American Journal of Hematology 37:147-151 (1991)
Plasma Level of Tumor Necrosis Factor in Disseminated Intravascular Coagulation Hideo Wada, Michiaki Ohiwa, Toshihiro Kaneko, Shigehisa Tamaki, Motoaki Tanigawa, Mikio Takagi, Yoshitaka Mori, and Shigeru Shirakawa Second Department of Internal Medicine, Mie University School of Medicine, Tsu City, Mie Ken, Japan
The plasma level of tumor necrosis factor (TNF) was determined in 20 normal individuals, 52 patients with disseminated intravascularcoagulation (DIC), 22 pre-DIC patients, and 39 non-DIC patients. TNF was not detected in the normal subjects, and the level was very low in non-DIC patients. However, the TNF level was significantly elevated in DIC patients, and it was moderately increased in pre-DIC patients shortly before the onset of DIC. This increase in circulating TNF may be associated with DIC. TNF was higher in DIC associated with solid cancer than in DIC associated with leukemia or sepsis. The increase in plasma TNF level was mildly correlated with DIC score, and it was significantly increased in patients with poor prognosis. However, the plasma TNF level in DIC patients with organ failure was not significantly different from those without organ failure. We conclude that the increase in circulating TNF reflects the pathogenic factors in DIC rather than being a consequence of organ failure due to DIC. Key words: TNF, organ failure, DIC
INTRODUCTION
Tumor necrosis factor (TNF) is an anti-tumoral cytokine discovered about 15 years ago and it first attracted attention as a possible anti-cancer agent without side effects [l]. However, it was thereafter identified as cachectin, a causative agent of chachexia, and a variety of biologic activities have been reported [2]. TNF is also involved in various inflammatory reactions [3] and is considered to have major effects on the hemostaticthrombogenic system, such as induction of the tissue factor activity by acting on the endothelial cells [4]. Because of these actions, TNF is increasingly regarded as a possible mediator of disseminated intravascular coagulation (DIC) and multiple organ failure (MOF). In this study, we measured the plasma level of TNF in DIC patients and evaluated the relationship between TNF and the pathology of DIC. SUBJECTS
The subjects were 20 normal volunteers, 52 DIC patients, 22 pre-DIC patients, and 39 non-DIC patients (Table I). Organ failure was observed in 24 of them. 0 1991 Wiley-Liss, Inc.
Blood samples from DIC patients was obtained at the time of diagnosis of DIC. Two weeks after treatment of DIC 25 patients were improved (good response group), but 27 patients were not improved (poor response group). The diagnosis of DIC was made according to the scoring system shown in Table 11, based on the diagnostic criteria by the Ministry of Health and Welfare [5]. The sum of the scores for 1, 2, 3, and 6 was 4 or more in leukemia patients and 7 or more in non-leukemia patients. Of the 52 DIC patients, 22 patients were examined within 1 week before the onset of DIC (usually 2 or 3 days before). The patients during this period were regarded as pre-DIC patients. Organ failure was considered to be present when the PaO, was 50 mmHg or less for the lung, when creatinine was 3 mg/dl or less for the kidney, when symptoms of shock of heart failure were present, and when the patient was in a coma or responded only to pain. Address reprint requests to Hideo Wada, Second Department of Internal Medicine, Mie University School of Medicine, 2- 174 Edobashi, Tsu City, Mie Ken 514, Japan. Received for publication April 18, 1990; accepted February 14, 1991.
148
Wada et al.
TABLE 1. Subjects
TABLE II. Diagnostic Criteria of DIC
DIC
Pre-DIC
N-DIC
Leukemia AML APL AMMoL CML, bc ALL ML stage IV Solid cancer Stomach cancer Hepatoma Lung cancer Esophagus carcinoma Colon cancer Breast cancer Others Sepsis
I . PT (sec)
15
Plasma Level of Tumor Necrosis Factor in Disseminated Intravascular Coagulation Hideo Wada, Michiaki Ohiwa, Toshihiro Kaneko, Shigehisa Tamaki, Motoaki Tanigawa, Mikio Takagi, Yoshitaka Mori, and Shigeru Shirakawa Second Department of Internal Medicine, Mie University School of Medicine, Tsu City, Mie Ken, Japan
The plasma level of tumor necrosis factor (TNF) was determined in 20 normal individuals, 52 patients with disseminated intravascularcoagulation (DIC), 22 pre-DIC patients, and 39 non-DIC patients. TNF was not detected in the normal subjects, and the level was very low in non-DIC patients. However, the TNF level was significantly elevated in DIC patients, and it was moderately increased in pre-DIC patients shortly before the onset of DIC. This increase in circulating TNF may be associated with DIC. TNF was higher in DIC associated with solid cancer than in DIC associated with leukemia or sepsis. The increase in plasma TNF level was mildly correlated with DIC score, and it was significantly increased in patients with poor prognosis. However, the plasma TNF level in DIC patients with organ failure was not significantly different from those without organ failure. We conclude that the increase in circulating TNF reflects the pathogenic factors in DIC rather than being a consequence of organ failure due to DIC. Key words: TNF, organ failure, DIC
INTRODUCTION
Tumor necrosis factor (TNF) is an anti-tumoral cytokine discovered about 15 years ago and it first attracted attention as a possible anti-cancer agent without side effects [l]. However, it was thereafter identified as cachectin, a causative agent of chachexia, and a variety of biologic activities have been reported [2]. TNF is also involved in various inflammatory reactions [3] and is considered to have major effects on the hemostaticthrombogenic system, such as induction of the tissue factor activity by acting on the endothelial cells [4]. Because of these actions, TNF is increasingly regarded as a possible mediator of disseminated intravascular coagulation (DIC) and multiple organ failure (MOF). In this study, we measured the plasma level of TNF in DIC patients and evaluated the relationship between TNF and the pathology of DIC. SUBJECTS
The subjects were 20 normal volunteers, 52 DIC patients, 22 pre-DIC patients, and 39 non-DIC patients (Table I). Organ failure was observed in 24 of them. 0 1991 Wiley-Liss, Inc.
Blood samples from DIC patients was obtained at the time of diagnosis of DIC. Two weeks after treatment of DIC 25 patients were improved (good response group), but 27 patients were not improved (poor response group). The diagnosis of DIC was made according to the scoring system shown in Table 11, based on the diagnostic criteria by the Ministry of Health and Welfare [5]. The sum of the scores for 1, 2, 3, and 6 was 4 or more in leukemia patients and 7 or more in non-leukemia patients. Of the 52 DIC patients, 22 patients were examined within 1 week before the onset of DIC (usually 2 or 3 days before). The patients during this period were regarded as pre-DIC patients. Organ failure was considered to be present when the PaO, was 50 mmHg or less for the lung, when creatinine was 3 mg/dl or less for the kidney, when symptoms of shock of heart failure were present, and when the patient was in a coma or responded only to pain. Address reprint requests to Hideo Wada, Second Department of Internal Medicine, Mie University School of Medicine, 2- 174 Edobashi, Tsu City, Mie Ken 514, Japan. Received for publication April 18, 1990; accepted February 14, 1991.
148
Wada et al.
TABLE 1. Subjects
TABLE II. Diagnostic Criteria of DIC
DIC
Pre-DIC
N-DIC
Leukemia AML APL AMMoL CML, bc ALL ML stage IV Solid cancer Stomach cancer Hepatoma Lung cancer Esophagus carcinoma Colon cancer Breast cancer Others Sepsis
I . PT (sec)
15
