Thrombocytopenia, usually defined as an absolute platelet count less than 150,000/mm³, is a common cause of bleeding in pediatric patients. A low platelet count can be the result of increased platelet destruction, reduced production, consumption, or sequestration (Table 91-1), and considering these distinctions will help in formulating a differential diagnosis. Formation of a platelet plug is vital to hemostasis. Regardless of the cause, when platelet numbers are decreased, there can be petechiae, bruising, or bleeding. The body has a remarkable capacity to maintain hemostasis despite low platelet numbers, so symptoms may not become evident until the platelet count is quite low—usually below 50,000/mm³. Patients with moderately decreased platelet counts may be asymptomatic, with the thrombocytopenia being noted incidentally. This chapter focuses on the major causes of thrombocytopenia and their evaluation and management.

THROMBOCYTOPENIC PURPURA

Clinical Presentation

The annual incidence of immune or idiopathic thrombocytopenic purpura (ITP) in children is about 50 per million, and it most commonly affects children between 2 and 6 years of age. The clinical definition of ITP was recently standardized to include peripheral blood platelet count less than 100 × 10⁹/L in the absence of other conditions associated with thrombocytopenia.¹ Immune thrombocytopenia is an autoimmune condition caused by antiplatelet antibodies, which leads to a drastically shortened platelet survival time due to platelet opsonization and enhanced clearance.² Primary ITP is the most common form (“typical ITP”), whereas secondary ITP can be ascribed to a secondary condition, such as administration of a live vaccine, viral infection, systemic lupus erythematosus, or human immunodeficiency virus.² A common presentation of primary ITP is an otherwise healthy child with the sudden onset of petechiae or bruising, or both, often with an antecedent febrile illness. As a general rule, thrombocytopenia is profound and typically the only abnormal finding in the complete blood count (CBC).

Differential Diagnosis

Since the age distribution and presenting symptoms of ITP can be very similar to that of acute leukemia, there is often some anxiety around the diagnostic workup for acute thrombocytopenia. In most cases, the history, physical examination, and review of the CBC parameters and peripheral blood smear can be used to differentiate ITP from acute leukemia or aplastic anemia (Table 91-2). One also needs to consider other causes of “secondary immune thrombocytopenia,” including drugs, infections, malignancy, and autoimmune disorders (Table 91-3). Systemic lupus erythematosus, rheumatoid arthritis, and human immunodeficiency virus infection, as well as other inflammatory diseases, must be considered in the differential diagnosis for children presenting with thrombocytopenia, especially teenagers. A number of congenital conditions may also cause thrombocytopenia, such as thrombocytopenia-absent radius syndrome, Wiskott-Aldrich syndrome, von Willebrand disease (type IIB), and congenital amegakaryocytic thrombocytopenia.³

Diagnostic Evaluation

The diagnosis of ITP is one of exclusion and is often apparent from a reliable and thorough history and physical. A CBC demonstrates a normal number of white blood cells and a relatively normal hematocrit. The platelet count is typically extremely low, often less than 10,000/mm³ and frequently as low as 1000/mm³. Other important laboratory tests include Rh blood group typing and a direct antiglobulin test to determine eligibility for anti-Rh₀D therapy and to rule out Evans syndrome, which is concurrent autoimmune cytopenia of more than one blood cell line. The peripheral blood film should be examined by an experienced hematologist or technician to ensure no blasts are present. Any aberrations in the history, physical examination, or laboratory findings warrant a bone marrow examination to rule out acute leukemia or aplastic anemia as a cause of thrombocytopenia, especially if steroids are being considered as treatment.

Management

Many physicians opt for close observation alone for a child with ITP who is not bleeding acutely and does not have evidence of significant blood loss, although many care providers and families of patients with ITP feel much more comfortable treating the thrombocytopenia rather than waiting for spontaneous resolution. Therapies may raise the platelet count, but most do not shorten the duration of the disease state. In general, physicians tend to treat ITP under the following circumstances: when the patient has active bleeding, when the platelet count is below 10,000/mm³, or when the patient is prone to trauma (e.g. toddlers or athletically active patients). Treatment of ITP includes corticosteroids, intravenous immunoglobulin (IVIG), anti-Rh₀D therapy (WinRho), rituximab (anti-CD20 monoclonal antibody treatment), and splenectomy (Table 91-4).³ Corticosteroids are the most cost-effective therapy and are easiest to administer, though they are associated with significant potential side effects, especially with long-term use. Before steroids are given, the clinician must be reassured that the child does not have acute leukemia, as steroids can induce a temporary remission in acute lymphoblastic leukemia and thus make the ultimate diagnosis and treatment more difficult. For ITP, a short course of steroids usually causes a rise in the platelet count in a few days, which is thought to mainly be a result of interference with splenic uptake of antibody-coated platelets. In most children steroids can be tapered quickly, and most will not relapse. In some patients, however, another course of steroids or a slower taper may be needed. The treatment that results in the most rapid rise in the platelet count is IVIG;^3,4 however IVIG is very expensive and generally involves hospitalizing the patient for the 8- to 12-hour infusion. In addition, many children experience headaches after the infusion, probably related to the increased protein load, and this often leads to imaging studies (e.g. CT scanning) to evaluate for possible intracranial hemorrhage. The use of anti-Rh₀D has increasingly gained popularity as a treatment option for ITP, but it is useful only in patients with an Rh-positive blood type. Administration of anti-Rh₀D causes a rise in platelet count with a predictable decline in hemoglobin, perhaps related to saturation of the reticuloendothelial system by opsonized red blood cells, although the precise mechanism remains unknown. Very rarely, a patient with ITP has a concomitant immune-mediated hemolytic anemia at presentation, a constellation of autoimmune processes known as Evans syndrome. In this setting, addition of more anti–red blood cell antibody to the system would exacerbate the hemolytic anemia. Therefore before using anti-Rh₀D the clinician must verify that the Coombs test (direct and indirect antiglobulin tests) is negative. After any of these treatments, the development of new petechiae/purpura should slow, and the platelet count typically rises over the next several days. In general, the platelet count should be measured 2 to 3 days after treatment and then again in 1 week if stable.