Child Kidney Dis.  2024 Oct;28(3):131-137. 10.3339/ckd.24.021.

Lupus anticoagulant-hypoprothrombinemia syndrome with lupus nephritis in a girl misdiagnosed with immunoglobulin A nephropathy: a case report

• Lee CH
• Ahn YH
• Kang HG
• Kim JH

• KMID: 2560483
• DOI: http://doi.org/10.3339/ckd.24.021

Abstract

Distinguishing lupus nephritis (LN) from other glomerulopathies, such as immunoglobulin A nephropathy (IgAN), poses a diagnostic challenge owing to overlapping clinical and histopathologic findings. Lupus anticoagulant-hypoprothrombinemia syndrome (LAHPS) is a rare and potentially fatal disorder characterized by the presence of lupus anticoagulant and acquired factor II deficiency. We report a pediatric case of LN with LAHPS, which was initially diagnosed as IgAN. An 8-year-old girl presented with gross hematuria with nephrotic syndrome. Based on the kidney biopsy results, treatment for IgAN with membranoproliferative pattern was initiated. Two months later, she developed left upper extremity swelling with multiple vein thromboses requiring anticoagulation; treatment led to remission, allowing discontinuation of immunosuppressants within 8 months. Gross hematuria recurred 10 months later and was accompanied by hypocomplementemia; positive antinuclear, anti-double stranded DNA, and triple antiphospholipid antibodies; and factor II deficiency, prompting revision of the diagnosis to LN and LAHPS. Initial delay in LN diagnosis was attributed to the patient’s young age, nonspecific symptoms, and inconclusive laboratory and histopathological findings. Immunosuppressive therapy for IgAN partially improved LN, further complicating the diagnosis. This case emphasized the importance of clinical suspicion; integrating clinical, serological, and histopathological data; and considering LAHPS in differential diagnosis of glomerulonephritis with coagulopathy.

Keyword

Glomerulonephritis, membranoproliferative; Hypoprothrombinemias; IgA nephropathy; Lupus coagulation inhibitor; Lupus nephritis; Case reports

Figure

• 

  Fig. 1. Kidney biopsy findings. (A, B) Light microscopy shows diffuse moderate hypercellularity of mesangial and endothelial cells and increased mesangial matrix, which shows a tram-track pattern (A: hematoxylin and eosin stain, ×200; B: methenamine silver Periodic acid-Schiff stain, ×400). (C-G) Immunofluorescence staining shows IgA(3+), IgG(2+), IgM(1+), C3(2+), and C1q(2+) (C, F, G: ×200; D, E: ×400). (H, I) Electron microscopy shows electron-dense deposits (+), moderate mesangial deposits, moderate subendothelial deposits, and marked focal effacement of foot processes. The thickness of the glomerular basement membrane is within the normal limits (H, I).

• 

  Fig. 2. Computed tomography angiography with three-dimensional upper extremity artery and vein (with contrast). There are multiple thromboses in the left axillary (A), subclavian (B), and brachial (C) veins (marked by a yellow circle and a white arrow).

Reference

References

1. Mazodier K, Arnaud L, Mathian A, Costedoat-Chalumeau N, Haroche J, Frances C, et al. Lupus anticoagulant-hypoprothrombinemia syndrome: report of 8 cases and review of the literature. Medicine (Baltimore). 2012; 91:251–60.

2. Acedo N, Alonso A, Feijoo ES, Garcia C, Ortiz AM, Alegre A. Lupus anticoagulant hypoprothrombinemia syndrome: a case report. Clin Case Rep. 2023; 11:e7071.

3. Kim JS, Kim MJ, Bae EY, Jeong DC. Pulmonary hemorrhage in pediatric lupus nticoagulant hypoprothrombinemia syndrome. Korean J Pediatr. 2014; 57:202–5.

4. Sarker T, Roy S, Hollon W, Rajpurkar M. Lupus anticoagulant acquired hypoprothrombinemia syndrome in childhood: two distinct patterns and review of the literature. Haemophilia. 2015; 21:754–60.

5. Schreiber K, Sciascia S, de Groot PG, Devreese K, Jacobsen S, Ruiz-Irastorza G, et al. Antiphospholipid syndrome. Nat Rev Dis Primers. 2018; 4:17103.

6. Thakral A, Klein-Gitelman MS. An update on treatment and management of pediatric systemic lupus erythematosus. Rheumatol Ther. 2016; 3:209–19.

7. Pattrapornpisut P, Avila-Casado C, Reich HN. IgA nephropathy: core curriculum 2021. Am J Kidney Dis. 2021; 78:429–41.

8. Anders HJ, Saxena R, Zhao MH, Parodis I, Salmon JE, Mohan C. Lupus nephritis. Nat Rev Dis Primers. 2020; 6:7.

9. Weening JJ, D’Agati VD, Schwartz MM, Seshan SV, Alpers CE, Appel GB, et al. The classification of glomerulonephritis in systemic lupus erythematosus revisited. Kidney Int. 2004; 65:521–30.

10. Bajaj SP, Rapaport SI, Fierer DS, Herbst KD, Schwartz DB. A mechanism for the hypoprothrombinemia of the acquired hypoprothrombinemia-lupus anticoagulant syndrome. Blood. 1983; 61:684–92.

11. Peralta-Amaro AL, Triana-Gonzalez S, Manzo-Carballo MF, Vera Lastra OL, Garcia-Chavez J, Lucas-Hernandez A. Antiphospholipid syndrome and lupus anticoagulant-hypoprothrombinemia. QJM. 2023; 116:308–9.

12. Lee YA. New classification criteria for systemic lupus erythematosus. Korean J Med. 2020; 95:151–61.

13. Levin A. Management of membranoproliferative glomerulonephritis: evidence-based recommendations. Kidney Int Suppl. 1999; 70:S41–6.

14. Andeen NK, Jefferson JA, Akilesh S, Alpers CE, Bissonnette ML, Finn LS, et al. IgA-dominant glomerulonephritis with a membranoproliferative pattern of injury. Hum Pathol. 2018; 81:272–80.

15. Iitaka K, Yamamoto A, Ogawa N, Sekine T, Tamai S, Motoyama O. IgA-associated glomerulonephritis with membranoproliferative glomerulonephritis-like pattern in two children. Clin Exp Nephrol. 2003; 7:284–9.