Thanks to Dr Mlaki G

1. ANAEMIA
KELVIN L. KANDIRA-MD5
SUPERVISOR; Dr. MWANYIKA
MD;MMED-PED

2. DEFINATION
• Anemia is defined as a reduction of the red blood cell (RBC)
volume or hemoglobin concentration below the range of
values occurring in healthy person.
mild-9-11
moderate-7-9
severe-5-7
very severe-<4
in g/dl

3. RBC POST NATAL CHANGES
• Erythropoietin (Epo) regulates the production of RBCs in
utero as well as after birth. Its secretion is stimulated by low
tissue oxygen
• The fetal liver initially produces Epo but during the 3rd
trimester the kidneys become the major source of this growth
factor.
• At the end of gestation, when the Epo concentration is at its
peak, erythropoiesis is approximately three to five times that
of normal adults.
• Subsequent to the onset of respiration and the increase in
PaO2, the stimulus for Epo release is eliminated. There is a
decline in both erythropoiesis and hemoglobin synthesis

4. • This is reflected in changes in hematologic values and RBC indices in the
first weeks and months of life.
• Normal levels of RBCs at birth range from 5.1 to 5.3 million/mm3 for term
newborns and 4.6 to 5.3 million/mm3 for premature neonates.
• Nucleated red blood cells (NRBC) are immature erythrocytes rarely found
in the peripheral circulation of adults in the absence of illness. It is normal
to see NRBCs in newborns shortly after the stress of delivery.
• This is likely reflective of elevated Epo levels in the presence of the
normally low oxygen tensions in utero. NRBCs generally disappear by 4
days and 7 days of life in term and premature neonates, respectively,
although they may persist longer than 1 week in very immature neonates.
• The continued presence of NRBCs for a longer than expected time may
indicate a pathologic condition.

5. • Because of active in utero erythropoiesis, the reticulocyte count at birth is 3
to 7% in full-term babies and 8 to 10% in premature babies.
• This declines to 0 to 1% by the first week of age, reflecting diminished
erythropoiesis.
• Reticulocyte counts are frequently increased in anemia and are useful in
differentiating acute from chronic anemia. "Increased numbers of immature
RBCs reflect the degree of hematopoietic activity in response to anemia.
• There is a delay between the onset of anemia and the stimulation of
erythropoiesis. Therefore, in acute anemia the reticulocyte count may be
normal whereas in chronic anemia the reticulocyte count would be
elevated.
• A neonate delivered after a placental abruption would be expected to have
anemia and a normal reticulocyte count. In the case of in utero hemolysis
due to ABO incompatibility, the neonate might be anemic with an elevated
reticulocyte count

6. • The life span of adult erythrocytes is 120 days. RBCs in term neonate will
survive between 60 and 90 days. Erythrocytes from premature neonates
have considerably shorter life spans, ranging from 35 to 50 days
• Mean Cell Volume. Early embryonic RBCs are large; diameters range from
20 to 25 µm with a mean cell volume (MCV) of 180 (fl) or µm3.
• Cell size decreases gradually during development reaching 130 fl at
midgestation and 115 fl at term. MCV at 1 year of age is 82 fl.
• It is important to recognize the MCV variations in childhood, because
many laboratories use only adult normal values, which differ considerably.
For every child with significant anemia, it also is essential to review the
appearance of RBCs on a peripheral blood smear
• The mean corpuscular hemoglobin concentration (MCHC) is fairly
constant from birth through adulthood.It averages 34 pg in full-term cord
blood, 35 pg on the first day of life, and 33 picograms (pg) at 1 week of
age. Premature neonates, however, have higher MCHCs; values range from
40 pg at 28 weeks to 38 pg at 34 weeks
• MCV is counted for age and gestation.

7. • Red cell distribution width (RDW) indicates variation in RBC
size and is used to detect anisocytosis.
• RDW can also be a sensitive and specific early indicator of iron
deficiency anemia especially in infants with cyanotic congenital
heart disease.
• Greater heterogeneity of cell size yields a larger RDW.
"Because immature cells are larger than older red cells, infants
with active erythropoiesis have elevated RDWs.
• Infants who have received blood transfusions have lower RDWs
since transfusions suppress erythropoiesis.
• Values in normal individuals vary from 11.5 to 14.5% while
RDWs in infants and children range from 1.5 to 15%.

