Thrombocytopenia (Low Platelet Count)

Symptoms of a low platelet count can be bleeding gums and nosebleeds.

• Thrombocytopenia refers to an abnormally low level of platelets in the bloodstream.
• Platelets are important for normal blood clotting.
• With severe thrombocytopenia, excessive bleeding may occur.
• Thrombocytopenia occurs because there is decreased production or increased destruction of platelets. It also can occur when the spleen enlarges and sequesters more platelets than usual.
• Heparin-induced thrombocytopenia (HIT) arises due to immune-mediated destruction of platelets that may occur with the blood thinner heparin and its related drugs.
• Other prescription drugs also may cause thrombocytopenia in certain cases.
• Viral infections may cause thrombocytopenia due to their effect on bone marrow, leading to decreased production of platelets.
• A blood test is used to diagnose thrombocytopenia. It often is identified when blood tests are ordered for other reasons or during routine screening.
• Signs of thrombocytopenia can include small pinpoint hemorrhages (petechiae) or bruises known as purpura.
• Treatment of thrombocytopenia, when necessary, consists of platelet transfusions. Most patients with thrombocytopenia do not require regular platelet transfusion. If surgery is planned in a patient with a platelet count less than 50,000, then transfusion may be necessary

Platelets (thrombocytes) are important elements in the blood that are important for blood coagulation (clotting and prevention of bleeding). Thrombocytopenia refers to having a low platelet count in the blood compared to the normal range.

• The normal platelet count ranges between 150,000 and 450,000 per microliter (one-millionth of a liter).
• Only about 2/3 of platelets released into the bloodstream circulate in the blood, and the remaining third are typically found in the spleen.
• The life cycle of platelets is usually about 7-10 days; therefore, the old ones are continuously being replaced by new ones.

Most people with thrombocytopenia have no symptoms directly associated with low platelets. They may show symptoms related to the underlying cause of thrombocytopenia, however.

In severe thrombocytopenia (platelet counts of less than 10,000 to 20,000), excess bleeding can occur if the person is cut or injured. Spontaneous bleeding can also happen when platelet numbers are severely diminished.

Signs and symptoms of bleeding related to thrombocytopenia can include:

• Easy bleeding or bruising
• Pinpoint hemorrhages into the skin or lining of the mouth (petechiae) or bruising (purpura)
• Nosebleeds
• Bleeding gums
• Heavy menstrual periods
• Blood in the stool or urine

Other signs and symptoms that may occur in people with thrombocytopenia can include:

• Enlargement of the spleen (splenomegaly)
• Fatigue
• Jaundice (yellowing of the skin and whites of the eyes)

Causes of thrombocytopenia can be divided into three categories

1. impaired production,
2. increased destruction or consumption, and
3. splenic sequestration.

The main causes in each category are outlined below, although there are other less common causes of low platelet count not mentioned in this article.

Low platelet count due to impaired production is generally due to problems with the bone marrow. Usually, other blood cells (red and white) are also affected by some of these processes, and their numbers may be abnormal.

Some viral infections can cause low platelet count by affecting the bone marrow, for example,

• parvovirus,
• rubella,
• mumps,
• varicella (chickenpox),
• hepatitis C,
• Epstein-Barr virus (EBV), and
• HIV.

Aplastic anemia (agranulocytosis) is the terminology for bone marrow failure leading to low platelet count usually associated with anemia (low red cell count) and leukopenia or leucopenia (low white cell count). Common causes of aplastic anemia include

• infections (parvovirus, HIV);
• some medications [chloramphenicol, gold, phenytoin (Dilantin), valproic acid (Depakene, Depakote, Depakote ER, Depacon);
• radiation; or
• congenital disorders (Fanconi's anemia).

Many chemotherapeutic drugs commonly cause bone marrow toxicity and thrombocytopenia.

Other causes of thrombocytopenia due to impaired bone marrow production of platelets include

• thiazine mediations;
• alcohol toxicity from long-term alcohol abuse;
• leukemia and lymphomas,
• cancers invading the bone marrow; and
• vitamin B12 deficiency.

Increased platelet destruction can cause thrombocytopenia by immunologic and non-immunologic mechanisms.

Immunologic causes of thrombocytopenia can be caused by

• certain medications, for example, sulfonamide antibiotics, carbamazepine (Tegretol, Tegretol XR , Equetro, Carbatrol), digoxin (Lanoxin), quinine (Quinerva, Quinite, QM-260), quinidine (Quinaglute, Quinidex), acetaminophen, and rifampin;
• transfusion reactions; and
• rheumatologic conditions (systemic lupus erythematosus or SLE).

Idiopathic thrombocytopenic purpura (ITP) is immunologic thrombocytopenia in which the immune system mistakenly attacks the circulating platelets (autoimmune). ITP is typically chronic (long-standing) in adults and acute in children.

Heparin-induced thrombocytopenia (HIT) is immune destruction of platelets mediated by the use of the blood thinner heparin and its related drugs (low molecular weight heparin, called enoxaparin [Lovenox]).

Non-immunologic platelet consumptive processes include; severe infections or sepsis, irregular blood vessel surface (vasculitis, artificial heart valve), or, rarely, disseminated intravascular coagulation or DIC (a serious complication of overwhelming infections, traumas, burns, or pregnancy).

Other non-immunologic causes of thrombocytopenia are two other rare, but related, conditions called hemolytic uremic syndrome (HUS) and thrombotic thrombocytopenic purpura (TTP). These may result from some viral illnesses, metastatic cancers, pregnancy, or chemotherapy. Other clinical manifestations of these conditions are hemolytic anemia, kidney failure, confusion, and fever. HUS is generally associated with infectious diarrhea in children caused by escherichia coli bacteria (E. coli O157:H7).

