What are the hematological manifestations of systemic lupus erythematosus (SLE)?

Hematological Manifestations of Systemic Lupus Erythematosus

Hematological abnormalities are among the most common manifestations of systemic lupus erythematosus (SLE), with anemia, lymphopenia, and thrombocytopenia being the predominant findings that significantly impact morbidity and mortality. 1, 2

Common Hematological Manifestations

Anemia

• Anemia of chronic disease (46% of cases) - most common type 3
• Autoimmune hemolytic anemia (28% of cases) 3
  • Positive direct Coombs test in 22% of patients
• Severe anemia has been associated with:
  • Organ involvement
  • Disease progression
  • Worse prognosis 4

White Blood Cell Abnormalities

• Leukopenia (<4.0 × 10^9/L): occurs in 57% of patients 3
• Lymphopenia (<1.5 × 10^9/L): most common white cell abnormality, affecting up to 76-82% of patients 3, 5
• Neutropenia (<1.8 × 10^9/L): seen in approximately 20% of patients 3
• Severe leukopenia and lymphopenia are associated with increased risk of infections 4

Platelet Abnormalities

• Thrombocytopenia (<150 × 10^9/L): occurs in 17-40% of patients 3, 5
  • Moderate thrombocytopenia (<100 × 10^9/L): 26% of patients
  • Severe thrombocytopenia (<50 × 10^9/L): 8% of patients
• Associated with:
  • Renal disease
  • Disease progression to end-stage renal disease
  • Worse prognosis 4

Antiphospholipid Syndrome (APS)

• Present in approximately 10% of SLE patients at diagnosis 3
• Associated with:
  • General disease activity
  • Thrombotic manifestations
  • Damage development
  • Pregnancy complications
  • Possible early graft loss in kidney transplant patients 4

Clinical and Laboratory Correlations

Disease Activity Markers

• Patients with cytopenia at diagnosis show:
  • Higher erythrocyte sedimentation rates (ESR)
  • More frequent C3 and C4 hypocomplementemia
  • Higher positivity for anti-ds-DNA antibodies 5
• Complement levels may correlate with disease activity, though they have no predictive value for disease flares 4

Associated Organ Involvement

• Cytopenia at diagnosis is associated with:
  • Photosensitivity
  • Renal involvement
  • Antiphospholipid syndrome 5
• Leukopenia is more common in patients with skin/mucosal involvement 3
• C3 hypocomplementemia is more prominent in cases with renal or serosal involvement 3

Diagnostic Considerations

• Hematological involvement often predominates during the first years of SLE and may be the initial manifestation of the disease 2
• Hemolytic anemia and immune thrombocytopenia may initially be classified as idiopathic before being recognized as SLE-related 2
• C-reactive protein (CRP) levels are rarely elevated in SLE; significant increases (>50 mg/L) should prompt evaluation for superimposed infection 4

Treatment Approaches

General Principles

• Corticosteroids remain the mainstay of treatment for SLE-related cytopenias 1
• Other conventional options include:
  • Azathioprine
  • Cyclophosphamide
  • Intravenous immunoglobulin 1
• Mycophenolate mofetil can act as a corticosteroid and cyclophosphamide-sparing agent 1

Novel Therapies

• Thrombopoietin receptor agonists for refractory thrombocytopenia
• B-cell depletion therapy for refractory cases
• Autologous hematopoietic stem cell transplantation in refractory SLE-APS 1

Monitoring Recommendations

• Complete blood count should be included in regular laboratory monitoring 6
• Monitor for medication-induced cytopenias, particularly with azathioprine (most common cause of drug-induced cytopenia in SLE) 5
• Distinguish between disease-related (83.4%) and medication-related (16.6%) cytopenias 5

Pitfalls and Caveats

• Treatment of hematological abnormalities can itself cause complications:
  • Granulocytosis due to high-dose steroids
  • Increased infection risk with immunosuppression 1
• Multifactorial causes of cytopenias must be considered for appropriate management 2
• Abrupt changes in hematological parameters during follow-up may indicate disease flare or medication toxicity rather than primary hematological disease

Hematological manifestations in SLE require careful monitoring and appropriate management to reduce morbidity and mortality, with treatment approaches tailored to the specific cytopenia and its severity.