Underlying thrombotic conditions in patients with splenic infarction: a 10-year retrospective analysis

Abstract

Background

Splenic infarction is a rare but clinically important condition that is usually associated with underlying hematological, cardiovascular, infectious, or malignant diseases. Due to its nonspecific clinical presentation, diagnosis may be delayed. This study aimed to evaluate the demographic characteristics, clinical findings, etiological factors, radiological features, treatment approaches, and outcomes of patients diagnosed with non-traumatic splenic infarction.

Methods

This retrospective study included 67 adult patients diagnosed with splenic infarction by contrast-enhanced abdominal computed tomography (CT) at Dicle University Faculty of Medicine Hospital between January 2014 and December 2023. Demographic characteristics, presenting symptoms, laboratory parameters, radiological findings, etiological factors, treatment modalities, length of hospital stay, and in-hospital mortality were evaluated.

Results

The mean age of the patients was 50.9 ± 16.3 years, and 64.2% were male. Abdominal pain was the most common presenting symptom and was present in all patients. Hematological disorders were the most common identifiable specific etiology (31.3%), while no identifiable cause was found in 23.9% of patients. Contrast-enhanced CT established the diagnosis in all patients, whereas ultrasonography detected infarction in only 29.9% of cases. JAK2 mutation analysis was positive in 4 of 16 tested patients with hematological disorders. Conservative management was sufficient in 89.6% of patients, while 10.4% required splenectomy because of splenic rupture, hemorrhagic infarction, or splenic abscess formation. In-hospital mortality occurred in four patients (6.0%).

Conclusions

Splenic infarction is an uncommon clinical entity that should be considered in patients presenting with unexplained abdominal pain, particularly in the presence of hematological or systemic disorders associated with thrombotic risk. Contrast-enhanced CT remains the most reliable diagnostic modality, whereas ultrasonography has limited sensitivity. Although conservative management is effective in most patients, severe complications may necessitate surgical intervention. Early diagnosis and comprehensive etiological evaluation are essential for appropriate management and improved clinical outcomes.

Clinical trial number

Not applicable.

Introduction

Splenic infarction results from ischemic necrosis of splenic parenchyma due to occlusion of the splenic artery or its intraparenchymal branches. Three overlapping pathophysiological mechanisms are generally implicated: (1) embolic occlusion originating from a cardiac source, such as atrial fibrillation, valvular heart disease, infective endocarditis, or mural thrombus, and less commonly paradoxical embolism through a patent foramen ovale; (2) in situ thrombosis related to a hypercoagulable state, including myeloproliferative neoplasms, hemoglobinopathies, antiphospholipid syndrome, and malignancy-associated coagulopathy; and (3) local vascular pathology, such as vasculitis, splenic artery atherosclerosis or aneurysm [1–4], and torsion of a wandering spleen [5–6].

In recent years, infectious diseases have increasingly been recognized as precipitants of splenic infarction. COVID-19 has been repeatedly associated with splenic infarction through a combination of endothelial injury, complement-mediated microangiopathy, and a systemic hypercoagulable state, even in patients without respiratory symptoms [7]. Similarly, Mycoplasma pneumoniae infection has been reported to cause splenic infarction through cold agglutinin-mediated hemolysis, transient antiphospholipid antibody production, and small-vessel vasculitis, occasionally without overt pneumonia [8]. Other infectious agents implicated include Epstein-Barr virus, cytomegalovirus, and septic emboli from infective endocarditis [2, 9].

The clinical presentation may vary widely, ranging from left upper quadrant pain to signs of acute abdomen; some patients may even remain asymptomatic. Dynamic abdominal computed tomography (CT) is typically used for diagnosis, revealing characteristic hypodense, wedge-shaped lesions. Treatment options vary based on the extent of infarction and the underlying cause, ranging from conservative approaches to surgical interventions [10–13].

This study aimed to retrospectively evaluate the demographic characteristics, clinical presentation, etiological factors, radiological findings, treatment approaches, and outcomes of patients diagnosed with non-traumatic splenic infarction, with the goal of providing clinicians with practical guidance for earlier recognition, targeted etiological work-up, and appropriate management of this potentially under-recognized condition.

