Early mobilization combined with intermittent pneumatic compression for deep vein thrombosis prevention after hepatocellular carcinoma surgery

Abstract

BACKGROUND

Hepatocellular carcinoma (HCC) remains a common malignancy, with surgical intervention being the main curative treatment. Postoperative deep vein thrombosis (DVT) incidence after HCC surgery is significantly high due to major surgical trauma, prolonged bed rest, and patient-specific risk factors such as cirrhosis and coagulation dysfunction. Current DVT prevention strategies, including pharmacological and physical prophylaxis, have reduced effectiveness when used separately. Early mobilization and intermittent pneumatic compression (IPC) have shown potential benefits, but evidence on their combinations remains unclear.

AIM

To investigate the efficacy and safety of early mobilization combined with IPC for lower extremity DVT prevention after HCC surgery.

METHODS

A retrospective analysis was conducted on 100 patients who underwent HCC surgery at our hospital from January 2020 to June 2025. Forty-eight patients who received standard care from January 2020 to June 2022 were assigned to the control group, and 52 patients who received early mobilization combined with IPC from July 2022 to June 2025 were assigned to the observation group. The observation group initiated a progressive early mobilization protocol 6-8 hours postoperatively, simultaneously applying IPC (pressure 40-60 mmHg, 30-45 minutes per session, twice daily, continued until postoperative day 7). The primary outcome was the incidence of lower extremity DVT. Secondary outcomes included pulmonary embolism (PE) incidence, coagulation parameters (D-dimer, fibrinogen, prothrombin time, activated partial thromboplastin time), lower limb circumference changes, and functional recovery indicators [Barthel Index (BI), Karnofsky Performance Status (KPS) score, independent walking distance].

RESULTS

The total incidence of lower extremity DVT was 5.8% in the observation group, lower than 18.8% in the control group (P = 0.045). D-dimer levels at postoperative days 7 and 14 were lower in the observation group compared to the control group (P = 0.002, P = 0.001). Calf circumference at postoperative day 7 was smaller in the observation group than the control group (P = 0.006). The observation group had earlier time to first ambulation than the control group (P < 0.001); BI scores, KPS scores, and independent walking distance at postoperative days 7 and 14 were all superior in the observation group compared to the control group (P < 0.001). There were no statistically significant differences in PE incidence or pain scores during activity between the two groups (P > 0.05).

CONCLUSION

This study demonstrated the safety and feasibility of implementing a combined early mobilization and IPC strategy to improve recovery for HCC surgery patients. The combined approach indicated reduced lower extremity DVT incidence, improved functional recovery, and good safety profile. Further prospective randomized controlled trials are needed to establish definitive efficacy and optimize protocol parameters.

Key Words: Hepatocellular carcinoma; Postoperative complications; Venous thrombosis; Early mobilization; Intermittent pneumatic compression; Prevention

Core Tip: Early mobilization and intermittent pneumatic compression (IPC) are two effective physical strategies for preventing postoperative deep vein thrombosis (DVT). However, their combined application in hepatocellular carcinoma (HCC) surgery has rarely been investigated. This retrospective study demonstrated that early mobilization combined with IPC significantly reduced postoperative DVT incidence, decreased D-dimer levels, improved limb function, and accelerated recovery without increasing adverse events. The findings suggest that this combined protocol is a safe, feasible, and enhanced recovery after surgery-based strategy for DVT prevention after HCC surgery.

INTRODUCTION

Primary hepatocellular carcinoma (HCC) is the sixth most common malignant tumor globally, and surgical resection remains the primary curative treatment[1]. However, HCC surgery is associated with major trauma, prolonged operative time, and extended postoperative bed rest. Combined with high-risk factors such as cirrhosis and coagulation dysfunction commonly present in patients, the incidence of postoperative lower extremity deep vein thrombosis (DVT) is significantly higher than other abdominal surgeries, with reported rates ranging from 15% to 25%[2]. DVT increases the risk of postoperative complications and potentially leads to fatal pulmonary embolism (PE) in severe cases, significantly affecting patient prognosis and quality of life. It has been raised a significant concern in postoperative management of HCC patients.

Pharmacological and physical prophylaxis have been the two main clinical methods for preventing postoperative DVT. Although anticoagulants such as low molecular weight heparin (LMWH) have some preventive effect, their application in HCC patients requires balancing bleeding risk, and pharmacological prophylaxis alone has limited effectiveness[3]. Among physical prophylaxis measures, early mobilization is considered an effective means to promote lower extremity venous return and reduce DVT occurrence. However, in traditional nursing models, patients generally mobilize too late postoperatively with insufficient activity levels[4]. Intermittent pneumatic compression (IPC) promotes venous blood return through cyclical inflation and deflation, and has been proven to effectively reduce DVT incidence after various surgeries[5]. However, there are currently few studies on the application of early mobilization combined with IPC in DVT prevention after HCC surgery, and whether the combined application of these two methods can produce synergistic effects and their safety remain insufficiently supported by clinical evidence[6].

