Systemic blood coagulation activation in acute coronary syndromes

Abstract

We evaluated systemic alterations to the blood coagulation system that occur during a coronary thrombotic event. Peripheral blood coagulation in patients with acute coronary thrombosis was compared with that in people with stable coronary artery disease (CAD). Blood coagulation and platelet activation at the microvascular injury site were assessed using immunochemistry in 28 nonanticoagulated patients with acute myocardial infarction (AMI) versus 28 stable CAD patients matched for age, sex, risk factors, and medications. AMI was associated with increased maximum rates of thrombin-antithrombin complex generation (by 93.8%; P < .001), thrombin Bchain formation (by 57.1%; P < .001), prothrombin consumption (by 27.9%; P ‫؍‬ .012), fibrinogen consumption (by 27.0%; P ‫؍‬ .02), factor (f) Va light chain generation (by 44.2%; P ‫؍‬ .003), and accelerated fVa inactivation (by 76.1%; P < .001), and with enhanced release of platelet-derived soluble CD40 ligand (by 44.4%; P < .001). FVa heavy chain availability was similar in both groups because of enhanced formation and IntroductionAfter vascular injury, blood clotting is initiated when plasma factor (f) VIIa gains access to tissue factor (Tf). The resulting complex activates the plasma zymogens fIX and fX. 1 Factor Xa activates small amounts of thrombin, which activates platelets, and the procofactors fV and fVIII to their respective active forms. 2 These reactions result in the formation of the intrinsic fXase (fVIIIa-fIXa) and prothrombinase (fVa-fXa) on the activated platelet surface. 3 The major bolus of thrombin formed by the prothrombinase complex is largely responsible for the ultimate hemostatic process. 4 A potent, synergistic inhibitory system principally composed of tissue factor pathway inhibitor (TFPI), antithrombin (AT), and the thrombin-thrombomodulin (Tm)-catalyzed dynamic protein C (PC) system opposes thrombin generation. 5,6 The formation of fVa and its regulation by activated protein C (APC) are key processes for maintaining blood homeostasis. The fV activation process involves sequential cleavages to first produce a heavy chain (1-709) and subsequently a light chain resulting in the active cofactor. 7 The PC system inactivates fVa in a kinetically controlled series of cleavage reactions in which APC cleaves the heavy chain of fVa at 2 locations (R506 and R306); the resulting fVai can no longer function in the coagulation system. 8,9 The balance between activation and inactivation of fV is critical to the synergistic control of the coagulation process. 10 The activation of the Tf coagulation pathway appears to be central in arterial and venous thrombosis. 11 A major clinical manifestation of arterial thrombosis is represented by the acute coronary syndromes (ACS), which result from platelet-rich thrombus formation on the surface of ruptured or eroded atheromatosus plaque in the coronary artery. 12 Typical procoagulant abnormalities in ACS are increased circulating thrombin marker levels, such as prothrombin fragment 1.2 (F1.2) or thrombin-antithrombi...

Thrombus Aspiration Therapy and Coronary Thrombus Components in Patients with Acute ST-Elevation Myocardial Infarction

“…Moreover, MPO itself and MPO-derived reactive oxygen species have been shown to increase the expression of tissue factor, leading to a thrombotic state 91) , and influence erythrocyte deformation and aggregation, leading to membrane generation, rouleau formation and higher blood viscosity [92][93][94][95][96][97] . In addition, other cardiovascular risk factors (cigarette smoking, hyperglycemia) [98][99][100][101][102][103][104][105] and immune-inflammatory/oxidative stress-related factors (C-reactive protein, CD40 ligand, fibrinogen and D-dimer, lipoprotein (a)) 81, [106][107][108][109][110][111][112][113][114][115][116][117][118] have been reported to influence the platelet-fibrin clot structure and blood viscosity/erythrocyte aggregation. These findings are of considerable interest, since they suggest that some factors influencing blood thrombogenicity/ viscosity and erythrocyte properties (deformability and/or aggregability) may play important roles in the evolution of erythrocyte-rich large thrombi.…”

The endothelial protein C receptor (PROCR) Ser219Gly variant and risk of common thrombotic disorders: a HuGE review and meta-analysis of evidence from observational studies

“…32 All of these risk factors increase susceptibility to thrombus formation by modifying the coagulation and fibrinolytic systems. 33 The PROCR rs867186 variant has emerged as a candidate risk factor for both arterial and venous thrombotic disease because of the involvement of EPCR in APC-and FVII/FVIIa-mediated clotting and inflammation. However, evidence for an association between the PROCR rs867186 variant and arterial and venous thrombosis has been conflicting.…”

The Relationship between Hyperhomocysteinemia, Haemostatic Factors and Acute Coronary Syndrome in Southeastern Turkey: A Prospective, Comparative Study

“…However, it was reported in some clinical studies that the risk for AMI increased in individuals with elevated plasma procoagulant levels [39]. We found protein S (p = 0.42) and protein C (p = 0.130) levels significantly low in CAD group than controls.…”