In vitro assessment of the anti-biofilm activity of ethanol alone and in combination with enoxaparin 60IU.

INTRODUCTION: Catheter-related bloodstream infection (C-RBSI) can sometimes be managed without catheter removal by combining systemic therapy with catheter lock therapy. Most antiseptic lock solutions are made up of ethanol combined with an anticoagulant. However, data regarding the anti-biofilm activity of ethanol combined with enoxaparin are scarce. We aimed to assess the efficacy of ethanol at different concentrations combined with enoxaparin 60IU as a lock solution for eradication of the biofilm of different microorganisms. METHODS: Using a static 96-well plate in vitro model, we tested 30%, 35%, and 40% ethanol alone and combined with 60IU of enoxaparin against 24-h-old biofilm from the following microorganisms: Staphylococcus aureus, Staphylococcus epidermidis, Enterococcus faecalis, Escherichia coli, and Candida albicans. Time of exposure was assessed during a 2-h and 24-h regimen. We analysed the percentage reduction in metabolic activity using the XTT assay. We considered therapy to be successful when metabolic activity was reduced by >90%. RESULTS: In the 2-h regimen, the therapy was successful against all microorganisms at 35% and 40% ethanol without enoxaparin (p<0.001). In the 24-h regimen, the therapy was successful against all microorganisms at all ethanol solutions without enoxaparin (p<0.001). When ethanol was combined with enoxaparin, the therapy was only successful in the 24-h regimen in biofilms of S. epidermidis, C. albicans and E. coli at all concentrations of ethanol assessed. CONCLUSIONS: Our in vitro model demonstrated that when ethanol is combined with enoxaparin in a lock solution, it negatively affects ethanol anti-biofilm activity after both short and long exposures.

Update on Brazilian biosimilar enoxaparins.

INTRODUCTION: Brazil is among the first countries approving the commercialization and clinical use of biosimilar enoxaparins. Our research group has performed quality control assessments of these drugs over the last decade. Areas covered: We have not found noticeable differences between Brazilian biosimilar enoxaparins and the original product regarding their physicochemical properties, disaccharide composition, anticoagulant activity, bioavailability and safety. Expert commentary: In spite of clinical and pharmacological advantages of enoxaparin, subcutaneous formulations of unfractionated heparin are employed by the Brazilian public health system for prevention and treatment of thromboembolism. The underuse of both original and biosimilar enoxaparins in Brazil directly correlates with their high cost.

Analytical comparison of a US generic enoxaparin with the originator product: The focus on comparative assessment of antithrombin-binding components.

Enoxaparin sodium, a low-molecular-weight heparin (LMWH) prepared from porcine intestinal heparin, is widely used for the prevention and treatment of venous thromboembolism. The antithrombotic activity of heparin is mediated mainly through its activation of antithrombin (AT) and subsequent inhibition of coagulation factors. Heparin is a complex heteropolymer and the sulfation pattern of its alternating uronic acid and glucosamine sugar units is a major factor influencing its biological activity. The manufacturing process itself is associated with the introduction of exogenous microheterogeneities that may further affect its biological efficacy. This is important since enoxaparin is prepared by depolymerizing the heparin with the aim of optimizing its biological activity and safety. Changes during its manufacture could thus affect its biological activity and safety. The current study was performed to assess potential differences between the originator enoxaparin and a new generic enoxaparin commercialized by Teva. Heparinase digestion, AT affinity chromatography, gel permeation chromatography, anion exchange chromatography, and nuclear magnetic resonance methodologies were used. The results indicated differences in oligosaccharides related to the cleavage selectivity around the heparin AT-binding sequences of the Teva Enoxaparin Sodium Injection, USP and the originator Sanofi enoxaparin. These differences influence the strength of the AT-binding affinity of the individual oligosaccharides, their ability to activate AT and, therefore, the inhibitory potency on the proteases of the coagulation cascade. This study, together with other published analytical reports, describes specific compositional differences between generics and originator LWMHs. However, it is yet to be established whether such variations might have any clinical relevance.

Reproducibility of the anti-Factor Xa and anti-Factor IIa assays applied to enoxaparin solution.

