Hematology

Chapter 63 Hematology



Roger Berkow



IRON DEFICIENCY ANEMIA



ETIOLOGY



What Causes Iron Deficiency in Children?


Iron deficiency most often develops from poor gastrointestinal absorption of iron and poor bioavailability of iron from food, combined with microscopic gastrointestinal (GI) blood loss. Human milk has low iron content (0.5 to 1 mg/L) but high iron bioavailability (∼50% absorption) and provides breast-fed infants with adequate iron for the first 6 months of life, after which iron-containing foods should be introduced. Infant formula contains 12 mg/L of iron, of which ∼10% is absorbed. Unmodified cow’s milk has low iron content (0.5 mg/L), has poor iron bioavailability (3% to 5% absorption), and also irritates the infant gut mucosa, leading to chronic blood loss. Switching from breast milk or formula to unmodified cow’s milk before age 12 months is the leading cause of iron deficiency in the developed nations. In the developing world, parasitic infection is the leading cause of iron deficiency. Adolescent females may develop iron deficiency from heavy menstrual blood loss. Iron deficiency in children outside of infancy should lead to a search for blood loss and consideration of bowel pathology (polyps or Meckel’s diverticulum).



EVALUATION



How Should I Evaluate Suspected Iron Deficiency Anemia?


An anemic infant or child commonly has a history of pallor and of being switched to cow’s milk before age 12 months. Milk is usually the primary source of calories, but the child may eat other foods. No obvious blood loss is reported in most cases. The physical examination shows a pale child without bruising, petechiae, lymphadenopathy, or hepatosplenomegaly. A cardiac “flow” murmur may be heard. Complete blood count (CBC) shows anemia, microcytosis (low mean corpuscular volume [MCV]), and hypochromia (low mean corpuscular hemoglobin [MCH]). Reticulocyte count is low (see Table 50-1). The white blood cell (WBC) count and differential should be normal, but the platelet count is often elevated. If the tests are done, serum iron level will be low, total iron-binding capacity will be elevated, and iron saturation (iron ÷ total iron-binding capacity) and serum ferritin will be very low. The test for stool occult blood is often positive.



TREATMENT



How Is Iron Deficiency Anemia Treated?


Iron dose is 6 mg/kg/day of elemental iron. Ferrous sulfate, the most common form of iron used for children, has 20% elemental iron. The iron should be given separately from food to increase absorption. Response to treatment is marked by a rise in the reticulocyte count within 3 or 4 days and an increase in hemoglobin within 1 to 2 weeks. Treatment must be given for several months to replenish iron stores, and dietary iron supplementation is important after successful treatment. If a child remains anemic with microcytic red blood cells (RBCs) despite iron therapy, consider thalassemia, lead exposure, or copper deficiency (seen occasionally in severe nutritional deficiency).



HEMOLYSIS



ETIOLOGY



What Causes Hemolysis?


Hemolysis results from disorders that affect the RBC membrane, the cytoplasm, or the hemoglobin. Careful consideration of these RBC components must be a part of the evaluation. Extrinsic factors act on the membrane to cause hemolysis and intrinsic defects cause cell breakdown (Table 63-1).


Table 63-1 Red Blood Cell (RBC) Defects That Result in Hemolysis















Extrinsic Factors Intrinsic Factors
Antibody formation: autoimmune hemolysis, isoimmune hemolysis Genetic defects of membrane structural proteins: spherocytosis and elliptocytosis
Microangiopathic hemolysis: HUS, DIC, artificial hear t valves Genetic defect of the lipid layers, vitamin E deficiency
  Enzyme defects: pyruvate kinase, G-6-PD

DIC, Disseminated intravascular coagulation; G-6-PD, glucose-6-phosphate dehydrogenase; HUS, hemolytic uremic syndrome.



How Do Autoantibodies Cause Hemolysis?


The RBC membrane contains more than 200 different glycoprotein antigens. Autoantibodies directed against RBC antigens, other than the A, B, and Rh blood groups, shorten the life of the RBCs through a process known as autoimmune hemolytic anemia (AIHA). Part of the RBC membrane is removed as the antibody-coated RBC traverses the sinusoids of the spleen, leading to the formation of spherocytes that undergo hemolysis. Occasionally, intravascular hemolysis occurs in the presence of a strong complement-fixing antibody. In either case, rapid destruction of RBCs can lead to a potentially life-threatening anemia. The formation of “autoantibodies” can be an early sign of a more generalized autoimmune disorder.