HELLP is an acronym for a syndrome seen in pregnant women that causes hemolytic anemia (blood cells rupture), elevated liver enzymes, and low platelets.

Splenic sequestration occurs when the spleen enlarges (for example, due to cirrhosis of the liver or certain types of leukemia) and captures, or sequesters, more platelets from the circulation than normal. This could lead to thrombocytopenia.

In infants, many conditions similar to these listed above can lead to neonatal thrombocytopenia. There are also some rare genetic conditions that can also lead to thrombocytopenia in children at birth.

Pseudothrombocytopenia is term given to situations in which there is a falsely low platelet count on the blood smear reviewed by the laboratory. This can happen because of occasional clumping of the platelets together when the blood is drawn. Therefore, small number of individual platelets may be seen under the microscope, and this can be confused with true thrombocytopenia. A repeat blood draw, preferably in a tube which prevents clumping, typically solves this issue.

Dilutional thrombocytopenia is another condition that may be seen when several units of red blood cells have been transfused in a short period time. As the volume of blood expands, platelets may appear more scarce as they are distributed in a larger volume.

Thrombocytopenia may be identified during blood work ordered by a primary care provider, including internists, pediatricians, and family medicine specialists. Hematologists are specialists in blood disorders, and they may be called upon to treat patients with thrombocytopenia. Patients with thrombocytopenia due to an underlying disease or condition will also be managed by the specialists that treat these underlying conditions, including infectious disease specialists, rheumatologists, oncologists, and others.

Low platelet count is often discovered incidentally during routine blood work. Platelets are a component of the complete blood count (CBC) along with white blood cell and red blood cell counts. Pseudothrombocytopenia can be eliminated by repeating the CBC.

Investigation for low platelet count includes a comprehensive medical history and physical examination by the doctor. Review of all the medications, family history, and personal history of cancers, drug and alcohol use, bleeding problems, and other medical conditions (rheumatic diseases, liver problems, kidney disease) needs to be included in this evaluation. An enlarged spleen (splenomegaly), petechiae, and purpura are typically looked for on the physical examination in these patients.

Further diagnostic investigation for thrombocytopenia relies on a detailed review of the other values on the CBC (red cell count, hemoglobin, white blood cell count, mean platelet volume or MPV), the comprehensive blood chemistry panel (kidney function, liver function, electrolytes), blood coagulation panel (other components of the clotting system), and review of the blood smear under the microscope (looking for fragmented red cells, shape and size of white cells, red cells, platelets).

Tests for antibodies and other assays may be performed in cases in which HIT or ITP are suspected. Bone marrow biopsy is sometimes done to evaluate for aplastic anemia, leukemia, lymphoma, or metastatic cancer to the bone marrow.

The treatment for thrombocytopenia depends largely on its severity and the underlying cause.

• For the most part, patients with thrombocytopenia do not require regular platelet transfusion. If any surgery or other invasive procedure is planned in a patient with a platelet count less than 50,000, then transfusion may be necessary to keep the platelet count greater than 50,000.
• Other general recommendations for platelet transfusion are active bleeding in patients with platelet counts less than 20,000 to 50,000 (depending on the clinical picture) and patients with platelet counts less than 10,000 with or without active bleeding.

• In the majority of cases, the function of the platelets is normal despite the lower number, and this is typically sufficient to stop minor bleeding.
• However, individuals with severe thrombocytopenia (counts of less than 20,000) may have an increased risk of bleeding if they are cut or injured.

Medical treatment for any underlying cause of thrombocytopenia plays a key role in its treatment if at all possible. For example, treating sepsis (infections), lupus, or leukemia may be an essential part of treatment for low platelet count due to these causes.

• Medication-induced thrombocytopenia may be treated by discontinuation of the culprit medication under the direction of the physician. This is especially important in patients with HIT, which normally happens in the hospital setting in patients who are receiving blood thinners for other medical reasons. If this diagnosis is correctly made, then any heparin products [heparin, enoxaparin (Lovenox) must be discontinued immediately, and the patient may not receive any of these products in the future.
• In severe ITP, steroids are usually used to weaken the immune system in order to depress the autoimmune attack on platelets.
  • Intravenous antibodies or immunoglobulin (IVIG) can also be used at times for the same reason if the condition is not responsive to steroids.
  • Splenectomy (removal of the spleen) may be recommended in cases unresponsive to other treatments.
• Plasma exchange (plasmapheresis) is the treatment for TTP and HUS.
  • In these conditions, platelet transfusion is not routinely recommended because this could prolong the course of the disease.

The outlook for thrombocytopenia mainly depends on its cause and its severity.

• Only in very severe thrombocytopenia (platelet counts of less than 10,000 - 20,000), there may be a risk of spontaneous bleeding.
• Many cases of thrombocytopenia may be reversible (medication-induced, infectious), thus carrying a favorable prognosis. The function of platelets (clotting and prevention of bleeding) remains undisturbed in most cases, despite a low platelet count.

Thrombocytopenia may be preventable only if its underlying cause is known and preventable.

• For example, in patients with alcohol-induced thrombocytopenia, alcohol avoidance is recommended.
• In patients with HIT, any heparin products must be avoided in the future, as mentioned earlier.
• If any medication is known to cause low platelet count in an individual, then its future use in that person may be discouraged.