Splenic Artery Aneurysm Associated with Myelofibrosis Managed by Coil Embolization

Abstract

Myelofibrosis (MF) is a myeloproliferative neoplasm frequently complicated by splenomegaly, with vascular abnormalities, such as splenic artery aneurysm (SAA), rarely reported. We herein report a 74-year-old woman with secondary MF harboring a JAK2 V617F mutation who developed SAA requiring intervention because of its potential risk of rupture. Ruxolitinib therapy markedly reduced splenomegaly and improved constitutional symptoms, thereby optimizing hemodynamic conditions and overall status for safe spleen-preserving coil embolization. This case highlights the potential relationship between MF and aneurysm formation while demonstrating that concomitant Janus kinase inhibitor therapy may facilitate safe endovascular treatment in select patients.

Introduction

Myelofibrosis (MF) is a clonal myeloproliferative neoplasm characterized by bone marrow fibrosis, ineffective hematopoiesis, and extramedullary hematopoiesis, leading to progressive splenomegaly and systemic symptoms (1). Driver mutations, such as JAK2, CALR, and MPL, play a central role in disease pathogenesis, and inflammatory cytokines derived from megakaryocytes and monocytes contribute to fibrosis and vascular complications (2). Splenomegaly is a hallmark feature of MF that causes abdominal discomfort and induces non-cirrhotic portal hypertension, which predisposes patients to vascular abnormalities (3-5). Ruxolitinib, a Janus kinase (JAK) 1/2 inhibitor, has become the standard of care for symptomatic MF, effectively reducing splenomegaly and constitutional symptoms (6).

Although splenic artery aneurysm (SAA) is the most common visceral artery aneurysm and the third-most common abdominal aneurysm, it remains rare, with a prevalence of ＜1% in the general population (7). Although often asymptomatic, SAA carries a substantial risk of rupture, particularly when it is larger than 3 cm, and rupture is frequently life-threatening (8). Historically, open surgery and splenectomy have been common treatment strategies; however, recent guidelines recommend endovascular approaches, including coil embolization, as first-line treatment whenever anatomically feasible (8). The coexistence of MF and SAA is extremely rare, and whether a direct association exists between these two conditions remains uncertain. Prolonged splenomegaly with portal hypertension may contribute to aneurysm formation. Furthermore, recent studies have suggested a possible association between the JAK2 V617F mutation and aneurysm development (9,10), although the evidence remains limited and inconsistent.

We herein report a rare case of MF complicated by SAA that was successfully treated with endovascular coil embolization. The patient continued ruxolitinib therapy throughout the course of management, which allowed sustained control of splenomegaly and facilitated spleen preservation. This case highlights the importance of recognizing vascular complications in MF and demonstrates that JAK2 inhibitor therapy can be safely maintained, even in the presence of SAA.

Case Report

A 74-year-old woman was referred to our department for the reevaluation of secondary MF and assessment of eligibility for ruxolitinib therapy. Twenty-one years earlier, she presented with abdominal distension and was diagnosed with essential thrombocythemia (ET) with features of secondary MF based on marked thrombocytosis and bone marrow morphology. The patient was initially treated with hydroxycarbamide for cyto-reduction. Six years prior to the current presentation, progressive anemia and marked splenomegaly, prompting her transfer to our institution.

On admission, a physical examination revealed splenomegaly, with the spleen palpable 8 cm below the left costal margin, although the abdomen was soft and nontender. She reported pronounced fatigue and early satiety, attributable to splenomegaly. Her medical history included hypertension, dyslipidemia, and transient ischemic attacks. There was no family history of hematologic or vascular disease, including aneurysms.

Laboratory studies revealed leukocytosis and thrombocytosis, and the hemoglobin level was preserved. A peripheral blood smear revealed 1% blasts. The liver and renal function test results were within normal limits, and C-reactive protein levels were not elevated (Table). Genetic testing revealed a JAK2 V617F mutation. Bone marrow biopsy results confirmed the diagnosis of secondary MF, which was classified as intermediate-1 risk according to the Dynamic International Prognostic Scoring System (11), based on peripheral blood blasts. Hydroxycarbamide was discontinued, and ruxolitinib was initiated.

Table.

Laboratory Data at the Initiation of Ruxolitinib and at the Time of Coil Embolization.

