Fat embolism following organ transplantation: a systematic review of reported cases

Abstract

Background:

This systematic review consolidates reported cases of fat embolism following organ transplantation, analyzing patient demographics, donor characteristics, clinical features, diagnostic methods, management strategies, and outcomes.

Methods:

A systematic review following PRISMA guidelines was conducted across PubMed, Google Scholar, Cochrane, EMBASE, MEDLINE, and Scopus up to 31 August 2024. Case reports diagnosing fat embolism or fat embolism syndrome after organ transplantation in patients over 18 years were included. Data extraction was done using EndNote® X21.

Results:

Of the 889 studies identified, 13 met the inclusion criteria and encompassed data on 15 patients. The mean age of patients was 38.2 years, with 64.3% male. Lung transplants were the most common (60.0%), followed by liver and kidney transplants. The primary clinical features included respiratory distress (80.0%) and acute kidney injury (6.7%). The overall mortality rate was 53.3%, and supportive care was the primary treatment strategy.

Discussion:

This study highlights significant morbidity and mortality associated with fat embolism following organ transplantation. This review underscores the critical importance of early diagnosis, comprehensive donor screening, and the implementation of standardized management protocols. Further research is necessary to develop preventative strategies and improve patient outcomes in this rare but critical complication.

Introduction

Fat embolism is a complex and often underrecognized phenomenon that reaches far beyond its traditional ties to traumatic injuries.^[1^]. Fat embolism is the presence of fat globules in the circulatory system. Fat embolism syndrome is the widespread distribution of these emboli that disrupt the capillary bed and microcirculation, subsequently causing a systemic inflammatory response.^[2^]. Although initially linked to orthopedic trauma, theories explaining the occurrence of fat embolism in non-orthopedic scenarios have existed since at least 1927^[3^]. Fat embolism is well-documented in cosmetic procedures, such as liposuction and fat grafting^[4,5^], as well as in conditions like hemoglobinopathies and bone marrow biopsy^[6,7^].

The first documented case of fat embolism following organ transplantation was reported in 1965^[8^]. However, the literature on this rare complication remains sparse. This study systematically consolidates case reports and a series of data to address the knowledge gap surrounding the incidence, clinical features, and outcomes of fat embolism following organ transplantation. By systematically reviewing reported cases, this study aims to elucidate their clinical manifestations, diagnostic methods, management strategies, and outcomes. The findings aim to enhance understanding, identify critical risk factors, and guide early diagnosis and effective management strategies, ultimately improving patient outcomes in clinical practice.

HIGHLIGHTS

• This is the first systematic review of fat embolism (FE) following organ transplantation. It consolidates data from 13 case studies across eight countries.

• The study identifies key risk factors for FE, particularly donor trauma such as long-bone fractures, and examines its impact on post-transplant recipients.

• The mortality rate among affected patients was 53.3%, and many survivors experienced permanent sequelae.

• Early recognition, supportive care, and standardized diagnostic and management protocols are essential for achieving better outcomes.

• The review provides critical insights for clinical practice and future research on preventing and managing FE in organ transplant patients.

Material and methods

The present study was conducted as a systematic review following the PRISMA (Preferred Reporting Items for Systematic Reviews and Meta-analyses) and AMSTAR 2 (Assessing the Methodological Quality of Systematic Reviews) Guidelines^[9,10^]. This study was previously registered in the Prospective International Register of Systematic Reviews (PROSPERO) under the ID number CRD42024546530.

Eligibility criteria

This study included only studies with case presentations that met the following criteria:

• Diagnosis of fat embolism or fat embolism syndrome after organ transplantation.

• Patients older than 18 years.

Information sources

A comprehensive literature search was conducted in various medical databases, including PubMed, Google Scholar, Cochrane, EMBASE, MEDLINE, and Scopus. The study was conducted without a time limit until 31 August 2024. Studies without English-language abstracts were excluded from the study.

Search strategy

The following terms were queried: “Fat Embolisms,” “Fat Embolism,” “Fat Embolism Syndrome,” “Fat emboli,” “fat embolus,” “Embolism,” AND “Transplant,” “Transplantation, Organ,” “Organ Transplantations,” “Grafting, Organ,” “Graftings, Organ,” “Organ Grafting,” and “Organ Graftings.” In addition, we thoroughly checked the reference lists of the selected studies and the associated reviews to identify any relevant studies that may have been overlooked in the electronic search. The full text of non-English studies that contained English abstracts was translated using Google Translate, a translation program developed by Google in Mountain View, California, USA.

