Chronic immune thrombocytopenic purpura (ITP) is a disorder characterized by thrombocytopenia resulting from immune-mediated hyper-destruction of platelets, along with associated impaired thrombocyte synthesis. Chronic ITP occurs in both children and adults. In children, ITP is usually acute in onset and self-limiting, whereas in adults it runs a more chronic course.
The presentation mostly depends on the platelet count of the patient. The lower the platelet count, the worse the bleeding. Most patients are asymptomatic. The hallmark of presentation is the variation in the degree of bleeding. Patients may present with easy bruisability or mucosal bleeding or with more severe bleeding manifestations, which include menorrhagia, hemorrhage in the gastrointestinal and urinary tracts, and in some cases intracranial hemorrhage   .
Chronic ITP is a diagnosis of exclusion and hence, there is no standard laboratory investigation for the diagnosis of chronic ITP. It is important to rule out other causes of thrombocytopenia and the history, physical examination and investigations are tailored to this aim. The diagnosis should be constantly evaluated in light of an appearance of new clinical or laboratory features.
Amongst the investigations that are recommended are a complete blood count and a blood smear examination to exclude disorders like leukemia, thrombotic thrombocytopenic purpura, and pseudo-thrombocytopenia. A history of autoimmune disorders in the family should be enquired for. Viral screens to rule out HIV, hepatitis C and other viruses must be carried out. Some studies advocate a diagnosis of chronic ITP based on the patient response to intravenous immunoglobulins.
Other optional investigations would include an erythrocyte sedimentation rate (ESR), blood grouping, antibody testing such as ANA and anti-cardiolipin and a direct antiglobulin test. It is to be noted that thrombopoietin and anti-platelet antiphospholipid antibody levels are not routinely measured, despite their central role in the pathogenesis. Bone marrow evaluations and biopsy are usually only done prior to splenectomy in patients aged 60 years or more.
The treatment could be medical or surgical. The impact and side effects of all possible treatments should be fully discussed with patients. First-line therapy for individuals with low platelet counts is usually medical. Drugs are also used to manage recurrent cases of chronic ITP as well as patients who do not get better with splenectomy.
The first-line medications in the management of chronic ITP, as per national guidelines, include the use of oral corticosteroids. Second line drugs include intravenous immunoglobulins, rituximab, danazol, cyclosporine, mycophenolate mofetil or cytotoxic agents (e.g cyclophosphamide or azathioprine)    .
Despite the effectiveness of these drugs, their adverse drug reactions should also be considered . For example, patients receiving corticosteroids have an increased risk of suffering from obesity, gastrointestinal bleeding, myocardial infarction and osteoporosis . Danazol is associated with rashes and liver failure . Similarly, rituximab as an infusion may cause chills, fever or anaphylaxis . Cytotoxic drugs reduce the cell counts and could also predispose to secondary malignancies. Patients on immunosuppressive drugs have an increased risk of infection .
Surgery, in the form of splenectomy, is usually reserved for patients who do not respond to medical treatment or relapse after initial medical treatment. Splenectomy is also indicated in patients who require very high intolerable doses of oral drugs to achieve platelet counts that can maintain hemostasis . In about two third of patients who have had a splenectomy, long-term disease management was achieved. However, patients who undergo splenectomy are at an increased risk of developing severe sepsis.
The older the patient (greater than 60 years), the worse the prognosis. Patients with a platelet count of less than 30 x 109 /L are at a risk of severe and fatal bleeding. Such patients under 40 years of age have a 2.2% 5-year mortality rate, while patients older than 60 years have a 47.8% mortality rate within 5 years .
Immune thrombocytopenic purpura is a disorder affecting all age groups. In children, it mainly occurs secondary to a viral infection and most often has an acute presentation. In adults, it usually runs a more chronic course. Chronic ITP is usually idiopathic. ITP can also occur in individuals secondary to an underlying disorder such as systemic lupus erythematosus (SLE) and infections like autoimmune hepatitis C and human immunodeficiency virus (HIV) . Some studies indicate a correlation between chronic ITP and Helicobacter pylori infection, although this hasn’t been proven entirely yet.
ITP results from:
In chronic ITP, autoantibodies are formed that react against the platelet membrane glycoproteins.
Three-quarters of autoantibodies are formed against platelet GPIIb/IIIa or GPIb/IX GP complexes, while the remaining are formed against other platelet antigens, such as GPV, GPIa/IIa, or GPIV.
Splenic destruction of thrombocytes
In the spleen, there is increased phagocytosis of autoantibody coated platelets because of their sluggish movement through the sinusoids. It is also the site of production of such autoantibodies.
