Perioperative anticoagulation reduces the incidence of venous thromboembolism in patients undergoing gastrointestinal surgery

Abstract

BACKGROUND

The risk and mortality rate of venous thromboembolism (VTE) following gastrointestinal surgery remain high, and the symptoms are atypical. Therefore, it is necessary to identify the risk factors associated with the occurrence of VTE following gastrointestinal surgery and to implement appropriate prevention and treatment measures.

AIM

To assess the efficacy of perioperative anticoagulation for the prevention of postoperative VTE.

METHODS

This retrospective study enrolled 205 patients who underwent gastrointestinal surgery. In the observation group (n = 101), prophylactic anticoagulation was administered via hypodermic injection of low-molecular-weight heparin during the perioperative period, whereas the control group (n = 104) only received low-molecular-weight heparin treatment postoperatively. Blood coagulation parameters and the incidence of VTE of the bilateral lower limbs pre- and post-surgery were compared between groups. Postoperative VTE was transformed into a dichotomous variable, and influencing factors were explored using multivariate logistic regression analyses.

RESULTS

On the 7^th day postoperatively, the incidence of VTE of the bilateral lower limbs was significantly lower in the observation group than in the control group, as were the D-dimer levels (P < 0.05). At 1 month postoperatively, the incidence of VTE was significantly lower in the observation group than in the control group (P < 0.05). An age ≥ 65 years, a body mass index ≥ 24 kg/m², and malignant diseases of the digestive system were identified as risk factors for the occurrence of postoperative VTE in patients undergoing gastrointestinal surgery.

CONCLUSION

The incidence of VTE in patients who underwent gastrointestinal surgery peaked within 1 week postoperatively. The findings confirmed perioperative anticoagulation can safely and effectively reduce the incidence of postoperative VTE.

Key Words: Venous thromboembolism; Gastrointestinal surgery; Perioperative anticoagulation; Low-molecular-weight heparin; Risk factor

Core Tip: This retrospective study single-center observational study compared the outcomes of perioperative and postoperative venous thromboembolism (VTE) and investigated the risk factors in patients who underwent gastrointestinal surgery. The incidence of VTE peaked within 1 week post-surgery, and prophylactic anticoagulation therapy with low molecular weight heparin reduced the incidence of VTE and exhibited a good safety profile. An age ≥ 65 years, a body mass index ≥ 24 kg/m², and malignant diseases of the digestive system were identified as risk factors for the occurrence of postoperative VTE in patients undergoing gastrointestinal surgery.

INTRODUCTION

Venous thromboembolism (VTE) is defined as a medical condition in which an abnormal blood clot in a vein leads to complete or incomplete blockage of the vessel, according to the United States Centers for Disease Control and Prevention[1]. Deep vein thrombosis (DVT) is the most common type of post-surgical VTE and frequently occurs in the lower extremities[1]. A previous study demonstrated that the probability of developing DVT was approximately 40% among patients undergoing gastrointestinal surgery with no perioperative precautionary measures[2]. DVT ranks as the second most common complication among surgical patients in the USA, and it prolongs the average hospitalization period, increases mortality rates, and imposes excessive health-related financial burdens worldwide[3]. Malignant tumor cells can directly or indirectly activate the coagulation system, thereby inducing a hypercoagulable state in patients[3]; in addition, perioperative vascular wall damage and blood stasis can further aggravate this state, leading to the occurrence of DVT.

Due to the atypical symptoms of VTE, it can easily remain undiagnosed, and once a pulmonary embolism (PE) occurs, the fatality rate is high[4]. Despite the high incidence and severity of VTE following gastrointestinal surgery, it remains a preventable disease. Evidence suggests that the incidence of postoperative VTE can be reduced by more than half by using a comprehensive evaluation system and enforcing proper prevention and treatment measures[5]; therefore, it is important to implement these measures and identify risk factors associated with postoperative DVT following gastrointestinal surgery to improve clinical outcomes. Implementing correct prevention strategies and performing early assessments can reduce the risk of VTE by 50%-60% in the early postoperative period[6]. Surgery is the main treatment for patients with gastrointestinal conditions, and intraoperative vascular injury and postoperative immobility are important factors that may be related to VTE, which can eventually result in PE[7]. Previous studies have explored the role of prophylactic anticoagulation strategies in reducing the incidence of VTE in specific patient populations[7,8]; however, the results have been somewhat inconsistent, and there are still gaps in the literature that limit the understanding of the relationships between various factors.