Selection and data collection process

The search results were extracted and documented using EndNote® X21 software. Three authors independently screened the articles to remove duplicates. The lead author reviewed the extracted data. All discrepancies were resolved by consensus discussion in face-to-face meetings.

Data extraction

A standardized database for data extraction was created by compiling the following data: Authors, year of publication, country, study design, sample size, gender, age, body mass index, comorbidity, transplantation organ, donor characteristics, time interval, clinical manifestations, para-clinical and laboratory findings, authors final diagnosis, MIFE or MAFE, diagnostic methods, management, and outcomes. Data were classified as “Not mentioned or unavailable (Missing)” if specific characteristics were missing or unavailable. It is important to note that our methodology has some limitations. Specifically, the reliance on tools like Google Translate for non-English studies and the exclusion of non-English reports without abstracts may introduce biases and potentially limit the comprehensiveness of our findings.

Results

Included studies characteristics

A comprehensive database search yielded 651 studies, with an additional 238 obtained through a careful review of the citations. In total, 889 studies were identified. Following the deduplication process, 616 studies were selected. After completing the title, abstract, full-text screening, and eligibility assessment, 13 studies were deemed appropriate for inclusion in this review^[8,11-22^] (Fig. 1). These 13 studies comprised 11 case reports, one case series, and one letter to the editor, including 15 patients from 8 countries:

• The majority of studies originated from the United States (4/13, 30.8%) and Spain (3/13, 23.1%).

• The included studies comprised various organ transplants, with a predominance of lung transplants.

• Study characteristics are summarized in Table 1.

Figure 1.

Flowchart illustrating the study selection process.

Table 1.

Summary of included studies characteristics

Cases*	Author	Year	Country	Study type	Count
1	Glorion et al[22].	2021	France	Case report	1
2	Rossi et al[21].	2020	Italy	Case report	1
3,4	Rosenfeld et al[20].	2019	USA	Case report	2
5	Schweiger et al[19].	2017	Austria	Case report	1
6,7	Jacob et al[18].	2016	USA	Case report	2
8	López‐Sánchez et al[17].	2010	Spain	Case report	1
9	Najafizadeh et al[16].	2009	Iran	Case report	1
10	González-Fernández et al[15].	2009	Spain	Letters to editor	1
11	Padilla et al[14].	2007	Spain	Case report	1
12	Waller et al[13].	1995	UK	Case report	1
13	Lipton et al[12].	1987	Canada	Case report	1
14	Schober et al[11].	1973	USA	Case series	1
15	Jones et al[8].	1965	USA	Case report	1

Patient demographics and medical history

The age of the reported patients ranged from 18 to 59 years. Among 14 patients with available sex data, 9 (64.3%) were male and 5 (35.7%) were female. The most commonly transplanted organ was the lung (9/15, 60.0%), followed by liver and kidney (2/15, 13.4%), while single cases of kidney, liver, bone marrow, and heart transplantation were reported (1/15 each, 6.7%). Among lung transplant recipients:

• 5/9 (55.6%) received bilateral lung transplants.

• Primary conditions leading to lung transplantation:

  • Cystic fibrosis (4/9, 44.4%)
  • Silicosis (2/9, 22.2%)
  • Interstitial lung disease (2/9, 22.2%)
  • Pulmonary hypertension (1/9, 11.2%)

For liver transplant recipients, the primary underlying conditions included alcoholic cirrhosis (1/3, 33.3%) and hepatitis C with hepatocellular carcinoma (1/3, 33.3%). A complete summary of patient demographics and medical history is provided in Table 2.

Table 2.

Summary of patients’ demographics and medical history

Cases	Age (years)	Sex	BMI (kg/m2)	Comorbidity/transplantation organ
1	22	Female	NM	Cystic fibrosis/lungs
2	51	Female	NM	Diabetes, meningioma, liver cirrhosis/kidney and liver
3	59	Male	23.1	Alcoholic cirrhosis, previous spontaneous bacterial peritonitis (SBP), and hepatorenal syndrome requiring hemodialysis/kidney and liver
4	56	Male	30.8	Hepatitis C with hepatocellular carcinoma/liver
5	21	NM	NM	Cystic fibrosis/lungs
6	54	Male	NM	Familial interstitial pneumonia related to short telomere syndrome/single lung
7	28	Male	NM	Cystic fibrosis/lungs
8	59	Male	NM	End-stage silicosis with massive progressive fibrosis and smoking history/single lung
9	36	Female	NM	Pulmonary fibrosis/single lung
10	41	Male	NM	Silicosis/single lung
11	18	Male	NM	Cystic fibrosis/lungs
12	40	Male	NM	10-year history of primary pulmonary hypertension/lungs
13	22	Female	NM	Acute lymphoblastic leukemia/bone marrow
14	41	Male	NM	NM/heart
15	25	Female	NM	End stage renal disease/kidney

