Effect of Total-Body Cold Exposure on Plasma Concentrations of von Willebrand Factor, Endothelin-1 and Thrombomodulin in Systemic Lupus erythematosus Patients with or without Raynaud’s Phenomenon

Abstract

The effect of total-body cold exposure on plasma concentrations of von Willebrand factor (vWF), endothelin-1 (ET) and thrombomodulin (TM), all of which are considered to be generated from the endothelium, was studied in systemic lupus erythematosus (SLE) patients with and without Raynaud’s phenomenon. The plasma levels of vWF, ET and TM in SLE patients, irrespective of the presence of Raynaud’s phenomenon, were significantly higher than in normal controls even before the cold provocation test. After the cold provocation test, plasma levels of vWF and ET were significantly higher in SLE patients with Raynaud’s phenomenon than in those without and in normal controls. No significant increase in TM was observed in either the SLE patients or the controls. These results suggest that SLE patients, regardless of the presence of Raynaud’s phenomenon, are in a hypercoagulable state and that this state may be further intensified by cold exposure. Hence, it is concluded that we should consider antithrombotic therapy for SLE patients, especially those with Raynaud’s phenomenon, to prevent unwanted activation of the coagulation system and possible endothelial damage.

Victims of lethal hypothermia have decreased levels of thrombomodulin in myocardium and urine

“…The TM concentration was higher in blood, but lower in urine in hypothermia deaths, compared with the baseline values of living healthy subjects (plasma, 4.00 ng/ml; urine 15.97 ng/ml; unpublished data). It seems that short-term cold exposure is not able to produce any significant changes in the circulating TM level [11], whereas induced hypothermia has been shown to increase TM concentration in blood after approximately 2 h of exposure [8]. According to our recent rat study, however, severe hypothermia caused an initial decrease in the blood TM concentration followed by an increase after prolonged cold exposure, while opposite changes were observed in urine [9].…”

Participation of endogenous endothelins in delayed eosinophil and neutrophil recruitment in mouse pleurisy

“…Endothelin-1 levels are increased in plasma of guinea pigs sensitized and challenged with ovalbumin (OVA) [10], in rats treated with bacterial endotoxins (LPS) [11,12], as well as in patients with systemic lupus erythematosus [13,14] and sepsis [15]. Levels of endothelin-1 are also enhanced in bronchoalveolar lavage fluid of asthmatic patients [16,17], and are particularly high in synovial fluid of subjects with rheumatoid arthritis, osteoarthritis or gout [18,19].…”

Whole‐body cooling increases plasma endothelin‐1 levels in women with primary Raynaud's phenomenon

“…In previous studies in which the importance of ET‐1 in the pathophysiology of Raynaud's phenomenon was investigated, conflicting results have been reported. Plasma ET‐1 levels were found to increase after cold exposure in patients with Raynaud's phenomenon in three studies (Zamora et al ., 1990; Biondi et al ., 1991; Matsuda et al ., 1992) and to decrease in one (Bottomley & Goodfield, 1994).…”

“…Furthermore, in some studies the authors did not take factors such as age, sex and the origin of Raynaud's phenomenon into consideration (Matsuda et al ., 1992). It is a well‐known fact that plasma ET‐1 levels increase with age and are lower in women than in men regardless of age (Miyauchi et al ., 1992).…”