The field of thromboprophylaxis for acutely ill medical patients, including those hospitalized for COVID-19, is rapidly evolving both in the inpatient setting and the immediate post-hospital ...discharge period. Recent data reveal the importance of incorporating holistic thromboembolic outcomes that encompass both venous thromboembolism (VTE) and arterial thromboembolism, as thromboprophylaxis with low-dose direct oral anticoagulants has been shown to reduce major and fatal vascular events, especially against a background of dual pathway inhibition with aspirin. In addition, recent post hoc analyses from randomized trial data have established 5 key bleeding-risk factors that, if removed, reveal a low-bleeding- risk medically ill population and, conversely, key individual risk factors, such as advanced age, a past history of cancer or VTE, an elevated D-dimer, or the use of a validated VTE risk score-the IMPROVE VTE score using established cutoffs-to predict a high-VTE-risk medically ill population that benefits from extended postdischarge thromboprophylaxis. Last, thromboprophylaxis of a high-thrombotic-risk subset of medically ill patients, those with COVID-19, is rapidly evolving, both during hospitalization and post discharge. This article reviews 3 controversial topics in the thromboprophylaxis of hospitalized acutely ill medical patients: (1) clinical relevance of key efficacy and safety outcomes incorporated into randomized trials but not incorporated into relevant antithrombotic guidelines on the topic, (2) the use of individual risk factors or risk models of low-bleeding-risk and high-thrombotic-risk subgroups of medically ill inpatients that benefit from extended thromboprophylaxis, and (3) thromboprophylaxis of hospitalized COVID-19 patients, including extended postdischarge thromboprophylaxis.
In acutely ill patients, 10 days of rivaroxaban was noninferior to 10 days of enoxaparin for thromboprophylaxis. Extended-duration rivaroxaban treatment (35 days) reduced the risk of venous ...thromboembolism. Rivaroxaban was associated with an increased risk of bleeding.
Patients with active cancer, stroke, myocardial infarction, or acute exacerbations of a variety of medical conditions are at increased risk for venous thromboembolism.
1
Prolonged immobilization and risk factors such as an age older than 75 years, chronic heart failure, a history of venous thromboembolism, and obesity can increase this risk further.
2
,
3
Randomized, controlled trials involving hospitalized patients at increased risk for venous thromboembolism have shown the benefits of administering anticoagulant agents for up to 14 days,
4
–
8
and guidelines recommend the use of unfractionated heparin, low-molecular-weight heparins, or fondaparinux in such patients.
9
There is some evidence that the risk . . .
The periprocedural management of patients receiving long-term oral anticoagulant therapy remains a common but difficult clinical problem, with a lack of high-quality evidence to inform best ...practices. It is a patient's thromboembolic risk that drives the need for an aggressive periprocedural strategy, including the use of heparin bridging therapy, to minimize time off anticoagulant therapy, while the procedural bleed risk determines how and when postprocedural anticoagulant therapy should be resumed. Warfarin should be continued in patients undergoing selected minor procedures, whereas in major procedures that necessitate warfarin interruption, heparin bridging therapy should be considered in patients at high thromboembolic risk and in a minority of patients at moderate risk. Periprocedural data with the novel oral anticoagulants, such as dabigatran, rivaroxaban, and apixaban, are emerging, but their relatively short half-life, rapid onset of action, and predictable pharmacokinetics should simplify periprocedural use. This review aims to provide a practical, clinician-focused approach to periprocedural anticoagulant management.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Thromboprophylaxis in critical care Helms, Julie; Middeldorp, Saskia; Spyropoulos, Alex C.
Intensive care medicine,
01/2023, Volume:
49, Issue:
1
Journal Article
Peer reviewed
Open access
Full text
Available for:
EMUNI, FIS, FZAB, GEOZS, GIS, IJS, IMTLJ, KILJ, KISLJ, MFDPS, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, SBMB, SBNM, UKNU, UL, UM, UPUK, VKSCE, ZAGLJ
Periprocedural bridging with unfractionated heparin or low-molecular-weight heparin aims to reduce the risk of thromboembolic events in patients receiving long-term vitamin K antagonists. Optimal ...periprocedural anticoagulation has not been established.
