Idiopathic Thrombocytopenic Purpura: Life in Purple

A 40-year-old lady was admitted in Owaisi hospital and Research Center, Hyderabad, India. She suffered from bleeding gums with the appearance of generalized purple spots all over the body, bleeding in the right eye and melena (dark sticky faeces with blood clusters predicting an internal bleeding) since last 10 days. It was recorded that she had some severe periods of abdominal pain at alternating days. Clinical and haematological surveillance presented the reports, wherein haemoglobin was found to be as low as 3gm/100ml. Other parameters of the patient upon investigation on the first day showed blood pressure of 90/50mm Hg with a platelet count of 40×10³/mm³. It was therefore diagnosed to be a case wherein the haemoglobin level and the platelet count devastatingly declined.

Another case was observed when a patient, aged 28 was reported to Department of Oral Medicine and Radiology in Tamil Nadu Government Dental College and Hospital with the complaints of bleeding gums since past 2 weeks. History of illness revealed occurrence of bleeding from lower gums from the past 2 weeks. Another observation reported the presence of purpuric spots on body (legs, hands, and neck) since past 2 months. The patient was admitted immediately to the hospital. After several haematological tests, it was strangely concluded that all the parameters were perfectly normal except for the platelets count. The platelet count was found to be drastically depleted to 6000/mm³.

In yet another incident, an infant of mere 19 months had been observed with similar symptoms, but to varying degrees. The infant had red spots 1 day prior to presentation. She was brought to the hospital because of bleeding spot on the tongue and nosebleed. No blood was found in her urine or stool. She was playful and in no acute distress. There was no reporting of headache, lethargy, vomiting nor seizures. The rash was preceded with fever 6 days ago. Fever lasted 1 day and subsided. No other symptoms.
The infant was naturally born at term and weighed 3.2 kg. She had no prenatal or postnatal complications. All her immunizations were up to date with the MMR vaccine given 45 days prior to her illness. Her growth and development were normal. No allergies or negative family history was found.

By now, all three case studies have clearly pointed out the anomaly is somewhat related to decreased count of platelets. However, the details can’t be authenticated enough to claim whether the disease occurred due to lower platelet or whether it led to the same. Also, it can be established from the above links that the disease is not specific to any age and doesn’t have an age barrier. The disease we are referring to is called as Idiopathic Thrombocytopenic Purpura.

Introduction

Idiopathic Thrombocytopenic Purpura (ITP) can be very specifically defined by breaking its name into three of its components:
“Idiopathic” refers to the terminology used medically to define a disease that arises spontaneously. The disease is generally not associated with any cause or any probable reference.
“Thrombocytopenic” is referred to a condition of decreased number of platelets in the blood.
“Purpura”, substantially known as blood spots or skin hemorrhages, refer to purple-colored spots that are most recognizable on the skin. The spots may also appear on organs or mucous membranes, including the membranes on the inside of the mouth.

What is Purpura?

“Purpura” as a clinical symptom was recognized in the Greco-Roman period and writers such as Hippocrates and Galen described purpura, or “red eminences” or “red spots” associated with pestilential fevers.
Purpura as already defined, are purple or red colored spots that appear on various parts of the body. But, what leads to pupura? The primary explanation is the presence of bleeding that occurs beneath the skin. The reasons may be a list of diverse possibilities, including platelet disorders, cardiac disorders, coagulation disorders or vascular disorders. Purpura is common with typhus fever as has been evidently reported by the sufferers of the same. In particular, meningococcus (Neisseria meningitidis), a Gram-negative diplococcus organism, releases endotoxin when it lyses. Endotoxin activates the Hageman factor (clotting factor XII), which causes disseminated intravascular coagulation (DIC). The DIC is what appears as a rash on the affected individual. Summing it up, ITP can be defined as a low platelet count, which leads to excessive bleeding and formation of purple spots at various parts of the body.

For a newcomer, we can sufficiently explain the role of platelets to be a type of blood cell, responsible for preventing excessive bleeding. It does so by facilitating clotting of blood. Platelets are fragments of cytoplasm that are derived from the megakaryocytes of the bone marrow. In a normal individual, the range of platelet varies from anywhere between 1,50,000/mm³ to 4,50,000/mm³. A platelet count of less than 80,000/mm³ is called as thrombocytopenia. A person suffering from low platelet count will suffer from delay in clotting which leads to excessive bleeding. On the contrary, an increased platelet count is known as thrombocytosis. This patient may suffer from internalised clots which pose a danger to his health.
ITP is disorder that adults as well as children, either of them can develop. Based on this, it is of two types:

• Acute Thrombocytopenic Purpura:

This usually affects children aged between 2 to 6 years. The symptoms may follow a viral illness, such as chickenpox. Acute ITP usually elevates suddenly and the symptoms disappear in less than 6 months, or within a few weeks. Treatment is often not needed. The disorder usually does not recur. Acute ITP is the most common form of the disorder.

• Chronic Thrombocytopenic Purpura:

The onset of the disorder can happen at any age, and the symptoms can last a minimum of 6 months, several years, or a lifetime. This usually affects adults more often than children. Females subjects are found in a much greater frequency than males. Chronic ITP can recur often and requires continual follow-up care with a blood specialist (hematologist).

What is the history of ITP?

