REGULAR ARTICLEActivity and Antigen Levels of Thrombin-Activatable Fibrinolysis Inhibitor in Plasma of Patients With Disseminated Intravascular Coagulation
Section snippets
Materials and Methods
We examined 36 patients with DIC, 15 with pre-DIC, 63 without DIC and 17 healthy volunteers. The underlying diseases of the patients were leukemia (23 patients), malignant lymphoma (17 patients), infection (18 patients), solid cancer (16 patients), and other diseases (40 patients) (Table 1). The diagnosis of DIC was based on a modified version of the criteria established by the Japanese Ministry of Health and Welfare [9]. Patients with high levels thrombin–antithrombin III complex (TAT),
Results
The plasma levels of TAT, PPIC, D-dimer, thrombomodulin and tPA/PAI-1 complex (P<.01) were significantly higher in patients with DIC than in those with non-DIC and healthy control; the plasma levels of fibrinogen were significantly lower (P<.01) in patients with DIC than in those with non-DIC. The plasma levels of TAT, D-dimer and tPA/PAI-1 complex were significantly (P<.01) higher in patients with DIC than in those with pre-DIC. Plasma levels of D-dimer and thrombomodulin were significantly
Discussion
The plasma levels of TAT, PPIC and D-dimer were significantly increased and the plasma levels of fibrinogen were significantly decreased in patients with DIC as compared to non-DIC patients, suggesting the occurrence of hypercoagulability and hyperfibrinolysis in DIC patients [10]. Bleeding tendency is frequently observed in DIC, particularly in case of acute promyelocytic leukemia. Previous studies [10], [11] have showed that significant changes in the plasma levels of fibrinogen, PPIC and
Acknowledgements
This work was supported in part by a Grant-In-Aid for Cancer Research from the Ministry of Education, Science and Culture, Japan.
References (16)
- et al.
Thrombin, thrombomodulin and TAFI in the molecular link between coagulation and fibrinolysis
Thromb Haemostasis
(1997) - et al.
TAFI, or plasma procarboxypeptidase B, couples the coagulation and fibrinolytic cascades through the thrombin–thrombomodulin complex
J Biol Chem
(1996) - et al.
Characterisation of a carboxypeptidase in human serum distinct from carboxypeptidases N
J Clin Chem Clin Biochem
(1989) - et al.
Plasma carboxypeptides as regulators of the plasminogen system
J Clin Invest
(1995) - et al.
Prognosis in acute organ-system failure
Ann Surg
(1985) Multiple progressive or sequential systems failure
Arch Surg
(1975)- et al.
Plasminogen activator inhibitor 1. A new prognostic marker in septic shock
Thromb Haemostasis
(1989) - et al.
Generation in plasma of a fast-acting inhibitor of plasminogen activator in response to endotoxin stimulation
J Clin Invest
(1985)
Cited by (69)
Serum des-R prothrombin activation peptide fragment 2: A novel prognostic marker for disseminated intravascular coagulation
2013, Thrombosis ResearchCitation Excerpt :Since thrombin-activatable fibrinolysis inhibitor (TAFI) is one of the plasma carboxypeptidases that removes the carboxyl-terminal lysine residue from fibrin [19], TAFI may degrade the terminal arginine from prothrombin fragment 2. Furthermore, plasma TAFI levels have been shown to be significantly reduced in DIC [20,21]. Accordingly, the consumption of TAFI in the hypercoagulable state of overt DIC would have led to the decreased level of serum des-R F2.
Thrombin-activatable fibrinolysis inhibitor (TAFI) is enhanced in major trauma patients without infectious complications
2013, ImmunobiologyCitation Excerpt :TAFI deficient mice were protected from liver damage caused by intra-peritoneal administration of Escherichia coli (Morser et al. 2010; Renckens et al. 2005). In human studies, TAFI levels (activity and/or antigen) were decreased in septic patients but also in healthy volunteers with low-grade endotoxemia (Verbon et al. 2003; Watanabe et al. 2001; Zeerleder et al. 2006). However, as TAFI is involved in both the inflammation and coagulation systems but its role in trauma patients suffering from post-injury complications remain unclear, we hypothesized that in trauma patients both TAFI and TAFIa levels would inversely correlate with complications.
Activated thrombin-activatable fibrinolysis inhibitor (TAFIa) levels are decreased in patients with trauma-induced coagulopathy
2013, Thrombosis ResearchCitation Excerpt :Overall, these time courses for TAFI and TAFIa, mirror the current understanding of trauma-associated hemostatic changes, recently described by Gando et al. [4], with an initial activation of coagulation and fibrinolysis followed by a suppression of fibrinolysis. For non-trauma patients, Watanabe and coauthors [17], found that patients with disseminated intravascular coagulation (DIC) had both lower plasma TAFI antigen and TAFIa activity than non-DIC patients. They concluded, that TAFI might play an important role in the development of DIC and that the decrease in TAFI levels might result from increased utilization during DIC.
A low TAFI activity and insufficient activation of fibrinolysis by both plasmin and neutrophil elastase promote organ dysfunction in disseminated intravascular coagulation associated with sepsis
2012, Thrombosis ResearchCitation Excerpt :However, the most probable explanation is that excessive thrombin activation results in the consumption of TAFI, because a significant negative correlation was observed between soluble fibrin and TAFI activity, and a multiple regression analysis showed that soluble fibrin was an independent predictor of a decrease in TAFI activity. The same correlations were also observed between thrombin generation markers such as thrombin antithrombin complex, prothrombin fragment F1 + 2, and TAFI antigen and activity in previous studies, supporting the consumption-mediated decrease in TAFI levels [12,25]. The TAFI antigen and activity were significantly correlated in the present study, however, there were some differences in the dynamics between the levels of antigen and activity, especially in subjects with MODS.