Initial Treatment Of Venous Thromboembolism Research Articles

Use of anticoagulants in elderly patients: practical recommendations

Elderly people represent a patient population at high thromboembolic risk, but also at high hemorrhagic risk. There is a general tendency among physicians to underuse anticoagulants in the elderly, probably both because of underestimation of thromboembolic risk and overestimation of bleeding risk. The main indications for anticoagulation are venous thromboembolism (VTE) prophylaxis in medical and surgical settings, VTE treatment, atrial fibrillation (AF) and valvular heart disease. Available anticoagulants for VTE prophylaxis and initial treatment of VTE are low molecular weight heparins (LMWH), unfractionated heparin (UFH) or synthetic anti-factor Xa pentasaccharide fondaparinux. For long-term anticoagulation vitamin K antagonists (VKA) are the first choice and only available oral anticoagulants nowadays. Assessing the benefit-risk ratio of anticoagulation is one of the most challenging issues in the individual elderly patient, patients at highest hemorrhagic risk often being those who would have the greatest benefit from anticoagulants. Some specific considerations are of utmost importance when using anticoagulants in the elderly to maximize safety of these treatments, including decreased renal function, co-morbidities and risk of falls, altered pharmacodynamics of anticoagulants especially VKAs, association with antiplatelet agents, patient education. Newer anticoagulants that are currently under study could simplify the management and increase the safety of anticoagulation in the future.

Cancer-Associated Venous Thrombosis in the Surgical Setting

Cancer patients are at a relatively high risk of venous thromboembolism (VTE), and this has implications for surgical outcome. English literature search including the keywords cancer, surgery and VTE was undertaken to review the risk, etiology, prevention and treatment of VTE in surgical oncology patients. Malignant disease is highlighted as an important risk factor for VTE with an odds ratio of 6.5. The risk factors include higher age, previous VTE, advanced cancer, length of operation and immobility. Use of in-hospital thromboprophylaxis with low-molecular-weight heparin (LMWH) or low dose unfractionated heparin with graded stockings has been validated both in terms of safety and efficacy and should be considered for all patients. Subcutaneous LMWH has replaced unfractionated heparin for the initial treatment of VTE. The use of long-term LMWH instead of oral anticoagulants can substantially reduce the risk of recurrent VTE without increased bleeding. Recently, results of few trials have shown that LMWH may improve patient survival.

Treatment of venous thromboembolism in patients with cancer: Subgroup analysis of the Matisse clinical trials

In the initial treatment of venous thromboembolism (VTE) fondaparinux, a pentasaccharide, is a good alternative to heparin. Whether this is also true for cancer patients is unknown. We performed two post-hoc analyses of two randomized studies to compare efficacy, safety and overall survival of fondaparinux to standard initial (low-molecular-weight) heparin (LMWH) treatment in cancer patients with venous thromboembolism. Two hundred thirty-seven cancer patients with deep venous thrombosis (DVT) were initially treated with fondaparinux or enoxaparin. Two hundred forty cancer patients with pulmonary embolism (PE) received fondaparinux or unfractionated heparin. The initial treatment was followed by vitamin K antagonists. In DVT patients, the three-month recurrence rate was 5.4% in the enoxaparin recipients compared to 12.7% in those treated with fondaparinux [absolute difference 7.3%, 95% CI 0.1, 14.5]. A recurrence was observed in 8.9% of the PE patients treated with fondaparinux compared to 17.2% in the unfractionated heparin recipients [absolute difference -8.3, 95% CI -16.7, 0.1]. In both studies no difference in bleeding and overall survival was observed. Regarding overall survival and bleeding fondaparinux is comparable to enoxaparin and unfractionated heparin in cancer patients. No significant differences in recurrent VTE were observed when comparing fondaparinux with unfractionated or LMWH. Because of study limitations these results should be considered hypothesis-generating.

