Overview
This lecture covers the hematological manifestations of systemic lupus erythematosus (SLE), including common blood abnormalities, their mechanisms, clinical implications, diagnosis, and management strategies.
Case Discussions
- Hematological abnormalities may precede, occur at diagnosis, or develop during SLE.
- Cases included autoimmune hemolytic anemia, immune thrombocytopenic purpura (ITP), microangiopathic hemolytic anemia (e.g., TTP), and recurrent venous thrombosis with antiphospholipid syndrome.
History and Pathogenesis of SLE
- SLE evolved from being seen as a skin disease to a multisystem autoimmune disorder.
- Pathogenesis involves genetic, hormonal, and environmental factors with immune dysregulation.
- Failure to clear apoptotic cells leads to formation of autoantibodies and immune complexes, causing tissue damage.
Diagnostic Criteria and Key Blood Abnormalities
- SLICC and EULAR/ACR criteria are used for SLE diagnosis, requiring clinical and immunologic features.
- Hematological abnormalities included in these criteria: hemolytic anemia, leukopenia, thrombocytopenia, and antiphospholipid antibodies.
Spectrum of Hematological Abnormalities in SLE
- Common abnormalities: anemia, leukopenia (neutropenia or lymphopenia), thrombocytopenia, and coagulopathies (especially antiphospholipid syndrome).
- Causes can be immune-mediated, related to disease complications, or treatment side effects.
Types and Mechanisms of Cytopenias
- Anemia in SLE: most commonly anemia of chronic disorder due to inflammation-induced iron sequestration.
- Immune-mediated anemia includes autoimmune hemolytic anemia (Coombs positive), pure red cell aplasia, and aplastic anemia.
- Leukopenia: mediated by anti-neutrophil or anti-lymphocyte antibodies; lymphopenia especially affects CD4+ T cells.
- Thrombocytopenia: caused by antibodies against platelet membrane proteins and may be triggered or worsened by antiphospholipid antibodies.
Key Hematological Syndromes
- Immune thrombocytopenia (ITP): presents with skin/mucous bleeding, low platelets, managed with steroids/immunosuppression.
- Thrombotic thrombocytopenic purpura (TTP): caused by ADAMTS13 deficiency, presents as microangiopathic hemolytic anemia and thrombocytopenia, treated with plasmapheresis.
- Antiphospholipid syndrome: prothrombotic state due to antiphospholipid antibodies, associated with thrombosis and pregnancy loss.
Management Principles
- Asymptomatic cytopenias may not need treatment, but severe or symptomatic cases require specific therapy.
- Treat underlying SLE activity to improve blood counts.
- First-line therapies: steroids for cytopenias, immunosuppressives or biologics for refractory cases.
- Avoid platelet transfusion in TTP unless life-threatening bleeding occurs.
- Antiphospholipid syndrome managed with long-term anticoagulation.
Clinical Implications and Prognosis
- Cytopenias can signal active disease, flares, or severe SLE manifestations (e.g., nephritis, neuropsychiatric disease).
- Some cytopenias (like thrombocytopenia or autoimmune hemolytic anemia) are associated with poorer prognosis.
South African Experience
- Hematological abnormalities are common in local SLE patients, with anemia being most frequent.
- Benign ethnic neutropenia (neutrophil count 1–1.5 x10^9/L) is normal in African populations and does not increase infection risk.
Key Terms & Definitions
- Autoimmune hemolytic anemia — destruction of red blood cells by autoantibodies, confirmed by a positive Coombs test.
- Immune thrombocytopenic purpura (ITP) — autoimmune destruction of platelets causing low counts and bleeding.
- Thrombotic thrombocytopenic purpura (TTP) — microangiopathic hemolytic anemia and thrombocytopenia due to ADAMTS13 deficiency.
- Antiphospholipid syndrome — autoimmune disorder causing thrombosis due to antiphospholipid antibodies.
- Benign ethnic neutropenia — chronically low neutrophil count found in certain ethnic groups, not linked to increased infection.
Action Items / Next Steps
- Screen unexplained cytopenias, especially in young females, for SLE and autoimmune markers.
- Review the latest SLE diagnostic criteria.
- Follow up on assigned readings or guidelines for management of hematological complications in SLE.