Based on this, this study retrospectively compared the efficacy and safety of early mobilization combined with IPC vs standard care in preventing postoperative DVT after HCC surgery, aiming to provide an optimized clinical protocol for DVT prevention after HCC surgery, with the goal of reducing DVT incidence, promoting postoperative recovery, and improving clinical outcomes[7].

MATERIALS AND METHODS

Study subjects

A retrospective analysis was conducted on 100 patients who underwent HCC surgery in the Department of Hepatobiliary Surgery at our hospital from January 2020 to June 2025. According to chronological order, 48 patients who received standard care from January 2020 to June 2022 were enrolled in the control group, and 52 patients who received early mobilization combined with IPC from July 2022 to June 2025 were enrolled in the observation group. This study was approved by the hospital ethics committee, complied with relevant requirements of the Declaration of Helsinki, and was exempted from informed consent as a retrospective study. Although the two groups had similar baseline characteristics, the 5.5-year retrospective design still has limitations. These include minor changes in surgical techniques, anesthetic protocols, perioperative fluid management strategies, nursing team education, and institutional focus on enhanced recovery after surgery (ERAS) principles. Such changes may explain the observed differences between groups.

Inclusion criteria: (1) Age 18-75 years; (2) Pathologically confirmed primary HCC; (3) First-time radical resection or partial hepatectomy for HCC; (4) Basically normal preoperative coagulation function; (5) No thrombosis found on preoperative lower extremity vascular ultrasound examination; (6) Complete clinical data; and (7) Expected survival > 3 months.

Exclusion criteria: (1) Pre-existing lower extremity DVT or history of PE before surgery; (2) Severe cardiopulmonary insufficiency unable to tolerate early mobilization; (3) Postoperative severe complications (such as major bleeding, liver failure) requiring immobilization; (4) Hematologic disorders or long-term anticoagulant use; (5) Open wounds, skin infections, or phlebitis in lower extremities; (6) Pregnant or lactating women; (7) Mental disorders unable to cooperate with treatment; and (8) Transfer to another hospital or lost to follow-up.

Intervention methods

The control group received standard care and prophylactic measures, including bed rest for 24-48 hours postoperatively, during which patients were instructed to perform ankle pump exercises for 10-15 minutes each time, 3-4 times daily, elevate the affected limb 15°-30°, encouraged to drink plenty of water to maintain daily urine output > 1500 mL, coagulation function monitoring according to Caprini thrombosis risk score, and when the score was ≥ 5 points, LMWH calcium 4100 IU (0.4 mL) was administered subcutaneously once daily, continued until postoperative day 7-10 or until adequate patient mobilization, whichever came first. Ambulation was initiated gradually with nursing assistance 48-72 hours postoperatively.

The observation group received early mobilization and IPC in addition to control group measures, with the same anticoagulation treatment standards as the control group. The early mobilization protocol consisted of: Starting active limb exercises in bed 6-8 hours postoperatively (after vital signs stabilized), including ankle dorsiflexion and plantarflexion, knee flexion and extension, quadriceps isometric contractions, etc., 10-15 repetitions of each movement, performed once every 2 hours; sitting at bedside for 15-30 minutes with nursing assistance 2-3 times daily at 24 hours postoperatively; standing at bedside and short-distance walking (5-10 m) with nursing accompaniment 3-4 times daily at 48 hours postoperatively; gradually increasing activity level from postoperative day 3 onwards with free ambulation in the ward for cumulative daily activity time ≥ 2 hours. During activity, vital signs and drainage conditions were closely monitored, and if dizziness, palpitations, blood pressure fluctuations, or significantly increased drainage (> 50 mL increase compared to previous hour) occurred, activity was immediately stopped and the physician notified.

IPC used an air wave pressure therapy device starting 6-8 hours postoperatively (after vital signs stabilized), with pressure cuffs wrapped around both lower extremities (from feet to thighs). Treatment parameters were set at pressure 40-60 mmHg, inflation time 12 seconds, deflation time 38 seconds, interval time 10 seconds, cycle period 60 seconds, 30-45 minutes per treatment session, twice daily (once in morning and afternoon), continued until postoperative day 7 and when patient’s daily autonomous activity time exceeded 4 hours, with both conditions met before discontinuation. During use, lower extremity skin conditions were observed, and if skin breakdown, allergies, or other adverse reactions occurred, use was immediately discontinued. Both measures could be performed simultaneously or alternately to avoid prolonged immobilization.

