Anexo 2 – Análisis PESTEL

• Cirrhosis of the liver • Malignant hypertension • Th rombosis

• Th rombotic thrombocytopenia purpura • Amyloidosis

• Chronic relapsing schistocytic hemolytic anemia

• Burns

• Connective tissue disorders STOMATOCYTE

(Area of central pallor is more slit-like than round)

• Present in small numbers in normal individuals

• Stomatocytosis (hereditary) • Th alassemia

NUCLEATED RED BLOOD CELLS (Normal on a peripheral blood smear in the fi rst week of life only)

• Normal newborns

• Signifi cant bone marrow stimulation • Congenital infections

• Hyposplenism or postsplenectomy • Leukoerythroblastic reaction, particularly

with severe infections and leukemias or metastatic tumors in the bone marrow • Megaloblastic anemia

• Dyserythropoietic anemias

a_{Frequently, normal blood smears will contain abnormal-appearing RBCs that are simply an artifact of trauma during the}

blood draw or ex vivo processing of the blood.

G6PD, glucose-6-phosphate dehydrogenase; RBC, red blood cell.

Modifi ed from Nathan DG, Orkin SH. A diagnostic approach to the anemic patient. In: Nathan and Oski’s Hematology of Infancy and Childhood. 5th ed. Philadelphia, PA: WB Saunders; 1998.

Serum iron and ferritin levels are low, whereas the total iron-binding capacity is elevated. Many children also have an elevated platelet count.

When a primary care physician is treating a child with hypochromic, microcytic anemia found on a routine screening blood cell count, and a history of poor iron intake or excessive milk intake is elicited, a reasonable approach would be to give a trial of supplemental iron

Table 5-2

Classifi cation of Anemia in Childhood

MICROCYTIC NORMOCYTIC MACROCYTIC

Iron defi ciency anemia Lead poisoning Copper defi ciency Malnutrition Chronic disease Thalassemia Hemoglobin E trait Sideroblastic anemia Atransferrinemia

Inborn errors of metabolism

Infection Acute blood loss Renal disease

Connective tissue disorder Hepatic disease Hemolysis Hypersplenism Malignancy Aplastic anemia Dyserythropoietic anemia Drugs

Megaloblastic anemias from B₁₂ or folate defi ciency

Reticulocytosis Postsplenectomy Myelodysplastic syndrome Aplastic anemia Fanconi anemia Diamond-Blackfan syndrome Pearson syndrome Dyskeratosis congenita

Paroxysmal nocturnal hemoglobinuria Down syndrome

Hypothyroidism Hepatic disease, jaundice

Anemia and Pallor 53

(6 mg/kg of elemental iron per day divided into 2 or more doses) rather than to draw addi- tional blood for biochemical analysis. Th e reticulocyte count should increase within 5 to 7 days once therapy is initiated. Assuming the dietary defi ciency is corrected, supplemental iron should continue for 2 to 3 months after the hemoglobin concentration has normalized to replenish iron stores fully. For patients with a hypochromic microcytic anemia who do not seem to be at risk based on diet alone, and for those who do not respond to supplemental iron, additional testing is required. Iron defi ciency, although common, is still abnormal, and the etiology of the defi ciency should be clearly defi ned.

Th alassemias

Th e thalassemias are a heterogenous group of disorders of hemoglobin production. Th e ␣-thalassemias have defi cient production of the ␣ chain, and the ␤-thalassemias have defi - cient production of the ␤ chain. In either case, the excess of one chain relative to the other results in precipitation and destruction of the RBCs.

␤-THALASSEMIA. Th alassemia minor (or thalassemia trait) is common among black patients and results from a mutation of 1 of the 2 genes on chromosome 11 encoding for the ␤-chain. When only 1 gene is aff ected, a mild decrease in ␤-chain production occurs, resulting in a mild anemia. Patients with thalassemia trait frequently have a hypochromic, microcytic anemia found on a routine complete blood count, similar to patients with iron defi ciency anemia. Target cells are also common to both diseases. However, patients with thalassemia trait usually have an increase in the number of RBCs, whereas patients with iron defi ciency commonly have a decrease in RBC number. A hemoglobin electrophoresis may also be helpful in diagnosing thalassemia trait. Both the hemoglobin F and hemoglobin A₂ levels are commonly elevated. Although treatment is not necessary, diagnosing thalassemia trait is important so that appropriate genetic counseling may be off ered to patients and families.4

THALASSEMIA MAJOR. Th alassemia major (Cooley anemia) results from defects in both ␤-globin genes and manifests as a severe hemolytic anemia. Marked compensatory erythropoiesis causing expansion of the medullary space results in a prominence of the cheeks and frontal bossing.4 _{Long-term transfusion therapy is required for these patients,} and immediate referral to a hematologist is necessary.

␣-THALASSEMIA. Each chromosome 16 contains 2 identical genes (4 genes total) for the ␣ chain. Abnormalities in these genes, most commonly seen in blacks and Asians, result in ␣-thalassemia.5 _{When 1 gene is aff ected, the patient will be asymptomatic, with} little or no abnormality on routine testing. ␣-Th alassemia trait is the result of a mutation in 2 genes. Patients with ␣-thalassemia trait are also asymptomatic. Th ey have laboratory fi ndings similar to patients with ␣-thalassemia trait or iron defi ciency (microcytic, hypo- chromic) anemia. However, unlike ␣-thalassemia trait, the anemia is usually less severe, and the hemoglobin electrophoresis is normal. Th e diagnosis is based on the fi ndings of a microcytic, hypochromic mild anemia in patients of Asian or black descent with a normal electrophoresis and no evidence of iron defi ciency. Molecular genetic testing of

HBA1 and HBA2 detects deletions in about 90% and point mutations in about 10% of

aff ected individuals.6 _{For purposes of genetic counseling, the typical Asian genotype, with} both abnormal genes on the same chromosome, is of more concern than the usual genotype in black patients, with 1 abnormal gene on each chromosome 16. When 3 of the 4 genes are aff ected, hemoglobin H disease is the result. Patients with hemoglobin H disease may

be asymptomatic but on laboratory testing show a moderate to severe anemia (hemoglobin, 7–10 g/dL). Th e anemia is microcytic and hypochromic, with RBC fragments visible on review of the peripheral blood smear. A hemoglobin electrophoresis shows 5% to 30% hemoglobin H (hemoglobin consisting of 4 ␤ chains). In the newborn period, hemoglobin Barts may be detected, which consist of 4 gamma chains. With mutations in all 4 genes, no normal hemoglobin is made, and unless the diagnosis is made prenatally to allow for intrauterine transfusions, the fetus will die with hydrops fetalis.4