Associations of plasma fibrinogen assays, C-reactive protein and interleukin-6 with previous myocardial infarction

Background: The association of plasma fibrinogen with myocardial infarction (MI) may (like that of C-reactive protein, CRP) be a marker of subclinical inflammation, mediated by cytokines such as interleukin-6 (IL-6). There are well- recognized discrepancies between commonly performed fibrinogen assays. Increased ratio of clottable fibrinogen to intact fibrinogen (measured by a recently developed immunoassay) has been proposed as a measure of hyperfunctional fibrinogen, and is elevated in acute MI.<br/> Objective: To compare the associations of intact fibrinogen and four routine fibrinogen assays (two von Clauss assays; one prothrombin-time derived; and one immunonephelometric) in a case-control study of previous MI. Patients/methods: Cases (n = 399) were recruited 3-9 months after their event; 413 controls were age- and sex-matched from the case-control study local population. Intact fibrinogen was measured in 50% of subjects. Results: All routine fibrinogen assays showed high intercorrelations (r = 0.82-0.93) and significant (P lt 0.0001) increased mean levels in cases vs. controls. These four routine assays correlated only moderately with intact fibrinogen (r = 0.45-0.62), while intact fibrinogen showed only a small, nonsignificant increase in cases vs. controls. Consequently, the ratio of each of the four routine assays to the intact fibrinogen assay was significantly higher (P lt 0.0003) in cases vs. controls. Each fibrinogen assay correlated with plasma levels of CRP and IL-6 (which were also elevated in cases vs. controls). Each routine fibrinogen assay remained significantly elevated in cases vs. controls after further adjustment for C-reactive protein and interleukin-6. Conclusions: These data provide evidence for acquired, increased hyperfunctional plasma fibrinogen in MI survivors, which is not associated with markers of inflammatory reactions. The causes and significance of these results remain to be established in prospective studies

Are there differences in acute phase inflammation markers regarding the type of heart failure?

This study aimed to determine if there are differences in inflammatory markers in the acute phase between systolic heart failure and heart failure with preserved systolic function. One hundred and thirty-one patients with acute heart failure were recruited consecutively. At admission, plasma fibrinogen, C-reactive protein, sialic acid, von Willebrand factor, vascular endothelial growth factor, interleukin-6 and NTproBNP were all evaluated. If the ejection fraction was 45% or over patients were included in the HF-PSF group; the remaining patients were included in the SHF group. The HF-PSF patients were older (72±10 vs 63±12 years, P<0.001), presented a higher rate of atrial fibrillation (56.1 vs 21.3%, P<0.001), and had a lower rate of hemoglobin (12.2±2 vs 13.3±2.1 g/dL, P<0.01). No significant differences were observed in the inflammation markers analyzed among SHF and HF-PSF groups. In the acute phase of heart failure there is a marked elevation of inflammatory markers but there are no differences in the inflammatory markers analyzed between the two different types of heart failure

Influence of prolonged dalteparin treatment on coagulation, fibrinolysis and inflammation in unstable coronary artery disease

BACKGROUND. Unstable coronary artery disease (CAD) is a multi-factorial disease involving thrombotic and inflammatory processes. Short-term low molecular weight (LMW) heparin treatment reduces coagulation activity and clinical events. We investigated the influence of prolonged treatment on coagulation, fibrinolysis and inflammation. METHODS AND RESULTS. Serial blood samples were obtained from 555 of 2,267 unstable CAD patients in the FRISC II study. Patients were treated with the LMW heparin dalteparin 120 IU kg(-1) s.c. twice daily for 5-7 days and randomized to placebo (n=285) or gender and weight-adjusted doses of dalteparin (5,000 or 7,500 IU) twice daily (n=270) for 3 months. Dalteparin persistently depressed coagulation activity with, when compared with placebo, lower median levels of factor VIIa (63 IU mL(-1) vs. 84 IU mL(-1)), prothrombin fragment 1 + 2 (0.86 nmol L(-1) vs. 1.09 nmol L(-1)) and D-dimer (21 microg L(-1) vs. 43 microug L(-1)) after 3 months, all P&lt;0.01. Reactivation of coagulation activity was observed after cessation of both short-term and prolonged dalteparin treatment. Higher levels of tPA/PAI-1 complex (11.7 microg L(-1) vs. 6.5 microg L(-1), P&lt;0.001) and von Willebrand factor (162% vs. 136%, P&lt;0.001) were found during prolonged dalteparin treatment. Interleukin-6, C-reactive protein and fibrinogen levels were unaffected by dalteparin treatment. CONCLUSIONS. Three months dalteparin treatment resulted in a sustained and pronounced reduction of coagulation activity, which corresponds to the observed reduction in death and myocardial infarction during the initial 6 weeks in the FRISC II study. The persistently elevated levels of tPA/PAI-1 complex and von Willebrand factor might reflect effects on platelets and endothelial cells and thus contribute to the gradually decreased efficacy by prolonged dalteparin treatment in unstable CAD.</p

Thromboelastometry (ROTEM) in children: age-related reference ranges and correlations with standard coagulation tests

BACKGROUND: The small sample volume needed and the prompt availability of results make viscoelastic methods like rotational thromboelastometry (ROTEM) attractive for monitoring coagulation in small children. However, data on reference ranges for ROTEM parameters in children are scarce. METHODS: Four hundred and seven children (ASA I and II) undergoing elective surgery were recruited for this prospective, two-centre, observational study. Subjects were grouped as follows: 0-3, 4-12, 13-24 months, 2-5, 6-10, and 11-16 yr. Study objectives were to establish age-dependent reference ranges for ROTEM assays, analyse age dependence of parameters, and compare ROTEM data with standard coagulation tests. RESULTS: Data from 359 subjects remained for final analysis. Except for extrinsically activated clot strength and lysis, parameters for ROTEM assays were significantly different among all age groups. The most striking finding was that subjects aged 0-3 months exhibited accelerated initiation (ExTEM coagulation time: median 48 s, Q1-Q3 38-65 s; P=0.001) and propagation of coagulation (α angle: median 78(o), Q1-Q3 69-84(o); P<0.001) and maximum clot firmness (median 62 mm, Q1-Q3 54-74 mm), although standard plasma coagulation test results were prolonged (prothrombin time: median 13.2 s, Q1-Q3 12.6-13.6 s; activated partial thromboplastin time: median 42 s, Q1-Q3 40-46 s). Lysis indices of <85% were observed in nearly one-third of all children without increased bleeding tendency. Platelet count and fibrinogen levels correlated significantly with clot strength, and fibrinogen levels correlated with fibrin polymerization. CONCLUSIONS: Reference ranges for ROTEM assays were determined for all paediatric age groups. These values will be helpful when monitoring paediatric patients and in studies of perioperative coagulation in children