Use Of Low Molecular Weight Heparin In Patients Research Articles

Routine use of LMWH prophylaxis is associated with a lower incidence of venous thromboembolic events following an ankle fracture

BackgroundVenous thromboembolic events (VTE) are well-known and serious complications following a trauma to the lower extremities. There is an ongoing debate on the benefit of low-molecular-weight heparin (LMWH) as prophylaxis following ankle fracture treatment. We examined the association between the incidence of VTE and the use of LMWH-prophylaxis following an ankle fracture, as well as factors affecting the risk of VTE. MethodsIn this retrospective cohort study, data on ankle fractures and fracture treatment from the Swedish Fracture Register was linked to data from the Swedish National Patient Register and the Swedish Prescribed Drug Register. Patients with VTE and patients who received LMWH prophylaxis were identified. The treating orthopedic departments were sent a questionnaire about their guidelines regarding the use of LMWH prophylaxis. Results222 cases of diagnosed VTE were identified among 14,954 ankle fractures. Orthopedic departments with higher-than-average use of LMWH prophylaxis among non-operatively treated ankle fractures had a lower incidence of VTE (OR 0.60, CI 0.39–0.92). Among operatively treated patients, departments with a guideline for the routine use of LMWH prophylaxis also had lower incidence of VTE (OR 0.56, CI 0.37–0.86). A later onset of VTE was seen among patients prescribed LMWH prophylaxis, with a mean of 56 days to onset (CI 44–67), compared to 39 days (CI 33–45) in patients without prescribed prophylaxis. During the first two weeks following injury, there was only one case of VTE in patients with prescribed LMWH, compared to 39 cases of VTE among patients without prescribed prophylaxis. ConclusionsRoutine use of LMWH in patients with operatively treated ankle fractures was associated with a lower incidence of VTE. A more frequent use of LMWH among patients with non-operatively treated ankle fractures were associated with a lower incidence of VTE. The onset occurred later among patients with LMWH-prophylaxis who still suffered a VTE.

Tinzaparin Sodium Pharmacokinetics in Patients with Chronic Kidney Disease: Practical Implications.

Low-molecular-weight heparins (LMWHs) are the mainstay of the prophylaxis and treatment of venous thromboembolism (VTE). Due to their renal elimination, the risk of accumulation with the related bleeding risk may represent a limitation for the use of LMWHs in patients with chronic kidney disease (CKD) as the risk of major bleeding is increased in patients with creatinine clearance (CrCl) < 30 mL/min, especially in patients with cancer. LMWH structure and molecular weight (MW) are heterogeneous among available agents. The elimination of tinzaparin, which has the highest mean MW among LMWHs, is less dependent on renal function as it is also metabolized through the reticuloendothelial system. A subcutaneous therapeutic dose of tinzaparin (175 IU/kg) once daily has been shown to cause no accumulation of anti-factor Xa activity in patients with CrCl ≥ 20 mL/min. Clinical experience from randomized controlled studies has shown no significant impact of CKD on bleeding risk in cancer patients receiving treatment doses of tinzaparin. This suggests that in these patients the use of treatment doses of tinzaparin does not require anticoagulation monitoring or dose adjustment.

The effect of low molecular weight heparin on survival in cancer patients: an updated systematic review and meta‐analysis of randomized trials

Tumors may exploit the coagulation system to enhance the survival and dissemination of cancer cells. Some studies have suggested that heparin and low molecular weight heparin (LMWH) have antitumor effects. We reported a previous meta-analysis that suggested a modest improvement in overall survival with the use of LMWH in patients with cancer. Herein, we present the results of an updated systematic review and meta-analysis. To evaluate the effect of LMWH as compared with placebo or no anticoagulant on the overall survival in patients with solid cancers. We conducted a systematic review and meta-analysis of randomized trials evaluating the use of LMWH vs. placebo or no anticoagulant in cancer patients without venous thrombosis. A meta-analysis was conducted with a random-effects model, and data were analyzed by the use of odds ratios (ORs) and relative risks (RRs) calculated for 1-year overall mortality. We identified 724 potentially relevant studies, nine of which met our inclusion criteria, and reported data on 1-year overall mortality. Studies were heterogeneous regarding types of cancer and interventions, and included 5987 patients, 98.4% of whom had advanced-stage disease (III and IV). There was no discernible effect on mortality with the use of LMWH (pooled OR0.87, 95%CI0.70-1.08; RR0.94, 95%CI0.86-1.04). In contrast to the previous study, these results did not show a survival benefit in cancer patients receiving LMWH. The effect of LMWH on overall survival in patients with limited-stage disease still is unknown.