Anticoagulation for the initial treatment of venous thromboembolism in patients with cancer

The authors compared the relative efficacy and safety of low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) for the initial treatment of venous thromboembolism (VTE) between patients with and without cancer. By using Cochrane methodology for systematic reviews, separate meta-analyses were conducted for subgroups of patients with and without cancer, and relative risks (RRs) were compared for statistical significance. The methodologic quality for each outcome was assessed by using the Grading of Recommendations Assessment, Development, and Evaluation approach. LMWH reduced mortality significantly compared with UFH in patients with cancer (RR of 0.71; 95% confidence interval [95% CI], 0.52-0.98 [moderate-quality evidence]) but not in patients without cancer (RR of 0.97; 95% CI, 0.65-1.46 [low-quality evidence]). However, the difference in the RR for the 2 subgroups did not reach statistical significance (P = .113). The difference between LMWH and UFH in the effect on recurrent VTE was not statistically significant in the subgroup with cancer (RR of 0.78; 95% CI, 0.29-2.08 [low-quality evidence]), in the subgroup without cancer (RR of 0.94; 95% CI, 0.60-1.46 [low-quality evidence]), or between the 2 subgroups (P = .367). No data were available for bleeding outcomes, thrombocytopenia, or postphlebitic syndrome. The current results indicated that LMWH most likely is superior to UFH in reducing mortality in the initial treatment of VTE for patients with cancer. There is a need for more and better designed trials to confirm these findings.

Anticoagulation in patients with cancer: an overview of reviews

Relative benefits and harms of anticoagulants are required for judgments regarding appropriate anticoagulation in patients with cancer. To review the benefits and harms of anticoagulants for prophylactic, therapeutic, and survival improvement indications in patients with cancer. Overview of 6 systematic reviews of anticoagulation in cancer following the Cochrane Collaboration and Grading of Recommendations Assessment, Development and Evaluation methodology. Central venous catheters thromboprophylaxis with heparin or warfarin does not significantly reduce the incidence of symptomatic deep vein thrombosis (DVT) (relative risk [RR] 0.43, 95% CI 0.18-1.06 and RR 0.62, 95% CI 0.30-1.27 respectively). For perioperative thromboprophylaxis, low-molecular-weight heparin (LMWH) and unfractionated heparin (UFH) have similar effects on mortality (RR 0.89, 95% CI 0.61-1.28) and morbidity outcomes. For the initial treatment of venous thromboembolism (VTE), LMWH compared with UFH reduces mortality at 3 months (RR 0.71, 95% CI 0.52-0.98). For the long-term treatment of VTE, LMWH compared with vitamin K antagonists reduces VTE recurrence (hazard ratio [HR] 0.47, 95% CI 0.32-0.71) but not mortality (HR 0.96, 95% CI 0.81-1.14). As interventions to improve survival, warfarin suggests a survival benefit at 6 months in the subgroup of small cell lung cancer (SCLC) (RR 0.69, 95% CI 0.50-0.96) while heparin suggests a survival benefit in patients with cancer in general (HR 0.77, 95% CI 0.65-0.91) and in those with limited SCLC in particular (HR 0.56, 95% CI 0.38-0.83). In patients with cancer, current evidence does not support routine use of thromboprophylaxis for central venous catheters or a specific anticoagulant for perioperative thromboprophylaxis. Anticoagulants may improve survival, but more data will be useful in deciding which subgroups benefit most.

Long-Term Administration of a Low-Molecular-Weight Heparin Contributed to Successful Treatment in a Patient With Primary Mediastinal Large B-Cell Lymphoma and Venous Thromboembolism

The case of a 16-year-old girl with primary mediastinal large B-cell lymphoma who had thrombosis in the brachiocephalic, subclavian, and internal jugular veins at presentation is reported. MACOP-B chemotherapy plus radiation therapy could be the first-line strategy, but MACOP-B increases the risk of thrombosis. Although an effective method for initial treatment of venous thromboembolism (VTE) in cancer patients has not been established, recent studies revealed that the administration of a low-molecular-weight heparin (LMWH) was effective for secondary prevention of VTE. Therefore, the patient in this case was treated with MACOP-B plus rituximab followed by radiation therapy, and an LMWH was administered through the course of treatment. She achieved complete remission and never suffered from VTE. This case suggests that long-term administration of an LMWH contributes to the primary improvement and secondary prevention of VTE even in patients who are at high risk for thrombosis.