To date, no study has definitively confirmed whether perioperative anticoagulation therapy can effectively reduce the incidence of postoperative VTE in patients undergoing gastrointestinal surgery. Therefore, to fill this void in the literature, the aim of this retrospective study was to investigate whether perioperative anticoagulation therapy administered in gastrointestinal surgery cases could help prevent postoperative VTE. By doing so, we hope to provide valuable insights for clinicians to facilitate more informed decision-making regarding the prevention of VTE in patients undergoing gastrointestinal surgery, which could ultimately improve patient outcomes and reduce the associated morbidity and mortality.

MATERIALS AND METHODS

Participant selection

Medical records of 205 patients who had been definitively diagnosed with gastrointestinal disease based on routine pathology and underwent surgical treatment at the Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University from December 2022 to January 2024 were retrospectively collected. This study was approved by the Medical Ethics Committee of Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University.

Patients were included if they met the following criteria: (1) Age ≥ 18 years; (2) Elective or limited surgery was performed for the treatment of gastrointestinal diseases; (3) No contraindications to anticoagulants, as described in the product monograph; (4) Availability of complete clinical information that met the observational criteria; and (5) No obvious coagulation dysfunction or related coagulation disorders before surgery.

Patients were excluded if they met the following criteria: (1) No surgical treatment received during hospitalization; (2) A history of coagulation dysfunction; (3) A history of immune system disorders; (4) The definitive presence of preoperative VTE; (5) Any underlying thrombotic diseases; and (6) Being pregnant or breastfeeding.

Interventions

According to the anticoagulation strategy, the observation group was administered a prophylactic dose of low-molecule-weight heparin (LMWH) (2500 IU of bemethoate sodium) via subcutaneous injection from 10 hours to 24 hours before surgery and once a day for 7 consecutive days starting at 12 hours after surgery as a perioperative anticoagulation strategy. The control group only received the same prophylactic dose of LMWH (2500 IU of bemethoate sodium) once a day for 7 consecutive days starting at 12 hours post-surgery. The patients in both groups were treated with interstitial pneumatic compression of both lower limbs twice a day.

On the first postoperative day, patients were allowed to get out of bed without any special conditions. Preoperative (before administration of LMWH) and postoperative ultrasonography of the veins of both lower extremities was conducted 7 days and 1 month postoperatively; if symptoms of DVT formation manifested after the operation, ultrasonography of the veins of both lower extremities was performed immediately. If VTE was detected in patients using color doppler ultrasonography, they were administered oral anticoagulants such as warfarin or rivaroxaban for 3 months.

Observational indicators

The primary outcomes were the incidence of VTE and coagulation function. Data pertaining to the occurrence of intraoperative hemorrhage, operative time, drainage volume, drainage time, and postoperative bleeding were collected. Blood samples were collected to measure hemoglobin levels and red blood cell, white blood cell, and platelet counts, as well as indicators of coagulation function, including the prothrombin time, fibrinogen and D-dimer (DDi) levels, activated partial thromboplastin time, International Normalized Ratio of the prothrombin time, and thrombin time preoperatively (before the administration of LMWH) and on postoperative days 3 and 7.

Statistical analysis

All statistical analyses were conducted using SPSS 27.0 statistical software. For normally distributed variables, values were expressed as the mean ± SD, and two-tailed Student’s t-tests were used for intergroup comparisons. For non-normally distributed variables, values were expressed as the median with 25^th and 75^th percentiles [M (P25, P75)], and rank-sum tests were used for intergroup comparisons. Count data were expressed as frequencies (%), and χ² tests were used for group comparisons. Differences were considered statistically significant at P < 0.05.

RESULTS

Demographic and clinical information

The baseline characteristics of the patients in the observation and control groups were similar (Table 1), and no significant differences were observed with respect to sex, age, body mass index (BMI), smoking history, drinking history, hypertension, diabetes, and heart disease (all P > 0.05).