Low Molecular Weight Heparin: An Evaluation of Current and Potential Clinical Utility in Surgery.

Heparin, a mixture of glycosaminoglycans of various sizes, is a potent natural anticoagulant. Low molecular weight heparins (LMWH) contain only the polymers of smaller size, which appear to possess most of the antithrombotic potential. Pharmacological differences between the two suggest a number of advantages with LMWH therapy. Our objective was to establish the utility of LMWHs in comparison to the current practice of anticoagulation in surgical patients. Articles were obtained through MEDLINE and CURRENT CONTENTS queries. The searches were limited to English and French-language articles and included published overviews containing relevant individual trials. We examined the current literature, consisting of 1,730 published reports from 1979-1998, regarding the biochemistry, pharmacology, physiology, and clinical applications of LMWH in comparison with current therapy. Studies were selected based on their relevance to LMWHs, the size and methods of trials, and their application to clinical care. Peer-reviewed published data were critically evaluated by independent extraction by several authors. Established rules for levels of evidence were used to objectively evaluate the strength of evidence supporting recommendations in each clinical area. LMWHs provide superior anticoagulation in the prophylaxis of DVT following orthopedic, general, and trauma surgery. Further studies should establish which other patients may benefit from such prophylaxis. Current evidence does not support the use of LMWHs in patients with mechanical heart valves or those on mechanical cardiac support devices; however, it may have a role in the maintenance of vascular graft patency. Further studies should examine the role of LMWHs in transplant atherosclerosis, and in patients requiring long-term anticoagulation at high risk for bleeding with warfarin therapy. The economic implications of LMWH administration remain unclear. On the basis of the information presented in this review, LMWHs are promising new agents in prophylaxis and treatment of both arterial and venous thrombosis. In the near future, LMWHs are likely to supplant UFH and perhaps warfarin in many applications.http://link.springer-ny.com/link/service/journals/00547/bibs/8n4p203.html</hea

Low‐molecular‐weight heparin in patients with advanced cirrhosis

The use of low-molecular-weight heparins (LMWH) in patients with advanced liver diseases is frequently avoided because of the enhanced risk of bleeding complications. However, many patients with impaired liver function are at a high risk of thrombosis or have an indication for therapeutic anticoagulation. Therefore, the aim of this study was to evaluate the pharmacokinetics of LMWH in patients with cirrhosis. Eighty-four consecutive patients with cirrhosis and a clinical indication for prophylactic or therapeutic anticoagulation were included. The LMWH doses were chosen according to current guidelines. Antifactor Xa activity (anti-Xa) was assessed on two consecutive days, 4 h after drug administration. The severity of liver disease was quantified using Child-Turcotte-Pugh score, the MELD score and clinical features and was correlated with the anti-Xa value and the occurrence of complications. Antifactor Xa activity was negatively correlated with the severity of the liver disease, and a positive correlation was observed between antithrombin-III (AT) levels and anti-Xa value. AT itself was negatively correlated with the severity of liver disease. Seven patients had an episode of variceal bleeding. No patient died during the observation interval and no thromboembolic events occurred. Prophylactic use of LMWH in patients with cirrhosis appears to be safe. A decreased anti-Xa value in cirrhotic patients and a negative correlation with liver function challenge the unconditional use of anti-Xa assays in LMWH monitoring in cirrhotic patients and reveals a potential limitation of anti-Xa analysis in these patients. Low levels of AT, because of reduced hepatic synthesis, are the most likely cause of this phenomenon.

Low-molecular-weight heparin in patients with renal insufficiency.

