Idiopathic thrombocytopenic purpura

DEFINITION

Patient asks to mbah dukun: "Mbah, my name is Painem, im from Belgia, i have a problem. my son's legs frequently bruising, red spots appear, these has been about 6 months, intermittent, sometimes accompanied by fever, DHF-like disease. Would you tell me what is that?

Mbah Dukun anwers:

ITP, primary immune thrombocytopenia (also called immune (idiopathic) thrombocytopenic purpura), is an autoimmune disease. In autoimmune diseases, the body mounts an immune attack toward one or more seemingly normal organ systems. In ITP, platelets are the target. They are marked as foreign by the immune system and eliminated in the spleen and sometimes, the liver. In addition to increased platelet destruction, some people with ITP also have impaired platelet production.

Thrombocytopenic "means the blood does not have enough red blood cells (platelets). "Purpura" means a person has a lot of bruises (excessive).
ITP occurs when immune system cells (specialized lymphocytes) produce antibodies that cause the destruction of platelets in the spleen and other organs. As such, ITP historically has been considered a disease of platelet destruction. However, recent data also suggest that low platelet counts in the blood may be caused by the inability of the body’s natural processes to produce platelets. Therefore, increasing the rate of platelet production may help address low platelet counts associated with ITP.
There are 2 types of ITP. The first type usually attacks young children, while other types of attacking adults. Children aged 2 to 4 years who generally suffer from this disease. While the ITP for adults, mostly experienced by young women, but can also occur in anyone. ITP is not a hereditary disease.

ETIOLOGY

Patient asks to mbah dukun:What are cause ITP, mbah?
Mbah Dukun anwers:


The specific cause of ITP is unknown. In some cases, ITP has appeared following a viral or bacterial infection, immunizations, exposure to a toxin, or in association with another illness such as lupus or the human immunodeficiency virus (HIV).
Platelets, also called thrombocytes, are specialized blood cells needed to prevent bleeding. Low platelet counts leave adult patients with ITP at risk for bleeding events. The risk of a serious bleeding event increases when platelet counts drop to less than 30,000 platelets per microliter of blood. In extreme cases, death can occur due to an intracerebral hemorrhage (bleeding into the brain).
Normal platelet counts range from 150,000 to 400,000 per microliter of blood. People with platelet counts under 10,000 are more prone to bleed. For many, a count of 30,000 is sufficient to prevent a catastrophic bleed. Individual reactions to low platelet counts differ.

PATHOGENESIS

Autoimmune disease, with anti-platelet antibody formation (usually specific for the platelet GPIIbIIIa receptor) and peripheral platelet destruction. Acute ITP usually occurs in children, follows an acute viral infection or recent live virus immunization, and usually undergoes a spontaneous remission within two months. Chronic ITP is more common in adults, shows an insidious presentation, and lasts > 6 months. The pathogenesis is complex and multifactorial, including a failure of self-antigen recognition and tolerance, altered cytokine secretion, impaired megakarypoiesis, and impaired cellmediated cytotoxicity.

 SYMPTOMS

Patients asks: What are the symptoms of ITP?
Mbah Dukun answers: 

People with ITP often have bruises or small purple spots on their skin (petechiae) where their blood has escaped from their veins or capillaries. Spontaneous bleeding can also occur in the mucus membranes on the inside of the mouth or in the gastrointestinal tract. It is possible, with a decreased number of platelets, to have a spontaneous cerebral hemorrhage.   

In children, signs of serious injury or internal head bleeding include: dizziness, headache that doesn’t go away or gets worse, vomiting, confusion, unusual sleepiness, slurred speech, weakness, numbness or tingling in hands or feet, stiff neck, seizures, eyes not moving together, or inability see. Call your doctor or hospital immediately if your child falls resulting in hitting their head or for any event that causes your child to lose consciousness.
Call your doctor or other healthcare provider immediately if you hit your head or have a serious accident. Watch for a large number of bruises and petechiae, or other signs of severe bleeding, which can indicate a very low platelet count. Signs of bleeding in the brain include: a headache that won’t go away, dizziness, vomiting, unusual sleepiness, confusion, slurring of speech, eyes not moving together, weakness on one side of the body, stiff neck or back, seizures, and inability to see or hear. Notify your doctor about nosebleeds, bleeding gums, or blood in urine, stool or vomit. Even when ITP patients are in remission they should watch for these symptoms so that they can contact their healthcare provider immediately if any of these occur.

