Endothelin-1 as an aggravating factor of disseminated intravascular coagulation associated with malignant neoplasms

Cancer. 1994 Jan 1;73(1):191-5. doi: 10.1002/1097-0142(19940101)73:1<191::aid-cncr2820730133>3.0.co;2-x.

Abstract

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.

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Antithrombin III / analysis
  • Disseminated Intravascular Coagulation / blood
  • Disseminated Intravascular Coagulation / etiology*
  • Disseminated Intravascular Coagulation / physiopathology*
  • Endothelin-1
  • Endothelins / blood
  • Endothelins / physiology*
  • Female
  • Fibrin Fibrinogen Degradation Products / analysis
  • Fibrinogen / analysis
  • Humans
  • Lymphoma / complications
  • Male
  • Middle Aged
  • Multiple Myeloma / complications
  • Neoplasm Metastasis
  • Neoplasms / complications*
  • Platelet Count
  • Protein Precursors / blood
  • Protein Precursors / physiology*
  • Prothrombin Time

Substances

  • Endothelin-1
  • Endothelins
  • Fibrin Fibrinogen Degradation Products
  • Protein Precursors
  • Antithrombin III
  • Fibrinogen