Pulmonary Embolism Following Living Donor Hepatectomy: A Report of 4 Cases and Literature Review

Introduction

Liver transplantation is a well-established treatment for end-stage liver disease. However, the shortage of deceased donor organs has been a major limitation, especially as the number of patients awaiting transplantation continues to rise [1]. Living donor liver transplantation (LDLT) has become a way to expand the source of donors, and an effective method to replace cadaveric liver transplantation in areas with insufficient cadaver liver supply. In Asian countries, LDLT is becoming more widely adopted [2,3]. Given that living donors are typically healthy individuals, ensuring donor safety is crucial to the success of LDLT [4]. Despite thorough preoperative evaluations for such donors, the occurrence of nonsurgical complications like pulmonary embolism (PE) remains unpredictable. Although rare, with an incidence of approximately 0.174%, PE is a significant cause of morbidity and mortality in living donor following liver donor hepatectomy (LDH) [5]. This report presents 4 cases of acute PE in living donors undergoing LDH and discusses their clinical features, diagnosis, and treatment.

Case Reports

ETHICAL APPROVAL:

This study was approved by the Ethics Committee of the Beijing Friendship Hospital, Capital Medical University (No. 2024-P2-362-01).

CASE 1:

A 46-year-old male donated the right half liver for his brother with end-stage liver disease due to hepatitis B. The preoperative evaluation met the criteria for a living liver donation, and the patient underwent a laparotomy right hepatectomy under general anesthesia. The patient had a history of smoking 20 cigarettes per day for 20 years. His preoperative blood test results were as follows: hemoglobin 142 g/L, platelets 375×10⁹/L, prothrombin time (PT) 11.6 s, activated partial thromboplastin time (APTT) 34 s, and D-dimer 0.08 mg/L. His chest computed tomography (CT) scan was normal, and no lower-extremity vascular ultrasound was performed. The patient received standard anesthetic management. Low central venous pressure (LCVP) technique was used to reduce intraoperative bleeding, and Pringle’s maneuver was not used. The intraoperative blood loss was 100 mL, urine output was 500 mL, total fluid intake was 1700 mL, and no blood products were transfused.

On postoperative day (POD) 2, approximately 180ml of bile-like fluid was drained from the abdominal drainage tube, and the abdominal ultrasound results suggested bile leakage. Later in the evening, he experienced chest tightness, discomfort, and a drop in pulse oxygen saturation (SpO2) to 89%. The D-dimer level was elevated at 5.112 mg/L, and arterial blood gas analysis showed hypoxemia (PaO2: 52.4 mmHg). The patient was administered 3 L/min of oxygen via nasal cannula, and SpO2 increased to 95%. To rule out the possibility of PE, an enhanced CT scan was performed immediately, which revealed filling defects in the branches of both pulmonary arteries, indicating pulmonary embolism (Figure 1A). Venous ultrasound revealed deep vein thrombosis (DVT) in both legs (Thrombosis was detected in both posterior tibial and peroneal veins, as well as in the left anterior tibial and intermuscular veins of the calf). It was considered that the acute pulmonary embolism (APE) might have been caused by the dislodgement of a deep vein thrombosis from the lower limbs.

He was treated with warfarin (4.5 mg/day) and nadroparin calcium (0.4 mL/day) while being advised to remain on bed rest and avoid physical activity. By postoperative day 15, the patient’s clinical symptoms had improved, and a follow-up D-dimer test revealed a level of 1.642 mg/L, indicating an improvement in the hypercoagulable state. The patient was discharged in good condition. A follow-up ultrasound of the lower-limb veins 1 month after surgery still showed thrombosis in the left posterior tibial vein, but by 2-month follow-up, lower-limb deep venous blood flow had returned to normal.

CASE 2:

A 42-year-old woman donated the left half liver for her son, who suffered from urea cycle disorder.

She was previously healthy, with no history of blood clots, smoking or alcohol consumption. The preoperative blood test results were as follows: hemoglobin 132 g/L, platelets 259×10⁹/L, PT 11.5 s, APTT 29.1 s, and D-dimer 0.078 mg/L. No lower-extremity vascular ultrasound was performed. Anesthesia management and operative procedures were to be performed according to our center’s specific expertise and clinical routine. The patient underwent a laparotomy left lobectomy with the middle hepatic vein (MHV) under general anesthesia. The intraoperative blood loss was 200 mL, urine output 200 mL, total fluid intake 1300 mL, and no blood products transfused. She was extubated one hour after being transferred to the intensive care unit (ICU).