BMI: body mass index, NM: not mentioned.

Donors’ characteristics

Donor characteristics were reported in 11 out of 15 (73.3%) cases. Lung donors ranged from 17 to 37 years old, with 75.0% (6/8) being male.

• All lung donors had trauma-induced brain death.

• Fractures were common among lung donors:

  • 5/9 (55.6%) had long-bone fractures.
  • 3/9 (33.3%) had other fractures (scapula, ribs, face, spine).
  • One donor had no reported fractures.

Additionally, hepatic steatosis was reported in two liver donors. A summary of donor characteristics is listed in Table 3.

Table 3.

Summary of donors’ characteristics

Cases	Donor characteristics
1	27-year-old male with brain death after a motor vehicle accident resulting injuries involved the head and the extremities (long-bone fractures)
2	NM
3	50‐year‐old man, BMI 28.0 kg/m2, with intracranial hemorrhage (cardiac death), liver macroscopic appearances were steatotic
4	49‐year‐old woman, BMI 42 kg/m2, with traumatic brain injury, preimplant liver biopsies showed approximately 40% macrovesicular steatosis
5	21-year-old male 2 days after polytrauma, severe parenchymal brain injury, fracture of the scapula, the blood gases during organ procurement were 555 mmHg pO2 and 43 mmHg pCO2 at 100% FiO2
6	31-year old man who had been in motor vehicle collision and suffered multiple facial and rib fractures without pelvic or long-bone fractures. He had a cardiac arrest and closed chest CPR.
7	26-year old male who had suffered blunt head trauma including comminuted fracture of the anterior arch of C1 but no known pelvic or long-bone fracture.
8	22-yr-old woman with fatal head injury and skeletal trauma (stable left pelvic fracture and closed fractures of the right tibia and fibular diaphyses) following motor vehicle accident
9	Brain-dead patient with the cause of death being a car accident with no evidence of bone fracture
10	17-year-old man, smoker, brain dead after a traffic accident; fractured right femur
11	31-year-old woman, nonsmoker, with brain death due to head injury after a traffic accident and fractures of the sternum, pelvis, and right femur
12	37-year-old man who had fallen 6 m, fatal head injury, bilateral rib fractures, and a fractured right femoral shaft
13	NM
14	NM
15	NM

Timing and clinical features of patients

The onset of fat embolism-related symptoms varied among patients:

• Immediate onset after transplantation: 8/15 (53.3%)

• Within 72 hours post-transplantation: 3/15 (20.0%)

• Delayed onset (5 days–9 months post-transplantation): 3/15 (20.0%)

The primary clinical features observed were:

• Respiratory/cardiac symptoms: 12/15 (80.0%)

• Acute kidney injury: 1/15 (6.7%)

• Altered mental status: 1/15 (6.7%)

• Gastrointestinal symptoms + petechial rash: 1/15 (6.7%)

A detailed breakdown of clinical features and timing per patient is provided in Table 4.

Table 4.

Summary of primary clinical manifestations

Cases	Timing*	Primary signs and symptoms
1	Immediately after	Severe hypoxia following upon reperfusion of the second allograft
2	2 days after	Acute kidney injury
3	Immediately after	Pulseless electrical activity, vasodilatory shock and respiratory failure following upon reperfusion of the second allograft (kidney)
4	Immediately after	Cardiac arrest following upon reperfusion of the allograft, respiratory failure
5	Immediately after	At the end of the procedure, the lungs became increasingly edematous with rising respiratory effort
6	12 hours after	Significant hypoxemic respiratory failure
7	Immediately after	Marked hypoxemia
8	Immediately after	Hemodynamic instability, respiratory failure
9	5 days after	Acute respiratory distress
10	Less than 24 hours after	Respiratory failure, renal insufficiency (5 days after)
11	Immediately after	Respiratory failure
12	Immediately after	Pulmonary edema developed rapidly
13	9 weeks after	Dyspnea, cough, chest pain
14	Less than 72 hours after	Altered mental status
15	9 months after	Abdominal pain, nausea, vomiting, petechial rash

^*Timing: interval time between the end of the procedure and the presentation of first signs or symptoms.

