Idiopathic thrombocytopenic purpura

Idiopathic thrombocytopenic purpura (ITP) is the condition of having a low platelet count (thrombocytopenia) of no known cause (idiopathic). As most causes appear to be related to antibodies against platelets, it is also known as immune thrombocytopenic purpura. Although most cases are asymptomatic, very low platelet counts can lead to a bleeding diathesis and purpura.

Signs and symptoms

ITP occurs most often in women over 40 years of age. It may be acute, lasting for 6 months or less, or chronic, lasting for over a year. The acute type is more often seen in children and will cure itself in more than 80% of cases. The chronic type is more commonly seen in adults and it tends to get worse as the disease progresses.

Occasionally, ITP patients suffer from bruising, nosebleeds, and bleeding gums; this is the characteristic pattern of bleeding in platelet disorders. Bleeding normally does not occur unless the platelet count is very low (below about 10,000 per mm³, compared to a normal range of 150,000–400,000 per mm³).

Subarachnoid and intracerebral hemorrhage are very serious possible complications of this disease. Fortunately, these are rare in patients who are being treated.

Pathogenesis

In many cases, the cause is not actually idiopathic but autoimmune, with antibodies against platelets being detected in approximately 80% of patients. Most often these antibodies are against platelet membrane glycoproteins IIb-IIIa or Ib-IX, and are of the IgG type. The coating of platelets with IgG renders them susceptible to opsonization and phagocytosis by splenic macrophages.

The IgG autoantibodies are also thought to damage megakaryocytes, the precursor cells to platelets, but this is thought to contribute only slightly to the decrease in platelet numbers.

Diagnosis

When measuring the platelet count, one has to bear in mind that the "normal values" for laboratory measures are all statistical. They are defined by the upper and lower 2.5th percentile. It is therefore possible to be completely healthy but to have a decreased platelet count. There is, however, a higher chance of pathology.

The diagnosis of ITP is a clinical one and is a diagnosis of exclusion. Low platelet count can be a feature of a large number of diseases and, when serious, warrants investigation by a hematologist. Secondary causes include leukemia, medications (e.g. quinine, heparin), lupus erythematosus and some other autoimmune disorders, cirrhosis (leading to thrombocytopenia from hypersplenism), HIV, congenital causes, and antiphospholipid syndrome. A bone marrow examination may be performed on patients over the age of 60 and people who do not respond to treatment, or when the diagnosis is in doubt.

Despite the destruction of platelets by splenic macrophages, the spleen is normally not enlarged. In fact, an enlarged spleen should lead a clinician to investigate other possible causes for the thrombocytopenia.

Accelerated formation of platelets results in the presence of abnormally large platelets which are seen in a peripheral blood smear. Overall bleeding time is prolonged in these patients, but prothrombin time (PT) and partial thromboplastin time (PTT) are normal (because the problem is with the platelets, not with the coagulation cascade).

Occasionally, autoimmune hemolytic anemia and immune thrombocytic purpura may coexist, which is a condition called Evans syndrome.

Treatment

Mild ITP does not require treatment. When platelet counts fall under 10,000 per microliter, or under 50,000 when hemorrhage occurs (e.g. in the digestive tract or in a severe nosebleed) treatment is generally initiated with steroids. Intravenous immunoglobulin (IVIg) is used for life threatening cases. Later, so-called steroid-sparing agents (alternatively called DMARDs) may be used. When these strategies fail, splenectomy (removal of the spleen) is often undertaken, as platelets targeted for destruction will often meet their fate in the spleen. A relatively new strategy is treatment with anti-D, an agent used in mothers who have been sensitized to rhesus antigen by a Rh+ baby, but the patient must be Rh+. Immunosuppresants like mycophenolate mofetil and azathioprine are becoming more popular for their effectiveness. Rituximab has also been used with some success for some patients.

Extreme cases (very rare, especially rare in children) may require vincristine, a chemotherapy agent, to stop the immune system from destroying platelets.

Intravenous immunoglobulin, while sometimes effective although not all patients respond, is expensive and the improvement is temporary (generally lasting less than a month). However, in the case of a pre-splenectomy ITP patient with dangerously low platelet counts, and a poor response to other treatments, IVIg treatment can increase platelet counts, making the splenectomy operation less dangerous.

Platelet transfusion is not normally recommended and is usually unsuccessful in raising a patient's platelet count. This is because the underlying autoimmune mechanism that destroyed the patient's platelets to begin with will also destroy donor platelets. An exception to this rule is when a patient is bleeding profusely, when transfusion of platelets can quickly form a platelet plug to stop bleeding.

Synonyms

ITP knows many synonyms, but idiopathic or immunological thrombocytopenic purpura are the most common names. There's also an eponym, Werlhof's disease, but this is used infrequently.

Other synonyms include: essential thrombocytopenia, haemogenia, haemogenic syndrome, haemorrhagic purpura, idiopathic thrombopenic purpura, morbus haemorrhagicus maculosus, morbus maculosis haemorrhagicus, morbus maculosus werlhofii, peliosis werlhofi, primary splenic thrombocytopenia, primary thrombocytopenia, primary thrombocytopenic purpura, purpura haemorrhagica, purpura thrombocytopenica, purpura werlhofii, splenic thrombocytopenic purpura, thrombocytolytic purpura.

References

Cines DB, Blanchette VS. Immune thrombocytopenic purpura. N Engl J Med 2002;346:1008. PMID 11919310.
Blood review article, October 1, 2005.
Provan D, Newland A. Fifty years of idiopathic thrombocytopenic purpura (ITP): management of refractory ITP in adults. Br J Haematol 2002;118:933-44. Fulltext. PMID: 12199770.
ITP Primer: ITP (idiopathic thrombocytopenic purpura, immune thrombocytopenic purpura)
Kumar, Vinay, Abul Abbas, and Nelson Fausto. Robins and Cotran Pathologic Basis of Disease, 7th ed. (2004). ISBN 81-8147-528-3
Sacher, Ronald A. and Richard A. McPherson. Wildman's Clinical Interpretation of Laboratory Tests, 11th ed. (2000). ISBN 0-8036-0270-7
Drug Induced Thrombocytopenia
- Paul Gottlieb Werlhof

Hematology