ITP is characterized more by its description than the specific properties of the disease. It is the diagnosis when platelets are abnormally low and other diseases that could cause low platelets have been ruled out. Usually there is the presence of antiplatelet antibodies indicating that the body has decided to consider the platelets foreign. It attacks them with an antibody as it would bacteria. The body then does what it is programmed to do with bacteria: eliminate them. This is done in the spleen or liver.
ITP can present itself with small purple spots called petechiae in the mouth and legs, nose bleeds, and bleeding gums during normal dental care. Some people develop bruises on their arms and legs with no provocation. It is often accompanied by fatigue and sometimes depression.
There are many types of ITP. ITP in children is not the same as adult ITP. Children have a much greater chance of recovering with little or no intervention. Adolescent ITP has more of the characteristics of adult ITP.
While most cases of ITP are controlled, it can be fatal in a small percentage of ITP patients.
PLATELETS
All blood cells originate and mature in the bone marrow. They begin in 'stem' cells, then differentiate into the red cells, white cells, and platelets. The white blood cells include three varieties, granlocytes, monocytes (macrophages) and lymphocytes.
Normal platelet counts range from 150,000 to 400,000 per cu/ml. Those with ITP have a lower platelet count. It can range from severe cases that hover close to zero to more mild cases where the counts stay in closer to 100,000. 30,000 is often considered a ‘safe’ count’, one that is high enough to protect against cerebral hemorrhage.
In people with ITP the platelets are often enlarged. They stay in the blood stream from a few hours to close to the normal eight to ten days depending on the severity of the disease.
Platelets play a crucial part in the blood clotting process by forming a platelet plug. This is a two step process. First, single platelets bind to the site of the wound (adhesion). Next, the platelets bind to each other (activation). Activation can be stimulated by components released when the blood vessel is damaged and by thrombin, released during the blood clotting process. When platelets become activated they change. They release agents which recruit and activate the surrounding platelets. The result of these two processes is the formation of fibrin which stabilizes the platelet plug, stops bleeding and allows injuries to heal.
In your body, 2% of the serotonin, a mood elevating neurotransmitter, is stored in platelets. In addition to serotonin, your platelets also carry its 'parent' or precursory chemical L-tryptophan. While serotonin can't pass through the blood brain barrier, L-tryptophan can. These substances are involved in such processes as sleep/wake cycles, biological rhythms, appetite, mood regulation, etc.
ITP IN CHILDREN
ITP in children is often considered a different disease than ITP in adults because it goes into remission more easily. According to Dr. Bussel, a children's ITP specialist in NYC, 80% of children become well again within 6 - 12 months. In most cases, their ITP goes away within the first two months, tends not to lead to other problems, and does not return. The most feared complication is intracranial hemorrhage, a bleed to the brain, like a stroke. Fortunately, this is rare, occurring in less than .5 to 1.0% of the cases.
Treatments for children are similar to the treatments for adults. Often IVIg or WinRho is used to sustain a reasonable count until the child's own immune system can overcome the disease.
TREATMENTS
Anti-D
Used to achieve a temporary elevation of the platelet count. It has the advantage over IVIg of being administered via injection rather than an IV infusion.
Chemotherapy
Various chemotherapy drugs have been used as an almost last resort for chronic ITP patients. Vincristine and Cytoxan (cyclophosphamide) are the ones that are most frequently prescribed. Each has a slightly different profile of side effects. They include hair loss, decreased immunity, and damage to the central and peripheral nervous systems.
Danazol (danocrine)
This drug is also used to treat endometriosis. It is a synthetic androgen (male sex hormone) It disrupts the action of the pituitary gland and reduces estrogen, halts menses, and promotes the growth of facial hair and acne.
Excorim System
This is an antibody removal system (Citem 10 Immunsosorba) used mostly in Europe and recently approved to treat hemophilia in the US. According to the manufacturer, it can be used for ITP. More information can be found at the manufacturer's site.
Decadron (dexamethasone)
A steroid, similar to prednisone in its effects on the body. It is often given in pulses, doses of a shorter duration that are repeated. Long term use can result in altered mood and personality, cataracts, glaucoma, hypertension, arrhythmias, peptic ulcers, pancreatitus, osteoporosis, and increased susceptibility to infections.
Imuran (azathioprine)
An anti-arthritic and immunosuppressive drug. It is also used to prevent the rejection of transplanted organs and in the treatment of rheumatoid arthritis and lupus. It can reduce the level of white blood cells, cause liver damage and increase the risk of malignancy.
IVIg
This is an intravenous infusion of immunoglobulin, a type of antibody. The antibodies attach to the receptors in the spleen, sparing the removal of antibody coated platelets. 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. The side effects include allergic reactions and heart palpitations.