NM: not mentioned.

Laboratory findings

Regarding laboratory findings, PaO2/FiO2 less than 200 mmHg (moderate respiratory distress) was reported in 4/4 (100%) patients. Hypertriglyceridemia was reported in two patients. The summary of laboratory findings for each patient is shown in Table 5.

Table 5.

Summary of laboratory findings

Cases	Laboratory findings
1	PaO2/FiO2: 70 mmHg
2	Creatinine: 5.2 mg/dl from 0.8 mg/dl, bilirubin: 25 mmol/l, alanine aminotransferase: 49 U/l, aspartate aminotransferase: 63 U/l, alkaline phosphatase: 48 U/l), triglycerides: 221 mg/dl
3	NM
4	NM
5	NM
6	NM
7	NM
8	PaO2/FiO2 = 40 mmHg
9	NM
10	PaO2/FiO2 = 160 mmHg
11	PaO2/FiO2 = 151 mmHg
12	NM
13	NM
14	NM
15	Sever hypertriglyceridemia

Imaging and other para-clinical findings

Post-transplant imaging revealed significant abnormalities:

• Donor chest imaging was normal in 3 cases (2 chest X-rays, 1 chest CT).

• Post-transplant chest X-ray findings:

  • ARDS/interstitial infiltration: 6/8 (75.0%)
  • Pulmonary edema: 2/8 (25.0%)

• Post-transplant chest CT findings:

  • Consolidations, multifocal patchy opacities (ARDS), and expanded infiltrations were observed in 3 patients.

• Transesophageal echocardiography (TEE) (n = 6):

  • Normal findings: 3/6 (50.0%)
  • Pulmonary hypertension: 2/6 (33.3%)
  • Right ventricular dilatation: 1/6 (16.7%)

Histopathological findings:

• Pulmonary fat embolism was found in all 12 cases (100%).

• Bone marrow cell embolism was reported in 4/12 (33.3%).

• Renal fat embolism was noted in 3 patients, while cerebral fat embolism was identified in two patients.

• Macroscopic pulmonary fat embolism was observed in two donor lungs during retrograde flushing.

A summary of imaging and other para-clinical findings is provided in Tables 6 and 7.

Table 6.

Summary of imaging studies and findings

Cases	Imaging studies and findings
1	Donor preoperative chest CTs: normal/postoperative CXR: ARDS, TEE: no heart failure, mean PAP: 36 mmHg
2	No
3	Postoperative CXR: ARDS, TEE: normal ventricular function
4	Postoperative CXR: ARDS, TEE: right ventricular dilatation and intact left ventricular function
5	Postoperative CXR: bilateral, patchy infiltrates, which gradually resolved during the early postoperative course
6	Postoperative Chest CTs: interval development of consolidations in the donor lung, particularly in the middle and lower lobes, TEE: normal
7	Postoperative Chest CTs: multifocal patchy opacities concerning for acute respiratory distress syndrome (ARDS), TEE: normal
8	Postoperative CXR: severe reperfusion edema on the grafted lung, TEE: pulmonary hypertension
9	Postoperative Chest CTs: expanded infiltrations on the grafted lung
10	Postoperative CXR: confluent alveolar pattern, ARDS
11	Donor preoperative CXR: normal/Postoperative CXR: a significant pattern of pulmonary edema
12	Donor preoperative CXR: normal
13	CXR: interstitial infiltrates at the bases of both lung fields
14	NM
15	Abdominal series X-ray: small bowel obstruction

CTs: computed tomography scan, CXR: chest X-ray, ARDS: acute respiratory distress syndrome, TEE: transesophageal echocardiography, PAP: pulmonary artery pressure.

Table 7.