Baseline data

General and preoperative data were collected for both groups, including: (1) Demographic data: Age, sex, body mass index (BMI, kg/m²), smoking history, alcohol consumption history; (2) Disease-related data: HCC TNM stage, maximum tumor diameter, tumor number, Child-Pugh classification of liver function, serum alpha-fetoprotein (AFP, ng/mL) level, underlying diseases [hypertension, diabetes, chronic obstructive pulmonary disease (COPD), etc.]; and (3) Thrombosis risk assessment: Preoperative Caprini thrombosis risk score.

Primary outcome

Lower extremity DVT incidence: Two ultrasound physicians with more than 5 years of experience used color Doppler ultrasound (Philips EPIQ 7 color Doppler ultrasound diagnostic instrument, probe frequency 5-12 MHz) to examine the bilateral lower extremity deep venous system. The examination range included common femoral vein, superficial femoral vein, deep femoral vein, popliteal vein, anterior tibial vein, posterior tibial vein, and peroneal vein. Examination times were 1 day preoperatively, and postoperative days 1, 3, 7, and 14. DVT diagnostic criteria referred to the “Guidelines for Diagnosis and Treatment of DVT (Third Edition)”, with diagnostic basis including: (1) Visible substantive hypoechoic or isoechoic filling defect in venous lumen; (2) Vein cannot be compressed with probe pressure; (3) Color Doppler flow imaging showing weakened or absent blood flow signal in lumen; and (4) No blood flow enhancement after Valsalva maneuver. According to thrombus location, DVT was classified as proximal DVT (popliteal vein and above) and distal DVT (deep veins of calf below popliteal vein). For quality control, when the two ultrasound physicians’ diagnostic opinions were inconsistent, a third senior ultrasound expert made the final determination.

Secondary outcomes

Secondary outcomes included five aspects: (1) PE incidence: For patients with clinical manifestations such as chest pain, dyspnea, hemoptysis, syncope, or significantly elevated D-dimer (> 2.0 mg/L FEU), computed tomography pulmonary angiography examination was performed for definitive diagnosis; (2) Coagulation parameters: Venous blood was collected on an empty stomach in the early morning 1 day preoperatively and on postoperative days 1, 3, 7, and 14. An automated coagulation analyzer (Sysmex CS-5100) was used to detect D-dimer (normal reference value < 0.5 mg/L FEU), fibrinogen (Fib, normal reference value 2.0-4.0 g/L), prothrombin time (PT, normal reference value 11-13 seconds), and activated partial thromboplastin time (APTT, normal reference value 25-35 seconds); (3) Lower limb circumference changes: Preoperatively and on postoperative days 3, 7, and 14, the same trained nursing staff used a standard soft ruler to measure bilateral lower limb circumference. Measurement sites were 10 cm above the superior border of patella (thigh circumference) and 10 cm below the inferior border of patella (calf circumference), with each site measured 3 times and averaged. Unilateral lower limb circumference increase > 2 cm compared to contralateral side suggested possible DVT requiring immediate ultrasound examination for confirmation; (4) Early mobilization compliance and functional recovery indicators: Time to first ambulation, daily activity time on postoperative days 3 and 7, and activity tolerance were recorded. Visual Analog Scale (VAS) was used to assess pain levels during activity on postoperative days 3 and 7 (0-10 points, 0 = no pain, 10 = excruciating pain). Barthel Index (BI) was used to assess patients’ activities of daily living including feeding, bathing, grooming, dressing, bowel and bladder control, toileting, bed-to-chair transfer, ambulation, and stair climbing, with 10 items totaling 0-100 points (higher scores indicate stronger daily living ability). Karnofsky Performance Status (KPS) was used to assess patients’ overall functional status with scoring range 0-100 points in 10-point increments (scores ≥ 80 indicate good functional status with ability for normal activities, 60-70 indicate basic self-care but limited activities, < 60 indicate need for assistance or inability for self-care). The above functional assessments were performed 1 day preoperatively and on postoperative days 7 and 14. Independent walking distance on postoperative days 7 and 14 was also recorded; and (5) Safety events were recorded.