ITP affects 5 in 100,000 children and 2 in 100,000 adults every year . ITP presents in 2 distinct forms, the acute variant found more frequently in children while the chronic type is predominantly a disease of adults. Chronic ITP is more commonly seen in women, with most patients aged 20-50 years.
Chronic ITP is an interplay between the following mechanisms: immune-system led destruction of platelets and reduced production of platelets from the bone marrow, both cumulatively resulting in thrombocytopenia.
T cells stimulate B cells to produce antiplatelet antibodies, which then coat the platelets. These opsonized platelets bind to antigen presenting cells via Fcγ receptors and are hence, phagocytosed and destroyed. Most drugs used in the treatment of chronic ITP are targeted at reducing this platelet destruction.
There is also reduced marrow platelet production as shown by the role of thrombopoietin (TPO), an enzyme which helps in thrombopoiesis. Studies have shown a remarkable increase in the platelet count in individuals who were given TPO mimetics.
Therapy is aimed at reducing the hyper-destruction of platelets by the immune system and hence, immunosuppressant drugs are the treatment of choice for this disease. Ongoing research indicates a future role for TPO in this treatment regimen.
No preventive strategies are currently known.
Immune thrombocytopenic purpura (ITP) is a bleeding disorder characterized by thrombocytopenia resulting primarily from premature destruction of autoantibody-coated platelets. A disease of both children and adults, it presents mainly with an acute and self-limited course in the former, while a more persistent, recurrent version occurs in adults.
The first mention of this disease was made in 1735 in P.G Werlhof’s "Morbus Maculosus Hemorrhagicus" . Since then, multiple studies (e.g. Harrington's studies) have confirmed the central role played by the immune system in this disease . Platelets, coated with autoantibodies, become a target for destruction by the reticuloendothelial system, especially the spleen. Platelet synthesis and maturation are also affected due to the autoantibodies reacting with the megakaryocytes. Thrombocytopenia in chronic ITP is thus a consequence of both increased platelet destruction (primarily) and a decrease in platelet production.
Chronic ITP is a peculiar disease owing to it being a diagnosis of exclusion. A proper history, physical examination, a complete blood count and peripheral smear are needed to rule out the other causes of thrombocytopenia, including infections, autoimmune diseases, drugs, malignancies etc. . Autoantibodies are usually not measured due to their lack of sensitivity . Bone marrow examination may be needed in some patients such as in the elderly, those with an atypical presentation or in those requiring a splenectomy.
Chronic immune thrombocytopenic purpura (ITP) is a disease in which the immune system of the body attacks its own platelets, thereby reducing the platelet count of the body. Platelets are responsible for prevention of bleeding and hence, these patients with low platelet counts present with various forms of bleeding (e.g. purpura). The body's immune system, for reasons not fully understood, creates autoantibodies against its own platelets. These autoantibodies also cause damage to the platelet-producing cells, the megakaryocytes.
Most patients are asymptomatic and are discovered during routine investigations. Patients may face similar situations upon ingesting certain drugs like quinidine, quinine or sulfa-like drugs. This disorder may be linked to other diseases such as systemic lupus erythematosus, lymphoproliferative disorders (e.g. non-Hodgkin lymphoma) or infections (e.g., HIV disease, cytomegalovirus infection or hepatitis).
Most patients with chronic ITP are asymptomatic. The typical presentation includes pin point bruises on the lower limbs, bleeding from the nose and gums, blood in urine or rarely bleeding from the stomach and bowel. Ingestion of certain drugs (e.g. ibuprofen, aspirin) that interfere with platelet function may worsen the bleeding manifestations. Women may have increased menstrual bleeding while children may show bleeding manifestations in the brain vault.
Chronic ITP is a diagnosis of exclusion and there is no definitive test to make or exclude its diagnosis. As such other causes leading to thrombocytopenia, including bone marrow disorders (e.g. aplastic anemia, leukemia) must be ruled out. Following investigations ordered for other purposes, a low platelet count may be discovered in otherwise healthy individuals or asymptomatic patients.
It is possible the platelets may appear low due to clumping and this differentiation can be made clearly on examination under a microscope. It is also important to check the size of the platelets and to ascertain that the other blood cells are normal. This also rules out leukemia or anaplastic anemia as possible causes. Furthermore, a bone marrow biopsy may be conducted to gain further clarity on the diagnosis.
To summarize, the diagnosis of chronic ITP is considered in an otherwise healthy patient who has thrombocytopenia and no other abnormality on the complete blood count and also has taken no new medications or has a family history of thrombocytopenia.
The first line medications in the management of chronic ITP are oral corticosteroids according to national guidelines. Other agents that may be used include intravenous immunoglobulins and intravenous corticosteroids. Surgery in the form of splenectomy is an option in serious cases. A combination of these treatments may be used if chronic ITP recurs.