immune or idiopathic thrombocytopenic purpura (ITP)

Introduction

A diagnosis of exclusion.

Classification

Childhood ITP

• usually preceded by viral-like prodome
• self-limited
• spontaneously resolves in weeks to months

Adult ITP

• occasionally preceded by viral-prodrome
• seldom self-limited
• relapse after glucocorticoid treatment in 80% of patients
• 10% of cases resistant to all therapies
• females affected more than males
  • pregnancy is a common setting for ITP
  • estrogens thought to play an etiologic or aggravational role
• generally occurs in younger patients with no other health problems
• may occur in the elderly

Etiology

• pharmacologic agents
  • vancomycin
• associated diseases
  • connective tissue diseases, especially SLE
  • lymphoma (Hodgkin's disease)
  • chronic lymphocytic leukemia (CLL)
  • ulcerative colitis
  • solid tumors (uncommon)
• infections - HIV1 infection, hepatitis C, H pylori
• idiopathic

Pathology

• generally an IgG antibody to platelets is present
  • anti-platelet glycoprotein IIb-IIIa
• platelet attachment to immune complexes formed as a result of
  • pharmacologic agents
  • diseases
  • infections
• platelets are young & hyper-functional
• impaired production of platelets may play role

Clinical manifestations

• purpura
  • non-pruritic, non-blanching red macular rash
• mucous membrane hemorrhage
• gastrointestinal bleeding
• cerebromeningeal bleeding
• splenomegaly (10%)
• accessory spleen in 10%
• bleeding generally does not occur until platelet count drops below 5000-10,000/uL
• in older adults, there is often a history of intermittent bruising or petechiae
• unlikely to develop with 5 days of hospital discharge

Laboratory

• complete blood count (CBC)
  • isolated thrombocytopenia
  • platelet count < 50,000/uL* (< 10,000/uL in 30%)
  • WBC count is generally normal
  • hemoglobin & hematocrit are generally normal
    • anemia does not exclude ITP if anemia can be explained by bleeding
• peripheral blood smear
  • myeloid & erythroid cells are normal
  • extreme thrombocytopenia & large platelets imply a destructive process
• HIV1 testing & hepatitis C serology for patients at risk
• H pylori serology
• bone marrow biopsy
  • indications
    • to establish diagnosis in patient > 60 years of age
    • patients who are candidates for splenectomy
    • abnormalities in 2 cells lines
    • abnormal peripheral smear
    • anemia or leukopenia
    • not routinely indicated
  • ITP -> increased numbers of megakaryocytes
  • drug-induced thrombocytopenia -> decreased numbers of megakaryocytes
• platelet antibody testing not recommended
  • specificity high 93%, but sensitivity low 53%

* defined as platelets < 100,000/uL (other causes ruled out)

Complications

• 2-fold risk of venous thromboembolism
• peristent thrombocytopenia despite splenectomy

Differential diagnosis

• myelodysplastic syndrome
  • generally occurs in the elderly
  • teardrop cells (RBC) &/or leukopenia with dysplastic myeloid cells
• drug-induced thrombocytopenia
  • accounts for most cases of transient thrombocytopenia in adults
  • heparin-induced thrombocytopenia (most common)
• alcohol or other toxins
• splenomegaly: cirrhosis
• thrombocytopenia associated with arthritis suggests connective tissue disease - systemic lupus erythematosus
• microangiopathic hemolytic anemia (schistocytes on peripheral smear)
  • thrombotic thrombocytopenic purpura
  • disseminated intravascular coagulation
  • HELLP syndrome
• aplastic anemia: anemia, leukopenia, leukocytosis
• pseudothrombocytopenia - platelet clumps
• other causes of thrombocytopenia

Management

• glucocorticoids
  • prednisone 1 mg/kg/day for up to one month
  • 70% of patients initially respond
  • dexamethasone 40 mg/day for 4 days, repeated every 28 days for 12 months for resistant or relapsing ITP
  • indications:
    • platelet count < 30,000/uL
    • platelet count 30,000-50,000/uL with clinically significant bleeding
  • sustained remissions uncommon (10-20%); relapses common (50%)
• severe life-threatening bleeding
  • intravenous gamma globulin
  • anti Rho(D) (Rh+ patients) with intact spleen
    • Ab binds D-antigen on RBC
    • immune-mediated clearance of Ab-coated RBC occupies Fc-gamma receptors in the spleen, reducing clearance of ITP Ab-coated platelets
  • packed RBCs
  • platelets
  • methylprednisolone 1 g/day for 3 days
• platelet transfusions not indicated unless there is active bleeding
  • asymptomatic patients with platelet counts > 30,000/uL need only observation
  • asymptomatic patients with platelet count > 30,000-40,000/uL
    • low risk of more severe thrombocytopenia (15%)
    • observation is appropriate
  • platelet counts < 30,000/uL may require treatment
• thrombopoietin receptor agonists for refractory ITP
  • eltrombopag (oral) 20-40% response
  • romiplostim (injection)
  • preferable to rituximab
• rituximab plus dexamethasone
  • effective, but high risk of adverse effects, 26% vs 13% with dexamethasone alone
  • rituximab preferable to splenectomy
• splenectomy
  • persistent thrombocytopenia for > 6 months
  • frequent relapses (40-50%)
  • no response to steroids or relapse during steroid taper
  • complete remission in 2/3 of patients
  • 10% of patients have accessory spleen
  • if asymptomatic thrombocytopenia after splenectomy, observe
• immunosuppressive agents
  • cyclophosphamide (Cytoxan)
  • azathioprine (Imuran)
  • cyclosporin A
  • vincristine (Oncovin)
  • vinblastine
  • colchicine
  • mycophenolate
• multidrug combination 71% response rate
  • methylprednisolone 30 mg/kg
  • intravenous gamma-globulin (1 g/kg)
  • vincristine (0.03 mg/kg) &/or anti-D# (75 ug/kg)
• plasmapheresis with staphylococcal protein A absorption
• danazol
• test for & eradicate H pylori
  • treatment of H pylori may induce platelet recovery in ITP
• temporary treatment during surgery or acute bleeding
  • IV immunoglobulin
  • vincristine
• HIV1 patients
  • generally NOT treated with glucocorticoids or splenectomy because of risk of further immunosuppression
  • intravenous gamma globulin or anti Rho(D)#
  • interferon-alpha
  • antiretroviral therapy
• newly diagnosed patients with ITP
  • hospitalization for platelet count < 20,000/uL
  • prednisone or pulse dexamethasone as initial therapy
  • maximum duration of prednisone 6 weeks
  • children with minimal or no bleeding
    • observation without hospitalization
    • do no use prednisone > 7 days in newly diagnosed children

# (Rh+ patients)

More general terms

• thrombocytopenia
• autoimmune disease
• hemorrhage (bleeding)

Additional terms

• Evan's syndrome

Patient information

immune or idiopathic thrombocytopenic purpura (ITP) patient information