Summary of patients’ other para-clinical findings

Cases	Other para clinical findings
1	Pulmonary histopathological analysis: histological evaluation of the unused donor lung pieces showed occlusion of pulmonary arterioles by adipose cell islands and hematopoietic bone marrow cells; both suggestive of fat embolism
2	Kidney histopathological analysis: renal fat embolism
3	Pulmonary histopathological analysis: intravascular and capillary distribution of fat droplets/liver histopathological analysis: evidence of zone 3 preservation reperfusion injury including hepatocyte necrosis, hepatocyte dropout, lipopeliosis, extensive lipid presence and hemorrhage.
4	Pulmonary histopathological analysis: intravascular and capillary distribution of fat droplets/liver histopathological analysis: evidence of zone 3 preservation reperfusion injury including hepatocyte necrosis, hepatocyte dropout, lipopeliosis, extensive lipid presence and hemorrhage.
5	Surgical findings: during retrograde flushing massive fat embolism became evident at the back-table.
6	Pulmonary histopathological analysis: histological evaluation of the unused donor lung revealed global fat embolism.
7	Surgical findings: detailed inspection of the donor pulmonary artery prior to anastomosis revealed yellow, opaque material consistent with fat embolism.
8	Pulmonary histopathological analysis: histological evaluation of the transplanted lung revealed global fat emboli.
9	Pulmonary histopathological analysis: histological evaluation of the unused donor lung revealed fat, bone marrow materials, and bone particles embolism.
10	Pulmonary and kidney histopathological analysis: fat embolism.
11	Pulmonary histopathological analysis: histological evaluation of the unused donor lung pieces showed occlusion of pulmonary arterioles by adipose cell islands and bone marrow cells
12	Pulmonary histopathological analysis: the pulmonary vasculature was found to be laden with fat and bone marrow cells.
13	Pulmonary histopathological analysis: transbronchial lung biopsy showed pulmonary fat embolism.
14	Cerebral and pulmonary histopathological analysis: fat embolism
15	Histopathological analysis: systematic fat embolism (cerebral, pulmonary, renal)

Final diagnosis and diagnostic methods

The authors’ final diagnoses included:

• Donor-acquired fat embolism (DA-FE) or donor-acquired fat embolism syndrome (DA-FES): 7/15 (46.6%)

• Fat embolism syndrome (FES): 3/15 (20.0%)

• Pulmonary fat embolism: 3/15 (20.0%)

• Cerebral and pulmonary fat embolism: 1/15 (6.7%)

• Systemic fat embolism: 1/15 (6.7%)

Diagnostic methods included clinical manifestations (n = 13), histopathological assessments (n = 13), and donor surgical findings (n = 2). Based on the clinical evolution reported in each study, we identified macroscopic fat embolism (MAFE) and microscopic fat embolism (MIFE) as final diagnoses. MAFE is diagnosed through imaging studies like CT or MRI, revealing fat droplets in the vasculature, or through direct assessment of tissue samples from biopsies or autopsies, with confirmation requiring fat globules in the pulmonary, cerebral, or ocular circulation causing vascular occlusion. MIFE, equivalent to FES, is diagnosed based on clinical symptoms such as respiratory distress, neurological symptoms, and petechial rash, supported by imaging studies and laboratory results. We identified no patients with MAFE post-transplantation. All patients were diagnosed with MIFE. Diagnostic methods in patients included clinical manifestations (n = 13), histopathological assessments (n = 13), and donor surgical findings (n = 2). A full summary is provided in Table 8.

Table 8.

Summary of final diagnosis and diagnostic methods

Cases	Authors’ final diagnosis	MIFE	MAFE	Diagnostic methods
1	DA-FES	Yes	No	Clinical manifestation, imaging, microscopic autopsy assessment
2	FES	Yes	No	Clinical manifestation, microscopic biopsy assessment
3	FES	Yes	No	Clinical manifestation, imaging, microscopic autopsy assessment
4	FES	Yes	No	Clinical manifestation, imaging, microscopic autopsy assessment
5	DA-FE	Yes	No	Clinical manifestation, imaging, surgical findings
6	DA-FES	Yes	No	Clinical manifestation, imaging, microscopic autopsy assessment
7	DA-FES	Yes	No	Clinical manifestation, imaging, surgical findings
8	Pulmonary FE	Yes	No	Clinical manifestation, imaging, microscopic autopsy assessment
9	Pulmonary FE	Yes	No	Clinical manifestation, imaging, microscopic autopsy assessment
10	DA-FES	Yes	No	Clinical manifestation, imaging, microscopic autopsy assessment
11	DA-FE	Yes	No	Clinical manifestation, imaging, microscopic autopsy assessment
12	DA-FES	Yes	No	Clinical manifestation, imaging, microscopic autopsy assessment
13	Pulmonary FE	Yes	No	Clinical manifestation, imaging, microscopic biopsy assessment
14	Cerebral and pulmonary FE	Yes	No	Microscopic autopsy assessment
15	Systematic FE	Yes	No	Microscopic autopsy assessment

DA-FES: donor-acquired Fat embolism syndrome, FE: fat embolism, MAFE: macroscopic fat embolism. MIFE: microscopic fat embolism.