Prednisone
This steroid is often used in the treatment of allergies and other autoimmune diseases. For ITP, typically the dose is initially quite high then gradually tapered. Sometimes the platelets remain elevated after the prednisone is tapered. In most cases the platelet count recedes as the prednisone is reduced.
The side effects can be uncomfortable and grow in severity if the treatment is continued for a long time. They often include weight gain, mood changes, elevated blood pressure, insomnia, blood sugar changes, calcium loss, muscle wasting, and increased susceptibility to infections.
Protein A Immunoadsorption
The treatment is usually administered in a series of six individual sessions. A percentage of the blood is removed. The plasma is separated and run through a special column to remove the antibodies, then returned to the body. The side effects can include blood pressure swings, allergic reactions such as fever and chills, nausea, joint pain, increased liver enzyme, and general trauma from having the blood removed and returned.
Rituxan
This is a monoclonal antibody approved by the FDA to treat lymphoma. There has been some initial success in its use to treat ITP.
Sandimmune (cyclosporine)
Helps prevent the organ rejection in kidney, liver, and heart transplants by inhibiting some white blood cells and their growth factors. It can cause excessive hair growth, liver toxicity, a low white blood cell count, and lymphoma.
Splenectomy
This is a surgical procedure where the spleen is removed. The spleen acts like a giant lymph node. It plays a part in maintaining a healthy immune system and cleans the blood of foreign matter. It helps eliminate the platelets that have antibodies bound to them. Theoretically, if the spleen is removed, the platelets will stay.
The spleen can be removed via a large incision or by laproscopic surgery. Patients who have experienced the laproscopic technique report that they recovered more quickly and had smaller incisions over time.
A splenectomy does not always result in a sustained elevated platelet count. Read the journal article section for published statistics. Pay close attention to the success criteria.
After a splenectomy, the patients’ immune system is compromised. Immunizations are given before the operation and periodically after. Some hematologists suggest the patient take antibiotics as a preventative measure. Others do not.
The first large series describing Evans syndrome in childhood was published in 1980 by Pui, Wilimas and Wang. They reported 11 patients that had both autoimmune hemolytic anemia and thrombocytopenia during the study period covering the years 1962 -1979. In their study the criteria for diagnosis of Evans syndrome were 1) hemolytic anemia with a positive direct Coombs test and thrombocytopenia occurring either simultaneously or in succession, and 2) the absence of any known underlying etiology. Patients were considered to have neutropenia when the neutrophil count was less than or equal to 1,500/mm3 , lymphopenia with the lymphocyte count was less than or equal to 1,000/mm3 , and thrombocytopenia when platelet count was less than or equal to 100,000/mm3.
The combination of autoimmune hemolytic anemia and thrombocytopenia has been noted in a number of diseases and therefore in their patients they initiated a search for a specific underlying disorder. Diseases associated with autoimmune hemolytic anemia and thrombocytopenia include SLE, scleroderma, mixed connective tissue disease, Hashimoto thyroiditis, thrombotic thrombocytopenic purpura, liver cirrhosis, leukemia, and sarcoidosis. Among their 11 patients, 3 had SLE and 1 had aplastic anemia. Neutropenia was noted in 4 of their 7 patients and lymphopenia was found in 1 patient.
The presence of granulocytotoxic and lymphocytotoxic antibodies in the serum of these patients suggest an autoimmune process. The disease process is characterized by multiple remissions and exacerbations of both hemolytic anemic and thrombocytopenia. The experience of Pui et al indicated a similar course in children. Many patients are hematologically normal between relapses which may involve depressions in 1, 2, or all 3 cell lines.
The etiology as stated above appears to be autoantibodies directed against various cell lines. Pegels, et al reported in the British Journal of Hematology in 1982 a characterization of the autoantibodies responsible for the abnormalities noted in Evans syndrome. They analyzed 24 patients with the simultaneous occurrance of autoimmune hemolytic anemia, idiopathic thrombocytopenia, and/or idiopathic neutropenia. With the help of the immunofluorescence test on their paraformaldehyde-fixed cells, they confirmed the suspected autoimmune nature of the cytopenia in all the patients. That the sera of most of the patients reacted only with one type of blood cell, and not with the others, made it likely that they were dealing with different cell specific autoantibodies. It became evident that, in the majority of the patients, platelet and granulocyte antibodies were demonstrable, but mostly only on the patients own cells. Only in a few of the patients were the antibodies demonstrable, in the serum. By absorption of sera containing antibodies of sufficient strength and of eluates prepared from the cells of some of these patients, they proved that separate antibodies, directed against autoantigens specific for each type of blood cell, are indeed responsible for the syndrome.
It should be noted that in other studies not only have antibodies directed against red cells, leukocytes and platelets been demonstrated, but as well suppression of hematopoietic cell maturation by T-cells has been demonstrated.