Statistical analysis

SPSS 26.0 statistical software (IBM Corporation, United States) was used for data analysis. Quantitative data were first tested for normality (Shapiro-Wilk test) and homogeneity of variance (Levene’s test). Data with normal distribution and homogeneous variance were expressed as mean ± SD, and independent samples t-test was used for between-group comparisons. Data not conforming to normal distribution were expressed as median (interquartile range) [M (P25, P75)], and Mann-Whitney U test was used for between-group comparisons. Categorical data were expressed as n (%), and χ² test or Fisher’s exact test (when theoretical frequency < 5) was used for between-group comparisons. Ordinal data were compared using Mann-Whitney U test. Multiple time point comparisons used Bonferroni correction for multiple comparisons. P < 0.05 was considered statistically significant.

RESULTS

Baseline data comparison

The two groups showed no statistically significant differences in age, sex, BMI, smoking history, alcohol consumption history, HCC TNM stage, maximum tumor diameter, tumor number, Child-Pugh classification, AFP level, underlying diseases (hypertension, diabetes, COPD), or preoperative Caprini thrombosis risk score (P > 0.05), demonstrating comparability (Table 1).

Table 1 Comparison of baseline data between two groups, n (%).

Indicator	Control group (n = 48)	Observation group (n = 52)	Statistics	P value
Age (years, mean ± SD)	59.8 ± 10.2	60.5 ± 9.7	t = -0.374	0.709
Sex			χ2 = 0.087	0.768
Male	37 (77.1)	41 (78.8)
Female	11 (22.9)	11 (21.2)
BMI (kg/m2, mean ± SD)	23.6 ± 2.8	23.9 ± 2.6	t = -0.572	0.568
Smoking history	22 (45.8)	25 (48.1)	χ2 = 0.052	0.82
Alcohol consumption history	18 (37.5)	19 (36.5)	χ2 = 0.010	0.92
TNM stage			χ2 = 0.428	0.807
Stage I	16 (33.3)	19 (36.5)
Stage II	24 (50.0)	25 (48.1)
Stage III	8 (16.7)	8 (15.4)
Maximum tumor diameter (cm, mean ± SD)	5.4 ± 2.1	5.6 ± 2.3	t = -0.462	0.645
Tumor number			χ2 = 0.196	0.658
Solitary	35 (72.9)	40 (76.9)
Multiple	13 (27.1)	12 (23.1)
Child-Pugh classification			χ2 = 0.182	0.67
Grade A	40 (83.3)	45 (86.5)
Grade B	8 (16.7)	7 (13.5)
AFP [ng/mL, M (P25, P75)]	286.5 (45.8, 1024.3)	312.4 (52.6, 1158.7)	Z = -0.513	0.608
Hypertension	13 (27.1)	12 (23.1)	χ2 = 0.210	0.647
Diabetes	6 (12.5)	8 (15.4)	χ2 = 0.173	0.677
COPD	4 (8.3)	3 (5.8)	1	0.715
Caprini score (points, mean ± SD)	5.2 ± 1.4	5.4 ± 1.3	t = -0.763	0.447

¹Fisher’s exact test.

BMI: Body mass index; COPD: Chronic obstructive pulmonary disease; AFP: Alpha-fetoprotein.

Primary outcome

The total incidence of DVT was 5.8% (3/52) in the observation group, lower than 18.8% (9/48) in the control group (χ² = 4.024, P = 0.045). Exploratory analysis showed that the incidence of proximal DVT was 1.9% (1/52) in the observation group, lower than 8.3% (4/48) in the control group (P = 0.182); the incidence of distal DVT was 3.8% (2/52) in the observation group, lower than 10.4% (5/48) in the control group (P = 0.241), but neither difference reached statistical significance (Table 2).

Table 2 Comparison of deep vein thrombosis incidence between two groups, n (%).

Indicator	Control group (n = 48)	Observation group (n = 52)	Statistics	P value
Total DVT incidence	9 (18.8)	3 (5.8)	χ2 = 4.024	0.045
Proximal DVT	4 (8.3)	1 (1.9)	1	0.182
Distal DVT	5 (10.4)	2 (3.8)	1	0.241

¹Fisher’s exact test.

Proximal and distal deep vein thrombosis comparisons are exploratory analyses and were not adjusted for multiple comparisons.DVT: Deep vein thrombosis.

Secondary outcomes

PE occurred in 2 cases (4.2%) in the control group and in 0 cases (0%) in the observation group, with no statistically significant difference between groups (P = 0.228). Due to the small sample size and low event rate, this result should be interpreted with caution.

There were no statistically significant differences in preoperative coagulation parameters between the two groups (P > 0.05). On postoperative days 1, 3, 7, and 14, D-dimer and Fib levels increased compared to preoperative levels, and PT and APTT were prolonged compared to preoperative values in both groups. Using Bonferroni correction for multiple comparisons of 5 time points for each coagulation indicator (corrected α = 0.05/5 = 0.01), D-dimer levels were significantly lower in the observation group than the control group on postoperative day 7 (P = 0.002) and day 14 (P = 0.001). There were no statistically significant differences in Fib, PT, or APTT at any time point between the two groups (P > 0.05) (Table 3).

