Immune Thrombocytopenic Purpura
last authored: April 2012, Dave LaPierre
last reviewed:
Introduction
Immune thrombocytopenic purpura (ITP) is the most common cause of isolated thrombocytopenia, or level of platelets <100,000/ml. It is a diagnosis of exclusion, and other causes of low platelets, such as disease or toxic exposure must be ruled out.
The Case of Gordon P.
Gordon is a 13 year-old boy who is brought the emergency department because of bruising and nosebleeds that began one day ago. He feels, and appears otherwise well. Bloodwork reveals a platelet count of 15,000/ml.
- What questions do you ask?
- What tests do you consider?
- Do you begin treatment for Gordon?
Causes and Risk Factors
Acute ITP usually begins at age 2-6 with abrupt duration, lasts for weeks, and spontaneously remits in >80% of cases. Counts can often decrease to less than 20,000. Cases very frequently follow infection with varicella, CMV, EBV, or other viruses.
Chronic ITP peaks at ages 20-40, has insidious onset, and lasts months to years, with rare remission. Platelet count tends to be 30,000-80,000. Cases can follow conditions including:
- HIV
- H pylori
- Graves disease, Hashimoto thyroiditis
- sarcoidosis
- systemic lupus erythematosus
Pathophysiology
ITP follows platelet destruction and increased decreased levels of production.
Coating of platelets by antibodies (IgG, often against glycoproteins IIB-IIIa or Ib-IX) leads to their phagocytosis by splenic macrophages. These antibodies are also thought to reduce megakaryocyte production.
Signs and Symptoms
- history
- physical exam
History
Acute ITP often begins as sudden onset petechiae, purpura, and epistaxis in an otherwise well child.
Symptoms to ask about include:
- gingival bleeding
- gastrointestinal bleeding
- menorrhagia
- neurological symptoms (intracerebral bleeding)
- a relapsing-remitting course
- mild fevers
- left upper quadrant discomfort due to splenic enlargement
- bleeding following low doses of NSAID
Physical Exam
Evaulate for evidence of bleeding:
- peticheal hemorrhage
- purpura
- mucocutaneous hemorrhage
No lymphadenopathy or hepatosplenomegaly are present; if the spleen is enlarged, the diagnosis is wrong!
Investigations
- lab investigations
- diagnostic imaging
Lab Investigations
CBC
- thrombocytopenia (often 5,000-75,000)
- occasional lymphocytosis
- anemia
Peripheral smear
- platelets that are frequently large. If abnormal cells seen, biopsy bone marrow to rule out leukemia.
In order to rule out other conditions, order:
- PT and PTT for hemophilia
- urea and creatinine for hemolytic-uremic syndrome
Bone marrow biopsy should be done in patients over 60, or if cases are refractory. It can show increased number of megakaryocytes.
Serum platelet-associated IgG testing may be done, but is not helpful for guiding treatment decisions, and is complicated by high levels of false positive and negative testing.
Diagnostic Imaging
A CT of the head should be done to rule out bleeding if signs and symptoms suggest.
Differential Diagnosis
Diagnosis is one of exclusion. It is important to rule out other causes of thrombocytopenia, including:
- malignancy (suspect if fever, hepatosplenomegaly, lymphadenopathy, pancytopenia, or otherwise abnormal CBC)
- drug-induced thrombocytopenia (over 150 drugs have been identified)
- viral infection
- thrombotic thrombocytopenic purpura
- hemolytic uremic syndrome
- factitious: platelet clumping
- sepsis, disseminated intravascular coagulation
- alcohol-induced thrombocytopenic purpura
- myelodysplastic syndrome
- post-transfusion
- gestational thrombocytopenia
- isoimmune neonatal purpura
- congenital thrombocytopenia
- pre-eclampsia and HELLP syndrome
Treatments
Patients should avoid contact sports or other activities that could increase risk of injury. ASA, clopidogrel, and other platelet-inhibiting drugs should be avoided.
Treatment should be instituted in the following cases:
Children
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Adults
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Patients should be admitted if they are actively bleeding, or if counts are <20,000 (which increases risk of bleeding).
First-line treatment
Oral steroids (2-6 weeks, then tapered) are the first line and are indicated for:
- continued falling of count
- persistent low count
- risks of bleeding (peptic ulcer disease, hypertension)
Platelet counts should be repeated after 1-2 days, and monitored weekly while on steroid treatment. If there is no change, diagnosis should be confirmed with further evaluation (including by bone marrow aspiration).
Second-line treatment
IV immune globulin or Anti-Rh can be used if steroids fail.
- risk of aseptic meningitis within 1-2 days
- blood product: small risk of infection
- expensive
- avoid in patients with IgA deficiency
Splenectomy is the next best management and may be necessary if bleeding is life-threatening. Accessory spleen should be considered if splenectomy is not curative. Following splenectomy, specific vaccination and antibiotic prophylaxis should be provided.
Other treatments to consider include:
- azathioprine
- cyclophosphamide
- vincristine
- danazol
- cyclosporin A
- rituxamab
- mycophenolate mofetil
Platelet transfusions are not routinely helpful, as antibodies will simply inactivate them. However, in situations with significant bleeding, they can be life-saving.
Consequences and Course
Over 80% of cases of acute ITP are recovered within 6 months. Between 5-15% of patients proceed to chronic ITP.
Chronic ITP cases spontaneously recover in 10-20% of cases. The majority of these cases see persistent low levels for months or years. Approximately 10% of cases are resistent to all therapy, including medication and splenectomy.
Mortality is rare, with rates at 1-2%. Complications include:
- cerebral hemorrhage
- hemorrhage
- side effects of steroid use
- infection (following splenectomy)
Resources and References
Godeau B, Provan D, Bussel J. 2007. Immune thrombocytopenic purpura in adults. Curr Opinion in Hematology. 14:535-56.
Tarantino MD. 2006. The threatment of immune thrombocytopenic purpura in children. Curr Opinion in Hematology. 5:89-94.
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