Risk factors for deep venous thrombosis following total hip arthroplasty: a meta-analysis

Abstract

AbstractSection Objective

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We aim to investigate the predictors of deep venous thrombosis (DVT) following total hip arthroplasty (THA) by meta-analysis.

AbstractSection Methods

We collected potential indicators of DVT from related literature in the English databases of PubMed, Embase, and the Cochrane Library. We used RevMan 5.3 and STATA 12.0 to analyze potential indicators of DVT after THA.

AbstractSection Results

Finally, there were 6 English articles included in our study, and the rate of DVT after THA was 18.9% (270 of 1428 patients). Our findings indicated that advanced age [p<0.00001, OR = 4.51, 95% CI (2.91, 6.10)], female patients [p = 0.008, OR = 0.65, 95% CI (0.47, 0.89)], body mass index [p = 0.01, OR = 0.76, 95% CI (0.15, 1.37)], diabetes [p = 0.01, OR = 1.85, 95% CI (1.14, 3.01)], malignancy [p = 0.001, OR = 2.54, 95% CI (1.46, 4.41)], uncemented prosthesis[p = 0.0003, OR = 0.22, 95% CI (0.10, 0.50)], and longer operation time [p<0.00001, OR = 33.50, 95% CI (23.59, 43.41)] were predictors for DVT following THA.

AbstractSection Conclusions

Many factors were found to be associated with DVT after THA. We provided references when we met the above characteristics of patients.

Introduction

Total hip arthroplasty (THA) is mainly used to treat joint pain and dysfunction due to hip joint diseases, including hip joint osteoarthritis, femoral head necrosis, and bone neck fractures [1]. Nowadays, more than 500,000 patients globally receive THA due to hip diseases each year, and it is estimated to be up to 40% in 2030 [2,3,4]. Venous thromboembolism (VTE) is a common or even fatal complication after THA. The incidence of DVT, which is a life-threatening complication because it can lead to fatal PE, can be as high as 40–60% [5] following THA. Therefore, it is urgent to find a valid prediction of DVT during the perioperative period.

Recently, increasing number of studies have focused on this hot topic. Yu [6] found that age > 70 years old, BMI ≥ 28 kg/m², diabetes, bilateral joint replacements, duration of surgery ≥ 120 min, cemented prosthesis, and duration of days in bed > 3 days were the risk factors of DVT after THA, while Wakabayashi [7] demonstrated that increased age, rheumatoid arthritis, and a history of major surgery were related to DVT. Although ongoing research has investigated DVT after THA, its risk factors remain poorly understood. As we know, this is the first meta-analysis to evaluate the predictors of DVT following THA.

Methods

Search strategy

Two authors searched PubMed, Embase, and Cochrane Library for titles from the inception of the database to January 2025 through an iterative process using a combination of keywords and mesh terms: “deep venous thrombosis”, “total hip arthroplasty”, AND “risk factors” OR “preditors” in the English databases, such as PubMed, Embase, and Cochrane Library. The purpose, research question, and eligibility criteria for the search were determined a priori. No restrictions on the language or date of publication were imposed. The primary author met with a senior author to review the syntax, spelling, and general search strategy to ensure that the search was comprehensive.

Study screening and selection

The targeted studies were included if they met the following inclusion criteria: (1) patients received THA; (2) focused on predictors for DVT. Articles were removed if they met exclusion criteria: (1) abstracts, letters, reviews, or case reports; (2) contained repeated data; (3) posters presented at conferences/congresses; (4) trials without sufficient data to obtain outcomes of interest.

The data included the general characteristics of each study and the outcomes measured. General characteristics included frst author, year of publication, country, the number of patients, and type of article. Two authors performed a systematic screening approach. To maximize the sensitivity of the screen, once disagreements between the two authors at the title, abstract or full-text stages were resolved by consensus decision from a third senior reviewer. The redundant and unrelated records were removed by reading titles and abstracts. Then, the full texts of remainders were downloaded to confrm their eligibility based on above criteria.

Quality assessment

We used the Newcastle Ottawa Quality Assessment Scale (NOQAS) to assess the quality of each study due to retrospective studies. Three points for the quality of participant selection, comparability, exposure, and outcomes in this study. The bias assessment commonly included randomized sequence generation, allocation concealment, performance bias, detection bias, attrition bias, reporting bias, and other biases.