Table 3 Comparison of coagulation parameters between two groups (mean ± SD).

Indicator	Time	Control group (n = 48)	Observation group (n = 52)	t value	P value
D-dimer (mg/L)	1 day preoperatively	0.42 ± 0.15	0.44 ± 0.16	-0.655	0.514
	Postoperative day 1	2.68 ± 0.82	2.54 ± 0.76	0.901	0.37
	Postoperative day 3	3.24 ± 0.95	2.98 ± 0.88	1.434	0.155
	Postoperative day 7	2.86 ± 0.91	2.35 ± 0.72	3.156	0.0021
	Postoperative day 14	1.95 ± 0.68	1.52 ± 0.54	3.558	0.0011
Fib (g/L)	1 day preoperatively	2.95 ± 0.52	3.02 ± 0.48	-0.716	0.476
	Postoperative day 1	4.26 ± 0.78	4.18 ± 0.72	0.546	0.586
	Postoperative day 3	4.82 ± 0.85	4.65 ± 0.81	1.041	0.3
	Postoperative day 7	4.35 ± 0.76	4.22 ± 0.69	0.914	0.363
	Postoperative day 14	3.68 ± 0.64	3.55 ± 0.58	1.083	0.281
PT (seconds)	1 day preoperatively	12.1 ± 0.8	12.2 ± 0.7	-0.673	0.502
	Postoperative day 1	13.8 ± 1.2	13.6 ± 1.1	0.885	0.378
	Postoperative day 3	14.2 ± 1.3	13.9 ± 1.2	1.212	0.228
	Postoperative day 7	13.5 ± 1.1	13.3 ± 1.0	0.967	0.336
	Postoperative day 14	12.8 ± 0.9	12.6 ± 0.8	1.188	0.238
APTT (seconds)	1 day preoperatively	29.8 ± 3.2	30.1 ± 3.4	-0.461	0.646
	Postoperative day 1	35.6 ± 4.1	35.2 ± 3.8	0.516	0.607
	Postoperative day 3	36.8 ± 4.5	36.3 ± 4.2	0.588	0.558
	Postoperative day 7	34.2 ± 3.9	33.8 ± 3.6	0.545	0.587
	Postoperative day 14	31.5 ± 3.5	31.2 ± 3.3	0.451	0.653

¹Statistically significant difference after Bonferroni correction (each indicator was corrected separately for 5 time points, corrected α = 0.01).

Fib: Fibrinogen; PT: Prothrombin time; APTT: Activated partial thromboplastin time.

There were no statistically significant differences in preoperative thigh or calf circumference between the two groups (P > 0.05). Using Bonferroni correction for multiple comparisons (corrected α = 0.05/4 = 0.0125), calf circumference on postoperative day 7 was significantly smaller in the observation group than the control group (P = 0.006). There were no statistically significant differences in thigh or calf circumference at other time points between the two groups (P > 0.0125) (Table 4 and Figure 1).

Figure 1 Comparison of lower limb circumference changes between two groups. A: Presents thigh circumference 10 cm above the patella; B: Shows calf circumference 10 cm below the patella. Measurements were taken preoperatively and on postoperative days 3, 7, and 14. The purple line represents the control group and the blue line represents the observation group. results show that the control group had significant increases in lower limb circumference postoperatively, while the observation group demonstrated relatively stable changes with significantly smaller increases, suggesting that early mobilization combined with intermittent pneumatic compression may effectively reduce postoperative lower limb swelling and decrease deep vein thrombosis risk. POD: Postoperative day.

Table 4 Comparison of lower limb circumference changes between two groups (cm, mean ± SD).

Indicator	Time	Control group (n = 48)	Observation group (n = 52)	t	P value
Thigh circumference	Preoperatively	48.6 ± 4.2	49.1 ± 4.5	-0.585	0.56
	Postoperative day 3	50.8 ± 4.6	49.5 ± 4.3	1.497	0.137
	Postoperative day 7	51.2 ± 4.8	49.2 ± 4.2	2.257	0.026
	Postoperative day 14	50.1 ± 4.5	48.9 ± 4.1	1.407	0.162
Calf circumference	Preoperatively	35.2 ± 3.1	35.6 ± 3.3	-0.634	0.527
	Postoperative day 3	37.1 ± 3.5	36.0 ± 3.2	1.664	0.099
	Postoperative day 7	37.8 ± 3.7	35.9 ± 3.2	2.785	0.0061
	Postoperative day 14	36.5 ± 3.4	35.7 ± 3.1	1.259	0.211

¹Statistically significant difference after Bonferroni correction (corrected for 4 time points, corrected α = 0.0125).