What Are Isohemagglutinins and When Do They Cause Hemolysis?


The A and B antigens on RBCs are similar to naturally occurring proteins and cause the formation of isohemagglutinins: anti-A antibodies in type O and B individuals and anti-B antibodies in type O and A individuals. These antibodies are not the same as the autoantibodies discussed earlier. When a mother with blood type O has a baby with blood type A (known as an “ABO setup”), isohemagglutinins can cross the placenta and induce hemolysis, causing isoimmune hemolytic anemia of the newborn. Anti-A and anti-B antibodies can also cause hemolysis after transfusion if blood is not carefully cross-matched or if clerical errors lead to mismatched transfusion.



What Is Rh Incompatibility?


The Rh blood group does not mimic naturally occurring antigens, so prior exposure to Rh-positive RBCs must occur for antibodies to form. This most often occurs when an Rh-negative mother gives birth to an Rh-positive infant. The baby’s RBCs enter the mother’s circulation and trigger anti-Rh antibody production. The Rh-negative mother must be given anti-Rh globulin to destroy any fetal or infant cells to which she is exposed. If this does not occur, or if anti-Rh antibodies form despite attempts to remove Rh-positive RBCs, the mother is said to be “Rh sensitized.” Any subsequent pregnancy in which the fetus is Rh positive will be at risk, because the anti-Rh antibodies cross the placenta and cause hemolysis in the fetus.



What Causes Mechanical Red Blood Cell Damage?


The hemolysis that occurs in hemolytic uremic syndrome (HUS), in disseminated intravascular hemolysis, and in the presence of giant hemangiomas (Kasabach-Merritt syndrome) results from damage to the RBCs during passage through fibrin-coated microvasculature. This process is called microangiopathic hemolytic anemia and produces fragments of RBCs called schistocytes. Extrinsic damage to RBCs can also occur as the cells pass through an artificial heart valve or an enlarged spleen and from extremes of temperatures, as can be seen in burn victims.



Do Red Blood Cell Membrane Abnormalities Cause Hemolysis?


The RBC membrane is a lipid bilayer into which glycoprotein antigens and channels for the transport of electrolytes are inserted. Underlying and attached to the membrane are structural proteins that help support the shape and flexibility of the RBC. Disorders that affect the structural protein layer or the lipid bilayer will cause hemolysis. The defects may be within the membrane itself or may be caused by damage from enzyme or cofactor deficiencies.



What Structural Protein Abnormalities Cause Hemolysis?


Hereditary spherocytosis (HS) and hereditary elliptocytosis (HE) are the most common disorders resulting from intrinsic abnormalities of the RBC membrane. They are inherited as autosomal dominant traits, although 20% to 25% of patients have no family history and most likely have new mutations in structural proteins, such as spectrin, actin, ankyrin, and others. The severity of hemolysis in HS or HE varies greatly: Some children require repeated transfusion therapy, whereas others are identified only by a routine screening CBC.



How Do Hemoglobin Abnormalities Cause Hemolysis?


The predominant abnormalities of hemoglobin that lead to hemolysis are the sickling disorders: hemoglobin SS, SC, and S-β thalassemia. Sickle cell disease (Hb SS) results from the substitution of valine for glutamine at the sixth amino acid position on the β chain of hemoglobin. This autosomal recessive disorder is characterized by polymerization of the hemoglobin molecule in conditions of low oxygen. These polymers induce changes in the RBCs that lead to hemolysis. The RBCs also take on a sickle shape, which leads to occlusion of blood flow through small blood vessels and leads to pain, splenic infarction, stroke, pulmonary infarction, and priapism. The progressive splenic infarction places affected children at high risk for life-threatening infection from encapsulated bacteria (Streptococcus pneumoniae, Neisseria meningitidis, Haemophilus influenzae type b, and Salmonella species).



Do Red Blood Cell Enzyme Abnormalities Cause Hemolysis?


The cytosol contains the key enzymes that provide the energy to maintain cellular activities and membrane transport (glycolytic pathway). Cytosol also contains the antioxidants that protect the hemoglobin from oxidative damage (pentose phosphate pathway). Deficiencies in any of the components of these pathways result in hemolysis.

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Jun 19, 2016 | Posted by in PEDIATRICS | Comments Off on Hematology

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