8. PHYSIOLOGY
• RBCs play role in the support of tissue metabolism. Contains hemoglobin,
which transports oxygen to and removes carbon dioxide from tissues.
• RBC production involves a series of maturational steps, beginning with a
pluripotent cell that differentiates into erythroid
• As the cells undergo maturational changes, they lose their nuclei and
acquire hemoglobin.Once RBCs have achieved their normal life span,
usually about 120 days, they become sequestered and destroyed in the
spleen. Liberated iron is then recycled for use by the marrow in further
RBC production
• Hemoglobin is a molecule composed of two globulin chains and four heme
groups.
• It is described as the respiratory protein of the RBC due to its important
role in the transport of oxygen and carbon dioxide.

9. • Hemoglobin is able to bind reversibly with oxygen, which allows it to be
released to the tissues when needed.
• Carbon dioxide is then picked up by unbound hemoglobin for transport to
the lungs and excretion.
• The fetus produces unique type of hemoglobin, fetal hemoglobin (HbF),
which more efficiently binds and releases oxygen within the relatively
hypoxic intrauterine environment.
• Reduction in the amount of circulating hemoglobin decreases the oxygen-
carrying capacity of the blood.
• Clinical disturbances occur when hemoglobin level falls below 7–8 g/dL.
where pallor becomes evident in the mucous membranes.
• Physiologic adjustments to anemia then occur which includes increased
cardiac output, increased oxygen extraction (increased arteriovenous
oxygen difference), and a shunting of blood flow toward vital organs and
tissues.

10. • Also as oxygen delivery by RBCs to tissues decreased, concentration of
2,3-diphosphoglycerate (2,3-DPG) increases within the RBC. This reduce
the affinity of hemoglobin for oxygen, results in more complete transfer of
oxygen to the tissues.
• Other mechanism involves higher levels of erythropoietin (EPO) which
help the body to compensate for the deficiency.

11. CAUSES OF ANAEMIA
• INCREASE DESTRUCTION.
• DECREASE PRODUCTION.
• ACUTE BLOOD LOSS.

12. DECREASE PRODUCTION
MEGALOBLASTIC ANAEMIA.
• The RBCs are larger than normal at every stage of development and have
an open, finely dispersed nuclear chromatin and an asynchrony between the
maturation of nucleus and cytoplasm, with the delay in nuclear progression
becoming more evident with further cell divisions.
• In the peripheral blood, red cells are large (increased mean corpuscular
volume, MCV) .
• Vitamin B-12 and folic acid deficiencies, direct interference of DNA
synthesis by HIV infections and certain medications are the most common
causes of megaloblastic anemia, a macrocytic anemia.
• Vitamin B-12 differs from other water-soluble vitamins in that it is stored in
the liver. In addition, vitamin B-12 has to be protected during its passage
through the gastrointestinal tract to the distal ileum, the site of B-12
absorption.

13. Pathophysiology
• The common feature in megaloblastosis is a defect in DNA synthesis in
rapidly dividing cells. To a lesser extent, RNA and protein synthesis are
impaired. Unbalanced cell growth and impaired cell division occur since
nuclear maturation is arrested. More mature RBC precursors are destroyed
in the bone marrow prior to entering the blood stream (intramedullary
hemolysis).

14. FOLATE DEFICIENCY
• Folates are abundant in green vegetables, fruits, and animal organs
(liver, kidney). Folic acid is absorbed throughout the small intestine
• Surgical removal or disorders of the small intestine may lead to
folate deficiency.
• Dietary deficiency is usually compounded by rapid growth or
infection, which may increase folic acid requirements.
• Normal adult daily requirement is about 100 microgram/24 hr,
which rises to 350 microgram/24 hr in pregnancy.
• The requirements on a weight basis are higher in the pediatric age
range in comparison to adults due to the increased needs of growth.
The needs are also increased with accelerated tissue turnover, as in
hemolytic anemia.
• Human and cow's milks provide adequate amounts of folic acid.
Goat's milk and powered milk is deficient

