Download Idiopathic Thrombocytopenic Purpura

CSC – NR addendum Dec-03
Idiopathic Thrombocytopenic Purpura
Cheng et al. “Initial Treatment of Immune Thrombocytopenic Purpura with High-Dose Dexamethasone.” NEJM 349(9): 831-6.
Cines DB, Blanchette VS. Immune Thrombocytopenic Purpura. NEJM 346 (13): 995-1008.
Emilia G et.al. H. pylori eradication can induce platelet recovery in ITP. Blood. 2001; 97: 812-4.
George JN. Idiopathic Thrombocytopenic Purpura: A practice guideline developed by explicit methods for the American Society of
Hematology. Blood 1996; 88:3.
Michel M. et al. Autoimmune thrombocytopenic purpura and Helicobacter pylori infection. Arch Intern Med 2002; 162: 1033-36.
UptoDate v10.3.
Key Points:
• Differential diagnosis of ITP includes other autoimmune thrombocytopenias, infections, liquid tumors,
drug effects, and hypersplenism
• Once you’ve done a careful history and physical, CBC and blood smear, the only other tests required to
give a clinical dx of ITP are an HIV test and a bone marrow biopsy in older patients
• Rate of major bleeding is low since platelets are functional
I.
Epidemiology:
• 50% kids, 50% adults
• Among adults, affected women outnumber affected men by 2:1
II. Pathophysiology:
• Thought to result from autoantibodies to platelets (surface glycoproteins), which are then cleared by
splenic macrophages
• Most but not all patients have a compensatory increase in platelet production
III. Differential Diagnosis: for ISOLATED thrombocytopenia
• Autoimmune disorders: SLE, antiphospholipid antibody syndrome
• Infections: HIV, HCV, EBV
• Neoplastic: CLL, lymphoma, large granular lymphocytic leukemia, MDS
• Drug effect: Heparin, quinidine, sulfa, gold
• Hypersplenism
• Isolated thrombocytopenia of pregnancy
• Congenital (Wiskott-Aldrich, Bernard-Soulier, Fanconi’s anemia, etc)
• Rare: Pure megakaryocyte aplasia
IV. ITP Pearls:
• The presence of significant splenomegaly (other than just a spleen tip) argues strongly against ITP
• Per consensus statement by American Society of Hematology in 1996, the only tests required other
than a careful H&P, CBC and smear to exclude other causes of thrombocytopenia are as follows:
„ HIV testing
„ Bone marrow bx in patients older than 60 to r/o MDS
• Other groups lower the age of BMBx to 40
• Platelet auto-antibodies: Test characteristics are not good enough at this point to make them
clinically useful
• Remember that the platelets are completely functional and therefore the rate of major bleeding is low
V. Treatment:
• Generally begun once platelet count < 30,000-50,000; for those who present with higher platelet
counts, only 10% will develop severe thrombocytopenia at 5 yrs
• Spontaneous remission is the norm in children but occurs in only 9% of adults
• Rx choices:
„ Generally begin with prednisone 1 mg/kg/day orally, duration determined by response to
Rx
„ High dose methylprednisolone for those refractory to PO steroids
CSC – NR addendum Dec-03
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VI.
IVIG and/or WinRho (the latter for Rh+ patients only, where it works by binding to RBC
antigen and thereby busying the Fc receptors in the reticuloendothelial system so they can’t
chomp up the platelets)
Splenectomy: usually reserved for cases of severe thrombocytopenia that fail steroids;
remission rate 50-65% post-splenectomy
Other options for chronic refractory ITP: Danazol, Dapsone, cyclophosphamide
Role of H. pylori?
• Original case report in 1998; plausible mechanism suggested is that H. pylori may initiate
autoreactivity through molecular mimicry
• Subsequent small study in 2001 of 30 patients with ITP. 13 of those were found to be H. pylori
positive, and eradication was attempted in 12 of them. Of those 12 patients, 6 had a significant
increase in platelet count in the absence of any new immunosuppressive or ITP-directed therapy.
Similar study from Japan published in 2002 that demonstrated a 63% response rate (12/19 patients).
• Case-control study in Archives of Internal Medicine examining 51 patients with ITP and 35 controls
without ITP. Seroprevalence of H. pylori (antibodies) was not different in the two groups. They
also found no difference in outcome between the ITP patients with H. pylori and the sero-negative
ITP patients. This study also found no evidence of anti-H. pylori antibodies in platelet eluates of
patients with ITP.
VII. High-dose dexamethasone
• NEJM study 8/03
• Treated patients with plt <20K or <50K with bleeding with oral dexamethasone 40mg/day X
4d
• Response defined: count >50K with increase >30K and cessation of bleeding by day 10
• Sustained response defined: >50K after 6 months
• Excluded: relapsed ITP, recent steroids, adverse effects to steroids in past, HTN/DM
uncontrolled, active infection, pregnancy
• 157 patients -> 125 eligible -> 106 ressponded (85%) -> half sustained and half relapsed (repulsed with maintenance prednisone +/- other treatments
• No control group – compared to previously reported responses to chronic steroids
• Editorial felt not yet ready for prime time – further studies needed