Assessing protein coding region integrity in cDNA sequencing projects

BACKGROUND: Low molecular weight heparin (LMWH) provides a safe and effective alternative for hemodialysis anticoagulation. While unfractionated (UF) heparin has been implicated in hyperlipidemia, the effect of LMWH on the lipid profile in nondiabetic patients is controversial in chronic hemodialysis. The effect of LMWH in diabetic patients, a high risk group of hyperlipidemia, has not been studied. METHOD: LMWH was tested for its safety and efficacy in 10 nondiabetic Taiwanese patients. To evaluate influence of lipid profile, a crossover study was carried out in 10 type II diabetic patients with poor blood sugar control associated with high triglyceride (430.4 +/- 101.1 mg/dl) and total cholesterol levels (219.2 +/- 12.7 mg/dl) using UF heparin for more than 1 year. These patients were subjected to Fraxiparine, an LMWH, for 6 months and then switched back to UF heparin for another 6 months. Lipid profiles were measured every 2 months without prescribing lipid-lowering agents and the blood sugar was maintained at stationary levels. RESULTS: LMWH is safe and effective in Taiwanese patients as a single bolus injection and maintains a 9.4% higher platelet count immediate postdialysis compared to UF heparin. With high HbA1c levels (9.6 +/- 0.6%), mean triglyceride and VLDL levels started to decrease at the 4th month after LMWH treatment and reached a 34% reduction in triglyceride, a 26.2% reduction in VLDL, and a 19% reduction of total cholesterol/HDL ratio at the 6th month. Increments of triglyceride levels were found at the 6th month after a switch back to UF heparin. The levels of total cholesterol, LDL-cholesterol, HDL-cholesterol, apolipoprotein A-1 and B remained unchanged. CONCLUSION: LMWH may be beneficial to lipid control in hyperlipidemic diabetic patients on hemodialysis.     

Heparin-induced hyperkalemia in chronic hemodialysis patients: comparison of low molecular weight and unfractionated heparin

Aldosterone suppression and subsequent hyperkalemia are well described reversible side effects of prolonged treatment with heparin. This study was designed to examine whether the discontinuous use of heparin three times a week to prevent thrombosis formation during hemodialysis sessions could also induce hypoaldosteronism and might contribute to increased predialysis kalemia in hemodialysis patients. Two different heparinization regimens were prospectively compared in a crossover study of 11 chronic hemodialysis patients. During 2 consecutive weeks, the patients were dialyzed each week with either their usual doses of unfractionated heparin (UH) (6,160 IU +/- 1,350 IU) or low molecular weight heparin (LMWH) (15 anti-Xa activity [aXa] U/kg + 5 aXa U/kg/h). In all but 2 patients, the predialysis level of plasma K+ was higher with UH than with LMWH, and the mean value was higher (5.66+/-0.83 versus 5.15+/-0.68 mM, p = 0.01) while no differences in the predialysis plasma concentrations of creatinine, phosphate, urea, and bicarbonate were observed, excluding the potential role of differences in diet and dialysis efficacy in explaining the higher plasma K+ concentration with UH. The mean plasma aldosterone to plasma renin activity (pRA) ratio was higher with LMWH than with UH (149.54+/-123.1 versus 111.91+/-86.22 pg/ng/ h, p < 0.05). Individual plasma aldosterone values were found to be correlated to pRAs both during the UH period and the LMWH period, and the slope of the positive linear relation between plasma aldosterone and pRA was lower during the UH treatment period (63 versus 105 pg/ng/h). Finally, a negative linear correlation was found between the differences in individual predialysis plasma K+ observed during the 2 protocols and the differences in the corresponding plasma aldosterone levels, suggesting a link between the higher kalemia and the lower aldosterone responsiveness to angiotensin with unfractionated heparin. Although it cannot be concluded whether or not LMWH inhibits aldosterone synthesis, should LMWH decrease aldosterone production, this side effect is 33% less marked than that of UH so that the predialysis plasma K+ levels are 10% lower. This property makes LMWH use preferable to that of UH in patients with elevated predialysis kalemia.     