15. Other causes of Folic Acid Defiency
• MEGALOBLASTIC ANEMIA OF PREGNANCY : Folate requirements
increase markedly during pregnancy. Decreases in serum folate levels
occur at term and may be aggravated by infection. Folate supplementation,
1 mg/24 hr, - during the last trimester.
• Mothers with folate deficiency may have babies with normal folate stores
due to selective transfer of folate to the fetus via placental folate receptors.
• FOLIC ACID DEFICIENCY IN MALABSORPTION SYNDROMES:
Diffuse inflammatory or degenerative disease of the intestine
• CONGENITAL FOLATE MALABSORPTION: An autosomal recessive
defect.
• FOLIC ACID DEFICIENCY ASSOCIATED WITH
ANTICONVULSANTS AND OTHER DRUGS : phenytoin, primidone,
phenobarbital(impared absorption and increase utilization)

16. JUVENILE PERNICIOUS ANEMIA
• This rare autosomal recessive disorder caused by inability of absorption of
Vitamin B-12 due to a lack of intrinsic factor in gastric (stomach)
secretions.
• Intrinsic factor is a protein the body uses to absorb vitamin B12. When
gastric secretions do not have enough intrinsic factor, vitamin B12 is not
adequately absorbed, resulting in pernicious anemia.
• Intrinsic factor is produced by cells within the stomach
• It differs from the typical disease in adults in that the stomach secretes acid
normally and is histologically normal.
TOTAL GASTRECTOMY.
OTHERS, INFLAMMATORY BOWEL DISEASE, SPRUE, OR ILEAL
RESECTION.

17. Clinical Manifestations
• Btwn 9 mo to 1 yr of age. During this interval stores of vitamin B12
acquired in utero is used.
• As the anemia becomes severe, weakness, irritability, anorexia, and
lethargy occur.
• The tongue is smooth, red, and painful.
• Neurologic manifestations include ataxia, paresthesias, hyporeflexia,
Babinski responses, clonus, and coma.
• Some patients can have gastrointestinal symptoms such as loss of appetite,
weight loss, nausea, and constipation. Patients may have a sore tongue and
canker sores.
• peripheral neuropathy, can occur in both folate and cobalamin deficiencies.
Peripheral neuropathy presents as numbness, pain, tingling, and burning in
a patient’s hands and feet.

18. • Pernicious anemia:
• These patients may have signs of other autoimmune disorders such as
thyroid disorders, type I diabetes, or Addison disease.
• Other potential causes of macrocytosis (liver disease, hypothyroidism, and
hemolytic anemia) should be considered in the differential diagnosis

19. WORKUP
• Initial workup for megaloblastic anemia should include a complete blood
count (CBC), RBC indices, peripheral smear, reticulocyte count, lactate
dehydrogenase (LDH elevated), indirect bilirubin, iron and ferritin assays,
serum cobalamin and serum folate, and possibly an RBC folate evaluation
• Bone marrow aspiration
PRIMARY TEST FOR B-12 AND FOLATE.
• Serum B-12 (cobalamin)
Diagnostic of B-12 deficiency: < 150 mg/L.
• Serum folate
Folate deficiency likely : < 2.5 ng/mL

20. Lab tests to confirm and distinguish B-12 and folate deficiencies
• Serum homocysteine and methylmalonic acid (MMA) levels are helpful
confirmatory tests for cobalamin and folate deficiencies. Both are increased
in cobalamine deficiency. Homocysteine is increased in folate deficiency.
Homocysteine and MMA levels should be used if the clinical presentation
and serum vitamin B-12 and folate levels are ambiguous.
Schilling test
• (a radiometric test) is that it can confirm B-12 deficiency, can be done after
patient has been given B-12 therapy, and can distinguish between
pernicious anemia and failure in transport or ileal uptake.

21. TREATMENT
• Cobalamin therapy
0.2 µg/kg for 2 days, but usually a 1000 µg dose is recommended which may
be continued for the first 7 days.
If there is neurologic involvement, 1 mg should be injected intramuscularly
daily for at least 2 wks
Maintainance;IM 1mg monthly for life
• Folic acid therapy
Folic acid - orally - - in a dose of 1–5 mg/24 hr.
Reticulocyte response is seen within 72 hr.
Blood transfusions are indicated - when the anemia is severe or the child is
very ill.
Folic acid therapy should be continued for 3–4 wk.

