Active tissue factor and activated factor XI in circulating blood of patients with systolic heart failure due to ischemic cardiomyopathy

Institute of Cardiology, Jagiellonian University Medical College, Kraków, Poland.
Polskie archiwum medycyny wewnȩtrznej (Impact Factor: 2.12). 09/2010; 120(9):334-40.
Source: PubMed


Elevated clotting factors and thrombin generation have been reported to occur in patients with heart failure (HF). Circulating activated factor XI (FXIa) and active tissue factor (TF) can be detected in acute coronary syndromes and stable angina.
We investigated circulating FXIa and active TF and their associations in patients with systolic HF due to ischemic cardiomyopathy.
In an observational study, we assessed 53 consecutive patients, aged below 75 years, with stable HF associated with documented coronary artery disease (CAD). Atrial fibrillation, recent thromboembolic events, and current anticoagulant therapy were the exclusion criteria. Plasma TF and FXIa activity was determined in clotting assays by measuring the response to inhibitory monoclonal antibodies.
Coagulant TF activity was detected in 20 patients (37.7%), and FXIa in 22 patients (41.5%). Patients with detectable TF activity and/or FXIa were younger, had a history of myocardial infarction more frequently, significantly higher F1+2 prothrombin fragments, larger left atrium (LA) and right ventricular diastolic diameter, and higher right ventricular systolic pressure than the remaining subjects (P ≤ 0.01 for all). Circulating FXIa was positively correlated with F1+2 levels (r = 0.69; P < 0.001).
Circulating active TF and FXIa occurred in about 40% of patients with systolic HF due to ischemic cardiomyopathy. The presence of these factors was associated with enhanced thrombin formation. Associations between both factors and LA diameter and right ventricular parameters might suggest that TF and FXIa predispose to thromboembolic complications of HF.