Low-molecular-weight heparins (LMWH) have been shown to be safer, more effective and more convenient than unfractionated heparin (UFH) in many clinical situations. However, their use is limited in patients with renal insufficiency (RI) due to bioaccumulation. The literature is critically reviewed and known pharmacokinetic properties are summarised. An approach to using LMWH in patients with RI is proposed on the basis of currently available evidence. Pharmacokinetic data of commonly used LMWH and of UFH are summarised in respect of RI. Most data are known on enoxaparin. A dose reduction is recommended in patients with severe RI. Limited data on dalteparin and tinzaparin suggest that there is less bioaccumulation. However, further studies are needed, in respect of long-term use and clinical end-points in particular.There are no data on certoparin and only very limited data on nadroparin. A detailed approach is suggested for the use of LMWH in patients with severe RI. Briefly: (1) before using LMWH, evaluate the patient's renal function, ist expected course, imminent interventions, and general bleeding risk; (2) prefer LMWH to UFH in view of better efficacy and lower bleeding risk in general; (3) however, prefer i.v. UFH to s.c. LMWH if a patient is unstable, is awaiting emergency interventions, or has a high bleeding risk, since UFH can be stopped more quickly due to i.v. administration, has a shorter half-life time, and can be effectively antagonised; (4) prefer a well documented LMWH; use established dosing schemes; (5) monitor LMWH with peak anti-Xa levels in patients with severe RI regularly, and adjust dose to be in target range; (6) do not use LMWH in patients with severe RI if there is no possibility of measuring anti-Xa levels. LMWH may be considered for patients with severe RI. However, experience, judicious choice and careful monitoring of patients with severe RI treated with LMWH are necessary.

Low-molecular-weight heparin in patients with renal insufficiency.

Low-molecular-weight heparins (LMWH) have been shown to be safer, more effective and more convenient than unfractionated heparin (UFH) in many clinical situations. However, their use is limited in patients with renal insufficiency (RI) due to bioaccumulation. The literature is critically reviewed and known pharmacokinetic properties are summarised. An approach to using LMWH in patients with RI is proposed on the basis of currently available evidence. Pharmacokinetic data of commonly used LMWH and of UFH are summarised in respect of RI. Most data are known on enoxaparin. A dose reduction is recommended in patients with severe RI. Limited data on dalteparin and tinzaparin suggest that there is less bioaccumulation. However, further studies are needed, in respect of long-term use and clinical end-points in particular.There are no data on certoparin and only very limited data on nadroparin. A detailed approach is suggested for the use of LMWH in patients with severe RI. Briefly: (1) before using LMWH, evaluate the patient's renal function, ist expected course, imminent interventions, and general bleeding risk; (2) prefer LMWH to UFH in view of better efficacy and lower bleeding risk in general; (3) however, prefer i.v. UFH to s.c. LMWH if a patient is unstable, is awaiting emergency interventions, or has a high bleeding risk, since UFH can be stopped more quickly due to i.v. administration, has a shorter half-life time, and can be effectively antagonised; (4) prefer a well documented LMWH; use established dosing schemes; (5) monitor LMWH with peak anti-Xa levels in patients with severe RI regularly, and adjust dose to be in target range; (6) do not use LMWH in patients with severe RI if there is no possibility of measuring anti-Xa levels. LMWH may be considered for patients with severe RI. However, experience, judicious choice and careful monitoring of patients with severe RI treated with LMWH are necessary.

Low-molecular-weight heparins should be used with caution in patients with chronic kidney disease

Although low-molecular-weight heparins (LMWHs) have largely replaced unfractionated heparin for the treatment of deep vein thrombosis and pulmonary embolism in the general population, sufficiently powered clinical studies on the use of LMWHs in patients with renal impairment are lacking. In this Viewpoint article, Gallieni and colleagues discuss reasons why LMWHs should be used with caution, at present, in patients with chronic kidney disease.

Low-molecular-weight heparins for the treatment of acute coronary syndrome and venous thromboembolism in patients with chronic renal insufficiency

The clinical management of patients with renal insufficiency who develop an acute coronary syndrome or venous thromboembolism is a common clinical scenario that is problematic because of the lack of well-designed randomized trials assessing management strategies in such patients. Impaired renal function is common in patients who develop thromboembolic disorders, particularly in elderly patients in whom renal insufficiency is under-recognized. Low-molecular-weight heparins (LMWHs), which are the most widely used anticoagulant for the treatment of patients with an acute coronary syndrome or venous thromboembolism, are eliminated primarily by the kidney and, therefore, pose treatment challenges in patients with impaired renal function. However, there is emerging evidence regarding the use of LMWHs in patients with impaired renal function suggesting that some preparations may be safe in such patients. The objective of this review is to discuss the clinical management of patients with renal insufficiency who develop an acute coronary syndrome or venous thromboembolism, and to explore similarities and differences of LMWHs when used in this clinical setting.