On POD 6, she reported chest tightness accompanied by fever and was diagnosed with bilateral pleural effusion and partial atelectasis through chest CT. Arterial blood gas analysis showed a PaO₂ of 86.2 mmHg and a PaCO₂ of 25.3 mmHg. The blood test revealed a C-reactive protein level of 17.9 mg/L. Pneumonia was suspected, and the patient was treated with intravenous cefoperazone-sulbactam (1.5 g) for infection, resulting in relief of symptoms.

On POD 8, after activity, she developed dyspnea and was diagnosed with PE through pulmonary vascular enhanced CT which showed multiple filling defects in the pulmonary arteries (Figure 1B). Ultrasound confirmed DVT in the right leg. She was treated with nadroparin calcium (0.4 mL/day) and switched to rivaroxaban (10 mg/day) after 5 days. After anticoagulant treatment, the donor’s symptoms improved and discharged on POD 15. A follow-up chest CT 3 months post-surgery showed no significant embolism.

CASE 3:

A 65-year-old male donated the right half liver for his son with liver failure caused by hepatitis B. The donor had a 2 years history of hypertension (grade 1, moderate risk), which was managed with regular oral nifedipine sustained-release tablets, with blood pressure generally well controlled. He had no history of smoking or alcohol consumption. The patient previously underwent internal fixation surgery for a fracture of the left forearm. The preoperative blood test results were as follows: hemoglobin 123 g/L, platelets 226×10⁹/L, PT 11.1 s, APTT 31.3 s, and D-dimer 0.125 mg/L. CT examination was conducted preoperatively, but the lower limbs were not examined for venous thrombus formation. Under general anesthesia, the patient underwent a laparotomy right hepatectomy. Intraoperatively, central venous pressure (CVP) was lowered with tachycardia (10 mg), nitroglycerine (0.3–0.5 ug/kg/min), and combined with reverse Trendelenburg position. Dopamine and norepinephrine were pumped to maintain blood pressure. The intraoperative blood loss was 800 mL, urine output was 600 mL, total fluid intake was 2200 mL. Postoperatively, the patient was transferred to the ICU and was extubated 5 hours later.

On POD 2, he developed nausea, cyanosis, and severe hypoxemia (SpO₂: 82%). Heart rate was 94 bpm, and blood pressure 111/62 mmHg. Auscultation revealed decreased breath sounds in the left lung. Arterial blood gas analysis showed a PaCO₂ of 34.2 mmHg, PaO₂ of 48.9 mmHg, and the serum D-dimer level was 6.402 mg/L. An urgent CT scan of chest indicated left lower lobe atelectasis, partial right lower lobe atelectasis, and bilateral pleural effusion. The patient was given nasal oxygen at 4 L/min, with SpO₂ fluctuating between 80% and 85%. Due to poor improvement in SpO₂, the oxygen flow rate was adjusted to 5 L/min, resulting in symptom relief and SpO₂ rising to 95–97%. Additionally, nadroparin calcium injection (0.4 mL/day) was used to prevent thrombosis.

The repeated D-dimer was elevated to 8.012 mg/L on POD 3. Enhanced CT scan of pulmonary vasculature revealed a thrombus in the right lower lung lobe (Figure 1C). Concurrently, the lower-extremity venous ultrasound showed thrombosis in the left peroneal vein and partial thrombosis in the intermuscular veins of both calves. Based on these findings, the donor was diagnosed with APE, and continued to receive a subcutaneous injection of nadroparin calcium (0.4 mL/day) for anticoagulant therapy.

After 9 days of nadroparin treatment, his condition improved and a follow-up venous ultrasound showed partial recanalization of the veins. Both the pulmonary atelectasis and pleural effusion showed improvement. Nadroparin calcium was discontinued and he was switched to rivaroxaban 10 mg administered orally once-daily. The donor recovered well and was discharged on POD 19.

CASE 4:

A 57-year-old woman donated the left half liver for her son with liver failure. The patient had a history of splenectomy due to trauma 20 years earlier. She was no history of blood clots, smoking or alcohol consumption. Preoperative blood tests revealed: hemoglobin 142 g/L, platelets 360×10⁹/L, PT 11.2 s, APTT 20 s, and D-dimer 0.175 mg/L. Preoperatively, the patient did not undergo lower-extremity vascular ultrasound. Laparotomy left hepatectomy with middle hepatic vein was performed under general anesthesia with intraoperative application of bilateral lower-limb compression devices for deep vein thrombosis prophylaxis. The intraoperative blood loss was 200 mL, urine output was 700 mL, total fluid intake was 1600 mL.

