Academic journal article International Journal of Child Health and Human Development

Neonatal Hematology

Academic journal article International Journal of Child Health and Human Development

Neonatal Hematology

Article excerpt


Hematopoiesis and hemostasis in the newborn is not fully mature. Adult levels of most procoagulant and anticoagulant proteins are reached by age six months, some do not reach adult levels till adolescence (1). Immaturity of hematopoietic system makes a newborn vulnerable to hematologic disorders such as anemia, neutropenia and thrombocytopenia. Anemia, thrombocytopenia, neutropenia and bleeding triggered by passage through birth canal are some of the reasons for hematology consult in the newborn period.

Normal development of hematopoiesis

Hematopoiesis is a complex process of cell renewal as red blood cells (RBC), white blood cells (WBC) and platelets senesce and regenerate. The hematopoietic germ cell originates from mesodermal germ cell layer (1, 2). Hematopoiesis begins early in embryonic life and gradually moves to aorto-gonado-mesonephron (AGM), to liver and then to bone marrow. Tightly regulated by specific cell growth factors each cell line undergoes changes specific to its developmental age. These changes impact the clinical manifestation, laboratory diagnosis and management of hematologic disorders in the newborn period.


Embryonic hematopoiesis starts in the yolk sac and moves from the ventral aspect of the aorta to liver and then to the bone marrow as the fetus matures. Microenvironment in each location affects the RBC size and other characteristics. Erythropoietin (EPO) is produced by liver in early fetal life with transition to kidneys occurring postnatally. EPO concentration decreases at birth and reaches a nadir at 4-6 weeks of life. This is followed by a gradual increase to adult levels by 10-12 weeks of life. Hemoglobin is a tetrameric molecule consisting of two pairs of polypeptide chains.

Changes in hemoglobin structure and transition from embryonic (ζ2[varepsilon]2), fetal HbF (α2γ2) to adult hemoglobin HbA (α2β2) occur to accommodate for oxygen needs of developing fetus. Gamma chain synthesis starts early and peaks mid gestation. Beta chain synthesis starts in 6th week of life with a subsequent steady increase throughout fetal life.


Megakaryopoiesis is the process of platelet production. Similar to erythropoiesis the site of production of platelets changes during embryonic and fetal life with bone marrow being the major site of production at birth. Megakaryocyte nucleus has the unique ability to undergo endomitosis and increase nuclear ploidy and DNA without undergoing cell division. The number of platelets produced by a megakaryocyte is directly proportional to its nuclear ploidy. Although platelet number reaches near adult values in early fetal life the megakaryocytes at birth are smaller with lower nuclear ploidy, <8N, and produce fewer platelets.

White blood cells

Macrophages are the early white blood cells produced in yolk sac and liver. Neutrophils become primary WBC once bone marrow hematopoiesis starts around 10-11 weeks of gestation. Hemoglobin and WBC at birth are higher and red cells are larger in size but platelet count is normal (see Table 1).

Hemostatic disorders

Hemostasis is a complex process that involves endothelium, subendothelium, platelets and a number of proteins. A delicate balance between procoagulant factors (F I-XIII), natural anticoagulants protein C, S and antithrombin (AT), fibrinolytic system, plasminogen, plasmin and inhibitors of fibrinolytic system keeps the blood in the fluid state. Platelet disorders and procoagulant protein deficiencies are major causes of bleeding in the newborn period and are discussed below.

Coagulation disorders

Coagulation factors (F1-XIII) do not cross the placenta; hence the newborn has to synthesize all the factors de-novo. Levels of FV,VIII, fibrinogen and von Willebrand factors at birth are normal whereas Factor XII, XI, X, IX, VII, II, protein C and S and AT are present at 30-50% of adult levels (2,3). The relevance of developmental hemostasis to hemorrhagic disorders in newborn is well described; low levels of vitamin K dependent factors (F II, VII, IX, X, proteins C and S) and immaturity of liver results in decreased levels of all clotting proteins. …

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