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.