Sequential Splenic and Cerebral Infarctions Revealing Triple-Positive Antiphospholipid Antibodies in an Adolescent with Systemic Lupus Erythematosus: A Case Report

Introduction

Systemic lupus erythematosus is a chronic multisystem autoimmune disease characterised by immune dysregulation, autoantibody production and immune-mediated tissue injury. Childhood-onset SLE may have more severe organ involvement than adult-onset disease.[1-4] Antiphospholipid antibodies occur in a substantial proportion of patients with SLE and are associated with arterial and venous thrombosis. Cerebral arterial events are common, whereas visceral events such as splenic infarction are uncommon and may present with acute abdominal pain.[5–7] Autoimmune haemolytic anaemia is a recognised haematological manifestation of SLE, and aPL positivity has been associated with a higher prevalence of haemolytic anaemia in SLE.[8,9] We report an adolescent with SLE who developed sequential splenic and cerebral arterial infarctions during the same illness, with a triple-positive aPL profile at the time of the thrombotic events. Follow-up aPL testing in 2024 remained positive for anticardiolipin and anti-β2-glycoprotein I antibodies. The case highlights the diagnostic significance of visceral infarction, rapid involvement of multiple arterial territories, and the importance of considering aPL-associated thrombosis alongside active lupus.[10]

Case Presentation

2.1 Patient Information and First Admission

A previously well 14-year-old female presented with a one-month history of fever. She had been evaluated and diagnosed with SLE based on a positive antinuclear antibody (ANA 3+), anti-dsDNA antibody and low C3 and C4 complement levels. She had been started on corticosteroids and hydroxychloroquine, but treatment adherence was poor.

She was admitted to our institution with persistent fever unrelieved by antipyretics. On examination, blood pressure was 100/70 mmHg and pulse rate was 92 beats/min. Discoid lupus lesions were present over the chest and bilateral upper limbs, together with oral mucosal ulcers (Figure 1). The remainder of the systemic examination was unremarkable. Taken together, the mucocutaneous findings, positive ANA and anti-dsDNA antibodies and low complement levels satisfied both the SLICC[11] and the 2019 EULAR/ACR[12] classification criteria for SLE.

Initial investigations revealed a haemoglobin of 7.9 g/dL, total leucocyte count of 5,200/mm³ (neutrophils 89%, lymphocytes 7%) and a platelet count of 113,000/mm³. The erythrocyte sedimentation rate was 150 mm/hour and C-reactive protein was 1.2 mg/dL; renal function was normal. The extended ANA profile was positive for anti-dsDNA, anti-histone, anti-nucleosome and anti-mitochondrial (AMA-M2) antibodies. Blood culture grew Klebsiella pneumoniae, and urine culture demonstrated a non-lactose-fermenting Gram-negative organism, consistent with concurrent infection in an immunosuppressed host. The SLEDAI-2K score[13] at this presentation was 6, accounting for rash, mucosal ulcers, fever and thrombocytopenia.

She was treated with prednisolone 40 mg/day and intravenous antibiotics guided by culture sensitivity. A peripheral blood smear showed microcytic hypochromic anaemia without an overt haemolytic picture. She improved symptomatically, requested discharge, and was discharged on corticosteroids with advice for close outpatient follow-up.

2.2 Second Admission: Acute Abdominal Pain

Two weeks after discharge, she was readmitted with one day of diffuse abdominal pain and vomiting, maximal in the left hypochondrium. Discoid lesions and an oral ulcer persisted, and non-scarring alopecia was newly noted.

Blood pressure was 100/80 mmHg and pulse rate 97 beats/min. The abdomen was soft with diffuse tenderness, greatest in the left hypochondrium, without guarding, rigidity or organomegaly; the remainder of the examination was unremarkable.

Haemoglobin was 8.2 g/dL, platelet count 49,000/mm³, total leukocyte count 5,600/mm³ and reticulocyte count 3.9%; urine protein was 2+. The platelet count subsequently recovered to 130,000/mm³ and then 250,000/mm³.

Acute abdomen and mesenteric ischaemia were initially considered. On day 2, contrast-enhanced CT of the abdomen demonstrated a peripheral splenic infarct without mesenteric ischaemia or thrombosis (Figure 2). She was transferred to the intensive care unit, received intravenous methylprednisolone 500 mg/day for 3 days, and was started on unfractionated heparin 5,000 IU IV every 6 hours.

