Search PubMed⌕ Search

Biomedical subjects

K A Bauer

Publications and source records attributed to K A Bauer.

At least 19 recordsLinked to original sources
PubMed2006

Hormonal factors and risk of recurrent venous thrombosis: the prevention of recurrent venous thromboembolism trial.

BACKGROUND: In some but not all studies, men with venous thrombosis had a higher risk of recurrence than women. Information on women with initial hormone-related thrombosis is scant. OBJECTIVE: We assessed the incidence of recurrent thrombosis by gender, and among women using exogenous hormones or pregnant/postpartum at the time of index thrombosis. PATIENTS/METHODS: A total of 508 men and women with one or more previous venous thrombosis episodes were observed while participating in a randomized trial of low-intensity warfarin or placebo for 2.1 years. Index thrombosis events during treatment with postmenopausal hormones, oral contraceptives, or during pregnancy, or the puerperium were considered to be hormone-related events. RESULTS: Among 268 men the 3-year probability of recurrent thrombosis was 18.4% (95% confidence intervals; CI 12.3-24.4). Among 109 women without hormone-related thrombosis, the rate was 15.0% (95% CI 6.3-23.8). Among 129 women with hormone-related thrombosis, the rate was 5.0% (95% CI 1.1-8.9). Adjusting for other risk factors and treatment assignment, women had a 39% lower thrombosis recurrence risk than men: hazard ratio (HR) 0.61 (95% CI 0.34-1.08). Women with hormone-related thrombosis had a 58% lower risk than men: HR 0.42 (95% CI 0.19-0.97); and a 46% lower recurrence risk than other women; HR 0.54 (95% CI 0.19-1.54). Women without hormone-related index events had a recurrence rate similar to men; HR 0.83 (95% CI 0.42-1.66). CONCLUSIONS: In this trial population, women had a lower risk of recurrent venous thrombosis than men. This difference was explained by a low risk of recurrence among women with hormone-related index thrombosis.

Aged↗
PubMed2006

D-dimer, factor VIII coagulant activity, low-intensity warfarin and the risk of recurrent venous thromboembolism.

BACKGROUND: Elevated plasma D-dimer and factor VIII coagulant activity (FVIIIc) may be associated with the risk of recurrent venous thromboembolism (VTE). OBJECTIVES: To evaluate D-dimer and FVIIIc as risk factors for recurrent VTE and assess the efficacy of extended low-intensity warfarin (target International Normalized Ratio 1.5-2.0) in preventing recurrence by biomarker level. PATIENTS AND METHODS: In the Prevention of Recurrent Venous Thromboembolism trial, 508 idiopathic VTE patients treated for > or = 3 months with full-intensity warfarin, and who had stopped warfarin for 7 weeks on average, were randomized to low-intensity warfarin or placebo and followed for 2.1 years for recurrent VTE. Prerandomization blood samples were analysed for D-dimer and FVIIIc. RESULTS: One-third of participants had elevated baseline D-dimer (> or = 500 ng mL(-1)) and one-fourth, elevated FVIIIc (> or = 150 IU dL(-1)). Adjusting for other risk factors, the hazard ratios (HRs) for recurrent VTE with elevated D-dimer or FVIIIc were 2.0 [95% confidence interval (CI) 1.2-3.4] and 1.5 (95% CI 0.8-2.8), respectively. The association of elevated D-dimer with recurrence was larger among patients with one prior VTE (HR 3.2, 95% CI 1.3-8.0) than in patients with more than one event (HR 1.4, 95% CI 0.7-2.2). For patients with one prior VTE on placebo, the annual recurrence incidence was 10.9% with elevated D-dimer and 2.9% with normal values. Low-intensity warfarin was equally effective in recurrence risk reduction in those with normal or elevated biomarkers. CONCLUSIONS: Among patients with idiopathic VTE, measurement of D-dimer, but not FVIIIc, might be useful for risk stratification. The efficacy of extended low-intensity warfarin therapy did not vary by biomarker level.