Measurement sites are 10 cm above the superior border of patella (thigh circumference) and 10 cm below the inferior border of patella (calf circumference).

The observation group had earlier time to first ambulation than the control group (P < 0.001). Using Bonferroni correction for comparison of 2 time points for daily activity time on postoperative days 3 and 7 (corrected α = 0.05/2 = 0.025), daily activity time on postoperative days 3 and 7 was significantly longer in the observation group than the control group (P < 0.001). There were no statistically significant differences in preoperative BI or KPS scores between the two groups (P > 0.05). Using Bonferroni correction for comparison of 3 time points for BI and KPS scores respectively (corrected α = 0.05/3 = 0.0167), BI and KPS scores on postoperative days 7 and 14 were significantly higher in the observation group than the control group (P < 0.001). The approximately 9-point difference in BI at postoperative day 7 (62.5 ± 8.6 vs 71.3 ± 9.2) represents a clinically meaningful improvement, as changes of 5-10 points on this 100-point scale are generally considered indicative of functional gains in activities of daily living. Similarly, the 10-point increments in KPS scores correspond to observable changes in functional status and independence level. Using Bonferroni correction for comparison of 2 time points for independent walking distance on postoperative days 7 and 14 (corrected α = 0.05/2 = 0.025), independent walking distance on postoperative days 7 and 14 was significantly longer in the observation group than the control group (P < 0.001). There were no statistically significant differences in VAS pain scores during activity on postoperative days 3 and 7 between the two groups (postoperative day 3: P = 0.418; postoperative day 7: P = 0.340) (Table 5).

Table 5 Comparison of early mobilization compliance and functional recovery indicators between two groups.

Indicator	Control group (n = 48)	Observation group (n = 52)	Statistics	P value
Time to first ambulation (hour, mean ± SD)	54.6 ± 8.2	26.8 ± 4.5	t = 20.894	< 0.001
Daily activity time on postoperative day 3 (minutes, mean ± SD)	45.3 ± 12.6	128.5 ± 24.3	t = -21.643	< 0.0012
Daily activity time on postoperative day 7 (minutes, mean ± SD)	92.6 ± 18.4	185.7 ± 32.5	t = -17.434	< 0.0012
VAS pain score (points, mean ± SD)
Postoperative day 3	3.9 ± 1.3	3.7 ± 1.2	t = 0.813	0.418
Postoperative day 7	3.6 ± 1.1	3.4 ± 1.0	t = 0.958	0.34
BI score (points, mean ± SD)
1 day preoperatively	95.2 ± 5.8	94.8 ± 6.2	t = 0.341	0.734
Postoperative day 7	62.5 ± 8.6	71.3 ± 9.2	t = -5.017	< 0.0011
Postoperative day 14	78.4 ± 7.9	86.2 ± 8.5	t = -4.802	< 0.0011
KPS score (points, mean ± SD)
1 day preoperatively	88.3 ± 6.5	89.0 ± 6.8	t = -0.532	0.596
Postoperative day 7	64.2 ± 7.8	72.5 ± 8.3	t = -5.210	< 0.0011
Postoperative day 14	75.6 ± 7.2	82.8 ± 7.6	t = -4.889	< 0.0011
Independent walking distance (m, mean ± SD)
Postoperative day 7	28.5 ± 8.6	65.3 ± 12.4	t = -17.262	< 0.0013
Postoperative day 14	58.7 ± 12.3	125.8 ± 18.6	t = -21.229	< 0.0013

¹Statistically significant difference after Bonferroni correction (Barthel Index and Karnofsky Performance Status were each corrected for 3 time points, corrected α = 0.0167).

²Statistically significant difference after Bonferroni correction (corrected for postoperative days 3 and 7, 2 time points, corrected α = 0.025).

³Statistically significant difference after Bonferroni correction (corrected for postoperative days 7 and 14, 2 time points, corrected α = 0.025).

VAS: Visual Analog Scale; BI: Barthel Index; KPS: Karnofsky Performance Status.

