Thromboprophylaxis in Nonsurgical Patients: Guidelines for Preventive Treatment With LMWH
Introduction
A European study investigating the incidence of venous thromboembolism (VTE) among hospitalized and ambulatory patients found an annual incidence of 148 cases per 100,000 individuals—83 cases among hospitalized patients and 65 cases among ambulatory patients. (1) The study also reported that 71% of hospitalized patients diagnosed with VTE died. (1)
The benefits of thromboprophylaxis are well established in the medical literature and are reflected in current clinical practice guidelines. High-risk periods for VTE have been clearly identified in orthopedic and general surgery, and evidence-based pharmacological thromboprophylaxis protocols have significantly reduced the incidence of VTE in surgical patients. (2)
In contrast, thromboprophylaxis is believed to be underutilized in patients admitted to medical wards. (2) Moreover, hospitalized medical patients diagnosed with VTE have been shown to experience higher rates of fatal pulmonary embolism (PE) and fatal or major bleeding than surgical patients with VTE. (3) Several randomized clinical trials have demonstrated both the efficacy and safety of pharmacological thromboprophylaxis in hospitalized medical patients. (4–6)
Many risk factors for VTE are shared by both hospitalized and ambulatory patients. (7) In addition, many ambulatory patients who develop VTE ultimately require hospitalization. (8,9) The benefits of continuing thromboprophylaxis after hospital discharge have been demonstrated in selected patient populations, including individuals older than 75 years, women, and patients with severe mobility limitations who are unable to leave their beds. (10)
In recent years, several VTE risk assessment models have been developed to identify hospitalized patients at increased risk of thromboembolic events. Some of these scoring systems have subsequently been modified for use in ambulatory patients. (11–13) Additional studies have evaluated VTE risk among patients treated at home because of acute illness or reduced mobility. (14–16) Other investigations have assessed the adequacy of thromboprophylaxis in patients discharged directly from emergency departments. (17,18)
However, until recently, no study had specifically evaluated VTE risk among medical patients discharged from emergency departments without hospitalization. To address this gap, the URGENTV study was conducted. Its primary objective was to identify patients at moderate or high risk of VTE who were discharged from emergency departments without receiving appropriate thromboprophylaxis. Secondary objectives included evaluating factors influencing physicians' decisions not to prescribe thromboprophylaxis and determining the incidence of pulmonary embolism during the first month after discharge.
This article summarizes the design and findings of the URGENTV study. (21) The results demonstrate that only a small proportion of eligible patients discharged from emergency departments received thromboprophylaxis despite strong evidence supporting its use and recommendations from clinical guidelines. The article also presents a VTE risk assessment model for non-surgical patients together with recommendations for low-molecular-weight heparin (LMWH) prophylaxis based on the patient's estimated VTE risk.
Thromboprophylaxis in Non-Surgical Patients
The benefits of VTE prophylaxis have been firmly established in surgical patients. In contrast, relatively few clinical trials have focused on hospitalized medical patients and ambulatory populations.
Available epidemiological data indicate that 50–70% of symptomatic VTE events and 70–80% of fatal pulmonary embolism cases occur in hospitalized medical patients. Autopsy studies support these findings, showing that approximately 75% of patients who died in hospital from pulmonary embolism had not undergone recent surgery.
Hospitalization for an acute medical illness increases the relative risk of VTE approximately eightfold. Patients admitted with acute myocardial infarction, stroke, severe infections, or inflammatory bowel disease have a risk of deep vein thrombosis (DVT) comparable to that of surgical patients, approaching 25%. Furthermore, most medical patients have multiple concurrent VTE risk factors, resulting in cumulative increases in thromboembolic risk.
URGENTV Study Design
URGENTV was a multicenter observational epidemiological study based on retrospective data collection.
The study included adults aged 18 years or older who were discharged from emergency departments after evaluation for acute or chronic infectious diseases, dyspnea, pulmonary disorders, or cardiovascular diseases.
