Elevated levels of activated and inactivated thrombin-activatable fibrinolysis inhibitor in patients with sepsis

Rojin Park; Jaewoo Song; Seong Soo A. An

doi:10.5045/kjh.2010.45.4.264

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Original Article

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Korean J Hematol 2010; 45(4):

Published online December 31, 2010

https://doi.org/10.5045/kjh.2010.45.4.264

Elevated levels of activated and inactivated thrombin-activatable fibrinolysis inhibitor in patients with sepsis

Rojin Park¹, Jaewoo Song², and Seong Soo A. An^3*

Author Info. +

¹Department of Laboratory Medicine, Soonchunhyang University Hospital, Seoul, Korea.

²Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea.

³Department of Bionano Technology, Kyungwon University, Seongnam, Korea.

Correspondence to : Correspondence to Seong Soo A. An, Ph.D. Department of Bionano Technology, Kyungwon University, Sujung-gu, Seongnam 401-761, Korea. Tel: +82-31-750-8755, Fax: +82-31-750-8755, seongaan@kyungwon.ac.kr

Received: May 31, 2010; Revised: December 6, 2010; Accepted: December 8, 2010

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

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Abstract

Background

In sepsis, large scale inflammatory responses can cause extensive collateral damage to the vasculature, because both coagulation and fibrinolysis are activated unevenly. Thrombin-activatable fibrinolysis inhibitor (TAFI) plays a role in modulating fibrinolysis. Since TAFI can be activated by both thrombin and plasmin, it is thought to be affected in sepsis. Hence, activated and inactivated TAFI (TAFIa/ai) may be used to monitor changes in sepsis.

Methods

TAFIa/ai-specific in-house ELISA can detect only the TAFIa/ai form, because the ELISA capture agent is potato tuber carboxypeptidase inhibitor (PTCI), which has selective affinity towards only the TAFIa and TAFIai isoforms. TAFIa/ai levels in plasma from 25 patients with sepsis and 19 healthy volunteers were quantitated with the in-house ELISA.

Results

We observed increased TAFIa/ai levels in samples from patients with sepsis (48.7±9.3 ng/mL) than in samples from healthy individuals (10.5±5.9 ng/mL). In contrast, no difference in total TAFI concentration was obtained between sepsis patients and healthy controls. The results suggest that TAFI zymogen was activated and that TAFIa/ai accumulated in sepsis.

Conclusion

The detection of TAFIa/ai in plasma could provide a useful and simple diagnostic tool for sepsis. Uneven activation of both coagulation and fibrinolysis in sepsis could be caused by the activation of TAFI zymogen and elevation of TAFIa/ai. TAFIa/ai could be a novel marker to monitor sepsis and other blood-related disturbances.

Keywords Sepsis, TAFI isoforms, TAFIa, TAFIai, Diagnosis

Article

Original Article

Korean J Hematol 2010; 45(4): 264-268

Published online December 31, 2010 https://doi.org/10.5045/kjh.2010.45.4.264

Elevated levels of activated and inactivated thrombin-activatable fibrinolysis inhibitor in patients with sepsis

Rojin Park¹, Jaewoo Song², and Seong Soo A. An^3*

¹Department of Laboratory Medicine, Soonchunhyang University Hospital, Seoul, Korea.

²Department of Laboratory Medicine, Yonsei University College of Medicine, Seoul, Korea.

³Department of Bionano Technology, Kyungwon University, Seongnam, Korea.

Correspondence to: Correspondence to Seong Soo A. An, Ph.D. Department of Bionano Technology, Kyungwon University, Sujung-gu, Seongnam 401-761, Korea. Tel: +82-31-750-8755, Fax: +82-31-750-8755, seongaan@kyungwon.ac.kr

Received: May 31, 2010; Revised: December 6, 2010; Accepted: December 8, 2010

Abstract

Background

Methods

Results

Conclusion

Keywords: Sepsis, TAFI isoforms, TAFIa, TAFIai, Diagnosis

Abstract

Fig 1.

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Figure 1.

Thrombin-activatable fibrinolysis inhibitor (TAFI) isoforms in plasma. Thrombin/thrombomodulin or plasmin can activate TAFI (zymogen, 60 kDa), yielding TAFIa (active form, 35 kDa). Subsequently, TAFIa is thermally inactivated (triangle) to TAFIai (shaded). All 3 TAFI isoforms, TAFI, TAFIa, and TAFIai, are found in plasma. TAFIa/ai-specific ELISA measured only TAFIa and TAFIai, not TAFI.

Blood Research 2010; 45: 264-268https://doi.org/10.5045/kjh.2010.45.4.264

Fig 2.

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Figure 2.

Schematic diagram of activated and inactivated thrombin-activatable fibrinolysis inhibitor (TAFIa/ai)-specific ELISA. Diluted plasma was applied to a potato tuber carboxypeptidase inhibitor (PTCI)-coated microtiter plate and incubated for an hour at 37℃. Following washes, the TAFIa/ai bound to the PTCI-coated plate was quantitated with anti-human TAFI antibody and horseradish peroxidase (HRP)-conjugated anti-mouse IgG antibody.

Blood Research 2010; 45: 264-268https://doi.org/10.5045/kjh.2010.45.4.264

Fig 3.

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Figure 3.

Quantitation of activated and inactivated thrombin-activatable fibrinolysis inhibitor (TAFIa/ai) levels in plasma from sepsis patients. TAFIa/ai levels were quantitated in 25 plasma samples from sepsis patients (black circles) and in 19 healthy control plasma samples (white circles) using TAFIa/ai-specific ELISA. The average values of TAFIa/ai in sepsis and normal plasma samples were 48.7±9.3 ng/mL and 10.5±5.9 ng/mL (P<0.001), respectively. All sepsis patient plasma samples showed elevated TAFIa/ai levels.

Blood Research 2010; 45: 264-268https://doi.org/10.5045/kjh.2010.45.4.264

Table 1 . Comparison of activated and inactivated thrombin-activatable fibrinolysis inhibitor (TAFIa/ai)levels and other coagulation parameters between sepsis patients and healthy controls..

Abbreviations: FDP, Fibrin Degradation Product; PT, prothrombin time; aPTT, activated partial thromboplastin time; Plt, platelet..