22. Monitoring response to Rx
• Complete blood cell count
• Reticulocyte count
• Lactate dehydrogenase (LDH) level
• Indirect bilirubin
• Hemoglobin level
• Serum potassium level
• Serum ferritin

23. IRON DEFICIENCY ANAEMIA
• Iron deficiency is defined as a decreased total iron body content. Iron
deficiency anemia occurs when iron deficiency is severe enough to
diminish erythropoiesis and cause the development of anemia.
• most common hematologic disease of infancy and childhood
• Normal-term infants are born with sufficient iron stores to prevent iron
deficiency for the first 4–5 months of life.
• Thereafter, enough iron needs to be absorbed to support the needs of rapid
growth. For this reason, nutritional iron deficiency is most common
between 6 and 24 months of life
• A deficiency earlier than age 6 months may occur if iron stores at birth are
reduced by prematurity, small birth weight, neonatal anemia, or perinatal
blood loss or if there is subsequent iron loss due to hemorrhage

24. ETIOLOGY
DIETARY FACTOR
• Meat provides a source of heme iron.
• The prevalence of iron deficiency anemia is low in geographic areas where
meat is an important constituent of the diet. In areas where meat is sparse,
iron deficiency is commonplace.
• Substances that diminish the absorption of ferrous and ferric iron include
phytates, oxalates, phosphates, carbonates.

25. HEMORRHAGE
• Bleeding for any reason produces iron depletion.
• If sufficient blood loss occurs, iron deficiency anemia occur.
• A single sudden loss of blood produces a post hemorrhagic anemia that is
normocytic. The bone marrow is stimulated to increase production of
hemoglobin, thereby depleting iron in body stores.
• Once they are depleted, hemoglobin synthesis is impaired and microcytic
hypochromic erythrocytes are produced.
• The peripheral smear shows a dimorphic population of erythrocytes,
normocytic cells produced before bleeding, and microcytic cells produced
after bleeding.
• This is reflected in the red blood cell distribution width (RDW); thus, the
earliest evidence of the development of an iron-deficient erythropoiesis is
seen in the peripheral smear, in the form of increased RDW.

26. HEMOSIDERINURIA, HEMOGLOBINURIA, AND PULMONARY
HEMOSIDEROSIS
• Investigate renal loss of iron by staining the urine sediment for iron.
• Hemosiderin is detected intracellularly. Most of these patients have a low
or absent plasma haptoglobin.
• Similarly, pulmonary hemosiderosis can result in sufficient loss of iron as
hemosiderin from the lungs.

27. MALABSORPTION OF IRON
• Prolonged achlorhydria may produce iron deficiency because acidic
conditions are required to release ferric iron from food.
• Then, it can be chelated with mucins and other substances (eg, amino acids,
sugars, amino acids, or amides) to keep it soluble and available for
absorption in the more alkaline duodenum.

28. IRON-REFRACTORY IRON DEFICIENCY
• Iron-refractory iron deficiency anemia (IRIDA) is a hereditary disorder
marked by with iron deficiency anemia that is typically unresponsive to
oral iron supplementation and may be only partially responsive to
parenteral iron therapy.
• IRIDA results from variants in the TMPRSS6 gene that lead to uninhibited
production of hepcidin.
• IRIDA is characterized by microcytic, hypochromic anemia and serum
hepcidin values that are inappropriately high for body iron levels
HOOKWORM INFESTATION
DYSENTRY
LBW
PREMATURITY

29. CHRONIC DISEASE
• Such as chronic immune activation,chronic infection and malignancy
produce massive elevation of interleukin 6.
• This stimulate hepcidin production and release from liver which in turn
reduce the iron carrier protein(ferroportin).
• Access of iron to the circulation reduced
• Also direct reduction in erythropoiesis.

30. Physical examination
• These include esophageal webbing, koilonychia, glossitis, angular
stomatitis,pollor and gastric atrophy
• Splenomegaly may occur with severe, persistent, untreated iron deficiency
anemia.
CLINICALLY
• In infants with more severe iron deficiency, pallor, fatigue, irritability, and
delayed motor development are common.
• Pagophagia, the desire to ingest unusual substances such as ice or dirt.

