Approach to the child with anemia
- 1. Approach to the child with anemia 1
- 2. Outline DeFinitiOn OF AneMiA OVeRVieW OF eRYtHROPOieSiS ClASSiFiCAtiOnS OF AneMiA HiStORY AnD PHYSiCAl eXAMinAtiOn lABORAtORY eXAMinAtiOn iROn-DeFiCienCY AneMiA HeMOlYtiC AneMiA PHYSiOlOgiC AneMiA OF inFAnCY 2
- 3. DEFINITION OF ANEMIA Anemia may be defined as a reduction in red blood cell mass or blood hemoglobin concentration. In practice, anemia most commonly is defined by reductions in one or both of the following: 1. Hematocrit (HCT) — The hematocrit is the fractional volume of a whole blood sample occupied by red blood cells (RBCs); it is expressed as a percentage. 3
- 4. DEFINITION OF ANEMIA cont… 2. Hemoglobin (HGB) — This is a measure of the concentration of the RBC pigment hemoglobin in whole blood, expressed as grams per 100 mL (dL) of whole blood. The age variation for HGB and HCT is pronounced in the pediatric population; thus, it is particularly important to use age and sex adjusted norms when evaluating a pediatric patient for anemia 4
- 5. OVERVIEW OF ERYTHROPOIESIS • Developmental hematopoiesis occurs in three anatomic stages: mesoblastic, hepatic, and myeloid. • Fetal erythropoiesis begins with primitive megaloblastic erythropoiesis; these cells can be identified at approximately four to five weeks gestation . • A transition is made to normoblastic erythropoiesis at approximately six weeks gestation. • At this time, blood formation begins in the liver, which is the primary organ of hematopoiesis from the third to sixth month of gestation . 5
- 6. OVERVIEW OF ERYTHROPOIESIS cont.. At approximately the third month of gestation, hematopoiesis begins in the spleen, thymus, and lymph nodes. The liver and spleen continue to produce blood cells into the first week of postnatal life. Bone marrow hematopoiesis begins around the fourth month of gestation and increases throughout intrauterine development. 6
- 7. OVERVIEW OF ERYTHROPOIESIS cont.. Erythropoiesis decreases dramatically after birth. Red cell production decreases by a factor of 2 to 3 in the first few days of life and by a factor of 10 in the week following birth. This decrease is initiated by the increase in tissue oxygen level that occurs at birth and is accompanied by a decrease in erythropoietin production resulting in the "physiologic anemia of infancy" 7
- 8. OVERVIEW OF ERYTHROPOIESIS cont.. Red cell production is at a minimum during the second week after birth and subsequently rises to maximum values at approximately three months. The net result of these changes is an anemia that typically nadirs at 6 to 9 weeks of age. Anemia in preterm infants may be more pronounced because of the shorter life span of preterm red cells. 8
- 9. CLASSIFICATIONS OF ANEMIA Anemias may be classified on either -pathophysiologic mechanisms or -a morphologic basis. Physiologic etiologies for anemia may be classified: Disorders resulting in an inability to adequately produce red blood cells (i.e. bone marrow depression). Disorders resulting in rapid RBC destruction (hemolysis) RBC losses from the body (bleeding) These categories are not mutually exclusive 9
- 10. CLASSIFICATIONS OF ANEMIA cont… Morphologic classification -Anemias may be classified also according to RBC size (mean corpuscular volume, MCV), hemoglobin content (mean corpuscular hemoglobin, MCH), or hemoglobin concentration (mean corpuscular hemoglobin concentration, MCHC). 10
- 11. Approach to the patient HISTORY AND PHYSICAL EXAMINATION HISTORY: When evaluating an anemic child in addition to the age and sex of the child, Severity and initiation of symptoms Acute anemia Chronic anemia Prior episodes of anemia may indicate inherited forms, whereas anemia in a patient with previously documented normal blood counts suggests an acquired etiology. 11