Subcutaneous low-molecular-weight heparin for treatment of Trousseau's syndrome

We report the case of a 76-year-old man with recurrent thromboses despite oral anticoagulation with phenprocoumon and low-grade chronic disseminated intravascular coagulation. Workup revealed a bronchial carcinoma (NSCCL) with hilar and mediastinal lymph node metastases. The clinical condition was consistent with Trousseau's syndrome. Based on reports in the literature, the therapy was changed to intravenous unfractionated heparin (UFH), which was effective in controlling the thrombotic coagulopathy. For practical reasons, despite a lack of evidence of its effectiveness in Trousseau's syndrome, therapy with UFH was changed to subcutaneous low-molecular-weight heparin (LMWH, nadroparine) in therapeutic doses of 100 IU/ kg body wt. 12 hourly. On an outpatient basis, five chemotherapy cycles were administered, and after metastases of the brain had been detected radiotherapy was initiated. Following 7.5 months of progressive neoplastic disease the patient died. He had remained free of thromboembolic complications under continued LMWH therapy during the last 6.5 months of his life. LMWH might be a convenient alternative to the established therapy with UFH in Trousseau's syndrome.     

Efficacy of a low molecular weight heparin administered intravenously or subcutaneously in comparison with intravenous unfractionated heparin in the treatment of deep venous thrombosis. Certoparin-Study Group

BACKGROUND: The main objective of the study presented was to test if thrombus regression can be improved by treatment with an intravenously or subcutaneously administered low molecular weight heparin (LMWH). Patients with acute deep vein thrombosis were randomly assigned to receive either intravenous UFH (131 patients), intravenous (i.v.) LMWH (128 patients), or 8000 IU of the same LMWH bid subcutaneously (s.c.) (128 patients). All patients were treated with heparin for 14 to 16 days. Vitamin-K-antagonist prophylaxis was started between Day 12 and Day 14 after enrollment into the study. METHODS: Phlebographies and perfusion/ventilation lung scans were performed at baseline and on Days 12 to 16. Primary endpoint of the study was a reduction of the phlebographic Marder score. Secondary endpoints were recurrent thrombosis and pulmonary embolism (PE), major and minor bleedings and the rate of PE at inclusion and at the end of the study assessed by ventilation/perfusion scans. RESULTS: The Marder score improved by at least 30% in 32.4% (95% CI: 22.6 ... 42.2) of the patients receiving UFH, in 34.0% (95% CI: 24.9 ... 44.0) receiving LMWH i.v. and in 42.6% (95% CI: 32.8 ... 52.8) treated with the low molecular weight heparin s.c. The difference between LMWH s.c. and UFH was 10.2% (95% CI: -3.7% ... +24.5%) (p = 0.11). PE with clinical signs confirmed by objective methods occurred in three patients of the UFH group, one of whom died and was not observed in patients of the i.v. or s.c. LMWH-groups. During the first 15 days no patient receiving UFH or i.v. LMWH, and one patient on s.c. LMWH had a recurrent thrombosis. Major bleedings were observed in four patients receiving i.v. UFH compared to nine patients on i.v. LMWH (one of these patients died) and one patient on s.c. LMWH. Perfusion ventilation lung scans were obtained from 287 patients at baseline and from 246 patients on Days 12-16. PE, defined according to PIOPED-criteria as intermediate or high probability scans, was observed in 38.0% of the patients entering the study and in 18.3% on Days 12 to 16. New asymptomatic PE occurred less frequently in the groups on LMWH (7.1%, 7.5%, respectively) than in the UFH-group (12.6%) (not significant). CONCLUSIONS: S.c. treatment with a LMWH (certoparin) (b.i.d.) is at least as effective as UFH i.v. The hypothesis of increased efficacy of subcutaneous LMWH in resolving venous thrombi will have to be confirmed by an independent study comparing s.c. LMWH with UFH. The i.v. continuous infusion of the LMWH for 12 to 16 days does not result in a higher venous re-opening rate than intravenous standard heparin.     

Increased kidney xanthine oxidoreductase activity in salt-induced experimental hypertension

OBJECTIVES: To assess the efficacy and safety of low molecular weight heparin (LMWH) as deep venous thrombosis (DVT) prophylaxis following total knee arthroplasty. DATA SOURCES: Medline 1986 to June 1997, Embase, and manufacturers were used to identify randomized controlled trials. REVIEW METHODS: Trials included were randomized studies of LMWH with routine radiological screening for DVT. Placebo or active controls were included. Two reviewers independently screened trials for inclusion, and assessed their quality. Pooled relative risk estimates of DVT and proximal DVT rates were calculated using a DerSimonian and Laird random effects model. Sensitivity of the results to the type of control used and the quality of the trial was assessed. RESULTS: The relative risk of DVT for a patient given LMWH is 0.73 (95% CI 0.66 to 0.80) when compared with patients treated with adjusted dose heparin or warfarin controls. The relative risk for proximal DVT is 0.58 (95% CI 0.38 to 0.90). The relative risk of pulmonary emboli in the LMWH group was 0.55 (95% C.I. 0.20 to 1.57). No excess of bleeding was recorded in the LMWH group. CONCLUSIONS: Low molecular weight heparin is more efficacious than either adjusted dose heparin or adjusted dose warfarin, when used to prevent DVT and proximal DVT following total knee arthroplasty.     

