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.