Management and patients’ outcomes

Supportive care was the primary treatment for all patients.

• 6 patients were admitted to the ICU.

• 9/10 (90.0%) required mechanical intubation.

• ECMO was used in 4 patients.

• Corticosteroids (6 patients) and anticoagulants (4 patients) were administered.

• In two patients, corticosteroid doses were reduced due to concerns about corticosteroid-induced fat embolism.

The overall mortality rate was 53.3% (8/15), with 1 of 7 surviving patients (14.3%) experiencing permanent renal failure (Table 9).

Table 9.

Summary of managements and patients outcomes

Cases	ICUa	MVa	Other	Corticosteroids	Anticoagulants	Hospital stays (days)	Outcome/timinga/PODa
1	Y	Y	ECMOa	NM	Y	31	Alive/-/No
2	NM	N	Dialysis	Y	NM	NM	Alive/-/Y: RF
3	Y	Y	-	Y	Y	<1	Death/2 hours/-
4	Y	Y	-	Y	Y	<1	Death/<1 day/-
5	Y	Y	ECMO	Y	NM	6	Alive/-/NM
6	NM	Y	-	Y	NM	31	Alive/-/No
7	Y	Y	ECMO	NM	NM	39	Alive/-/No
8	Y	Y	ECMO	NM	Y	2	Death/45 hours/-
9	NM	NM	-	Y	NM	10	Death/10 days/-
10	NM	Y	-	NM	NM	15	Death/15 days/-
11	NM	Y	-	NM	NM	34	Alive/-/No
12	NM	Y	-	NM	NM	<1	Death/11 hours/-
13	NM	NM	-	Yb	NM	NM	Alive/-/No
14	NM	NM	NM	NM	NM	3	Death/3 days/-
15	NM	NM	NM	Yb	NM	NM	Death/10 months/-

^aICU: intensive care unit admission, MV: mechanical ventilation, Timing: the interval time between procedure and occurrence of death (days), POD: permanent organ failure/disability, ECMO: extracorporeal membrane oxygenation.

^bThe post-transplant corticosteroid doses reduced.

Underlying causes of post-transplant fat embolism

In several cases, the fat embolism was linked to femoral fractures sustained by the donor, with the embolic material consisting of fat and bone marrow cells found in the pulmonary vasculature of the recipient. However, in some cases, no significant findings were present in donor imaging or initial examinations, such as the case where fat embolism was later diagnosed despite the absence of any pre-transplant abnormalities in radiographs or bronchoalveolar lavage analysis. Fat embolism likely resulted from embolized fat and bone marrow cells entering the recipient’s circulation during transplantation. Other contributing factors included:

• Prolonged mechanical ventilation and ischemia during organ preservation.

• Corticosteroid-induced fat embolism in recipients with prolonged immunosuppressive therapy.

• Hepatic steatosis in liver donors, potentially facilitating fat embolization.

Discussion

This systematic review aimed to elucidate the characteristics of fat embolism in patients undergoing organ transplantation. Understanding the distinctive pathophysiological mechanisms and clinical presentations of post-transplant fat embolism is crucial for enhancing clinical awareness and optimizing management strategies. The reviewed cases underscore the complexity of this condition, which involves donor-related factors such as trauma-induced fat emboli and recipient-related risk factors, including immunosuppressive therapy. Lung transplantation, especially from donors with long-bone fractures or trauma-induced brain death, emerges as the most frequently associated procedure, accounting for 60% of cases.

The findings align with previous studies that highlight fat embolism as a multifactorial condition, primarily reported in orthopedic trauma but increasingly recognized in non-orthopedic scenarios^[4,23^]. In this review, pulmonary manifestations were the most common clinical presentation, consistent with FES’s pathophysiology involving microvascular occlusion and inflammatory response in the lungs. Histopathological findings of microscopic fat emboli in all cases further confirm the diagnosis.

