TY  - JOUR
AU  - Mulkidjanian, A. Y.
AU  - Cherepanov, D. A.
AU  - Heberle, J.
AU  - Junge, W.
TI  - Proton transfer dynamics at membrane/water interface and mechanism of biological energy conversion
JO  - Biochemistry
VL  - 70
SN  - 0006-2960
CY  - Columbus, Ohio
PB  - American Chemical Society
M1  - PreJuSER-45389
SP  - 251 - 256
PY  - 2005
N1  - Record converted from VDB: 12.11.2012
AB  - Pathogenesis of idiopathic pulmonary arterial hypertension (iPAH) includes endothelial dysfunction and in situ thrombosis. A hypercoagulable state has also been postulated but never demonstrated. Our objective was to determine whether patients with iPAH had a hypercoagulable state using calibrated automated thrombography (CAT), a new tool to phenotype coagulation in vitro.16 patients with iPAH and 29 controls were studied. In vitro platelet dependent coagulation phenotyping by CAT monitored the activity of thrombin generation over time. Plasma levels of soluble thrombomodulin, tissue factor pathway inhibitor (TFPI) and von Willebrand factor (VWF) were measured as endothelial biomarkers.Endogenous thrombin potential (ETP) in the absence of activated protein C (APC) tended to be increased in patients compared to controls (1769 versus 1656 nM.min; p=0.053). ETP was higher in the presence of APC 25 nM (ETP-APC) in patients (781 versus 494 nM.min; p=0.005). Five patients had ETP-APC higher than the 95th centile of controls. Other CAT parameters (lag time, peak thrombin and time to peak) were all consistent with some degree of hypercoagulability in patients. Regarding endothelial plasma biomarkers sTM was lower (28.4 versus 40.6 μg/l, p=0.0108) in patients; TFPI antigen and activity (respectively: 14.3 versus 10.5 μg/l, p=0.0167; 1.155 versus 1.070, p=0.0021) and VWF (1300 versus 976%, p=0.0108) were higher in patients.We have demonstrated that at least some patients with iPAH have a hypercoagulable phenotype.
KW  - Adolescent
KW  - Adult
KW  - Aged
KW  - Aged, 80 and over
KW  - Automation
KW  - Blood Coagulation Tests: methods
KW  - Blood Coagulation Tests: standards
KW  - Calibration
KW  - Case-Control Studies
KW  - Endothelium: metabolism
KW  - Endothelium: pathology
KW  - Female
KW  - Humans
KW  - Hypertension, Pulmonary: blood
KW  - Hypertension, Pulmonary: pathology
KW  - Hypertension, Pulmonary: physiopathology
KW  - Male
KW  - Middle Aged
KW  - Prospective Studies
KW  - Pulmonary Artery: metabolism
KW  - Pulmonary Artery: pathology
KW  - Thrombophilia: blood
KW  - Thrombophilia: diagnosis
KW  - Thrombophilia: pathology
KW  - Thrombophilia: physiopathology
KW  - Young Adult
KW  - J (WoSType)
LB  - PUB:(DE-HGF)16
C6  - pmid:20888030
UR  - <Go to ISI:>//WOS:000227736500020
DO  - DOI:10.1007/s10541-005-0108-1
UR  - https://juser.fz-juelich.de/record/45389
ER  -