31. workup
• Complete blood count (CBC)
• Peripheral smear
• Serum iron
• Total iron-binding capacity (TIBC)
• Serum ferritin
• Stool for occult blood
• Urine for occult blood

32. TREATMENT
IRON SUPLEMENTS
• Parenteral:
• oral: 6 mg/kg of elemental iron in three divided doses. Continue for 8wks
after blood value are normal.
BLOOD TRANSFUTION.
• Packed or sedimented red cells should be administered slowly severely
anemic children with hemoglobins under 4 g/dL - given only 2–3 mL/kg of
packed cells at any one time (furosemide may also be administered as a
diuretic)

33. APLASTIC ANAEMIA
ETIOLOGY
Inherited Bone Marrow Syndromes Associated with Pancytopenia
• Fanconi's Anemia
• Dyskeratosis Congenita
• Shwachman-Diamond Syndrome
• Cartilage-Hair Hypoplasia
• Pearson's Syndrome
• Down Syndrome
• Familial Marrow Dysfunction

34. FANCONI ANAEMIA
• Fanconi anemia is an autosomal recessive disease in more than 99% of
patients (FANCB is X-linked recessive)
• Each patient with Fanconi anemia is homozygous or doubly heterozygous
for mutations in 1 of the 15 genes known to be responsible for Fanconi
anemia.
• Fanconi anemia is the most frequently reported of the rare inherited bone
marrow failure syndromes (IBMFSs).
• Occur concurently with other physical abdomalities

35. History
• During childhood, short stature and skin pigmentation, including café au
lait spots, may become apparent.
• The first sign of a hematologic problem is usually petechiae and bruises,
with later onset of pallor, fatigue, and infections.
Physical Examination
• About 75% of patients with Fanconi anemia have birth defects, such as
altered skin pigmentation and/or café au lait spots (>50%), short stature
(50%), thumb or thumb and radial anomalies (40%), abnormal male gonads
(30%), microcephaly (25%), eye anomalies (20%), structural renal defects
(20%), low birth weight (10%), developmental delay (10%), and abnormal
ears or hearing (10%).

36. WORKUP
• CBC count
• Chromosome breakage test
• Flow cytometry

37. MEDICATIONS
Androgenic agents(epo)
• Oxymetholone (Anadrol-50)
• 17 Alpha-ethynyl testosterone (Danazol,Danocrine
Antifibrinolytic agents(bleeding)
• Aminocaproic acid (Amicar)
Hematopoietic growth factors
• Filgrastim (G-CSF, Neupogen)
Hematopoietic Stem Cell Transplantation

38. DYSKERATOSIS CONGENITA
• Is a rare inherited bone marrow failure (BMF) syndrome with X-linked,
autosomal dominant, and autosomal recessive inheritance.
• Classically BMF in DC patients is associated with the mucocutaneous triad,
including abnormal pigmentation, dystrophic nails, and mucosal
leukoplakia.
• About 85% of patients with classic DC are initially found to have cytopenia
of one or more lineages, and pancytopenia develops in more than 95% of
patients by 40 years of age.
• Complications of BMF, such as hemorrhage or opportunistic infection,
represent the major cause of death in patients with DC.DC is a cancer
predisposition syndrome

39. WORKUP
PERIPHERAL BLOOD
• Cytopenia of one or more lineages (80%)Initial manifestation highly
variable macrocytosis with or without anemia, thrombocytopenia
neutropenia pancytopenia
• Low number of circulating progenitor cells, Elevated hemoglobin F,
Elevated von Willebrand factor
BONE MARROW EXAMINATION
• Hypocellular bone marrow affecting all three lineages
• Increased number of mast cells
• Dyserythropoiesis Hypocellular myelodysplastic syndrome
• Myelodysplastic syndrome/acute myeloid leukemia

40. Inherited Bone Marrow Failure Syndromes Associated with Isolated Cytopenia
• Diamond-Blackfan Anemia
• Congenital Dyserythropoietic Anemia
• Severe Congenital Neutropenia
• Inherited Thrombocytopenia
• Amegakaryocytic thrombocytopenia
• Thrombocytopenia with Absent Radii,

41. DIAMOND-BLACKFAN ANEMIA
• Is a congenital erythroid aplasia that usually presents in infancy.
• DBA causes low red blood cell counts (anemia), without substantially
affecting the other blood components (the platelets and the white blood
cells), which are usually normal.
• Most pedigrees suggest an autosomal dominant mode of inheritance with
incomplete penetrance.
• Approximately 10–25% of DBA occurs with a family history of disease.
• DBA red cells characteristically have increased adenosine deaminase
activity.
• DBA is a rare disease with a frequency of 2 to 7 per million live births and
has no ethnic or gender predilection

42. Symptoms & signs
• Diamond–Blackfan anemia is characterized by normocytic or macrocytic
anemia (low red blood cell counts) with decreased erythroid progenitor
cells in the bone marrow.
• This usually develops during the neonatal period. About 47% of affected
individuals also have a variety of congenital abnormalities.
• Including craniofacial malformations, thumb or upper limb abnormalities,
cardiac defects, urogenital malformations, and cleft palate. Low birth
weight and generalized growth delay are sometimes observed.
• DBA patients have a modest risk of developing leukemia and other
malignancies.

