Biomedical subjects

A Siegbahn

Publications and source records attributed to A Siegbahn.

At least 19 recordsLinked to original sources

PubMed2006

Low molecular weight dextran sulfate: a strong candidate drug to block IBMIR in clinical islet transplantation.

The instant blood-mediated inflammatory reaction (IBMIR) is triggered in clinical islet transplantation when human pancreatic islets come in contact with blood and may explain the initial tissue loss associated with this procedure. Low molecular weight dextran sulfate (LMW-DS; MM 5000), today available for clinical use, inhibits both complement and coagulation activation. In a tubing loop model, LMW-DS at concentrations ranging from 0.01 to 1 g/L showed a dose-dependent inhibition of IBMIR with an inhibition of coagulation and complement activation and less consumption of platelets and other blood cells. In blood or plasma APTT was demonstrated to be an excellent method for monitoring the LMW-DS concentration both in vitro and in vivo in a nonhuman primate model. The toxicity was assessed using a glucose challenge test and the pharmacokinetics was tested in the nonhuman primate model. Here, we present a tentative protocol for using LMW-DS in clinical islet transplantation.

Anticoagulants↗

PubMed2005

The influence of different heparin surface concentrations and antithrombin-binding capacity on inflammation and coagulation.

The corline heparin surface (CHS) used in the extracorporeal circuit during coronary artery bypass grafting is shown to decrease the activation of inflammation and coagulation. Synchrotron radiation studies have shown that a single layer of the CHS may not completely cover the substrate surface. However, a double layer of CHS results in a uniform surface. We investigated the effect of surfaces with different surface concentrations of heparin on cell activation and coagulation compared to an uncoated surface. The CHS is prepared by a conditioning layer of polymeric amine onto which a macromolecular heparin conjugate is attached. We used PVC tubing, uncoated or modified with a single or double layer of the CHS, and circulated fresh whole blood from healthy volunteers in a loop model system at 37 degrees C up to 4 h. Blood was drawn from the loops at different times and activation of inflammation and coagulation was studied by real-time PCR, flow cytometry and ELISA. The activation of leukocytes and platelets and formation of leukocyte-platelet aggregates were reduced by use of the single-layered CHS compared to the uncoated surface. Use of double-layered CHS resulted in significantly reduced cell activation and thrombin generation. Development of the CHS obtained by the double layer of the coating has improved the biocompatibility of the surface.

Antithrombins↗

PubMed2005

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<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<0.001) and von Willebrand factor (162% vs. 136%, P<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.

Aged↗

PubMed2005

Long-term treatment with ximelagatran, an oral direct thrombin inhibitor, persistently reduces the coagulation activity after a myocardial infarction.

BACKGROUND: In the ESTEEM study, patients with a recent myocardial infarction were treated with aspirin and randomized to one of four doses (24-60 mg b.i.d) of the oral direct thrombin inhibitor ximelagatran or placebo for 6 months. Ximelagatran and aspirin reduced the risk of recurrent ischemic events compared with aspirin alone. In the present substudy we evaluated the different doses of ximelagatran on pharmacokinetics as measured by plasma concentration of the active compound melagatran and activated partial thromboplastin time (APTT) and pharmacodynamics as related by markers for coagulation activity, prothrombin fragment 1 + 2 (F1 + 2) and D-dimer. METHODS AND RESULTS: Plasma samples from 518 patients were collected before, during and after the treatment period. There was a linear dose-concentration relation at peak and trough and a linear relation between concentration and APTT (P < 0.001). F1 + 2 and D-dimer were decreased by 25% and 52% at 1 week (P < 0.001) in the ximelagatran groups compared with the placebo group and the reductions were maintained during the 6 months treatment. There were no differences detected in F1 + 2 or D-dimer levels between the different ximelagatran dosages. There was no correlation between the melagatran concentration and the change in F1 + 2 and D-dimer levels. After cessation of ximelagatran F1 + 2 and D-dimer levels returned to the initial levels. CONCLUSION: The dose of ximelagatran and APTT are linearly related to the plasma concentration of melagatran. Ximelagatran induces a sustained and stable reduction of thrombin generation and fibrin turnover without any relation to dose above 24 mg b.i.d. These properties indicate that long-term treatment with a low dose of ximelagatran may provide valuable depression of coagulation activity in aspirin treated post myocardial infarction patients.