Are All Low Molecular Weight Heparins Equivalent in the Management of Venous Thromboembolism?

Low molecular weight heparins are replacing unfractionated heparin in a number of clinical indications because of their improved subcutaneous bioavailability and more predictable antithrombotic response. Clinical trials have demonstrated that low molecular weight heparins are at least as safe and effective as unfractionated heparin for the initial treatment of venous thromboembolism, and unfractionated heparin and warfarin for primary and secondary thromboprophylaxis. The mechanism behind the antithrombotic action of low molecular weight heparins is not fully understood but is likely to involve inhibition of coagulation factors Xa and IIa (thrombin), release of tissue-factor-pathway inhibitor, and inhibition of thrombin activatable fibrinolytic inhibitor. Different low molecular weight heparins have been shown to have various effects on coagulation parameters. Seven low molecular weight heparins are currently marketed worldwide, each demonstrated distinct chemical entities with unique pharmacokinetic and pharmacodynamic profiles. Each low molecular weight heparin is approved for specific indications based on the available efficacy and safety data for that product. The relative efficacy and safety of the low molecular weight heparins are unclear because there have been very few direct comparisons in randomized clinical trials. While recommending low molecular weight heparins for the prevention and treatment of venous thromboembolism, clinical guidelines have not specified individual agents. National and international organizations recognize that low molecular weight heparins are distinct entities and that they should not be used interchangeably in clinical practice. Each low molecular weight heparin should be used at the recommended dose when efficacy and safety data exist for the condition being treated. When these data are not available, the dosing and administration of low molecular weight heparins must be adapted from existing data and recommendations.

Management of Thromboembolism in Hematologic Malignancies

Patients with hematologic malignancies have increased risks of thromboembolism or bleeding. The commonest thrombotic complication is venous thromboembolism (VTE). Other thrombotic conditions occur in association with specific disorders, such as thrombotic thrombocytopenic purpura in hematopoietic stem cell transplantation and disseminated intravascular coagulation in acute promyelocytic leukemia. Clinical trials show that unfractionated heparin (UFH) and low molecular weight heparin (LMWH) are efficacious for VTE prophylaxis in cancer patients after major surgery or when hospitalized for acute medical illnesses. These findings in cancer patients are probably applicable to patients with hematologic malignancies, in whom there are very few studies. However, the effectiveness of anticoagulant VTE prophylaxis is not established in ambulatory patients with cancer except for multiple myeloma patients treated with thalidomide and chemotherapy. LMWH is widely used as initial treatment for VTE because it enables home therapy without laboratory monitoring, thereby improving the patient's quality of life. UFH is preferred in patients with high bleeding risks and renal impairment. In cancer patients, vitamin K antagonists for the long-term treatment of VTE are increasingly replaced by LMWH, which show superior efficacy. When prescribing anticoagulant prophylaxis or treatment to patients with hematologic malignancies, clinical benefits must be weighed carefully against the risks of bleeding.

Frequency of renal impairment, advanced age, obesity and cancer in venous thromboembolism patients in clinical practice.

