Mechanism of Platelet Destruction in Acute Immune Thrombocytopenic Purpura
The primary mechanism of platelet destruction in acute ITP is the removal of antibody-coated platelets by splenic macrophages. 1
Pathophysiology of Platelet Destruction in ITP
Primary Mechanism: Antibody-Mediated Destruction
In acute ITP, the immune system produces autoantibodies (primarily IgG) that bind to specific platelet membrane glycoproteins, most commonly GPIIb-IIIa and/or GPIb-IX. These antibody-coated platelets are then recognized and removed by macrophages in the reticuloendothelial system, particularly in the spleen, through Fc receptor-mediated phagocytosis 1, 2.
The evidence supporting this mechanism includes:
- Infusion of ITP plasma into normal recipients can result in thrombocytopenia 2
- Decreased intravascular survival of radiolabeled platelets in most ITP patients 2
- Morphological and in vitro evidence of platelet phagocytosis 2
Secondary Mechanisms
While Fc-dependent macrophage-mediated clearance is the predominant mechanism, other processes may contribute to platelet destruction in acute ITP:
Complement-mediated platelet lysis: Some patients may experience direct complement activation leading to platelet destruction 3
Cytotoxic T-cell mediated destruction: Evidence shows that cytotoxic T lymphocytes can induce lysis of autologous platelets in some ITP patients 2
Impaired platelet production: Recent evidence indicates that autoantibodies can also bind to megakaryocytes, resulting in decreased thrombopoiesis 4
Immune Dysregulation in ITP
The loss of self-tolerance appears to be a fundamental mechanism underlying the pathogenesis of ITP. This involves:
- Immunological imbalance triggered by external antigenic stimulation (molecular mimicry) or inflammatory processes 1
- Altered equilibrium among T-lymphocyte populations with:
- Selective activation of CD4+ type-1 helper T-lymphocytes (Th1)
- Functional inhibition of FOXP3+ CD4+ T-regulatory lymphocytes (Tregs) 1
- Uncontrolled proliferation and activation of cytotoxic CD8+ T lymphocytes
- Aberrant production of plasma cells and generation of self-antibodies against platelets 1
Clinical Implications
Understanding that the primary mechanism is removal of antibody-coated platelets by splenic macrophages explains why:
- Splenectomy has historically been an effective treatment for refractory ITP 1
- Therapies that interfere with Fc-receptor function (such as IVIg and anti-D) can rapidly increase platelet counts 1
- Thrombopoietin receptor agonists (TPO-RAs) are effective by increasing platelet production to overcome destruction 1
Conclusion
The correct answer is A. removal of antibody-coated platelets by splenic macrophages. This represents the primary mechanism of platelet destruction in acute ITP, though other mechanisms like complement-mediated lysis, T-cell cytotoxicity, and decreased platelet production may also contribute to the overall pathophysiology of the disease.