Adult↗
PubMed2005

Plasma fibrinogen level and the risk of major cardiovascular diseases and nonvascular mortality: an individual participant meta-analysis.

CONTEXT: Plasma fibrinogen levels may be associated with the risk of coronary heart disease (CHD) and stroke. OBJECTIVE: To assess the relationships of fibrinogen levels with risk of major vascular and with risk of nonvascular outcomes based on individual participant data. DATA SOURCES: Relevant studies were identified by computer-assisted searches, hand searches of reference lists, and personal communication with relevant investigators. STUDY SELECTION: All identified prospective studies were included with information available on baseline fibrinogen levels and details of subsequent major vascular morbidity and/or cause-specific mortality during at least 1 year of follow-up. Studies were excluded if they recruited participants on the basis of having had a previous history of cardiovascular disease; participants with known preexisting CHD or stroke were excluded. DATA EXTRACTION: Individual records were provided on each of 154,211 participants in 31 prospective studies. During 1.38 million person-years of follow-up, there were 6944 first nonfatal myocardial infarctions or stroke events and 13,210 deaths. Cause-specific mortality was generally available. Analyses involved proportional hazards modeling with adjustment for confounding by known cardiovascular risk factors and for regression dilution bias. DATA SYNTHESIS: Within each age group considered (40-59, 60-69, and > or =70 years), there was an approximately log-linear association with usual fibrinogen level for the risk of any CHD, any stroke, other vascular (eg, non-CHD, nonstroke) mortality, and nonvascular mortality. There was no evidence of a threshold within the range of usual fibrinogen level studied at any age. The age- and sex- adjusted hazard ratio per 1-g/L increase in usual fibrinogen level for CHD was 2.42 (95% confidence interval [CI], 2.24-2.60); stroke, 2.06 (95% CI, 1.83-2.33); other vascular mortality, 2.76 (95% CI, 2.28-3.35); and nonvascular mortality, 2.03 (95% CI, 1.90-2.18). The hazard ratios for CHD and stroke were reduced to about 1.8 after further adjustment for measured values of several established vascular risk factors. In a subset of 7011 participants with available C-reactive protein values, the findings for CHD were essentially unchanged following additional adjustment for C-reactive protein. The associations of fibrinogen level with CHD or stroke did not differ substantially according to sex, smoking, blood pressure, blood lipid levels, or several features of study design. CONCLUSIONS: In this large individual participant meta-analysis, moderately strong associations were found between usual plasma fibrinogen level and the risks of CHD, stroke, other vascular mortality, and nonvascular mortality in a wide range of circumstances in healthy middle-aged adults. Assessment of any causal relevance of elevated fibrinogen levels to disease requires additional research.

Adult↗
PubMed2005

EPCR Ser219Gly: elevated sEPCR, prothrombin F1+2, risk for coronary heart disease, and increased sEPCR shedding in vitro.

We have progressively analysed three studies of coronary heart disease (CHD) for a variant in EPCR (Ser219Gly). Initially, in a prospective study, NPHSII, while no overall CHD-risk was identified in heterozygotes, homozygotes for 219Gly exhibited a three-fold elevated risk (HR 3.3, CI 1.22-8.96). In diabetics within NPHSII, there was a suggestion that 219Gly+ was associated with elevated CHD-risk (HR 1.89, CI 0.39-9.06) although numbers were small. To further assess the effect of the variant in diabetes, a case-control study of MI, HIFMECH, was used, in which previous analysis had defined a group with metabolic syndrome, by factor analysis. A significant CHD-risk interaction was identified between genotype and the 'metabolic syndrome' factor (interaction p=0.009). To further assess CHD-risk for this variant in type-2 diabetes and to assess the effect of the variant upon thrombin generation and plasma levels of soluble EPCR, a cross-sectional study of type-2 diabetes was used. A significant CHD-risk was identified for European Whites (OR 2.84, CI 1.38-5.85) and Indian Asians in this study (OR 1.6, CI 1.00-2.57) and the frequency of 219Gly was two-fold higher in Indian Asians. Soluble EPCR levels were strongly associated with genotype, with homozygotes for 219Gly having four-fold higher levels (p<0.0001). In vitro studies of EPCR-transfected cells suggested increased basal release of sEPCR from cells expressing the 219Gly EPCR phenotype. Furthermore, in base-line samples from NPHSII and in the diabetic study, a significant increase in prothrombin F1+2 level was observed for 219Gly. The increased CHD-risk and thrombin generation appears to be acting through increased shedding of the Gly allele from the cell surface.

