# The Prevalence of Anemia and Diagnostic Usefulness of Ferritin and Hepcidin in Antiphospholipid Syndrome and Systemic Lupus Erythematosus Patients

**Authors:** Natasa Stanisavljevic, Ljudmila Stojanovich, Aleksandra Djokovic, Violeta Dopsaj, Neda Milinkovic, Dusica Mrdaković, Olivera Markovic, Marija Zdravkovic, Dragomir Marisavljevic

PMC · DOI: 10.3390/diseases14030101 · 2026-03-11

## TL;DR

This study examines the types of anemia in antiphospholipid syndrome and systemic lupus erythematosus patients, finding that iron deficiency anemia is most common in APS, while ferritin and hepcidin are useful in diagnosing anemia types.

## Contribution

The study introduces the use of hepcidin as a more reliable marker than ferritin for distinguishing anemia types in APS patients.

## Key findings

- Iron deficiency anemia (IDA) was most common in primary APS patients.
- Hepcidin proved more valuable than ferritin in distinguishing anemia types when ferritin levels were inconclusive.
- Inflammatory markers like IL-6 correlated with ferritin and hsCRP but not with hepcidin.

## Abstract

Background: Anemia is common among patients with antiphospholipid syndrome (APS). It can persist alone (primary APS—pAPS) or with another associated disease (secondary APS—sAPS), predominantly systemic lupus erythematosus (SLE). There are no systematic reviews addressing the type of anemia (iron deficiency without anemia—IDWA, iron deficiency—IDA, and anemia of chronic disease—ACD) in these patients. Objectives: This study aimed to assess the type of anemia and to compare the usefulness of common diagnostic anemia parameters and their mutual relations. Methods: A cross-sectional study involving 163 patients was conducted at the University Clinical Center Bezanijska kosa from June 2022 to June 2024, including 79 patients with pAPS, 47 with sAPS and 37 patients diagnosed with SLE. We compared the usefulness of iron metabolism markers (serum iron—Fe; total iron-binding capacity—TIBC; ferritin; hepcidin) in the presence of inflammatory markers such as high-sensitivity (hsCRP) and IL6 in determining the type of anemia. Results: The most common types were IDA (61.9%) and IDWA (64.3%) in pAPS patients. In contrast, ACD was equally distributed across the three groups, with prevalences of 32%, 32%, and 36% (pAPS, sAPS, and SLE, respectively). A higher frequency of thrombosis was significantly associated with a high ferritin level ≥100 (p = 0.017) and high IL6 levels (p = 0.033) as well as fetal losses (p = 0.034 and p = 0.019, respectively). The logistic regression model identified ferritin as the only significant predictor of IDA (p = 0.023). For IDWA, both ferritin (p = 0.017) and hepcidin (p = 0.038) were significant predictors of this type of iron depletion. IL-6 levels were significantly correlated with ferritin and hsCRP levels (p = 0.004 and p = 0.007, respectively). In contrast, hepcidin did not show a statistically significant correlation with inflammatory markers. A total of 40% of patients with IDA had hepcidin levels below 10, and 48% of those with ACD had hepcidin levels above 10 (p = 0.036). Conclusions: It was found that iron deficiency anemia was the most common form in pAPS, while anemia of chronic disease was equally present across all patient groups. Ferritin emerged as an independent marker for identifying iron deficiency anemia in APS patients. Although hepcidin reflects a low-inflammatory state in APS, it proved to be a more valuable tool than ferritin in distinguishing the type of anemia, especially when ferritin levels were inconclusive. Clinical manifestations in APS patients correlated with inflammatory markers. Liver function or any drug used alone or in combination had no impact on anemia type.

