Monday, July 28, 2014

Thrombocytopenia

Definition

Thrombocytopenia is a condition in which there is a deficient number of circulating platelets.

Description

Thrombocytopenia may be congenital or acquired.

The acquired form is more common, especially among elderly. In either case, it usually results from decreased or defective production of platelets in the bone marrow (for example, in leukemia, aplasticanemia and with toxicity from certain drugs), increased destruction outside the marrow caused by an underlying disorder (such as cirrhosis of the liver, disseminated intravascular coagulation and severe infection) or dilution of platelets.

Less commonly, thrombocytopenia results from increased sequestration of platelets in the spleen.

Causes

Acquired thrombocytopenia may result from the use of certain drugs, such as quinine, quinidine, rifampin, heparin, nonsteroidal anti-inflammatory agents, histamine blockers, most chemotherapeutic agents, allopurinol and alcohol.

Impaired production of platelets usually occurs when stem cells are injured or prevent their proliferation in bone marrow. Thrombocytopenia may be accompanied by varying degrees of anemia (low red blood cells) and leukopenia (low white blood cells). Diagnosis of a platelet production defect is established by examination of a bone marrow aspirate or biopsy.

The most common causes of decreased platelet production are marrow aplasia (when the marrow is not developing naturally), fibrosis (an abnormal formation) or infiltration with malignant cells.

Since one-third of the platelet mass is normally sequestered in the spleen, a splenectomy may increase the platelet count by 30 percent. In contrast, when the spleen enlarges, the fraction of sequestered platelets increases, lowering the platelet count. The most common causes of splenomegaly (enlarged spleen) are portal hypertension secondary to liver disease and splenic infiltration with tumor cells, or with macrophages in storage disorders (like Gaucher's disease).

Many common drugs can cause thrombocytopenia. Many chemotherapeutic agents are cytotoxic and depress megakaryocyte production. Ingestion of large quantities of alcohol has a similar marrow-depressing effect leading to transient thrombocytopenia. The syndrome is particularly common in binge drinkers.

Thiazide diuretics, which are commonly used to treat hypertension or congestive heart failure, can produce mild thrombocytopenia which may persist for several months after the drug is discontinued.

The best proof of a drug-induced etiology is a prompt rise in the platelet count when the suspected drug is discontinued. Most people recover within seven to 10 days and do not require therapy.

Thrombocytopenia may also occur transiently after a viral infection (such as Epstein-Barr) or infectious mononucleosis. Another form of thrombocytopenia is idiopathic thrombocytopenic purpura (ITP), an autoimmune disorder. Finally, there is thrombotic thrombocytopenic purpura (TTP), which is an uncommon disorder associated with anemia. Both ITP and TTP typically occur in adults, ages 20 through 50.

Symptoms

Typically, a patient with thrombocytopenia reports a sudden onset of petechiae and ecchymoses, from bleeding into mucous membranes or on the skin.

Painless, round and pinpoints (1 to 3 mm in diameter), petechiae usually appear and fade, and sometimes group to form ecchymoses. Another type of blood leakage (and larger than petechiae), ecchymoses are purple, blue or yellow-green bruises that vary in size and shape. They can occur anywhere on the body from a traumatic injury.

A person with thrombocytopenia may also complain of malaise, fatigue and general weakness (with or without accompanying blood loss). In acquired thrombocytopenia, the patient's history may include the use of one or several offending drugs.

Inspection typically reveals evidence of bleeding (petechiae or ecchymoses), along with slow, continuous bleeding from any injuries or wounds. Adults may have large, blood-filled bullae in the mouth. If the person's platelet count is between 30,000 and 50,000/mm3, bruising with minor trauma may be expected; if it is between 15,000 and 30,000/mm3, spontaneous bruising will be seen (mostly on the arms and legs).

Diagnosis

A thorough history must be taken to rule out the following: exposure to drugs known to cause increased platelet destruction in sensitive people; the presence or absence of a fever associated with viruses; and recent systemic diseases or a recent blood transfusion. Also, a complete physical examination needs to be done, including the palpation of the size of the spleen.

Lab tests to determine the platelet count and clotting function may also be done. In severe thrombocytopenia, a bone marrow study can determine the number, size and maturity of the megakaryocytes (the bone marrow cells that release mature platelets). This information may identify ineffective platelet production as the cause of thrombocytopenia and rule out a malignant disease process at the same time.

Treatment

Treatment of thrombocytopenia varies according to the cause. If thrombocytopenia is drug-induced, then removal of the offending agents should correct the condition.

Corticosteroids may be used to increase platelet production. Lithium carbonate or folate may also be used to stimulate the bone marrow production of platelets. Platelet transfusions may be used to stop episodic abnormal bleeding caused by a low platelet count. However, if platelet destruction results from an immune disorder, platelet infusions may have only a minimal effect and may be reserved for life-threatening bleeding.

Splenectomy may be necessary to correct thrombocytopenia caused by platelet destruction. A splenectomy should significantly reduce platelet destruction because the spleen acts as the primary site of platelet removal and antibody production.

Patients with idiopathic thrombocytopenic purpura (ITP) may require high-dose intravenous immunoglobulin. Patients with thrombotic thrombocytopenic purpura (TTP) will probably require large-volume plasmapheresis (plasma exchange).

Questions

What tests are needed for a diagnosis?

Is a bone marrow biopsy needed now or at a future time?

What is the cause of the thrombocytopenia?

Will you be prescribing any medication to help my condition? What are the side effects?

Are there any signs or symptoms that need to be reported immediately?

Are there any activities or anything that should be avoided that may increase bleeding?

What are some of the complications of this disease?

Is this disease reversible?