Animals↗
PubMed2005

BAY 59-7939: an oral, direct factor Xa inhibitor for the prevention of venous thromboembolism in patients after total knee replacement. A phase II dose-ranging study.

BACKGROUND: BAY 59-7939, a novel, oral, direct factor Xa inhibitor, is in clinical development for the prevention of venous thromboembolism (VTE), a frequent complication following orthopaedic surgery. METHODS: In a multicenter, parallel-group, double-blind, double-dummy study, 621 patients undergoing elective total knee replacement were randomly assigned to oral BAY 59-7939 (2.5, 5, 10, 20, and 30 mg b.i.d., initiated 6-8 h postsurgery), or subcutaneous enoxaparin (30 mg b.i.d., initiated 12-24 h postsurgery). Treatment was continued until mandatory bilateral venography 5-9 days after surgery. The primary efficacy endpoint was a composite of any deep vein thrombosis (proximal and/or distal), confirmed non-fatal pulmonary embolism and all-cause mortality during treatment. The primary safety endpoint was major, postoperative bleeding during treatment. RESULTS: Of the 613 patients treated, 366 (59.7%) were evaluable for the primary efficacy analysis. The primary efficacy endpoint occurred in 31.7%, 40.4%, 23.3%, 35.1%, and 25.4% of patients receiving 2.5, 5, 10, 20 and 30 mg b.i.d. doses of BAY 59-7939, respectively (test for trend, P = 0.29), compared with 44.3% in the enoxaparin group. The frequency of major, postoperative bleeding increased with increasing doses of BAY 59-7939 (test for trend, P = 0.0007), with no significant difference between any dose group compared with enoxaparin. Bleeding endpoints were lower for the 2.5-10 mg b.i.d. doses compared with higher doses of BAY 59-7939. CONCLUSIONS: Oral administration of 2.5-10 mg b.i.d. of BAY 59-7939, early in the postoperative period, showed potential efficacy and an acceptable safety profile, similar to enoxaparin, for the prevention of VTE in patients undergoing elective total knee replacement.

Administration, Oral↗
PubMed2004

Bilateral vs. ipsilateral venography as the primary efficacy outcome measure in thromboprophylaxis clinical trials: a systematic review.

Contrast venography, in combination with symptomatic venous thromboembolism (VTE), is the standard efficacy outcome measure in clinical trials of thromboprophylaxis in major orthopedic surgery. It is uncertain whether performing bilateral venography offers any real advantage over venography of the operated leg alone. This study was undertaken to determine the risk of isolated contralateral deep vein thrombosis (DVT) following major orthopedic surgery and to evaluate whether bilateral venography, rather than venography on the operated leg alone, offers any gain in DVT detection and, thereby, improves efficiency in clinical study design. A systematic review of prospective studies that reported DVT incidence as the primary efficacy outcome based on mandatory bilateral venography in patients undergoing elective hip or knee arthroplasty or hip fracture repair was conducted. Based on the use of bilateral venography as a primary efficacy outcome measure, the incidence of any DVT is 16.7% following total hip replacement, 18.8% after hip fracture repair, and 33.8% after total knee replacement. While DVT risk in the operated leg varies depending on the type of surgery, the risk of isolated DVT in the non-operated leg is approximately 4% to 5% in all three procedures. By increasing the detection of any DVT, the use of bilateral venography reduces required sample size by 16% to 25% compared to ipsilateral venography. In clinical trials evaluating the efficacy of thromboprophylaxis in major orthopedic surgery, bilateral venography reduces the risk of undiagnosed DVT in the non-operated leg and improves the efficiency of study design by substantially reducing the sample size requirement.