Patients were excluded if they were already receiving anticoagulant therapy, had hypersensitivity to low-molecular-weight heparin (LMWH), had a history of heparin-induced thrombocytopenia, had experienced upper gastrointestinal bleeding within the previous three months, had liver failure, or had coagulation disorders associated with an increased risk of bleeding.
The following variables were collected for each participant:
- demographic characteristics (age, sex, body weight, height, and body mass index);
- hospital characteristics (public or private institution) and referral source (home, emergency medical services, primary care, or another hospital);
- comorbidities, including diabetes mellitus, hypertension, dyslipidemia, arrhythmias, ischemic heart disease, colitis, liver disease, renal insufficiency, neurodegenerative disorders, and cerebrovascular disease;
- VTE risk assessment and thromboprophylaxis recommendations.
VTE risk was assessed using the 2007 PRETEMED risk assessment model. (13) Patients were classified as low, moderate, or high risk. Pharmacological thromboprophylaxis with LMWH was recommended for all patients classified as having moderate or high VTE risk.
Patients were followed for one month after discharge, and all diagnoses of deep vein thrombosis and pulmonary embolism were recorded.
Results of the URGENTV Study
The study included 2,280 patients who met all inclusion criteria. Among them, 1,850 patients (81.1%) were classified as having a moderate or high risk of VTE.
The most common risk factors included acute infection (22.3%), New York Heart Association class III heart failure (16.5%), malignancy (18.3%), and exacerbation of chronic obstructive pulmonary disease (COPD) (20.2%). Other frequently observed risk factors included diabetes mellitus, antidepressant use, age over 60 years, smoking, obesity, and physical disability.
Pharmacological thromboprophylaxis with LMWH was prescribed to only 57.9% of patients classified as having moderate or high VTE risk. The mean duration of treatment was 16.4 ± 14.3 days.
Consequently, 42.1% of patients in the moderate- and high-risk groups were discharged from the emergency department without receiving thromboprophylaxis.
Multivariate statistical analysis identified several factors independently associated with failure to prescribe thromboprophylaxis, including sudden loss of mobility, a history of neurodegenerative disease, an emergency department stay longer than 12 hours, and older age.
One month after discharge, follow-up data were available for 887 of the 1,850 patients (47.9%) classified as having moderate or high VTE risk. Among these patients, 28 (3%) developed VTE, including 19 cases of deep vein thrombosis and 9 cases of pulmonary embolism.
Of these 28 patients who subsequently developed VTE after discharge, 19 (67.9%) had not received thromboprophylaxis before leaving the emergency department (Table 1).
Table 1. Incidence of Venous Thromboembolism Within 1 Month After Discharge From the Emergency Department
| Moderate and High VTE Risk (PRETEMED), n = 1,850 | Low VTE Risk (PRETEMED), n = 430 | |
|---|---|---|
| Patients evaluated 1 month after discharge, n (%) | 887 (47.9) | 178 (41.4) |
| Patients diagnosed with VTE, n (%) | 28 (3.2) | 8 (4.5) |
| Patients diagnosed with VTE who received thromboprophylaxis, n (%) | 9 (32.1) | – |
| Patients diagnosed with VTE who did not receive thromboprophylaxis, n (%) | 19 (67.9) | – |
VTE – venous thromboembolism.
Table 2. VTE Risk Assessment
| Category | 1 Point | 2 Points | 3 Points | 4 Points |
|---|---|---|---|---|
| Medical conditions | Pregnancy; Postpartum period; Lower limb paralysis | Cancer; Heart failure; Nephrotic syndrome; Acute infectious disease | Decompensated COPD; Stroke with lower limb paralysis | Acute myocardial infarction |
| Medications | Tamoxifen; Raloxifene; Hormone replacement therapy; Oral contraceptives | Chemotherapy | – | – |
| Local conditions | Central venous catheter (CVC) | Previous VTE; Lower limb cast; Bed rest >4 days | – | – |
| Other | Age >60 years; Obesity (BMI >28); Smoking (>35 cigarettes/day) | – | – | – |
CVC – central venous catheter; HF – heart failure; CKD – chronic kidney disease; COPD – chronic obstructive pulmonary disease; VTE – venous thromboembolism.
