Idiopathic thrombocytopenic purpura may result from medicines that cross-react with platelets, or specific bacteria or viruses. Read more at Meri Sehat.

Idiopathic Thrombocytopenic Purpura (ITP)

A. JABBAR DENTAL CLINIC

Sadia Khan

Overview

Formerly known as idiopathic thrombocytopenic purpura (ITP), immune thrombocytopenia is an autoimmune disease characterized by a low platelet count, purpura, and bleeding episodes due to anti-platelet antibodies. 
&nbsp;

Immune thrombocytopenic purpura has an incidence rate of 1.6 to 3.9 per 100,000 patients per year, directly proportional to age and predominant in females<a href="#accordion">[6]</a>.

Sometimes, ITP presents as an asymptomatic condition, but when symptoms do appear, bleeding is most commonly observed. It can be either mild and present as petechial, purpura and epistaxis, or severe and fatal due to an intracranial haemorrhage, and gastrointestinal or urinary tract bleeding.

Moreover, a platelet count of less than 10-20 &times; 10/L<a href="#accordion">[9]</a>, higher age and a history of minor bleeding are all predisposing factors for major bleeding, most commonly in newly diagnosed patients of acute ITP.

Patients may also complain of fatigue and a decreased quality of life. However, it improves with specific treatment and an improved platelet count. Long-term follow-ups have revealed an increased risk of venous and arterial thromboembolism, hematologic malignancy, and increased deaths than the general population<a href="#accordion">[6]</a>.&nbsp; 
&nbsp;

Immune thrombocytopenic purpura can co-exist with infections such as <a href="https://merisehat.pk/disease/hiv-61">HIV</a>, malignancies such as adenocarcinoma and <a href="https://merisehat.pk/disease/hodgkins-lymphoma">lymphoma</a>, and a few immunodeficiency diseases like systemic lupus erythematosus, autoimmune hepatitis, and thyroid disease. The formation of anti-platelet antibodies leads to platelet destruction in these diseases. Moreover, certain drugs may also cause autoimmune thrombocytopenia, such as acetazolamide, aspirin, aminosalicylic acid, carbamazepine, cephalothin, digitoxin, phenytoin, meprobamate, methyldopa, quinidine, rifampin, and sulfamethazine<a href="#accordion">[1]</a>. 
&nbsp;

Essentially there are two types of ITP:<a href="#accordion">[1]</a> <a href="#accordion">[4]</a> 
&nbsp;

<ul>
	<li>
	<h5>Acute Thrombocytopenic Purpura</h5>
	</li>
</ul>

Acute ITP is the most common form of the disease. It mostly affects children aged 2 to 6 years and follows viral illnesses like chickenpox. Approximately 85% of children have a mild course of the disease and do not require treatment<a href="#accordion">[1]</a>. Acute ITP has a sudden onset and symptoms commonly resolve in less than 6 months, even within a few weeks. Moreover, there is no recurrence of the disorder. 
&nbsp;

<ul>
	<li>
	<h5>Chronic Thrombocytopenic Purpura</h5>
	</li>
</ul>

Unlike acute ITP, symptoms in chronic ITP last for more than 6 months, a few years, or for the rest of the patient&rsquo;s life. The onset of the disorder is independent of age, but mostly affects adults aged 20-50 years. Moreover, females are more commonly affected, with a female/male ratio of 3:1<a href="#accordion">[1]</a>. Chronic ITP can often recur and requires regular follow-up care with a haematologist. 
&nbsp;

Signs and Symptoms

A platelet count of 150,000 to 450,000 is normal. However, in ITP, your platelet count drops to less than 100,000 and by the time you start exhibiting major bleeding, it may have dropped to a count of less than 10,000. In short, the lower the platelet count falls, the greater the risk of bleeding. This is because platelets aid in stopping a bleed and the symptoms of ITP are directly related to an increased bleeding episode. However, symptoms vary from patient to patient. 
&nbsp;

Immune thrombocytopenia is often asymptomatic. But when symptoms do occur, they may&nbsp; include<a href="#accordion">[2]</a>:

<ul>
	<li>Purplish discolouration of the skin, or bruises, may appear without any known injury. A bruise is essentially pooled blood under the skin and can appear at sites such as your joints like the elbows and knees just by moving.</li>
	<li>Small red spots (petechiae) because of extremely small bleeds under the skin. These mostly appear on the lower legs</li>
	<li>Epistaxis (bleeding from the nose)</li>
	<li>Bleeding from the gums</li>
	<li>Menorrhagia (heavy menstrual periods)</li>
	<li>Hematemesis, hematuria and melena/hematochezia</li>
	<li>Bleeding in the brain is also the most feared symptom of ITP. If you endure a head injury that has occurred in the absence of enough platelets, it can prove fatal. 
	&nbsp;</li>
</ul>

The symptoms of ITP may be confused with other diseases. Hence it is crucial to consult your doctor and discuss the possibility of ITP. 
&nbsp;

Causes

Immune thrombocytopenia is characterized by the immune system attacking the body&#39;s platelets. This results from the body producing antibodies against the platelets. Often, a type of white blood cell called T-cell directly attacks the body&rsquo;s platelets. 
&nbsp;

The immune system dysfunction can result from the following reasons<a href="#accordion">[7]</a>:

<ul>
	<li>Medications, including over-the-counter medications, can cross-react with platelets due to an allergy and kill them.</li>
	<li>Infections, typically viral infections, including the viruses that cause chicken pox, hepatitis C, and <a href="https://merisehat.pk/disease/aids">AIDS</a>, can trigger antibodies which then cross-react with platelets.</li>
	<li>Pregnancy</li>
	<li>Auto-immune disorders including <a href="https://merisehat.pk/disease/rheumatoid-arthritis">rheumatoid arthritis</a> and systemic lupus erythematosus (SLE)</li>
	<li>Conditions like low-grade lymphomas and leukaemia may produce abnormal antibodies against the platelets.</li>
	<li>Some cases may be idiopathic, meaning that the reason is unknown. 
	&nbsp;</li>
</ul>

There are no screening tests for ITP. However, a detailed history might go a long way in helping your healthcare provider reach a diagnosis. 
&nbsp;

Diagnosis

Diagnosis of ITP includes a detailed history of the patient and a physical exam. Moreover, your healthcare provider may also order the following tests<a href="#accordion">[4]</a>: 
&nbsp;

<ul>
	<li>Complete Blood Count (CBC)</li>
</ul>

A CBC measures the size, number, and maturity of different blood cells in your body. This test aims to evaluate your platelets. 
&nbsp;

<ul>
	<li>Blood And Urine Tests</li>
</ul>

This specific reporting tells your doctor if there is a possibility of any infection, along with a special blood test referred to as an antiplatelet antibody test. 
&nbsp;

<ul>
	<li>Bone Marrow Examination</li>
</ul>

A bone marrow exam is often conducted in adults to rule out other diseases. In ITP, it may show an increased number of megakaryocytes. 
&nbsp;

<ul>
	<li>Platelet Coomb&#39;s Test</li>
</ul>

The platelet Coomb&rsquo;s test can help detect anti-platelet antibodies on the surface of the patient&rsquo;s platelets. 
&nbsp;

<ul>
	<li>Bone Marrow Biopsy (In some cases)</li>
</ul>

Previously, bone marrow aspiration was essential for diagnosing ITP. It has now become evident that the test is not needed in case of a positive antiplatelet antibody test. However, it is still commonly administered by doctors to assess for platelet production and look for any abnormal cells in the bone marrow. It should be noted that a bone marrow aspiration is essential for confirming your diagnosis if the antiplatelet antibody testing has turned out to be negative. 
&nbsp;

Treatment

The usual management plan for people diagnosed with mild immune thrombocytopenia includes regular monitoring of platelet levels. Younger children usually improve without any specific treatment, whereas adults eventually need treatment as the condition can aggravate with time.

When treatment is initiated, it may include multiple approaches, like medications to improve your platelet count or surgery to completely remove your spleen (splenectomy). 
&nbsp;

<h5>Medications</h5>

Your doctor might suggest over-the-counter medications.&nbsp; They may also consider supplementation for you to take or stop using if there is any chance that it might inhibit the platelet function. Examples of these substances include aspirin, ibuprofen and ginkgo biloba: 
&nbsp;

<ul>
	<li>Steroids</li>
</ul>

Oral corticosteroid, for example, prednisone is often prescribed. The steroids are gradually tapered off as the platelet count reaches a safe level. Long-term use of steroids is typically avoided due to their side effects such as the increased risk of infections, high blood pressure, diabetes, and osteoporosis. 
&nbsp;

