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Reducing circulating levels of plant sterols by ezetimibe favorably increases platelet counts in sitosterolemia patients (117.7)
Author(s) -
Othman Rgia,
Myrie Semone,
Mymin David,
Merkens Louise,
Roullet JeanBaptiste,
Steiner Robert,
Jones Peter
Publication year - 2014
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.28.1_supplement.117.7
Subject(s) - campesterol , platelet , medicine , bilirubin , ezetimibe , chemistry , hemoglobin , sterol , cholesterol , endocrinology
Macrothrombocytopenia and hemolytic anemia is correlated with increased plant sterol (PS) levels in patients (pts) with sitosterolemia (STSL). To determine if ezetimibe (EZ), a sterol‐absorption inhibitor, improves platelet count and morphology, and reduces markers of red blood cell hemolysis (RBCH: serum lactate dehydrogenase and bilirubin), 8 STSL pts were first taken off their EZ therapy for 14 wks then treated with EZ (10 mg/d) for another 14 wks. Blood samples were collected at the end of each study phase (off and on EZ). Plasma (pl) and RBC sterol concentrations were analysed by gas chromatography. Complete blood cell count and serum RBCH markers were determined by automated analyzers. In pts off EZ, platelet count was inversely related to pl campesterol (r=‐0.85, p<0.05), total PS (r=‐0.77, p<0.05) and total PS‐to‐cholesterol ratio (PS/Chol, r=‐0.96, p<0.01, n=7). Platelet size was positively correlated with pl total PS and PS/Chol ratio (all r=0.93, p<0.05, n=5), and RBC PS and PS/Chol were inversely related to mean corpuscular hemoglobin (Hb) concentration (MCHC) (p<0.01). EZ reduced pl and RBC sitosterol (‐35±4 and ‐28±3%), campesterol (‐47±4 and ‐40±4%), total PS (‐37±4 and ‐28±3%, all p<0.0001) and PS/Chol (‐27±4 and ‐28±4%, p<0.01). EZ increased platelet count (+23±9%, p<0.05), decreased platelet size (‐10±3%, p<0.05), and had no effect on RBCH, RBC mean corpuscular volume, or Hb concentration but slightly increased (p=0.03) MCHC. MCHC was negatively correlated with RBC (r=‐0.76) and pl (r=‐0.85, all p<0.05) campesterol in pts on EZ. In pts off EZ, RBC Chol was inversely related to sitosterol (p<0.05), total PS (p<0.05) and PS/Chol (p<0.01), suggesting reciprocity between Chol and PS. EZ tended to lower pl Chol concentrations (‐12±6%, p=0.09) but not RBC Chol (+0.3±3%, NS). These results indicated that EZ reduced pl and RBC PS contents, increased platelet count and decreased platelet size without affecting RBC Chol levels in STSL pts. Grant Funding Source : NIH, CIHR