Statistical analysis

Only continuous outcomes were mentioned in our study, so odd ratios (OR) and 95% confidence intervals (CI) were calculated for those outcomes. A p value<0.05 was judged statistically significant. We used random-effects or fixed-effects models according to the heterogeneity of the included studies. Heterogeneity was analyzed with both the Chi squared test (p<0.10) and the I square test (I²>50%). We used Review Manager version 5.3 (The Cochrane Collaboration, Oxford, UK) and STATA 12.0 (Stata Corporation, College Station, TX, USA) to analyze the potential indicators. We used the funnel plot to assess publication bias. We applied Egger and Begg tests to measure the funnel plot asymmetry with a significance level of p<0.10. Because of the low heterogeneity of every factor, we do not calculate sensitive analyses.

Results

Study selection and quality assessment

At first, we collected 53 English articles. Forty-seven articles were excluded due to repetition, inclusion criteria or exclusion criteria, which is shown in Fig. 1. Finally, six English articles, including 270 patients with DVT and 1158 patients without DVT met our inclusion criteria. Table 1 showed the main characteristics of six included English articles (1428 patients) up to October 2023. Three studies scored eight points, and another three scored seven points. Hence, the quality of each study was relatively high. (Table 2).

Fig. 1

Flow diagram of study selection

Table 1 Characteristics of included studies

Table 2 The quality assessment according to the Newcastle Ottawa quality assessment scale (NOQAS) of each study

Age

Five studies [6,7,8,9,10] reported the relationship between age at surgical time and DVT. There was low heterogeneity for age (p for heterogeneity = 0.77, I² = 0%, Fig. 2). We found that advanced age was a predictor for DVT after THA [fixed-effects model; p<0.00001, OR = 4.51, 95% CI (2.91, 6.10), Fig. 2].

Fig. 2

Forest plot showing age in 2 groups. CI = confidence interval, df = degrees of freedom, M-H = Mantel–Haenszel

Sex

Six studies [6,7,8,9,10,11] reported the relationship between sex and DVT. There was low heterogeneity for sex (p for heterogeneity = 0.77, I² = 0%, Fig. 3). We found that female patient was a predictor for DVT after THA [fixed-effects model; p = 0.008, OR = 0.65, 95% CI (0.47, 0.89), Fig. 3].

Fig. 3

Forest plot showing gender in 2 groups. CI = confidence interval, df = degrees of freedom, M-H = Mantel–Haenszel

Body mass index

Five studies [6,7,8,9,10] reported the relationship between body mass index (BMI) and DVT. There was low heterogeneity for BMI (p for heterogeneity = 0.16, I² = 40%, Fig. 4). We found that BMI was a predictor for DVT after THA [fixed-effects model; p = 0.01, OR = 0.76, 95% CI (0.15, 1.37), Fig. 4].

Fig. 4

Forest plot showing body mass index in 2 groups. CI = confidence interval, df = degrees of freedom, M-H = Mantel–Haenszel

Diabetes

Four studies [7, 9,10,11] reported the relationship between a history of diabetes and DVT. There was low heterogeneity for diabetes (p for heterogeneity = 0.26, I² = 25%, Fig. 5). We found that diabetes was a predictor for DVT after THA [fixed-effects model; p = 0.01, OR = 1.85, 95% CI (1.14, 3.01), Fig. 5].

Fig. 5

Forest plot showing diabetes in 2 groups. CI = confidence interval, df = degrees of freedom, M-H = Mantel–Haenszel

Hypertension

Four studies [6, 7, 9, 10] reported the relationship between a history of hypertension and DVT. There was low heterogeneity for hypertension (p for heterogeneity = 0.91, I² = 0%, Fig. 6). We found that hypertension was not a predictor for DVT after THA [fixed-effects model; p = 0.10, OR = 1.36, 95% CI (0.94, 1.96), Fig. 6].

Fig. 6

Forest plot showing hypertension in 2 groups. CI = confidence interval, df = degrees of freedom, M-H = Mantel–Haenszel

Malignancy

Four studies [7, 9,10,11] reported the relationship between a history of malignancy and DVT. There was low heterogeneity for malignancy (p for heterogeneity = 0.92, I² = 0%, Fig. 7). We found that malignancy was a predictor for DVT after THA [fixed-effects model; p = 0.001, OR = 2.54, 95% CI (1.46, 4.41), Fig. 7].

Fig. 7

Forest plot showing malignancy in 2 groups. CI = confidence interval, df = degrees of freedom, M-H = Mantel–Haenszel

Smoking

Two studies [10, 11] reported the relationship between a history of smoking and DVT. There was low heterogeneity for smoking (p for heterogeneity = 0.08, I² = 68%, Fig. 8). We found that smoking was not a predictor for DVT after THA [random-effects model; p = 0.46, OR = 0.37, 95% CI (0.03, 5.11), Fig. 8].