Aged↗

PubMed2005

FRISC score for selection of patients for an early invasive treatment strategy in unstable coronary artery disease.

OBJECTIVE: To develop a scoring system for risk stratification and evaluation of the effect of an early invasive strategy for treatment of unstable coronary artery disease (CAD). DESIGN: Retrospective analysis of a randomised study (FRISC II; fast revascularisation in instability in coronary disease). SETTING: 58 Scandinavian hospitals. PATIENTS: 2457 patients with unstable CAD from the FRISC II study. MAIN OUTCOME MEASURES: One year rates of mortality and death/myocardial infarction (MI). METHODS: Patients were randomly assigned to an early invasive or a non-invasive strategy. From the non-invasive cohort independent variables of death or death/MI were identified. RESULTS: Seven factors, age > 70 years, male sex, diabetes, previous MI, ST depression, and increased concentrations of troponins and markers of inflammation (interleukin 6 or C reactive protein), were associated with an independent increased risk for death or death/MI. In patients with > or = 5 of these factors the invasive strategy reduced mortality from 15.4% (20 of 130) to 5.2% (7 of 134) (risk ratio (RR) 0.34, 95% confidence interval (CI) 0.15 to 0.78, p = 0.006). Death/MI was also reduced in patients with 3-4 factors from 15.7% (80 of 511) to 10.8% (58 of 538) (RR 0.69, 95% CI 0.50 to 0.94, p = 0.02). Neither death nor death/MI was reduced in patients with 0-2 risk factors. CONCLUSION: In unstable CAD, this scoring system based on factors independently associated with an adverse outcome can be used shortly after admission to the hospital for risk stratification and for selection of patients to an early invasive treatment strategy.

Aged↗

PubMed2004

Activation of coagulation and fibrinolytic systems in patients with CLI is not normalized after surgical revascularisation.

OBJECTIVE: To study the activation of coagulation and fibrinolysis before, during and after surgical revascularisation in patients with critical limb ischemia (CLI). DESIGN: Prospective clinical study. MATERIALS AND METHODS: Forty patients with CLI underwent femoro-popliteal or femoro-distal reconstruction and were compared to a control-group. Measurements of prothrombin-fragment 1+2 (F1+2) and thrombin-antithrombin complex (TAT) assessed activation of coagulation. Fibrinolysis was determined by tissue plasminogen activator (tPA), plasminogen activator inhibitor (PAI-1) and fibrin degradation product (D-dimer). The inflammatory mediators: Interleukin 2 receptor (IL-2-rec), Interleukin 6 (IL-6), Interleukin 10 (IL-10) and Monocyte chemoattractant protein 1 (MCP-1) was also analysed. RESULTS: Patients (in 35 of the 40 reconstruction was possible) were operated upon using either vein (n=23) or ePTFE (n=12) grafts. Patients with CLI had a preoperative prothrombotic state as indicated by high TAT-levels and also ongoing fibrinolysis with high levels of t-PA and D-dimer. After reperfusion an ongoing prothrombotic state for the first week was demonstrated. A significant as well as defective fibrinolysis was also seen with increased levels of tPA and D-dimer unopposed by PAI-1 after one week and also after 30 days. Increased levels of inflammatory mediators IL-6, IL-10 and MCP-1 was observed after reperfusion and normalised after 30 days. CONCLUSION: This study demonstrates significant disturbances of both the coagulation and fibrinolytic systems before, during and after revascularisation for CLI. This was accompanied by release of inflammatory mediators. A prothrombotic state and increased fibrinolysis were evident also 30 days after successful revascularisation.

