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Biomedical subjects

P M Sandset

Publications and source records attributed to P M Sandset.

At least 19 recordsLinked to original sources
PubMed2007

The association between the proximal extension of the clot and the severity of pulmonary embolism (PE): a proposal for a new radiological score for PE.

BACKGROUND: The aim of the study was to investigate the association between the proximal level of the clot and the severity of pulmonary embolism (PE). METHODS: The cohort consisted of 99 consecutive patients with PE diagnosed by multi-detector computed tomography. A new score was constructed by calculating the mean value of the largest affected vessel [sub-segmental = 1, segmental = 2, lobar = 3, main pulmonary artery (MPA) = 4] in each lung. RESULTS: A significant association was found between the most proximal level of PE and pulmonary artery obstruction index (PAOI) (P < 0.0001), right ventricular (RV)/left ventricular (LV) ratio (P < 0.0001), and PaO(2) (P = 0.004). No significant association was found between systolic blood pressure and the level of PE. Troponin-T was elevated in none of the sub-segmental, 5% of segmental, 20% of lobar, and in 56% of PEs in the MPA (P = 0.001). Significant association was found between the proposed score and PAOI (P < 0.0001), RV/LV ratio (P < 0.0001), PaO(2) (P < 0.008). Troponin-T was elevated in 10% of level 1, 0% of level 2, 43% level of 3, 66% of level 4 PE (P < 0.0001). Cut-off level score 4 yielded a sensitivity of 84% and a specificity of 74% for the detection of elevated troponin-T. CONCLUSIONS: In conclusion, the study indicates that both the most proximal level of PE and the proposed score are related to the severity of PE as determined by blood oxygenation, biochemical and radiological parameters and could therefore be of value for rapid risk stratification of PE. However, the prognostic value of these classifications and their clinical significance needs to be evaluated in properly designed studies.

Carbon Dioxide↗
PubMed2006

Validation of a new D-dimer microparticle enzyme immunoassay (AxSYM D-Dimer) in patients with suspected pulmonary embolism (PE).

OBJECTIVES: The aim of the study was to evaluate a new automated assay for D-dimer testing (AxSYM D-Dimer) based on microparticle enzyme-immunoassay technology by comparing it with three well established D-dimer assays. PATIENTS AND METHODS: The performance of the new assay was evaluated in 280 plasma samples that were collected prospectively from out-patients included in a management study evaluating a decision based algorithm. RESULTS: 58/280 patients (21%) had PE diagnosed by CT. Median values of AxSYM D-dimer in patients with PE were 3689 ng/mL (range 775-9000). Comparison analysis displayed excellent agreement with VIDAS (kappa=0.84) and Asserachrom (kappa=0.81) D-dimer assays. A strong correlation was found between AxSYM and the VIDAS (r=0.96) and Asserachrom (r=0.89) D-dimer assays. The highest cut-off value for AxSYM that yielded a sensitivity of 100% was 765 ng/mL with a specificity of 50%. At the cut-off level <500 ng/mL, the sensitivity and specificity of AxSYM D-dimer were 100% and 34%; VIDAS 100% and 42%; Asserachrom 100% and 40%; and STALiatest 100% and 37%, respectively. AxSYM D-dimer was negative in 75 patients (33.8%). None of these had PE at the initial work-up or VTE during the 3-month follow-up. CONCLUSIONS: AxSYM D-dimer seems to be safe and effective in ruling out PE in out-patients. The cut-off level can be set at 500 to 750 ng/mL, at which the assay displays a performance that is comparable to that of the ELISA based assays. However, further studies are needed to confirm the safety of the assay and to determine the most optimal cut-off level in patients with venous thromboembolism.

Adolescent↗
PubMed2006

D-dimer level is associated with the extent of pulmonary embolism.