Methods

Study design and patient selection

This retrospective study was conducted at Dicle University Faculty of Medicine Hospital and included adult patients diagnosed with splenic infarction between January 1, 2014, and December 31, 2023. Patients were identified through the hospital electronic medical record system and radiology database. The diagnosis of splenic infarction was confirmed by contrast-enhanced abdominal computed tomography (CT).

Patients younger than 18 years of age, those with traumatic splenic injury, and patients with incomplete medical records were excluded. A total of 67 patients met the study criteria and were included in the final analysis.

Data collection

Demographic characteristics, presenting symptoms, physical examination findings, laboratory parameters, radiological findings, comorbid conditions, etiological factors, treatment modalities, length of hospital stay, and in-hospital mortality data were retrieved from electronic medical records and hospital archive systems.

Laboratory parameters included white blood cell count, hemoglobin level, platelet count, lactate dehydrogenase (LDH), and other routinely available biochemical measurements obtained at admission.

Treatment modalities were categorized as conservative management or splenectomy. Indications for surgical intervention were recorded when available.

Data extraction and verification were independently performed by all co-authors, who cross-checked the extracted clinical, laboratory, radiological, and outcome data against the original electronic medical records to ensure accuracy and completeness; any discrepancies were resolved by consensus.

Laboratory abnormalities were defined according to the reference ranges of our institution’s clinical laboratory: leukocytosis as a white blood cell count > 10.8 × 10³/µL, anemia as a hemoglobin level < 13.5 g/dL in men and < 12.0 g/dL in women, thrombocytopenia as a platelet count < 150 × 10³/µL, and elevated LDH as a level > 247 U/L.

Radiological evaluation

Review of medical records showed that abdominal ultrasonography had been performed as the initial imaging modality in all patients, followed by contrast-enhanced CT based on clinical suspicion, irrespective of ultrasonographic findings. Splenic infarction was diagnosed based on contrast-enhanced abdominal CT findings. Typical radiological findings included one or more peripheral wedge-shaped hypodense areas without contrast enhancement within the splenic parenchyma. Ultrasonographic findings were also reviewed and recorded for comparison. Radiological reports were evaluated through the hospital archive system.

Etiological assessment

Etiological classification was performed after reviewing clinical history, laboratory investigations, imaging findings, hematological evaluations, cardiological assessments, and discharge diagnoses. Patients were categorized into four groups according to the most likely underlying etiology: hematological disorders, cardiovascular diseases, other systemic diseases, and idiopathic cases in whom no definite cause could be identified despite available investigations.

Molecular testing, including JAK2 mutation analysis, was performed in selected patients with suspected myeloproliferative disorders according to the treating physician’s clinical judgment.

Statistical analysis

All statistical analyses were performed using SPSS software version 22.0 (IBM Corp., Armonk, NY, USA). Continuous variables were expressed as mean ± standard deviation (SD) or median (minimum–maximum), depending on data distribution. Categorical variables were presented as frequencies and percentages.

Results

A total of 67 patients diagnosed with splenic infarction were included in the study. The mean age was 50.9 ± 16.3 years (range, 19–86 years), and the median age was 53 years. Of the patients, 43 (64.2%) were male and 24 (35.8%) were female.

Abdominal pain was the most common presenting symptom and was reported in all patients (100%). Fever was present in 27 patients (40.3%), while nausea and/or vomiting were observed in 21 patients (31.3%). Physical examination revealed left upper quadrant tenderness in all patients. Splenomegaly was detected in 54 patients (80.6%), with spleen length ranging from 110 mm to 340 mm.

Laboratory evaluation demonstrated a mean white blood cell count of 13.1 ± 10.2 × 10³/µL, a mean hemoglobin level of 10.8 ± 3.4 g/dL, a mean platelet count of 167.4 ± 139.3 × 10³/µL, and a mean lactate dehydrogenase (LDH) level of 549.9 ± 512.5 U/L. The mean C-reactive protein (CRP) level was 11.3 ± 4.7 mg/dL among patients with available data. Leukocytosis was observed in 42 patients (62.7%), anemia in 43 patients (64.2%), thrombocytopenia in 36 patients (53.7%), and elevated LDH levels in 49 patients (73.1%).