Enoxaparin is a widely used subcutaneously administered antithrombotic agent comprising a complex mixture of glycosaminoglycan chains. Owing to this complexity, its antithrombotic potency cannot be defined by physicochemical methods and is therefore evaluated using an enzymatic assay of anti-Xa and anti-IIa activity. Maintaining consistent anti-Xa activity in the final medicinal product allows physicians to ensure administration of the appropriate dosage to their patients. Bioassays are usually complex and display poorer reproducibility than physicochemical tests such as HPLC assays. Here, we describe the implementation of a common robotic platform and standard release potency testing procedures for enoxaparin sodium injection (Lovenox, Sanofi, Paris, France) products at seven quality control sites within Sanofi. Qualification and analytical procedures, as well as data handling, were optimized and harmonized to improve assay reproducibility. An inter-laboratory study was performed in routine-release conditions. The coefficients of variation for repeatability and reproducibility in assessments of anti-Xa activity were 1.0% and 1.2%, respectively. The tolerance interval in reproducibility precision conditions, expressed as percentage potency, was 96.8-103.2% of the drug product target of 10,000 IU/ml, comparing favorably with the United States of America Pharmacopeia specification (90-110%). The maximum difference between assays in two different laboratories is expected to be 4.1%. The reproducibility characteristics of anti-IIa activity assessments were found to be similar. These results demonstrate the effectiveness of the standardization process established and allow for further improvements to quality control in Lovenox manufacture. This process guarantees closeness between actual and target potencies, as exemplified by the results of release assays obtained during a three-year period.

Comparative pharmacodynamic assessment of the antiangiogenesis activity of heparin and low-molecular-weight heparin fractions: structure-function relationship.

Effects of unfractionated heparin and low-molecular-weight heparins (LMWHs) on human microvascular endothelial cell sprouting (tube formation assay) in vitro were determined. Antiangiogenesis efficacy of commercially available LMWHs tinzaparin and enoxaparin in the chick chorioallantoic membrane (CAM) model of growth factor-induced angiogenesis was compared. The LMWH tinzaparin was fractionated into different molecular weight (MW) pools by size exclusion chromatography; they inhibited CAM angiogenesis depending on their MW distribution, with optimal inhibition at 8 to 12 kDa and no inhibition at <2 kDa. Tinzaparin demonstrated greater antiangiogenesis efficacy than enoxaparin (P < .001); these CAM results correlated with the endothelial tube formation assay results (P < .001, tinzaparin vs enoxaparin). These data point to the variable antiangiogenesis efficacy of different LMWHs as a function of MW and perhaps other structural differences. Our hypothesis confirmed a relationship between lower release of tissue factor pathway inhibitor by lower MW fractions of tinzaparin or enoxaparin leading to reduced antiangiogenesis efficacy.

Prolonged postoperative venous thrombo-embolism prophylaxis is cost-effective in advanced ovarian cancer patients.

OBJECTIVE: The purpose of this study was to investigate the cost-effectiveness of prolonged prophylaxis with enoxaparin in high-risk surgical patients with ovarian cancer. In addition, we sought to quantify the impact of prolonged prophylaxis (PP) on the incidence of venous thromboembolism (VTE), its related complications, and overall patient survival. METHODS: A Markov decision analytic model was used to estimate the costs, resource allocation and outcomes associated with the prolonged use of enoxaparin, for a total of four weeks after surgery, in patients undergoing primary debulking surgery for stage IIIC ovarian cancer. We estimated incremental cost per quality-adjusted life-year (QALY) at one and five year intervals; the estimated reduction in VTE episodes, bleeding episodes, and survival at the five year interval for a simulated cohort of 10,000 women. RESULTS: The incremental cost effectiveness ratio (ICER) for prolonged prophylaxis (PP) was $5236/QALY and $-1462/QALY at one and five years respectively. For patients receiving PP, the model estimated a 12% reduction in the clinically evident VTE episodes and a higher five-year survival (31.61% vs. 29.96%; p<0.0001). Resource allocation analysis reveals that 95% of initial investment cost of prolonged enoxaparin is recovered within one year. CONCLUSIONS: In ovarian cancer patients undergoing open abdominal surgery, prolonged VTE prophylaxis not only improves patient outcomes, but is also a cost saving strategy when modeled over five years. A significant reduction in the episodes of VTE and a higher overall survival warrants consideration for the routine use of PP in this patient population.

Assessment of anti-metastatic effects of anticoagulant and antiplatelet agents using animal models of experimental lung metastasis.