Aged↗

PubMed2004

Reference intervals for plasma levels of fibronectin, von Willebrand factor, free protein S and antithrombin during third-trimester pregnancy.

During pregnancy, significant changes occur in the hemostatic system and in the plasma levels for several plasma proteins, especially towards term. In this study changes occurring during normal pregnancy and immediately postpartum were investigated to establish adequate reference intervals for important hemostatic parameters. Blood samples were collected during pregnancy weeks 33, 36, 39 and 1-3 h after delivery from 153 healthy pregnant women with at least one previous normal pregnancy. The plasma samples were analyzed for antithrombin, von Willebrand factor (vWf), free protein S and fibronectin. Fibronectin and vWf are contact-promoting proteins responsible for adhesion and aggregation during primary hemostasis, but are also released from thrombocytes during activation of the coagulation process. Antithrombin is the most important primary physiological inhibitor of activated serine proteases related to the coagulation cascade. Protein S is a co-factor to protein C and in cooperation is also an important inhibitor of the coagulation cascade. During third-trimester pregnancy, vWf was higher than in non-pregnant women, and continued to increase postpartum. The fibronectin plasma level was mostly unchanged in comparison with non-pregnant values. Within this reference interval it gradually increased during the third trimester, but fell slightly postpartum. Antithrombin decreased slightly during the third trimester and even further, postpartum. Free protein S decreased markedly but to a stable level from week 33 to 39, decreasing even more postpartum. The present results are concordant with clinical knowledge of increased risk of thrombosis during pregnancy and early puerperium, with increased levels of vWf and fibronectin and decreased levels of antithrombin and free protein S. Clearly, current reference values based on healthy non-pregnant subjects are not usable during late pregnancy and immediately postpartum.

Adult↗

PubMed2003

Myocardial damage, inflammation and thrombin inhibition in unstable coronary artery disease.

AIM: Unstable coronary artery disease (CAD) is a multifactorial disease involving both thrombotic and inflammatory processes. We have assessed the time-course and the influence of thrombin inhibitors on changes in fibrinogen and C-reactive protein levels, and their relation to myocardial ischaemia in unstable CAD. METHODS AND RESULTS: Three hundred and twenty patients were randomized to 72 h infusion with three different doses of inogatran, a direct thrombin inhibitor, or unfractionated heparin. There were no significant differences between the treatment groups in fibrinogen or C-reactive protein levels. Overall, the fibrinogen levels were significantly increased in the first 24-96 h and still elevated at 30 days. The C-reactive protein levels showed a more pronounced increase during the first 24-96 h, but then markedly decreased over 30 days. Troponin-positive compared to troponin-negative patients had higher fibrinogen and C-reactive protein levels up to 96 h, although there was an increase compared to pre-treatment levels in both groups. A high fibrinogen level (pre-treatment top tertile) was associated with an increased rate of death or myocardial (re-)infarction at 30 days, 13% vs 5.6%, P=0.03, and increased long-term mortality. A high C-reactive protein level was related to increased 30-day mortality, 4% vs 0%, P=0.01. CONCLUSION: Myocardial cell injury was related to a high degree of inflammation, only some of which is an acutephase response due to tissue damage. The rise in fibrinogen was sustained, which might reflect low grade inflammation with long-term risk of thrombosis. The transient elevation of C-reactive protein levels might indicate a propensity to a pronounced inflammatory response and is associated with increased mortality.

Adult↗

PubMed2003

Low utilisation of unactivated protein C in a patient with meningococcal septic shock and disseminated intravascular coagulation.