Molecular genetic testing for the JAK2 mutation was performed in 16 of the 21 patients with hematological disorders. Four patients (25.0% of those tested; 6.0% of the overall cohort) were positive for the JAK2 mutation. Thrombophilia screening, including Factor V Leiden mutation, prothrombin gene mutation, MTHFR mutation analysis, and protein C, protein S, and antithrombin III levels, was negative or within normal limits in all tested patients.

Radiologically, medical records showed that abdominal ultrasonography had been performed as the initial imaging modality in all patients, followed by contrast-enhanced CT based on clinical suspicion, irrespective of ultrasonographic findings. Splenic infarction was confirmed by contrast-enhanced CT in all patients (100%), whereas ultrasonography identified infarct lesions in only 20 of the 67 patients (29.9%). Representative CT images are shown in Fig. 1.

Fig. 1.

(A, B, C, D) Contrast-enhanced abdominal CT images show hypodense areas in the spleen (indicated by arrows), consistent with splenic infarction

Etiological evaluation revealed hematological disorders in 21 patients (31.3%), including acute myeloid leukemia, chronic myeloid leukemia, myelofibrosis, polycythemia vera, myelodysplastic syndrome, chronic myelomonocytic leukemia, paroxysmal nocturnal hemoglobinuria, and sickle cell anemia. Cardiovascular diseases were identified in 8 patients (11.9%), including atrial fibrillation, heart failure, and aortic coarctation. Other systemic diseases were present in 22 patients (32.8%), including diabetes mellitus, liver cirrhosis, alcoholic hepatitis, pancreatic cancer, acute pancreatitis, and sepsis. No identifiable etiology was found in 16 patients (23.9%) despite available investigations (Tables 1 and 2).

Table 1.

Demographic characteristics, clinical findings, laboratory results, imaging findings, and outcomes of patients with splenic infarction

Variable	Value
Demographic Characteristics
Age, years, mean ± SD (median, range)	50.9 ± 16.3 (53, 19–86)
Male sex, n (%)	43 (64.2)
Female sex, n (%)	24 (35.8)
Presenting Symptoms
Abdominal pain, n (%)	67 (100)
Fever (> 38 °C), n (%)	27 (40.3)
Nausea and/or vomiting, n (%)	21 (31.3)
Physical Examination
Left upper quadrant tenderness, n (%)	67 (100)
Splenomegaly, n (%)	54 (80.6)
Laboratory Findings
White blood cell count (×10³/µL), mean ± SD	13.1 ± 10.2
Hemoglobin (g/dL), mean ± SD	10.8 ± 3.4
Platelet count (×10³/µL), mean ± SD	167.4 ± 139.3
LDH (U/L), mean ± SD	549.9 ± 512.5
CRP (mg/dL), mean ± SD	11.3 ± 4.7
Leukocytosis, n (%)	42 (62.7)
Anemia, n (%)	43 (64.2)
Thrombocytopenia, n (%)	36 (53.7)
Elevated LDH, n (%)	49 (73.1)
JAK2 mutation positivity (4/16 tested), n (%)	4 (6.0)
Positive thrombophilia panel, n (%)	0 (0)
Imaging Findings
Ultrasonography detecting infarction, n (%)	20 (29.9)
Contrast-enhanced CT detecting infarction, n (%)	67 (100)
Treatment and Outcomes
Conservative treatment, n (%)	60 (89.6)
Splenectomy, n (%)	7 (10.4)
Length of hospital stay, days (mean, range)	6.1 (1–24)
In-hospital mortality, n (%)	4 (6.0)

Table 2.

Etiological classification of splenic infarction

Etiology	n (%)
Hematologic diseases	21(%31.3)
- Acute myeloid leukemia	6
-Polycythemia vera	2
-Chronic myelomonocytic leukemia	2
-Myelodysplastic syndrome	2
-Chronic myeloid leukemia	3
-Myelofibrosis	3
-Paroxysmal nocturnal hemoglobinuria	1
-Sickle cell anemia	2
Cardiovascular diseases	8 (%11.9)
- Atrial fibrillation	4
- Heart failure	2
- Aortic coarctation	2
Other systemic diseases	22 (%32.8)
- Diabetes mellitus	6
- Liver cirrhosis	5
- Alcoholic hepatitis	2
- Pancreatic cancer	3
- Acute pancreatitis	2
- Sepsis	4
Unknown etiology	16 (%23.9)

Regarding treatment, 60 patients (89.6%) were managed conservatively, whereas 7 patients (10.4%) required splenectomy. Indications for splenectomy included splenic rupture in 3 patients, hemorrhagic splenic infarction in 2 patients, and splenic abscess formation in 2 patients. The mean length of hospital stay was 6.1 days (range, 1–24 days). In-hospital mortality occurred in 4 patients (6.0%), all of whom had severe underlying systemic conditions, including malignancy or sepsis.