Low molecular weight heparin and unfractionated heparin for prevention of thrombo-embolism in general surgery: a meta-analysis of randomised clinical trials

Low molecular weight heparin (LMWH), unfractionated heparin (UFH) and warfarin were compared with respect to efficacy and safety in the prevention of thrombo-embolism in general surgery. Meta-analysis (MA) with a priori definition of the MA protocol was used to combine the results from randomised trials with patients who underwent general surgery and deep-vein thrombosis (DVT) prophylaxis with LMWH, UFH or warfarin. Forty-four studies were identified for assessment and 33 were included, however, none for warfarin. For efficacy (DVT and pulmonary embolism) and major bleeding, no significant difference between the LMWH- and UFH-treated groups was demonstrated. The relative risk of minor bleedings for LMWH versus UFH was 0.75 (0.64-0.88; 95% confidence interval) and is significant (p < 0.05). Within the limitations of the MA, LMWH and UFH did not differ significantly in terms of prevention of thrombo-embolism, but LMWH had a significantly better safety profile. On this basis, LMWH may be preferable to UFH in the prevention of thrombo-embolism in general surgery.     

Low molecular weight heparin and unfractionated heparin in thrombosis prophylaxis after major surgical intervention: update of previous meta-analyses

BACKGROUND: Previous meta-analyses comparing low molecular weight heparin (LMWH) and unfractionated heparin for thrombosis prophylaxis after surgical interventions need updating. METHODS: This is a publication-based meta-analysis of 36 double-blind studies including 16583 patients. Main outcome measures are incidence of deep vein thrombosis (efficacy) and wound haematoma (safety). RESULTS: In general surgery there is no increased efficacy in favour of LMWH (odds ratio (OR) 0.88, 95 per cent confidence interval (c.i.) 0.60-1.30) but there exists a higher incidence of bleeding complications (OR 1.47, 95 per cent c.i. 1.07-2.01). Low-dose LMWH is equally efficacious (OR 1.03, 95 per cent c.i. 0.85-1.26) but safer than unfractionated heparin (OR 0.68, 95 per cent c.i. 0.56-0.82). In orthopaedic surgery there is a trend towards an increased efficacy for LMWH (OR 0.83, 95 per cent c.i. 0.68-1.02) with equivalent safety (OR 0.96, 95 per cent c.i. 0.68-1.36). CONCLUSION: A superiority of LMWH is suggested but heterogeneity might make generalizability to future patients questionable. A meta-analysis on individual patient data should be the next step before randomizing additional patients in future trials.     

Vasoflux, a new anticoagulant with a novel mechanism of action

BACKGROUND: Heparin and direct thrombin inhibitors, such as hirudin, have limitations in the treatment of acute coronary syndromes. Heparin does not inactivate fibrin-bound thrombin, whereas hirudin fails to block thrombin generation. In contrast, Vasoflux is a novel anticoagulant that inactivates fibrin-bound thrombin and attenuates factor Xa generation. METHODS AND RESULTS: Vasoflux is prepared by depolymerization of heparin, restricting molecular size to between 3000 and 8000 Da, and reducing antithrombin affinity by periodate oxidation. Vasoflux catalyzes fibrin-bound thrombin inactivation by heparin cofactor II (HCII) and inhibits factor IXa activation of factor X independently of antithrombin and HCII. Compared with other anticoagulants in a thrombogenic extracorporeal circuit, Vasoflux maintains filter patency at concentrations that produce an activated clotting time (ACT) of 220 seconds. In contrast, to maintain filter patency, heparin, low-molecular-weight heparin (LMWH), and hirudin require concentrations that produced an ACT of 720, 415, and >1500 seconds, respectively, whereas dermatan sulfate was ineffective at concentrations that produced an ACT of 360 seconds. CONCLUSIONS: Vasoflux is more effective than heparin and LMWH because it inactivates fibrin-bound thrombin and is superior to hirudin and dermatan sulfate because it also blocks factor Xa generation.     

