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Understand Childhood Cancers and Blood Disorders

Thrombocytopenia/ ITP

Thrombocytopenia means that there are fewer platelets in the blood than normal. Platelets are tiny cells that flow in our blood along with the red and white blood cells. Like the red and white blood cells, platelets are made in the bone marrow. Their job is to help clot the blood whenever there is an injury to a blood vessel. Platelets contain multiple granules that have chemicals that are released whenever the platelets become active. These chemicals help the platelets stick to each other as well as to the wall of the injured blood vessel. These platelets that are stuck together, along with other materials, form what is known as a "platelet plug" which will help to immediately stop the flow of blood. Later on, the clotting system strengthens that platelet plug and makes it sturdier. If one cannot make that initial platelet plug, abnormal bleeding will result.

Normally, we have anywhere between 150,000 and 400,000 platelets in one cubic centimeter (CC) of blood. Platelet counts vary from day to day and even within the same day. When platelet counts fall below 150,000, we call it thrombocytopenia. There are two main problems that lead to thrombocytopenia -
  1. The body does not make enough platelets
  2. Platelets are removed or destroyed too rapidly from the blood
The risk of severe bleeding from thrombocytopenia is not very significant unless -
  • Platelet counts are falling rapidly
  • Platelet counts are very low (especially under 10,000 platelets per CC of blood)
  • Platelets do not function properly. Platelets may not function normally (regardless of their number) when patients take certain medications (e.g., Aspirin, Advil, Motrin, Aleve, etc). Platelets may also work improperly when patients have certain inherited disorders that affect the platelet function (for example, Von Willebrand Disorder, etc).
When platelet counts fall below 50,000, bruising becomes more pronounced. As the counts decrease further, the number of bruises increases and they begin to be seen in unusual places on the body (like the chest, back, belly, and buttocks). Bruises (also called ecchymoses) are deep bleeds under the skin. When the platelet counts continue to drop to around 20,000 or less, you might see both bruises (ecchymoses) and small red dots over the face and body (looking like pin-prick reddish dots, called petechiae). Sometimes many such red dots can bunch up together and appear like a red rash on the skin. This "rash" is called purpura.

False (Deceptive) thrombocytopenia - this can happen when there is a blood clot in the tube. The clot literally traps many platelets and makes it look like thrombocytopenia. It can also happen when many platelets bunch up together and escape detection by the Complete Blood Count (CBC) machine because of the preservative in the blood tube itself. When the doctors suspect this is the case, they order a repeat CBC or CBC collected into another type of tube to get the correct platelet count.

Congenital (Inherited) Thrombocytopenia - there are several rare inherited disorders characterized by thrombocytopenia, including: May-Hegglin Anomaly (bleeding is not very severe or common), Bernard-Soulier Syndrome (low platelet count and poor platelet function resulting in frequent and potentially serious bleeding), and Wiskott - Aldrich syndrome (characterized by platelets that are few and very tiny, eczema, and frequent infections). Another rare inherited abnormality is Thrombocytopenia and Absent Radii (TAR), where children are born missing their forearm bones and also have thrombocytopenia.

Defective Platelet Production - Since platelets are made in the bone marrow, anything that affects the marrow, can affect platelet production. Examples include the following:
  • Leukemia, lymphoma and other cancers
  • Other abnormal cells such as histiocytes
  • "Storage" Disorders where a missing or defective enzyme leads to deposits of abnormal material in the marrow.
In such situations, the abnormal cells "take over" and multiply inside the bone marrow. Eventually, they crowd out all the normal cells in the marrow, including the cells that manufacture platelets.

Sometimes, platelet production is slowed down or reduced by other causes, including:
  • An abnormal bone marrow - a condition called myelodysplasia or aplastic anemia.
  • Medications - some antibiotics, chemotherapy, and anti-convulsants can slow down the production of platelets.
  • Nutritional reasons - vitamin B12 or folic acid deficiency may lead to thrombocytopenia (those vitamin shortages will also cause anemia and can lower the white blood cell count)
  • Kidney or liver failure
  • Excessive alcohol drinking
There are also rare disorders where the bone marrow structure is abnormal, where supporting cells, called "stroma", are abnormal, affecting the manufacturing process. Examples include the following:
  • Osteopetrosis - in this very rare disease, the bone itself takes too much space, not leaving enough room for normal marrow cells.
  • Myelofibrosis - an extremely rare disorder in children, where fibrous or 'stringy' tissue crowds out the normal cells that make our blood.
Increased Platelet Destruction - Bone marrow normally makes enough platelets to replace those that are 'busy' clotting blood or dying. Normal platelets only live for 10 days before they die. In some conditions, the platelets are destroyed so rapidly that the bone marrow simply cannot catch up. The result is thrombocytopenia.