Low-molecular-weight heparin (LMWH) dosed by weight is recommended as first-line therapy for the initial treatment of venous thromboembolism (VTE) and as monotherapy for long-term treatment of cancer-related VTE. In 'special populations' such as those with renal impairment or the elderly, weight-based dosing may be excessive, and capping the dose in obese patients may lead to inadequate dosing. We determined the frequency of 'special population' characteristics (renal impairment, advanced age, obesity) and cancer among VTE patients in clinical practice, and assessed whether these characteristics appeared to influence the type and dose of anticoagulants prescribed. During 2004-2005, among consecutive patients with VTE at two large Canadian hospitals, the proportions with the above characteristics were calculated and treatments prescribed were determined. Of 524 VTE patients, 31% were aged > 75 years. Moderate renal impairment [creatinine clearance (CrCl) 30-59 mL min(-1)] was present in 20% of patients, and severe renal impairment (CrCl < 30 mL min(-1)) in 5% of patients. LMWH was prescribed to 67% of patients with severe renal impairment and to 83% of patients with moderate renal impairment. Body weight was > 100 kg in 15% of patients. Underdosing of LMWH by > 10% was documented in 36% of such patients compared with 8% of patients < 100 kg (P < 0.001). Among 26% of patients with active cancer, only one-third were prescribed LMWH monotherapy. In clinical practice, renal impairment, advanced age, obesity and cancer are frequently present in patients with VTE. A considerable proportion of these patients may not receive the optimal type or dose of medication to treat VTE.

Use of Therapeutic Dose Low Molecular Weight Heparin in Patients with Renal Insufficiency: Analysis of Anti-Xa Levels and Creatinine Clearance.

Low molecular weight heparin (LMWH) is predominantly eliminated by the kidneys. In patients with severe renal impairment, use of therapeutic dose LMWH may be associated with accumulation and a resultant bleeding risk. Tinzaparin may be less dependent on renal clearance due to its higher molecular mass and greater negative charge compared to other LMWHs. The objective of this prospective cohort study was to serially measure the anti-Xa anticoagulant effect of therapeutic dose tinzaparin over 5–7 days, used for the initial treatment of venous thromboembolism (VTE) in patients with varying degrees of renal insufficiency. We present the anti-Xa results from the first 78 patients enrolled in the study, correlated with renal function. In this study, consecutive in- and outpatients with objectively confirmed VTE requiring anticoagulation were enrolled and stratified into 4 groups based on the calculated Cockcroft-Gault creatinine clearance (CrCl): > 60 mL/min, 30–60 mL/min, ≤ 30 mL/min and hemodialysis-dependent. Tinzaparin 175 IU/kg was administered subcutaneously once daily for 5–7 days or until the INR ≥ 2.0 with warfarin therapy. Trough anti-Xa levels were measured prior to the 3rd, 5th and/or 7th tinzaparin doses. Patients with anti-Xa level > 0.5 IU/mL received tinzaparin dose adjustment using a standardized nomogram. Bleeding and recurrent VTE events were recorded. The relationship between anti-Xa levels and CrCl is shown in Figure 1. Based on our predefined anti-Xa threshold of 0.5 IU/mL, 5 of 78 patients (6.4%) required dose adjustment; 1 hemodialysis dependent patient, 2 patients with CrCl < 30 mL/min, 1 patient each with CrCl 30–60 and > 60 mL/min, respectively. None of these patients developed bleeding or recurrent VTE. Among all 78 patients, 1 hemodialysis-dependent patient developed a hematoma following a traumatic line insertion, and no patients developed recurrent VTE. In conclusion, in a cohort of 78 patients with differing degrees of renal function including patients requiring hemodialysis, use of therapeutic-dose tinzaparin for the initial treatment of VTE resulted in accumulation (defined by trough anti-Xa > 0.5 IU/mL) in 6% of patients. There appears to be a weak inverse relationship between renal function and trough anti-Xa levels, but does not result in clinically significant accumulation when tinzaparin is used for up to 7 days. Further evaluation of tinzaparin in patients with severe renal insufficiency is required. [Display omitted]

Frequency of “Special Population” Characteristics among Venous Thromboembolism Patients in Clinical Practice: Implications for Anticoagulant Therapy.