It is well established that the blood coagulation system is activated in cancer. In addition, there is considerable evidence to suggest that clotting activation plays an important role in the biology of malignant tumors, including the process of blood-borne metastasis. For many years our laboratory has used experimental models of lung metastasis to study the events that follow the introduction of procoagulant-bearing tumor cells into circulating blood. This chapter focuses on the basic methods involved in assessing the anti-metastatic effects of anticoagulants and anti-platelet agents using rodent models of experimental metastasis. In addition, it summarizes our experience with these models, which collectively suggests that intravascular coagulation and platelet activation are a necessary prelude to lung tumor formation and that interruption of coagulation pathways or platelet aggregation may be an effective anti-metastatic strategy.

Bioequivalence of generic and branded subcutaneous enoxaparin: a single-dose, randomized-sequence, open-label, two-period crossover study in healthy Chinese male subjects.

BACKGROUND: Enoxaparin is a low-molecular-weight heparin (LMWH) indicated for antithrombosis. A branded formulation of subcutaneously administered enoxaparin has been available in China since 2000, and a generic formulation is being developed. In a literature search of the key term enoxaparin (publication years not restricted), no published data were identified regarding the pharmacokinetic profile of generic enoxaparin in Chinese subjects. OBJECTIVE: The aim of this study was to determine the bioequivalence of generic (test) and branded (reference) formulations of enoxaparin 60 mg (6000 IU anti-Xa) SC in healthy subjects for the purpose of meeting regulatory requirements for marketing the generic formulation in China. METHODS: Healthy Chinese male volunteers were eligible for this single-dose, randomized-sequence, open-label, 2-period crossover study. Participants were randomly assigned to receive the test and reference formulations of enoxaparin 60 mg SC injection (fasting state) in randomized order, with the 2 study periods separated by a 1-week washout period. For the assessment of anti-Xa and anti-IIa activities (surrogates used to describe the pharmacokinetic properties and bioavailability of LMWH), heparin clotting assay, and activated partial thromboplastin time (aPTT), blood samples were obtained before (hour 0; baseline) and at 0.5, 1, 2, 3, 4, 5, 6, 8, 10, 12, 14, and 24 hours after study drug administration. The 2 formulations were to be considered bioequivalent if the 90% CIs for the logarithm-transformed values of C(max), T(max), AUC(0-t), and AUC(0-infinity) fell within the predetermined range of 80% to 125%. Tolerability was assessed by questioning subjects about symptoms of possible adverse events and using laboratory analysis (hematology, biochemistry, hepatic function tests, and urinalysis). RESULTS: Twenty-two subjects participated in the study (mean [SD] age, 21.10 [1.02] years [range, 19-23 years]; weight, 64.07 [5.93] kg [range, 54-75 kg]; and height, 173 [5] cm [range, 163-187 cm]). For anti-Xa activity, the 90% CIs of C(max), AUC(0-t), and AUC(0-infinity) were 100.4% to 106.7%, 100.7% to 105.8%, and 100.7% to 106.1%, respectively. Corresponding values for anti-IIa activity were 85.0% to 102.4%, 80.4% to 94.8%, and 80.1% to 96.0%. For the hepa-rin clotting assay, the values were 97.4% to 102.4%, 98.2% to 102.4%, and 96.0% to 102.7%; and for aPTT, values were 98.2% to 104.3%, 97.4% to 101.6%, and 93.4% to 117.4%. No adverse events were reported during the study. CONCLUSIONS: Based on the 90% CIs of anti-Xa and anti-IIa activities, heparin clotting assay results, and aPTT in these healthy Chinese male subjects, the test and reference formulations of enoxaparin 60 mg SC met the regulatory requirements for bio-equivalence. Both formulations were well tolerated.

Clinical and economic outcomes in patients at risk of venous thromboembolism receiving appropriate enoxaparin or unfractionated heparin prophylaxis.