Platelets are sometimes 'tagged' and designated by the body's immune system for destruction. The body normally makes antibodies against germs, but it sometimes can make abnormal antibodies against its own cells, including platelets. Those tagged platelets travel with the blood through the spleen where special 'killer cells' trap and destroy them. There are several examples:
  • Infections - Human Immunodeficiency Virus (HIV).
  • Medications - can sometimes induce production of antiplatelet antibodies.
  • Autoimmune disorders - such as Systemic Lupus Erythematosus, or, simply Lupus. In Lupus, the body makes abnormal antibodies against many of its own normal cells (kidneys, joints, and platelets).
  • Immune Thrombocytopenic Purpura (ITP) - this is a common disorder in children; by far more common than all the other conditions in this discussion. ITP usually occurs in children who are normal and healthy, often after the child has recovered from a minor infection (most commonly a virus, a cold, etc). The body, in its efforts to kill the virus, also makes antibodies against platelets. The most common symptoms of ITP are:
    • Small skin bruises, such as petechiae.
    • Ecchymoses (bruises). Little children often fall during normal play and many have bruises, mainly on their legs. That's a normal finding. But in ITP, you will see bruises in unusual places on your child's body (the buttocks, chest, back, and often - the entire body).
    • Prolonged nose bleeds.
ITP happens most frequently in young children (ages three to five years), but can occur at any age, including adulthood. Although children can have extremely low platelet counts, they rarely suffer any life-threatening bleeds. Most children (about 80 percent), recover from ITP in a few days or weeks, although sometimes it can last longer. ITP very rarely recurs. It does not progress to leukemia and is not contagious or inherited.

Once the diagnosis of ITP is made, the treatment depends very much on the age of the child, how low the platelet count is, and whether or not the child has any serious bleeding. In some cases, no treatment is needed and the doctors will only follow your child closely with platelet counts. When the doctors decide to treat ITP, they have several choices (medications such as WinRho, IVGG, and steroids). Platelet transfusions are given only to patients with life-threatening bleeding. Sometimes it is necessary to give treatment for ITP in the hospital, but usually treatments can be easily given either in an office or even at home.
  • Disseminated Intravascular Coagulation (DIC) - in this condition, the platelets are used up very rapidly by the body. DIC occurs in very sick children, most commonly with serious infections (such as meningitis and sepsis). DIC can rarely be seen in some cancers and as a complication of labor and delivery.
  • Thrombotic Thrombocytopenic Purpura (TTP)
  • HUS (hemolytic-Uremic Syndrome) - is another rare condition occurring in children. HUS is often the result of an infection caused by bacteria called E.Coli. The patient can have thrombocytopenia along with a kidney failure.
Disappearance of platelets from the circulation - In some situations, there are neither decreased production, nor increased destruction, of platelets. There are two main examples:
  • Enlarged spleen - patients with very large spleens (from any cause), may have thrombocytopenia. The reason for the low platelet count is that the platelets are 'pooled' or 'trapped' inside the large spleen.
  • Red blood cell transfusions - red blood cell bags do not contain platelets. Therefore, when patients receive many red blood cell transfusions at a time (for example, as a result of car accidents or major surgery), they sometimes develop thrombocytopenia. The low platelet count in this case is caused simply by dilution. If the patient receives only red blood cells, his or her platelets get diluted.

Diagnosis of Thrombocytopenia

Doctors start by asking you many questions about your child's health, both past and present. A physical examination follows those questions and doctors pay careful attention to abnormal bleeding symptoms (petechiae, purpura, etc). CBC will be drawn and be analyzed by a machine. In addition, the doctors look at the blood under a microscope. A bone marrow test is very rarely needed, and only in situations when the doctors suspect disorders of platelet production.

Treatment of Thrombocytopenia

We started discussing treatment of thrombocytopenia in the section dealing with ITP. In general, treatment of thrombocytopenia very much depends on the cause of the low platelet count. In part, it also depends on the age of the child and his or her level of activity. Finally, and most importantly, treatment is decided by the severity of the bleeding symptoms. While it is unpleasant and worrisome for you to see your child covered with bruises and red dots from head to toe, it is important to know that bruising in itself is not dangerous. Treatment decisions can include any of the following:
  • Follow up - sometimes, the best treatment is no treatment at all.
  • If a medication is suspected as the cause of a child's thrombocytopenia, the doctors may sometimes recommend changing that medication.
  • If a bacterial infection is suspected as the cause of a child's thrombocytopenia, treatment with antibiotics may gradually increase the platelet count.
  • If a viral infection is suspected, follow up would be recommended. No antibiotics are available for most viral infections.
  • If the cause of thrombocytopenia is cancer, one must kill the uninvited cancer cells. As cancer cells are removed from the bone marrow, normal production of platelets can start again.
  • If the cause of thrombocytopenia is an autoimmune disease (like Lupus), one must treat the underlying condition.
Medical treatments available for thrombocytopenia include the following (sometimes a combination of more than one choice):
  • Platelet transfusions
  • Corticosteroids
  • WinRho
  • Intra-Venous Gamma Globulin
  • Rituximab
  • Vincristine
Finally, while this is still in research, we expect to have medications that stimulate the bone marrow to manufacture platelets at a faster rate in the next few years.
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