On POD 3, she suddenly developed dyspnea after ambulation. An emergent arterial blood gas analysis was performed, showing a PaCO2 of 26.9 mmHg, PaO2 of 70.7 mmHg, and a SpO2 of 95.80%. The serum D-dimer level was found to be 2.489 mg/L. At this time, the enhanced CT scan of pulmonary arteries showed extensive PE in both lungs (Figure 1D). Subsequent ultrasonography of the lower-extremity veins further revealed the presence of venous thrombosis.

Due to the extent of the embolism, intravenous heparin therapy was initiated for anticoagulation treatment, with close monitoring of coagulation function. The heparin dose was gradually adjusted according to the coagulation results. On POD 8, the patient developed hematuria and abdominal hematomas. Due to the risk of bleeding, intravenous heparin infusion was discontinued and switched to subcutaneous injection of nadroparin calcium.

On postoperative day 12, a follow-up CT scan showed no significant filling defects in the pulmonary arteries and its branches. The lower-limb venous ultrasound indicated patency of the deep veins in both legs, with continued thrombosis in the left calf intermuscular veins. The patient’s clinical symptoms improved, and treatment was switched to oral rivaroxaban (10 mg/day). Finally, the patient was discharged on POD 20.

The general information and treatment summary of the 4 patients are shown in Table 1.

Discussion

LDLT is a life-saving procedure for recipients with end-stage liver disease, but provides no direct therapeutic benefit for the donor. Zero donor mortality remains the ideal goal of LDLT. However, PE is an unpredictable but potentially fatal complication following LDH, it is also a major risk factor for perioperative disability. Although PE is relatively rare, there have been reports of deaths directly related to PE in living liver donors postoperatively [6]. The death of a donor can greatly affect the donor’s willingness to donate and increase their concern about the risks of the surgery. The occurrence of PE may also prolong hospital stay, increase medical expenses, raise in-hospital mortality, and reduce satisfaction among patients and their families. Therefore, early diagnosis and timely treatment are crucial for patient survival.

PE is a serious medical condition, typically results from thrombus formation in the lower-limb, which can dislodge and travel to the lungs, causing obstruction by preventing the circulation of distal blood flow [7]. Thrombosis risk factors include venous stasis, blood hypercoagulability, and endothelial damage (Virchow’s triad) [8,9]. There are several risk factors for thrombosis, including age 40 years or older, obesity, smoking, a history of thrombosis, surgery, hospitalization, varicose veins, thrombophilia, oral contraceptive use, and pregnancy [10]. In hepatic resection, the incidence of PE exceeds 6% [11]. Melloul et al [12] identified major liver resection in normal liver parenchyma as an independent risk factor for PE, likely due to the disruption of coagulation balance in the early postoperative period, which creates a procoagulant state. Thromboelastography performed on living liver donors also demonstrated that 50% of donors showed a sustained hypercoagulable state for up to 10 days after surgery [13]. Therefore, early postoperative procoagulant features may increase the risk of venous thromboembolism (VTE) after LDH.

We report 4 cases of acute pulmonary thromboembolism arising from lower-limb venous thrombosis dislodgement following LDH. The patients, aged 42 to 65 years, included 1 patient who was 65 at the time of surgery, notably older than previously reported PE patients. Preoperative lower-extremity venous ultrasound to exclude thrombosis was not performed, and none of the 4 cases received prophylactic anticoagulation. Fortunately, these patients were promptly diagnosed via enhanced CT scans and lower-extremity venous ultrasound, and the final prognosis was favorable by anticoagulation. Although 4 patients underwent open surgery, no postoperative PE has been observed in donors undergoing LDH at our center. This does not imply a lower incidence of perioperative PE in laparoscopic surgery compared to open surgery. PE is an obstruction within the pulmonary vasculature caused by blood clots, air, tumors, or fat. During laparoscopic hepatectomy, LCVP, reverse Trendelenburg position, and pneumoperitoneum increase the risk of gas embolism, potentially leading to higher mortality and postoperative complications [14]. Intraoperatively, findings of elevated blood CO2 levels, decreased blood pressure, and arrhythmia should raise suspicion of gas embolism. The detection of a large amount of gas in the right heart via transesophageal ultrasound is helpful for diagnosis PE [15].