2.3 Development of Acute Cerebral Infarction

On day 3, one day after the splenic infarct was identified, right upper-limb weakness with reduced hand grip was recognized on awakening, consistent with a wake-up acute ischaemic stroke. The exact onset time was unknown. Brain CT demonstrated an acute infarct involving the left caudate nucleus and anterior limb of the internal capsule (Figure 3). Antiplatelet therapy was initiated. Intravenous thrombolysis was not appropriate because of severe thrombocytopenia and recent heparin exposure with anticoagulant effect.

Because infarctions occurred in two arterial territories within 1 day, an underlying thrombotic disorder was investigated. The aPL profile at the time of the thrombotic episode was triple-positive for anticardiolipin antibodies, lupus anticoagulant and anti-β2-glycoprotein I antibodies. The direct antiglobulin test was positive, and SLEDAI-2K increased to 16. She was subsequently followed, and repeat aPL testing in June 2024 again demonstrated anticardiolipin and anti-β2-glycoprotein I antibody positivity, while lupus anticoagulant was absent.

The clinical picture was consistent with SLE-associated arterial thrombosis in the setting of triple-positive aPL, with sequential splenic and cerebral infarctions. Coombs-positive anaemia with laboratory features suggestive of autoimmune haemolysis and severe thrombocytopenia occurred concurrently.

Discussion

This case demonstrates the clinical importance of recognizing aPL-associated thrombosis in an adolescent with SLE. The defining feature was the rapid sequence of two objectively demonstrated arterial infarctions in different vascular territories during the same acute illness: splenic infarction followed within approximately 24 hours by cerebral infarction.

3.1 Thrombotic Manifestations

Splenic infarction is an uncommon but important manifestation of arterial thrombosis. In this patient, acute left hypochondrial pain initially raised concern for an acute abdomen and mesenteric ischaemia. Contrast-enhanced CT instead demonstrated a peripheral splenic infarct and excluded mesenteric disease. The abdominal presentation therefore represented the first objective evidence of arterial infarction. In a patient with SLE, particularly when aPL are present, unexplained abdominal pain should prompt consideration of visceral ischaemia and appropriate vascular imaging.[5–7]

The subsequent neurological event established involvement of a second arterial territory. Right upper-limb weakness was recognized on awakening, and brain CT demonstrated an acute infarct involving the left caudate nucleus and anterior limb of the internal capsule. The close temporal sequence of splenic and cerebral infarction, together with the triple-positive aPL profile during the acute illness, strongly supported a systemic thrombotic mechanism.[3,16–18] The major clinical lesson is that visceral infarction may precede a more readily recognized cerebral arterial event. In SLE, acute abdominal pain should not automatically be attributed to gastrointestinal inflammation or infection when the clinical picture suggests vascular disease. Early recognition of splenic infarction may provide an opportunity to investigate aPL-associated thrombosis before additional arterial territories become involved. The neurological deficit and CT findings confirmed an acute cerebral infarction occurring shortly after the splenic event. Because the stroke was recognized on awakening with unknown onset time, and severe thrombocytopenia and recent heparin exposure were present, intravenous thrombolysis was not appropriate in the clinical context.

3.2 Haematological Manifestations

Anaemia and thrombocytopenia accompanied the thrombotic events. The platelet count fell to 49,000/mm³ before recovering to 250,000/mm³ with treatment. The direct antiglobulin test was positive, with reticulocytosis, LDH 509 U/L and indirect bilirubin 1.5 mg/dL, whereas the initial peripheral smear had shown only microcytic hypochromic anaemia without an overt haemolytic picture. Taken together, these findings support Coombs-positive anaemia with laboratory features suggestive of autoimmune haemolysis, rather than unequivocal active autoimmune haemolytic anaemia.[8,9]

3.3 Disease Activity and Treatment Context

3.4 Antiphospholipid Antibodies and Haematological Abnormalities

The coexistence of thrombocytopenia, Coombs-positive anaemia and aPL positivity illustrates the overlapping haematological and thrombotic manifestations that can occur in SLE. Severe thrombocytopenia is particularly challenging when antithrombotic treatment is required, making individualized assessment of thrombosis and bleeding risk essential.[6,7,17]

3.5 Diagnostic and Classification Considerations

The combination of established SLE, objectively confirmed splenic and cerebral arterial infarctions, and triple-positive aPL during the acute illness provides a strong clinical basis for an aPL-associated thrombotic syndrome. Although individual antibody titres from the first assessment are not available for direct comparison, the repeat positive profile obtained more than 12 weeks later (detailed below) supports ongoing aPL positivity, and the overall clinical picture is strongly suggestive of thrombotic APS.