BACKGROUND: Activated protein C has recently been shown in a multicentre trial to significantly reduce mortality in patients with septic shock. There are also some case reports and minor studies demonstrating promising results with the unactivated form of protein C. However, in children with severe meningococcal infection, skin biopsies have demonstrated low expression of endothelial thrombomodulin and protein C receptors, suggesting low protein C activation capacity in severe meningococcal sepsis. METHODS: A patient with meningococcal septic shock was treated with two doses of the unactivated form of protein C, the first during intense activation of the coagulation system and the second during a phase of low grade or no activation. Repeated plasma samples were analysed for protein C concentration, which made it possible to compare pharmacokinetics and half-lives of the two administrations. A shorter half-life during intense coagulation was expected if there was an activation and consumption of the protein C administered. RESULTS: The calculated half-lives of protein C during intense and low grade activation were 32 h and 19 h, respectively, a magnitude similar to that reported in protein C-deficient patients without infection. CONCLUSION: The result indicates that whole body utilisation of the unactivated protein C was low. Endothelial impairment of protein C activation does not seem to be restricted to the skin vessels only.

Adult↗

PubMed2002

Cell adhesion and tissue factor upregulation in oxygenators used during coronary artery bypass grafting are modified by the Corline Heparin Surface.

OBJECTIVE: Cardiopulmonary bypass (CPB) is associated with inflammatory response and activation of coagulation. We investigated the influence of a new heparin surface on the activation of cells retrieved from oxygenators used during coronary artery bypass grafting (CABG). DESIGN: Sixty patients undergoing CABG with CPB were randomly assigned to either uncoated or completely Corline Heparin Surface (CHS)-coated circuits with one of three different levels of systemic heparin: standard, high or low. At end of surgery adhered cells were retrieved from the oxygenators and cell count, tissue factor (TF)- and CD11b-expression on monocytes and monocytic TFmRNA were analysed. RESULTS: The heparin coating of the oxygenator prevented adhesion of granulocytes, monocytes and platelets. TF-expression on monocytes from the oxygenators was significantly higher than on circulating cells in all groups. Monocytes from the uncoated oxygenators showed low levels of TF-expression with high levels of TFmRNA. The coated group with high level of heparin showed higher surface-expression of TF with low levels of TFmRNA. CONCLUSION: The CHS was most biocompatible with the standard level of heparin used during CABG whereas elevation of systemic heparin rather increased the activation and TF upregulation in monocytes from oxygenators.

Aged↗

PubMed2001

Relationship between interleukin 6 and mortality in patients with unstable coronary artery disease: effects of an early invasive or noninvasive strategy.

CONTEXT: Inflammatory activity is associated with high rates of long-term mortality in unstable coronary artery disease (CAD). Interleukin 6 (IL-6) induces C-reactive protein and fibrinogen, systemic markers of inflammation. OBJECTIVES: To determine whether plasma levels of IL-6 are predictive of mortality and to evaluate the interaction of IL-6 levels with the effects of invasive vs noninvasive treatment strategies in unstable CAD patients. DESIGN, SETTING, AND PATIENTS: The prospective, randomized Fragmin and Fast Revascularisation During Instability in Coronary Artery Disease II trial, conducted among 3489 patients, 3269 of whom had plasma samples analyzed for IL-6 levels, with diagnosed unstable CAD (67% male; median age, 67 years) at 58 Scandinavian hospitals between June 1996 and August 1998. INTERVENTIONS: Patients were randomly assigned to receive either an early invasive (n = 1222) or a noninvasive treatment strategy (n = 1235). The latter group, as well as 666 patients with contraindications to invasive therapy, were further randomized to 90-day treatment with low-molecular-weight heparin (dalteparin, 5000-7500 IU twice per day; n = 1140) or placebo (n = 1127). MAIN OUTCOME MEASURE: Mortality at 6 and 12 months in the medically and interventionally randomized cohorts, respectively, in relation to IL-6 levels, measured at randomization. RESULTS: Plasma levels of IL-6 that were at least 5 ng/L compared with levels lower than 5 ng/L were associated with greatly increased mortality in the noninvasive group (7.9% vs 2.3%; relative risk [RR], 3.47; 95% confidence interval [CI], 1.94-6.21) and in the placebo-treated group (7.9% vs 2.5%; RR, 3.19; 95% CI, 1.77-5.74). The association remained significant after adjustment for most established risk indicators. An early invasive treatment strategy strongly reduced 12-month mortality among those with elevated IL-6 levels (5.1% absolute reduction; P =.004) whereas mortality was not reduced among patients without elevated IL-6 concentrations. Those taking dalteparin with elevated IL-6 levels experienced lower 6-month mortality than those who did not take dalteparin (3.5% absolute reduction; P =.08). CONCLUSIONS: Circulating IL-6 is a strong independent marker of increased mortality in unstable CAD and identifies patients who benefit most from a strategy of early invasive management.

