Welcome to the Rare Classroom, a new series from Patient Worthy. Rare Classroom is designed for the curious reader who wants to get informed on some of the rarest, most mysterious diseases and conditions. There are thousands of rare diseases out there, but only a very small number of them have viable treatments and regularly make the news. This series is an opportunity to learn the basics about some of the diseases that almost no one hears much about or that we otherwise haven’t been able to report on very often.
Eyes front and ears open. Class is now in session.
The disease that we will be learning about today is:
Immune Thrombocytopenia
Also called immune thrombocytopenic purpura and idiopathic thrombocytopenic purpura, or autoimmune thrombocytopenic purpura.
What is Immune Thrombocytopenia?
- ITP – Immune thrombocytopenia (also known as immune or idiopathic thrombocytopenic purpura) is a bleeding disorder in which the immune system destroys platelets, which are necessary for normal blood clotting
- The acute form often follows an infection and has a spontaneous resolution within 2 months
- Chronic idiopathic thrombocytopenic purpura persists longer than 6 months with a specific cause being unknown
- Usually chronic in adults
- With ITP, platelets are marked as foreign by the immune system and eliminated in the spleen, the liver, and by other means
- Platelet destruction in ITP is accompanies by suboptimal platelet production
- If someone has a platelet count lower than 100,000/microliter of blood with no other reason for low platelets, that person is considered to have ITP
- The incidence of ITP is estimated at 50–100 new cases per million per year, with children accounting for half of that amount
- The probability of remission in adults is 20-40%
- The male to female ratio in the adult group varies from 1:1.2 to 1.7 in most age ranges
- The ratio between male and female adult cases tends to widen with age
- The median age of adults at the diagnosis is 56–60
- In the US, the adult chronic population is thought to be approximately 60,000—with women outnumbering men approximately 2 to 1
- ITP is designated as an orphan disease in the US
How Do You Get It?
- The cause of ITP is poorly understood
- In around 60 percent of cases, IgG antibodies against platelets can be detected
- The suspected cause of these antibodies is abnormal T-cell activity
What Are The Symptoms?
- In some cases, there are no noticeable symptoms, but when present they can include:
- Petechiae – small, reddish-purple spots that look like a rash, but are not raised
- Bruising or purpura – dark red or purple bruises with no known cause
- Any bleeding that may be unusual, heavier, or lasting longer than usual: heavy menses in women, frequent, heavy, or persistent nosebleeds, bleeding inside the mouth on the cheeks (blood blisters) or from the gums with no known cause, blood in urine or stool, fatigue, depression
- Low platelet count
How Is It Treated?
- Treatment type is dependent on symptoms, platelet count, and other factors
- The main goal of treatment is to maintain the platelet count
- This reduces the risk of bleeding
- Managing treatment toxicity is the other main concern
- Adults with mild cases may only require regular monitoring and platelet checks
- First line therapy when treatment is needed is corticosteroids, usually prednisone
- Helps raise platelet count by decreasing the activity of the immune system
- Usually tapered of corticosteroids after 2-6 weeks
- Many experience a relapse after discontinuing corticosteroids
- Long term use not recommended due to serious side effects
- Intravenous immune globulin (IVIG)
- Used for critical bleeding or to quickly increase blood count before surgery
- Quick and effective but generally wear off in a few weeks
- Rho(D) Immune Globulin may also be an option in certain patients
- Splenectomy
- An option if ITP is severe and corticosteroids have not been effective
- Improves platelet count as the spleen is responsible for much platelet destruction
- Does not work in all patients
- Permanently increases risk of infection
- Thrombopoietin receptor agonists
- Newest medications to treat ITP
- Promacta® (eltrombopag) and Nplate (romiplostim)
- Help bone marrow produce more platelets
- TPO receptor agonists are novel treatments for patients with chronic ITP aimed at increasing platelet production through interactions with the TPO receptor on megakaryocytes
- Thrombopoietin receptor agonists (TPOr) are typically used in patients with ITP who have failed to respond to corticosteroids, and who have either had a splenectomy which has not resolved the ITP, are not candidates for splenectomy, or have refused splenectomy
- Have been shown to increase platelet counts, decrease bleeding events and reduce the need for adjunctive or rescue treatments
- Uncertainty remains regarding the risk of thromboembolism
- Recently published American Society of Hematology guidelines on ITP suggest initiating treatment with TPO receptor agonists in patients at risk of bleeding who relapse following splenectomy or have a contraindication to splenectomy and previous treatment failure
- Remissions of ITP have been reported after TPO receptor agonist discontinuation, though thrombocytopenia usually recurs, requiring long-term use of these drugs
- Platelet count should be measured weekly until a stable platelet count that is associated with an absence of bleeding symptoms is achieved for 4 weeks without adjustment and then measured monthly thereafter
- Promacta® is indicated for the treatment of thrombocytopenia in patients with chronic immune (idiopathic) thrombocytopenia (ITP) who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy
- Promacta® is taken daily in pill form on an empty stomach, allowing 4 hours between taking Promacta® and other medications, foods or supplements containing polyvalent cations
- Most common adverse effects: nausea, diarrhea, upper respiratory tract infection, vomiting, increased ALT, myalgia, urinary tract infection, oropharyngeal pain, increased AST, pharyngitis, back pain, influenza, paresthesia, and rash
- Warnings include: hepatotoxicity requiring monitoring of the liver before and during treatment, new or worsened cataracts and thrombotic/thromboembolic complications resulting from increasing platelet counts.
- Nplate is indicated for the treatment of thrombocytopenia in patients with ITP who have had an insufficient response to corticosteroids, immunoglobulins, or splenectomy
- Nplate is administered once weekly as a subcutaneous injection by a healthcare provider
- Most common adverse reactions are arthralgia, dizziness, insomnia, myalgia, pain in extremity, abdominal pain, shoulder pain, dyspepsia and paresthesia
- Warnings include: thrombotic/thromboembolic complications resulting from increasing platelet counts and loss of response to Nplate requiring prompt investigation including sending blood samples to Amgen to test for antibodies to Nplate
- Until December of 2011, Nplate was only available through a REMS program. That was discontinued as more safety data was made available on the drug
- Biologic therapy
- Rituxan (rituximab) helps reduce the immune system response
- Used for severe ITP
- Emergency Treatment
- Occasionally ITP can result in severe bleeding which could require transfusion of platelet concentrates, intravenous methylprednisolone and intravenous immune globulin
- Less Commonly Used Treatment
- Immunosuppressant drugs (Cytoxan, Imuran, Azasan) – can cause significant side effects
- H. pylori Treatment – If patient is infected with Helicobacter pylori, eliminating the bacteria has been effective in treating some patients
- The probability of remission in chronic ITP is 20-40%
- The mortality rate due to chronic ITP is usually higher than the general population. The increased rate of death is generally concentrated in the middle aged and elderly.
- Hemorrhage is rare with chronic ITP, but can occur and can be fatal
- The most frequent cause of death in association with ITP is spontaneous or accidental trauma-induced intracranial bleeding – most cases occur in those with platelet counts of less than 10,000
- Those who have had a splenectomy need to watch closely for signs of infection
Where Can I Learn More???
- Check out our cornerstone on this disease here.
- Learn more about this illness from the Platelet Disorder Support Association.
