Thrombocytopenia may be congenital or acquired; the acquired form is more common. In either case, it usually results from decreased or defective production of
platelets in the marrow (for example, in leukemia, aplastic anemia, and toxicity with certain drugs) or from increased destruction outside the marrow caused by an underlying disorder (such as cirrhosis of the liver, disseminated intravascular coagulation, and severe infection).

Less commonly, thrombocytopenia results from sequestration (hypersplenism and hypothermia) or platelet loss. Acquired thrombocytopenia may result from the use of certain drugs, such as quinine, quinidine, rifampin, heparin, nonsteroidal anti-inflammatory drugs, histamine blockers, most chemotherapeutic agents, allopurinol, and alcohol.

Thrombocytopenia may also occur transiently after a viral infection (such as Epstein-Barr) or infectious mononucleosis. (See Causes of decreased circulating platelets.) An idiopathic form of thrombocytopenia also occurs. (See “Idiopathic thrombocytopenic purpura” page 471.)

Complications of thrombocytopenia are usually related to bleeding. Severe thrombocytopenia can cause acute hemorrhage, which may be fatal without immediate therapy. The most common sites of severe bleeding include the brain and the GI tract, although intrapulmonary bleeding and cardiac tamponade can also occur.

Typically, a patient with thrombocytopenia reports sudden onset of petechiae and ecchymoses from bleeding into mucous membranes (GI, urinary, vaginal, or respiratory). He 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, ecchymoses), along with slow, continuous bleeding from any injuries or wounds. Painless, round, and as tiny as pinpoints (1 to 3 mm in diameter), petechiae usually occur on dependent portions of the body, appearing and fading in crops and sometimes grouping to form ecchymoses. Another form 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 traumatic injury. In patients with bleeding disorders, they usually appear on the arms and legs. In adults, inspection may reveal large, blood-filled bullae in the mouth. Gentle palpation of edematous ecchymotic areas may cause pain, indicating that these areas are actually hematomas. Superficial hematomas are red; deep hematomas are blue. They typically exceed 1 cm in diameter.

If the patient’s platelet count is between 30,000 and 50,000/mm³, expect bruising with minor trauma; if it’s between 15,000 and 30,000/mm³, expect spontaneous bruising and petechiae, mostly on the arms and legs. With a platelet count below 15,000/mm³, expect spontaneous bruising or, after minor trauma, mucosal bleeding, generalized purpura, epistaxis, hematuria, and GI or intracranial bleeding. Female patients may report menorrhagia. Remember to look for both obvious and insidious sources of bleeding.

The following laboratory findings help establish a diagnosis of thrombocytopenia:

Platelet antibody studies can help determine why the platelet count is low and help direct treatment. Platelet survival studies help differentiate between ineffective platelet production and inappropriate platelet destruction. (Platelet production disorders may occur after radiation exposure, medication ingestion, or an infectious disease. They may also occur idiopathically. Inappropriate platelet destruction may occur with splenic disease and platelet antibody disorders.

In severe thrombocytopenia, a bone marrow study determines the number, size, and cytoplasmic 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.