Anticoagulants↗
PubMed2004

Increased incidence of neoplasia of the digestive tract in men with persistent activation of the coagulant pathway.

BACKGROUND: Thrombin promotes angiogenesis and cell proliferation in cancer. Whether thrombin turnover influences cancer incidence is unknown. OBJECTIVES: To explore the relation between the status of the coagulant pathway and cancer incidence by population survey. METHODS: Of 4,009 middle-aged men clinically free of malignancy, 3052 (76.1%) were recruited. Measurements of hemostatic status were made annually for 4 years, and follow-up for morbidity and mortality was maintained thereafter. Persistent activation of the coagulant pathway was diagnosed when prothrombin fragment 1+2 and fibrinopeptide A concentrations exceeded the upper quartiles of the population distribution in two consecutive annual examinations. Cancer incidence rates in men developing persistent activation (taking the time of onset of activation as baseline) were compared with those in men remaining free of this condition. RESULTS: Persistent activation of the hemostatic pathway was a distinct entity found in 111 men [43 expected by chance alone (P <0.001)], and associated with activation throughout the coagulation pathway. Total mortality (/1000 person-years) was higher in those with persistent activation than in others (17.1 and 9.7, respectively, P=0.015), owing to a higher mortality from all cancers (11.3 and 5.1, respectively, P=0.01), due in turn largely to a higher mortality from cancers of the digestive tract (6.3 and 1.9, respectively, P=0.004). Trends were similar for non-fatal cancers. CONCLUSIONS: Persistent activation of the coagulant pathway plays a role in the preclinical phase of cancer and is associated with an increased incidence of clinical malignancy, especially of the digestive tract.

Coagulants↗
PubMed2004

Thrombosis and ELISA optical density values in hospitalized patients with heparin-induced thrombocytopenia.

The natural history of heparin-induced thrombocytopenia (HIT) in the absence of thrombosis was previously established using functional assays for confirmation of diagnosis (e.g. 14C serotonin release assay). An enzyme-linked immunosorbent assay (ELISA) that detects the presence of antibodies directed against the heparin-platelet factor-4 (PF4) complex has largely replaced functional assays in many medical centers. Although the ELISA is highly sensitive for detecting HIT antibodies, its usefulness for predicting thrombotic outcomes has not been clearly established. We performed a retrospective chart review of all hospitalized patients at a university hospital who tested seropositive for HIT by a commercial ELISA during 2001 and 2002. A total of 63 inpatients were identified as HIT positive by ELISA. Forty-eight patients had no apparent HIT-associated thrombosis at the time of HIT seropositivity (i.e. isolated HIT) and only one was treated prophylactically with a direct thrombin inhibitor. The 30-day thrombosis rate for patients with isolated HIT was 17% (eight of 48). Higher ELISA optical density (OD) measurements correlated significantly with thrombosis (1.41 +/- 0.87 vs. 0.79 +/- 0.46, P <0.001). Patients with isolated HIT and an OD measurement of > or = 1.0 demonstrated nearly a 6-fold increased risk of thrombosis compared with those with OD values between 0.4 and 0.99 (odds ratio 5.74, 95% confidence interval 1.73, 19.0; absolute rate of thrombosis, 36% vs. 9%, respectively, P=0.07). We conclude that in hospitalized patients with isolated HIT, the presence of heparin-PF4 antibodies detected by ELISA was associated with a significant risk of subsequent thrombosis and higher ELISA values were observed among patients suffering thrombotic events.

Aged↗
PubMed2004

Heritability of plasma concentrations of clotting factors and measures of a prethrombotic state in a protein C-deficient family.

