Increased P-selectin expression on platelets and decreased plasma thrombomodulin in Fontan patients.
BACKGROUND
Thromboembolic events account for significant morbidity and mortality after the Fontan procedure, but the underlying mechanisms remain unclear. P-selectin on platelets indicates platelet activation. Thrombomodulin (TM), a receptor for thrombin and a major anticoagulant proteoglycan on the endothelial membrane, reflects the anticoagulant activity of the endothelium. The present study investigated the hypothesis that the balance between platelet activation and endothelial biological function is impaired in Fontan patients.


RESULTS
Platelet P-selectin as a marker of platelet activation, plasma TM levels and protein C activity, as markers of anticoagulant activity of the endothelium, and thrombin-antithrombin complex III (TAT) were examined in 43 Fontan patients. P-selectin levels on platelets (4.5 +/-1.4 vs 3.4 +/-0.4 mean fluorescence intensity, P<0.001) and TAT levels (80.2 +/-322.6 vs 1.9 +/-0.9 ng/ml, P<0.05) were significantly higher in Fontan patients than in control subjects. On the other hand, plasma TM levels (1.5 +/-0.8 vs 2.2 +/-0.3 FU/ml, P<0.01) and protein C activity (71 +/-35 vs 118 +/-25%, P<0.001) were significantly lower in Fontan patients compared with controls. These abnormalities were not seen in patients after other surgical procedures for congenital heart disease.


CONCLUSIONS
Platelet activation is enhanced and endothelial function is impaired in patients after the Fontan procedure, which may partly explain the thromboembolic complications in Fontan patients.
Kajimoto
Hidemi
H
Department of Pediatric Cardiology, Heart Institute of Japan, Tokyo Women's Medical University, Tokyo, Japan.
Nakazawa
Makoto
M
Murasaki
Kagari
K
Hagiwara
Nobuhisa
N
Nakanishi
Toshio
T
D000293:Adolescent; D000328:Adult; D000990:Antithrombin III; D015415:Biomarkers / Q000097:blood; D001777:Blood Coagulation; D001792:Blood Platelets / Q000378:metabolism*; D016022:Case-Control Studies; D002648:Child; D002675:Child, Preschool; D015536:Down-Regulation; D004730:Endothelium, Vascular / Q000378:metabolism* / Q000503:physiopathology; D005260:Female; D018729:Fontan Procedure / Q000009:adverse effects*; D006801:Humans; D008297:Male; D019007:P-Selectin / Q000097:blood*; D010447:Peptide Hydrolases / Q000097:blood; D015539:Platelet Activation; D011486:Protein C / Q000378:metabolism; D012307:Risk Factors; D013923:Thromboembolism / Q000097:blood* / Q000209:etiology / Q000503:physiopathology; D018180:Thrombomodulin / Q000097:blood*; D015854:Up-Regulation; D055815:Young Adult
D015415:Biomarkers; D019007:P-Selectin; D011486:Protein C; D018180:Thrombomodulin; C046193:antithrombin III-protease complex; D000990:Antithrombin III; D010447:Peptide Hydrolases