Idiopathic thrombocytopenic purpura pathophysiology

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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]

Overview

AITP is characterized by the production of autoreactive antibodies against one's own platelets, resulting in increased platelet destruction by RES phagocytes

Pathophysiology

Pathogenesis

Acute ITP: Mainly affects children and usually follows a viral or bacterial infection

• Antigenic mimicry - Similar molecular structures on both host cells and infectious agents, inducing a self immune response which cross reacts with the host antigens.
  • In acute ITP - anti-viral or anti-bacterial antibodies cross reacts against the patient's platelets.
• Mostly acute ITP is self resolving as infectious agents and antibodies are cleared from the body, causing the loss of anti-platelet reactivity.
• T cells are not involved in the parthenogenesis of acute ITP

Chronic AITP: (platelet counts < 150,000 x 10⁹ per liter x 6 months) usually in adults

• Autoantibody‐induced platelet destruction:
• immune-targeted tissue abnormally expresses selfantigens that are then recognized by autoreactive Th cells.
• true organ-specific autoimmune disorder
• no previous history of an infectious event and almost always requires some form of immunosuppressive therapy
• anti- 72 COOPAMAH ET AL body specificities are directed against several platelet glycoprotein epitopes
• associated with T-cellrelated and cytokine abnormalities
  • Autoantibody‐induced platelet destruction:
    • Abnormal IgG auto-antibody recognizes glycoprotein IIb/IIIa, glycoprotein Ib/IX complex, GP Ia/IIa, and GP VI etc
    • IgG auto-antibody binds to the circulating platelet membranes through glycoproteins
    • Autoantibody-coated platelets induce Fcg receptors and bind to antigen-presenting cells (Splenic macrophages or dendritic cells) where the platelets undergoes phagocytosis.
    • phagocytosis in the reticuloendothelial system
    • Platelet phagocytosis by splenic macrophages and peripheral blood neutrophils
    • Abnormal IgG auto-antibody recognizes glycoprotein IIb/IIIa, glycoprotein Ib/IX complex, GP Ia/IIa, and GP VI etc
    • IgG auto-antibody binds to the circulating platelet membranes through glycoproteins
    • Autoantibody-coated platelets induce Fcg receptors and bind to antigen-presenting cells (Splenic macrophages or dendritic cells) where the platelets undergoes phagocytosis.
    • Antigen-presenting cells degrade glycoproteins and and not only degrade glycoprotein IIb/IIIa (light blue oval), thereby amplifying the initial immune response, but also may generate cryptic epitopes from other platelet glycoproteins
    • Activated antigen-presenting cells
    • express these novel peptides on the cell surface along with costimulatory help (represented in part by the interaction between CD154 and CD40) and the relevant cytokines that facilitate the proliferation of the initiating CD4-positive T-cell clones (T-cell clone 1) and those with additional specificities (T-cell clone 2)
    • B-cell immunoglobulin receptors that recognize additional platelet antigens (B-cell clone 2) are thereby also induced to proliferate and synthesize anti–glycoprotein Ib/IX antibodies (green) in addition to amplifying the production of anti–glycoprotein IIb/IIIa antibodies (orange) by B-cell clone 1
  • Autoreactive T lymphocyte‐mediated platelet lysis
    • chronic AITP may be the result of an abnormal Th cell defect that could direct autoreactive B cells to differentiate and secrete IgG autoantibodies.
    • act upon megakaryocytes in the bone marrow
    • Antibody production in ITP appears to be driven by CD4-positive helper T cells reacting to platelet surface glycoproteins, possibly involving CD40:CD40L co-stimulation . Splenic macrophages appear to be the major antigen-presenting cells
• Immune‐mediated decreased platelet production:
  • abnormal thrombopoiesis
  • degenerative changes in both nuclei and cytoplasm
  • reduced platelet turnover
  • megakaryocyte damage
  • autoantibody‐induced suppression of in vitro megakaryocytopoiesis

Associated Conditions

Conditions associated with

Gross Pathology

On gross pathology, characteristic findings of itp include:

• Acute
• Chronic

Microscopic Pathology

On microscopic histopathological analysis, characteristic findings of itp include:

• Acute
• Chronic