Circulating platelet-derived microparticles with procoagulant activity may be a potential cause of thrombosis in uremic patients.
BACKGROUND
Clinical experience indicates that bleeding and thrombotic tendencies co-exist in uremic patients. Numerous studies have shown that platelet functional defects contribute to the bleeding tendency in uremic patients. In contrast, there are no solid studies clarifying the pathogenesis of the prothrombotic state in uremic patients. Platelet-derived microparticles (PMPs), which are small vesicles with procoagulant activity released from activated platelets, are thought to be involved in clinical thrombogenesis. This study addressed the question of why uremic patients are thrombophilic even though they have a bleeding tendency, focusing on the clinical significance of PMPs.


METHODS
The subjects were pre-dialyzed patients, patients under hemodialysis (HD) or continuous ambulatory peritoneal dialysis (CAPD) therapy, and age-matched healthy controls. Analyses of PMPs were performed using a flow cytometer. Annexin V was used to probe procoagulant activity of PMPs. The impacts of the HD procedure, arteriovenous (AV) fistula, and recombinant human erythropoietin (rHuEPO) treatment on the release of PMPs were additionally assessed.


RESULTS
Major results are: (1) PMP counts were significantly greater in each uremic group than in controls. The PMP counts were not different among three types of uremic groups; (2) PMP counts were significantly higher in uremic patients with thrombotic events than in those without thrombotic events; and (3) the HD procedure and existence of AV fistula did not affect PMP counts, but rHuEPO treatment possibly enhanced the PMP release in these patients.


CONCLUSIONS
Elevated PMP counts may trigger thrombosis in uremic patients. The primary cause of PMP elevation in uremia was not clarified in this study.
Ando
Minoru
M
Division of Nephrology, Department of Medicine, Tokyo Metropolitan Geriatric Hospital, and Department ofMedicine, Kidney Center, Tokyo Women's Medical University, Tokyo, Japan. nephrol@tmgh.metro.tokyo.jp
Iwata
Akiko
A
Ozeki
Yasushi
Y
Tsuchiya
Ken
K
Akiba
Takashi
T
Nihei
Hirosh
H
D000368:Aged; D001166:Arteriovenous Shunt, Surgical; D001777:Blood Coagulation; D001792:Blood Platelets / Q000502:physiology* / Q000648:ultrastructure; D004921:Erythropoietin / Q000008:administration & dosage; D005434:Flow Cytometry; D006801:Humans; D008875:Middle Aged; D010316:Particle Size; D010531:Peritoneal Dialysis, Continuous Ambulatory; D011994:Recombinant Proteins; D006435:Renal Dialysis; D013927:Thrombosis / Q000209:etiology* / Q000503:physiopathology*; D014511:Uremia / Q000150:complications* / Q000503:physiopathology* / Q000628:therapy
D011994:Recombinant Proteins; D004921:Erythropoietin