Clinical and economic outcomes were compared following appropriate prophylaxis with enoxaparin or unfractionated heparin (UFH) in a large, real-world population of US hospitalised medical and surgical patients at risk of venous thromboembolism (VTE). Discharges from the Thomson Reuters MarketScan Hospital Drug Database (January 2004-March 2007) of patients aged > or =40 years, at risk of VTE according to the 7(th) American College of Chest Physicians (ACCP) guidelines, who spent > or =6 days in hospital and received appropriate ACCP-recommended enoxaparin or UFH prophylaxis were included. Patients with contraindications to anticoagulation were excluded. Hospital-acquired VTE, adverse events, and hospital costs for enoxaparin versus UFH were compared using univariate and multivariate analyses. Of the 5,136 discharges included, 4,014 (78%) received enoxaparin and 1,122 (22%) received UFH. Compared with UFH, enoxaparin was associated with significantly lower risk of hospital-acquired VTE (adjusted odds ratio [OR] 0.51, 95% confidence interval [CI] 0.30-0.86, p = 0.012), pulmonary embolism (adjusted OR 0.33, 95% CI 0.14-0.79, p = 0.013) or adverse events (adjusted OR 0.73, 95% CI 0.54-0.98, p = 0.034). Total hospital costs per discharge were lower for enoxaparin (US $16,865 +/- 10,979) than UFH (US $19,252 +/- 14,970), with a mean difference of US $2,388 in favour of enoxaparin (p < 0.001) (adjusted difference US $439, 95% CI US $ -39 to 909, p = 0.072). In patients at risk of VTE, appropriate enoxaparin prophylaxis was associated with a reduction in hospital-acquired VTE, adverse events, and costs compared with appropriate UFH prophylaxis. Increased appropriate use of enoxaparin in patients at risk of VTE may help to reduce the clinical and economic burden of this condition.

Assessment of heparin binding to the AN69 ST hemodialysis membrane: I. Preclinical studies.

The AN69 ST membrane was designed to render the surface of the native polyacrylonitrile polymer less cationic. This was achieved by layering the membrane with the polycationic biopolymer polyethyleneimine. This new membrane is able to bind heparin to its surface, through electrical interactions, without altering the reactivity of the sulfonate groups of the membrane, regularly distributed in the membrane bulk. The kinetics of unfractionated or low-molecular-weight heparins were studied in vitro and in vivo in sheep. Encouraging results were obtained indicating that heparin-coated hemodialyzers are potent anticoagulants. Priming the AN69 ST membrane-equipped hemodialyzer with heparin, as in regular hemodialysis, could allow drastic reduction of heparin consumption in hemodialysis.

Enoxaparin: a review of its use as thromboprophylaxis in acutely ill, nonsurgical patients.

Enoxaparin (Clexane), Lovenox) is a low molecular weight heparin (LMWH) that has been widely used in the prevention of venous thromboembolism (VTE) in surgical patients. More recently, with the recognition of the high incidence of VTE in acutely ill medical (nonsurgical) patients, enoxaparin has been evaluated for thromboprophylaxis in this patient population. Subcutaneous enoxaparin 40 mg once daily has shown efficacy in the short-term thromboprophylaxis of VTE in nonsurgical patients with severely restricted mobility due to acute illness in well controlled clinical trials. The drug is at least similar in efficacy to unfractionated heparin (UFH) and its pharmacological profile allows once-daily administration, in contrast to the twice- or three-times-daily administration required with UFH. The tolerability profile of enoxaparin is also similar to that of UFH, except that the incidences of local haematomas and increased liver enzymes are lower with enoxaparin. The optimal duration of prophylaxis in nonsurgical patients is currently being evaluated and the results of extended prophylaxis with enoxaparin evaluated in the EXCLAIM (EXtended CLinical prophylaxis in Acutely Ill Medical patients) trial are awaited with interest. Currently, short-term enoxaparin appears to provide a cost-effective treatment alternative to UFH for VTE prophylaxis in nonsurgical patients.

Validation of the anti-factor IIa assay and potency assessment of enoxaparin in pharmaceutical formulations.

The low molecular weight heparin enoxaparin sodium is used clinically for the prevention and treatment of venous and arterial thrombosis. An anti-factor IIa assay was applied and validated for the potency evaluation of the pharmaceutical formulations. Investigating the parameters of range, linearity (r(2)=0.9912), precision, accuracy and robustness, the biological assay incorporated a chromogenic end-point and detection at 405 nm. The method yielded good results with a detection limit of 0.01 IU/ml and a quantitation limit of 0.03 IU/ml. Sodium enoxaparin pharmaceutical products were evaluated by the anti-factor Xa assay and the anti-factor IIa assay giving potencies between 97.18% and 106.50%, with an anti-factor Xa/anti-factor IIa ratio between 3.9 and 4.2. The results demonstrated the validity of the anti-factor IIa assay that together with the anti-factor Xa are useful methodologies for the routine quality control of enoxaparin in pharmaceutical products.

Clinical application of enoxaparin.