- 12. HISTORY AND PHYSICAL EXAMINATION cont.. Questions relating to hemolytic episodes: changes in urine color, jaundice associated with the symptoms of anemia should be asked. Any family history of anemia. symptoms consistent with pica. Birth history — A birth and neonatal history including infant and mother's blood type, any history of exchange , and a history of anemia in the early neonatal period should be obtained. 12
- 13. HISTORY AND PHYSICAL EXAMINATION cont.. Physical examination : Areas of particular importance on the physical examination include: the skin, eyes, mouth, facies, chest, hands, and abdomen. Pallor should be assessed by examining sites where capillary beds are visible through the mucosa (e.g. conjunctiva, palm, and nail beds). Jaundice and hepatosplenomegaly resulting from increased red cell destruction Patients with hemolytic anemia. 13
- 14. LABORATORY EXAMINATION a complete blood count including red blood cell indices, a reticulocyte count, and a review of the peripheral blood smear. Blood smear- a review of the peripheral smear is an essential part of any anemia evaluation. – The diameter of a normal RBC should be the same as the diameter of the nucleus of a small lymphocyte The mean corpuscular volume (MCV) is perhaps the most useful RBC parameter used in the workup of anemia 14
- 15. LABORATORY EXAMINATION Mean corpuscular hemoglobin concentration — The MCHC is a calculated index (MCHC= HGB/HCT), yielding a value of grams of HGB per 100 mL of RBC. Red cell distribution width -the red cell distribution width (RDW) is a quantitative measure of the variability of RBC sizes in the sample (anisocytosis). -values lower than normal indicate the presence of hypochromia. 15
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- 18. Approach to Common Causes of Anemia in Children Is anemia associated with other hematologic abnormalities? If yes, consider Aplastic anemia Leukemia Other bone marrow replacement disorders Is anemia associated with reticulocytosis? If yes, usually a consequence of bleeding or ongoing hemolysis 18
- 19. Approach to Common Causes of Anemia in Children Is there associated hyperbilirubinemia or increased serum lactate dehydrogenase If yes, usually due to hemolysis Review of peripheral blood smear Spherocytes (hereditary spherocytosis, autoimmune hemolytic anemia, Wilson disease) Sickle forms (sickle cell disease, sickle-ß-thalassemia) Target cells (hemoglobin SC disease) 19
- 20. Approach to Common Causes of Anemia in Children Hypochromic RBC, nucleated RBC (homozygous ß- thalassemia, ) Microangiopathy (hemolytic-uremic syndrome, thrombotic thrombocytopenia) Bite cells/blister cells (G6PD deficiency) 20
- 21. Approach to Common Causes of Anemia in Children Is anemia associated with a lower than appropriate reticulocyte response? If yes, assess red blood cell size o Are red blood cells microcytic? If yes, usually due to defect in hemoglobin synthesis Iron deficiency Hemoglobin E disorders Lead poisons 21
- 22. Approach to Common Causes of Anemia in Children Are red blood cells macrocytic? If yes, is there neutrophil hypersegmentation (megaloblastic changes)? If yes, consider – Folate deficiency, vitamin B12 deficiency, inborn errors of metabolism If no, consider – Diamond-Blackfan anemia – Congenital dyserythropoietic anemia – Pearson syndrome 22
- 23. Approach to Common Causes of Anemia in Children Are red blood cells normocytic? If yes, consider Anemia of chronic disease usually (associated comorbid conditions) Anemia of renal disease (renal failure) Transient erythroblastopenia of childhood Anemia associated with hypothyroidism 23
- 24. IRON BALANCE The major role of iron in mammals is to carry O2 as part of hemoglobin. The majority of iron (75 percent) is bound in heme proteins (hemoglobin and myoglobin). The remainder is bound in the storage proteins ferritin and hemosiderin 3 percent of iron is bound in critical enzyme systems, such as catalase and cytochromes . In normal subjects, only a small amount of iron enters and leaves the body on a daily basis. the body must protect itself from free iron, which is highly toxic in that it participates in chemical reactions that generate free radicals such as singlet O2 or OH–. Most iron is recycled from the breakdown of old red blood cells by macrophages of the reticuloendothelial system 24