We reviewed previously published literature and found several reports of PE occurring in living liver donors postoperatively. Notably, an international survey on VTE events after liver donor hepatectomy reported data from 51 transplant centers from 20 countries, which performed a total of 11500 LDLT between 2016 and 2020. Of these centers, 20 (39%) and 15 (29%) reported at least one perioperative DVT or PE event, respectively. One donor’s death was directly related to postoperative PE. The overall incidence of DVT and PE in living donor liver resection was 3.65 and 1.74 per 1,000 cases, respectively [5]. However, this survey did not provide detailed information on the diagnosis and treatment of PE cases. Reviewing 5 case reports [16–20] and one single-center retrospective study [6] (Table 2), we found detailed descriptions of PE diagnosis and treatment in living liver donors, with one case resulting in death due to PE. Of note, all donors had undergone preoperative evaluations that did not identify any contraindications to donation or a history of thrombosis. Among the reported cases, 3 of the donors underwent right hepatectomy, and 3 had left hepatectomy. In our study, 2 patients underwent right hepatectomy, and 2 had left hepatectomy. Major hepatectomy, the presence of underlying malignancies, and the absence of DVT prophylaxis are key risk factors for postoperative PE [21]. Furthermore, many studies have shown that right liver lobe of donors tends to have a higher complication rate compared to left lateral or left liver lobe of donor [3,22].

The symptoms of PE are non-specific, making it challenging to identify. PE should be suspected in patients who present with chest pain or difficulty breathing without an obvious cause. D-dimer testing and chest imaging, particularly pulmonary angiography and CT, are crucial in diagnosing PE. D-dimer is a specific degradation product formed from the activation and breakdown of fibrin, primarily reflecting fibrinolytic function [23]. A D-dimer threshold of 500 ng/mL offers a negative predictive value for PE of 97% to 100%. However, due to its potential low specificity and sometimes limited sensitivity, D-dimer testing is mainly used to rule out PE in clinical practice. Some centers recommend performing contrast-enhanced CT scans for patients with elevated D-dimer levels ≥20 ng/mL, regardless of clinical symptoms, to exclude PE or other VTE [19]. Currently, enhanced CT scan of the pulmonary angiography is the preferred method for diagnosing PE due to its non-invasive nature, convenience, and high sensitivity and specificity [24]. In our center, all 4 cases of PE were confirmed via enhanced CT of chest within 2 to 8 days postoperatively, with initial symptoms of chest tightness, dyspnea, and decreased oxygen saturation. Simultaneously, doppler ultrasound of the lower limbs revealed DVT in all cases. As a non-invasive, safe, and highly accurate diagnostic tool, lower-limb venous ultrasound is now the preferred method for diagnosing DVT. A history of VTE is one of the most significant risk factors for postoperative VTE. Therefore, preoperative screening with venous ultrasound should be standard for all potential donors, and donors with a prior history or evidence of VTE should be excluded from donation to ensure donor safety.

For patients with suspected PE and hemodynamic instability (defined as systolic blood pressure <90 mmHg and end-organ hypoperfusion), point-of-care ultrasound (PoCUS) can be valuable in identifying non-specific signs of PE, such as right ventricular dilation, a flattened interventricular septum, and the McConnell’s sign (characterized by decreased motion of the free wall of the right ventricle with normal or even hyperdynamic motion of the apex) [25]. In rare cases, PoCUS may directly detect a thrombus moving between the heart and pulmonary arteries, providing a definitive diagnosis of PE. The advantage of PoCUS lies in its role as a diagnostic rather than an exclusionary tool. For patients with a high clinical suspicion of PE who are unstable or in the acute phase, PoCUS can be employed to make rapid treatment decisions and provide invaluable immediate information before performing more comprehensive chest imaging safely.

Preventive measures for VTE include both pharmacological thromboprophylaxis (PTP) and mechanical thromboprophylaxis (MTP). Among 6 case reports, 1 donor did not receive any thromboprophylaxis measures, 1 female donor received both PTP and MTP, and the other 4 received only 1 form of prevention. In our report, 3 of the 4 donors used compression stockings intraoperatively to prevent thrombosis, and 1 female donor received MTP (intermittent pneumatic compression). None of the 4 patients received PTP treatment. Recent studies support the use of PTP in liver surgery and have found that PTP combined with MTP significantly reduces the incidence of VTE without increasing the risk of bleeding after liver resection [26]. An international survey has shown that dual-mode thromboprophylaxis is the most common strategy, although some transplant centers still use a single-mode prevention or no routine prevention [5]. All donors should receive an individualized prophylactic anticoagulation regimen after surgery. For living liver donors with a higher risk of thrombosis, a single prevention mode may be insufficient; thus, a combined pharmacological and mechanical dual-mode prevention strategy should be considered for optimal protection.

Conclusions

PE is a potentially life-threatening severe complication following LDH, requiring rapid diagnosis and intervention. Targeted preventive measures and intensified postoperative monitoring should be implemented for individuals at high risk of thrombosis perioperatively. Suspicion of PE should prompt rapid diagnosis by clinical evaluation, D-dimer testing, pulmonary angiography, and PoCUS. Early diagnosis and timely treatment are critical to prevent mortality in living liver donors due to PE.