OBJECTIVES: Our aim was to study the association between the level of D-dimer and the severity of pulmonary embolism (PE) as determined by various biochemical and radiological prognostic markers in order to investigate the potential value of D-dimer as a prognostic marker for the severity of PE. PATIENTS AND METHODS: PE was diagnosed in 100 consecutive out-patients by multi-detector computerized tomography. One patient was excluded and the final cohort consisted of 99 patients. Pulmonary Artery Obstruction Index (PAOI) and Right Ventricular/Left Ventricular (RV/LV) ratio were assessed. RESULTS: The median value for D-dimer was 5.0 mg/L (inter-quartile range: 1.8, 12.2). There was a significant association between log D-dimer, and between log RV/LV (r=0.45), log PAOI (r=0.5), and PaO(2) (r=0.40). The multivariate analysis showed an increased association between log D-dimer and between log RV/LV ratio (r=0.54) and log PAOI (r=0.52) after adjusting for age, gender and for the duration of symptoms. Significant association was found between the level of D-dimer and the most proximal level of PE (p<0.0005). There was a significant dose-response relationship between the level D-dimer and between Troponin-T and the frequency of thrombolysis (p<0.0005). In the subgroup of patients with D-Dimer over the upper quartile (>12.2), 12 (67%) patients had elevated Troponin-T and 8 (32%) patients received thrombolysis, compared to 1 (5%) patient with elevated Troponin-T and none treated with thrombolysis in the subgroup of patients with D-dimer<lower quartile. CONCLUSIONS: We have shown that the level of D-dimer is related to the severity of PE assessed by various radiological, biochemical and clinical markers and might have a potential value as prognostic marker for the severity of PE.

Biomarkers↗
PubMed2006

Conventional-dose hormone therapy (HT) and tibolone, but not low-dose HT and raloxifene, increase markers of activated coagulation.

OBJECTIVES: Hormone therapy (HT) is associated with a modest, but significantly increased risk for arterial and venous thromboembolism. We have compared the effects of estrogen, tibolone, and raloxifene on relevant markers of coagulation activation and investigated whether there is a dose-response relationship of oral HT. METHODS: Randomized, open-label, comparative study of 202 healthy women who were assigned to receive treatment for 12 weeks with either low-dose hormone therapy containing 1 mg 17beta-estradiol + 0.5 mg norethisterone acetate (NETA) (n=50), conventional-dose HT containing 2 mg 17beta-estradiol and 1 mg NETA (n=50), 2.5 mg tibolone (n=51), or 60 mg raloxifene (n=51). RESULTS: The groups were comparable with regard to demographic characteristics and laboratory variables at baseline. D-dimer increased markedly in the conventional-dose HT group, but remained unchanged in the low-dose HT group. Tibolone was associated with a medium increase, whereas raloxifene was associated with a decrease in D-dimer levels. Changes in prothrombin fragment 1 + 2 showed a similar pattern for all four groups, whereas no significant differences in changes of thrombin-antithrombin complex were observed. CONCLUSIONS: Our data suggest that low-dose HT is associated with less activation of coagulation than conventional-dose HT. This finding may be of clinical importance since randomized clinical trials showing increased risk of thrombosis have utilized conventional-dose HT.

Antineoplastic Agents, Hormonal↗
PubMed2006

The performance of STA-Liatest D-dimer assay in out-patients with suspected pulmonary embolism.

Several studies have shown that D-dimer can reliably rule out pulmonary embolism (PE) in out-patients. However, various assays have different sensitivities and specificities to detect thrombosis. Our aim was to evaluate the performance of STA-Liatest D-Di in out-patients referred for suspected PE in a prospective outcome study. 495 consecutive patients referred to Østfold Hospital Trust-Fredrikstad, Norway for suspected PE between February 2002 and December 2003, were recruited in a study evaluating a decision-based algorithm combining clinical probability (CP), D-dimer, and multi-slice computer tomography (MSCT). D-dimer was performed as a first step test. No further testing was carried out in patients with D-dimer < or =0.4 mg/l and low/intermediate CP. The remaining patients proceeded to MSCT. All patients were followed up for 3 months to assess the 3-month thromboembolic risk. The final cohort consisted of 432 patients. PE was diagnosed in 102 (23%) patients. At a D-dimer cut-off point of 0.4 mg/l the tests had the highest sensitivity (100%) and specificity (36%). It safely ruled out PE in 120 (28%) patients. Kappa-coefficients for comparisons versus VIDAS and Asserachrom showed good concordance. STA-Liatest is a reliable and effective assay that can safely rule out PE in out-patients with a performance comparable with that of enzyme-linked immunosorbent assay-based d-dimer levels.