DISCUSSION

Venous stasis is one of the core mechanisms of DVT formation. Early mobilization promotes lower extremity venous return through activation of the muscle pump effect and represents the most physiologically appropriate intervention for DVT prevention[8]. In this study, the observation group began in-bed limb exercises 6-8 hours postoperatively, achieved bedside sitting within 24 hours, and completed ambulation within 48 hours. This progressive approach led to much more mobilization time than traditional nursing models. Studies have shown that early postoperative immobilization is an independent risk factor for DVT development, with each 24-hour delay in ambulation increasing DVT risk by approximately 15%-20%[9]. In this study, the time to first ambulation in the observation group was nearly 28 hours earlier than that in the control group, which may contribute to the significant reduction in DVT incidence.

Early mobilization may also have certain impact on the coagulation system. In this study, D-dimer levels on postoperative days 7 and 14 were significantly lower in the observation group than in the control group. This finding suggests that early mobilization may reduce excessive activation of the coagulation system by improving blood rheological status. Relevant studies have revealed that moderate exercise can enhance fibrinolytic system and decrease Fib and platelet aggregation rates, thereby reducing microthrombus formation[10]. Additionally, this study found no significant differences in conventional coagulation indicators such as Fib, PT, and APTT between groups, while D-dimer, as a secondary fibrinolysis marker, more sensitively reflects the dynamic balance of microthrombus formation and dissolution, consistent with previous literature[11].

However, implementing early mobilization in postoperative HCC patients has several challenges. Liver surgery causes major trauma, severe postoperative pain, and the need for multiple drainage tubes. Therefore, patients often have low willingness and tolerance for activity[12]. This study developed individualized, progressive mobilization protocols, including close monitoring and gradual activity increases. This approach achieved both activity safety and high compliance. On postoperative day 3, the observation group reached a daily activity time of 128.5 minutes, and on day 7 it reached 185.7 minutes. These times were significantly longer than those in the control group (45.3 minutes and 92.6 minutes, respectively). Moreover, pain scores during activity did not differ significantly between groups, indicating good tolerability. This finding has promise for clinical use of early mobilization[13].

IPC promotes venous return through mechanical cyclical inflation and deflation, which mimics the muscle pump action. It also generates vascular endothelial shear stress that stimulates the release of endogenous anticoagulant substances[14]. IPC reduces postoperative DVT incidence by 40%-60%, and its preventive effect is also well established[15]. The IPC strategies used in this study (pressure 40-60 mmHg, inflation 12 seconds, deflation 38 seconds) followed international guidelines. These settings ensured effective venous emptying and avoided potential tissue damage from excessive pressure[16].

The combination of early mobilization and IPC is a key feature of this study. Early mobilization promotes blood circulation through active muscle contraction, while IPC provides passive mechanical assistance to maintain venous return during patient rest or sleep[17]. Importantly, this study allowed both measures to be performed simultaneously or alternately. This ensured continuous DVT prevention after surgery and avoided the temporal limitations of single measures. However, the retrospective design prevents a definitive assessment of whether the observed benefits are true synergistic or simply additive. On postoperative day 7, calf circumference was significantly smaller in the observation group than in the control group. This finding indicated that the combined intervention effectively reduced lower extremity edema and venous stasis, which may suggest an important mechanism for its superior DVT prevention effect compared to standard care alone[18].

Notably, although the observation group had lower incidence rates of both proximal and distal DVT compared to the control group, these differences did not reach statistical significance. It possibly related to the relatively small sample size and low event rates. Previous studies have shown that proximal DVT carries higher risk of PE, suggesting the significance of its prevention[19]. In this study, 2 of 4 proximal DVT cases in the control group had concurrent PE, while the observation group had only 1 proximal DVT case without PE occurrence. Although there was no statistical difference in PE incidence between groups (4.2% vs 0%, P = 0.228), this trend suggests that combined intervention may have protective effects against severe thrombotic events. Further studies with a larger sample size should be conducted to verify these findings[20].

Early mobilization combined with IPC also improved postoperative functional recovery. On postoperative days 7 and 14, BI and KPS scores were significantly higher in the observation group than the control group. Independent walking distances reached 65.3 m and 125.8 m respectively, more than double the control group. The results are consistent with ERAS concepts, and suggest that early mobilization may prevent DVT and improve recovery quality[21].

Early mobilization also promotes functional recovery. It reduces postoperative muscle atrophy and joint stiffness, helping maintain muscle strength and joint range of motion[22]. Bed rest can cause a 1%-3% daily lose in muscle strength, and early mobilization can prevent this decline[23]. Mobilization also stimulates gastrointestinal motility recovery, increases appetite, and improves nutritional intake. This provides the material basis for tissue repair[24]. In addition, early activity improves mood and confidence. These psychological benefits can help break the traditional concept of “postoperative need for rest”, and improve patients’ initiative in recovery[25].