Bleeding Manifestations after Early Use of Low-Molecular-Weight Heparins in Blunt Splenic Injuries

Low-molecular-weight heparins (LMWHs) have emerged as an effective method for deep venous thrombosis (DVT) prophylaxis after major trauma. The early use of LMWH in patients with splenic injuries may result in increased rates of blood transfusions and failure of nonoperative management. A retrospective review of the records of all patients > or = 18 years old that sustained blunt splenic injuries from April 2000 to July 2002 was performed. Patients were divided in two groups based on whether they received LMWH during the first 48 hours (early group) or not (late group). A total of 188 patients were evaluated. One hundred fourteen patients had their splenic injuries managed nonoperatively and were included in the study. Fifty patients were assigned to the early group and 64 to the late group. There was no statistical difference between groups regarding basic demographic data, initial laboratory results, and severity of their splenic injuries. In the early group, two (4%) patients failed nonoperative management compared with four (6%) patients in the late group (P = 0.593). The number of patients requiring blood transfusions within the first 5 days after admission was 25 (50.0%) in the early group and 36 (56.2%) in the late group (P = 0.507). The average number of blood units given per patient within the first 5 days after admission were 3.2 +/- 1.5 in the early group and 3.0 +/- 1.8 in the late group (P = 0.782). This study suggests that the early use of LMWH in trauma patients with splenic injuries is not associated with an increased rate of blood transfusion requirements or an increased rate of failure of nonoperative management.

Combining enoxaparin and glycoprotein IIb/IIIa antagonists for the treatment of acute coronary syndromes: final results of the National Investigators Collaborating on Enoxaparin-3 (NICE-3) study

Background In high-risk patients with acute coronary syndromes (ACS), there have been concerns relating to the safety of using low molecular weight heparins (LMWH) in combination with a glycoprotein (GP) IIb/IIIa antagonist, and the continued use of LMWH in patients brought to the cardiac catheterization laboratory for percutaneous coronary intervention (PCI). Methods The National Investigators Collaborating on Enoxaparin-3 (NICE-3) study was an open-label observational study of enoxaparin in combination with any 1 of 3 available GP IIb/IIIa antagonists in patients presenting with non-ST–elevation ACS. The primary end point was the incidence of major bleeding not related to coronary artery bypass graft (CABG) surgery. Data were also recorded on the incidence of death, myocardial infarction (MI), and urgent revascularization for repeat ischemia. Results A total of 671 patients with validated data were treated with enoxaparin; 628 of these patients also received a GP IIb/IIIa antagonist (tirofiban, n = 229; eptifibatide, n = 272; abciximab, n = 127); 283 of 628 underwent percutaneous coronary intervention (PCI). The 30-day incidence of non-CABG major bleeding was 1.9%, and was not significantly higher than a prespecified historical control rate of 2.0%. Outcome events included death (1.0% at hospital discharge and 1.6% at 30 days), MI (3.5% and 5.1%, respectively), and urgent revascularization (2.7% and 6.8%, respectively). Conclusions The safety of enoxaparin plus a GP IIb/IIIa antagonist was comparable to that of unfractionated heparin plus a GP IIb/IIIa antagonist, as reported in other recent major trials. Patients undergoing PCI can be safely managed with enoxaparin and a GP IIb/IIIa antagonist, without supplemental use of unfractionated heparin.

Defining the scope of evidence-based practice for low-molecular-weight heparin therapy in high-risk patients with unstable angina and non-ST-elevation myocardial infarction.

Various therapies have been utilized for the treatment of unstable angina and non-ST-elevation myocardial infarction (NSTEMI). Each therapy has both advantages and disadvantages with regard to clinical outcomes and an increased risk of bleeding. One emerging primary therapy is low-molecular-weight heparin (LMWH). Concerns have emerged, however, over the use of LMWH in patients going to the catheterization laboratory or who receive platelet glycoprotein IIb/IIIa inhibitors. Available trial data point to the safety and efficacy of LMWH in these patients. Eventually, LMWH will probably replace unfractionated heparin (UFH) for the majority of patients with acute coronary syndromes (ACS). At present, however, practitioners need to consider individually how comfortable they are with the available data.