ITP is severely classified as a rare disease. Population-based studies have shown that ITP has an incidence of up to 6.4 per 1,00,000 children and 3.3 per 1,00,000 adults per year. It remained undiagnosed for several years due to the following reasons:
Purpura, initially recognized in ancient times, was defined into clinical syndromes in the 16th, 17th and 18th centuries. With advances in microscope science in the nineteenth century, the platelet was identified which led to the recognition of the thrombocytopenic component of ITP. The 20th century brought recognition of the pathophysiology of the disorder and the clinical states were refined and treatments for ITP developed. The latter half of the 20th century has focused on the auto-immune components of ITP, attempting to develop diagnostic tests and apply new therapies.

Causes

Although, ITP is an idiopathic disease which dictates about the absence of any probable underlying cause. Some cases have been found which on specific studies showed it to occur due to own body cells. ITP, therefore can be categorised as an autoimmune disorder. Briefly explaining, autoimmune disorders are those conditions in which the body cannot differentiate between self and non self cells and thereby, due do faulty symptoms, starts creating antibodies for its own cells. In ITP, the immune system is stimulated to attack your body’s own platelets. It does so by forming antibodies against the platelets. Most often these antibodies are against platelet membrane glycoproteins IIb-IIIa or Ib-IX, and are of the immunoglobulin G (IgG) type. The coating of platelets with IgG renders them susceptible to opsonization and phagocytosis by splenic macrophages. It has been recently found that the stimulus for autoantibody production in ITP is due to abnormal T-helper cells reacting with platelet antigens on the surface of antigen presenting cells. This immune system error may be a result of any of the following:

1. Medications: They can cause an allergy that cross-reacts with platelets. This cross reaction in turn, leads to damaging of the platelets thereby decreasing their count.
2. Infections: Typically viral infections, including the viruses that cause chicken pox, hepatitis C, and AIDS, can prompt antibodies that cross-react with platelets.
3. Pregnancy: Anti-platelet autoantibodies in a pregnant woman with ITP will attack the patient’s own platelets and will also cross the placenta and react against fetal platelets. Therefore, ITP is a significant cause of fetal and neonatal immune thrombocytopenia.
4. Immune disorders: (such as rheumatoid arthritis and lupus) RA and lupus are yet another examples of autoimmune disorders which in chain can lead to ITP, due to production of antibodies attacking their own cells.
5. Low-grade lymphomas and leukemias may also lead to ITP by producing abnormal antibodies against platelet proteins.

Symptoms

Normal platelet count is in the range of 1,50,000 to 4,50,000. With ITP, the platelet count is less than 1,00,000. By the time significant bleeding occurs, you may have a platelet count of less than 10,000. The lower the platelet count, the greater the risk of bleeding.

Because platelets help stop bleeding, the symptoms of ITP are related to increased bleeding. However, each person may experience symptoms differently. Symptoms may include:

• The purple color of the skin after blood has “leaked” under it. A bruise is blood under the skin. Patient with ITP may have large bruises from no known injury. Bruises can appear at the joints of elbows and knees just from movement.
• Tiny red dots under the skin that are a result of very small bleeds.
• Nosebleeds
• Bleeding in the mouth and/or in and around the gums
• Heavy menstrual periods
• Blood in the vomit, urine, or stool
• Bleeding in the head. This is the most dangerous symptom of ITP. Any head injury that occurs when there are not enough platelets to stop the bleeding can be life threatening.
• The symptoms of ITP may look like other medical problems. Always consult your health care provider for a diagnosis.

Treatment

There is usually no treatment to ITP or rather, to the decreased cell count of platelets. However, there are some guidelines suggested to prevent the severity of the same:

• Steroids. Steroids help prevent bleeding by reducing the rate of platelet destruction. Steroids, if effective, will result in an increase in platelet counts seen within 2 to 3 weeks. Side effects may include irritability, stomach irritation, weight gain, high blood pressure, and acne.
• Intravenous gamma globulin (IVGG). Intravenous gamma globulin (IVGG) is a protein that contains many antibodies and also slows the destruction of platelets. IVGG works faster than steroids (within 24 to 48 hours). Intravenous gamma globulin (IVGG) may be infused in some cases in order to decrease the rate at which macrophages consume antibody-tagged platelets. However, while sometimes effective, it is costly and produces improvement that generally lasts less than a month. IVGG can rapidly increase platelet counts, and can also help reduce the risk of major bleeding by transiently increasing platelet counts.
• Splenectomy (removal of the spleen) may be considered in some patients who are either unresponsive to steroid treatment, or cannot be tapered off steroids after a few months. Platelets which have been bound by antibodies are taken up by macrophages in the spleen (which have F_c receptors), and so removal of the spleen reduces platelet destruction. The procedure however, is potentially risky in ITP cases due to the increased possibility of significant bleeding during surgery.
• Platelet transfusion. Transfusion alone is normally not recommended except in an emergency. It is usually unsuccessful in producing a long-term platelet count increase. This is because the underlying autoimmune mechanism that is destroying the patient’s platelets will also destroy donor platelets, and so platelet transfusions are not considered a long-term treatment option.

Take your Call!!

By now, you are already familiar with this segment of blog. This is the segment where we conclude the article by presenting an epilogue of what we think could be done to improve the condition with respect to above mentioned subject.

Living with a rare disease:

An individual might be living with a disease as evident as Albinism, or as camouflaged as ITP. The major concern with rare diseases is their timely diagnosis and accurate treatment. Specifically for India, science has always stayed a step back from the reality. Such diseases generally remain undiagnosed and are often diagnosed at a stage when they can’t be cured. ITP, although, is not a fatal disease and has high frequency of cured patients, still poses consequences to the subjects. The subjects are prone to bruises even under negligible incidents of wounds. The acknowledgement of such diseases needs to be highlighted in India to make it a more practical approach to life sciences and research in the same.