Low-molecular-weight heparins have several important advantages over unfractionated heparin (UFH). Due to a longer plasma half life together with high bioavailability and a linear dose-response relationship, the drugs can be safely and effectively administered in the hospital or ambulatory settings without the need to monitor the anticoagulant effect. Enoxaparin (Lovenox), Aventis Pharma) is a low-molecular-weight heparin which has been studied in a variety of clinical situations. In general surgery the efficacy of enoxaparin to prevent venous thromboembolism is similar to UFH but the tolerability is better. In patients undergoing cancer, orthopedic or vascular surgery the efficacy of enoxaparin is significantly higher with similar rates of bleeding complications. The database for enoxaparin in nonsurgical patients is smaller compared with surgical groups. There is evidence that the efficacy of enoxaparin may be superior to UFH in patients with severe cardiac disease. Efficacy and safety of UFH and enoxaparin are similar for the treatment of deep vein thrombosis. However, enoxaparin can be safely administered by the patients at home which is not possible with UFH. In patients with acute coronary syndromes, enoxaparin has been shown to reduce the rate of deaths and serious cardiac events in comparison with UFH. Furthermore, exonaparin treatment has been shown to be cost-effective, and therefore is the therapy of choice in this setting. In addition, enoxaparin has been shown to be a safe and effective alternative to the combination of UFH and phenprocoumone therapy in patients undergoing electrical cardioversion for atrial fibrillation.

Efficiency in clinical research: assessment in vitro of potential anti-thrombotic drug interactions.

OBJECTIVE: To determine whether testing in vitro of combinations of anti-thrombotic agents can identify potentially important interactions, we evaluated the combination of rNAPc2 with antagonists of platelet GP IIb-IIIa to identify potentially altered anticoagulant properties, antiplatelet effects, or both. METHODS: Blood was obtained from healthy subjects who were taking aspirin (325 mg/day). Selected concentrations of rNAPc2, enoxaparin, and GP IIb-IIIa inhibitors were added in vitro. Platelet function was assessed with the use of flow cytometry. RESULTS: No effect on clotting or platelet inhibition was apparent when abciximab was added to the combination of aspirin, enoxaparin, and rNAPc2 at concentrations up to 250 ng/ml. A modest (less than 10%, P <0.02) effect on the time to clot assessed with the activated clotting time was demonstrated when either eptifibatide or tirofiban was combined with aspirin and enoxaparin plus rNAPc2. rNAPc2 did not alter antiplatelet effects of eptifibatide. By contrast, a modest, approximately 10%, increase in the inhibition of fibrinogen binding (P <0.01) was seen when rNAPc2 was added to the combination of aspirin, enoxaparin, and tirofiban. CONCLUSIONS: The lack of an exaggerated effect on clotting and platelet function when GP IIb-IIIa inhibitors were combined with rNAPc2, aspirin, and enoxaparin suggests that no substantial increment in the incidence of bleeding would be observed when concentrations of rNAPc2 up to 250 ng/ml were to be used in clinical studies. More extensive use of testing in vitro in advance of large-scale clinical trials of anti-thrombotic agents and regimens is likely to enhance their design and implementation.

Validation of the anti-factor Xa assay for the potency assessment of enoxaparin in pharmaceutical formulations.

Enoxaparin is a low-molecular weight heparin used clinically for the prevention and treatment of venous and arterial thrombosis. An anti-factor Xa assay was used to evaluate the potency of the final drug preparation. Method validation investigated parameters such as the range, linearity (r2 = 0.9971), precision, accuracy, and robustness; the biological assay incorporated a chromogenic endpoint and detection at 405 nm. The method yielded good results with a quantitation limit of 0.037 IU/mL and a detection limit of 0.011 IU/mL. The results demonstrated the validity of the anti-factor Xa assay for the determination of enoxaparin.

The role of low-molecular-weight heparin in the management of acute coronary syndromes.

A substantial number of clinical studies have consistently demonstrated that low-molecular-weight heparin (LMWH) compounds are effective and safe alternative anticoagulants to unfractionated heparins (UFHs). They have been found to improve clinical outcomes in acute coronary syndromes and to provide a more predictable therapeutic response, longer and more stable anticoagulation, and a lower incidence of UFH-induced thrombocytopenia. Of the several LMWH agents that have been studied in large clinical trials, including enoxaparin, dalteparin, and nadroparin, not all have shown better efficacy than UFH. Enoxaparin is the only LMWH compound to have demonstrated sustained clinical and economic benefits in comparison with UFH in the management of unstable angina/ non-ST-segment elevation myocardial infarction (NSTEMI). Also, LMWH appears to be a reliable and effective antithrombotic treatment as adjunctive therapy in patients undergoing percutaneous coronary intervention. Clinical trials with enoxaparin indicate that LMWH is effective and safe in this indication, with or without the addition of a glycoprotein IIb/IIIa inhibitor. The efficacy demonstrated by enoxaparin in improving clinical outcomes in unstable angina/NSTEMI patients has led to investigations of its role in the management of ST-segment elevation myocardial infarction. Initial results are very encouraging, and they indicate that enoxaparin may potentially substitute for UFH as adjunctive therapy in fibrin-specific thrombolytic regimens and improve coronary reperfusion rates in streptokinase-based regimens.

