Immune Thrombocytopenic Purpura

What is Immune Thrombocytopenic Purpura?

Immune thrombocytopenic purpura (ITP) is a condition caused by a type of antibody (immunoglobulin G – IgG) targeting the body’s own cells called platelets. Symptoms include low platelet count leading to purplish patches on the skin (purpura) and episodes of bleeding. It is diagnosed primarily by eliminating other known causes of a low platelet count. This condition can affect both adults and children. According to the American Society of Hematology, ITP is characterized by a widespread purplish rash, a platelet count less than 100,000/μL, and normal levels of both white blood cells and hemoglobin. If a patient has abnormal levels of white blood cells or hemoglobin, it could indicate a different medical problem and further tests should be carried out.

There are two types of ITP, primary and secondary. Primary ITP develops without a known cause, while secondary ITP occurs due to other medical conditions like drug reactions, autoimmune diseases (like systemic lupus erythematosus), certain forms of cancer (like chronic lymphocytic leukemia), and infections like HIV. Primary ITP is classified further based on the timing and persistence of symptoms. Newly diagnosed ITP refers to the first 3 months following diagnosis. If symptoms continue between 3 to 12 months following diagnosis, it is labelled as persistent ITP. Chronic ITP describes symptoms persisting beyond a year from diagnosis. Refractory ITP refers to cases that do not improve even after removal of the spleen.

A very low platelet count, below 20,000/μL, is considered severe and requires medical treatment, often with drugs that suppress the immune system.

Platelets have a key role in blood clotting. They come from cells in the bone marrow called megakaryocytes through a process known as “thrombopoiesis.” Usually, the number of platelets in the blood is between 150,000 to 350,000 per μL, and they live for about 7 to 10 days. A hormone known as thrombopoietin (TPO), mainly produced in the liver, kidneys, and bone marrow, controls platelet production. Infections, inflammation, or bleeding can trigger a surge in platelet production to keep their level normal.

Platelets are distinctive. They’re disc-shaped, don’t have a nucleus (the centre of a cell where DNA is stored), and have many tiny granules containing clotting factors and inflammation-triggering substances. A receptor, called Glycoprotein IIb/IIIa, on the platelet surface is key to allowing platelets to clump together and help form blood clots. The spleen plays an important role in platelet health as well by removing old or damaged platelets from the circulation.

What Causes Immune Thrombocytopenic Purpura?

Infections and changes to the immune system are the two main triggers of Immune Thrombocytopenia (ITP), a disorder that affects blood platelets. Often, viral illnesses come before infection-linked cases of ITP. Our bodies make proteins called antibodies to fight off the viral infections, but sometimes these proteins can mistakenly attack our own healthy platelet cells. Common viral infections that are related to ITP include HIV, hepatitis C, cytomegalovirus, and chickenpox.

ITP can also occur due to changes in the immune system brought on by autoimmune disorders, which cause the body to mistakenly attack its own cells. Autoimmune disorders that often cause ITP include antiphospholipid syndrome, Lupus, Evans syndrome (a rare autoimmune disorder), bone marrow transplant, common variable immunodeficiency (a disorder that impairs the immune system), and autoimmune lymphoproliferative syndrome (a condition affecting how the body gets rid of immune cells).

Certain medications are known to cause ITP, some of which include:

– Abciximab
– Certain types of antibiotics
– Carbamazepine
– Eptifibatide
– Gold compounds
– Heparin
– Phenytoin
– Linezolid
– Measles, mumps, and rubella vaccine
– Piperacillin
– Quinine
– Various types of sulfonamide medicines
– Vancomycin
– Tirofiban
– Rifampin
– Trimethoprim-sulfamethoxazole

Certain types of cancer, like chronic lymphocytic leukemia (CLL), adenocarcinoma, and lymphoma, can cause ITP. Hormonal disorders like hypothyroidism and Addison’s disease can also contribute to ITP symptoms. Autoantibody production, which is essentially the body attacking its own cells and the failure of self-tolerance (the body’s ability to recognize and not attack its own cells) are thought to be the main causes in all these cases.

Risk Factors and Frequency for Immune Thrombocytopenic Purpura

Pediatric ITP, or Pediatric Immune Thrombocytopenia, affects between 1 and 6.4 out of every 100,000 people each year. Some researchers believe this number might actually be higher, as not all cases are reported or require hospital stays. The illness can affect children at any age, but it is most common in toddlers aged 2 to 5, and teenagers. Younger children of male gender are more likely to get this illness, but once individuals reach their teens or become young adults, females tend to develop ITP more frequently. This is believed to be due to the effects of estrogen, a hormone found in greater amounts in females, which can sometimes affect immune functions.