Adult↗

PubMed2001

Blood cell activation, coagulation, and inflammation in men and women with coronary artery disease.

We investigated in some detail the immunologic and procoagulant activation patterns in men and women with unstable (UA, n=26) versus stable (SA, n=40) coronary artery disease (CAD). Leukocyte activation and platelet-leukocyte complex formation were assessed by flow cytometry. Plasma markers of coagulation and inflammation were analyzed. Unstable patients displayed higher levels of platelet-leukocyte complexes (P<.001), of leukocyte CD11b (P<.01), and of T cell HLA-DR (P<.05) than healthy controls did. Female UA patients presented the highest degree of complexes. SA patients only differed significantly from controls with respect to HLA-DR (P=.02). UA patients had higher levels of C-reactive protein (P<.01), IL-6 (P<.001), IL-10 (P<.01), and soluble fibrin (P<.001) than did stable ones. Regarding P-selectin levels, 25% of SA and 50% of UA patients were above normal range. Again, UA women presented the highest marker amounts. As for soluble tissue factor, women had higher levels than men regardless of the severity of disease (P<.001 in SA). We conclude that in unstable coronary syndromes, there is an activation of both coagulation and inflammation that coincides with an increased activation of platelets and leukocytes. Cellular interactions may contribute to the systemic responses observed. Women have different patterns of cellular activation than men, indicating differences in pathogenetic mechanisms.

Aged↗

PubMed2001

Coagulation and fibrinolysis in chronic venous insufficiency.

BACKGROUND: Varicose veins (VV) are common, but only some patients will develop chronic venous insufficiency (CVI) with skin changes or venous ulcer. The pathophysiology of venous ulcer development is complex, and may involve abnormalities in coagulation, fibrinolysis and proinflammatory cytokines. The purpose of this study was to correlate plasma markers within these systems and skin pathology. METHOD: A group of twenty consecutive patients with active or recent venous ulcer were matched for sex and age with further three groups of individuals i.e. controls and patients with VV with and without skin changes respectively. Blood samples were analysed for hemoglobin (HB), total platelet count (TPC), C-reactive protein (CRP), activated partial thromboplastin time (APTT), prothrombin complex (PT), fibrinogen, interleukin-1 beta (IL-1 beta), tumor necrosis factor alpha (TNF alpha), D-dimer, tissue plasminogen activator (t-PA), plasminogen activator inhibitor 1 (PAI-1), prothrombin fragments 1 and 2 (F1 + 2), and thrombin antithrombin III complex (TAT). RESULTS AND CONCLUSION: There was an increase of systemic levels of PAI-1 activity and tPA with progressive skin pathology in patients with CVI, and in the group with active ulcer there was an elevation of F1 + 2. Those findings could reflect a defect fibrinolysis, a thrombotic potential or a damaged endothelium.

Aged↗

PubMed2001

Coagulation activity and clinical outcome in unstable coronary artery disease.

