Primary disorders of megakaryopoiesis (platelet production)are rare in childhood, other than as part of an aplastic syndrome. Thrombocytopenia with absent radii syndromeis characterized by severe thrombocytopenia in association with orthopedic abnormalities, especially of the upper
DIC, Disseminated intravascular coagulation; PFA, platelet function analyzer-100; RBC, red blood cell.
extremity. The thrombocytopenia usually improves over time.Amegakaryocytic thrombocytopenia presents at birth or shortly thereafter with findings of severe thrombocytopenia,but no other congenital anomalies. The marrow is devoid ofmegakaryocytes and usually progresses to aplasia of all hematopoietic cell lines.
Acquired thrombocytopenia as a result of decreased production is rarely an isolated finding. It is seen more often inthe context of pancytopenia resulting from bone marrow failure caused by infiltrative or aplastic processes. Certain chemotherapeutic agents may affect megakaryocytes selectively
ITP 2 to SLE, HIV Drug-induced
Figure 151-4 Differential diagnosis of childhood thrombocytopenic syndromes. The syndromes initially are separated by their clinical appearances. Clues leading to the diagnosis are presented in italics. The mechanisms and common disorders leading to these findings are shown in the lower part of the figure. Disorders that commonly affect neonates are listed in the shaded boxes. HSM, Hepatosplenomegaly; ITP, idiopathic immune thrombocytopenic purpura; NATP, neonatal alloimmune thrombocytopenic purpura; SLE, systemic lupus erythematosus; TAR, thrombocytopenia with absence of radius (syndrome); TTP, thrombotic thrombocytopenic purpura; UAC, umbilical artery catheter; WBC, white blood cell. (From Scott JP: Bleeding and thrombosis. In Kliegman RM, Greenbaum LA, Lye PS, editors: Practical Strategies in Pediatric Diagnosis and Therapy, Philadelphia, 2004, Saunders, p 920.) more than other marrow elements. Cyanotic congenital heart disease with polycythemia often is associated with thrombocytopenia, but this is rarely severe or associated with significant clinical bleeding. Congenital (TORCH [toxoplasmosis,other agents, rubella, cytomegalovirus, herpes simplex]) andacquired viral infections (human immunodeficiency virus[HIV], Epstein-Barr virus, and measles) and some drugs (anticonvulsants, antibiotics, cytotoxic agents, heparin, and quinidine) may induce thrombocytopenia. Postnatal infections anddrug reactions usually cause transient thrombocytopenia,whereas congenital infections may produce prolonged suppression of bone marrow function.
Etiology. In a child who appears well, immune-mediated mechanisms are the most common cause of thrombocytopeniaresulting from rapid peripheral destruction of antibody-coatedplatelets by reticuloendothelial cells. Neonatal alloimmune thrombocytopenic purpura (NATP) occurs as a result of sensitization of the mother to antigens present on fetal platelets. Antibodies cross the placenta and attack the fetal platelet (see Chapter 59). Many platelet alloantigens have been identified and sequenced, permitting prenatal diagnosis of the condition in an at-risk fetus. Mothers with idiopathic thrombocytopenic purpura (maternal ITP) or with a history of ITP may have passive transfer of antiplatelet antibodies, with resultant neonatal thrombocytopenia (see Chapter 59). The maternal platelet count is sometimes a useful indicator of the probability that the infant will be affected.