<ul>
	<li>Immune Globulin</li>
</ul>

If ITP does not respond to corticosteroids, doctors may prescribe an injection of immune globulin. Intravenous gammaglobulin (IVGG) can also be used to treat critical bleeding or when there&#39;s a need to raise the blood count before surgery. The drug contains antibodies and slows down platelet destruction. 
&nbsp;

<ul>
	<li>Drugs To Improve Platelet Production</li>
</ul>

Drugs including romiplostim and eltrombopag aid in platelet production by triggering the bone marrow to produce more. However, these drugs might increase the risk of developing blood clots. 
&nbsp;

<ul>
	<li>Miscellaneous Drugs</li>
</ul>

Rituximab is a targeted cancer drug which helps in raising your platelet count by decreasing your immune system&rsquo;s response, the major reason behind the destruction of your platelets. However, this drug may also reduce the efficacy of vaccinations, which are needed before splenectomy. These vaccinations include Meningococcal, Pneumococcal and HiB (Haemophilus Influenzae Type B). 
&nbsp;

<h5>Surgery</h5>

If medications are unable to control your disease and it has aggravated over time, regardless of the initial drug treatment, your healthcare provider may suggest a splenectomy. This helps by quickly eliminating the major source of platelet destruction in the body, which in turn improves your platelet count. However, a detailed discussion is necessary for this decision as it doesn&#39;t work for everyone. Moreover, it should be kept in mind that living without your spleen increases your risk of infections. 
&nbsp;

<h5>Emergency Treatment</h5>

Severe bleeding may warrant emergent treatment in patients with ITP. Emergency care includes transfusions of platelet concentrates. Moreover, intravenous steroids and immune globulin may also be administered. 
&nbsp;

A rare but deadly complication of ITP is bleeding into the brain tissue. Moreover, if a woman is pregnant and her platelet count drops very low or has an active bleed, she is at a greater risk of heavy bleeding during delivery. 
&nbsp;

ITP has a predilection towards young women. Moreover, the risk is higher in people who have diseases such as rheumatoid arthritis, lupus and antiphospholipid syndrome simultaneously. 
&nbsp;

Prevention of ITP is entirely subject to its underlying cause. In most cases, ITP can&#39;t be prevented. However, the following steps can help prevent the development of complications: 
&nbsp;

<ul>
	<li>Drinking alcohol can slow down the production of platelets. Therefore, quitting alcohol can help prevent complications associated with thrombocytopenia</li>
	<li>Avoid exposure to chemicals such as pesticides, arsenic, and benzene. These chemicals have also been shown to slow the production of platelets.</li>
	<li>Do not use medicines that decrease your platelet count. Medications such as aspirin and ibuprofen can increase the risk of bleeding and should be avoided</li>
	<li>You should get vaccinated for mumps, measles, rubella, and chickenpox.&nbsp; 
	&nbsp;</li>
</ul>

Previously, the management of ITP mainly included immune system suppression. However, relatively newer studies have shown that this older methodology has failed to decrease morbidity and is linked with a poor quality of life for the patient. Newer treatments, like the thrombopoietin receptor agonists, have truly revolutionized ITP management. The drugs have a higher efficacy and are well tolerated which in turn improves the patient&#39;s quality of life. It was the greater understanding of the underlying pathology of this disease which has helped in developing a series of new targeted therapies which include inhibitors of the neonatal Fc receptors, Bruton tyrosine kinase and complement pathway. 
&nbsp;