BACKGROUND: Earlier studies found strong support for a genetic basis for regulation of coagulation factor levels and measures of a prethrombotic state (d-dimer, prothrombin fragment 1.2). OBJECTIVES: Estimation of how much of the variation in the levels of coagulation factors and measures of a prethrombotic state, including measures of protein C activation and inactivation, could be attributed to heritability and household effect. PATIENTS AND METHODS: Blood samples were collected from 330 members of a large kindred of French-Canadian origin with type I protein C deficiency. Heritability and common household effect were estimated for plasma concentrations of prothrombin, factor (F)V, factor VIII, factor (F)IX, fibrinogen, von Willebrand factor (VWF), antithrombin, protein C, protein S, protein Z, protein Z-dependent protease inhibitor (ZPI), fibrinopeptide A (FPA), protein C activation peptide (PCP), activated protein C-protein C inhibitor complex (APC-PCI), activated protein C-alpha1-antitrypsin complex (APC-alpha1AT), prothrombin fragment 1.2 (F1.2) and d-dimer, using the variance component method in sequential oligo-genic linkage analysis routines (SOLAR). RESULTS: The highest heritability was found for measures of thrombin activity (PCP and FPA). High estimates were also found for prothrombin, FV, FIX, protein C, protein Z, ZPI, APC-PCI and APC-alpha1AT. An important influence of shared household effect on phenotypic variation was found for VWF, antithrombin, protein S and F1.2. CONCLUSIONS: We found strong evidence for the heritability of single coagulation factors and measures of a prethrombotic state. Hemostatic markers with statistically significant heritability constitute potential targets for the identification of novel genes involved in the control of quantitative trait loci.

Adolescent↗
PubMed2003

ARP1 interacts with the 5' flanking region of the coagulation factor VII gene.

Factor (F)VII plays a critical role in initiation of coagulation. Several segments within the 5' flanking region of the FVII gene were previously demonstrated to recognize hepatic nuclear proteins, but few have been identified. To identify a regulatory protein binding the nuclear hormone response region (-237 to -200) of the FVII 5' flanking region and demonstrate that the interaction is functional. Electrophoretic mobility shift assays and mutation analysis showed that ARP1, an orphan nuclear hormone receptor, interacted with two regions of the FVII 5' flanking region, the hepatic nuclear factor 4 binding region (-77 to -47) and the nuclear hormone response region (-237 to -200). Transfection experiments demonstrated that reporter gene expression was decreased from vectors including the nuclear hormone response segment compared with that containing only the minimal promoter between positions -109 and +1, and that ARP1 also repressed expression through an interaction with the minimal promoter. These data indicate a role for ARP1 in transcriptional modulation of the FVII gene.

5' Flanking Region↗
PubMed2003

Management of thrombophilia.

It is now possible to identify acquired and hereditary risk factors in a substantial percentage of patients presenting with a venous thrombotic event. Discovery of the factor V Leiden and prothrombin G20210A mutations has greatly increased the percentage of patients in whom venous thrombosis can be attributed to hereditary thrombophilia. There is, however, considerable uncertainty as to how this information should be used in patient management. Although prolonged anticoagulation at an international normalized ratio of 2-3 is highly effective in preventing thrombotic recurrences, this benefit is partially offset by major bleeding which occurs at an average rate of 2%-3% per year. A decision as to the overall benefit of extended anticoagulation in the individual patient requires assessment of the risk of recurrence in the absence of treatment vs. the bleeding risk associated with prolonged anticoagulation. Low-intensity warfarin therapy or novel anticoagulants such as oral direct thrombin inhibitors may prove effective strategies for preventing recurrent venous thromboembolism in patients with thrombophilia.

Anticoagulants↗
PubMed2003

A functional haplotype in the 5' flanking region of the factor VII gene is associated with an increased risk of coronary heart disease.

