Pediatric Hematology

·         "B is Bad, but A is Awful." The A antigen is more antigenic than B, and anti-A antibodies tend to cause more severe hemolysis.

·         Infants with pyruvate kinase deficiency have anemia at birth, invariably develop prolonged hyperbilirubinemia, and will typically have a very high nucleated RBC count. The latter is pathognomonic since mature RBCs have almost no enzyme and cannot survive, and it is the normal RBCs that perform most RBC functions. Similar to G6PD deficiency, the erythroid marrow is markedly hypertrophied.

·         Some silent carriers of a-thalassemia produce small quantities of an unusual hemoglobin called Constant Spring. This hemoglobin was named after a small Jamaican town in which the first family known to carry the gene resided.

·         In normal RBCs, a small amount of MetHb is constantly being formed, but the level remains low (<1% of total Hb) because of the presence of two enzyme systems, the NADH-dependent cytochrome b5 MetHb reductase system and NADH diaphorase. Cytochrome b5 reductase uses NADH to reduce cytochrome b5, which in turn reduces MetHb to Hb. A small amount of MetHb is reduced to hemoglobin by NADPH diaphorase. The latter mechanism is enhanced by methylene blue, the standard treatment for methemoglobinemia. Cellular antioxidants such as vitamin C and glutathione may reduce MetHb to Hb nonenzymatically.

During the period up to 6 months of age, there is a relative deficiency of NADPH diaphorase. This deficiency not only predisposes persons to methemoglobinemia but also leads to a lack of response to methylene blue. Fetal hemoglobin is more sensitive to oxidation than adult hemoglobin.

·         Anemia of prematurity is not responsive to nutritional support with iron, folate, or vitamin E. Transfusions may be necessary if the infant is ill or has cardiovascular manifestations of anemia. EPO has been used with mixed results in this condition.

·         Neonatal alloimmune thrombocytopenia (NAIT): Just as RBCs have surface antigens that make it possible to classify persons into "blood groups," platelets have surface antigens as well. These are now called human platelet antigens (HPAs). There are over 10 different HPAs. NAIT is a platelet incompatibility between mother and fetus analogous to Rh disease. As with Rh disease, the mother makes antibody against "paternal" antigens (most commonly HPA-1a, previously called PLA-1). The antibody crosses the placenta and binds fetal platelets, resulting in their destruction. The antibody can also cause a defect in platelet aggregation.

·         The absence of bleeding at routine circumcision does not rule out the diagnosis of severe hemophilia.

·         Deficiencies of factor XII, prekallikrein, and high-molecular-weight kininogen. (contact factors) they are critical to initiating the activation of coagulation in the in vitro clotting assays but do not contribute significantly to hemostasis in vivo. Although there is no true factor deficiency, it is important to keep in mind that heparin contamination may result in a prolonged PTT without bleeding.

Factor XIII deficiency is a clinical bleeding disorder in which the screening tests, PT, PTT, and platelet count are all normal.

·         Testing a newborn is not recommended because the levels of the von Willebrand's factors may be falsely high in the perinatal period as a result of the effect of maternal hormones. For this reason, infants with type I do not present with bleeding symptoms during this time. Testing is best performed after the age of 6 months and includes assays for factor VIII, von Willebrand's antigen, and the ristocetin cofactor. Further testing of the multimer distribution is warranted if type II is suspected.