경희대학교 의과대학·의학전문대학원

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(1)

Hereditary

Hereditary

Hemolytic

Hemolytic

Anemia

Anemia

Young-shil, Park, M.D.

Young-shil, Park, M.D.

Division of Hematology-Oncology Department of Pediatrics

(2)

Introduction

Hemolysis

 the premature destruction of red blood cells (RBCs)

Normal RBC

 survival time ; 110–120 days (half-life, 55–60 days)  approximately 0.85% of RBCs (the senescent ones)

; removed each day and replaced by the marrow to maintain the RBC count

(3)

During hemolysis

 RBC survival is shortened  the RBC count falls

 erythropoietin is increased

 the stimulation of marrow activity results in heightened

RBC production

 an increased percentage of reticulocytes in the

(4)

The marrow can increase

its output two- to threefold acutely, with a maximum of six- to eightfold

 reticulocyte count

 hemolysis

 response to acute blood loss

 for a short period after replacement therapy for iron,

(5)
(6)

Figure. Red cell destruction and catabolism of hemoglobin (Hb) based on the description by Hillman and Finch. Fe, iron. (From Hillman RS, Finch CA: Red Cell Manual. Philadelphia, FA Davis, 1983.)

(7)

Hereditary spherocytosis

Hereditary elliptocytosis

Hereditary stomatocytosis

Hemoglobin disorders

Enzyme defects

(8)
(9)

 common cause of hemolysis and hemolytic

anemia

 prevalence of approximately 1/5,000 in people of

Northern European descent

 most common inherited abnormality of the red

blood cell (RBC) membrane.

 without anemia

with minimal hemolysis

(10)

Etiology

 autosomal dominant

 less frequently, autosomal recessive

(11)

 most common molecular defects

(12)
(13)

Table 458-1. Common Gene Mutations in Hereditary Spherocytosis (HS) PROTEIN BAND ON GEL GENE PROPORTION OF PATIENTS WITH HS INHERITANC E

Ankyrin 2.1 ANK1 50-67% Dom and Rec

Band 3 3 AE1 (SLC4A1) 15-20% Mostly Dom

β Spectrin 2 SPTB 15-20% Dom

α Spectrin 1 SPTA1 <5% Rec

Protein

(14)

 loss of membrane surface area without a

proportional loss of cell volume → sphering of the RBCs

associated increase in cation permeability cation transport

(15)

 decreased deformability of the spherocytic RBCs

impairs cell passage from the splenic cords to the splenic sinuses

 spherocytic RBCs are destroyed prematurely in

the spleen.

 Splenectomy markedly improves RBC life span

(16)

Clinical manifestations

in the newborn

 anemia and hyperbilirubinemia

⇒ phototherapy or exchange transfusions 

The severity in infants and children is

(17)

 After infancy

 splenomegaly

 pigmentary (bilirubin) gallstones ; as early as age 4–5 yr

 susceptible to aplastic crisis

 primarily as a result of parvovirus infection  Such erythroid marrow failure

⇒ profound anemia (hematocrit <10%) high-output heart failure, hypoxia cardiovascular collapse, and death

(18)
(19)

Laboratory findings

reticulocytosis & indirect

hyperbilirubinemia

Peripheral blood smear

Hereditary Spherocytosis

(20)

confirmed with an

osmotic fragility test

RBC membrane protein analysis using

gel

(21)
(22)

Differential diagnosis

large numbers of spherocytes

1) Isoimmune hemolytic disease

, particularly due to ABO incompatibility

2) thermal injury

3) clostridial septicemia with exotoxemia 4) Wilson disease

(23)

Treatment

splenectomy

eliminates most of the hemolysis

After splenectomy, osmotic fragility often

improves

 because of diminished splenic conditioning and less

RBC membrane loss; the anemia, reticulocytosis, and hyperbilirubinemia then resolve.

(24)

 For patients with more severe anemia

reticulocytosis

those with hypoplastic or aplastic crises

poor growth cardiomegaly splenectomy

-> recommended after age 5-6 yr to avoid the heightened risk of postsplenectomy sepsis in younger children

(25)

Vaccines (conjugated and/or capsular) for

encapsulated organisms, such as

pneumococcus, meningococcus, and

Haemophilus influenzae type b

,

should be administered before splenectomy

prophylactic oral penicillin V (age <5 yr, 125 mg

twice daily; age 5 yr through adulthood, 250 mg

twice daily) administered thereafter.

(26)

Hereditary Elliptocytosis

less common disorder than spherocytosis that also

varies markedly in severity

The blood film is the most important test to establish

hereditary elliptocytosis

Increased thermal instability

no treatment is necessary

Splenectomy

(27)

Hereditary stomatocytosis

(28)

Hemoglobinopathies

Hemoglobin ; tetramer consisting of 2 pairs of

globin chains.

