What causes Immune Thrombocytopenic Purpura (ITP)?

Causes of Immune Thrombocytopenic Purpura (ITP)

Immune Thrombocytopenic Purpura (ITP) is primarily caused by autoimmune destruction of platelets and impaired platelet production, with various underlying triggers including infections, autoimmune disorders, medications, and lymphoproliferative disorders. 1, 2

Primary ITP

• Primary ITP is an autoimmune disorder characterized by immunologic destruction of otherwise normal platelets with no identifiable underlying cause 1
• It involves complex dysregulation of the immune system with loss of tolerance to platelet antigens 2
• Antiplatelet antibodies mediate accelerated clearance of platelets via the reticuloendothelial system 2
• Cellular immunity is perturbed with T-cell and cytokine profiles shifted toward proinflammatory immune responses 2
• Both antibody-mediated and T cell-mediated platelet destruction are key pathogenic processes 3

Secondary ITP

Secondary ITP develops in the context of other disorders with distinct pathobiological mechanisms:

Infections

• HIV infection can generate antibodies that cross-react with platelet antigens and impair platelet production by infecting megakaryocyte progenitor cells 4
• Hepatitis C virus (HCV) can cause thrombocytopenia through immune complexes binding to platelet Fcgamma receptors and decreased thrombopoietin production 4
• Helicobacter pylori infection may trigger cross-reactive antibodies against platelets 1, 4
• Viral infections including Epstein-Barr virus, cytomegalovirus, and varicella zoster virus can cause sudden thrombocytopenia through cross-reacting antibodies 4

Autoimmune Disorders

• Systemic lupus erythematosus (SLE) 1, 4
• Antiphospholipid antibody syndrome (APS) 1, 4
• Immune thyroid disease 4
• Evans syndrome 4
• Common variable immune deficiency 1

Lymphoproliferative Disorders

• Chronic lymphocytic leukemia 1, 4
• Large granular T-lymphocyte lymphocytic leukemia 4
• Other lymphoproliferative malignancies 1

Other Causes

• Medications can induce secondary ITP 1, 4
• Recent vaccinations (particularly measles, mumps, and rubella in children) 4
• Bone marrow transplantation side effects 1

Pathophysiological Mechanisms

• Accelerated platelet destruction through antibody-mediated clearance via the reticuloendothelial system 2, 3
• Impaired platelet production by megakaryocytes 5, 2
• T-cell mediated immune dysregulation 2, 3
• Cytokine imbalances contributing to immune dysfunction 2, 3
• Genetic predisposition may play a role in both developing ITP and response to therapy 2

Diagnostic Considerations

• ITP remains a diagnosis of exclusion, with no single "gold standard" test 6
• Diagnosis requires ruling out other causes of thrombocytopenia through history, physical examination, complete blood count, and peripheral blood smear 6
• Physical examination should be normal aside from bleeding manifestations; presence of splenomegaly, hepatomegaly, or lymphadenopathy suggests secondary causes 6, 7
• Testing for HIV, HCV, and H. pylori should be considered in adults with suspected ITP 6, 1
• Bone marrow examination may be necessary in selected patients, particularly those over 60 years or with systemic symptoms 1, 7

Common Pitfalls in Diagnosis

• Failing to recognize secondary causes of ITP, which have different natural histories and responses to therapy 4
• Mistaking pseudothrombocytopenia (EDTA-dependent platelet agglutination) for true thrombocytopenia 6, 7
• Not considering inherited thrombocytopenias that may present with similar clinical features 6
• Overlooking drug-induced thrombocytopenia, which may be difficult to exclude 7
• Missing constitutional symptoms (fever, weight loss) that suggest underlying disorders rather than primary ITP 6, 7