Table 1 Demographic and clinical characteristics of the patients.

Variables	Observation group (n = 101)	Control group (n = 104)	t or χ2	P value
Sex	-	-	2.537	0.111
Female	49	39	-	-
Male	52	65	-	-
Age (years), M (Q1, Q3)	66 (56.5, 76)	60.5 (52, 69.25)	4.452	0.065
BMI (kg/m2), mean ± SD	23.14 ± 3.03	22.79 ± 3.16	0.800	0.425
Smoking history	-	-	0.180	0.671
Yes	35	39	-	-
No	66	65	-	-
Drinking history	-	-	0.547	0.460
Yes	41	37	-	-
No	60	67	-	-
Hypertension	19	20	0.058	0.939
Diabetes	11	13	0.128	0.720
Heart disease	0	2	0.505	0.477

M: Median; Q1: 25^th percentile; Q3: 75^th percentile; BMI: Body mass index.

Intergroup comparison of surgical conditions

Both groups successfully completed the surgical intervention, and there were no statistically significant difference between the surgical conditions of the two groups (all P > 0.05; Table 2).

Table 2 Comparison of surgical conditions between the two groups.

Variables	Observation group (n = 101)	Control group (n = 104)	t or χ2	P value
Intraoperative hemorrhage volume (mL)	30.0 (20.0-50.0)	30.0 (20.0-50.0)	0.125	0.945
Operative time (minute)	140.0 (120.0-174.0)	135.0 (105.0-175.0)	0.667	0.505
Drainage volume (mL)	710.0 (435.0-1140.0)	720.0 (480.0-1205.0)	0.092	0.824
Drainage time (day)	4.0 (3.0-5.8)	4.0 (3.0-6.0)	0.852	0.463
Postoperative bleeding	2	1	0.846	0.378
Pathological findings	-	-	1.856	0.366
Gastric cancer	12	8	-	-
Intestinal cancer	42	32	-	-
Others	44	62	-	-

Intergroup comparison of the incidence of postoperative VTE

Among the 101 patients in the observation group, 86 underwent doppler ultrasonography of both lower limbs on postoperative day 7, while 86 out of 104 patients in the control group completed the same assessment. The incidence of VTE on day 7 was significantly lower in the observation group than in the control group (P < 0.05). At 1 month postoperatively, 96 patients in the observation group and 95 patients in the control group underwent repeated Doppler ultrasonography (including most of the patients assessed on day 7), and the difference in VTE incidence between the groups remained statistically significant (P < 0.05; Table 3). Patients who missed their scheduled ultrasonography were excluded from the imaging-based outcome analysis for that time point. Their absence was primarily due to early discharge, transfer to other care facilities, or failure to return for follow-up imaging.

Table 3 Comparison of venous thromboembolism incidence between the two groups.

Variables	7 days postoperatively			1 month postoperatively
	Observation group (n = 86)	Control group (n = 86)	χ2/P value	Observation group (n = 96)	Control group (n = 95)	χ2/P value
VTE occurrence	-	-	3.956/0.028	-	-	4.026/0.038
Yes	11	24	-	15	28	-
No	75	62	-	81	67	-
SVT	1	5	-	3	8	-
DVT	10	19	-	12	20	-
PE	0	0	-	0	0	-

VTE: Venous thromboembolism; SVT: Superficial vein thrombosis; DVT: Deep venous thrombosis; PE: Pulmonary embolism.

Intergroup comparison of indicators of coagulation function

Indicators of coagulation function were compared between the two groups. The DDi level was significantly lower in the observation group than in the control group on postoperative day 3 (P < 0.05). No statistically significant intergroup differences were observed for any of the other coagulation indices either preoperatively or on postoperative days 3 and 7 (Table 4).

Table 4 Comparison of coagulation function indicators between the two groups, mean ± SD.