Background: Consensus guidelines recommend the use of low molecular weight heparin (LMWH), dosed by patient weight, over unfractionated heparin (UFH) as first-line therapy for the initial treatment of venous thromboembolism (VTE) and as monotherapy for the long-term treatment of cancer-related VTE. However, caution is advised for certain “special populations”: in patients with renal impairment or in the elderly, weight-based dosing may be excessive, while capping the dose in obese patients as recommended by some LMWH manufacturers may lead to inadequate dosing.Objectives: We evaluated the frequency of characteristics such as renal impairment, advanced age, obesity and cancer among patients diagnosed with VTE in clinical practice, and assessed the impact of these characteristics on type and dose of medication prescribed to treat VTE.Methods: Medical records, thrombosis clinic charts and vascular lab reports from April 1, 2004 to March 31, 2005 were systematically searched to identify consecutive patients with objectively diagnosed VTE at 2 large university-affiliated hospitals in Canada. Trained research assistants abstracted patient records using study-specific case report forms. Data on age, sex, serum creatinine at time of VTE diagnosis, weight, presence of active cancer, type of VTE event, treatment initiated and dose of LMWH were recorded. Creatinine clearance (CrCl) was calculated using the Cockcroft Gault formula. Proportions of patients with renal impairment, advanced age, obesity and cancer were calculated. Type of treatment and appropriateness of LMWH dosing in various patient subgroups were determined.Results: 524 patients (Montreal 293; London 231) with VTE were identified, of whom 19% had PE and 81% had DVT. The average age was 62 years, with 31% of patients >75 years and 18% patients > 80 years. Overall, treatment initiated was LMWH and warfarin (71%), LMWH monotherapy (13%), UFH and warfarin (4%), IVC filter alone (4%) and other (8%). Moderate renal impairment (CrCl 30–50 ml/min) was present in 11% of patients and severe renal impairment (CrCl <30 ml/min) in 5%; only 58% of patients had normal renal function (CrCl >80 ml/min). Although mean CrCl was lower in patients who received UFH vs. LMWH (64 vs. 96 ml/min, p=0.003), an anticoagulant regimen that included LMWH was administered to 67% of patients with severe renal impairment and 83% of patients with moderate renal impairment. Body weight was >100 kg in 15% of patients. Underdosing of LMWH by 10% or more was documented in 36% of patients >100 kg compared with 8% of patients < 100 kg (p<0.001). Active cancer was present in 26% of patients. Patients with active cancer were more likely to be treated with LMWH monotherapy that those without cancer (32% vs. 7%, p<0.001).Conclusions: In clinical practice, renal impairment, advanced age, obesity and cancer are frequently present in patients with VTE. A significant proportion of patients with these features did not receive recommended type or dose of medication to treat VTE. Further research should address ways to improve implementation of VTE treatment guidelines into day-to-day clinical practice.

Low-molecular-weight heparin, bemiparin, in the outpatient treatment and secondary prophylaxis of venous thromboembolism in standard clinical practice: the ESFERA Study

The objective of this study is to assess the clinical and economic outcomes associated with outpatient treatment and secondary prophylaxis of acute venous thromboembolism (VTE) with a low-molecular-weight heparin, bemiparin. This study was designed as an open-label, multicentre, prospective, cohort study in standard clinical practice. Sixty-three investigators from 54 Spanish centres participated in the study. Five hundred eighty-three patients (434 outpatients and 149 inpatients) with acute VTE were followed up for 98 days (median). Outcome measures were costs and adverse events during initial VTE treatment with bemiparin (outpatient vs. inpatient cohorts) and long-term treatment [bemiparin (BEM) vs. vitamin K antagonists (VKA) cohorts]. Mean total costs per patient were lower in the outpatient cohort as compared with those in the inpatient cohort (1206 vs. 5191 euros; difference = -3985 euros; p < 0.001), with similar rates of adverse events (5.1 outpatient vs. 7.4% inpatient; p = 0.196) over 98 days. Mean total costs per patient were similar in the BEM/BEM and BEM/VKA cohorts (3616 vs. 3831 euros; difference = -215 euros; p = 0.412), but patients on long-term bemiparin treatment had lower rates of major bleeding (0.4 vs. 1.7%; p = 0.047), minor bleeding (1.8 vs. 6%; p = 0.032) and total adverse events (2.9 vs. 9.5%; p = 0.007) than patients in the BEM/VKA cohort. Outpatient management of VTE with bemiparin in selected patients resulted in significant cost-savings compared to inpatient treatment, while maintaining effectiveness and safety. Bemiparin may be a safer and cost-neutral alternative to VKA for long-term treatment of VTE.

