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ADP‐degrading enzymes inhibit platelet activation in bile duct‐ligated rats
Author(s) -
WITTERS P.,
HOYLAERTS M.,
FRESON K.,
DE VOS R.,
VAN PELT J.,
NEVENS F.,
VAN GEET C.,
CASSIMAN D.
Publication year - 2010
Publication title -
journal of thrombosis and haemostasis
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.947
H-Index - 178
eISSN - 1538-7836
pISSN - 1538-7933
DOI - 10.1111/j.1538-7836.2009.03684.x
Subject(s) - platelet , medicine , endocrinology , ligation , chemistry , bile duct , hemostasis , platelet rich plasma
Summary. Background: The effect of cholestatic liver disease on primary hemostasis function remains ill‐defined. Objectives: To determine platelet function and identify the mechanisms involved in the observed platelet function in cholestatic rats. Methods: Platelet function was studied in a model of 2‐week bile duct ligation and compared to that in sham‐operated rats with and without a storage pool defect. Results: ADP‐induced and collagen‐induced platelet aggregation were clearly impaired following bile duct ligation ( P < 0.01 for areas under the curve). Crossover experiments, with sham platelets in bile duct‐ligated plasma and vice versa, demonstrated that this is due to inhibition by a plasmatic factor, as sham platelets aggregated less in cholestatic plasma ( P < 0.03) and to an equal extent as platelets from bile duct‐ligated rats when they were in the same sham or cholestatic plasma. Moreover, in bile duct‐ligated rats, platelet ultrastructure was unaffected and platelet aggregation was similar to that of sham platelets when resuspended in the same plasma ( P ‐value not significant). Aditionally, studies in storage pool‐deficient rats showed no role of platelet exhaustion. The plasmatic factor causing impaired aggregation was shown to be increased total activity of ADP‐degrading enzymes upon bile duct ligation ( P < 0.01), as there was no decreased aggregation with a stable ADP analog in bile duct‐ligated rats ( P ‐value not significant vs. sham‐operated rats). Furthermore, preincubation of plasma from bile duct‐ligated rats with ADP decreased aggregation more than was seen with sham plasma ( P < 0.01). Conclusions: Bile duct ligation does not affect intrinsic platelet function, but impairs platelet activation via release of ADP‐degrading enzymes in the circulation.