43. Diagnosis
• Typically, a diagnosis of DBA is made through a blood count and a bone
marrow biopsy.
• A diagnosis of DBA is made on the basis of anemia, low
reticulocyte(immature red blood cells) counts.
• Diminished erythroid precursors in bone marrow. Features that support a
diagnosis of DBA include the presence of congenital abnormalities,
macrocytosis, elevated fetal hemoglobin.
• elevated adenosine deaminase levels in red blood cells

44. TREATMENT
 CORTICOSTEROIDS
• Prednisone (or prednisolone) therapy is usually initiated at a dosage of 2
mg/kg/day
 BLOOD TRANSFUSIONS
 BONE MARROW TRANSPLANTATION

45. Aquired Aplastic Anaemias
• Drugs: Chloramphenicol, phenylbutazone, and goldbenzene exposure
• Infectious causes such as hepatitis viruses, Ebstein-Barr virus (EBV), HIV,
parvovirus, and mycobacterial infections
• Autoimmune such as paroxysmal nocturnal hemoglobinuria (PNH) is
relatively rare. Has been correctly classified as a hemolytic anemia;
however, the frequent co-existence of other cytopenias has hinted strongly
at a more complex pathogenesis. Cytotoxic T cell attack, with production of
type I cytokines, leads to hematopoietic stem cell destruction and
ultimately pancytopenia.
.

46. INCREASE DESTRUCTION
HEMOLYTIC ANAEMIA
Classification of Hemolytic anemias
I. Red cell abnormality (Intracorpuscular factors)
A. Hereditary Membrane defect (spherocytosis, elliptocytosis).
B. Metabolic defect (Glucoze-6-Phosphate-Dehydrogenaze (G6PD)
deficiency, Pyruvate kinase (PK) deficiency) Hemoglobinopathies
(unstable hemoglobins, thalassemias, sickle cell anemia )
C. Acquired Membrane abnormality-paroxysmal nocturnal hemoglobinuria
(PNH)

47. HEREDITARY SPHEROCYTOSIS
• is a familial hemolytic disorder associated with a variety of mutations that
lead to defects in red blood cell (RBC) membrane proteins.
• HS usually is transmitted as an autosomal dominant trait, and the
identification of the disorder in multiple generations of affected families is
the rule
• The morphologic hallmark of HS is the microspherocyte, which is caused
by loss of RBC membrane surface area

48. Pathophysiology
• In HS, intrinsic defects in erythrocyte membrane proteins result in RBC
cytoskeleton instability.
• Loss of erythrocyte surface area leads to the production of spherical RBCs
(spherocytes), which are culled rapidly from the circulation by the spleen.
Hemolysis primarily is confined to the spleen and, therefore, is
extravascular.
• Splenomegaly commonly develops.
The following four abnormalities in RBC membrane proteins have been
identified in HS:
• Spectrin deficiency alone
• Combined spectrin and ankyrin deficiency
• Band 3 deficiency
• Protein 4.2 defects

49. Laboratory inv
• Complete blood cell count
• Reticulocyte count
• Mean corpuscular hemoglobin concentration (MCHC)
• Peripheral blood smear
• Hyperbilirubinemia
• Abdominal uss

50. Treatment
• Red blood cells are transfused to patients whenever Hb drops under 7gm/dl
or clinical status is deteriorated.
• Splenectomy usually is curative.
• Fatal sepsis caused by capsulated organisms (eg, Streptococcus
pneumoniae, Haemophilus influenzae) is a complication in children who
had a splenectomy.
• Bilirubin gallstones are found in approximately 50% of patients.
Splenectomy for children with HS should be performed when the child is
older than 6 years.
• Before having a splenectomy, anyone with HS should have the
pneumococcal vaccine.
• Folic acid, an important cofactor for enzymes used in production of RBCs
is given at a dose of 1 mg/day
• The prognosis (outlook) after splenectomy is for a normal life and a normal
life expectancy.