Discussion

Splenic infarction is an uncommon clinical condition that is increasingly recognized due to the widespread use of advanced imaging modalities. In the present study, we evaluated the demographic characteristics, clinical presentations, etiological factors, radiological findings, treatment approaches, and outcomes of 67 patients diagnosed with splenic infarction over a 10-year period at a tertiary referral center.

The mean age of our patients was 50.9 years, and there was a predominance of male patients (64.2%). Similar demographic characteristics have been reported in previous studies, suggesting that splenic infarction occurs more frequently in middle-aged and older adults and may show a slight male predominance [1, 2]. However, demographic characteristics alone are insufficient for diagnosis, as the clinical presentation of splenic infarction is often nonspecific.

Abdominal pain was present in all patients and represented the most common presenting symptom. Fever and nausea/vomiting were also frequently observed. These findings are consistent with previous reports describing left upper quadrant pain as the hallmark symptom of splenic infarction [3, 10]. Nevertheless, the clinical presentation may mimic several common abdominal emergencies, including acute pancreatitis, renal colic, appendicitis, or other causes of acute abdomen. Consequently, delayed diagnosis remains a significant clinical challenge, particularly in patients without obvious thromboembolic risk factors.

One of the most important findings of our study was the etiological distribution of splenic infarction. Hematological disorders represented the most common identifiable cause, accounting for 31.3% of all cases, whereas cardiovascular diseases accounted for only 11.9%. This observation differs from some contemporary studies in which cardioembolic disorders, particularly atrial fibrillation, constituted the leading cause of splenic infarction [14–16]. As shown in Table 3, the etiological distribution of splenic infarction varies considerably among published series. These differences likely reflect variations in study populations, referral patterns, geographic characteristics, and the prevalence of underlying hematological, cardiovascular, and systemic diseases (Table 3).

Table 3.

Comparison of etiological factors in different patient series

Study	Number of Patients (n)	Most Common Etiologies
Nores et al. (1998)	n = 59	Hematologic disorders (n = 35), thromboembolic disorders (n = 17), other causes (n = 7)
Antopolsky et al. (2009)	n = 48	hypercoagulability (n = 22), cardiac causes (n = 22)
Lawrence et al. (2010)	n = 26	Hematologic malignancies (n = 6), cardiac thrombus and endocarditis (n = 8)
Schattner et al. (2015)	n = 32	Cardioembolic events (n = 20), autoimmune (n = 4), infectious causes (n = 4)
Chieh Ching Yen et al. (2021)	n = 130	Hypertension (n = 60), atrial fibrillation (n = 32), diabetes mellitus (n = 30)
Cox et al. (2016)	n = 123	Malignancy (n = 40)
Brett et al. (2020)	n = 163	Celiac/splenic artery atherosclerosis (n = 34), malignant tumor (n = 32), sepsis (n = 27)a
Bewersdorf et al. (2021)	n = 206	Thromboembolic events (n = 42)
Hakoshima et al. (2023)	n = 18	Cancer (n = 6), atrial fibrillation (n = 4), infection (n = 4)
Present study	n = 67	Other systemic diseases (n = 22; e.g., DM, cirrhosis, sepsis, malignancy), hematologic diseases (n = 21), unknown etiology (n = 16)

ᵃCategories are not mutually exclusive; 40% of patients had more than one predisposing condition

Notably, Brett et al. evaluated 163 patients with CT-confirmed splenic infarction and found that the most frequently associated conditions were celiac or splenic artery atherosclerosis (21%), malignant tumor (20%), sepsis (17%), and atrial fibrillation (16%), with 40% of patients having more than one predisposing condition [3]. Hakoshima et al. reported a smaller, older cohort (n = 18; mean age, 78 years) in which cancer (33.3%), atrial fibrillation (22.2%), and infection (22.2%) were the leading associated conditions, with one-third in-hospital mortality; their accompanying review of 466 case reports (1975–2021) further highlighted a marked recent rise in infection-related splenic infarction, particularly COVID-19, and identified elevated LDH and blood urea nitrogen as potential prognostic markers [4].