- 25. Iron-Deficiency Anemia Lack of sufficient iron for synthesis of hemoglobin is the most common hematologic disease of infancy and childhood. Iron store in the new born is 0.5gm & that of adult is 5gm. For this discrepancy, an average of 0.8mg of iron must be absorbed each day during the first 15 yr of life. Normal losses of iron by shedding of cells. So, to maintain positive iron balance in childhood, about 1mg of iron must be absorbed each day. 25
- 26. Iron-Deficiency Anemia cont.. Iron is absorbed in the proximal small intestine, Absorption of iron is about 10% Nutrient containing 8-10mg of iron is mandatory. Iron is absorbed two to three times more efficiently from human milk than from cow's milk, partly because of differences in calcium content. Infants breast-fed exclusively should receive iron supplementation from 4 mo of age. Adolescents are also susceptible to iron deficiency because of high requirements due to the growth spurt, dietary deficiencies, and menstrual blood loss.26
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- 28. Iron-Deficiency Anemia cont.. Etiology. Low birth weight and unusual perinatal hemorrhage are associated with decreases in neonatal hemoglobin mass and stores of iron. Hook worm infestation, peptic ulcer, Meckel diverticulum, polyp, or hemangioma, or by inflammatory bowel disease. In term infants it is unusual before 6 mo and usually occurs at 9–24 mo of age. 28
- 29. Cont… Low birth weight Premature birth Perinatal blood loss Poor supplementation Intestinal malabsorption Occult blood loss milk protein–induced inflammatory colitis, peptic ulcer, Meckel diverticulum, polyp, or hemangioma, or inflammatory bowel disease Hook worm infestations & H.pylori 29
- 30. Clinical Manifestations Pallor is the most important sign of iron deficiency. In mild to moderate(Hgb levels of 6–10g/dL), compensatory mechanisms, increased levels of 2,3- DPG. Irritability, Pagophagia, When the hemoglobin level falls below 5g/dL, irritability and anorexia are prominent. Tachycardia and cardiac dilation occur, and systolic murmurs are often present 30
- 31. Cont… Impaired psychomotor and/or mental development Cognitive impairment in adolescents Palmar, nailbed, and conjunctival pallor Pagophagia, the desire to ingest unusual substances such as ice or dirt Irritability and anorexia characteristic of advanced cases Attention span, alertness, and learning in both infants and adolescents is decreased 31
- 32. Cont… Typical of IDA KOILONYCHIA( SPOON NAILS) BLUE SCLERA PICA & PAGOPHAGIA PATERSON-KELLY/PLUMMER-VINSON SYNDROME Dysphagia Oesophageal web Atrophic glossitis 32
- 33. Laboratory Findings In progressive iron deficiency, a sequence of biochemical and hematologic events occurs. First, the tissue iron stores represented by bone marrow hemosiderin disappear. Next, serum iron level decreases, the iron-binding capacity of the serum (serum transferrin) increases, and the percent saturation (transferrin saturation) falls below normal. 33
- 34. Cont.. CBC &ESR RBC INDICES PERIPHERAL SMEAR IRON STUDIES Serum iron Serum ferritin Serum Tf, TIBC 34
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- 37. Treatment The regular response of iron-deficiency anemia to adequate amounts of iron is an important diagnostic and therapeutic feature. Oral administration of simple ferrous salts (sulfate, gluconate, fumarate) provides inexpensive and satisfactory therapy. Tolerable in young children unless there is malabsorption. 37
- 38. Treatment… General principles of iron treatment Iron is absorbed in the duodenum & pro.jejunem Shouldn’t be given with food Best absorbed in a mildly acidic media UGI discomfort is directly related to the amount of iron 38
- 39. Treatment… Oral preparation Ferrous sulfate 65mg of elemental iron Ferrous fumarate 106mg of elemental iron Ferrous gluconate 28-36mg of elemental iron Ferrous sulfate elixir 44mg/5ml Side effect GI upset 39
