Platelet Disorders
A platelet count less than 150 × 109/L is abnormal in term and premature infants (249). The level of platelets in the blood reflects a balance between their production and destruction. Thrombocytopenia may result from decreased production, increased destruction, sequestration, or some combination of these mechanisms. Examination of a well-stained smear of peripheral blood to assess platelet morphology and number, and of bone marrow to assess megakaryocyte morphology and number, has traditionally yielded important information concerning the mechanism of thrombocytopenia in older children. Decreased numbers of platelets and megakaryocytes indicate a production defect, and megakaryocytic hyperplasia and the presence of megathrombocytes (young large platelets) in a peripheral blood smear are characteristic of thrombocytopenic states in which there is increased peripheral destruction of platelets. In newborn infants these indices have not proved as useful as in older children because bone marrow sampling is more challenging and an adequate specimen is often not obtained. Recently, however, Sola and colleagues (250) have published a technique for bone marrow biopsies in neonates that yields small but high-quality specimens thus allowing accurate assessment of cellularity and megakaryocyte numbers.
Neonatal Immune Thrombocytopenia
Immune thrombocytopenia occurs when antibody-sensitized platelets are prematurely destroyed in the reticuloendothelial system, particularly the spleen. Characteristic laboratory features include isolated thrombocytopenia and an increased number of immature megakaryocytes in a bone marrow aspirate.
TABLE 46-9 CAUSES OF NEONATAL THROMBOCYTOPENIA | |
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A variety of conditions are associated with the transplacental passage of maternal antiplatelet antibodies into the fetus, resulting in immunologic destruction of platelets and fetal thrombocytopenia. The antibody may be formed against an antigen on the platelets of the infant (isoimmune or alloimmune thrombocytopenia, in which case the mother’s platelet count is normal) or an antigen present on the platelets of the mother (autoimmune thrombocytopenia, in which case both the mother and child may have thrombocytopenia), as occurs in maternal immune thrombocytopenic purpura (ITP) or thrombocytopenia associated with a collagen vascular disorder such as systemic lupus erythematosus.
Neonatal Alloimmune Thrombocytopenia.
In neonatal alloimmune thrombocytopenia, the infant possesses a platelet antigen of paternal origin that is lacking in the mother. Typically, the infant’s platelets cross the placenta into the maternal circulation during pregnancy or at the time of delivery and cause immunization of the mother, with the formation of antibodies against the foreign platelet antigen. Less frequently, the cause of immunization is exposure of an antigen-negative mother to antigen-positive platelets during transfusion. During pregnancy, transplacental passage of the maternal IgG antibodies leads to sensitization of fetal platelets. Sensitized platelets are rapidly destroyed in the fetal reticuloendothelial system, particularly the spleen, and the result may be thrombocytopenia in utero and in the infant at the time of delivery. This mechanism is analogous to that causing hemolytic disease of the newborn.
The platelet-specific antigen system most often involved in cases of neonatal alloimmune thrombocytopenia is HPA-1a (PlA1) (Table 46-10) (255). Other platelet-specific antigens are involved less frequently (256,257,258,259,260,261,262,263 and 264). In the largest series of cases of suspected neonatal alloimmune
thrombocytopenia, 91% (120 of 132) of serologically proven cases involved HPA-1a (PlA1) alloantibodies (265). Of the remaining 12 cases, the pathologic alloantibodies were anti-HPA 5b (Bra)-9, anti-HPA-1b (PlA2)-1, anti-HPA-3a (Baka) with HLA antibody-1, and blood group B isoagglutinins-1. Although HLA alloantibodies often develop as a result of pregnancy, they rarely are the cause of severe neonatal thrombocytopenia.
thrombocytopenia, 91% (120 of 132) of serologically proven cases involved HPA-1a (PlA1) alloantibodies (265). Of the remaining 12 cases, the pathologic alloantibodies were anti-HPA 5b (Bra)-9, anti-HPA-1b (PlA2)-1, anti-HPA-3a (Baka) with HLA antibody-1, and blood group B isoagglutinins-1. Although HLA alloantibodies often develop as a result of pregnancy, they rarely are the cause of severe neonatal thrombocytopenia.
TABLE 46-10 PLATELET-SPECIFIC ALLOANTIGENS | |||||||||||||||||||||||||||||||||||||||
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The incidence of neonatal alloimmune thrombocytopenia, based on data collected in prospective studies, is estimated to be in the order of 1 in 1800 live-born infants (255). In 85% of cases in which serological information was available, neonatal alloimmune thrombocytopenia reflected fetomaternal incompatibility for the HPA-1a (PlA1) alloantigen. Prospective studies of HPA-1a (PlA1) antigen negative pregnant women provide complementary information reviewed in (255). Fifty-seven of 851 HPA-1a negative women were found to have HPA-1a alloantibodies, 48 during pregnancy and 9 in the postpartum period yielding an overall incidence of HPA-1a (PlA1) alloimmunization of approximately 1 per 650 pregnancies. Thirty infants manifested thrombocytopenia suggesting an incidence of neonatal alloimmune thrombocytopenia as a result of HPA-1a (PlA1) alloantibodies in the order of 1 per 1200 pregnancies in a Caucasian population. Two important points emerge from these prospective screening studies: first, not all pregnancies involving an HPA-1a (PlA1) alloimmunized mother will result in a thrombocytopenic fetus/neonate; and second, the appearance of HPA-1a (PlA1) alloantibodies, similar to red blood cell alloantibodies in cases of hemolytic disease of the newborn, may occur for the first time in the postpartum period.
The typical infant with neonatal alloimmune thrombocytopenia is term, and thrombocytopenia is unexpected. Cutaneous manifestations of severe thrombocytopenia (e.g., bruising, a petechial rash) are often the only abnormalities found on physical examination. A complete blood count shows severe isolated thrombocytopenia with a normal hemoglobin and leukocyte count.
Affected infants are at risk of serious hemorrhage, particularly into the central nervous system (CNS). In a review by Pearson and colleagues (266), the incidence of fatal hemorrhage was 10% to 15%. In some cases, CNS hemorrhage occurs in utero before delivery (267,268,269,270 and 271). Bussell and associates (272) estimated that as many as 25% of CNS hemorrhage cases of associated with neonatal alloimmune thrombocytopenia occur antenatally.
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