Vascular thrombosis fulfils the clinical component of APS classification when objectively confirmed. Under the revised Sydney framework, laboratory confirmation requires qualifying aPL positivity on two occasions at least 12 weeks apart.[3,12] In this case, a previous aPL assessment on 11 September 2022 was documented as positive, and repeat testing on 8 June 2024 again demonstrated positive anticardiolipin and anti-β2-glycoprotein I antibodies, with lupus anticoagulant absent. The case is therefore best reported as SLE with arterial thrombotic manifestations and aPL positivity, with the clinical picture being strongly suggestive of thrombotic APS.

Conclusion

Sequential splenic and cerebral infarctions represent an important thrombotic presentation of SLE in an adolescent. The rapid progression from abdominal symptoms caused by splenic infarction to cerebral infarction in a second arterial territory highlights the systemic nature of aPL-associated thrombosis. The initial triple-positive aPL profile and subsequent positive aPL testing during follow-up reinforce the importance of recognizing aPL-associated thrombosis. In patients with SLE, unexplained abdominal pain should raise suspicion for visceral arterial ischaemia, particularly when thrombocytopenia and aPL positivity are present. Early recognition of the first infarct, prompt evaluation for additional vascular involvement, and coordinated immunosuppressive and antithrombotic management are central to care.

Declarations

Ethics Statement

Ethical approval was not required for this single-patient case report in accordance with institutional policies.

Consent for publication

Written informed consent was obtained from the patient for publication of this case report and accompanying clinical images. Identifying features have been cropped from the photographs to protect patient anonymity.

Author Contributions

JS and MN contributed to the conceptualization, case report design, literature search, evidence analysis and interpretation, and manuscript drafting. JS, MN, and SS critically reviewed and edited the manuscript, approved the final version, and accepted responsibility for its integrity and accuracy.

Funding

This case report received no specific grant from any funding agency in the public, commercial, or not-for-profit sectors.

Conflict of Interest

The authors declare no conflict of interest.

Publisher’s Note

All claims expressed in this article are solely those of the author and do not necessarily represent those of the author’s affiliated organization, the publisher, the editors, or the reviewers. Any product evaluated in this article, or claim made by its manufacturer, is neither guaranteed nor endorsed by the publisher.