Abnormalities in these proteins are referred to

(29)
(30)

Hb F (α2γ2) Hb A2 (α2δ2)

(31)

Sickle Cell Disease

Hemoglobin S (Hb S)

 result of a single base pair change, thymine for

adenine, at the 6th codon of the β-globin gene

In sickle cell anemia, Hb S ; commonly as high as

90% of the total hemoglobin.

Hb SS

In sickle cell disease, Hb S is >50% of all

(32)
(33)
(34)
(35)

Treatment

 need continuous treatment

 Supplementation with folic acid, an essential element

in producing red blood cells,

(36)

 Children with sickle cell anemia ; deficient levels of

serum opsonins of the alternate complement pathway against pneumococci.

 increased risk for infection and death as a result of

bacterial infection, particularly with encapsulated

organisms, such as Streptococcus pneumoniae and Haemophilus influenzae type B

 should receive prophylactic oral penicillin VK at least

(37)

Thalassemia Syndromes

genetic disorders in globin chain production

β-thalassemia ; either a complete absence of β-globin gene

production (β0-thalassemia) or a partial reduction (β+

-thalassemia)

α-thalassemia ; α-globin gene production is either absent or

partially reduced

 The primary pathology in thalassemia stems from the quantity of

globin gene production, whereas in sickle cell disease, the primary pathology is the quality of globin production.

(38)

 particularly prevalent among Mediterranean people  Middle Easterners, North Africans, and South Asians

(39)
(40)

 Figure 462-7 Ineffective

erythropoiesis in an

untransfused 3 yr old patient with thalassemia major. A,

Massive widening of the diploic spaces of the skull as seen on MRI. B, Radiographic

appearance of the trabeculae as seen on plain radiograph, and C, obliteration of the maxillary

sinuses with hematopoietic tissue as seen on CT scan.

(41)

chronic blood transfusion therapy

iron chelation

Splenectomy

(42)

Enzyme defects

 Various red blood cell (RBC) enzymatic defects

produce hemolytic anemias.

(43)
(44)

1. Pyruvate Kinase Deficiency

 The clinical manifestations vary from severe neonatal hemolytic

anemia to mild, well-compensated hemolysis first noted in adulthood.

Severe jaundice and anemia in the neonatal period  kernicterus

 The hemolysis in older children and adults varies in severity, with

hemoglobin values ranging from 8-12 g/dL associated with some pallor, jaundice, and splenomegaly.

(45)

2. Glucose-6-Phosphate Dehydrogenase

Deficiencies

 episodic hemolytic anemia induced by infections, certain drugs or, rarely, fava beans, and spontaneous chronic nonspherocytic hemolytic anemia

 In the usual pattern of G6PD deficiency, symptoms develop

24-48 hr after a patient has ingested a substance that has oxidant properties.

(46)

Table 463-1. Agents Precipitating Hemolysis in Glucose-6-Phosphate Dehydrogenase Deficiency MEDICATIONS Antibacterials Sulfonamides Trimethoprim-sulfamethoxazole Nalidixic acid Chloramphenicol Nitrofurantoin Antimalarials Primaquine Pamaquine Chloroquine Quinacrine Others Phenacetin Vitamin K analogs Methylene blue Probenecid Acetylsalicylic acid Phenazopyridine CHEMICALS Phenylhydrazine Benzene Naphthalene ILLNESS Diabetic acidosis Hepatitis Sepsis

수치

Table 458-1. Common Gene Mutations in Hereditary Spherocytosis (HS) PROTEIN BAND  ON GEL GENE PROPORTION OF  PATIENTS WITH HS INHERITANCE

Table 458-1.

Common Gene Mutations in Hereditary Spherocytosis (HS) PROTEIN BAND ON GEL GENE PROPORTION OF PATIENTS WITH HS INHERITANCE p.13
Table 463-1. Agents Precipitating Hemolysis in Glucose-6-Phosphate  Dehydrogenase Deficiency MEDICATIONS Antibacterials Sulfonamides  Trimethoprim-sulfamethoxazole Nalidixic acid Chloramphenicol Nitrofurantoin Antimalarials Primaquine Pamaquine Chloroquine

Table 463-1.

Agents Precipitating Hemolysis in Glucose-6-Phosphate Dehydrogenase Deficiency MEDICATIONS Antibacterials Sulfonamides Trimethoprim-sulfamethoxazole Nalidixic acid Chloramphenicol Nitrofurantoin Antimalarials Primaquine Pamaquine Chloroquine p.46

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