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.
Horigome
Hitoshi
H
Department of Pediatrics, Institute of Clinical Medicine, University of Tsukuba, 1-1-1 Tennodai, Tsukuba, Ibaraki 305-8575, Japan. hhorigom@md.tsukuba.ac.jp
Murakami
Takashi
T
Isobe
Takeshi
T
Nagasawa
Toshiro
T
Matsui
Akira
A
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