51. GLUCOSE-6-PHOSPHATE DEHYDROGENASE DEFICIENCY(G6PD)
• is the most common enzyme deficiency in humans, affecting 400 million
people worldwide.
• It has a high prevalence in persons of African, Asian, and Mediterranean
descent. It is inherited as an X-linked recessive disorder.
• G6PD deficiency is polymorphic, with more than 300 variants.
• G6PD deficiency confers partial protection against malaria , which
probably accounts for the persistence and high frequency of the responsible
genes
• G6PD deficiency can present as neonatal hyperbilirubinemia.

52. Pathophysiology
• The G6PD enzyme It catalyzes the oxidation of glucose-6-phosphate and
the reduction (NADP+) to (NADPH).
• NADPH maintains glutathione in its reduced form, which acts as a
scavenger for dangerous oxidative metabolites.
• Therefore, red blood cells depend on G6PD activity to generate NADPH
for protection.
• Thus, red blood cells are more susceptible to oxidative stresses than other
cells.
• In persons with G6PD deficiency, oxidative stresses can denature
hemoglobin and cause intravascular hemolysis.
• Denatured hemoglobin can be visualized as Heinz bodies in peripheral
blood smears

54. History
• Most pt are asymptomatic. Neonatal jaundice may occur.
• Jaundice usually appears within 24 hours after birth
• Most patients are usually not anemic, but episodes of intravascular
hemolysis and consequent anemia can be triggered by infections, medicines
that induce oxidative stresses and ketoacidosis.
• Hemolysis begins 24 to 72 hours after exposure to oxidant stress. When
hemolysis is severe, patients present with weakness, tachycardia, jaundice,
and hematuria
• Jaundice and splenomegaly may be present.
• right upper quadrant tenderness due to hyperbilirubinemia and
cholelithiasis.

55. Tests to diagnose hemolysis include the following:
• Complete blood cell count (CBC) and reticulocyte count
• Lactate dehydrogenase (LDH) level
• Indirect and direct bilirubin level
• Serum haptoglobin level
• Urinalysis for hematuria
• Urinary hemosiderin
• Peripheral blood smear

56. TREATMENT
• Exchange Transfusion
• Transfusion With G6pd-normal Blood
• Phototherapy
• Avoid Oxidant Drug
• Pharmacologic Not Applicable

57. PAROXYSMAL NOCTURNAL HEMOGLOBINURIA (PNH)
• Was previously classified as purely an acquired hemolytic anemia due to a
hematopoietic stem cell mutation defect.
• This classification was abandoned because of the observation that surface
proteins were missing not only in the RBC membrane but also in all blood
cells, including the platelet and white cells.
• The essential group of membrane proteins that are lacking in all
hematopoietic cells are called complement-regulating surface proteins,
including the decay-accelerating factor
• The absence of these regulating proteins results in uncontrolled
amplification of the complement system.
• This leads to intravascular destruction of the RBC membrane, to varying
degrees
• Breakdown of RBC membranes by complement leads to the release of
hemoglobin into the circulation.
• Hemoglobin is bound to haptoglobin for efficient clearance from the
circulation

58. II. Extracorpuscular factors
A. Immune hemolytic anemias Autoimmune hemolytic anemia caused by
warm-reactive antibodies caused by cold-reactive antibodies Transfusion
of incompatible blood
B. Nonimmune hemolytic anemias Chemicals Bacterial infections, parasitic
infections (malaria), venons Hemolysis due to physical trauma hemolytic
- uremic syndrome (HUS) thrombotic thrombocytopenic purpura (TTP)
prosthetic heart valves Hypersplenism

59. ACUTE BLOOD LOSS
• Acute blood loss anemia is often caused by a large hemorrhage.
• This involves a trauma to a large blood vessel.
• The typical symptoms of blood loss anemia due to a hemorrhage include
rapid pulse, dizziness, sweating, and faintness.
• Blood vessels are constricted in this situation, which may cause the red
blood count and hemoglobin levels to temporarily be high.
• But these levels will usually drop within a couple hours or less, once the
body switches into emergency mode and starts replacing the missing blood
with tissue fluid.