Conclusions of the URGENTV Study
The authors of the URGENTV study noted that they were unable to identify any previous studies evaluating the frequency of thromboprophylaxis prescriptions for patients discharged directly from emergency departments with acute or chronic medical conditions. Their findings showed that most patients identified as having a moderate or high risk of VTE were discharged without receiving thromboprophylactic treatment. Failure to prescribe low-molecular-weight heparin (LMWH) was associated with unexpectedly reduced mobility, a history of neurodegenerative disease, prolonged stays in the emergency department, and older age. The incidence of VTE observed in this study was consistent with rates reported in previous research involving patients with similar risk profiles. However, direct comparisons with other studies of discharged emergency department patients were not possible because comparable data are currently lacking. Compared with other cohort studies, patients discharged home were less likely to receive thromboprophylaxis than hospitalized patients, among whom prophylaxis was prescribed more frequently. Previous studies also reported that a smaller proportion of hospitalized medical patients required thromboprophylaxis than in the URGENTV study.
The reasons why some moderate- and high-risk patients were not prescribed thromboprophylaxis were not fully explored. Evidence from a recent multicenter study conducted in the United States suggests that physicians may have insufficient familiarity with current clinical practice guidelines, including indications and contraindications for thromboprophylaxis. Overall, the URGENTV study suggests that patients discharged without indicated thromboprophylaxis were typically ambulatory, older adults, often with dementia and multiple comorbidities. Importantly, ambulatory patients may be mistakenly perceived as being at low risk for VTE. Other factors are more difficult to explain, as thromboprophylaxis is generally recommended for such patients. One possible explanation is that physicians weighed the potential bleeding risk more heavily than the risk of thromboembolism, leading them to withhold anticoagulant therapy because bleeding is considered an iatrogenic complication, whereas VTE is viewed as a disease-related complication.
One limitation of the study is that emergency department physicians were provided with thromboprophylaxis guidelines and VTE risk assessment tools before the study, which may have increased the rate of thromboprophylaxis prescribing. Another limitation is that bleeding complications associated with anticoagulant therapy were not evaluated because patients at high risk of bleeding were excluded from the study. Despite these limitations, the URGENTV study provided valuable information regarding thromboprophylaxis practices in patients discharged from emergency departments.
Table 3. LMWH Thromboprophylaxis Recommendations
| VTE Risk | LMWH Dosing |
|---|---|
| 4 points (based on all categories in Table 2) | Lower-dose LMWH administered subcutaneously once daily. Duration: 7–10 days or until mobility is restored. If the condition associated with the increased risk persists, thromboprophylaxis should be continued at home. |
| >4 points, or 4 points with additional risk factors from the medical conditions or local conditions categories | Higher-dose LMWH administered subcutaneously once daily. Prophylactic treatment should be continued according to the treating physician's recommendations while the increased risk persists or until mobility is restored. The usual duration of prophylaxis is 7–10 days, although it may be extended if the risk of VTE remains elevated. If the condition associated with the increased risk persists, thromboprophylaxis should be continued at home. |
VTE – venous thromboembolism; LMWH – low-molecular-weight heparin.
LMWH Thromboprophylaxis Recommendations for Non-Surgical Patients
Regardless of the estimated VTE risk, every patient should undergo an appropriate clinical assessment.
Thromboprophylaxis in medical patients should only be prescribed after an individualized assessment that considers the patient's overall condition, medical history, and risk factors. Standardized risk assessment tables have been developed to facilitate this process by assigning points to individual risk factors (Table 2). For medical patients with a total risk score of 1–3 points, thromboprophylaxis is generally not required, provided that normal mobility is restored promptly. Recommended thromboprophylaxis according to risk category is presented in Table 3.
Prepared by Dr. Rasa Geigalienė