Adolescent↗
PubMed2005

A novel anticoagulant activity assay of tissue factor pathway inhibitor I (TFPI).

Tissue factor (TF) pathway inhibitor I (TFPI) is the physiological inhibitor of TF-induced blood coagulation. Circulating blood contains full-length TFPI and TFPI truncated at the C-terminal end. Previous studies have shown that full-length TFPI exerts a stronger anticoagulant effect on diluted prothrombin time (DPT) than truncated TFPI, and it has been suggested that full-length TFPI is biologically more important in vivo. The objective of this study was to develop and validate an assay of TFPI anticoagulant activity. TFPI anticoagulant activity was assayed using a modified DPT assay. Plasmas were incubated in the absence and the presence of TFPI-blocking antibodies. Results were expressed as a ratio with the clotting time in the presence of anti-TFPI as the denominator. The ratio was normalized against a ratio obtained with a reference plasma. The assay was compared with assays of TFPI free antigen, total antigen, and bound TFPI, and TFPI chromogenic substrate activity. We performed all tests in 436 healthy individuals. The normalized TFPI anticoagulant ratio was strongly associated with TFPI free antigen (r = 0.73) but was weakly associated with TFPI chromogenic substrate activity (r = 0.46), TFPI total antigen (r = 0.48), and bound TFPI (r = 0.30). TFPI chromogenic substrate activity was strongly associated with TFPI total antigen (r = 0.73). We have developed a novel assay of TFPI anticoagulant activity in plasma, which may be considered a functional assay of full-length TFPI. Further studies are needed to establish the role of TFPI anticoagulant activity for thrombotic disorders.

Anticoagulants↗
PubMed2005

Determinants of the APTT- and ETP-based APC sensitivity tests.

BACKGROUND: A reduced sensitivity for activated protein C (APC) is associated with an increased risk of venous thrombosis even in the absence of the factor (F)V Leiden mutation. This risk has been demonstrated with two APC sensitivity tests, which quantify the effects of APC on the activated partial thromboplastin time (APTT) and the endogenous thrombin potential (ETP), respectively. OBJECTIVES: We examined determinants of both APC sensitivity tests in the control group of the Leiden Thrombophilia Study (LETS). METHODS: Multiple linear regression analysis was performed with normalized APC-SR(APTT) or APC-SR(ETP) as dependent variable and putative determinants [levels of FII, FV, FVII, FVIII, FIX, FX, FXI, FXII, FXIII A subunit, FXIII B subunit, protein S total, protein S free, protein C, tissue factor pathway inhibitor (TFPI) total, TFPI free, antithrombin and fibrinogen] as independent variables. RESULTS AND CONCLUSIONS: The major determinant of the APTT-based test was FVIII level, followed by FII level. The ETP-based test was influenced most by free protein S and free TFPI levels. In both tests FXa formation plays a major role, as the effect of FVIII and TFPI on the tests seems to be executed via FXa. The ETP-based test was also strongly influenced by oral contraceptive use, even when we adjusted for all the clotting factors listed above. This means that the effect of oral contraceptives on the ETP-based test is not fully explained by the changes of coagulation factor levels investigated in this study, and that the molecular basis of acquired APC resistance during use of oral contraceptives remains to be established.

Adolescent↗
PubMed2005

Management of suspected pulmonary embolism (PE) by D-dimer and multi-slice computed tomography in outpatients: an outcome study.

OBJECTIVES: A prospective outcome study designed to evaluate a simple strategy for the management of outpatients with suspected pulmonary embolism (PE), based on clinical probability, D-dimer, and multi-slice computed tomography (MSCT). METHODS: A cohort of 432 consecutive patients admitted to the emergency department with suspected PE was managed by sequential non-invasive testing. Patients in whom PE was ruled out were not given anticoagulants, but were followed-up for 3 months. RESULTS: Normal D-dimer and low-intermediate clinical probability ruled out PE in 103 patients [24% (95% CI 20-28)]. Seventeen patients had normal D-dimer, but high clinical probability and proceeded to MSCT. All patients proved negative for PE. A total of 329 (76%) patients underwent MSCT examination. Pulmonary embolism was diagnosed in 93 patients [21.5% (95% CI 18-26)] and was ruled out by negative MSCT in 221 patients [51% (95% CI 46-56)]. MSCT scans were determined as inconclusive in 15 (4.5%) patients. No patient developed objectively verified venous thromboembolism (VTE) during the 3-month follow-up period. However, the cause of death was adjudicated as possibly related to PE in two patients, resulting in an overall 3-month VTE risk of 0.6% (95% CI 0-2.2%). The diagnostic algorithm yielded a definite diagnosis in 96.5% of the patients. CONCLUSIONS: This simple and non-invasive strategy combining clinical probability, D-dimer, and MSCT for the management of outpatients with suspected PE appears to be safe and effective.