- 40. Cont… 4–6 mg/kg /day of elemental iron in 3 divided doses. Blood transfusion: if Hgb is less than 4mg/dl transfuse with packed or whole blood. Prevention- iron-fortified formula or cereals during infancy (started at 4-6 months for term and earlier for preterm ) Duration of treatment Continue after normalization of HGB to replenish the iron stores 3-6months after normalization of HGB 40
- 41. Responses to Iron Therapy in Iron- Deficiency Anemia Time After Iron Administration Response 12–24 hr Replacement of intracellular iron enzymes; subjective improvement; decreased irritability; increased Appetite 36–48 hr Initial bone marrow response; erythroid hyperplasia 48–72 hr Reticulocytosis, peaking at 5–7 days 4–30 days Increase in hemoglobin level 1–3 mo Repletion of stores 41
- 42. Hemolytic anemias Different ways of classification of causes of HA Intracorpuscular/ Extracorpuscular Inherited/ Acquired Intravascular/ extravascular Immune-mediated/ non-immune mediated Immune mediated Warm/ cold Antibody 42
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- 44. Definitions and Classification of Hemolytic Anemias Hemolysis is defined as the premature destruction of red blood cells (RBCs). Anemia results when the rate of destruction exceeds the capacity of the marrow to produce RBCs. Normal RBC survival time is 110–120 days. 0.85% of the most senescent RBCs are removed and replaced each day. During hemolysis, RBC survival is shortened, the RBC count falls, erythropoietin is increased, and the stimulation of marrow activity results in heightened RBC production. Elevated reticulocyte count Hemolysis acute blood loss replacement therapy for iron, vitamin B12, or folate deficiency. 44
- 45. DIAGNOSTIC APPROACH Classic case New onset of pallor or anemia Jaundice ( high indirect bilirubin) Gallstones Splenomegaly Presence of circulating spherocytic RC Increased LDH Decreased serum haptoglobin + Coomb’s test High retic % or ARC 45
- 46. Peripheral smear Spherocytes Fragmented RBC Acanthocytes (spur cell) Teardrop cell Blister or “ bite” cells RBC inclusions Parasites 46
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- 48. Physiologic Anemia of Infancy Normal newborn infants have higher hemoglobin and hematocrit levels with larger red blood cells (RBCs) than older children and adults. Within the first week of life, a progressive decline in hemoglobin level begins and persists for 6–8 wk. HGB-oxygen saturation increases from 50-95%. High oxygen affinity fetal HGB replaced by low oxygen affinity adult HGB. 48
- 49. Cont… Factors involved. With the onset of respiration at birth, considerably more oxygen is available for binding to hemoglobin, and the hemoglobin-oxygen saturation increases from 50 to 95% or more. developmental switch from fetal to adult hemoglobin synthesis actively replaces high-oxygen-affinity fetal hemoglobin with lower-oxygen-affinity adult hemoglobin the increase in blood oxygen content and tissue oxygen delivery downregulates EPO production 49
- 50. Cont… The hemoglobin concentration continues to decrease until tissue oxygen needs are greater than oxygen delivery. Normally, this point is reached between 8–12 wk of age, when the hemoglobin concentration is 9–11 g/dL. As hypoxia is detected by renal or hepatic oxygen sensors, EPO production increases and erythropoiesis resumes. The iron previously stored in reticuloendothelial tissues can be used for hemoglobin synthesis 50
- 51. physiologic anemia (Premature infants ) The decline in hemoglobin level is both more extreme and more rapid. The same factors are operative as in term infants, but they are exaggerated. Short survival of the RBCs of premature infants Rapid expansion of the RBC mass that accompanies growth. Inadequate synthesis of EPO in response to hypoxia. Blunted EPO response seen in premature infants. TREATMENT. Physiologic anemia requires no therapy other than folic acid and iron. 51
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