Review: once daily LMWH is as effective as twice daily LMWH for initial treatment of venous thromboembolism

Review: once daily LMWH is as effective as twice daily LMWH for initial treatment of venous thromboembolism

Anticoagulants versus non-steroidal anti-inflammatories or placebo for treatment of venous thromboembolism

Venous thromboembolism (VTE) is the term given to any thromboembolic event (blocking of a blood vessel by a blood clot) occurring in the venous system. The current treatment recommended for VTE is anticoagulation (reduction of the blood's ability to clot). The aim of this review is to summarize results from randomized controlled trials (RCTs) for the effectiveness of anticoagulants (heparins, including low molecular weight heparins and vitamin K antagonists) in the treatment of VTE, compared to non-steroidal anti-inflammatory drugs (NSAIDs) or placebo. To examine the randomized controlled evidence for the effectiveness and safety of anticoagulant treatment compared to NSAIDs or placebo in patients with VTE on the incidence of fatal and non-fatal pulmonary emboli (PE) and the recurrence or extension of deep vein thrombosis (DVT). The Cochrane Peripheral Vascular Diseases (PVD) Group searched their Specialized Trials Register (last searched 26 July 2005) and the Cochrane Central Register of Controlled Trials (CENTRAL) database (last searched Issue 3, 2005). In addition, DKC also searched reference lists and contacted pharmaceutical companies and experts in the field. All randomized trials of anticoagulants versus NSAIDs or placebo in the initial treatment of VTE (DVT or PE or both). DKC and JM independently assessed trial quality and extracted data. JCP (biostatistician) analyzed the design elements and feasibility of a future randomized controlled trial to determine definitively efficacy and safety of anticoagulants in VTE treatment. Two RCTs were included. Data were not pooled because of heterogeneity between the studies. The two RCTs were too small to determine any difference in mortality, occurrence of pulmonary emboli, progression or return of DVT between patients treated with anticoagulation and those receiving no anticoagulation. The limited evidence from RCTs of anticoagulants versus NSAIDs or placebo is inconclusive regarding the efficacy and safety of anticoagulants in VTE treatment. The use of anticoagulants is widely accepted in clinical practice, so a further RCT comparing anticoagulants to placebo could not ethically be carried out.

Initial treatment of venous thromboembolism

Immediate anticoagulant treatment is essential to reduce morbidity and mortality in patients with acute venous thromboembolism (VTE). Currently, rapid anticoagulation can only be achieved with parenteral anticoagulants, such as heparin or low-molecular-weight heparin (LMWH). Weight-adjusted LMWH is the treatment of choice, because it produces predictable anticoagulation and does not require coagulation monitoring. If heparin is used, the activated partial thromboplastin time must be monitored and the heparin dose adjusted to ensure a therapeutic level of anticoagulation. Heparin is recommended for patients with renal impairment and for those at high risk of bleeding. The selective factor Xa inhibitor fondaparinux is a recently introduced alternative to heparin or LMWH for initial VTE treatment. Heparin, LMWH, or fondaparinux should be given for at least five to seven days. Vitamin K antagonists should be initiated on the first day, or as soon as possible, in patients who are candidates for an oral anticoagulant. An oral anticoagulant agent to be used without laboratory monitoring for both acute and long-term treatment of VTE remains an unsolved clinical need in the treatment of VTE.