## Linked entities

- **Proteins:** ferritin (soma ferritin-like), HAMP (hepcidin antimicrobial peptide), IL6 (interleukin 6)
- **Diseases:** antiphospholipid syndrome (MONDO:0017278), systemic lupus erythematosus (MONDO:0007915), anemia (MONDO:0002280), iron deficiency anemia (MONDO:0001356), anemia of chronic disease (MONDO:0020725)

## Full-text entities

- **Genes:** SLC17A5 (solute carrier family 17 member 5) [NCBI Gene 26503] {aka AST, ISSD, NSD, SD, SIALIN, SIASD}, MTOR (mechanistic target of rapamycin kinase) [NCBI Gene 2475] {aka FRAP, FRAP1, FRAP2, RAFT1, RAPT1, SKS}, HAMP (hepcidin antimicrobial peptide) [NCBI Gene 57817] {aka HEPC, HFE2B, LEAP1, PLTR}, TF (transferrin) [NCBI Gene 7018] {aka HEL-S-71p, PRO1557, PRO2086, TFQTL1}, IL6 (interleukin 6) [NCBI Gene 3569] {aka BSF-2, BSF2, CDF, HGF, HSF, IFN-beta-2}, APOH (apolipoprotein H) [NCBI Gene 350] {aka B2G1, B2GP1, BG}, ALB (albumin) [NCBI Gene 213] {aka FDAHT, HSA, PRO0883, PRO0903, PRO1341}, GGTLC5P (gamma-glutamyltransferase light chain 5 pseudogene) [NCBI Gene 653590] {aka GGT}, CRP (C-reactive protein) [NCBI Gene 1401] {aka PTX1}, CYGB (cytoglobin) [NCBI Gene 114757] {aka HGB, NOD, STAP}, GPT (glutamic--pyruvic transaminase) [NCBI Gene 2875] {aka AAT1, ALT, ALT1, GPT1, SGPT}, PON1 (paraoxonase 1) [NCBI Gene 5444] {aka ESA, MVCD5, PON}
- **Diseases:** LA (MESH:C531622), injury to (MESH:D014947), Anemia (MESH:D000740), infection (MESH:D007239), Antiphospholipid syndrome (MESH:D016736), liver or renal impairments (MESH:D017093), Lupus (MESH:D008180), GI blood loss (MESH:D016063), bleeding (MESH:D006470), autoimmune conditions (MESH:D001327), hemolytic anemia (MESH:D000743), IDA (MESH:D018798), toxicity (MESH:D064420), critical illness (MESH:D016638), liver diseases (MESH:D008107), iron malabsorption (MESH:D008286), autoimmune hemolysis (MESH:D006461), inflammatory bowel disease (MESH:D015212), pAPS (MESH:C535787), ACD (MESH:C535474), MS (MESH:D009103), renal insufficiency (MESH:D051437), Thrombotic (MESH:D013927), Inflammation (MESH:D007249), RA (MESH:D001172), vascular injury (MESH:D057772), malignancy (MESH:D009369), ACD (MESH:D002908), acute or chronic liver disease (MESH:D065290), GI bleeding (MESH:D006471), Hyperferritinemia (MESH:D000085583), ID (MESH:D000090463), hematinic deficiency (MESH:D007153), Fetal (MESH:D005315), hypermenorrhea (MESH:D008595), gastrointestinal (GI) malignancy (MESH:D005770), AHA (MESH:D000744), chronic renal insufficiency (MESH:D051436), Obstetric (MESH:D048949)
- **Chemicals:** G phospholipid (-), reactive oxygen species (MESH:D017382), folic acid (MESH:D005492), creatinine (MESH:D003404), vitamin C (MESH:D001205), Fe (MESH:D007501), cyclophosphamide (MESH:D003520), ASA (MESH:D001241), urea (MESH:D014508), Hydroxychloroquine (MESH:D006886), Prednisone (MESH:D011241), warfarin (MESH:D014859), Rapamycin (MESH:D020123), bilirubin (MESH:D001663), potassium (MESH:D011188), EDTA (MESH:D004492)
- **Species:** Homo sapiens (human, species) [taxon 9606]

## Figures

1 figure with captions in the complete paper: https://tomesphere.com/paper/PMC13025763/full.md

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Source: https://tomesphere.com/paper/PMC13025763