Evidence for an increased generation of prostacyclin in the microvasculature and an impairment of the platelet alpha-granule release in chronic renal failure.
The formation of prostacyclin (PGI2) and thromboxane A2 and the release of beta-thromboglobulin (beta-TG) at the site of platelet-vessel wall interaction, i.e. in blood emerging from a standardized injury of the microvasculature made to determine bleeding time, was studied in patients with end-stage chronic renal failure undergoing regular haemodialysis and in normal subjects. In the uraemic patients, levels of 6-keto-prostaglandin F1 alpha (6-keto-PGF1 alpha) were 1.3-fold to 6.3-fold higher than the corresponding values in the control subjects indicating an increased PGI2 formation in chronic uraemia. Formation of thromboxane B2 (TxB2) at the site of plug formation in vivo and during whole blood clotting in vitro was similar in the uraemic subjects and in the normals excluding a major defect in platelet prostaglandin metabolism in chronic renal failure. Significantly smaller amounts of beta-TG were found in blood obtained from the site of vascular injury as well as after in vitro blood clotting in patients with chronic renal failure indicating an impairment of the alpha-granule release in chronic uraemia. We therefore conclude that the haemorrhagic diathesis commonly seen in patients with chronic renal failure is--at least partially--due to an acquired defect of the platelet alpha-granule release and an increased generation of PGI2 in the microvasculature.
Kyrle
P A
PA
Department of Medicine I, University of Vienna, Austria.
Stockenhuber
F
F
Brenner
B
B
Gössinger
H
H
Korninger
C
C
Pabinger
I
I
Sunder-Plassmann
G
G
Balcke
P
P
Lechner
K
K
D015121:6-Ketoprostaglandin F1 alpha / Q000096:biosynthesis; D000293:Adolescent; D000328:Adult; D000368:Aged; D001760:Bleeding Time; D001792:Blood Platelets / Q000378:metabolism*; D001808:Blood Vessels / Q000378:metabolism*; D002648:Child; D011464:Epoprostenol / Q000096:biosynthesis*; D005260:Female; D006801:Humans; D007676:Kidney Failure, Chronic / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D006435:Renal Dialysis; D013928:Thromboxane A2 / Q000096:biosynthesis; D013929:Thromboxane B2 / Q000096:biosynthesis; D001620:beta-Thromboglobulin / Q000096:biosynthesis
D001620:beta-Thromboglobulin; D013929:Thromboxane B2; D013928:Thromboxane A2; D015121:6-Ketoprostaglandin F1 alpha; D011464:Epoprostenol