Meta-analysis of venous thromboembolism prophylaxis in medically Ill patients

doi:10.1016/j.clinthera.2007.11.015

Clinical Therapeutics

Volume 29, Issue 11, November 2007, Pages 2395-2405

https://doi.org/10.1016/j.clinthera.2007.11.015 Get rights and content

Abstract

Background: Venous thromboembolism (VTE) prophylaxis in medically ill patients has received a level 1A recommendation in previously published clinical guidelines. Pharmacologic prophylaxis for VTE includes unfractionated heparin (UFH), low-molecular-weight heparin (LMWH), and fondaparinux. Few direct comparisons between anticoagulants exist in medically ill patients.

Objective: This meta-analysis was conducted to assess UFH and LMWH (including the selective factor Xa inhibitor fondaparinux) in the reduction of in-hospital VTE in unselected medically ill patients.

Methods: We searched MEDLINE, EMBASE, and the Cochrane Controlled Trials Registry databases from January 1981 through September 2007 (English language) for randomized controlled trials using the following terms: dalteparin, enoxaparin, fondaparinux, nadroparin, and heparin. References of included articles and key review papers for additional studies were also searched. Data from studies were included in the analysis if the studies included medically ill patients with risk factors for VTE who had been followed up for 7 to 21 days.

Results: A total of 12,391 patients (of whom 8357 were in placebo-controlled trials) from 9 studies were included. Mean age for the entire cohort was 72.8 years; mean (SD) body mass index, 25.6 kg/m2; and mean (SD) actual body weight, 68.2 kg. Deep vein thrombosis (DVT) was significantly reduced with the addition of an LMWH compared with placebo (odds ratio [OR], 0.60; 95% CI, 0.47-0.75; P ≤ 0.001), but rates of DVT were similar when comparing LMWH with UFH (OR, 0.92; 95% CI, 0.56-1.52). No significant differences in pulmonary embolism (PE) or death were found among the UFH, LMWH, and placebo groups. LMWH was associated with a significant increased risk for minor bleeding compared with placebo (OR, 1.64; 95% CI, 1.18-2.29; P = 0.003). However, no significant difference was found between LMWH and UFH (OR, 0.68; 95% CI, 0.27-1.70). Major bleeding events were similar among all groups: LMWH/fondaparinux versus placebo, OR, 1.65 (95% CI, 0.8-3.4); LMWH/fondaparinux versus UFH, OR, 0.69 (95% CI, 0.29-1.68); LMWH/fondaparinux versus UFH or placebo, OR, 1.16 (95% CI, 0.66-2.04).

Conclusions: This analysis suggests that VTE prophylaxis with an LMWH (including fondaparinux) or UFH is effective in reducing the rate of DVT, but this benefit did not extend to enhanced protection against PE. Additionally, LMWH and UFH had similar bleeding outcomes.