The predominance of hematological disorders in our cohort may reflect the referral pattern of our tertiary-care center, where patients with hematological malignancies and myeloproliferative neoplasms are frequently evaluated. In addition, a substantial proportion of patients (23.9%) remained idiopathic despite available investigations. Similar rates of unexplained splenic infarction have been reported previously and may be attributable to occult malignancy, undiagnosed thrombophilic conditions, transient embolic events, or unidentified prothrombotic states [14, 17]. Notably, infectious causes such as COVID-19 and Mycoplasma pneumoniae, which have increasingly been recognized as precipitants of splenic infarction, were not systematically screened for in our cohort and may account for a proportion of the idiopathic cases [7, 8].

The spleen is particularly vulnerable to ischemic injury because of its terminal arterial circulation and limited collateral blood supply. Consequently, embolic or thrombotic events affecting the splenic artery or its segmental branches may readily result in tissue infarction. This unique vascular anatomy may explain why a wide spectrum of systemic disorders, including hematological, cardiovascular, infectious, and malignant diseases, can ultimately manifest as splenic infarction [17, 18].

The association between hematological disorders and splenic infarction deserves particular attention. Myeloproliferative neoplasms, leukemias, and other hematologic diseases may predispose patients to arterial and venous thrombosis through multiple mechanisms, including hyperviscosity, platelet activation, endothelial dysfunction, and abnormal coagulation pathways [17, 18]. In our cohort, JAK2 mutation analysis was performed in 16 patients with hematological disorders, and four patients were found to be positive. JAK2 mutations are recognized risk factors for thrombotic complications and have been strongly associated with myeloproliferative neoplasms [9, 19]. Therefore, molecular evaluation should be considered in selected patients presenting with splenic infarction and suspected hematological disease.

Malignancy-related splenic infarction is another clinically important entity. Previous studies have demonstrated that malignancies may contribute to splenic infarction through cancer-associated hypercoagulability, vascular invasion, and systemic inflammatory responses [20, 21]. In our cohort, several patients had pancreatic cancer and other malignancies, supporting the concept that splenic infarction may occasionally represent a manifestation of an underlying neoplastic process. Therefore, clinicians should maintain a high index of suspicion for occult malignancy, particularly in patients with no apparent alternative etiology.

Laboratory findings in our study demonstrated frequent leukocytosis, anemia, thrombocytopenia, and elevated LDH levels. Elevated LDH has been repeatedly reported as a common laboratory abnormality in splenic infarction and reflects tissue ischemia and cellular necrosis [4, 22]. Similarly, leukocytosis and elevated inflammatory markers may result from both tissue injury and associated systemic inflammatory responses. Although these laboratory findings are nonspecific, they may support the diagnosis when interpreted in conjunction with clinical and radiological findings.

Radiologically, contrast-enhanced abdominal CT established the diagnosis in all patients and proved to be the most reliable imaging modality. Characteristic wedge-shaped hypodense lesions were identified consistently, confirming previous reports regarding the diagnostic value of CT imaging [12, 22]. In contrast, ultrasonography detected splenic infarction in only 29.9% of cases. While ultrasonography is often used as an initial imaging modality because of its accessibility and low cost, its limited sensitivity may lead to missed diagnoses, particularly in early-stage infarction. Our findings further support the routine use of contrast-enhanced CT when splenic infarction is clinically suspected despite nondiagnostic ultrasonographic findings.

Regarding treatment, conservative management was sufficient in the majority of patients (89.6%). These findings are in agreement with previous reports indicating that most cases of splenic infarction can be managed successfully with supportive treatment and management of the underlying cause [12, 22]. Nevertheless, surgical intervention remains necessary in selected patients. In our study, splenectomy was performed in seven patients due to splenic rupture, hemorrhagic infarction, or splenic abscess formation. These complications highlight the importance of close clinical monitoring and individualized treatment strategies.

