This is a newborn female born to a 17 year old gravida 1, para 0, B+, mother at 39 weeks gestation. Maternal risk factors include a kidney infection in the second trimester. All other risk factors are negative. After an uneventful vaginal delivery, the infant is discharged at two days of life breast feeding at home. On the third day of life, moderate jaundice is noted and a bilirubin in the primary care doctor's office is 18. Home phototherapy is started, but on day six, the bilirubin is 22.9 with the direct component of 0.4. She is hospitalized for inpatient phototherapy. Her hemoglobin was 15.7 earlier, and it has now dropped to 13.4. The bilirubin continues to rise to 25.6 in spite of phototherapy. A G6PD is normal and the reticulocyte count is 3.1. Stools are negative for occult blood. The blood smear shows moderate aniso and poikilocytosis.
She is transferred to a tertiary pediatric center where she is noted to be normal except for marked jaundice. Her mother is of German decent and her father is Caucasian and Puerto Rican. Her mother was treated for newborn jaundice due to presumed ABO incompatibility. Others in her family also had neonatal jaundice. The father's history is unremarkable. No other family member had neonatal jaundice or anemia or gallstones.
Upon admission, vital signs are normal. She is visibly jaundiced and a spleen tip is palpable. Labs show a bilirubin of 25, white count of 17.5, platelets of 230,000 and an unremarkable differential. The hemoglobin is now down to 10.7 in spite of a reticulocyte count of 4%. In addition, the smear now shows moderate schistocytes with burr cells and moderate spherocytes. Blood type is B+ and the Coombs is negative. She is transfused and phototherapy continues until the bilirubin falls to 12. The infant has an otherwise uneventful course in the hospital and the final diagnosis is hyperbilirubinemia and anemia due to hereditary spherocytosis. In addition, alpha thalassemia trait is found on her newborn screen. Incubated red cell osmotic fragility studies on the mother and other maternal family member are consistent with hereditary spherocytosis.
At the moment of birth, the physician can be confronted with complex hematologic problems seen at no other time in life. Newborn red cells are much different than in older children and white cell and platelet disorders can be quite unique. Coagulation factors are abnormal and hemostasis can be markedly altered. Normal values for most newborn blood tests are different compared to children and adults. Interpretation of results in term and premature newborns can be critical.
Significant red cell disorders in the newborn period may be associated with a family history of anemia, jaundice, falling hemoglobin and reticulocytosis in addition to abnormal RBC morphology. The presence of surface antibodies (e.g., anti-A and/or anti-B) may be helpful or the deficiency of intraerythrocytic enzymes (e.g., G6PD deficiency). Finally hemoglobinopathies and thalassemia may offer an almost infinite combination of symptoms and signs in the newborn. Virtually all red cell problems are isolated and the rest of the hemogram is normal. Marrow failure resulting in pancytopenia with associated infections and altered hemostasis is vary rare. Definitive studies on red cells can be delayed for three months when the infant is well and their blood volume is larger. As in the above case, studies of maternal family members subsequently confirmed the diagnosis of hereditary spherocytosis. It is important to remember that in the perinatal period (28 weeks gestation to 28 days after birth) there are normal physiologic changes occurring in red cells. Some of these changes include switching from fetal to adult hemoglobin production, a 30% drop in hemoglobin, a fall in mean red cell volume (MCV) as well as changes in membrane pliability and intracellular enzyme levels. RBC survival is further impacted by acquired infections, medications, and other high-risk conditions. Repeated monitoring of hemoglobin and reticulocyte counts is warranted in the sick and unstable newborn.
Hydrops fetalis results from severe intrauterine hemolysis and anemia necessitating emergency exchange transfusion. The cause is usually due to severe alpha thalassemia, red cell surface antibodies or congenital infections. Rh incompatibility usually presents with rapid hemolysis and varying degrees of anemia and jaundice (depending on the extent of maternal sensitization and antibody production).
White blood cell abnormalities may be asymptomatic and incidental or associated with fever, infection, and altered host resistance. Wide fluctuation in the WBC count can be noted depending on marrow production of granulocytes. Infection, antibodies, and medications call all affect the circulating neutrophil pool. This is the pool of granulocytes sampled with a venipuncture. Interpretation of a peripheral WBC count can be difficult when trying to determine the risk of infection or underlying pathophysiology. A bone marrow examination can be very helpful in assessing granulocyte production and the risk of infection. Most WBC aberrations are secondary or reactive to a disease process, but occasionally rare hereditary disorders can present in the neonate. These are usually associated with an increased risk of infection (e.g., chronic granulomatous disease) or as part of a recognizable syndrome (e.g., Jobs syndrome). Congenital leukemia is extremely rare but striking leukemoid reactions can occur. Of note is the transient myeloproliferative condition or pseudoleukemia that may be observed in neonates with Down syndrome. Of prime importance when evaluating infants with any white cell aberration is the real risk of infection and the need for antimicrobials.
Platelet problems in the newborn present almost exclusively with thrombocytopenia and bleeding. Thrombocytopenia can be isolated or associated with other cytopenias. A low platelet count results from either decreased production or peripheral consumption of platelets. By examining the bone marrow and/or the mean platelet volume (MPV usually higher in younger platelets seen in consumptive disorders), the underlying pathophysiology can usually be identified. Most thrombocytopenias are consumptive and due to maternal antiplatelet antibodies, congenital infections, or part of complex DIC seen in sick newborns. It is paramount to compare the amount of clinical bleeding to the degree of thrombocytopenia in order to quickly make the right diagnosis and determine the need for transfusion or other therapy.
Hemorrhagic disease of the newborn is usually seen from day 2 to 4 of life resulting from vitamin K deficiency and the subsequent failure to produce clotting factors II, VII, IX and X. The prothrombin time is markedly prolonged and serious life threatening hemorrhaging can occur in many organ systems. This transient deficiency of vitamin K is thought to result from poor placental transfer, marginal content in breast milk, inadequate intake of breast milk and a sterile gut (lack of vitamin K producing GI flora). Hemorrhaging can be prevented by the intramuscular administration of prophylactic vitamin K shortly after birth.
Questions
1. True/False: Newborns with Down syndrome and elevated white counts and immature forms frequently progress to leukemia.
2. True/False: Factor VIII deficiency is on the vitamin K dependent factors leading to Hemorrhagic disease of the newborn.
3. Rh antibodies in mothers can result from:
. . . . . a. previous mismatched transfusions
. . . . . b. prior miscarriages
. . . . . c. fetal maternal transfusion
. . . . . d. all of the above.
4. True/False: Red cell problems are usually seen with abnormalities of white cells and platelets.
5. True/False: Neonatal immune thrombocytopenia can result from maternal auto sensitization or fetal maternal transfusion.
6. True/False: Thalassemia and hemoglobinopathies can present in the neonatal period with severe anemia.
References
1. Andrew M. Chapter 5-Developmental Hemostasis: Relevance to Newborns and Infants. In: Nathan DG, Orkin SH (eds). Nathan and Oski's Hematology of Infancy and Childhood, 5th edition. 1998, Philadelphia: W.B. Saunders, pp. 114-157.
2. Christensen RD. Hematologic Problems of the Neonate. 2000, Philadelphia: W.B Saunders.
Answers to questions 1.F, 2.F, 3.d, 4.F, 5.T, 6.T