AIMS: The aim of this study was to investigate associations between coronary heart disease risk and polymorphisms in the coagulation factor (F)VII gene in participants of a large prospective study. METHODS: One thousand nine hundred and fifty-seven men were genotyped for four FVII polymorphisms, -670A-->C, -402G-->A, a 10 base pair insertion at -323 (0 > 10) in the promoter, and R353Q in the structural gene. Associations among genotypes and estimated haplotypes, plasma FVII levels, and coronary heart disease risk were evaluated, and the function of the promoter polymorphisms was assessed in reporter gene assays. RESULTS: The -670A-->C and -402G-->A polymorphisms were in complete allelic association. The haplotype containing -670C and -402A (frequency =0.23) was associated with significantly increased plasma FVII coagulant activity and increased risk of an initial coronary event, particularly acute myocardial infarction, which remained after correction for conventional risk factors. In contrast, the -323 insertion and Q353 alleles (frequency =0.11 and 0.10, respectively) were associated with decreased plasma FVII levels, but hazard ratios for coronary events in carriers of these alleles were not significantly different from unity. In transiently transfected hepatoma cells, increased basal expression of the reporter gene was directed by a promoter fragment with rare haplotype -670C/-630G/-402A rather than by a promoter fragment with common haplotype -670A/-630A/-402G; -402A was not responsible for this effect. CONCLUSIONS: The promoter haplotype, -670C/-630G/402A, was associated with significantly increased plasma FVII coagulant activity, risk of an initial coronary event, particularly acute myocardial infarction, and reporter gene expression.

Alleles↗
PubMed2002

Does inflammatory proteolytic activity contribute to the increased factor IX activation peptide in men at high risk of coronary heart disease? A preliminary study.

In the Second Northwick Park Heart Study, the activation peptides of factor IX (FIXpep) and factor X (FXpep) were measured in 1261 middle-aged men by double-antibody radioimmunoassay. During follow-up 147 men who had a first coronary heart disease (CHD) event were found to have had an increased FIXpep (p = 0.003) and a reduced FXpep (p = 0.05) at baseline compared with those remaining CHD-free (controls). Plasma FIXpep and FXpep were positively associated, but the rate of rise in FIXpep with increasing FXpep was higher in cases than controls (p for interaction = 0.01). In a sample of 87 controls, FIXpep was positively and independently related to the concentrations of a polymorphonuclear-specific fibrinogen degradation product (p = 0.036) and FXpep (p = 0.004), but in larger samples no statistically significant associations were found either with C-reactive protein or with fibrinogen concentration. The findings suggested that the increased FIXpep in men at high CHD-risk may have been partly due to the generation of factor IX inactivation peptides by inflammatory proteolysis and their recognition together with true FIXpep in the radioimmunoassay. Direct evidence for this hypothesis requires development of assays for human elastase-specific factor IX inactivation peptides.

Case-Control Studies↗
PubMed2001

Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after elective major knee surgery.

BACKGROUND: Despite thromboprophylaxis, major knee surgery carries a high risk of venous thromboembolism. Fondaparinux, the first of a new class of synthetic antithrombotic agents, may reduce this risk. METHODS: In a double-blind study, we randomly assigned 1049 consecutive patients undergoing elective major knee surgery to receive subcutaneous doses of either 2.5 mg of fondaparinux once daily or 30 mg of enoxaparin twice daily, with both treatments initiated postoperatively. The primary efficacy outcome was venous thromboembolism up to postoperative day 11, defined as deep-vein thrombosis detected by mandatory bilateral venography, documented symptomatic deep-vein thrombosis, or documented symptomatic pulmonary embolism. The primary safety outcome was major bleeding. RESULTS: The primary efficacy outcome was assessed in 724 patients. The fondaparinux group had a significantly lower incidence of venous thromboembolism by day 11 (12.5 percent [45 of 361 patients]) than the enoxaparin group (27.8 percent [101 of 363 patients]; reduction in risk, 55.2 percent; 95 percent confidence interval, 36.2 to 70.2; P<0.001). Major bleeding (including overt bleeding with a bleeding index of 2 or more) occurred more frequently in the fondaparinux group (P=0.006), but there were no significant differences between the two groups in the incidence of bleeding leading to death or reoperation or occurring in a critical organ. CONCLUSIONS: In patients undergoing elective major knee surgery, postoperative treatment with 2.5 mg of fondaparinux once daily was significantly more effective in preventing deep-vein thrombosis than 30 mg of enoxaparin twice daily.