In-hospital mortality occurred in four patients, all of whom had severe underlying systemic illnesses, including malignancy and sepsis. This finding emphasizes that mortality in splenic infarction is frequently related to the underlying disease rather than the infarction itself. Accordingly, identifying and treating the primary etiology remains a crucial component of patient management.

The strengths of this study include the comprehensive evaluation of clinical, laboratory, radiological, etiological, and outcome data in patients with splenic infarction over a 10-year period at a tertiary referral center. Furthermore, the study provides regional epidemiological data from southeastern Turkey and contributes to the limited literature regarding the clinical spectrum and etiological distribution of splenic infarction in this population. In addition, the diagnosis was confirmed by contrast-enhanced CT in all patients, increasing the reliability of the findings.

Several limitations should be acknowledged. First, the retrospective single-center design may have resulted in incomplete documentation of certain clinical and laboratory variables and may limit the generalizability of the findings. Second, detailed radiological characteristics, including infarct size, extent of splenic involvement, lesion distribution, and the presence of splenic artery thrombosis, were not consistently available, precluding further analysis of their relationship with treatment decisions and clinical outcomes. Third, detailed information regarding medical therapies and long-term follow-up outcomes, including recurrence and readmission, was unavailable.

In addition, because of the retrospective design, the temporal relationship between the diagnosis of splenic infarction and that of the underlying etiological condition (hematological, cardiovascular, or other systemic disease) could not be reliably reconstructed from the available medical records; consequently, we were unable to determine what proportion of cases represented a pre-existing diagnosis versus a new diagnosis first identified during the work-up for splenic infarction.

Finally, comparative analyses between etiological subgroups and the identification of predictors of mortality or surgical intervention could not be performed because of limited subgroup-specific data and the relatively small number of outcome events. Future multicenter prospective studies are needed to better define prognostic factors and optimize management strategies in patients with splenic infarction.

Conclusions

Taken together, these findings carry practical implications for clinical care. Patients with splenic infarction lacking an evident cardioembolic source warrant thorough hematologic evaluation, including JAK2 mutation testing when a myeloproliferative disorder is suspected. Given the limited sensitivity of ultrasonography, contrast-enhanced CT should be pursued whenever splenic infarction is clinically suspected, even with a negative ultrasonographic examination. As most patients were managed successfully with conservative treatment, an initial conservative strategy with close monitoring for complications warranting splenectomy appears reasonable.

Splenic infarction is an uncommon but clinically important condition that should be considered in patients presenting with unexplained abdominal pain, particularly in the presence of hematological, cardiovascular, or systemic diseases associated with thrombotic risk. In our cohort, hematological disorders represented the most common underlying etiology, whereas nearly one-quarter of patients remained idiopathic despite extensive evaluation. Contrast-enhanced abdominal CT was the most reliable diagnostic modality, while ultrasonography demonstrated limited sensitivity. Conservative management was effective in most patients; however, splenic rupture, hemorrhagic infarction, and splenic abscess formation may necessitate surgical intervention. Early recognition, prompt etiological investigation, and appropriate management of the underlying disease are essential to improve clinical outcomes and prevent complications.

Author contributions

Conceptualization, U.K. and B.E.; methodology, R.Y. and Y.U.; formal analysis, F.Y.O.; investigation, B.E. and M.K.; resources, U.K. and B.E. and R.Y.; data curation, R.Y. and Y.U.; writing-original draft preparation, U.K.; writing review and editing, U.K. and B.E. and F.Y.O. and R.Y. and Y.U. and M.K.; visualization, U.K.; supervision, B.E.; project administration R.Y. All authors read and approved the final manuscript.

Funding

This research received no external funding.

Data availability

The datasets generated and/or analyzed during the current study are not publicly available due to patient privacy and institutional restrictions but are available from the corresponding author on reasonable request.

Declarations

Ethics approval and consent to participate

The study was approved by the Clinical Research Ethics Committee of Dicle University Medical Faculty (Approval No: 157; May 17, 2023). Due to the retrospective design of the study and the use of anonymized medical records, the requirement for informed consent was waived by the Ethics Committee of Dicle University Faculty of Medicine. All procedures were conducted in accordance with the ethical standards of institutional and national research committees and the Declaration of Helsinki (1964).

Consent for publication

Not applicable.

Competing interests

The authors declare no competing interests.