	Initiation of Ruxolitinib	Time of Coil Embolization			Initiation of Ruxolitinib	Time of Coil Embolization
WBC	14.8	2.7	×103/µL	TP	7.1	7.2	g/dL
Stab	4.2	2	%	T-Bil	0.4	0.5	mg/dL
Seg	83.6	79	%	AST	18	33	U/L
Lym	3.4	11.5	%	ALT	11	28	U/L
Mono	2.6	5	%	LD	563	359	U/L
Eosino	1.4	0	%	ALP	225	241	U/L
Baso	2	2	%	γ-GT	31	33	U/L
Myelo	1.6	0.5	%	Na	141	142	mmol/L
Blast	1	0	%	K	4.4	4.6	mmol/L
RBC	3.76	3.61	×106/µL	Cl	106	106	mmol/L
HGB	12.4	11.5	g/dL	BUN	20	20	mg/dL
HCT	37.4	34.5	%	Creatinine	0.84	1.03	mg/dL
MCV	99.5	95.6	fL	eGFR	53.1	45.2	mL/min/1.73 m2
MCH	33	31.9	pg	CRP	0.05	0.02	mg/dL
MCHC	33.2	33.3	%
PLT	578	216	×103/µL

ALP: alkaline phosphatase, ALT: alanine aminotransferase, AST: aspartate aminotransferase, Baso: basophil, BUN: blood urea nitrogen, Cl: chloride, CRP: C-reactive protein, Eosino: eosinophil, eGFR: estimated glomerular filtration rate, γ-GT: gamma- glutamyl transpeptidase, HCT: hematocrit, HGB: hemoglobin, K: potassium, LD: lactate dehydrogenase, Lym: lymphocyte, MCH: mean corpuscular hemoglobin, MCHC: mean corpuscular hemoglobin concentration, MCV: mean corpuscular volume, Mono: monocyte, Myelo: myelocyte, Na: sodium, PLT: platelet, RBC: red blood cell, Seg: segmented neutrophil, Stab: stab neutrophil, T-Bil: total bilirubin, TP: total protein, WBC: white blood cell

Baseline computed tomography demonstrated massive splenomegaly and an SAA measuring 27×21 mm (Figure A), accompanied by dilatation of the splenic and portal veins and increased portal venous pressure. Two weeks after starting ruxolitinib treatment, the spleen size decreased to 3 cm below the costal margin and the platelet count normalized. After one month, the spleen was no longer palpable and constitutional symptoms improved substantially (Figure B). Subsequently, splenomegaly remained stable with continued ruxolitinib therapy. During the follow-up, the size of the splenic artery aneurysm remained stable. Given the risk of rupture, endovascular coil embolization was performed (Figure C, D). The procedure was technically successful, and the postoperative course was uneventful. Consequently, the patient maintained a stable disease profile with a sustained reduction in splenomegaly and no complications, such as splenic infarction or thrombosis.

Figure.

Radiological findings of the SAA and its endovascular management. (A) Baseline abdominal CT showing massive splenomegaly and an SAA (arrow). (B) Follow-up CT one year later showing marked reduction of splenomegaly with stable size of the SAA (arrow). (C) Digital subtraction angiography revealing the SAA. (D) Post-embolization angiography confirming successful coil deployment with complete occlusion of the aneurysm sac. CT: computed tomography, SSA: splenic artery aneurysm

Discussion

SAA is an uncommon vascular complication and its coexistence with MF has rarely been reported. This report describes a patient with MF and long-standing splenomegaly who developed SAA. Notably, ruxolitinib therapy led to a marked reduction in splenomegaly and an improvement in constitutional symptoms, which together facilitated a return to a stable condition for safe spleen-preserving coil embolization. To our knowledge, published reports on SAA in MF are very limited, and detailed descriptions of its management remain scarce. Similar cases have also been described in other myeloproliferative neoplasms, including polycythemia vera (12), although such reports remain uncommon within these disorders. Our case shows that concomitant JAK inhibitor therapy may facilitate safe endovascular treatment in selected patients.

MF is characterized by progressive bone marrow fibrosis and extramedullary hematopoiesis, often leading to marked splenomegaly. Prolonged splenomegaly has been associated with non-cirrhotic portal hypertension, which is a recognized risk factor for the development of visceral aneurysms (3-5). Portal hypertension occurs in approximately 10% of patients with MF, which may account for the vascular remodeling that predisposes them to aneurysm formation (13). In our case, long-standing splenomegaly likely contributed to the increased portal venous pressure and the subsequent development of SAA.