• Pediatric ITP can take an acute or chronic form.
• The acute form usually appears in childhood, often after a viral infection, and gets better on its own within three months.
• The chronic form is more likely to occur in adults, and the triggering factor is often unclear. Some possible contributors may be changes in the immune system due to aging, underlying health conditions, or certain medications.
• About 1 in 4 children in the United States may develop a persistent or chronic form of ITP, where the associated low platelet count (thrombocytopenia) can lead to dangerous bleeding.

Doctors have also noticed that more children seem to get ITP in the spring and early summer, which coincides with common viral infection seasons. As for adults, ITP affects approximately 1 to 6 out of every 100,000 people each year as well, but it’s more often a chronic illness in this age group. Consequently, about 12 in every 100,000 adults are living with ITP at any given time. The incidence peaks at approximately age 60, but the numbers increase with age and are almost equal between the sexes in those aged 60 and above.

Signs and Symptoms of Immune Thrombocytopenic Purpura

Immune Thrombocytopenia (ITP) is a condition that can sometimes cause no symptoms, but if symptoms are present, they can vary from mild to severe. The most common symptom is mucocutaneous bleeding, which can show up as minor spots under the skin (petechiae) and nosebleeds or as severe, potentially life-threatening bleeding in the stomach, brain, or urinary tract. Other symptoms can include bruises, a rash, and feeling tired, although tiredness usually gets better with treatment and increasing platelet counts. Risk factors for severe bleeding include a very low platelet count, particularly in older individuals, and minor bleeding episodes shortly after being diagnosed with ITP.

Some patients may experience additional symptoms such as a fever, weight loss, lack of appetite, night sweats, or bone pain. Female patients may notice changes in their menstrual cycle. It’s also important to consider dietary factors, as certain foods and drinks like tonic water and “jello shots” contain substances that could trigger a low platelet count. A personal history of bleeding, family history of bleeding or platelet disorders, recent medication changes, or certain existing medical conditions could help in diagnosing ITP.

During a physical examination, the doctor will pay special attention to vital signs, skin and mucous membranes, the head and neck area, the abdomen, and neurological status. ITP can cause bleeding in areas such as the nasal passages, oral cavity, gastrointestinal and genitourinary tracts. However, it’s rare to see bleeding in the eyes. Most children with ITP seem healthy and have normal vital signs, but they often have a characteristic rash of tiny red spots that don’t fade when pressed. On the other hand, about two-thirds of adults with ITP have bleeding that can range from a rash to moderate mucosal bleeding and, in rare cases, haemorrhage. In severe cases of ITP, individuals might show neurological symptoms due to hemorrhaging in the brain.

Testing for Immune Thrombocytopenic Purpura

ITP, which stands for Idiopathic Thrombocytopenic Purpura, is a condition where your immune system mistakenly targets your own body’s platelets, which are cells that help the blood clot. Diagnosing ITP often involves ruling out other conditions that could cause similar symptoms.

In the initial stages of assessment, doctors typically request a few blood tests, such as a Complete Blood Count (CBC), which measures the amount of different types of cells in your blood, and a Peripheral Blood Smear (PBS), which examines those cells under a microscope. People with ITP usually have normal red and white blood cell counts, but a low platelet count, usually less than 100,000 per microlitre of blood. However, these results can vary depending on other health conditions or recent infections. For example, bacterial infections can lead to an increased number of a type of white blood cell called neutrophils, while viral infections can result in reduced overall white cell counts.

Reviewing the CBC and PBS tests, doctors expect to see low platelet counts with otherwise normal-looking red and white cells. The count of immature red blood cells, or reticulocytes, is typically normal unless there’s a significant blood loss. The presence of certain white cell types could suggest conditions like cancer which are causing the low platelet count. If the red blood cells appear oddly shaped or colored under the microscope, this could suggest other types of anemia, where the blood cell count or function is impaired.

Blood typing is important, especially if you might need a blood transficusion. However, some tests like the antiplatelet antibody test, aren’t usually recommended for diagnosing ITP. This is because these tests have high specificity (meaning they are good at identifying true cases of ITP) but low sensitivity (meaning they are not very good at ruling out ITP if the test result is negative).

If your doctors suspect that you might have an immune system disorder, they may conduct tests to assess levels of different immune cells. They usually avoid bone marrow tests unless they suspect cancer or severe damage to your marrow, causing it to make fewer blood cells.