Variables	Observation group			Control group			t or χ2/P value
	0 day	3 day	7 day	0 day	3 days	7 days	0 day	3 days	7 days
PT (seconds)	11.20 (10.90-11.70)	11.60 (11.20-12.00)	11.80 (11.30-12.43)	11.20 (10.90-11.80)	12.03 (11.85-12.20)	11.90 (11.35-12.45)	0.169/0.865	1.443/0.152	0.415/0.678
Fib (g/L)	2.64 (2.44-3.15)	6.50 (6.30-7.10)	5.84 (5.26-6.44)	2.97 (2.71-3.35)	6.67 (6.35-7.13)	6.39 (5.81-6.73)	2.091/0.077	0.693/0.488	0.447/0.655
DDi (mg/L)	0.19 ± 0.11	0.80 ± 0.25	2.97 ± 0.45	0.28 ± 0.09	0.98 ± 0.32	2.37 ± 0.55	1.380/0.168	2.374/0.018	0.698/0.485
APTT (seconds)	25.50 (24.0-27.1)	30.16 (28.14-32.46)	26.96 (25.68-28.04)	25.00 (24.0-26.20)	30.28 (28.36-32.08)	27.86 (25.54-29.65)	0.369/0.712	0.124/0.901	0.762/0.496
INR (%)	0.89 ± 0.07	0.94 ± 0.06	0.94 ± 0.09	0.89 ± 0.07	0.95 ± 0.07	0.94 ± 0.09	0.077/0.939	0.722/0.472	0.652/0.647
TT (seconds)	16.30 ± 2.45	14.10 ± 1.96	14.65 ± 1.88	16.20 ± 2.11	13.90 ± 1.75	14.50 ± 2.23	1.149/0.251	0.931/0.352	0.669/0.474

PT: Prothrombin time; Fib: Fibrinogen; DDi: D-dimer; APTT: Activated partial thromboplastin time; INR: International Normalized Ratio; TT: Thrombin time.

Clinical characteristics of VTE in patients 1 month after gastrointestinal surgery

Data were collected from 191 patients who underwent Doppler ultrasonography of both lower limbs at 1 month postoperatively. VTE was observed in 43 cases (incidence rate of 22.51). In these patients, asymptomatic intermuscular VTE was the predominant type. DVT occurred in 32 cases, with the most common site of occurrence being the left lower limb (16 cases), although there were also seven cases involving the right lower limb and nine cases involving both lower limbs (Table 5).

Table 5 Clinical characteristics of venous thromboembolisms experienced by patients 1 month after gastrointestinal surgery.

Variables	n = 43	Proportion (%)
Type of VTE
Asymptomatic intermuscular VTE	41	95.35
Peroneal VTE	2	4.65
Body part with DVT
Left lower extremity	16	50.00
Right lower extremity	7	21.88
Both lower extremities	9	28.13

VTE: Venous thromboembolism; DVT: Deep venous thrombosis.

Comparison of general information between the VTE and non-VTE groups

The 191 patients who underwent Doppler ultrasonography were divided into a VTE group (n = 43) and a non-VTE group (n = 148) for intergroup comparisons. Statistically significant differences were observed between the groups in terms of age (P = 0.030), BMI (P = 0.005), the nature of the disease (benign or metastatic) (P = 0.036), the surgical methods employed (P = 0.026), and long-term postoperative bedrest (P = 0.024) (Table 6).

Table 6 Comparison of general information between the venous thromboembolism and non-venous thromboembolism groups, n (%).

Variables	VTE group (n = 43)	Non-VTE group (n = 148)	χ2	P value
Age (years)			4.706	0.030
< 65	20 (46.51)	96 (64.86)
≥ 65	23 (53.49)	52 (35.14)
Sex			0.133	0.716
Male	26 (60.47)	94 (63.51)
Female	17 (39.53)	54 (36.49)
BMI (kg/m2)			7.971	0.005
< 24	16 (37.21)	91 (61.49)
≥ 24	27 (62.79)	57 (38.51)
Nature of disease			4.387	0.036
Benign diseases of the digestive system	5 (11.63)	40 (27.03)
Malignant diseases of the digestive system	38 (88.37)	108 (72.97)
Surgical methods			4.978	0.026
Open surgery	26 (60.47)	61 (41.22)
Laparoscopic surgery	17 (39.53)	87 (58.78)
Operative time (minute)			0.105	0.745
< 120	9 (20.93)	31 (20.95)
≥ 120	34 (79.07)	117 (79.05)
Long-term postoperative bedrest			5.113	0.024
Yes	31 (72.09)	78 (52.70)
No	12 (27.91)	70 (47.30)

VTE: Venous thromboembolism; BMI: Body mass index.