How I treat venous thromboembolism in patients with cancer

Venous thromboembolism (VTE) is a frequent complication in cancer patients and represents an important cause of morbidity and mortality. Especially in patients who have a poor life expectancy, preventing death from pulmonary embolism is the mainstay of treatment. Critically ill patients should promptly be administered thrombolytic drugs. Except for selected patients requiring aggressive therapy, the initial VTE treatment should be conducted with either adjusted-dose unfractionated heparin or fixed-dose low-molecular-weight heparin (LMWH). LMWHs have the potential to greatly simplify the initial treatment of VTE, making the treatment of suitable patients feasible in an outpatient setting. During anticoagulant therapy, cancer patients have a 2- to 4-fold higher risk of recurrent VTE and major bleeding complications when compared with noncancer patients. The long-term administration of LMWH should be considered as an alternative to anti-vitamin K drugs in patients with advanced disease and in those with conditions limiting the use of oral anticoagulants. Prolongation of anticoagulation should be considered for as long as the malignant disorder is active. The evidence of lowered cancer mortality in patients on LMWH has stimulated renewed interest in these agents as antineoplastic drugs and raises the distinct possibility that cancer and thrombosis share common mechanisms.

Anti-Xa Levels and Renal Function: Analysis of the First 32 Patients in the Tinzaparin in Renal Insufficiency for Venous Thromboembolism Study.

Background: Low-molecular-weight heparin (LMWH) is renally eliminated; its use in patients with renal insufficiency may be associated with accumulation and an increased bleeding risk. Due to its higher molecular weight and greater negative charge, tinzaparin may be less dependent on renal elimination compared to other LMWHs. As a result, tinzaparin may be less prone to accumulate in patients with renal insufficiency.Purpose: To measure the anticoagulant effect of a 5-day course of therapeutic-dose tinzaparin used for the initial treatment of venous thromboembolism (VTE) in patients with varying degrees of renal insufficiency. We present the anti-Xa results of the first 32 patients enrolled in the study, correlated with renal function.Design: Prospective cohort study.Methods: In- and out-patients requiring therapeutic dose anticoagulation were enrolled and stratified into 4 groups based on creatinine clearance (CrCl): > 60 ml/min, 30–60 ml/min, ≤ 30 ml/min and hemodialysis-dependent. Tinzaparin 175 IU/kg was administered once daily for 5 days or until the INR was ≥ 2.0 with warfarin therapy. Trough anti-Xa levels were measured prior to the 3rd (day 3) and 5th (day 5) tinzaparin doses. Patients with an anti-Xa level > 0.5 IU/mL received tinzaparin dose adjustment using a standardized nomogram.Results: The relationship between anti-Xa levels and CrCl is shown in figure 1. One patient with a CrCl of 47 ml/min had a day 3 anti-Xa level of 0.62 IU/ml and required dose adjustment, resulting in a day 5 anti-Xa of 0.22 IU/ml. There has been one minor bleeding event (hematoma) following a traumatic intravenous catheter insertion. No major bleeding or recurrent VTE events have occurred.Conclusions: In a cohort of 32 patients with differing degrees of renal function including patients requiring hemodialysis, use of therapeutic-dose tinzaparin for 5 days does not appear to result in accumulation of the anticoagulant effects. There is no apparent correlation between anti-Xa level and renal function. Our results support ongoing evaluation of tinzaparin in patients with severe renal insufficiency. [Display omitted]

Traitement de la maladie thromboembolique veineuse

Adequate initial anticoagulant treatment is required to prevent thrombus growth and recurrence. Intravenous unfractionated heparin is being replaced by low-molecular-weight heparin as the anticoagulant of choice for initial treatment of venous thromboembolism. Vitamin K antagonists remain the only oral anticoagulant available (target international normalized ratio: 2.5). The duration of therapy should be individualized according to the risk of recurrence and the risk of bleeding. Three months of treatment is usually adequate if thrombosis was provoked by a reversible risk factor such as surgery. For patients with unprovoked ("idiopathic") thrombosis, anticoagulant treatment for at least 6 months is indicated. For patients with a recurrence of venous thromboembolism or with an irreversible risk factor such as cancer, indefinite anticoagulant therapy is recommended. Long-term treatment with low-molecular-weight heparin is usually preferable for patients with active cancer. Systemic thrombolysis is indicated for patients with massive pulmonary embolism but controversy persists for those with isolated right ventricular dysfunction.