Those with severe ITP symptoms might undergo a few more tests. These could include coagnulation tests to see how well your blood clots, tests to check for infections that could cause ITP symptoms, or before surgical procedures, tests to check for any hormonal disorders that could complicate surgery. Also, since some people with ITP have other autoimmune disorders, doctors might conduct tests to check for conditions like Systemic Lupus Erythematosus (SLE), where the immune system targets the body’s own tissues and organs, and others.

So, although diagnosing ITP might seem complicated, remember that all of these tests help doctors gather the information they need to manage your condition in the safest and most effective way possible.

Treatment Options for Immune Thrombocytopenic Purpura

The American Society of Hematology (ASH) issued guidelines in 2019 regarding the care of adult and child patients with a condition called immune thrombocytopenia (ITP). These outlined a treatment plan depending on factors such as the presence and type of bleeding, the platelet count, patients’ risk of bleeding and other social factors, and any previous treatments.

When adults are first diagnosed with ITP with a platelet count less than 30,000 per unit of blood and experience minor bleeding, the ASH recommends treatments with corticosteroids over just observation. However, for adults with similar symptoms and a platelet count at least 30,000, ASH advises against corticosteroids, suggesting observation only. This could change based on factors such as platelet counts which are near the threshold, supplementary conditions, usage of anticoagulant or antiplatelet medication, upcoming procedures, and age (especially if older than 60).

For adults diagnosed with ITP with a platelet count of less than 20,000 and minor bleeding (or no symptoms), ASH recommends hospital admission as opposed to outpatient management. Patients not admitted to the hospital should receive education and quick follow-up appointments with a hematologist.

In contrast, outpatient management is suggested for children newly diagnosed with ITP with a platelet count of less than 20,000 and minor bleeding limited to skin appearances. The specific condition of each child must be taken into account, however, particularly factors such as diagnostic uncertainty, concerns regarding distance from the hospital, social factors, and follow-up uncertainties.

ASH proposes initial corticosteroid therapy (such as prednisone or dexamethasone) for adults newly diagnosed with ITP. In certain cases if corticosteroids are not suitable, the use of intravenous immunoglobulin (IVIG) or anti-D immunoglobulin may be considered. These treatments aim to help your immune system work properly.

If first-line therapies or chronic ITP do not improve health-related quality of life for children, ASH suggest trying out thrombopoietin receptor agonists (TPO-RAs, like eltrombopag or romiplostim). If these do not work, the next therapy of choice is rituximab.

Splenectomy, or the removal of the spleen, is typically reserved for more severe cases of thrombocytopenia. However, this procedure is usually delayed as long as possible due to potential risks, such as infection following the surgery.

There are also several medications under investigation for treating ITP. Some of these include efgartigimod, rozanolixizumab, sutimlimab, and rilzabrutinib, which may be useful in controlling symptoms. However, these drugs are still being studied and have not yet been approved for routine use.

Once a treatment is started, the platelet levels should be monitored every week after a dose or drug adjustment until the patient’s condition stabilizes on the current therapy. Platelet levels should also be checked whenever a mouth or skin bleeding occurs.

What else can Immune Thrombocytopenic Purpura be?

When looking for possible causes of low platelet count, or thrombocytopenia, doctors need to consider a variety of conditions. These can include:

• Leukemia, specifically acute lymphocytic leukemia,
• Active infections like HIV, Epstein-Barr virus, cytomegalovirus, and hepatitis C
• Autoimmune hemolytic anemia
• Systemic autoimmune diseases, such as SLE and autoimmune lymphoproliferative syndrome,
• Immunodeficiency syndromes, like common variable immunodeficiency
• DiGeorge syndrome,
• Wiskott-Aldrich syndrome
• Certain medications, such as heparin, quinidine, phenytoin, sulfonamides, valproate, and vancomycin
• Bone marrow failure such as aplastic anemia
• Hemolytic uremic syndrome,
• Thrombotic thrombocytopenic purpura,
• Disseminated intravascular coagulation related to sepsis, trauma, or cancer
• Posttransfusion purpura, a reaction to blood transfusion
• Neonatal immune thrombocytopenia originated from mother to newborn transmission of antiplatelet antibodies
• Sepsis,
• Vitamin B12 deficiency leading to megaloblastic anemia and thrombocytopenia
• Preleukemia, refractory anemias, and hematopoietic dysplasia,
• Hypersplenism, possible complication of liver cirrhosis.

These conditions can be carefully examined and ruled out using detailed clinical and laboratory testing. This is crucial in reaching the correct diagnosis and appropriate treatment for thrombocytopenia.

What to expect with Immune Thrombocytopenic Purpura

Most kids get better from Immune Thrombocytopenia (ITP), a disorder that can lead to easy or excessive bruising and bleeding, within 3 to 6 months after it first shows regardless of the treatment provided. Some research indicates that around 10% – 20% of these children might see the disorder becoming chronic, or long-lasting.

