We measured plasma levels of tissue factor (TF) and tissue factor pathway inhibitor (TFPI) in patients with thrombotic thrombocytopenic purpura (TTP) and disseminated intravascular coagulation (DIC) to examine the relationship between TFPI and vascular endothelial cell injury. TF antigen was detected in the plasma of healthy volunteers, and the levels were significantly increased in the patients with DIC, but decreased slightly in those with TTP. Plasma TFPI levels were significantly decreased in patients with TTP compared with those in healthy volunteers. The concentration of plasma thrombomodulin (TM) antigen was significantly higher in those with TTP than in normal volunteers. One month after treatment, TTP patients showed a significant decrease in plasma TM levels, and a significant increase, in plasma TFPI levels, but plasma levels of TF antigen were not significantly increased. As plasma TFPI/TF ratio was significantly increased after treatment, the hypercoagulable state was therefore improved after treatment. There was no significant difference in plasma TF and TFPI levels between those who achieved complete remission (CR) and those who died. However, plasma TM levels were significantly higher in those who died than in those who achieved CR. Plasma TFPI levels might reflect injury of vascular endothelial cells as do plasma TM levels, and decreased plasma TFPI/TF ratio and vascular endothelial cell injuries might play causative roles in TTP.
References
1
Rapaport SI.
The extrinsic pathway inhibitor: A regulation of tissue type factor-dependent blood coagulation. Thromb Haemost 1991; 66: 6-15
2
Broze GJ,
Warren LA,
Novotny WF,
Higuchi DA,
Girard TJ,
Miletich JP.
The lipoprotein-associated coagulation inhibitor that inhibits factor VII- tissue factor complex also inhibits Xa: Insight into its possible mechanism of action. Blood 1988; 71: 335-343
3
Wun TC,
Kretzmer KK,
Girard TJ,
Miletich JP,
Broze GJ.
Cloning and characterization of a cDNA coding for the lipoprotein associated coagulation inhibitor shows that it consists of three tandem Kunitz type inhibitory domains. J Biol Chem 1988; 263: 6001-6004
8
Amorosi EL,
Ultmann JE.
Thrombotic thrombocytopenic purpura – Report of the 16 cases and review of the literature. Medicine (Baltimore) 1966; 45: 139
12
Gulati SG,
Sordillo P,
Kemoin S,
Reich L,
Magill G,
Scheiner E,
Clarkson B.
Microangiopathic hemolytic anemia observed after treatment of epidermoid carcinoma with mitomycin C and 5-fluorouracil. Cancer 1980; 45: 2252-2257
14
Kobayashi N,
Maegawa T,
Takada M,
Tanaka H,
Gonmori H.
Criteria for diagnosis of DIC based on the analysis of clinical and laboratory findings in 345 DIC patients collected by the Research Committee on DIC in Japan. Bibl Haemotol 1987; 49: 265-275
17
Lian EC-Y,
Harkness DR,
Byrness JJ,
Wallach H,
Nunez R.
Presence of a platelet aggregation factor in the plasma of patients with thrombotic thrombocytopenic purpura (TTP) and its inhibition by normal plasma. Blood 1979; 53: 333-338
18
Takahashi H,
Tatewaki W,
Nakamura T,
Hanano M,
Wada K,
Shibata A.
Coagulation studies in thrombotic thrombocytopenic purpura, with special reference to von Willebrand factor and protein S. Amer J Hematol 1989; 30: 14-21
20
Wada H,
Ohiwa M,
Kaneko T,
Tamaki S,
Tanigawa M,
Takagi T,
Mori Y,
Shirakawa S.
Plasma level of tumor necrosis factor in disseminated intravascular coagulation. Amer J Hematol 1991; 37: 147-151
21
Wada H,
Tamaki S,
Tanigawa M,
Takagi M,
Mori Y,
Deguchi A,
Kata-yama N,
Yamamoto T,
Deguchi K,
Shirakawa S.
Plasma level of IL-1 in disseminated intravascular coagulation. Thromb Haemost 1991; 65: 364-368