Comparative Study of the Effects of Different Anticoagulation Regimens in Deep Vein Thrombosis Prevention After Intertrochanteric Fracture in Elderly

Summary

Hip fractures are a common but deadly elderly injury, and perioperative complications like deep vein thrombosis (DVT) can cause swelling, pain, and fatal embolism, even with anticoagulant treatment. This paper compares the effect of enoxaparin and lower limb circulation (LLC) on DVT prevention.

Abstract

The paper aims to investigate the difference between the effect of enoxaparin alone and enoxaparin + lower limb circulation (LLC) in the prevention of deep vein thrombosis (DVT) after intertrochanteric fracture in older people and to provide a basis for clinical anticoagulant therapy. A total of 121 patients undergoing hip fracture (HF) surgery were divided into the enoxaparin group (71 patients) and the enoxaparin + LLC group (50 patients) to compare the baseline features, changes in D-Dimer Index (DDI), and the incidence and distribution of DVT between the two groups. There was no significant difference between the baseline data of the two groups (p > 0.05). There was no significant difference between the D-Dimer Levels (DDL) 1 day after surgery (p = 0.191). But 3 days after surgery, the D-Dimer level was significantly lower in the enoxaparin + LLC group than in the enoxaparin alone group (p < 0.05). The incidence of DVT in both groups was 35.21% and 36.00% and was not statistically different (p > 0.05). No significant difference was seen in the distribution of DVT types between the two groups (p > 0.05). However, there were two popliteal vein thromboses and one femoral vein thrombosis in the enoxaparin alone group. The enoxaparin + LLC group was better at reducing the D-Dimer level than the enoxaparin group, but there was no significant difference in the incidence and distribution type of DVT. It is recommended that the proper anticoagulation regimen be selected based on the patient's risk and that the postoperative D-Dimer monitoring be supported.

Introduction

China's aging population increases the death rate, with new cases exceeding 1 million annually. Medical experts predict an annual increase of 1.3 million elderly HF patients by 2050^1,2. In patients with HF, deep-vein thrombosis (DVT) is one of the common and serious perioperative complications³. DVT can cause swelling and pain in the lower limbs and severe thrombus rupture into the pulmonary flow, causing fatal pulmonary embolism^4,5. One study has presented that the rate of preoperative lower limb DVT in HF was 38.25% and 56.83%; with anticoagulant treatment, the rate was between 25% and 30%.

Drug anticoagulation, surgical prevention, and early detection of movement are surgical treatments used periodically to decrease the rate of DVT^6,7. Regularly used drugs for treatment include warfarin, direct oral anticoagulants, and low-biological-weight drugs. However, the results and health benefits of these prescription medications differ significantly⁸. LMWH is commonly used in the prophylaxis of DVT after orthopedic surgery, but it can increase the risk of bleeding⁹. Clinical trials use direct oral anticoagulants as a cautious method of treatment; however, the high medical expenses related to these prescription medications prevent their intake in older people. Pressure devices and gradient pressure elastic stockings are physical measures that enhance blood circulation to the lower limbs during surgery. However, patients have distinct concerns regarding the line and its effectiveness. Preventing DVT involves early mobility and adaptive physical activity, but these precautions can be challenging to follow in older people with chronic cardiovascular disease, caused by symptoms and their physical conditions¹⁰.

The high rate of DVT after HF continues despite several preventive treatments¹¹. As a result, it is essential to adapt the anticoagulant treatment to the individual patient's specific condition^12,13. Standards and guidelines for avoiding DVT in heart attack and stroke patients keep changing at the national and international levels. However, problems continue in medical trials, including inaccurate DVT risk screening, poor use of precautionary therapy, and low patient acceptance of treatment among several patients¹⁴. The high risk and complexity of treatments with anticoagulants are better understood by the number of older people who have distinct symptoms of DVT illnesses¹⁵. Therefore, further investigation of the results of different anticoagulation approaches in preventing DVT after HF is essential in guiding clinical practice. To this end, in this study, by comparing the result of enoxaparin alone with the combination of mechanical prevention of DVT after HF, this study aims to provide a more effective anticoagulation approach, reduce the rate of DVT, and improve the prognosis and quality of life of patients¹⁶.