There are certain risk factors that contribute to ITP turning chronic. These include: the child being older when diagnosed, the disorder not being very severe at the beginning, experiencing slow-developing symptoms, and not having received a vaccination or had an infection prior to the diagnosis. It’s also a risk if the child did not display mucosal bleeding, or bleeding from places like the nose, mouth, and gastrointestinal tract, when first diagnosed.

About 50% of kids with chronic ITP recover spontaneously, usually within the first 2 years after diagnosis but it can also happen up to 5 years after the diagnosis. Kids younger than 10 years old are more likely to recover from chronic ITP than older children.

Death from ITP in children is rare, and it’s mostly caused by complications from bleeding, specifically Intracranial hemorrhage (ICH) or bleeding inside the brain. Most of the time, any other diseases or complications in children with chronic ITP are from the long-term use of medicine that suppresses the immune system, mainly due to infections.

Most adults with ITP reach a stable platelet count, which helps the blood clot, with one or more treatments. Spontaneous recovery happens in about 10% of adults, usually within the first 6 months. Around one to two-thirds of people who do not recover spontaneously reach a stable platelet count with initial, or first-line, treatments. The remaining adults have ITP that’s resistant to treatment, so they require more therapies or a splenectomy, a surgery that removes the spleen.

Mortality due to ITP in adults is slightly higher than for others in their age group. Like children, this is mainly due to complications from bleeding. But most patients with ITP are more likely to die from conditions that aren’t related to ITP, rather than from complications related to ITP or its treatments.

Possible Complications When Diagnosed with Immune Thrombocytopenic Purpura

The possibility of complications from ITP, or Immune Thrombocytopenia, can increase with the risk of bleeding. This is specifically true when the count of platelets in the blood is less than 20,000 per microliter. People with ITP usually experience bruising and small purple spots on the skin, known as petechiae. Some may also experience bleeding from the mucous membranes, such as nosebleeds or gum bleeding. Serious cases of ITP can lead to bleeding in the digestive tract, blood in urine, or heavy menstrual bleeding.

One of the most serious complications of ITP is ICH, or Intracranial Hemorrhage, a condition where there is bleeding in the brain. The risk of ICH in children with newly diagnosed ITP is around 0.5% and slightly higher in children with chronic ITP, though less than 1%. Most cases of ICH occur when the platelet count is less than 10,000 per microliter. Symptoms to look out for in both children and adults include headaches, constant vomiting, changes in mental state, seizures, localized neurological symptoms, and recent head trauma.

If someone with ITP starts showing signs of ICH, it is crucial to get urgent medical help, including brain imaging and treatment. Factors that increase the risk of ICH include a very low platelet count (less than 10,000 per microliter), head trauma, use of medication that inhibits platelets, and serious bleeding. Nosebleeds lasting from 5 to 15 minutes, bleeding in the digestive tract, or any severe mucosal bleeding that requires a hospital stay or blood transfusion can be considered serious bleeding.

ITP Complications to be Aware of:

• Bruising
• Petechiae (small purple spots on the skin)
• Nosebleeds
• Gum bleeding
• Bleeding in the digestive tract
• Blood in urine
• Heavy menstrual bleeding
• ICH (Intracranial Hemorrhage) characterized by symptoms such as constant headaches, persistent vomiting, changes in mental state, seizures, localized neurological symptoms, and recent head trauma.

Preventing Immune Thrombocytopenic Purpura

Patients who have been diagnosed with ITP, a condition that can lead to easy or excessive bruising and bleeding, and their families need to be well-informed about their condition. This includes the risks of bleeding, how to manage the condition properly, and why it’s important to follow the doctor’s instructions closely. Children with ITP should be careful to avoid activities that could lead to serious bleeding. This is especially important when their platelet count (the cells in the blood that help the body to stop bleeding) is less than 30,000 per microliter.

Shying away from contact and collision sports like football, boxing, and hockey is a good idea. Children should also avoid activities with a high risk of head injuries such as baseball, soccer, skiing, and gymnastics. Both children and adults who have been diagnosed with ITP should refrain from taking medications that might affect platelets such as aspirin and ibuprofen. Similarly, these patients should avoid medications like heparin, enoxaparin, and warfarin – these are called anticoagulants and they work by preventing the blood from clotting – if their platelet count drops below 20,000/μL.

It is essential for the patients and their caregivers to be taught about the correct way to treat this condition and when it’s appropriate to seek further medical help. This education is crucial to handle the condition effectively and correctly.