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American Society of Hematology 2021 guidelines for management of venous thromboembolism: Prevention and treatment in patients with cancer
2021, Blood Advances
Venous thromboembolism (VTE) is a common complication among patients with cancer. Patients with cancer and VTE are at a markedly increased risk for morbidity and mortality.
These evidence-based guidelines of the American Society of Hematology (ASH) are intended to support patients, clinicians, and other health care professionals in their decisions about the prevention and treatment of VTE in patients with cancer.
ASH formed a multidisciplinary guideline panel balanced to minimize potential bias from conflicts of interest. The guideline development process was supported by updated or new systematic evidence reviews. The Grading of Recommendations Assessment, Development, and Evaluation (GRADE) approach was used to assess evidence and make recommendations.
Recommendations address mechanical and pharmacological prophylaxis in hospitalized medical patients with cancer, those undergoing a surgical procedure, and ambulatory patients receiving cancer chemotherapy. The recommendations also address the use of anticoagulation for the initial, short-term, and long-term treatment of VTE in patients with cancer.
Strong recommendations include not using thromboprophylaxis in ambulatory patients receiving cancer chemotherapy at low risk of VTE and to use low-molecular-weight heparin (LMWH) for initial treatment of VTE in patients with cancer. Conditional recommendations include using thromboprophylaxis in hospitalized medical patients with cancer, LMWH or fondaparinux for surgical patients with cancer, LMWH or direct oral anticoagulants (DOAC) in ambulatory patients with cancer receiving systemic therapy at high risk of VTE and LMWH or DOAC for initial treatment of VTE, DOAC for the short-term treatment of VTE, and LMWH or DOAC for the long-term treatment of VTE in patients with cancer.
American Society of Hematology 2018 guidelines for management of venous thromboembolism: Prophylaxis for hospitalized and nonhospitalized medical patients
2018, Blood Advances
In October 2022, these guidelines were reviewed by an expert work group convened by ASH. Review included limited searches for new evidence and discussion of the search results. Following this review, the ASH Committee on Quality agreed to continue monitoring the supporting evidence rather than revise or retire these guidelines at this time. Limited searches and expert review will be repeated annually going forward until these guidelines are revised or retired.
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Objective: These evidence-based guidelines from the American Society of Hematology (ASH) intend to support patients, clinicians, and others in decisions about preventing VTE in these groups.
Methods: ASH formed a multidisciplinary guideline panel balanced to minimize potential bias from conflicts of interest. The McMaster University GRADE Centre supported the guideline-development process, including updating or performing systematic evidence reviews. The panel prioritized clinical questions and outcomes according to their importance for clinicians and adult patients. The Grading of Recommendations Assessment, Development and Evaluation approach was used to assess evidence and make recommendations, which were subject to public comment.
Results: The panel agreed on 19 recommendations for acutely ill and critically ill medical inpatients, people in long-term care facilities, outpatients with minor injuries, and long-distance travelers.
Conclusions: Strong recommendations included provision of pharmacological VTE prophylaxis in acutely or critically ill inpatients at acceptable bleeding risk, use of mechanical prophylaxis when bleeding risk is unacceptable, against the use of direct oral anticoagulants during hospitalization, and against extending pharmacological prophylaxis after hospital discharge. Conditional recommendations included not to use VTE prophylaxis routinely in long-term care patients or outpatients with minor VTE risk factors. The panel conditionally recommended use of graduated compression stockings or low-molecular-weight heparin in long-distance travelers only if they are at high risk for VTE.
A RCT study of Rivaroxaban, low-molecular-weight heparin, and sequential medication regimens for the prevention of venous thrombosis after internal fixation of hip fracture
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Therefore, the theory for the choice of anticoagulant drugs is yet controversial with regard to drug prevention of VTE following major orthopedic surgery [16,17]. Low-molecular-weight heparin remains the most widely accepted drug for the prevention of VTE following major orthopedic surgery [18–22]. However, subcutaneous administration of heparin causes a certain degree of trauma to the patients and is inconvenient in routine practice.
The guidelines for the prevention of venous thromboembolism in orthopedic surgeries have reached a consensus on the postoperative conventional anticoagulation. However, the choice of anticoagulant drugs is yet controversial. The use of the drug rivaroxaban is expensive. Since the compliance of patients with low-molecular-weight heparin is considerably low, a cost-effective, efficacious and convenient anticoagulant program is essential. The present study investigated the efficacy, safety, patient compliance, and cost-effectiveness of low-molecular-weight heparin with sequential Rivaroxaban anticoagulant therapy in patients with a hip fracture, following internal fixation. A total of 287 patients with hip fractures were randomized into three groups: Rivaroxaban alone, Enoxaparin alone, and Enoxaparin followed by Rivaroxaban. The primary endpoint was the incidence of postoperative VTE, whereas the secondary endpoints were the compliance and treatment costs. Adverse reactions included bleeding and wound complications. The incidences of VTE were 5.21%, 14.74%, and 10.42% in the Rivaroxaban, low-molecular-weight heparin, and sequential therapy groups, respectively. The VTE-related mortality rates were 0%, 1.05%, and 1.04%. The average hospital stay was 12 ± 8,15 ± 7, and 11 ± 5d, whereas the compliance rates of the three groups were 82.3%, 71.6%, and 88.5%, respectively. The incidences of adverse incisions were 14.6%, 4.2%, and 6.3% for the three groups examined. The effects and the incidence of postoperative bleeding in the treatment of low-molecular-weight heparin followed by Rivaroxaban did not differ significantly from that of Rivaroxaban alone. However, the postoperative drainage, the cost of treatment and the incidence of VTE reduced significantly, whereas the incidences of adverse incisions and the patient compliance were increased.
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Thrombotic episodes are far less common than bleeding complications after hematopoietic stem cell transplantation (HSCT). However, they lead to significant morbidity and mortality. These complications are classified into four groups, including venous thromboembolic events (VTE), catheter-induced thrombosis (CIT), transplant-associated thrombotic microangiopathy (TA-TMA) and sinusoidal obstruction syndrome (SOS) or veno-occlusive disease (VOD). The frequency of VTE is increased among patients undergoing HSCT due to some acquired conditions including underlying malignancy, infections, administration of myeloablative conditioning regimens and/or total body irradiation, prolonged hospitalizations leading to immobility and presence of central venous catheters. Central venous catheters provide a convenient long-term venous access during HSCT. But they may lead to VTE and related complications such as pulmonary embolism or post-thrombotic syndrome by inducing endothelial trauma and inflammation. TA-TMA is a heterogeneous, fatal disorder seen within 100 days post-transplant and presents with thrombocytopenia, hemolysis, acute renal failure, mental status changes and involvement of other organs. SOS or VOD is another life threatening complication occuring within the first 35–40 days following a myeloablative regimen and presents with painful hepatomegaly, weight gain and elevated serum bilirubin levels. In this review, we aimed to define the epidemiology, specific risk factors, prevention and management of each group of complications in view of the recent relevant literature.
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Meta-analysis of venous thromboembolism prophylaxis in medically Ill patients

Abstract

Clin Ther

AmJ Cardiol

Control Clin Trials

Control Clin Trials

Am Heart J

Thromb Res

Thromb Res

Epidemiology of pulmonary embolism

Semin Vasc Med

Prevention of venous thromboembolism: Adherence to the 1995 American College of Chest Physicians consensus guidelines for surgical patients

Arch Intern Med

Frequency and determinants of the postthrom- botic syndrome after venous thromboembolism

Curt Opin Pulm Med

High risk of the critically ill for venous thromboembolism

Crit Care Med

Prevention of deep vein thrombosis in medical patients by low-dose heparin

Scott Med J

Prevalence of deep venous thrombosis among patients in medical intensive care

JAMA

Trends in the incidence of deep vein thrombosis and pulmonary embolism: A 25-year population-based study

Arch Intern Med

Direct medical cost of managing deep vein thrombosis according to the occurrence of complications

Pharmacoeconomics

A population- based perspective of the hospital incidence and case-fatality rates of deep vein thrombosis and pulmonary embolism. The Worcester DVT Study

Arch Intern Med

The long-term clinical course of acute deep venous thrombosis

Ann Intern Med

Prevention of venous thromboembolism: The Seventh ACCP Conference on Antithrombotic and Thrombolytic Therapy

Chest