In traumatic fat embolism, symptoms typically appear within 24–72 hours post-injury^[24^], but the timing of onset in patients with fat post-transplant embolism shows notable differences. According to our findings, the first signs/symptoms occurred immediately after the organ transplantation in 8/15 (53.3%) of patients. In the remaining patients, the time to onset of symptoms ranged from less than 24 hours to up to 9 months, influenced by the underlying pathophysiology. The rapid onset of symptoms in most cases can be attributed to donor trauma. Fat embolism symptoms typically manifest within 24–72 hours after the traumatic event, explaining the immediate post-transplant clinical deterioration in many patients. However, delayed presentations may reflect additional factors, such as progressive microvascular occlusion or corticosteroid-induced fat mobilization in recipients.

Management strategies in the reviewed cases primarily involved supportive care tailored to the severity of clinical manifestations. Mechanical ventilation was required in 9/10 of patients, with 4/10 receiving extracorporeal membrane oxygenation (ECMO) for severe respiratory compromise. Corticosteroids and anticoagulants were administered in select cases to address inflammation and mitigate the risk of microvascular occlusion. Interestingly, corticosteroid doses were reduced in two patients due to their potential role in inducing fat embolism. Despite intensive management, the high mortality rate (53.3%) underscores the need for early recognition and intervention. Traumatic fat embolism syndrome (FES), typically resulting from orthopedic injuries, commonly presents with the classic triad of respiratory distress, neurological symptoms, and petechial rash, and it carries a moderate mortality rate of 7–36%^[25-27^]. In contrast, our findings revealed higher mortality and distinct clinical patterns in post-transplant fat embolism cases. Respiratory symptoms predominated, with neurological and petechial manifestations being less frequent. This disparity likely reflects differences in underlying mechanisms; post-transplant fat embolism often involves donor-related trauma and ischemia-reperfusion injury, compounding the complexity and severity of the clinical course.

To reduce the risk of fat embolism in organ transplantation, strategies should focus on minimizing donor-related risk factors and optimizing recipient care. Ensuring careful donor screening for fractures or traumatic injuries, particularly long-bone fractures, is crucial. Advanced imaging techniques may help detect fat emboli in donor organs before transplantation. In recipients, gradual reperfusion strategies could minimize ischemia-reperfusion injury. Additionally, tailored immunosuppressive regimens, avoiding excessive corticosteroid doses, may reduce corticosteroid-induced fat mobilization. Early recognition and intervention protocols for high-risk transplants could further improve outcomes.

The evidence included in this systematic review has several limitations. First, the data were derived primarily from case reports and small case series, which inherently lack generalizability and may introduce publication bias, as only severe or unique cases are more likely to be reported. Second, inconsistencies in diagnostic criteria and reporting standards across studies limited the ability to uniformly classify cases. Third, some reports lacked comprehensive donor and recipient data, which constrained the analysis of potential risk factors and mechanisms. Lastly, this review also has limitations regarding the lack of detailed information about surgical procedures and anesthesia methods.

The findings of this study have important implications for clinical practice, policy, and future research. Clinically, they highlight the need for rigorous donor assessment, including screening for traumatic injuries, and the adoption of early diagnostic and intervention protocols to reduce mortality. Policies should aim to standardize perioperative care, including reperfusion techniques and tailored immunosuppression regimens, to minimize risks. Future research should focus on prospective studies to better understand the mechanisms of fat embolism in transplantation, identify predictive biomarkers, and evaluate innovative preventative and therapeutic strategies.

Ethical approval

Ethics approval was not required for this systematic review.

Consent

Informed consent was not required for this systematic review.

Sources of funding

This research received no funding.

Author’s contribution

C.P.: study concept, design, data collection, writing the paper; K.R.J.: study design, data collection, writing the paper, data analysis or interpretation; A.M. and A.H.: data collection, writing the paper.

Conflicts of interest disclosure

All authors declare that they have no competing interests.

Research registration unique identifying number (UIN)

This study was previously registered in the Prospective International Register of Systematic Reviews (PROSPERO) under the ID number CRD42024546530. https://www.crd.york.ac.uk/prospero/display_record.php?RecordID=546530

Guarantor

Pouria Chaghamirzayi.

Provenance and peer review

Not commissioned, externally peer-reviewed.

Data availability statement

Any datasets generated during and/or analyzed during the current study are publicly available, available upon reasonable request, or if data sharing is not applicable to this article.