ABSTRACT
The hypothesis has been made that inhibition of prostacyclin (PG12) production may play a role in the pathogenesis of thrombosis in patients with the lupus anticoagulant (LA), but so far no evidence of reduced PG12 levels in vivo has been produced. We have tested the plasma levels of PG12 and thromboxane A2 (TXA2) and the platelet sensitivity to PG12 in 14 patients with and without LA and in 14 healthy controls. No significant difference in the prostanoid basal levels was detected among the groups; however, in some patients PG12 increments seemed to parallel the clinical course of the disease. Platelet sensitivity to exogenous PG12 was significantly enhanced in the LA + patients and correlated with PG12 values. We suggest that in these subjects additional factors, other than reduced PG12, may predispose to thrombosis.
Subject(s)
Blood Platelets/drug effects , Epoprostenol/pharmacology , Lupus Coagulation Inhibitor/physiology , Prostaglandins/metabolism , Adult , Blood Platelets/physiology , Epoprostenol/metabolism , Female , Humans , Lupus Erythematosus, Systemic/metabolism , Lupus Erythematosus, Systemic/physiopathology , Male , Middle Aged , Mixed Connective Tissue Disease/metabolism , Mixed Connective Tissue Disease/physiopathology , Scleroderma, Systemic/metabolism , Scleroderma, Systemic/physiopathology , Thromboxane A2/metabolismABSTRACT
Platelet sensitivity to prostacyclin (PG12) was determined in normal male and female subjects, and in patients with benign and malignant tumours of the breast. The IC50 overall mean values for PG12 on ADP-induced platelet aggregation were similar for normal men and women, being 0.97 +/- 0.05 ng ml-1 and 0.83 +/- 0.07 ng ml-1 respectively. However, there were significant differences in the IC50 values for women in the 1st (0.81 +/- 0.06 ng ml-1) vs. 2nd (1.37 +/- 0.13 ng ml-1) phase of the menstrual cycle; post-menopausal women gave similar values to normal males and to pre-menopausal women in the 1st phase of the cycle. No significant differences were found between normal subjects and patients with benign or malignant tumours of the breast when account was taken of the status of the patient in relation to the phase of the menstrual cycle and the menopause. The importance of the hormonal status in evaluating changes in platelet sensitivity in patients with breast cancer is strongly emphasised.
Subject(s)
Breast Neoplasms/blood , Epoprostenol/pharmacology , Platelet Aggregation/drug effects , Adenosine Diphosphate/pharmacology , Adult , Blood Platelets/physiology , Female , Humans , Male , Menopause , Menstruation , Middle AgedABSTRACT
The production of PGI2 (determined by bioassay), and of 6-keto-PGF1 alpha and TXB2 (determined by radioimmunoassay) by samples of human umbilical vessels have been measured. The results have been calculated on four bases: dry weight, wet weight, protein and DNA. There was a higher production of PGI2 and 6-keto-PGF1 alpha by umbilical veins than by umbilical arteries; no significant difference in TXB2 production was observed between umbilical veins and arteries. The ratio of 6-keto-PGF1 alpha: TXB2 production was about 100 for the samples of veins and about 40 for the samples of arteries. The best methods of expressing the results were on the bases of protein and DNA, the latter basis being marginally the best. The least satisfactory method for expressing the results was that based on dry weight. The physiological and practical implications of the results are discussed.
