American Journal of Hematology 41 :71-75 (1992)
Role of Endothelin in Disseminated lntravascular Coagulation H. Asakura, H. Jokaji, M. Saito, C. Uotani, 1. Kumabashiri, E. Morishita, M. Yamazaki, and T. Matsuda Department of Internal Medicine (Ill), Kanazawa University School of Medicine, 13-1 Takaramachi, Kanazawa, Japan
We examined the changes in plasma levels of endothelin-1 (ET-l), a potent vasoconstrictor peptide, in 47 cases of disseminated intravascular coagulation (DIC) to investigate the role of ET-1 in DIC and its relation to multiple organ failure (MOF). A significant elevation of plasma levels of ET-1 was observed in some cases of DIC, especially in patients with sepsis, blastic crisis of chronic myelogenous leukemia, and cancer. However, no such significant elevation was observed in patients with acute promyelocytic leukemia (APL), acute leukemias except for APL, or non-Hodgkin lymphoma. Plasma levels of El-1 were higher in patients with DIC with MOF than in those without MOF. Although the levels of ET-1 were decreasedor remained low with clinical improvement in most DIC patients, the levels were further increased or remained high in patients who showed no improvement in DIC. It is suggested that ET-1 must play an important role in further progression of MOF with the vasoconstriction and microcirculatory disorders. o 1992 Wlley-Liss, Inc. Key words: thrombomodulin, plasminogen activator inhibitor, acute promyelocytic leukemia
INTRODUCTION
Endothelin (ET)- 1 is a potent vasoconstrictor peptide with 2 1 amino acid residues first isolated from the supernatant of cultured porcine aortic endothelial cells [ 11. The existence of two other ETs, ET-2 and ET-3, has been predicted from analysis of human genomic DNA [2-4]. It was reported that the binding sites for ETs were extensively distributed and that ET-1 m-RNA was widely expressed in human tissue [5-71. These facts suggest that the majority of binding sites in vascular beds could be exposed to locally synthesized ET-1 and that ET-1 has effects on the underlying smooth muscle in most of the blood vessels in vivo. Although the role of ET in pathophysilogical states is not fully discussed, some reports have indicated the important role of ET in acute myocardial infarction [8], angina pectoris [9], hypertension [ 10,l I], intrauterine growth retardation [ 121, and chronic renal failure [ 13J. In this paper we examine the changes in plasma levels of ET- 1 in disseminated intravascular coagulation (DIC) caused by several underlying diseases and discuss the role of ET- 1 in DIC. 0 1992 Wiley-Liss, Inc.
MATERIALS AND METHODS Patients
The analysis of ET-1 was performed in 47 patients with DIC. They were classified according to the underlying diseases responsible for DIC as follows: 13 patients with acute promyelocytic leukemia (APL), 14 with acute leukemia except APL (AL), six with blastic crisis of chronic myelogenous leukemia (CMLIBC), five with nonHodgkin lymphoma (NHL), five with solid cancer, and four with sepsis. Leukemia was diagnosed according to the French-American British (FAB) criteria. The same analysis of ET- 1 was also performed in another group of patients without DIC: ten with AL, three with CML/BC, seven with NHL, five with solid cancer, and five with sepsis and also in 16 normal healthy subjects.
Received for Publication August 12, 1991; accepted January 30, 1992. Address reprint requests to H. Asakura, Department of Internal Medicine (111), Kanazawa University School of Medicine, 13-1 Takaramachi, Kanazawa, Japan.
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Asakura et al.
TABLE 1. Laboratory Findings for Patients With DIC Parameters PT (sec) Fbg (mg/dl) FDP (Fg/ml) TAT (ng/rnl) PIC (wug/ml)
Normal values
APL (n = 13)
AL (n = 14)
CML BC (n = 6)
NHL (n = 5)
Cancer (n = 5)
Sepsis (n = 4)
11.9-13.9 170-4 10
Role of Endothelin in Disseminated lntravascular Coagulation H. Asakura, H. Jokaji, M. Saito, C. Uotani, 1. Kumabashiri, E. Morishita, M. Yamazaki, and T. Matsuda Department of Internal Medicine (Ill), Kanazawa University School of Medicine, 13-1 Takaramachi, Kanazawa, Japan
We examined the changes in plasma levels of endothelin-1 (ET-l), a potent vasoconstrictor peptide, in 47 cases of disseminated intravascular coagulation (DIC) to investigate the role of ET-1 in DIC and its relation to multiple organ failure (MOF). A significant elevation of plasma levels of ET-1 was observed in some cases of DIC, especially in patients with sepsis, blastic crisis of chronic myelogenous leukemia, and cancer. However, no such significant elevation was observed in patients with acute promyelocytic leukemia (APL), acute leukemias except for APL, or non-Hodgkin lymphoma. Plasma levels of El-1 were higher in patients with DIC with MOF than in those without MOF. Although the levels of ET-1 were decreasedor remained low with clinical improvement in most DIC patients, the levels were further increased or remained high in patients who showed no improvement in DIC. It is suggested that ET-1 must play an important role in further progression of MOF with the vasoconstriction and microcirculatory disorders. o 1992 Wlley-Liss, Inc. Key words: thrombomodulin, plasminogen activator inhibitor, acute promyelocytic leukemia
INTRODUCTION
Endothelin (ET)- 1 is a potent vasoconstrictor peptide with 2 1 amino acid residues first isolated from the supernatant of cultured porcine aortic endothelial cells [ 11. The existence of two other ETs, ET-2 and ET-3, has been predicted from analysis of human genomic DNA [2-4]. It was reported that the binding sites for ETs were extensively distributed and that ET-1 m-RNA was widely expressed in human tissue [5-71. These facts suggest that the majority of binding sites in vascular beds could be exposed to locally synthesized ET-1 and that ET-1 has effects on the underlying smooth muscle in most of the blood vessels in vivo. Although the role of ET in pathophysilogical states is not fully discussed, some reports have indicated the important role of ET in acute myocardial infarction [8], angina pectoris [9], hypertension [ 10,l I], intrauterine growth retardation [ 121, and chronic renal failure [ 13J. In this paper we examine the changes in plasma levels of ET- 1 in disseminated intravascular coagulation (DIC) caused by several underlying diseases and discuss the role of ET- 1 in DIC. 0 1992 Wiley-Liss, Inc.
MATERIALS AND METHODS Patients
The analysis of ET-1 was performed in 47 patients with DIC. They were classified according to the underlying diseases responsible for DIC as follows: 13 patients with acute promyelocytic leukemia (APL), 14 with acute leukemia except APL (AL), six with blastic crisis of chronic myelogenous leukemia (CMLIBC), five with nonHodgkin lymphoma (NHL), five with solid cancer, and four with sepsis. Leukemia was diagnosed according to the French-American British (FAB) criteria. The same analysis of ET- 1 was also performed in another group of patients without DIC: ten with AL, three with CML/BC, seven with NHL, five with solid cancer, and five with sepsis and also in 16 normal healthy subjects.
Received for Publication August 12, 1991; accepted January 30, 1992. Address reprint requests to H. Asakura, Department of Internal Medicine (111), Kanazawa University School of Medicine, 13-1 Takaramachi, Kanazawa, Japan.
72
Asakura et al.
TABLE 1. Laboratory Findings for Patients With DIC Parameters PT (sec) Fbg (mg/dl) FDP (Fg/ml) TAT (ng/rnl) PIC (wug/ml)
Normal values
APL (n = 13)
AL (n = 14)
CML BC (n = 6)
NHL (n = 5)
Cancer (n = 5)
Sepsis (n = 4)
11.9-13.9 170-4 10