Aged↗
PubMed2001

Fondaparinux compared with enoxaparin for the prevention of venous thromboembolism after hip-fracture surgery.

BACKGROUND: Surgery for hip fracture carries a high risk of venous thromboembolism, despite the use of current thromboprophylactic treatments. Fondaparinux, a synthetic pentasaccharide, is a new antithrombotic agent that may reduce this risk. METHODS: In a double-blind study, were randomly assigned 1711 consecutive patients undergoing surgery for fracture of the upper third of the femur to receive subcutaneous doses of either 2.5 mg of fondaparinux once daily, initiated postoperatively, or 40 mg of enoxaparin once daily, initiated preoperatively, for at least five days. The primary efficacy outcome was venous thromboembolism up to postoperative day 11. Venous thromboembolism was defined as deep-vein thrombosis detected by mandatory bilateral venography, documented symptomatic deep-vein thrombosis, or documented symptomatic pulmonary embolism. The main safety outcomes were major bleeding and mortality from all causes. The duration of follow-up was six weeks. RESULTS: The incidence of venous thromboembolism by day 11 was 8.3 percent (52 of 626 patients) in the fondaparinux group and 19.1 percent (119 of 624 patients) in the enoxaparin group (P<0.001). The reduction in risk with fondaparinux was 56.4 percent (95 percent confidence interval, 39.0 to 70.3 percent). There were no significant differences between the two groups in the incidence of death or clinically relevant bleeding. CONCLUSIONS: In patients undergoing surgery for hip fracture, fondaparinux was more effective than enoxaparin in preventing venous thromboembolism and equally safe.

Aged↗
PubMed2001

Fondaparinux sodium: a selective inhibitor of factor Xa.

The pharmacology and mechanism of action of fondaparinux sodium are described. Fondaparinux sodium is the first agent of a new class of anticoagulants that selectively target factor Xa. It has a linear, dose-dependent pharmacokinetic profile, which provides a highly predictable response. It is 100% bioavailable, has a rapid onset of action, and has a half-life of 14 to 16 hours, allowing for sustained antithrombotic activity over a 24-hour period. The drug does not affect prothrombin time or activated partial thromboplastin time, nor does it affect platelet function or aggregation. Studies in patients with confirmed heparin-induced thrombocytopenia demonstrate that the drug is not associated with in vitro cross-reactivity to heparin antibodies. Fondaparinux sodium appears to meet the criteria for an ideal antithrombotic agent: equal or better effectiveness than currently available agents, a low bleeding risk, no need for laboratory monitoring, and once-daily administration.

Anticoagulants↗
PubMed2001

Thrombogenic potential of human coronary atherosclerotic plaques.

Higher levels of tissue factor (the initiator of blood coagulation) have been found in coronary atherosclerotic plaques of patients with unstable coronary artery disease, but it is not established whether they are associated with a different thrombotic response to in vivo plaque rupture. In 40 patients undergoing directional coronary atherectomy, prothrombin fragment 1 + 2, a marker of thrombin generation, was measured in intracoronary blood samples obtained proximally and distally to the coronary atherosclerotic plaque before and after the procedure. Before the procedure, plasma prothrombin fragment 1 + 2 levels were significantly increased across the lesion in patients with unstable, but not in those with stable, coronary disease (unstable, median increase, 0.37 nM; range, -0.35-1.16 nM) (stable, median increase, -0.065 nM; range, -0.58-1.06 nM) (P =.0021). After plaque removal, an increase in prothrombin fragment 1 + 2 across the lesion was observed only in patients with unstable coronary disease (unstable, median increase, 0.25 nM; range, -1.04-4.9 nM) (stable, 0.01 nM; range, -0.48-3.59 nM) (P =.036)]. There was a correlation between the tissue factor content of the plaque and the increase in thrombin generation across the lesion (rho = 0.33; P =.038). The higher tissue factor content found in plaques obtained from patients with unstable coronary disease was associated with a local increase in thrombin generation, thus suggesting a link with the in vivo thrombogenicity of the plaque.

Aged↗