Immune thrombocytopenic purpura

Immune thrombocytopenic purpura (ITP) is a disease characterized by thrombocytopenia (a decrease in the number of platelets in the blood), which can lead to hemorrhages in the skin and other organs.

It is important to differentiate this disease from the symptom known simply as "purpura". Purpura refers to the appearance of purplish spots on the skin, which is a symptom common to many different bleeding disorders (including ITP).

While ITP was previously referred to as idiopathic thrombocytopenic purpura, the preferred term is now immune thrombocytopenia purpura to avoid the term "idiopathic" and emphasize the immune mechanism behind the disease.

Additionally, the term "purpura" is considered inappropriate in many cases, as hemorrhagic symptoms may be minimal or entirely absent.

ITP is a very rare disease, making its diagnosis challenging.

Primary immune thrombocytopenia (ITP) is caused by the immune system producing antibodies, particularly immunoglobulin G (IgG), that target platelets. This causes the spleen to recognize platelets as foreign cells and destroy them.

In addition to increased platelet destruction, there is also a reduction in platelet production in the bone marrow, though the exact reason for this decrease is not fully understood.

As a result of these processes, the number of circulating platelets in the blood decreases.

The reasons for these immune changes may have a genetic basis and are often associated with certain diseases that trigger thrombocytopenia. Common triggers include viral infections (especially HIV and Hepatitis B and C), lymphoid tumors (such as chronic lymphocytic leukemia), and autoimmune diseases (like systemic lupus erythematosus). In some geographic areas, infection with Helicobacter pylori is also a contributing factor.

In children, ITP often appears following a viral infection. Acute ITP is most common in children between the ages of two and nine.

Platelets play an essential role in blood clotting, wound healing, and even in defending against infections. People with significant thrombocytopenia, including those with ITP, are therefore at increased risk of bleeding and infections.

Patients with ITP may remain asymptomatic, with the disease being detected incidentally through blood tests showing low platelet counts. In other cases, bleeding symptoms common to all forms of thrombocytopenia may occur, including:

• Persistent skin bleeding (especially in areas prone to trauma), such as:
  • Petechiae (small, pink-red spots on the skin).
  • Purpura (purple spots on the skin larger than 2.5 cm in diameter).
  • Ecchymoses (larger bruises on the skin).
  • Bleeding at puncture sites (from injections, blood tests, IV placements, etc.).
• Hemorrhages involving mucous membranes:
  • Epistaxis (nosebleeds).
  • Menorrhagia (heavy menstrual bleeding).
  • Gastrointestinal bleeding: blood in the stool or vomiting blood.
  • Hemoptysis (coughing up blood).
  • Hematuria (blood in the urine).
• Bruising (accumulation of blood in tissues or organs).
• Ocular bleeding: conjunctival and retinal hemorrhages.
• Internal bleeding and hemarthrosis (joint bleeding), though rare.

Paradoxically, some patients may also experience symptoms of thrombosis (excessive blood clot formation), though the cause is unclear, especially in the early stages of the disease.

In patients with ITP who have been treated, the risk of thrombosis increases due to the use of medications like corticosteroids and is further heightened if a splenectomy (removal of the spleen) is performed.

Other symptoms of ITP can include an increased susceptibility to infections and asthenia (fatigue).

The diagnosis of ITP is established through a combination of clinical history, physical examination, and platelet count.

Non-trauma-related bleeding is generally not concerning as long as the platelet count remains above 20,000/mm³. However, traumatic bleeding can occur when platelet counts are between 40,000 and 60,000/mm³. Other routine coagulation studies are usually normal, except for a prolonged bleeding time.

The primary goal of the diagnostic process is to exclude all other potential causes of thrombocytopenia, making ITP a diagnosis of exclusion.

The recommended tests when ITP is suspected include:

• Complete blood count (CBC) with reticulocyte countl.
• Peripheral blood smear: microscopic examination to assess the shape and size of platelets.
• Basic urinalysis: detecting blood in the urine is a sign of high risk.

Other tests, such as immunological evaluations, may be conducted by a hematologist depending on the specific case.

Treatment is not necessary for patients with mild thrombocytopenia and is typically reserved for those experiencing bleeding due to thrombocytopenia or for patients with platelet counts below 20,000/mm³. The primary goal of treatment is to stop bleeding and raise the platelet count above 20,000/mm³.

In high-risk cases, initial hospitalization may be required.

The treatment options include:

• Corticosteroids: Prednisone can be used for up to 6 weeks, with a success rate of up to 80%. Dexamethasone may also be used in cycles. Although long-term use of corticosteroids can cause side effects, prolonged treatments are rarely necessary. Modern approaches closely monitor and manage dosage, duration, and side effects.

If corticosteroids are ineffective, the next recommended treatments are:

• Thrombopoietin receptor agonists (TPO-RAs): Romiplostim and eltrombopag can be used in patients, whether they have undergone splenectomy or not. For cases unresponsive to corticosteroids, these are currently the most effective options.
• Splenectomy (surgical removal of the spleen): This is reserved for patients resistant to conservative treatments or those with hypersplenism. Splenectomy is rare in children and has a success rate of 60% to 80%. Laparoscopic splenectomy is preferred over laparotomy due to a lower risk of complications. After splenectomy, there is an increased risk of infections by encapsulated bacteria (e.g., pneumococcus), which is managed by administering pneumococcal vaccines every 5 years and using early antibiotic treatment (e.g., penicillin) at the first sign of infection. Splenectomy carries greater risks for obese patients, those over 60 years of age, and individuals with other underlying conditions.
• Other medications: Rituximab and fostamatinib are alternative treatments.

If patients do not respond to these treatments, a combination of medications may be considered, or the diagnosis of ITP may need to be re-evaluated.

Currently, there is no known way to prevent ITP.