Low–molecular-weight heparin therapy for non-ST-elevation acute coronary syndromes and during percutaneous coronary intervention: An expert consensus*

Background Therapy with either low-molecular-weight heparin (LMWH) or glycoprotein (GP) IIb/IIIa receptor antagonists is of benefit to patients with acute coronary syndromes (ACSs). However, algorithms that define how LMWH may be used in patients, proceeding from medical management to intervention and in conjunction with GP IIb/IIIa inhibitors, are lacking. The objectives of this task force were to formulate recommendations based on all available data for the use of LMWH, both with and without GP IIb/IIIa receptor antagonists, and to provide seamless integration of care during the transition from medical to interventional management. Methods and Results An international task force of 14 cardiologists with extensive experience in clinical trials was convened in New York in February 2001 to address issues related to the use of LMWH in patients with non-ST-elevation ACS. Evidence from randomized trials, observational studies, and other reports was discussed, and consensus recommendations were formulated. Conclusions Substantial evidence exists that patients receiving LMWH for an ACS can safely undergo cardiac catheterization and percutaneous coronary intervention. Concerns regarding the transition of these patients from the medical service to the cardiac catheterization laboratory should therefore not impede the upstream use of LMWH. Furthermore, LMWH and GP IIb/IIIa receptor antagonists can be used safely in combination, with no apparent increase in the risk of major bleeding. Consensus algorithms for therapy are presented. (Am Heart J 2002;144:615-24.)

Low-molecular-weight heparin for the treatment of patients with mechanical heart valves.

The interruption of oral anticoagulant (OAC) administration is sometimes indicated in patients with mechanical heart valves, mainly before noncardiac surgery, non-surgical interventions, and pregnancy. Unfractionated heparin (UH) is currently the substitute for selected patients. Low-molecular-weight heparin (LMWH) offers theoretical advantages over UH, but is not currently considered in clinical guidelines as an alternative to UH in patients with prosthetic valves. The aim of the present study was to review the data accumulated so far on the use of LMWH in this patient population and to discuss its applicability in common practice. For this paper, the current medical literature on LMWH in patients with mechanical heart valves was extensively reviewed. There were eight series and six case reports. None of the studies was randomized, and only one was prospective. Data to establish the thromboembolic risk were incomplete. After excluding case reports, the following groups were constructed: (a) short-term administration, after valve insertion (n = 212); (b) short-term, perioperative (noncardiac)/periprocedural (n = 114); (c) long-term, due to intolerance to OAC (n = 16); (d) long-term, in pregnancy (n = 10). The incidence rate of thromboembolism was 0.9% for all the studies and 0.5, 0, 20, and 0% in groups a, b, c, and d, respectively; for hemorrhage, the overall rate was 3.4% (3.8, 2.6, 10, and 0% for the respective groups). In patients with mechanical heart valves, short-term LMWH therapy compares favorably with UH. Data on mid- and long-term LMWH administration in these patients are sparse. Further randomized studies are needed to confirm the safety and precise indications for the use of LMWH in patients with mechanical heart valves.

Introduction: New treatment strategies for thrombotic disorders

THIS ISSUE OF Seminars reviews new drugs for thrombotic disorders that have been recently approved or are probably soon to be approved. Several articles also focus on the ways in which commonly used agents such as low molecular weight heparin (LMWH) and warfarin can be employed more safely for those patients who are at high risk for either thrombosis or bleeding. Stephan Moll and Harold Roberts provide the background and rationale for development of antithrombotic agents. They describe the benefits and disadvantages of current drugs and review our newer understanding of hemostasis, which provides the basis on which to develop drugs with specific targets, such as the tissue factor:factor VIIa complex. In addition, these authors provide an excellent summary of the pharmaceuticals that have been recently approved or are in development. Graham Turpie provides a thorough review of the preclinical and clinical trials that led to the recent approval by the Food and Drug Administration (FDA) of fondaparinux sodium (Arixtra, Sanofi-Synthelabo, Paris, France/Organon, Oss, The Netherlands) for prevention of venous thromboembolism after surgery for hip fracture or for hip or knee replacement. This pentasaccharide, which acts in conjunction with antithrombin to inhibit factor Xa, is synthesized rather than derived from animal origin; its long terminal half-life of 17 to 21 hours allows for once-daily dosing. The drug does not appear to inhibit platelet function or to interact with platelet factor 4, suggesting that it may have potential as alternative therapy in heparin-induced thrombocytopenia. Its disadvantages are that no antidote is available to neutralize its activity and it is cleared by the renal route, indicating cautious use in patients with any evidence of renal dysfunction. The FDA approval for the use of LMWH as treatment for acute venous thromboembolism has resulted in a revolution in the care ofmost patients with this disorder, with hospital days either completely eliminated or markedly reduced. However, many of the clinical trials that were designed to show efficacy of LMWH excluded patients with known underlying hypercoagulable states, or who were obese or had renal disease. These patients are now also receiving LMWH. SusanO’Shea and Thomas Ortel reviewwhat is known about the use of LMWH in patients who have renal insufficiency, cancer, or who are obese or pregnant. They also discuss the perioperative use of LMWH and the role of protamine in neutralizing the anticoagulant activity. The issues addressed in their article will also need to be considered for pentasaccharide. Jean Chai and Gail Macik discuss several factors that can affect the anticoagulant potency of warfarin. Polymorphisms in the cytochrome P450 CYP2C9 enzyme result in prolonged catabolism of the S enan-

