Endothelin-1 as an aggravating factor of disseminated intravascular coagulation associated with malignant neoplasms.
BACKGROUND
Vascular endothelial damage may play an important role in the pathophysiology of disseminated intravascular coagulation (DIC), a frequent complication of malignant neoplasms. It may mediate a variety of triggering events to initiate DIC and platelet aggregation, which in turn leads to additional endothelial destruction. If so, endothelin-1 (ET-1), the most potent vasoconstrictor of naturally occurring pressor substances known, may leak from injured endothelial cells and aggravate the disease process.


METHODS
The study included 36 patients with various malignant neoplasms in whom DIC developed. The authors measured plasma levels of ET-1 and big ET-1, a precursor peptide of ET-1, in these patients and compared them with other laboratory abnormalities during the course of DIC.


RESULTS
Plasma ET-1 and big ET-1 levels were elevated in most patients with DIC. When compared with the results of other diagnostic tests, elevated plasma big ET-1 was the most frequently found abnormality associated with DIC. Elevation of plasma ET-1 and big ET-1 levels was closely related to the initiation and progression of DIC and provided a higher degree of sensitivity and specificity than did other indicators in assessing patients with cancer and DIC.


CONCLUSIONS
Vascular endothelial damage with the resultant increases in plasma ET-1 and big ET-1 levels is universally associated with DIC caused by malignancy. Excessive secretion or leakage of ET-1 and big ET-1 from injured endothelial cells may cause vasospasm and aggravate the DIC process by facilitating the formation of intravascular microthrombi, ultimately leading to ischemic end-organ dysfunction. Plasma ET-1 and big ET-1 are sensitive and specific markers for vascular endothelial injury in DIC.
Ishibashi
M
M
Fourth Department of Medicine, Teikyo University School of Medicine, Kawasaki, Japan.
Ito
N
N
Fujita
M
M
Furue
H
H
Yamaji
T
T
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000990:Antithrombin III / Q000032:analysis; D004211:Disseminated Intravascular Coagulation / Q000097:blood / Q000209:etiology* / Q000503:physiopathology*; D019332:Endothelin-1; D016232:Endothelins / Q000097:blood / Q000502:physiology*; D005260:Female; D005338:Fibrin Fibrinogen Degradation Products / Q000032:analysis; D005340:Fibrinogen / Q000032:analysis; D006801:Humans; D008223:Lymphoma / Q000150:complications; D008297:Male; D008875:Middle Aged; D009101:Multiple Myeloma / Q000150:complications; D009362:Neoplasm Metastasis; D009369:Neoplasms / Q000150:complications*; D010976:Platelet Count; D011498:Protein Precursors / Q000097:blood / Q000502:physiology*; D011517:Prothrombin Time
D019332:Endothelin-1; D016232:Endothelins; D005338:Fibrin Fibrinogen Degradation Products; D011498:Protein Precursors; D000990:Antithrombin III; D005340:Fibrinogen