DIAGNOSIS

There are no specific tests for ITP; ITP can only be diagnosed by excluding other causes of a low
platelet count. Doctors call this a 'diagnosis of exclusion’. This situation is different from many other diseases. For example, a strep throat is diagnosed with certainty by a positive throat culture for the streptococcus germ, and most cancers are diagnosed with certainty by a positive biopsy. ITP has been defined as isolated thrombocytopenia with no clinically apparent associated conditions or other causes of thrombocytopenia. Isolated thrombocytopenia means that the other components of the blood counts (the red and white blood cells) are normal. The phrase 'clinically apparent’ means that there is no obvious evidence of other disease causing thrombocytopenia even though there might be abnormalities of laboratory tests that suggest another condition. For example, a positive test for antinuclear antibodies (ANA) can be associated with lupus, but when there are no signs or symptoms of another disease (such as lupus) then ITP remains the appropriate diagnosis. On the other hand, if a patient has clinically apparent lupus, with features such as rash, arthritis, kidney disease, and other abnormalities, then ITP is not an appropriate diagnosis because the patient's problems and management will be determined by the course of the lupus, not just by the low platelet count. Although it may seem difficult to make a diagnosis in the absence of a specific, defining 'gold standard’ laboratory test, the diagnostic evaluation for ITP is usually quite simple and straightforward. It most often includes only the basic examination, including a medical history, physical examination, and blood counts with examination of the blood smear. If these are compatible with the diagnosis of ITP and do not suggest other causes for the low platelet count, then the diagnosis is established. Specifically, tests for antibodies against platelets are not required and do not influence treatment decisions (even though antibodies against platelets are the cause of ITP). The indications for doing a bone marrow examination when evaluating a patient for ITP are controversial. In children, it has been recommended that a bone marrow examination is important before treatment with prednisone is begun. This rule was established because prednisone alone may be partially effective in treating for the type of leukemia which is most common in young children, acute lymphocytic leukemia. There is concern that prednisone treatment may thus temporarily mask the presence of leukemia and delay definitive treatment. In practice, however, many pediatric hematologists begin prednisone without doing a bone marrow examination. In older adults, other bone marrow disorders such as myelodysplasia may affect platelet production and a low platelet count may initially be the only abnormality. So in these older patients, a bone marrow examination may be appropriate. A bone marrow examination may also be performed in patients, either children or adults, who do not respond appropriately to treatment. Drug-induced thrombocytopenia, in which an allergic reaction to a drug can cause a low platelet count, is initially indistinguishable from ITP.
Laboratory studies are more valuable in the exclusion of other diseases than in providing definitive evidence of ITP. Variable thrombocytopenia with a normal white blood count and erythrocytic indices (in the absence of severe hemorrhage). Peripheral blood smear examination reveals thrombocytopenia with normal leukocytic and erythrocytic morphology. Coagulation assays are within normal limits. Bone marrow evaluation reveals normal to increased megakaryocytes with normal morphology. Assays for platelet-associated immunoglobulin by ELISA or flow cytometry may be positive, but these assays are presently considered unreliable. Pseudothrombocytopenia must be excluded by peripheral smear examination for platelet clumping. The exclusion of other causes of thrombocytopenia should include other laboratory assays, especially a CBC, Ddimer and FDP assay, LDH, viral serology (especially for HIV), anti-nuclear antibody, rheumatoid factor studies, and ESR, liver function studies, and pregnancy
test.