Algorithms↗
PubMed2005

Angiogenesis and hemostasis in hematological neoplasias.

Angiogenesis is essential for tumor growth and metastasis. This is firmly established in solid tumors, but accumulating evidence suggests that this is also an important event in hematological neoplasias. Angiogenesis is therefore a putative target for therapy. The potential application of different angiogenesis inhibitors is currently under intense clinical investigation, and we will here review a number of these trials. The association between cancer and thromboembolic disease is even better documented, and again, this is not limited to solid tumors. It appears that many patients with hematological malignancies have a dysfunctional hemostatic system, with increased risk of thromboembolism. Furthermore, effective antithrombotic therapy seems to reduce the risk of cancer progression and even prolongs overall survival. In this review we will thus discuss the mechanisms involved in the regulation of angiogenesis and hemostasis and present evidence for a shared biology. A number of factors regulating the hemostatic system also have pro- or anti-angiogenic properties. Tissue factor (TF) and TF pathway inhibitor (TFPI) seem to play a central role, and there are several lines of evidence suggesting a close cooperation between TF/TFPI and pro-angiogenic factors like members of the vascular endothelial growth factor family. A better understanding of this shared biology may reveal new targets, and will probably increase the safety of targeting the blood supply.

Angiogenesis Inhibitors↗
PubMed2003

Smoking and relation to other risk factors in postmenopausal women with coronary artery disease, with particular reference to whole blood viscosity and beta-cell function.

OBJECTIVES: To investigate possible associations between smoking habits and other coronary risk factors in postmenopausal women with known coronary heart disease (CHD). SETTING: The study was conducted at a university clinic. SUBJECTS: A total of 118 postmenopausal women with CHD verified with angiography, consecutively recruited. INTERVENTIONS: Conventional treatment for CHD. The women were randomized to hormone replacement therapy (HRT) with transdermal 17-beta oestradiol and medroxyprogesterone acetate, or to a control group. RESULTS: Smokers were younger (P = 0.005), had lower body mass index (P = 0.04) and lipoprotein Lp(a) levels (P = 0.02) compared with nonsmokers. Smokers had reduced beta-cell function (homeostasis model assessment, P = 0.006), whereas whole blood viscosity (WBV) was higher at all shear rates. WBV was not affected by HRT over a 12-month period. Oestrone levels were higher in smokers. CONCLUSIONS: Smoking adversely affects insulin secretion (beta-cell function) and WBV in postmenopausal women with established CHD, which could be of importance as a mechanism for the increased risk of CHD in smokers. The importance of smoking as a risk factor, overrides the effect of Lp(a), which is lower in smokers compared with nonsmokers.

Aged↗
PubMed2001

Serum lipids and regulation of tissue factor-induced coagulation in middle-aged men.

Formation of an occlusive thrombus by exposure of tissue factor (TF) to circulating blood and subsequent triggering of coagulation by TF-activated factor VII (FVIIa) complexes on ruptured atherosclerotic plaques is thought to be a key event in myocardial infarction. Tissue factor pathway inhibitor (TFPI) is a potent inhibitor of TF-induced coagulation in which the anticoagulant function most probably is restricted to free TFPI in human plasma. The present study was undertaken to assess the interrelations between serum lipids and components of TF-induced coagulation in 234 apparently healthy men aged 36-56 years recruited from the general population. Plasma free TFPI antigen (Ag) was positively correlated (P < .001) with total cholesterol, low-density lipoprotein (LDL) cholesterol, triglycerides, apolipoprotein B (apoB-100), fibrinogen, total amount of FVII (FVIIam), coagulation activity of factor VII (FVIIc), and FVIIa. The significant predictors for free TFPI Ag were total cholesterol, triglycerides, fibrinogen, FVIIc, and age, which explained 33% of the plasma variation in free TFPI Ag assessed by multiple regression analysis. A highly significant (P < .0001) linear trend for increase in atherogenic lipids (i.e., total cholesterol and triglycerides), FVII (i.e., FVIIc and FVIIa), and fibrinogen across quartiles of TFPI Ag was demonstrated after adjustment for confounders. These findings may indicate a compensatory increase in plasma free TFPI with lipid and hemostatic risk factors for atherothrombotic diseases in healthy middle-aged men.