Risk factors for postoperative VTE in patients undergoing gastrointestinal surgery

A multifactorial logistic regression equation was generated that incorporated age, BMI, the nature of the disease (benign or metastatic), the surgical methods employed, and long-term postoperative bedrest to explore the risk factors of VET. Age, BMI, and the nature of the disease had a statistically significant effect (P < 0.05) on VTE occurrence among patients who underwent gastrointestinal surgery; more specifically, an age ≥ 65 years, a BMI ≥ 24 kg/m², and malignant diseases of the digestive system were identified as risk factors for the occurrence of postoperative VTE (Table 7).

Table 7 Multivariate logistic regression analysis.

Variables	OR	95%CI	P value
Age	6.406	4.004-15.425	< 0.001
BMI	2.694	1.336-5.433	0.006
Nature of disease	1.762	2.785-5.028	0.021
Surgical methods	1.867	0.539-6.460	0.324
Long-term postoperative bedrest	0.737	0.162-3.348	0.693

OR: Odds ratio; CI: Confidence interval; BMI: Body mass index.

DISCUSSION

VTE remains a major complication of gastrointestinal surgery[9]. Surgery itself activates stress responses in the body, and prolonged operative times increase the duration of continuous anesthesia, causing prolonged flaccidity of the lower limb muscles in patients during the operation[10-12]. This state of muscle pump inactivity can lead to blood stagnation in the veins of the lower limbs, which induces venous dilatation, thereby decreasing blood flow velocity and increasing the concentrations of local procoagulant substances; these changes make it more likely for platelets to adhere to and aggregate with the blood vessel wall, accelerating thrombi formation[13,14]. In DVT, subsequent dislodgement of thrombi formed in the lower extremities can lead to occlusion of the pulmonary arteries, which is the main cause of fatal PE[15]. Currently, there is little effective evidence-based research on the prevention of DVT formation in the lower extremities following gastrointestinal surgery. Therefore, this study investigated the impact of perioperative anticoagulation strategies on thromboprophylaxis in patients undergoing gastrointestinal surgery. The results confirmed that the incidence of postoperative VTE was significantly lower in the observation group than in the control group at 7 days and 1 month after surgery.

In a randomized controlled study conducted by Christensen et al[16] on the prevention of postoperative VTE in lung cancer using LMWH, no VTE was observed in the test and control groups; however, they did not perform routine angiographic ultrasonography in the preoperative and postoperative periods, and the main observation group comprised symptomatic patients, which might have led to the omission of some asymptomatic patients who remained undiagnosed. Most of the VTEs in the present study involved clinically asymptomatic thromboses of the interosseous veins of the calf or the great/small saphenous vein. Furthermore, both groups of patients underwent preoperative and postoperative venous ultrasonography of the lower extremities, which allowed for the exclusion of cases involving preoperative VTE and the advanced detection of postoperative asymptomatic VTE, which may explain the higher incidence of VTE observed in this study compared to that in previous studies.

Coagulation function tests have been shown to be effective in assessing the hypercoagulable state of patients with tumors[17]. In the present study, there were no significant differences in the prothrombin time, activated partial thromboplastin time, International Normalized Ratio, and thrombin time indices between the two groups on postoperative days 3 and 7, and there was no indication of a postoperative hypercoagulable state, possibly owing to the smaller proportion of patients with tumors among the enrolled cases, the lower blood viscosity of non-tumor patients, and the absence of hypercoagulability in patients with early-stage tumors.