The prevalence of SAA in the general population is less than 1% (7), with conventional risk factors including advanced age, hypertension, atherosclerosis, and smoking (7,8). Our patient was an older adult with hypertension but lacked a history of smoking or a family history of aneurysms. Thus, it is reasonable to assume that MF-related splenomegaly and portal hypertension played a partial role in the development of SAA in the present case.

The JAK2 V617F mutation, the most common driver mutation in myeloproliferative neoplasms, is implicated in aneurysm formation. Yokokawa et al. demonstrated that 23% of patients with a JAK2 V617F mutation had concomitant aortic aneurysms, markedly exceeding the prevalence in the general population, and that the transplantation of JAK2 V617F-mutated hematopoietic cells promoted aneurysm formation in murine models through elastic fiber disruption, matrix metalloproteinase activation, and inflammatory cell infiltration. Notably, ruxolitinib reduced aneurysm development in this model (9). Complementing these findings, a large population-based cardiovascular screening study revealed that JAK2 V617F allele burden was associated with an increased risk of ascending aortic aneurysms in a dose-dependent manner, whereas no consistent association was observed for abdominal or visceral aneurysms after adjusting for confounders (10). More recently, somatic JAK2 V617F variants acquired later in life were found to be associated with thoracic aortic aneurysms, further supporting the potential role of JAK2 V617F in aneurysm development (14). Therefore, although the role of JAK2 V617F in aneurysm formation remains uncertain, its contribution, particularly through inflammatory and proteolytic mechanisms, cannot be entirely excluded. Furthermore, regression of the established SAA following reduction in JAK2 V617F allele burden has not been demonstrated, which may explain the stable aneurysm size in our patient.

Management of SAA depends on aneurysm size and clinical context. Current guidelines recommend intervention for aneurysms larger than 3 cm, with endovascular approaches such as coil embolization, which is considered the first-line treatment whenever anatomically feasible (8). Although the aneurysm in our patient was ＜3 cm, we proceeded with endovascular treatment considering the persistent symptoms related to massive splenomegaly, underlying hemodynamic burden of myelofibrosis, and favorable anatomy allowing for safe, spleen-preserving embolization. Splenectomy has traditionally been considered in cases of massive splenomegaly or hilar aneurysms, but in patients with MF, it carries substantial risks, including perioperative bleeding, infection, portal vein thrombosis, increased leukemic transformation, and reduced survival (15,16). Thus, avoiding splenectomy is clinically important. In this case, coil embolization was successfully performed without complications, underscoring its safety and efficacy even in the context of MF.

An important aspect of this case is that ruxolitinib therapy substantially reduced splenomegaly and improved constitutional symptoms before intervention. In myelofibrosis, massive splenomegaly can complicate invasive procedures by increasing splenic blood flow, predisposing patients to extensive infarction, infection, and hemodynamic instability after embolization. Furthermore, improvements in the overall condition and hematologic parameters with ruxolitinib may contribute to better tolerance of the procedure. In our patient, reduction in spleen size and improvement in symptoms likely facilitated safe and spleen-preserving coil embolization.

Several limitations associated with the present case report warrant mention. First, as a single case study, our findings have inherent limitations in establishing definitive causal relationships between MF, the JAK2 V617F mutation, and SAA development. Although our patient had long-standing splenomegaly and portal hypertension that likely contributed to aneurysm formation, we cannot definitively exclude other contributing factors or establish a direct mechanistic link. Second, the temporal relationship between ruxolitinib initiation and SAA stability during treatment may be coincidental rather than causally related because aneurysm growth rates vary significantly among individuals. Finally, the generalizability of our treatment approach is limited by the patient's unique clinical characteristics, including the specific aneurysm anatomy and intermediate-1 risk MF with a preserved performance status. The safety and efficacy of JAK inhibitor therapy during endovascular procedures may not be applicable to all patients with MF, particularly to those with advanced disease or marked cytopenia. Larger case series and longer follow-up studies are needed to better define the relationship between myeloproliferative neoplasms and vascular complications and to determine optimal treatment strategies for this rare clinical scenario.

In conclusion, although splenic artery aneurysms in myelofibrosis are exceedingly rare, they carry a significant risk of rupture, for which coil embolization remains the first-line treatment, particularly when the aneurysm size is large. Our case suggests that the concomitant use of ruxolitinib may facilitate safe and spleen-preserving management by controlling the splenomegaly.

Written informed consent for publication of this case was obtained from the patient.

The authors state that they have no Conflict of Interest (COI).