ITP

**Pathophysiology** - Autoantibodies (IgG) against platelet membrane glycoproteins (GP IIb/IIIa most common; also GP Ib/IX) opsonize platelets. Splenic macrophages (Fc receptors) phagocytose them -> peripheral destruction. Antibodies also impair megakaryocyte function/production, so TPO is normal or only mildly elevated. Type II hypersensitivity. - Megakaryocytes in bone marrow are normal or increased (compensatory).

**Types** - Childhood (acute): typically age 2-6, 1-4 weeks after a viral infection (or vaccination), abrupt onset, usually self-limited (most resolve within 6 months). Often managed with observation if no significant bleeding. - Adult (chronic): female predominance, ages 20-40, insidious onset, tends to be chronic/relapsing. Associated with SLE (may be the first manifestation), HIV, HCV, CLL/lymphoproliferative disorders, H. pylori, and antiphospholipid syndrome. Evans syndrome = ITP plus autoimmune hemolytic anemia.

**Clinical features** - Mucocutaneous bleeding: petechiae, purpura, epistaxis, gingival bleeding, menorrhagia, easy bruising. Risk of GI bleed and intracranial hemorrhage when platelets are very low (<10,000/µL), which is rare. - NO splenomegaly (if present, consider another cause: lymphoma, cirrhosis/hypersplenism, infection), no lymphadenopathy, and patient otherwise looks well.

**Diagnosis (exclusion)** - Isolated thrombocytopenia (<100,000/µL) with normal WBC and Hb (unless blood loss) and a normal peripheral smear apart from large platelets (increased MPV). - Exclude pseudothrombocytopenia (EDTA clumping), drugs (heparin, quinine, etc.), HIV/HCV, SLE, TTP/HUS, DIC, and bone marrow disorders. - Coagulation studies (PT/aPTT) are normal; bleeding time is prolonged (not needed). Bone marrow biopsy is not routinely required (consider if age >60, atypical features, or failure of therapy), and shows increased megakaryocytes. - Test for HIV, HCV, and H. pylori in adults.

**Treatment** - Children: observation if mild; IVIG, anti-D immunoglobulin (Rh+ only, with intact spleen), or steroids for significant bleeding. - Adults: treat if platelets <30,000/µL or if bleeding. First-line is glucocorticoids (prednisone or dexamethasone) ± IVIG (rapid rise in platelets, used for severe bleeding or pre-procedure). Anti-D (WinRho) is an option in Rh+ patients with a spleen, but it can cause hemolysis. - Second-line: TPO receptor agonists (romiplostim, eltrombopag, avatrombopag), rituximab, fostamatinib (Syk inhibitor), or splenectomy (the spleen is the site of destruction; give pneumococcal, meningococcal, and Hib vaccines first). - Emergent (life-threatening bleed): platelet transfusion + IVIG + high-dose steroids. - Treat the underlying H. pylori infection if present (eradication can improve counts).

**Key distinctions (high-yield)** - ITP vs TTP: TTP has schistocytes, MAHA, fever, renal and neurologic dysfunction (ADAMTS13 deficiency). ITP has a normal smear and no hemolysis. - ITP vs DIC: DIC has abnormal PT/aPTT, low fibrinogen, and elevated D-dimer. - ITP vs HIT: HIT occurs after heparin exposure (platelet factor 4 antibodies) and causes thrombosis, not bleeding. - Platelet transfusion is generally avoided in ITP unless there is life-threatening bleeding, because transfused platelets are rapidly destroyed. - Neonatal thrombocytopenia can occur in infants born to mothers with ITP (transplacental IgG), a distinct concept from neonatal alloimmune thrombocytopenia (NAIT).