Fig. 8

Forest plot showing smoking in 2 groups. CI = confidence interval, df = degrees of freedom, M-H = Mantel–Haenszel

Type of fixation

Two studies [7, 11] reported the relationship between type of fixation and DVT. There was low heterogeneity for type of fixation (p for heterogeneity = 0.08, I² = 68%, Fig. 9). We found that type of fixation was a risk factor for DVT after THA [fixed-effects model; p = 0.0003, OR = 0.22, 95% CI (0.10, 0.50), Fig. 9].

Fig. 9

Forest plot showing type of fixation in 2 groups. CI = confidence interval, df = degrees of freedom, M-H = Mantel–Haenszel

Operation time

Two studies [6, 7, 9, 10] reported the relationship between operation time and DVT. There was low heterogeneity for operation time (p for heterogeneity = 0.40, I² = 0%, Fig. 10). We found that longer operation time was a risk factor for DVT after THA [fixed-effects model; p<0.00001, OR = 33.50, 95% CI (23.59, 43.41), Fig. 10].

Fig. 10

Forest plot showing operation time in 2 groups. CI = confidence interval, df = degrees of freedom, M-H = Mantel–Haenszel

Hyperlipidemia

Three studies [6, 7, 9] reported the relationship between hyperlipidemia and DVT. There was low heterogeneity for hyperlipidemia (p for heterogeneity = 0.53, I² = 0%, Fig. 11). We found that hyperlipidemia was not a risk factor for DVT after THA [fixed-effects model; p = 0.27, OR = 1.33, 95% CI (0.80, 2.18), Fig. 11].

Fig. 11

Forest plot showing hyperlipidemia in 2 groups. CI = confidence interval, df = degrees of freedom, M-H = Mantel–Haenszel

White blood cell

Three studies [6, 7, 9] reported the relationship between white blood cell (WBC) and DVT. There was low heterogeneity for WBC (p for heterogeneity = 0.53, I² = 0%, Fig. 12). We found that WBC was not a risk factor for DVT after THA [fixed-effects model; p = 0.27, OR = 1.33, 95% CI (0.80, 2.18), Fig. 12].

Fig. 12

Forest plot showing white blood cell in 2 groups. CI = confidence interval, df = degrees of freedom, M-H = Mantel–Haenszel

D- dimer

Two studies [8, 9] reported the relationship between D-dimer and DVT. There was high heterogeneity (p for heterogeneity = 0.03, I² = 80%, Fig. 13). We found that D-Dimer was not a risk factor for DVT after THA [random-effects model; p = 0.76, OR = 0.19, 95% CI (-0.99, 1.36), Fig. 13].

Fig. 13

Forest plot showing D-dimer in 2 groups. CI = confidence interval, df = degrees of freedom, M-H = Mantel–Haenszel.a.injury side; b.injury mechanism

Activated partial thromboplastin time

Two studies [8, 9] reported the relationship between activated partial thromboplastin time (APTT) and DVT. There was low heterogeneity for APTT (p for heterogeneity = 0.58, I² = 0%, Fig. 14). We found that APTT was not a risk factor for DVT after THA [fixed-effects model; p = 0.96, OR=-0.03, 95% CI (-1.08, 1.03), Fig. 14].

Fig. 14

Forest plot showing activated partial thromboplastin time in 2 groups. CI = confidence interval, df = degrees of freedom, M-H = Mantel–Haenszel

International normalized ratio

Two studies [8, 9] reported the relationship between international normalized ratio (INR) and DVT. There was low heterogeneity for INR (p for heterogeneity = 0.17, I² = 47%, Fig. 15). We found that INR was not a risk factor for DVT after THA [fixed-effects model; p = 0.83, OR=-0.00, 95% CI (-0.03, 0.02), Fig. 15].

Fig. 15

Forest plot showing international normalized ratio in 2 groups. CI = confidence interval, df = degrees of freedom, M-H = Mantel–Haenszel

Publication bias

We found no publication bias for all included studies by STATA 12.0 (all P > 0.05).

