Soluble P-selectin and thrombomodulin-protein C-Protein S pathway in cyanotic congenital heart disease with secondary erythrocytosis.
BACKGROUND
The aim of the study was to elucidate the roles of soluble P-selectin and thrombomodulin (TM)-protein C-protein S pathway in the pathogenesis of coagulopathy or thrombosis in cyanotic congenital heart disease (CCHD) with secondary erythrocytosis, and their correlations with hematocrit (Hct) value.


METHODS
We studied 27 patients (age: 4.8 to 34.9, median 15) with cyanotic congenital heart disease complicated by secondary erythrocytosis (hematocrit >45%) and 26 patients with acyanotic congenital heart disease (ACHD). Plasma levels of P-selectin, beta-thromboglobulin (beta-TG), platelet factor 4 (PF4), thrombomodulin, protein S and activity of protein C were compared between the two groups, and the relationships between these indices and hematocrit value were evaluated.


RESULTS
Plasma levels of P-selectin, beta-thromboglobulin and platelet factor 4 [mean (S.D.)] were significantly high in cyanotic patients comparing with acyanotic patients [138 (70.1) vs. 82.5 (28.7), p<0.001; 94.4 (74.0) vs. 54.9 (19.7), p<0.01; 45.4 (48.7) vs. 22.7 (11.9), p=0.020, respectively]. Those of thrombomodulin and protein S and activity of protein C were significantly low in cyanotic patients comparing with acyanotic patients [22.1 (9.69) vs. 34.3 (27.4), p=0.029; 90.7 (15.1) vs. 112 (21.4D), p<0.0001; 88.8 (19.7) vs. 106 (27.7), p<0.01, respectively]. P-selectin (r=0.445, p=0.001) and beta-thromboglobulin (r=0.311, p=0.025) correlated positively, and platelet count (r=-0.418, p=0.0015), protein C (r=-0.322, p=0.018) and protein S (r=-0.368, p=0.007) correlated negatively with hematocrit.


CONCLUSIONS
Chronic platelet activation and suppression of the thrombomodulin-protein C-protein S pathway might play an important role in coagulopathies identified in patients with erythrocytosis. Hematocrit is an important determinant of such abnormalities.
Department of Pediatrics, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. hhorigom@md.tsukuba.ac.jp
Hitoshi
H
Horigome
Takashi
T
Murakami
Takeshi
T
Isobe
Toshiro
T
Nagasawa
Akira
A
Matsui
D000293:Adolescent; D000328:Adult; D002648:Child; D002675:Child, Preschool; D003490:Cyanosis; D006330:Heart Defects, Congenital / Q000097:blood* / Q000150:complications; D006400:Hematocrit; D006801:Humans; D019007:P-Selectin / Q000097:blood*; D010976:Platelet Count; D010978:Platelet Factor 4 / Q000378:metabolism; D011086:Polycythemia / Q000097:blood* / Q000150:complications; D011486:Protein C / Q000378:metabolism*; D012044:Regression Analysis; D018180:Thrombomodulin / Q000097:blood*
D019007:P-Selectin; D011486:Protein C; D018180:Thrombomodulin; D010978:Platelet Factor 4