In the current study, we investigated molecular markers of coagulation activity, ie, prothrombin fragment 1+2 (F1+2), thrombin-antithrombin (TAT) complex, soluble fibrin (SF), and D-dimer, and their relation to death, myocardial infarction, and refractory angina during and after anticoagulant treatment in unstable coronary artery disease. Patients with unstable coronary artery disease (N=320) were randomized to a 72-hour infusion with either inogatran, a low-molecular-mass direct thrombin inhibitor, or unfractionated heparin. During the 30-day follow-up, a 40% lower event rate was seen in patients with high compared with low baseline levels of TAT or SF. High baseline levels of coagulation activity were correlated with a larger decrease during treatment. Patients with decreased compared with raised F1+2 or TAT levels after 6 hours of treatment had a 50% lower event rate at 30 days (F1+2, P=0.04; TAT, P=0.02). At the cessation of antithrombin treatment, there was a clustering of cardiac events that tended to be related to a rise in the levels of TAT and the other markers. During long-term follow-up (median, 29 months), there was a relation between higher baseline levels of D-dimer (P=0.003) and increased mortality. High baseline levels of molecular markers of coagulation activity might identify patients with a thrombotic condition (as the major cause of instability) who are good responders to anticoagulant therapy, with a larger decrease in coagulation activity during treatment and a decreased risk of ischemic events. However, this early benefit is lost during long-term follow-up when high baseline levels of coagulation activity are associated with a raised risk of early reactivation and increased mortality.

Adult↗

PubMed2000

Binding of factor VIIa to tissue factor on human fibroblasts leads to activation of phospholipase C and enhanced PDGF-BB-stimulated chemotaxis.

Tissue factor (TF) is the cellular receptor for factor FVIIa (FVIIa), and the complex is the principal initiator of blood coagulation. The effects of FVIIa binding to TF on cell migration and signal transduction of human fibroblasts, which express high amounts of TF, were studied. Fibroblasts incubated with FVIIa migrated toward a concentration gradient of PDGF-BB at approximately 100 times lower concentration than do fibroblasts not ligated with FVIIa. Anti-TF antibodies inhibited the increase in chemotaxis induced by FVIIa/TF. Moreover, a pronounced suppression of chemotaxis induced by PDGF-BB was observed with active site-inhibited FVIIa (FFR-FVIIa). The possibility that hyperchemotaxis was induced by a putative generation of FXa and thrombin activity was excluded. FVIIa/TF did not induce increased levels of PDGF beta-receptors on the cell surface. Thus, the hyperchemotaxis was not a result of this mechanism. FVIIa induced the production of inositol-1,4, 5-trisphosphate to the same extent as PDGF-BB; the effects of FVIIa and PDGF-BB were additive. FFR-FVIIa did not induce any release of inositol-1,4,5,-trisphosphate. Thus, binding of catalytically active FVIIa to TF can, independent of coagulation, modulate cellular responses, such as chemotaxis.

Amino Acid Chloromethyl Ketones↗

PubMed2000

Markers of myocardial damage and inflammation in relation to long-term mortality in unstable coronary artery disease. FRISC Study Group. Fragmin during Instability in Coronary Artery Disease.

BACKGROUND: In patients with unstable coronary artery disease, there is a relation between the short-term risk of death and blood levels of troponin T (a marker of myocardial damage) and C-reactive protein and fibrinogen (markers of inflammation). Using information obtained during an extension of the follow-up period in the Fragmin during Instability in Coronary Artery Disease trial, we evaluated the usefulness of troponin T, C-reactive protein, and fibrinogen levels and other indicators of risk as predictors of the long-term risk of death from cardiac causes. METHODS: Levels of C-reactive protein and fibrinogen at enrollment and the maximal level of troponin T during the first 24 hours after enrollment were analyzed in 917 patients included in a clinical trial of low-molecular-weight heparin in unstable coronary artery disease. The patients were followed for a mean of 37.0 months (range, 1.6 to 50.6). RESULTS: During follow-up, 1.2 percent of the 173 patients with maximal blood troponin T levels of less than 0.06 microg per liter died of cardiac causes, as compared with 8.7 percent of the 367 patients with levels of 0.06 to 0.59 microg per liter and 15.4 percent of the 377 patients with levels of at least 0.60 microg per liter (P=0.007 and P=0.001, respectively). The rates of death from cardiac causes were 5.7 percent among the 314 patients with blood C-reactive protein levels of less than 2 mg per liter, 7.8 percent among the 294 with levels of 2 to 10 mg per liter, and 16.5 percent among the 309 with levels of more than 10 mg per liter (P=0.29 and P=0.001, respectively). The rates of death from cardiac causes were 5.4 percent among the 314 patients with blood fibrinogen levels of less than 3.4 g per liter, 12.0 percent among the 300 with levels of 3.4 to 3.9 g per liter, and 12.9 percent among the 303 with levels of at least 4.0 g per liter (P=0.004 and P=0.69, respectively). In a multivariate analysis, levels of troponin T and C-reactive protein were independent predictors of the risk of death from cardiac causes. CONCLUSIONS: In unstable coronary artery disease, elevated levels of troponin T and C-reactive protein are strongly related to the long-term risk of death from cardiac causes. These markers are independent risk factors, and their effects are additive with respect to each other and other clinical indicators of risk.