Download full-text


Available from: Michał Ząbczyk, Oct 13, 2014
20 Reads
  • Source
    • "Active factors are known to circulate in patients’ plasma in some medical conditions [3]–[5], [20], [21]. To find out whether they can induce spontaneous clotting in the Thrombodynamics assay, we compared test results obtained for patients’ plasmas and plasmas of healthy donors supplemented with factors that have long plasma lifetimes (comparable with time between venipuncture and beginning of a test): fVa, fVIIa, soluble TF, fIXa, and fXIa [22]–[24]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Using an in vitro experimental model of immobilized tissue factor-initiated clot growth in platelet-free plasma (thrombodynamics), we observed formation of activator-independent isolated spontaneous clots (SC) throughout the plasma volume in patients with cardiac infarction, acute leukemia, hemolytic anemia, and some other disorders. The aim of this work was to characterize this phenomenon and to identify the mechanisms of SC formation. Tissue factor inhibitor (VIIai) prevented SC in only 2 out of 23 patient plasma samples. Specific inhibitors of factors IXa and XIa were efficient in all 8 cases that we tested. Also, only factors IXa and XIa added to normal donors' plasma induced SC formations from isolated centers, in a pattern similar to that in patients' plasma. In contrast, factors VIIa, Va, tissue factor induced uniform plasma clotting. SC disappeared after high-speed centrifugation. However, phospholipid supplementation of centrifuged plasma returned them at least partially in 5 out of 22 patients' plasmas, indicating some other role of microparticles than providing phospholipid surface. Circulating procoagulant microparticles isolated from plasma directly activated factor XII in buffer and in diluted plasma. Flow cytometry revealed an increase in procoagulant microparticles in patients' plasmas with SC. Our data suggest that combination of circulating active factors (specifically, factors IXa and XIa) with circulating procoagulant and contact-pathway-activating microparticles is the predominant mechanism causing spontaneous clotting in patient plasma.
    PLoS ONE 01/2014; 9(1):e87692. DOI:10.1371/journal.pone.0087692 · 3.23 Impact Factor
  • Source
    • "A clot narrowing or occluding the vessel lumen is formed at the injury site. Endogenous fibrinolysis and complete clot lysis occur in less than 20% of the cases [11–16]. Much more frequently (in about 50-70% of the cases) clot dissolution is impaired and it grows uncontrollably, obstructing the vessel [10, 17]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Thrombosis (VTh) is a rare dangerous complication of pacemaker implantation (PM). The aim of the study was to determine the dynamics of change in selected thrombotic and inflammatory factors after PM. The study involved 81 patients (30 female, mean age: 71.1 years) with PM, divided into two groups. Group A (71 patients) consisted of patients without VTh, whereas group B (10 patients) comprised the patients with VTh. A transthoracic echocardiogram (TTE) and a venous ultrasound (VU) examination were performed. The levels of D-dimers, fibrinogen, tissue factor (TF), factor VII, plasminogen activator inhibitor-1 (PAI-1), interleukin-6 (IL-6) and high-sensitivity C-reactive protein (hsCRP) were determined in the venous blood. After PM, the TTE and VU examinations were repeated at 6 and 12 months, and blood analyses were performed within 7 days after PM, and subsequently at 6 and 12 months. In 10 patients of group B, symptomatic VTh occurred at a mean time of 13.06 months after PM. Initially, the levels of IL-6, hsCRP, D-dimers, fibrinogen, TF, VII factor and PAI-1 were considerably higher in group B than in group A. In all patients the levels of these factors kept on increasing for up to 7 days after the procedure. In group A they subsequently decreased, whereas in group B they continued to rise. Increased levels of inflammatory and thrombotic factors were observed in patients with VTh before and after PM. The factors of highest risk of VTh occurrence were D-dimers, fibrinogen and TF.
    Archives of Medical Science 12/2012; 8(6):1027-34. DOI:10.5114/aoms.2012.28600 · 2.03 Impact Factor
  • Source
    • "Fibrin clot structure and functions depend on several genetic and environmental factors present in both clinical entities, including enhanced inflammatory status and oxidative stress [10]. Altered fibrin clot architecture and function both in CAD and DM2 are characterized by lower fibrin clot permeability resulting from a smaller pore size in the fiber network, along with impaired susceptibility to lysis [7–12]. Specifically, the altered fibrin structure in DM2 is largely attributed to glycation of fibrinogen and fibrin [9], which may interfere with fibrin polymerization, cross-linking by FXIII, tissue plasminogen activator (tPA) and plasminogen binding and plasminogen to plasmin conversion [8]. "
    [Show abstract] [Hide abstract]
    ABSTRACT: Altered fibrin clot structure has been reported both in patients with coronary artery disease (CAD) and those with type 2 diabetes mellitus (DM2). The aim of the present study was to evaluate plasma fibrin clot permeability and susceptibility to lysis in patients with DM2 and CAD. We studied 132 consecutive CAD patients, including 67 subjects with DM2, scheduled for elective coronary artery bypass grafting surgery. Ex vivo plasma fibrin clot permeability (K(s)) and lysis time (t(50%)) induced by 1 μg/mL recombinant tissue plasminogen activator (tPA), along with plasma levels of plasminogen activator inhibitor-1 (PAI-1), thrombin activatable fibrinolysis inhibitor (TAFI), tPA, von Willebrand factor (vWF), P-selectin, soluble CD40 ligand (sCD40L), were measured. Diabetic and non-diabetic patients did not differ in regard to demographics and remaining cardiovascular risk factors. Concomitant DM2 was associated with higher glucose (+24.3 %, p < 0.001), fibrinogen (+9.0 %, p = 0.037), PAI-1 (+58.7 %, p < 0.001), tPA (+24.0 %, p < 0.001) and P-selectin (+12.2 %, p < 0.001). Compared with the non-diabetic group, the CAD patients with DM2 had lower K(s) (-6.1 %, p = 0.02) and prolonged t(50%) (+5.1 %, p = 0.04). Multiple regression analysis of the whole study group showed that vWF, PAI-1, fibrinogen and DM2 were the independent predictors of t(50%) (R (2) = 0.58, p < 0.001), while only vWF was an independent predictor of K(s) (R (2) = 0.22, p < 0.001). This study indicates that DM2 is potent enough to unfavorably affect plasma fibrin clot characteristics despite abnormal clot phenotype typically observed in CAD. Of note, platelet and endothelial markers appear to contribute to fibrin clot properties in CAD concomitant with DM2.
    Journal of Thrombosis and Thrombolysis 10/2012; 35(2). DOI:10.1007/s11239-012-0821-8 · 2.17 Impact Factor
Show more