MEDLINE, EMBASE, and Cochrane databases (2001-2010) were searched for English-language studies including patients receiving heparin bridging during interruption of vitamin K antagonists for elective procedures. Data were independently collected by 2 investigators (κ=0.90). The final review included 34 studies with 1 randomized trial. Thromboembolic events occurred in 73 of 7118 bridged patients (pooled incidence, 0.9%; 95% confidence interval CI, 0.0.0-3.4) and 32 of 5160 nonbridged patients (pooled incidence, 0.6%; 95% CI, 0.0-1.2). There was no difference in the risk of thromboembolic events in 8 studies comparing bridged and nonbridged groups (odds ratio, 0.80; 95% CI, 0.42-1.54). Bridging was associated with an increased risk of overall bleeding in 13 studies (odds ratio, 5.40; 95% CI, 3.00-9.74) and major bleeding in 5 studies (odds ratio, 3.60; 95% CI, 1.52-8.50) comparing bridged and nonbridged patients. There was no difference in thromboembolic events (odds ratio, 0.30; 95% CI, 0.04-2.09) but an increased risk of overall bleeding (odds ratio, 2.28; 95% CI, 1.27-4.08) with full versus prophylactic/intermediate-dose low-molecular-weight heparin bridging. Low-thromboembolic-risk and/or non-vitamin K antagonist patient groups were used for comparison. Study quality was poor with heterogeneity for some analyses.
Vitamin K antagonist-treated patients receiving periprocedural heparin bridging appear to be at increased risk of overall and major bleeding and at similar risk of thromboembolic events compared to nonbridged patients. Randomized trials are needed to define the role of periprocedural heparin bridging.
In a case series from China,2 increased D-dimer concentration at time of admission to hospital (>1 μg/mL) was associated with a risk of in-hospital mortality that was 18 times higher than among those ...with normal D-dimer concentrations, and the authors highlighted that “inadequate adherence to standard supportive therapy”, among other things, might have led to poor outcomes in some patients.2 Acutely ill patients with severe viral pneumonia and acute respiratory distress syndrome (ARDS), such as those with H1N1 infection, who have been admitted to hospital have a 23-times increased risk for pulmonary embolism,3 and guidelines support routine thromboprophylaxis in these patients.4 Increased D-dimer concentrations of more than double the upper limit of normal has emerged as a new biomarker to predict risk of venous thromboembolism in all patients in hospitals. Trial subgroup analyses, in which increased D-dimer concentration or admission to hospital with infection (particularly pneumonia) were incorporated as variables, show that extended thromboprophylaxis with direct oral anticoagulants has benefit compared with routine in-hospital thromboprophylaxis with low molecular weight heparin.5 Finally, empirical anticoagulation has been associated with improved thrombotic event-free survival in critically ill patients with ARDS due to influenza A H1N1.3 In light of this evidence, and the fact that hospitals might soon have a large number of patients with COVID-19 who might meet guideline requirements for thromboprophylaxis, we believe it seems prudent to use thromboprophylaxis in such patients, particularly those with evidence of activation of the coagulation system (eg, increased D-dimer concentrations) on admission. Of utmost importance will be the prospective, real-time data collection to assess whether use of thromboprophylaxis in patients with COVID-19 leads to improved outcomes, including improved survival, without clinically important bleeding.
Full text
Available for:
GEOZS, IJS, IMTLJ, KILJ, KISLJ, NLZOH, NUK, OILJ, PNG, SAZU, SBCE, SBJE, UILJ, UL, UM, UPCLJ, UPUK, ZAGLJ, ZRSKP
Summary
Acutelly-ill hospitalised medical patients are at risk of venous thromboembolism (VTE), both in-hospital and in the immediate post-discharge period, and mortality from VTE is thought to be ...particularly high in this patient population. However, despite previous mandates from international antithrombotic guidelines such as those of the American College of Chest Physicians (ACCP) for the “universal” use of thromboprophylaxis in hospitalised medical patients, global audits suggest that implementation of thromboprophylaxis continues to be challenging because of the perceived higher risk of bleeding and lower risk of VTE than that reported in clinical trials. Recent population-based studies also reveal that a “universal” hospital-only thromboprophylactic strategy does not reduce the community burden of VTE from this population, which may constitute nearly one quarter of the attributable risk of VTE. Lastly, four large randomised placebo-controlled trials of extended thromboprophylaxis have failed to show a definitive net clinical benefit in hospitalised medical patients. Recent large-scale efforts in deriving and validating scored VTE and bleed risk assessment models (RAMs) have been completed in the medically-ill population. In addition, an elevated D-dimer as a new biomarker to identify at-VTE risk medically ill patients has also undergone prospective evaluation. This paper will review current concepts of VTE and bleed risk in hospitalised medical patients, both in the hospital as well as the post-hospital discharge period, and will discuss new paradigms of thromboprophylaxis in this population using an individualised, patient-centered approach.
PDF