Patients in the hospital or recovering from surgery have a 60% lower chance of developing venous thromboembolism (VTE) if they use intermittent hydraulic compression devices and graduated compression stockings, according to the clinical study. However, rates of risk usually decline by less than 50% due to suffering and pain. Standard treatment involves using low-molecular-weight heparin therapy, which can cause problems like a higher chance of bleeding and negative effects on kidney function. To improve treatment results and patient safety, it is essential to establish personalized preventive trials that take into account each patient's unique risk factors, societal awareness levels, and surgical requirements.

Protocol

​This study strictly adhered to the principles of medical ethics and was approved by the hospital ethics committee of the Department of Orthopedics at Beijing Tongzhou District Integrated Traditional Chinese and Western Medicine Hospital, Beijing, China. All eligible participants are enrolled in the study according to the inclusion and exclusion criteria after obtaining informed consent.

Study subjects
This retrospective study includes 126 patients undergoing intertrochanteric fracture surgery in the hospital from January 2021 to December 2022. The inclusion of 121 patients in the study was subject to their successful completion of comprehensive medical screening and data verification measures¹⁷, and 5 patients were excluded for incomplete data or failed to meet the inclusion standards¹⁸. The inclusion criteria were (a) 65 years, clearly diagnosed with HF for < 21 days; (b) Postoperative anticoagulant therapy (enoxaparin regimen and enoxaparin + LLC regimen); (c) Complete clinical pre-and postoperative data and D-Dimer test results; (d) Provided informed consent, and the patient or family members agreed to contribute to the study. The exclusion criteria were : (a) Patients with hemorrhagic disease or severe coagulopathy; (b) A history of previous thrombotic disease or other definite high risk of thrombosis (e.g., malignancy); (c) Including allergy to heparin, high risk of postoperative bleeding, combined with severe cardiopulmonary dysfunction or multiple organ failure; (d) Non-primary fracture or other fracture site interfering with study results. The elimination criteria were: (a) missing key data before or after surgery (3 Cases); (b)Follow-up interrupted the D-Dimer Index (DDI) monitoring (1 Case); (c) Severe postoperative problems affecting the result of anticoagulant therapy (1 Case). Among the 121 patients, 71 patients in the enoxaparin-only group received a single enoxaparin anticoagulant regimen, and 50 patients in the enoxaparin + Lower Limb Circulation (LLC) group received enoxaparin combined with a mechanical drive device¹⁹.

The study uses patient weight to determine enoxaparin dosage as a 40 mg subcutaneous injection once daily for 7-10 days following surgical procedures. The LLC device used for patients in this group is listed in the Table of Materials and provides adjustable sequential compression therapy. Patients receive daily LLC treatment for 18 h starting from surgery until anticoagulation therapy ends, with the device inflating at 45 mmHg pressure with 45 s inflation periods alternating with 45 s deflation periods.

For D-Dimer testing, collect venous blood through the arm on postoperative days 1, 3, 7, 14, and 21. Use a 21G needle to obtain 5 mL of venous blood, which is placed in a blue-top tube containing citrate for coagulation tests. The laboratory receives blood samples within 2 h after mixing them 5x gently by inversion for analysis. The automated immunoassay analyzer (Table of Materials) determines D-Dimer levels through testing, which enables assessment of thrombosis risk by comparing them against the reference range (< 0.5 µg/mL). The laboratory maintains complete documentation about D-Dimer test outcomes for future examination purposes.

Study indicators
Baseline Data: It includes clinical data, age, gender, disease duration, fracture stability, surgical method, operation time, and hospitalization days. D-Dimer Indicators: Blood samples were collected on postoperative days 1, 3, 7, 14, and 21 to detect D-Dimer Levels (DDL) and assess the risk of thrombosis. Occurrence of DVT: The number of cases, time, and distribution sites (intermuscular vein, posterior tibial vein, popliteal vein) were recorded, and the incidence and type distribution of DVT in each group were counted.

