ITP

Question 1

Idiopathic thrombocytopenic purpura (ITP)

Answer 1

• Autoimmune disorder characterized by thrombocytopenia and induced by autoAbs against various platelet membrane receptors
• The opsonized platelets will be destroyed via phagocytosis by macrophages
• The Abs can also attack megakaryocytes in the BM, but this is less damaging
• There’s usually either normal or even slightly elevated megakaryocytic # in BM (due to decreased platelets)
• ITP is a form of increased destruction, but is also accompanied w/ ineffective production

Question 2

Types of ITP

Answer 2

• Can be acute or chronic
• Acute: duration of 6 mo or less (commonly in children), rapid onset usually following a viral illness, usually self-limiting
• Chronic: longer than 6 mo (commonly in adults), slow onset with no preceding viral infection and rare spontaneous remission (platelet counts may remain at 1/3rd of normal)

Question 3

Dx of ITP

Answer 3

• Propensity for bleeding
• Exclusion of other disorders that can cause thrombocytopenia (leukemia, aplastic anemia, BM disorders like myelodysplasia, infection)
• Hx and PE, CBC, blood smear should be used (look for family Hx of thrombocytopenia)
• Cutaneous manifestations of ITP include mucocutaneous petechiae, ecchymoses, and purpura
• Large platelets (young) in blood smear
• Absence of hepatosplenomegaly and lymphadenomegaly
• Response to ITP Rx: IVIg, anti-D Ig, steroids

Question 4

Pathophysiology of ITP

Answer 4

• GPIIb/IIIa and GPIb/IX are major targets for autoAbs (both on megakaryocytes and platelets)
• ITP involves: platelet destruction (both T and B cell mediated) and decreased production (due to Abs and CTLs attacking megakaryocytes)
• CTLs (CD8 Ts) are directed against platelets and megs, and CD4s are needed to induce B cell targeting of platelet Ags
• Patients w/ ITP are at increased risk of bleeding including from GI and intracranial

Question 5

Rx strategies

Answer 5

• Increase platelet count to prevent bleeding
• Minimize Rx-related toxicity
• Preserve patient activity
• Who you treat w/ what depends on the extent of the thrombocytopenia and past Hx

Question 6

Rx’s of ITP

Answer 6

• Initial Rx w/ corticosteroids (prednisone), which increases vascular integrity and platelet survival (due to decreased production of Abs against platelets), and decreased clearance of Ab coated platelets
• Can use repeated high-dose dexamethasone
• IVIg are used for those unresponsive to corticosteroids or w/ critical bleeding
• IVIg can rapidly increase platelet count (as can IV anti-D Ig)
• IVIg down-regulates Fc receptor expression, inhibits complement binding, and interferes w/ opsonization of Abs to platelets
• Splenectomy is an option, which will remove the site of phagocytosis of the platelets
• Can also use TPO agonists, anti-CD20 Ig to kill B cells and up regulate Tregs

Question 7

ITP vs TTP

Answer 7

• In TTP you see schistocytes due fragmentation hemolytic anemia (high bili/LDH, decreased BT and platelet count)
• Due to ADAMTS13 deficiency