References

1. 1.Aggarwal A, Fernandes TAP, Migowa A, Smith EMD, Hanif M, Webb K, Lewandowski LB. Childhood-Onset Systemic Lupus Erythematosus (cSLE): An International Perspective. Curr Allergy Asthma Rep. 2024;24:559–569. doi: 10.1007/s11882-024-01169-3.
2. 2.Charras A, Smith E, Hedrich CM. Systemic Lupus Erythematosus in Children and Young People. Curr Rheumatol Rep. 2021;23:20. doi: 10.1007/s11926-021-00985-0.
3. 3.Levy DM, Kamphuis S. Systemic lupus erythematosus in children and adolescents. Pediatr Clin North Am. 2012;59(2):345–364. doi: 10.1016/j.pcl.2012.03.007.
4. 4.Silva CA, Avcin T, Brunner HI. Taxonomy for systemic lupus erythematosus with onset before adulthood. Arthritis Care Res (Hoboken). 2012;64(12):1787–1793. doi: 10.1002/acr.21757.
5. 5.Ünlü O, Zuily S, Erkan D. The clinical significance of antiphospholipid antibodies in systemic lupus erythematosus. Eur J Rheumatol. 2016;3(2):75–84. doi: 10.5152/eurjrheum.2015.0085.
6. 6.Hadfield MJ, Thumar J. Antiphospholipid syndrome presenting with splenic infarct. J Clin Rheumatol. 2021;27(1):e19. doi: 10.1097/RHU.0000000000001207.
7. 7.Ashour A, Faisal M, Ibrahim E, Al-Madani M. Splenic infarcts in a lady with systemic lupus erythematosus and negative antiphospholipid antibodies—A rare case report. Clin Case Rep. 2023;11(3):e7092. doi: 10.1002/ccr3.7092.
8. 8.Bernardoff I, Picard A, Loiseau P, et al. Antiphospholipid antibodies and the risk of autoimmune hemolytic anemia in patients with systemic lupus erythematosus: a systematic review and meta-analysis. Autoimmun Rev. 2022;21(1):102913. doi: 10.1016/j.autrev.2021.102913.
9. 9.Ames PRJ, Merashli M, Bucci T, et al. Antiphospholipid antibodies and autoimmune haemolytic anaemia: a systematic review and meta-analysis. Int J Mol Sci. 2020;21(11):4120. doi: 10.3390/ijms21114120.
10. 10.Riley DS, Barber MS, Kienle GS, et al. CARE guidelines for case reports: explanation and elaboration document. J Clin Epidemiol. 2017;89:218–235. doi: 10.1016/j.jclinepi.2017.04.026.
11. 11.Petri M, Orbai AM, Alarcón GS, et al. Derivation and validation of the Systemic Lupus International Collaborating Clinics classification criteria for systemic lupus erythematosus. Arthritis Rheum. 2012;64(8):2677–2686. doi: 10.1002/art.34473.
12. 12.Aringer M, Costenbader K, Daikh D, et al. 2019 European League Against Rheumatism/American College of Rheumatology classification criteria for systemic lupus erythematosus. Ann Rheum Dis. 2019;78(9):1151–1159. doi: 10.1136/annrheumdis-2018-214819.
13. 13.Gladman DD, Ibañez D, Urowitz MB. Systemic lupus erythematosus disease activity index 2000. J Rheumatol. 2002;29(2):288–291.
14. 14.Miyakis S, Lockshin MD, Atsumi T, et al. International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS). J Thromb Haemost. 2006;4(2):295–306. doi: 10.1111/j.1538-7836.2006.01753.x.
15. 15.Barbhaiya M, Zuily S, Naden R, et al. 2023 ACR/EULAR antiphospholipid syndrome classification criteria. Arthritis Rheumatol. 2023;75(10):1687–1702. doi: 10.1002/art.42624.
16. 16.Levine JS, Branch DW, Rauch J. The antiphospholipid syndrome. N Engl J Med. 2002;346(10):752–763. doi: 10.1056/NEJMra002974.
17. 17.Ruiz-Irastorza G, Crowther M, Branch W, Khamashta MA. Antiphospholipid syndrome. Lancet. 2010;376(9751):1498–1509. doi: 10.1016/S0140-6736(10)60709-X.
18. 18.Cervera R, Piette JC, Font J, et al. Antiphospholipid syndrome: clinical and immunologic manifestations and patterns of disease expression in a cohort of 1,000 patients. Arthritis Rheum. 2002;46(4):1019–1027. doi: 10.1002/art.10187.
19. 19.Uthman I, Godeau B, Taher A, Khamashta M. The hematologic manifestations of the antiphospholipid syndrome. Blood Rev. 2008;22(4):187–194. doi: 10.1016/j.blre.2008.03.005.
20. 20.Groot N, de Graeff N, Avcin T, et al. European evidence-based recommendations for the diagnosis and treatment of childhood-onset systemic lupus erythematosus: the SHARE initiative. Ann Rheum Dis. 2017;76(11):1788–1796. doi: 10.1136/annrheumdis-2016-210960.
21. 21.Tektonidou MG, Andreoli L, Limper M, Amoura Z, Cervera R, Costedoat-Chalumeau N, et al. EULAR recommendations for the management of antiphospholipid syndrome in adults. Ann Rheum Dis. 2019;78(10):1296–1304. doi: 10.1136/annrheumdis-2019-215213.
22. 22.Prabhakaran S, Gonzalez NR, Zachrison K, et al. 2026 Guideline for the Early Management of Patients With Acute Ischemic Stroke: A Guideline From the American Heart Association/American Stroke Association. Stroke. 2026;57(8):e316–e436. doi: 10.1161/STR.0000000000000513.