen among patients with high TAFI levels and high levels of one of these factors. The relative risk (RR) for recurrence was highest among patients with high TAFI and high factor XI (RR, 2.9; 95% CI, 1.3-6.9), high factor VIII (RR, 6.5; 95% CI, 2.9-14.8), or high factor IX (RR, 2.0; 95% CI, 1.0-3.9) levels compared with patients with low levels of TAFI and one of these factors.

Evaluation of the profibrinolytic properties of an anti-TAFI monoclonal antibody in a mouse thromboembolism model

Blood ◽  
2011 ◽  
Vol 117 (17) ◽  
pp. 4615-4622 ◽  
Author(s):  
Ellen Vercauteren ◽  
Jan Emmerechts ◽  
Miet Peeters ◽  
Marc F. Hoylaerts ◽  
Paul J. Declerck ◽  
...  
Keyword(s):  
Monoclonal Antibody ◽  
Clot Lysis ◽  
Fibrin Deposition ◽  
Thrombin Activatable Fibrinolysis Inhibitor ◽  
First Report ◽  
Fibrinolysis Inhibitor ◽  
Thrombotic Diseases

Abstract The enhancement of fibrinolysis constitutes a promising approach to treat thrombotic diseases. Activated thrombin activatable fibrinolysis inhibitor (TAFIa) attenuates fibrinolysis and is an attractive target to develop profibrinolytic drugs. TAFI can be activated by thrombin, thrombin/thrombomodulin, or plasmin, but the in vivo physiologic TAFI activator(s) are unknown. Here, we generated and characterized MA-TCK26D6, a monoclonal antibody raised against human TAFI, and examined its profibrinolytic properties in vitro and in vivo. In vitro, MA-TCK26D6 showed a strong profibrinolytic effect caused by inhibition of the plasmin-mediated TAFI activation. In vivo, MA-TCK26D6 significantly decreased fibrin deposition in the lungs of thromboembolism-induced mice. Moreover, in the presence of MA-TCK26D6, plasmin-α2-antiplasmin complexes in plasma of thromboembolism-induced mice were significantly increased compared with a control antibody, indicative of an acceleration of fibrinolysis through MA-TCK26D6. In this study, we show that plasmin is an important TAFI activator that hampers in vitro clot lysis. Furthermore, this is the first report on an anti-TAFI monoclonal antibody that demonstrates a strong profibrinolytic effect in a mouse thromboembolism model.

The C1542G and G505A Polymorphisms of Thrombin-Activatable Fibrinolysis Inhibitor (TAFI) in Patients with Thrombotic Microangiopathies.

Blood ◽  
2005 ◽  
Vol 106 (11) ◽  
pp. 2141-2141
Author(s):  
Christoph Sucker ◽  
Firuseh Farokhzad ◽  
Fieras Dahhan ◽  
Michael Schmitz ◽  
Gerd R. Hetzel ◽  
...  
Keyword(s):  
Odds Ratio ◽  
Arterial Thrombosis ◽  
Case Control ◽  
Thrombotic Microangiopathies ◽  
Thrombin Activatable Fibrinolysis Inhibitor ◽  
Increased Risk ◽  
Fibrinolysis Inhibitor ◽  
Inflammatory Processes ◽  
History Of

Abstract Background Thrombotic microangiopathies are characterized by vascular microthromboses, microangiopathic hemolytic anemia, and thrombocytopenia. Although recent research has elucidated the pathogenesis of these rare thrombotic disorders to some extent, the determinants contributing to the onset and modulating the severity are largely unknown. It is likely that risk factors of venous and arterial thrombosis also play a role in this clinical setting. Patients and Methods In the present study, we used a case-control and a case-only design, enrolling 23 patients (mean age [± SD] 35 ± 11 years) with a history of thrombotic microangiopathy and 689 control subjects to assess the role of gene polymorphisms of the thrombin-activatable fibrinolysis inhibitor (TAFI). Results The prevalence of the TAFI decreasing G/G genotype of the C1542G polymorphism was significantly higher in patients compared to controls (odds ratio 3.88; 95 % CI 1.07 – 11.47; p=0.02). In addition, in a case-only design the TAFI 1542 G allele was more prevalent in patients suffering from a severe course compared to those with a mild or moderate course (odds ratio 20; 95 % CI 1.85 – 216.17; p=0.009). By contrast, no such association was found for the TAFI G505A polymorphism. Conclusions Our study shows an association of the TAFI decreasing 1542 G/G genotype with an increased risk for thrombotic microangiopathies and a more severe course. This finding might be explained by the role of TAFI as an inhibitor of local inflammatory processes.

Role of Zinc Ions in Activation and Inactivation of Thrombin-Activatable Fibrinolysis Inhibitor†

Biochemistry ◽  
2002 ◽  
Vol 41 (4) ◽  
pp. 1211-1216 ◽  
Author(s):  
Pauline F. Marx ◽  
Bonno N. Bouma ◽  
Joost C. M. Meijers
Keyword(s):  
Zinc Ions ◽  
Thrombin Activatable Fibrinolysis Inhibitor ◽  
Fibrinolysis Inhibitor
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