Inhibitory effect of low molecular weight heparin on the bronchoconstriction in ovalbumin-sensitized guinea pigs after antigen exposure

To elucidate the effect of low molecular weight heparin (LMWH) on the bronchoconstriction, we examined the serial changes of the resistance of respiratory system (Rrs) in ovalbumin (OA)-sensitized guinea pigs after antigen exposure. After sensitization of guinea pigs with repeated OA inhalation, Rrs was measured at immediate asthmatic response (IAR) and late asthmatic response (LAR) with or without LMWH inhalation. Alteration in the number of inflammatory cells of the lung by LMWH inhalation was examined in the broncholaveolar lavage fluid (BALF) and in the histological sections of airway walls. Peak Rrs at 1 min up to 9 min, except 8 min, after antigen exposure significantly decreased by the pretreatment with LMWH inhalation as compared with saline inhalation. Peak Rrs at LAR (after 4 hours up to 24 hours, except 6 hours) also showed a significant decrease in the pretreatment with LMWH inhalation. Pretreatment of LMWH exhibited a decrease of eosinophil percentage in BALF (5.5 +/- 1.2% from 8.2 +/- 0.4% in saline inhalation) and a decrease of infiltrated eosinophil count in airway walls (71.0 +/- 7.3 from 155 +/- 15.8 in saline inhalation). These data show LMWH might play an important role as an inhibitory factor to bronchial asthma.     

New anticoagulant strategies

The limitations of standard heparin have prompted the development of a variety of newer antithrombotic agents. In fact, a LMWH preparation has recently been approved for clinical use in North America. Of these novel preparations, LMWH, the direct thrombin inhibitors, and inhibitors of GPIIb-IIIa have been used clinically and are in advanced stages of evaluation. Not only is LMWH effective in the prevention of venous thromboembolic disease in high-risk patients, but its more predictable dose response makes it an ideal candidate for the treatment of venous thrombosis. Further studies are needed to determine whether LMWH is superior to standard heparin as adjunctive therapy in patients undergoing coronary thrombolysis or angioplasty. Particularly promising in the setting of arterial thrombosis are hirudin, hirulog, and 7E3. With the encouraging results reported to date, it is likely that these agents will soon find their way into the treatment armamentarium of arterial thrombosis.     

Low molecular weight heparins in special populations

Low molecular weight heparins (LMWH) are replacing unfractionated heparin (UH) as safe and effective agents for the prevention and treatment of thromboembolism. Although LMWH offer many advantages over UH, usage is less clearly defined in certain special populations, including renal dysfunction, obesity and pregnancy. This article will briefly review the pharmacology of LMWH and discuss usage in these special populations.     

Induction of the acute-phase reaction increases heparin-binding proteins in plasma

We have previously demonstrated that the nonspecific binding of unfractionated heparin (UFH) to plasma proteins has a marked modulating effect on its anticoagulant activity. Since some heparin-binding proteins are also acute-phase-reactant proteins, we explored the possibility that the induction of the acute-phase response can increase the plasma concentrations of heparin-binding proteins. The recovery of a fixed amount of UFH or low-molecular-weight heparin (LMWH) added in vitro to rat plasma samples obtained at various time intervals after the administration of intravenous endotoxin or subcutaneous turpentine was compared with that of saline-treated control animals. The anti-factor Xa activity was measured in the plasma samples before and after the addition of a chemically modified low-affinity heparin (LAH) to displace the proportion of the added heparin that is reversibly bound to plasma proteins. Our results show that at 6 hours post-endotoxin and at 24 hours post-turpentine treatment, virtually no anti-factor Xa activity could be measured in the plasma samples, while the expected levels were obtained for control plasma. After the addition of LAH to displace protein-bound UFH, essentially the same anti-factor Xa levels were measured in the plasma from all three treatment groups. These results indicate that induction of the acute-phase reaction can dramatically increase the levels of heparin-binding proteins in rat plasma. In addition, we compared the anti-factor Xa recovery of UFH with that of an LMWH from the plasma of endotoxin- and saline-treated rats and demonstrated that LMWH binds less to plasma proteins than UFH, even in plasma in which the levels of heparin-binding proteins are markedly elevated. The recovery of a fixed amount of UFH added in vitro to human plasma from septic patients was also reduced, but not to the same extent as seen in rat plasma. Removal of candidate heparin-binding and acute-phase proteins by immunodepletion indicated that vitronectin plays an important role in the nonspecific binding of UFH in patient plasma.     

