Which of the following does NOT cause secondary (reactive) thrombocytosis: systemic lupus erythematosus, rheumatoid arthritis, splenectomy, inflammatory bowel disease, or bleeding?

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Systemic Lupus Erythematosus Does NOT Cause Secondary Thrombocytosis

Systemic lupus erythematosus (SLE) is the answer—it causes thrombocytopenia, not thrombocytosis. 1

Understanding the Mechanism

SLE is fundamentally associated with autoimmune destruction of platelets, leading to thrombocytopenia (low platelet counts), not thrombocytosis (elevated platelet counts). 1 The pathophysiology involves antibody-mediated platelet destruction, making it a cause of secondary immune thrombocytopenia rather than reactive thrombocytosis. 2

Why SLE Causes Thrombocytopenia

  • Autoimmune platelet destruction is the primary mechanism, with antibodies targeting platelet surface antigens leading to accelerated clearance. 1, 2
  • Thrombocytopenia occurs frequently in SLE patients and is almost invariably autoimmune in nature. 3
  • SLE-associated thrombocytopenia may be severe enough to require aggressive treatment including splenectomy in refractory cases. 4, 3

The Rare Exception: Autosplenectomy

  • When thrombocytosis does appear in SLE (occurring in only 3.7-5.9% of patients), it is typically transient and reactive to other conditions such as iron deficiency anemia, polyarthritis, or cutaneous vasculitis. 5, 6
  • Persistent thrombocytosis in SLE should raise suspicion for functional autosplenectomy, particularly in patients with antiphospholipid antibodies. 5, 6
  • Only 0.9-1.4% of SLE patients develop persistent thrombocytosis, and this is due to loss of splenic function (autosplenectomy), not the SLE itself. 5, 6

Why the Other Options DO Cause Thrombocytosis

Rheumatoid Arthritis

  • Chronic inflammatory conditions like rheumatoid arthritis cause reactive thrombocytosis through cytokine-mediated stimulation of megakaryocyte production. 7

Splenectomy

  • Removal of the spleen eliminates the major site of platelet sequestration and destruction, directly causing thrombocytosis. 7
  • Post-splenectomy thrombocytosis is expected and can be marked. 5, 4

Inflammatory Bowel Disease

  • Active inflammation triggers reactive thrombocytosis through IL-6 and other inflammatory mediators that stimulate thrombopoietin production. 7

Bleeding

  • Acute or chronic blood loss stimulates compensatory megakaryocyte proliferation and platelet production, resulting in reactive thrombocytosis. 7

Critical Clinical Pitfall

Never assume thrombocytosis in an SLE patient represents disease activity—instead, investigate for autosplenectomy by examining peripheral blood smear for Howell-Jolly bodies, spherocytes, and target cells, and consider splenic imaging. 5, 6 The sudden appearance of thrombocytosis or apparent reversal of thrombocytopenia in SLE should prompt evaluation for functional asplenia, especially in patients with antiphospholipid antibodies. 6

References

Guideline

Guideline Directed Topic Overview

Dr.Oracle Medical Advisory Board & Editors, 2025

Research

Pathobiology of secondary immune thrombocytopenia.

Seminars in hematology, 2009

Guideline

Causes of Chronic Thrombocytopenia

Praxis Medical Insights: Practical Summaries of Clinical Guidelines, 2025

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This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.

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