Low Molecular Weight Heparin: An Evaluation of Current and Potential Clinical Utility in Surgery

Heparin, a mixture of glycosaminoglycans of various sizes, is a potent natural anticoagulant. Low molecular weight heparins (LMWH) contain only the polymers of smaller size, which appear to possess most of the antithrombotic potential. Pharmacological differences between the two suggest a number of advantages with LMWH therapy. Our objective was to establish the utility of LMWHs in comparison to the current practice of anticoagulation in surgical patients. Articles were obtained through MEDLINE and CURRENT CONTENTS queries. The searches were limited to English and French-language articles and included published overviews containing relevant individual trials. We examined the current literature, consisting of 1,730 published reports from 1979–1998, regarding the biochemistry, pharmacology, physiology, and clinical applications of LMWH in comparison with current therapy. Studies were selected based on their relevance to LMWHs, the size and methods of trials, and their application to clinical care. Peer-reviewed published data were critically evaluated by independent extraction by several authors. Established rules for levels of evidence were used to objectively evaluate the strength of evidence supporting recommendations in each clinical area. LMWHs provide superior anticoagulation in the prophylaxis of DVT following orthopedic, general, and trauma surgery. Further studies should establish which other patients may benefit from such prophylaxis. Current evidence does not support the use of LMWHs in patients with mechanical heart valves or those on mechanical cardiac support devices; however, it may have a role in the maintenance of vascular graft patency. Further studies should examine the role of LMWHs in transplant atherosclerosis, and in patients requiring long-term anticoagulation at high risk for bleeding with warfarin therapy. The economic implications of LMWH administration remain unclear. On the basis of the information presented in this review, LMWHs are promising new agents in prophylaxis and treatment of both arterial and venous thrombosis. In the near future, LMWHs are likely to supplant UFH and perhaps warfarin in many applications.

Low molecular weight heparin: An evaluation of current and potential clinical utility in surgery

Heparin, a mixture of glycosaminoglycans of various sizes, is a potent natural anticoagulant. Low molecular weight heparins (LMWH) contain only the polymers of smaller size, which appear to possess most of the antithrombotic potential. Pharmacological differences between the two suggest a number of advantages with LMWH therapy. Our objective was to establish the utility of LMWHs in comparison to the current practice of anticoagulation in surgical patients. Articles were obtained through MEDLINE and CURRENT CONTENTS queries. The searches were limited to English and French-language articles and included published overviews containing relevant individual trials. We examined the current literature, consisting of 1,730 published reports from 1979–1998, regarding the biochemistry, pharmacology, physiology, and clinical applications of LMWH in comparison with current therapy. Studies were selected based on their relevance to LMWHs, the size and methods of trials, and their application to clinical care. Peer-reviewed published data were critically evaluated by independent extraction by several authors. Established rules for levels of evidence were used to objectively evaluate the strength of evidence supporting recommendations in each clinical area. LMWHs provide superior anticoagulation in the prophylaxis of DVT following orthopedic, general, and trauma surgery. Further studies should establish which other patients may benefit from such prophylaxis. Current evidence does not support the use of LMWHs in patients with mechanical heart valves or those on mechanical cardiac support devices; however, it may have a role in the maintenance of vascular graft patency. Further studies should examine the role of LMWHs in transplant atherosclerosis, and in patients requiring long-term anticoagulation at high risk for bleeding with warfarin therapy. The economic implications of LMWH administration remain unclear. On the basis of the information presented in this review, LMWHs are promising new agents in prophylaxis and treatment of both arterial and venous thrombosis. In the near future, LMWHs are likely to supplant UFH and perhaps warfarin in many applications.