Thrombin generation in acute coronary syndrome and stable coronary artery disease: dependence on plasma factor composition.
BACKGROUND
Acute coronary syndrome (ACS) is associated with thrombin formation, triggered by ruptured or eroded coronary atheroma. We investigated whether thrombin generation based on circulating coagulation protein levels, could distinguish between acute and stable coronary artery disease (CAD).


RESULTS
Plasma coagulation factor (F) compositions from 28 patients with ACS were obtained after onset of chest pain. Similar data were obtained from 25 age- and sex-matched patients with stable CAD. All individuals took aspirin. Patients on anticoagulant therapy were excluded. The groups were similar in demographic characteristics, comorbidities and concomitant treatment. Using each individual's coagulation protein composition, tissue factor (TF) initiated thrombin generation was assessed both computationally and empirically. TF pathway inhibitor (TFPI), antithrombin (AT), factor II (FII) and FVIII differed significantly (P < 0.01) between the groups, with levels of FII, FVIII and TFPI higher and AT lower in ACS patients. When thrombin generation profiles from individuals in each group were compared, simulated maximum thrombin levels (P < 0.01) and rates (P < 0.01) were 50% higher with ACS while the initiation phases of thrombin generation were shorter. Empirical reconstructions of the populations reproduced the thrombin generation profiles generated by the computational model. The differences between the thrombin generation profiles for each population were primarily dependent upon the collective contribution of AT, FII and FVIII.


CONCLUSIONS
Simulations of thrombin formation based on plasma composition can discriminate between acute and stable CAD.
Brummel-Ziedins
K
K
Department of Biochemistry, University of Vermont, VT 05446, USA. kathleen.brummel@uvm.edu
Undas
A
A
Orfeo
T
T
Gissel
M
M
Butenas
S
S
Zmudka
K
K
Mann
K G
KG
D054058:Acute Coronary Syndrome / Q000097:blood* / Q000175:diagnosis; D000990:Antithrombin III; D001779:Blood Coagulation Factors / Q000032:analysis*; D003324:Coronary Artery Disease / Q000097:blood* / Q000175:diagnosis; D003937:Diagnosis, Differential; D005169:Factor VIII; D006801:Humans; D015233:Models, Statistical; D011516:Prothrombin; D013917:Thrombin / Q000096:biosynthesis*
D001779:Blood Coagulation Factors; D000990:Antithrombin III; D011516:Prothrombin; D005169:Factor VIII; D013917:Thrombin