TREATMENT

Patient asks to mbah dukun: So  What are the main treatments available for ITP?
 Mbah Dukun answers: 

1. Antibiotics
An ITP diagnosis is sometimes associated with an infection and antibiotics can raise the platelet count. There has been considerable research on the success of antibiotics used to treat H-pylori in those diagnosed with ITP. The eradication of other infections can also raise the platelet count.
2. Anti-D
Used to achieve a temporary elevation of the platelet count, the treatment can be repeated for a more extended remedy. The shorter infusion time and often lower cost is an advantage over IVIg. Win Rho SDF and Rhophylac are approved for the treatment of ITP in the US.
3. B-cell depletion
B-cell depletion by a monoclonal antibody (anti-CD20, rituximab) has not been approved by the FDA to treat ITP, although it has become a widely used treatment choice. It works by disabling and changing B-cells, a type of white blood cell. Other anti-CD20 options are in clinical trials.
4. Chemotherapy
Various chemotherapy drugs have been used as a second or third-line treatment choice for chronic ITP patients. Each has a slightly different side effect profile. They have been effective in a small percentage of cases and can be quite toxic. They have not been approved by the FDA to treat ITP.
5. Corticosteroids
Often the first-line treatment for ITP, the dose of corticosteroids (ex. Prednisone) is initially quite high then gradually tapered. Sometimes the platelets remain elevated but in most cases the platelet count recedes as the dose is reduced. An alternate method of administering corticosteroids is an extremely high dose for a few days with no taper. The side effects of corticosteroids can be uncomfortable and grow in severity if the treatment is continued for a long time. While the FDA mentions this as a first-line treatment, it has not been officially approved for the treatment of ITP.
6. Immunoglobulins
An IV drip of immunoglobulin, a type of antibody, is also referred to as IVIg, IGG or IGIV. This treatment is a temporary measure and is not expected to result in a sustained, elevated platelet count, although in some rare cases this does happen. It can be repeated for longer lasting results. IVIg is manufactured by several companies, some of which have received FDA approval for its use in the treatment of ITP.
7. Immunosuppressants
This class of drugs disables parts of the immune system and is often used to prevent the rejection of transplanted organs. These are second and third-line treatments for ITP and have been used to treat other autoimmune diseases such as MS and lupus. None have been approved by the FDA to treat ITP.
8. Modified Testosterone
A synthetic androgen (male sex hormone) is sometimes used to treat ITP when other treatments have failed. It disrupts the action of the pituitary gland, reduces estrogen, halts menses and can cause masculine features for women.
9. Platelet Growth Factors
The newest treatment approach for ITP is the use of platelet growth factors. These agents increase platelets by stimulating the bone marrow to produce more of them. Once thought to be only a disease of platelet destruction, recent research has shown that many people with ITP also have a platelet production problem. Nplate and Promacta have been approved for the treatment of ITP in this category.
10. Splenectomy
This is a surgical procedure where the spleen is removed. The spleen is a large blood filter which, for many people, removes antibody-coated platelets. Theoretically, if the spleen is removed, the platelets will remain in circulation. However, there are other ways the body removes platelets, so this treatment sometimes fails to have a lasting effect.Treatment for ITP is most often coordinated by a hematologist (doctor who specializes in blood disorders). The goals of ITP treatment are to ensure a safe platelet count, prevent bleeding complications, and minimize treatment side effects.

All of these treatments have their own benefits and risks. Side effects have been reported for each of the drugs and treatments for ITP. These side effects will vary from one person to another. You may experience all, some, or none of the side effects. Here are the side effects for frequently used treatments.



 Patient says: thank you mbah for explain, 6 million dollars, I give to mbah Dukun as dowry


references
1. http://www.pdsa.org
2. http://www.pathology.vcu.edu/clinical/coag/ITP.pdf
3. http://www.amgen.com/pdfs/misc/Fact_Sheet_ITP.pdf
4. http://www.ohiohealth.com
5. http://www.hoslink.com