Korean J Hematol.  2010 Dec;45(4):264-268. 10.5045/kjh.2010.45.4.264.

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

• Park R
• Song J
• An SS

• KMID: 2252039
• DOI: http://doi.org/10.5045/kjh.2010.45.4.264

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.

Keyword

Sepsis; TAFI isoforms; TAFIa; TAFIai; Diagnosis

MeSH Terms

Carboxypeptidase U
Enzyme-Linked Immunosorbent Assay
Fibrinolysin
Fibrinolysis
Humans
Organothiophosphorus Compounds
Plasma
Protein Isoforms
Sepsis
Solanum tuberosum
Thrombin
Carboxypeptidase U
Fibrinolysin
Organothiophosphorus Compounds
Protein Isoforms
Thrombin

Figure

• 

  Fig. 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.

• 

  Fig. 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.

• 

  Fig. 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.

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