DDi is a biomarker of coagulation and fibrinolysis and is the end product of fibrin cross-linking in plasma-induced fibrinolytic activity[18,19]. Thus, DDi has an important role in VTE monitoring and therapeutic efficacy evaluations[20]. Christensen et al[16] demonstrated that DDi levels were lower in the prophylactic anticoagulation group than in the control group on days 1 and 2 postoperatively, which is consistent with the present results. In this study, the operative time and intraoperative bleeding volume of the two groups were comparable, and two patients in the observation group experienced postoperative bleeding from drainage sites, although this improved after the discontinuation of LMWH, and they were successfully discharged from the hospital. The probability of postoperative bleeding was low when LMWH was administered for perioperative prophylactic anticoagulation, and the drainage volume and duration of retention of the drainage tube were comparable between the two groups; furthermore, no reoperations needed to be performed, and no deaths occurred due to postoperative bleeding. Thus, the anticoagulation strategy was considered to be safe overall.

At present, the risk factors, clinical characteristics, and specialized strategies to prevent and treat lower extremity DVT following gastrointestinal surgery remain controversial. In this study, the multifactorial logistic regression analysis revealed that an age ≥ 65 years was a high-risk factor for postoperative VTE in patients who underwent gastrointestinal surgery. This may be attributed to the fact that the production of procoagulant substances in blood components increases with age, including an upregulation in the levels of Fib and coagulation factors as well as enhanced platelet activity, resulting in increased blood viscosity, hypercoagulability, and a slower blood flow velocity[21]. Furthermore, elderly patients often have a high prevalence of comorbidities, which can further increase these degenerative changes in blood vessels and affect blood viscosity, leading to a higher incidence of VTE[22].

Numerous studies have confirmed that the risk of VTE is elevated as the BMI increases[23], especially in people with visceral obesity[24]. In this study, patients who underwent gastrointestinal surgery and had a BMI ≥ 24 kg/m² exhibited a 2.694-fold increased risk of developing postoperative lower extremity DVT compared with that in the non-overweight population, which was consistent with the findings of a previous study[25]. Moreover, the present study found that malignant diseases of the digestive system were independent risk factors for the development of postoperative VTE in patients undergoing gastrointestinal surgery. Patients with malignant diseases of the digestive system generally exhibit fibrinolytic system dysfunction and are in a prethrombotic state, and tumor tissues can affect the coagulation mechanism of the body through various pathways[26]. Moreover, patients with colorectal malignant tumors often receive radiotherapy in combination with other modalities in the comprehensive treatment of the disease, and the ionizing radiation produced by radiotherapy may damage the endothelium of the blood vessels, thereby promoting the release of procoagulant factors from these endothelial cells, leading to the formation of VTE[27].

This study has several limitations. First, the data were retrospectively extracted from electronic medical records, which may have introduced information bias. Additionally, unmeasured factors - such as surgeon preference, patient adherence, and baseline functional status - may have influenced both the choice of anticoagulation strategy and the risk of VTE. Moreover, not all patients underwent Doppler ultrasonography at the scheduled postoperative time points. As a result, VTE incidence was analyzed only among those with available imaging data, which may have introduced bias and reduced the statistical power of the findings. Future research should employ a prospective, randomized controlled design and include a broader range of clinically relevant variables to enhance internal validity and improve causal inference. Second, this was a single-center study conducted at the Affiliated Hangzhou First People’s Hospital, School of Medicine, Westlake University. The patient population at this center may possess specific demographic or institutional characteristics that limit the generalizability of the findings to broader surgical populations. Therefore, larger multicenter studies involving more diverse regional and demographic groups are warranted to further validate the efficacy and applicability of perioperative anticoagulation strategies for VTE prevention in gastrointestinal surgical patients. Third, although the present study focused primarily on clinical efficacy and safety outcomes, future prospective investigations should incorporate cost-benefit analyses to better assess the economic feasibility and support broader clinical implementation of perioperative LMWH use.

CONCLUSION

Ultimately, this study confirmed that the incidence of VTE in patients undergoing gastrointestinal surgery peaked within 1 week postoperatively, and prophylactic anticoagulation therapy with LMWH was safe and efficacious in reducing the incidence of postoperative VTE. An age ≥ 65 years, a BMI ≥ 24 kg/m², and malignant diseases of the digestive system were identified as risk factors for the occurrence of postoperative VTE in patients undergoing gastrointestinal surgery, which is helpful for clinicians to take corresponding measures to prevent and treat VET at an early stage.