Age Factors↗

PubMed2000

Coagulation activation after laparoscopic cholecystectomy in spite of thromboembolism prophylaxis.

BACKGROUND: The aim of this study was to determine whether laparoscopic cholecystectomy (LC), in spite of its minimally invasive nature, causes coagulation activation. METHODS: Sixty-four patients undergoing LC were included prospectively. All received either dextran or low-molecular-weight heparin (LMWH). Blood samples taken the morning of the operation and the following morning were analyzed for TAT, FM, fragment 1+2, tPA, PAI-1, vWf, D-dimer, Hb, hematocrit, and APC resistance. RESULTS: Significant increases in TAT, FM, fragment 1+2, and D-dimer were seen, whereas APC resistance, Hb, and hematocrit decreased significantly. Dextran led to a decrease in vWf and no change in tPA, whereas LMWH led to an increase in both these parameters. CONCLUSIONS: Laparoscopic cholecystectomy causes coagulation activation. There are differences in the response between patients receiving dextran and LMWH as thromboembolism prophylaxis. Since most patients are discharged the day after the operation, there could be practical as well as theoretical advantages to using dextran.

Adult↗

PubMed2000

No benefit of reduced heparinization in thoracic aortic operation with heparin-coated bypass circuits.

BACKGROUND: Heparin coating of the cardiopulmonary bypass circuit attenuates inflammatory response and confer clinical benefits in cardiac operations. The positive effects may be amplified with reduced systemic heparin dosage. We studied markers of inflammation and coagulation in thoracic aortic operations with heparin-coated circuits and standard vs reduced systemic heparinization. METHODS: Thirty patients were randomized to standard (group S; 300 IU/kg initially; activated clotting times [ACT] > 480 seconds; 5,000 IU in prime; n = 16) or reduced (group R; 100 IU/kg initially; ACT > 250 seconds; 2,500 IU in prime; n = 14) dose systemic heparin. The following markers were analyzed perioperatively: (a) inflammatory response; acute phase cytokine interleukin-6, and granulocytic proteins myeloperoxidase and lactoferrin; (b) complement activation; factor C3a and the C5a-9 terminal complement complex [TCC]; and (c) coagulation; thrombin-antithrombin III complex. RESULTS: The clinical outcome did not differ between groups. Four (29%) patients in group R had a perioperative thromboembolic event. All studied markers were significantly elevated during and throughout cardiopulmonary bypass in both groups. Maximal values were higher in group R for all variables except for TCC. There were no statistically significant intergroup differences regarding markers of inflammation, complement activation, or coagulation activation. CONCLUSIONS: The blood trauma in thoracic aortic operation is extensive, as reflected by the elevation of the studied biochemical markers, even when heparin-coated cardiopulmonary bypass circuits are used. In this study, we did not detect any benefits, either biochemical or clinical, of reducing the dose of systemic heparin.

Aged↗