ITP

Immune thrombocytopenic purpura, an acquired autoimmune d/o in which antiplatelet abs result in shortened platelet survival and suppress megakaryopoiesis, leading to thrombocytopenia and increased bleeding risk.

Classification:

    • Idiopathic (primary): Autoantibodies bind to Plt surface ags leading to premature clearance by the RES, and immune-mediated suppression of platelet production.

    • Secondary: Occurs with SLE, APA, HIV, HCV, H. pylori, and lymphoproliferative d/o

    • Drug induced: Drug-Plt interaction prompting ab binding. Medications implicated: quinidine, quinine, abciximab, eptifibatide, tirofiban, ticlopidine, rifampin, linezolid, sulfonamides, vancomycin. phenytoin, valproic acid, and carbamazepine, APAP, naproxen, diclofenac, cimetidine, chlorthiazide.

Dx:

    • Presents as mild mucocutaneous bleeding, petechiae (palatal)

    • Primary ITP has the scenario of isolated thrombocytopenia only.

    • Plts become normal when the offending drug is discontinued, and thrombocytopenia occurs when the drug is restarted.

    • Serological test for antiplatelet abs generally do not help in Dx of ITP because of poor sensitivity and low negative predictive value.

    • Lab test do not confirm the presence of primary ITP, although they help in excluding some secondary causes.

    • Dx generally does not require bone marrow bx and aspirate studies, though these tests help to exclude other causes in select patients such as those with age >60 yrs and those who do not respond to immune suppression therapy.

Tx:

    • Decision to treat primary ITP depends upon the severity of thrombocytopenia and concerns about bleeding.

    • Tx of secondary ITP includes treatment of underlying disease, or d/c of offending drug.

    • Glucocorticoids - predinisone 1 mg/kg/d. Non-responders or Pts with active bleeding also get IVIg (1g/kg x 2 days) or anti-D immunoglobulin (WinRho) if Rh-positive (ineffective postsplenectomy).

    • Most Primary ITP respond to therapy and thrombocytopenia resolves within 1-3 wks.

    • Non-responders and 30%-40% of Pts who relapse during a steroid taper have refractory ITP, for whom the therapeutic goal consists of a safe Plt count 30K-50k, and minimization of treatment-related toxicities.

    • 2/3rds of Pts with refractory ITP obtain durable complete response following splenectomy. Administer pneumococcal, meningococcal, and H. influenzae type B vaccines at least 2 week prior to splenectomy.

    • If splenectomy is not an option or failed splenectomy. Prednisone +/- IVIg and +/- danazol, other immunosuppressive agents or anti-CD20 monoclonal ab (rituximab)

    • In 2008, FDA approved TPO-R (thrombopoietin rcp) agonist for treatment of refractory primary ITP Pts with increased bleeding risk. Romiplostim (Nplate), dosed SC weekly, and eltrombopag (Promacta), taken orally daily, produce a durable Plt count improvements in a majority of refractory ITP patients beginning 5-7 days after initiation. Potential complications include thromboembolic events and bone marrow fibrosis.

    • For drug induced thrombocytopenia, platelet transfusions for severe thrombocytopenia may decrease the risk of bleeding, IVIg, steroids, and plasmapheresis have uncertain benefit.