Treatment in these patients has been unsatisfactory. Although corticosteroid therapy results in a transient remission in most patients, the majority become steroid dependent or refractory. Subsequent splenectomy has been shown to hold beneficial effect in some patients. Although chronic ITP and chronic autoimmune hemolytic anemia have 70% and 50% sustained remission rates following splenectomy, respectively, this procedure seldom results in prolonged complete remission in patients with Evans syndrome.
Usually prednisone therapy is effective in controlling the acute episodes and is not needed between relapses. However some patients have persistent immune cytopenia and require prolonged corticosteroid treatment. In that case alternate day steroid therapy should be used if possible. Intravenous immunoglobulin and plasmapheresis have also been used with limited success. Immunosuppressive agents, including azathioprine and mercaptopurine, have been reported to be beneficial in a few patients with refractory disease.
Autoimmune disorders in Kabuki syndrome - Am J Med Genet A. Nov 2;132A(3) pp 260-262 2004 Authors: Ming JE, Russell KL, McDonald-McGinn DM, Zackai EH
Kabuki make-up syndrome associated with chronic idiopathic thrombocytopenic purpura - Acta Paediatrica Japonica 36 pp.727-729 1994 Author: Watanabe T, et al.
Note: Numerous articles refer to ITP and anemia as being found in one or more of their patients, in particular the studies that include numerous children/adults.
Althought ITP can strike even the healthiest children, it has been reported as being problematic with Kabuki children. Jonathan has chronic ITP, 3 seperate incidences. His Hemotologist/Oncologist at Childrens Hospital in Seattle has seen a number of Kabuki kids with ITP over the years.
Not to scare anyone, but if you suspect that your child has ITP, it's important to get it checked right away. A simple blood test, platelet count, can give you the information you need. It is also important that if your child does have or had a case of ITP that they have a platelet count before any surgery. If the platelet count is critically low, a bump in the head can cause serious damage.
For those who have not read about Hemolytic Anemia before, in simple terms, it is when your own body's immune system (antibodies) get confused, attack and destroy the red blood cells (hemoglobin)in the body. Hematologists believe that when Evan gets a cold or picks up a virus, his antibodies kick in to fight if off and also think his blood is a virus. Therefore, destroys his red blood cells. If the hemoglobin drops too low, he will go into cardiac arrest.
Evan has been successful in bringing his red blood cells up to normal in the past with moderate doses of steroids. Unfortunately, since his first episode at Christmas, everytime his blood looks great, the medication is weined down to nothing and within 2 weeks his body attacks again. He hasn't been off of steroids for more than 2 weeks since December.
Unfortunately, I am writing today from the hospital. We have been here one week so far. Evan was weined off the prednisone 3 weeks ago and once again his blood cells were attacked. This time his usual dose of prednisone was not able to control the situation and his blood cells have dropped quickly. Evan currently has less than 1/2 the blood in his body that a normal child has. He is extremely jaundice and his urine looks like black coffee. For the past week the doctors here at BC Children's Hospital in Vancouver, Canada have tried power treatments of prednisone (steroids) to flush his system. Basically, he is getting 30 times the amount he would normally get in one day. Unfortunately, his count has dropped even lower and he is very close to needing a blood transfusion. An adult could not survive with such a low hemoglobin count. The doctors are obviously keeping a very close watch and are trying to avoid a transfusion as his antibodies will also attack the new blood within a few days. A transfusion can also bring on other complications. In this situation, it buys time only which could be necessary to keep Evan alive. So far, he is sitting on the fence and fighting as hard as he can. His little heart is working overtime. Through all of this, Evan remains his charming self (even flirting with the nurses).
He has now had 5 SUPER doses of prednisone and his body will not be able to take too many more large doses. Today they dropped it to 3/4 dose. The good news is that his count came up slightly and it is not at 56 anymore. However, he is far from being "out of the woods". There is another more experimental drug they may need to use. The other option is spleen removal, but it doesn't always work.
I have to say this is more stressful than his heart surgery. How would have guessed that such a disease even existed? Certainly not me!
Once Evan gets past this, the doctors are faced with the trying to figure out how to control his immune system so it doesn't attack again once he is taken off the steroids. It's a vicious circle! Long term steroids use is absolutely terrible for children and his hematologist team will not allow him to be on it too long.
It has been an emotional week and I have tried to only think positive. However, as I know it can be fatal if not controlled and I cannot help but feel anguish.
Does anyone have a [child with Kabuki] who fought this autoimmune disease? If so, I would be very interested in your story as it may be helpful to us. I do know of a few [children with Kabuki] that I was in contact with at Christmas, but I would like to know if there are more.
So, a spotty bleeding nose is probably just the dry winter air, but a gusher is definitely something to get checked out, as ITP seems to be something quite a few of our children with Kabuki have had. By the way, after a year, it went away, and there's been no signs of it since, and that was five years ago.