Discussion

THA, a widely used orthopedic procedure, has adequately improved the holistic function and quality of life in patients with hip diseases [1]. Annually, approximately 30,000 to 50,000 patients received THA in China [12, 13]. However, its derived complications can cause severe functional and psychological disorders, which is a tremendous challenge for orthopedic surgeons. DVT is one of the most common and troublesome complications after THA due to immobilization or medical problems of patients. Early prevention of DVT was beneficial in lowering the incidence of PE [11]. Plasminogen activator inhibitor-1 (PAI-1) was found to be an independent risk factor of DVT after THA [9]. Serum triglyceride levels were found to increase the risk of DVT after THA in female patients [10]. Wong did discover a close relationship between age, gender, race, presence of diabetes, history of malignancy, smoking habit, fixation type, operating time, and DVT [11].

Increasing research has been reported on the predictors of DVT after THA, yet they are still not completely understood. Therefore, the investigation of pointing out the potential indicators related to DVT in patients with THA is urgent. As we know, we are the first to assess the predictors for DVT after THA by meta-analysis. In our study, the rate of DVT was 18.9% (270 of 1428 patients). Our findings showed that advanced age, female patients, BMI, patients with a history of diabetes or malignancy, uncemented prosthesis, and longer operation time were relevant to DVT following THA.

Although previous articles have considered advanced age as an independent risk factor of DVT [14, 15], there remains debate after THA because half of the included articles in this study found no close relationship between age and DVT following THA. Our findings showed that advanced age was an independent predictor of DVT after THA. With the growing age of patients, the elasticity of blood vessels decreases, the blood vessel walls are easily damaged, and elderly patients have increased risks of some diseases closely related to DVT, such as diabetes [16]. Another debated factor was the gender of patients. Our findings indicated that female patients were more likely to suffer from DVT after THA. Two possible elements may account for the gender difference. First, it may be associated with the genetic differences and hormonal changes following menopause and its associated complications [17, 18]. Second, sex differences in DVT may be partially relevant to differing fat metabolism [19, 20]. In terms of BMI, it was larger in the DVT group than in the non-DVT group. Rising BMI was associated with venous thromboembolism due to multiple mechanisms and pathways contributing to this effect [21].

Some primary diseases, such as diabetes, were regarded as independent predictors of DVT based on prior literature [16]. However, there remains controversy in patients following because diabetes was found not to be associated with DVT after THA in half of the included articles. Interestingly, it is a risk factor for DVT after THA in our meta-analysis. It is easy to understand that patients undergoing orthopedic surgery are under stress. Blood glucose fluctuates more frequently in diabetes patients than in non-diabetic patients [22]. During surgery, the body releases various cytokines that rapidly activate the endogenous and exogenous coagulation systems and raise the risk of thrombosis [23]. The findings of this study indicate that blood glucose control in THA patients should be improved during surgery to lower the risk of DVT.

Similarly, we also found that patients with a history of malignancy were prone to suffer from DVT following THA. The potential reason that malignancy can affect various systems of the body can explain this. In the present study, operation time was significantly longer in the DVT group, which can be explained by the two following possible reasons. First, prolonged immobilization could cause venous congestion; second, vascular injury caused by surgery activated the coagulation system. Therefore, shortening surgery during is an effective measure to avoid DVT in patients who underwent THA. Additionally, our findings showed that patients with cemented prostheses tend to have DVT compared with those without it. Intraoperative bone cement can lead to the release of mononuclear cytokines, the separation and deformation of endothelial cells, and the addition of fibrinogen to the endothelial surface, which in turn activates the exogenous blood coagulation pathway, resulting in a high blood coagulation state, thereby increasing the risk of DVT in patients with cemented prostheses [24].

In terms of laboratory tests, D-dimer, which is influenced by numerous variables such as inflammation, age, surgery, hospitalization, COPD, and other acute disorders [25], is commonly utilized to detect DVT. In our research, no significant difference in D-dimer levels was identified between the DVT and non-DVT groups, which contradicted prior findings [14, 26]. Additionally, APTT and INR were also found to have no significant difference in two groups. Elderly patients, blood loss, and operation time surely make patients hypercoagulable in two groups. We still need more included studies to verify these results.

Although there was the first meta-analysis to explore the risk factors of DVT after THA, there were some flaws. First, there was no RCT article focused on this topic; second, due to the small number of included studies, subgroup analysis could not be analyzed, such as type of fixation (cemented vs. uncemented THA; third, most of the included articles originated from Asian countries, which may influence the accuracy of the results.

In summary, advanced age, female patients, BMI, patients with a history of diabetes or malignancy, uncemented prosthesis, and longer operation time were found to be related to DVT after THA. We hope our findings can provide orthopedic surgeons some novel discoveries.