Adult↗
PubMed2001

Hemostatic activation in acute ischemic stroke.

BACKGROUND AND PURPOSE: The purpose of this study was to examine the association between hemostatic activation and stroke severity, and to provide data on hemostatic variables in acute ischemic stroke. METHODS: The patient material comprised 76 consecutive patients with acute ischemic stroke (median 16 h, interquartile range 3-48). Levels of hemostatic variables were determined in blood samples collected on the day of hospitalization. Stroke severity was assessed on admission by the Oxfordshire Community Stroke Project (OCSP) classification, and on discharge (median 9 days, interquartile range 6-14) by Barthel Index (BI, scores 0-50, 55-90, or 95-100) and modified Rankin Scale (mRS, scores 0-1 or 2-6). Associations were assessed by multiple linear regression analyses. RESULTS: Levels of the fibrin degradation product D-Dimer and the activation peptide prothrombin fragment 1 + 2 (F1 + 2) were linearly related to stroke severity, whether assessed on admission (P = .001 and.03, respectively, for the OCSP classification), or on discharge (P = .009 and.43, respectively, for BI; and.001 and.05, respectively, for mRS). High levels of D-Dimer and F(1 + 2), as well as low levels of antithrombin and protein C were also present in patients with a presumed embolic source, and low antithrombin or protein C was borderline significantly associated with atrial fibrillation (P = .072 and.058, respectively). Low levels of protein C or protein S, and the presence of antiphospholipid antibodies, including lupus anticoagulant (LA), was detected in 13/73 (18%) and 15/70 (21%) of the patients, respectively. CONCLUSION: Activation of the hemostatic system is independently related to acute stroke severity and short-term outcome. Low levels of coagulation inhibitors or presence of antiphospholipid antibodies is a relatively frequent finding in unselected patients with acute ischemic stroke, but a causative role cannot be inferred from our study.

Adult↗
PubMed2001

Hormone replacement therapy and acquired resistance to activated protein C: results of a randomized, double-blind, placebo-controlled trial.

Recent studies suggest that low-dose oral contraceptives may cause acquired resistance to activated protein C (APC). The aims of this study were to determine whether hormone replacement therapy (HRT) may also induce acquired APC resistance and to study the effects of APC resistance on the risk of recurrent thrombosis. The patients comprised 140 females with at least one previous venous thromboembolism (VTE), who were randomized to receive continuous treatment with 2 mg 17-beta-oestradiol and 1 mg norethisterone acetate (n = 71) or placebo (n = 69). Normalized APC sensitivity ratios (nAPCsr) were calculated by measurement of the effect of APC on thrombin generation in plasma collected at baseline and after 3 months of treatment. Of the 140 women, 121 had plasma samples collected both at baseline and after 3 months. The nAPCsr increased significantly (P < 0.001) on HRT (n = 62), both in females not carrying the factor V(Leiden) mutation [mean change 0.57 (95% CI 0.45-0.70), n = 50] and in females heterozygous for the factor V(Leiden) mutation [mean change 1.10 (0.71-1.49), n = 12], but remained unchanged on placebo (n = 59). The baseline nAPCsr as well as the increase in nAPCsr associated with HRT use was not higher in the five women who subsequently developed recurrent VTE. Free protein S and free TFPI were both important parameters for the acquired APC resistant phenotype. We conclude that HRT diminishes the efficacy by which APC downregulates in-vitro thrombin formation in a similar fashion to that observed with low-dose oral contraceptives, but the increase in nAPCsr alone is not sufficient to explain the increased risk of VTE associated with use of HRT.

Activated Protein C Resistance↗