Subcutaneous unfractionated heparin compared with low-molecular-weight heparin for the initial treatment of venous thromboembolism

Low-molecular-weight heparin is the preferred choice for the initial treatment of acute, uncomplicated venous thromboembolism. In this context, unfractionated heparin is as safe and effective as low-molecular-weight heparin but requires strict laboratory monitoring. Twice-daily subcutaneous unfractionated heparin is more effective than, and as safe as, intravenous unfractionated heparin and may simplify patient treatment in or out of the hospital, being possibly cost saving, especially if it is used in weight-based, fixed, unadjusted doses. The present review focuses on the relative values of low-molecular-weight heparin and subcutaneous unfractionated heparin for the initial treatment of venous thromboembolism. The major advantages of low-molecular-weight heparin over unfractionated heparin seem to be ease of administration and cost savings associated with home therapy or early hospital discharge; however, many patients with venous thromboembolism are still admitted to the hospital for treatment, and unfractionated heparin is extensively used to this purpose, especially in the United States. Subcutaneous unfractionated heparin, adjusted according to activated partial thromboplastin time algorithms, is as safe and effective as low-molecular-weight heparin for the treatment of venous thromboembolism, allows for quick mobilization and early discharge of suitable patients, and represents a cost-effective strategy. Fixed-dose unfractionated heparin, like low-molecular-weight heparin, may be used for the home treatment of deep vein thrombosis. Subcutaneous unfractionated heparin, targeted on activated partial thromboplastin time results or in fixed doses, may be used in or out of the hospital for the treatment of venous thromboembolism, being possibly cost effective; however, these findings need confirmation through appropriate, large-sample, randomized clinical trials.

Correction

HomeCirculationVol. 110, No. 24_suppl_1Correction Free AccessCorrectionPDF/EPUBAboutView PDFView EPUBSections ToolsAdd to favoritesDownload citationsTrack citationsPermissions ShareShare onFacebookTwitterLinked InMendeleyReddit Jump toFree AccessCorrectionPDF/EPUBCorrection Originally published14 Dec 2004https://doi.org/10.1161/01.CIR.0000151806.62457.47Circulation. 2004;110:IV-33This article corrects the followingInitial Treatment of Venous ThromboembolismIn Issue 3 of the SVMB Supplement to Circulation, in the article by McRae and Ginsberg (McRae SJ, Ginsberg JS. Initial Treatment of Venous Thromboembolism. Circulation. 2004;110(suppl I): I-3–I-9), the legend to Table 2 should read, “For enoxaparin, 100 anti-Xa U/kg corresponds to a dose of 1 mg/kg” rather than “100 mg/kg.” Previous Back to top Next FiguresReferencesRelatedDetailsCited By Pocs M (2013) Legally compatible design of future biometric systems for crime prevention, Innovation: The European Journal of Social Science Research, 10.1080/13511610.2013.747659, 26:1-2, (36-56), Online publication date: 1-Mar-2013. Friedman R (2010) Simplifying Thromboprophylaxis Could Improve Outcomes in Orthopaedic Surgery, Thrombosis, 10.1155/2010/108049, 2010, (1-5), Online publication date: 13-Sep-2010. Related articlesInitial Treatment of Venous ThromboembolismSimon J. McRae, et al. Circulation. 2004;110:I-3-I-9 December 14, 2004Vol 110, Issue 24_suppl_1 Advertisement Article InformationMetrics https://doi.org/10.1161/01.CIR.0000151806.62457.47 Originally publishedDecember 14, 2004 PDF download Advertisement