Primary CD30-positive anaplastic large cell lymphoma of the lip

In this paper we report a case of 76-year-old white male patient with skin necrosis induced by subcutaneous prophylactic administration of low-molecular-weight heparin (LMWH). Skin necrosis occurred distant from heparin injection sites and without concomitant thrombocytopenia. This is the first reported case presenting these clinical findings.     

Low molecular weight heparin: a critical analysis of clinical trials

LMWHs are an important new class of antithrombotic agents. They differ from UFH in having relatively more anti-Xa activity, greater bioavailability at low doses, longer half-life, and more predictable anticoagulant response when administered in fixed doses. These properties allow LMWHs to be administered QD or at most BID and without laboratory monitoring. The incidence of heparin-induced thrombocytopenia also appears to be lower with an LMWH than with heparin. Given their favorable pharmacological profile, it was of interest to critically appraise clinical trials of thromboprophylaxis and treatment with these new agents. In orthopedic trials, it was noted that LMWH provided safe and effective thromboprophylaxis for patients undergoing major orthopedic surgery of the lower limb. In those having hip arthroplasty, LMWH was as effective as low-intensity warfarin therapy, but its use was associated with more wound hematomas. In those having total knee arthroplasty, LMWH was more effective than warfarin and did not increase bleeding. However, the prevalence of DVTs complicating this procedure as well as acute hip fracture remains unacceptably high, and additional studies of LMWH in combination with other prophylactic methods, such as external pneumatic compression, are needed. Only one adequately designed trial found less bleeding resulted from LMWH prophylaxis administered at an equivalent antithrombotic dose to UFH. In general medical patients, LMWH appeared to be as effective as UFH and had the advantages of less frequent injections and fewer injection site hematomas. In general surgical patients, there was a lower risk of thromboembolism but a trend toward an increase in bleeding events. Subjects with strokes and spinal cord injuries benefited from fewer thrombotic events, and the latter had fewer bleeding complications. Other potential indications for LMWH, such as cardiopulmonary bypass, hemodialysis, and preservation of graft patency, are presently under study. Perhaps the most impressive benefits of LMWH will be realized when it is used for the treatment of venous thromboembolism. The meta-analysis presented in this review showed a trend toward greater efficacy with LMWH and fewer major bleeding events in comparison with adjusted-dose intravenous UFH. Also, during the months following the thrombotic event, there was significantly less mortality in patients receiving LMWH. A further advantage was the subcutaneous route of administration and lack of requirement for laboratory monitoring. Additional treatment trials are presently in progress and may establish LMWH as the treatment of choice for patients with thromboembolic disorders.     

Low-molecular-weight heparins

Low-molecular-weight heparins (LMWH) are a new group of parenteral anticoagulants. They represent a major clinical advance in anticoagulation since the identification of unfractionated heparin (UFH) in 1922 and the introduction of the synthetic coumarin derivative, warfarin, in 1948. Their predictable pharmacokinetics, increased bioavailability, and longer plasma half-life allow for once- or twice-daily dosing and eliminate the need for routine laboratory monitoring. This simplified administration stands to alter the clinical practice of anticoagulation. This review high-lights recent clinical trials and focuses on studies comparing LMWH with the other two major anticoagulants: UFH and coumadin.     

Postoperative activation of the haemostatic system--influence of prolonged thromboprophylaxis in patients undergoing total hip arthroplasty

Tissue injury during hip surgery results in the activation of the haemostatic system. The aim of this study was to detect markers of haemostatic activity, i.e. prothrombin fragment 1 and 2 (F1+2), thrombin-antithrombin (TAT) complexes, fibrin degradation products (FbDP), and soluble fibrin monomers (SF), preoperatively, and on days 1, 7 and 35 in plasma of patients undergoing total hip arthroplasty. The study was part of a multicentre study in which the patients were randomized to receive a subcutaneous injection of low molecular weight heparin (LMWH, dalteparin, Fragmin) once daily for 5 weeks or placebo following a 1-week LMWH treatment (once daily). Bilateral phlebography was performed between days 33 and 35 or before if patients had clinical symptoms of deep vein thrombosis. A lung scan was performed in patients with clinical symptoms of pulmonary embolism. Levels of the markers were significantly increased on day 35 in the patients receiving LMWH for 7 days compared to patients receiving LMWH for 35 days. In patients receiving LMWH for 5 weeks, levels of FbDP and SF were significantly higher during the entire study period, but TAT and F1+2 were normalized on day 35. The markers were increased two to five times on the 1st postoperative day in patients with diagnosed venous thromboembolism.     