A randomized trial to compare the efficacy, safety, cost and platelet aggregation effects of enoxaparin and unfractionated heparin (the ESCAPEU trial).

OBJECTIVE: To compare the efficacy, safety, cost and effects on platelet aggregation of unfractionated heparin and low-molecular weight heparin in unstable angina patients. PATIENTS AND METHODS: Ninety-three patients with unstable angina were randomized to receive either unfractionated heparin (UFH) or enoxaparin in an open design clinical trial with blinded end point evaluation. The effects of the heparins on platelet aggregation were also compared. RESULTS: The composite end point of myocardial infarction, cardiac death, recurrent angina and need for intervention was observed in 62% of patients treated with UFH and in 37% of patients treated with enoxaparin (RR 1.7, 95% CI 0.75 to 3.71, p = 0.04). There was no difference in the frequency or severity of adverse events. A cost-effectiveness analysis showed both the heparins to be similar. Platelet aggregation was inhibited to a greater extent by UFH when compared to enoxaparin. CONCLUSIONS: Enoxaparin appears to be superior in efficacy to UFH and similar to UFH in safety. No difference in costs was detected in this study. The greater inhibition of platelet aggregation observed in the case of UFH compared to enoxaparin indicates that there may be more bleeding complications with UFH.

Novel, bedside, tissue factor-dependent clotting assay permits improved assessment of combination antithrombotic and antiplatelet therapy.

BACKGROUND: Because optimal use of combinations of antiplatelet and antithrombotic drugs requires improved methods for assessment of therapeutic efficacy, we developed an assay designed to increase sensitivity that is based on initiation of clotting by tissue factor in minimally altered whole blood. METHODS AND RESULTS: Blood samples were obtained from healthy subjects, and the contact pathway of coagulation was inhibited with corn trypsin inhibitor (a specific factor XIIa inhibitor without effect on other coagulation factors). Clotting was initiated with relipidated tissue factor and detected with a Hemochron ACT instrument. Results were reproducible with samples from 25 healthy volunteers (mean time to clot, 125+/-17 seconds). Blood was also exposed to pharmacological concentrations of antithrombotic and antiplatelet agents in vitro. Heparin (0.25 anti-IIa/Xa U/mL) prolonged the time to clot by 2.4-fold (172 seconds, P:<0.05); hirudin (1.0 anti-IIa U/mL), by 3-fold (250 seconds P:<0.05); and enoxaparin (0.6 anti-Xa U/mL), by 2 -fold (123 seconds, P:<0.05). Additive effects of antiplatelet agents were readily detectable with both heparin and hirudin. Thus, addition of 3 microg/mL abciximab to 1.0 anti-IIa/Xa U/mL heparin and to 1.0 anti-IIa U/mL hirudin further prolonged the times to clot by 140 and 67 seconds, respectively (P:<0.05 for each). Addition of abciximab to enoxaparin did not further prolong the time to clot (increment, 13 seconds; P:=NS). CONCLUSIONS: The assay developed should facilitate improved dose selection, titration, and monitoring of combination antithrombotic and antiplatelet treatment regimens.

Enoxaparin in the prevention of deep venous thrombosis.

Enoxaparin, a low-molecular-weigth heparin, has recently been approved for use in the prevention of deep venous thrombosis following elective hip replacement surgery. Clinical trials have demonstrated enoxaparin to be superior to placebo, dextran and unfractionated heparin in deep venous thrombosis prophylaxis. However, no published studies have compared the efficacy of enoxaparin with that of warfarin in the prevention of deep venous thrombosis. Advantages of enoxaparin include less frequent dosing, reduced need for laboratory monitoring and a lower incidence of adverse effects, including hemorrhage. Although enoxaparin is more expensive than unfractionated heparin, its potential benefits may offset its higher cost.