Key Points

<ul>
	<li>Immune thrombocytopenic purpura (ITP) is an autoimmune disease characterized by a low platelet count, purpura, and bleeding episodes due to the anti-platelet autoantibodies.</li>
	<li>Some drugs may also cause immune thrombocytopenia such as acetazolamide, aspirin and aminosalicylic acid.</li>
	<li>Immune thrombocytopenic purpura has an incidence rate of 1.6 to 3.9 per 100,000 patients per year, directly proportional to age and predominant in females</li>
	<li>A platelet count of less than 10-20 &times; 109/L, higher age and a history of minor bleeding are all predisposing factors for major bleeding, most commonly in newly diagnosed patients of acute ITP.</li>
	<li>ITP has been linked to an increased risk of venous and arterial thromboembolism, hematologic malignancy and increased deaths than the general population.</li>
	<li>Essentially there are two variants of ITP - acute and chronic</li>
	<li>The acute variant usually affects young children aged 2 to 6 years. Patients get symptomatic following a viral illness, such as chickenpox.</li>
	<li>The onset of chronic ITP is independent of age, and the symptoms, unlike the acute variant, can last for at least 6 months, a few years, or even for your entire life.</li>
	<li>A normal platelet count is considered to be a count of 150,000 to 450,000. However, in ITP, your platelet count drops to less than 100,000</li>
	<li>Symptoms of ITP include purplish discolouration of the skin, small red spots, bleeding from your nose, bleeding from your mouth and in your gums, menorrhagia, blood in the vomit, urine, or stool and bleeding in the brain.</li>
	<li>Causes of ITP include medicines that cross-react with your platelets due to an allergy and kill them; infections, typically viral infections, including the viruses that cause chicken pox, hepatitis C, and AIDS; and auto-immune disorders including rheumatoid arthritis and systemic lupus erythematosus.</li>
	<li>There are no screening tests for ITP. However, a detailed history might go a long way in helping your healthcare provider to reach a diagnosis.</li>
	<li>Diagnosis of ITP includes a detailed history of the patient and a physical exam. Moreover, your healthcare provider may also order a complete blood count, bone marrow exam, urine tests, and an antiplatelet antibody test.</li>
	<li>A bone marrow aspiration is essential for confirming your diagnosis only if the antiplatelet antibody testing has turned out to be negative.</li>
	<li>The usual management plan for people diagnosed with mild immune thrombocytopenia includes regular monitoring of the platelet count.</li>
	<li>Your healthcare provider will initiate a course of an oral corticosteroid, for example, prednisone. However, as soon as your platelet count reaches a safe level, it is gradually tapered off.</li>
	<li>If for some reason, ITP does not respond to corticosteroids, your healthcare provider may prescribe you an injection of immune globulin.</li>
	<li>Drugs including romiplostim and eltrombopag aid in platelet production by triggering your bone marrow</li>
	<li>Rituximab is a targeted cancer drug which helps in raising your platelet count by decreasing your immune system&rsquo;s response, the major reason behind the destruction of your platelets</li>
	<li>If medications are unable to control your disease and it has aggravated over time, regardless of the initial drug treatment, your healthcare provider may suggest a splenectomy</li>
	<li>A condition that may warrant emergent treatment in patients with ITP is severe bleeding. Emergency care includes transfusions of platelet concentrates.</li>
	<li>A rare but deadly complication of ITP is bleeding into the brain tissue. Moreover, if a woman is pregnant and her platelet count drops very low or has an active bleed, she is at great risk of heavy bleeding during delivery.</li>
	<li>ITP has a predilection towards young women. Moreover, the risk is higher in people who have diseases such as rheumatoid arthritis, lupus and antiphospholipid syndrome simultaneously.</li>
	<li>Preventive factors include quitting alcohol, avoiding exposure to chemicals such as pesticides, arsenic, and benzene, and receiving vaccinations for mumps, measles, rubella, and chickenpox.</li>
	<li>Previously, the management of ITP mainly included immune system suppression, however, relatively newer studies have shown that this older methodology has failed to decrease morbidity and is linked with a poor quality of life for the patient</li>
	<li>Newer treatments, like the thrombopoietin receptor agonists, have higher efficacy and are well tolerated which in turn improves the patient&#39;s quality of life. 
	&nbsp;</li>
</ul>

[1] Justiz Vaillant AA, Gupta N. ITP-Immune Thrombocytopenic Purpura. [Updated 2022 Jul 8]. In: StatPearls [Internet]. Treasure Island (FL): StatPearls Publishing; 2022 Jan-.

[2] Immune thrombocytopenia (ITP). Mayo Clinic.

[3] Screening and prevention of thrombocytopenia. Hematology-Oncology Associates of CNY.

[4] Idiopathic thrombocytopenic purpura. Idiopathic Thrombocytopenic Purpura | Johns Hopkins Medicine.

[5] Harrington CT, Hafid NA, Waters KA. Butyrylcholinesterase is a potential biomarker for sudden infant death syndrome. eBioMedicine. 2022;80:104041. doi:10.1016/j.ebiom.2022.104041