Hereditary antithrombin deficiency and pregnancy. Pregnancy course in six women with known hereditary antithrombin deficiency

Inherited antithrombin (AT) deficiency is a major cause of venous thromboembolism, especially in relation to surgery and pregnancy. We present six AT deficient pregnant women, who successfully delivered seven babies at the Department of Gynaecology/Obstetrics, Aalborg Hospital. From conception, or if possible prior to conception, the women were treated with unfractionated (UFH) or low molecular weight heparin (LMWH) throughout the pregnancy. If the pregnancy was without complication, AT substitution was only used at delivery and for approximately a week post-partum, when warfarin treatment was re-instituted.     

A phase II study of paclitaxel in heavily pretreated patients with small-cell lung cancer

Deep vein thrombosis (DVT) and pulmonary embolism (PE) are major complications associated with total knee arthroplasty. The American College of Chest Physicians recommends twice-daily, fixed-dose low-molecular-weight heparin (LMWH) as routine prophylaxis in this patient population. This study represents a cost analysis of ardeparin and enoxaparin, the two LMWHs currently available for this indication in the United States. Costs for treating DVT, PE, and major bleeding episodes were derived from values reported in the literature. Both ardeparin and enoxaparin were found to produce significant cost savings when used routinely as DVT prophylaxis after knee replacement surgery compared with no prophylaxis. Based on the currently available data, enoxaparin 40 mg once daily appears to be the least costly LMWH for routine pharmacoprophylaxis of DVT in patients undergoing knee replacement surgery.     

The home treatment of deep venous thromboses with low-molecular-weight heparin

Low-molecular-weight heparins (LMWH) have shown to be at least as safe and efficient as non-fractionated heparin in the treatment of deep-vein thrombosis (DVT). Moreover, no serial laboratory controls are required. Therefore, LMWH allow the patients to be treated at home. From July 1995 to July 1996, 30 consecutive patients with DVT were enrolled in a prospective study and treated with nadroparin. Ambulatory treatment was feasible in 24 patients (9 patients did not require admission and 15 patients were discharged in less than 6 days). The main causes for admission were the inability to obtain a diagnosis, the severity of symptoms in the involved limb, and the presence of associated disease. None of the 24 patients to whom the possibility of home therapy was offered desired to remain at hospital. The ambulatory care of these patients increased the burden on primary care teams. There was no case of clinical recurrent thromboembolism nor a major hemorrhagic complication. Ambulatory treatment of DVT with nadroparin seems to be feasible, efficient and safe. Nevertheless, before using this therapeutic alternative a series of factors should be considered, which include the severity of clinical presentation, the embolic and hemorrhagic risks, and the presence of associated diseases.     

IgG antibodies to chlamydial and mycoplasma infection plus C-reactive protein related to poor outcome in unstable angina

This postal survey among 174 UK palliative physicians, aimed to assess current practice and perceived problems within the management of venous thromboembolism (VTE) in patients with advanced cancer. The questionnaire was returned by 131 out of 174 (74%) of the doctors surveyed. The most common estimated incidence of patients with VTE was 1-5%. The diagnosis of VTE is usually confirmed by further investigation and in general, outpatients are more likely to be anticoagulated than inpatients. Problems with anticoagulation include bleeding, international normalized ratio instability, appropriateness of anticoagulation, practical difficulties associated with monitoring, and recurrent VTE. Although probably less effective, 77 out of 128 (60%) of respondents use subtherapeutic regimes in order to minimize the risks. Patients with advanced malignancy and VTE are anticoagulated, if considered appropriate, by the vast majority of palliative physicians in the UK. Warfarin has been abandoned in favour of low-molecular-weight heparin (LMWH) by 26%. LMWH provides anticoagulation with no need for monitoring, has no significant drug interactions and is not affected by liver dysfunction. Theoretically, LMWH is more effective than warfarin in the secondary prevention of VTE with less risk of bleeding.