IPC also contributes to functional recovery. It can reduce lower extremity swelling and discomfort, making patients more willing and able to participate in activity training[26]. In this study, calf circumference on postoperative day 7 was significantly smaller in the observation group than the control group (35.9 cm vs 37.8 cm). The reduced edema in the observation group may directly improve activity tolerance and comfort. Additionally, some evidence suggested that IPC may improve tissue oxygen supply. It may promote microcirculation, accelerate surgical wound healing, and indirectly support functional recovery[27].

Safety is critical in evaluating clinical interventions. In this study, the observation group reported no serious adverse events related to early mobilization. Pain scores during activity were similar to those in the control group. These results confirmed the safety of the combined protocol. This was achieved through a standardized activity protocol and close monitoring. Activity started only 6-8 hours postoperatively to ensure stable vital signs. Activity levels increased gradually to avoid excessive fatigue. Vital signs and drainage volumes were monitored in real time for timely detection of abnormal situations[28].

The safety of IPC also warrants attention. In this study, the pressure parameters (40-60 mmHg) were within the safe range. This range avoided potential superficial venous valve damage or deep vein thrombus dislodgement risks caused by excessive pressure[29]. Equipment-related skin damage, allergies, or other adverse reactions were not observed in this study. However, the proposed protocol was not applicable to patients with existing DVT, lower extremity open wounds, or severe complications to ensure safety[30].

This protocol requires moderate resources and is clinically feasible in most tertiary hospitals. Early mobilization depends mainly on nursing staff education and supervision and does not need expensive equipment. IPC devices are affordable and easy to operate. After brief training, patients or family members can use them. Both measures require little (IPC takes only 1-1.5 hours daily), and do not significantly increase healthcare worker burden. The protocol can also be adjusted flexibly according to individual patient needs, showing good adaptability.

This study has several limitations. First, the single-center retrospective design with relatively small sample size could potentially subject to selection bias and confounding factor influences. Although baseline data showed good balance between groups, the methodological limitations cannot completely exclude potential biases. Moreover, the 5.5-year study period from 2020 to 2025 introduces unavoidable temporal confounders, including potential changes in surgical techniques, anesthetic protocols, perioperative fluid management, nursing team education, and progressive institutional adoption of ERAS principles, which may have contributed to the observed differences and limit causal inference. Second, DVT diagnosis relied entirely on ultrasound examination without venography verification, potentially carrying missed diagnosis risk, particularly for asymptomatic small thrombi. Third, due to ethical and practical considerations, both groups of patients with Caprini scores ≥ 5 received prophylactic anticoagulation with LMWH, and this common intervention may have partially masked the exact effect of the combined protocol. Therefore, it is difficult to completely distinguish the respective contributions of physical prophylaxis measures and pharmacological prophylaxis. Fourth, the follow-up time was only 14 days postoperatively, lacking long-term DVT occurrence and functional recovery levels. Moreover, some delayed-onset DVT could be potentially missed. Fifth, the cost-effectiveness analysis was not performed, and the health economic value of this protocol was unable to evaluate.

Despite these limitations, this study provides early evidence that early mobilization combined with IPC may be a safe and feasible way to prevent DVT for HCC surgery patients. The reduced DVT incidence and improved functional recovery aligns with modern ERAS principles, but these findings should be interpreted as hypothesis-generating.

Future research should focus on the following directions: (1) Conduct multicenter, large-sample, prospective randomized controlled trials to further verify the efficacy and safety of this combined protocol and explore benefit situations in different patient subgroups (such as different Child-Pugh classifications, different surgical extents), providing evidence-based basis for individualized prevention protocol development in clinical practice; (2) Extend follow-up time to 1-3 months postoperatively to observe long-term DVT incidence, quality of life, and survival status, comprehensively evaluating the long-term impact of interventions; (3) Explore optimal intervention timing, activity intensity, and IPC parameters to optimize protocol details; (4) Include biomarker monitoring (such as tissue factor, thromboelastography, etc.) to deeply elucidate molecular mechanisms of combined intervention; (5) Conduct cost-effectiveness analysis to evaluate the health economic value of this protocol, providing economic support for medical decision-making; and (6) Explore extending this model to other high-risk populations (such as pancreatic cancer, colorectal cancer surgery patients) to verify its universality.

CONCLUSION

In conclusion, this study confirms that early mobilization combined with IPC can significantly reduce DVT incidence after HCC surgery and improve patient functional recovery. The combined approach demonstrates good safety and feasibility. It provides a new strategy for DVT prevention after HCC surgery and has the potential for clinical implementation. Future studies with higher quality are needed to verify its efficacy, optimize protocol parameters, and explore its application value in different populations.