Treatment regime
Carry out D-Dimer testing at three crucial time points, including before treatment, after enoxaparin administration, and at the 24 h mark following the first dose. The chosen time points enable proper evaluation of clotting indicators while validating anticoagulation treatment effectiveness. The anterolateral abdominal area is an accurate administration site for 40 mg of enoxaparin to achieve effective anticoagulation. Proper alignment of the Lower Limb Circulation device at 40 mmHg operation with a cycling rate of 3x a minute is required. The healthcare professional should obtain blood samples for D-Dimer testing from citrate tubes through a 21G needle while processing the specimens right away.

To ease pain or hematoma during enoxaparin injections, healthcare providers should change injection sites and improve their technique. The examination of LLC malfunction depends on both pressure testing and tubing inspection. A proper sample collection method with inversion and rapid processing must be used to obtain new blood specimens when results show hemolysis or clotting in D-Dimer tests. Patient discomfort from devices requires repositioning the equipment with subsequent calibration after temporarily stopping.

Statistical analysis
Statistical analysis was performed using SPSS 26.0 software. Data matching a normal distribution is expressed as x ± s for the measurement data. An independent samples t-test was used to compare the groups. For data that does not fit into a normal distribution, use the median (Interquartile Spacing)²⁰ and perform a non-parametric test (e.g., Mann-Whitney U-test). The count data is expressed as a percentage (%). To verify the normality of the data, all measurement data were tested by the Kolmogorov-Smirnov test before the t-test. Also, for the repeated measurement data, differences between and within groups were compared using repeated-measures ANOVA²¹, and multiple comparison correction was performed using the Bonferroni method^22,23. A two-sided p < 0.05 was considered statistically significant in all statistical analyses.

DDI assay
The D-Dimer assay involves incubation and must be performed under controlled laboratory conditions²⁴. Blood samples are collected in citrate tubes and centrifuged at 2000-3000 x g for 10-15 min at room temperature to obtain plasma. Depending on the laboratory setup, the D-Dimer analysis is typically conducted using an immunoturbidimetric assay or an ELISA-based method²⁵. For ELISA-based D-Dimer detection, samples are incubated at 37 °C for 30-60 min, followed by washing and adding detection reagents, with subsequent incubation steps at the same temperature²⁶. All assays should be performed in a temperature-controlled environment with minimal variation (± 1 °C)²⁷. Reagents must be brought to room temperature before use and stored per the manufacturer's recommendations (usually 2-8 °C)²⁸. Proper calibration of instruments and the use of quality control samples are essential to ensure the accuracy of the assay results²⁹. These detailed conditions ensure consistent and replicable D-Dimer measurement across study sites or replication attempts³⁰.

Results

Baseline data comparison
Table 1 concludes that the differences between the two groups in the baseline features of age, gender, disease duration, fracture stability, operation duration, hospitalization days, and operation methods were insignificant (p > 0.05); the baseline features were comparable and could be used for subsequent analysis.

DDI comparison
Table...

Discussion

This study showed no significant difference in baseline data (p > 0.05), including age, gender, disease duration, fracture stability, surgery time, and hospital days. This indicates a high comparability of the two groups, and the subsequent analysis results are reliable. In comparing the DDI, the D-dimer level was high 1 day after surgery, but no significant difference existed between groups (p = 0.191). The study showed that the increase of D-Dimer in the early postoperative period was mainly related to surgical tra...

Materials

List of materials used in this article

Name	Company	Catalog Number	Comments
Anticoagulant	Xarelto (Rivaroxaban)	Bayer AG	Pharmacologic prophylaxis
Elastic Stockings	JOBST Medical Legwear	Essity	Compression therapy
Intermittent Compression Device	SCD 700 Series	Cardinal Health	Mechanical prophylaxis for DVT prevention
Ultrasound Scanner	LOGIQ E10	GE Healthcare	Diagnostic imaging for thrombus detection