RBC Disorders 3

Question 1

Immunohemolytic Anemias (IHA)

Answer 1

• Caused by Abs that binds to RBC antigens
• Subdivided according to the characteristics of the offending antibodies into:
– Warm Antibody IHA – Cold Antibody IHA
• Cold Agglutinin Type • Cold Hemolysin Type
-extrinsic

Question 2

Nonimmune Hemolytic Anemias

Answer 2

– Mechanical trauma to red cells
– Infections (e.g. Malaria parasite)

Question 3

Warm Antibody Immunohemolytic Anemia

Answer 3

• Most antibodies are IgG class (active at 37°C)
• Antibody-coated RBCs are removed from the circulation
by phagocytes in the spleen (Extravascular Hemolysis)
• Most patients have chronic mild anemia and moderate
splenomegaly

Question 4

Cold Antibody Immunohemolytic Anemia: Cold Agglutinin Type

Answer 4

Are IgM antibodies that do not interact with RBCs at body temperature but react strongly at lower temperatures
Pathological cold agglutinins are produced either in : – Infections: Mycoplasma, EBV, HIV, CMV, influenza – Neoplastic growth: B-cell lymphomas

Question 5

Immune Hemolytic Anemias: Laboratory Diagnosis- Direct Coombs test

Answer 5

– Patient RBCs are incubated with antibodies against human immunoglobulin or complement
– Positive test result→RBC agglutination

Question 6

Immune Hemolytic Anemias -indirect coombs test (Indirect Antiglobulin Test- IDAT)

Answer 6

– Patient serum is tested for its ability to agglutinate test RBCs bearing defined surface antigens.

Question 7

1. Hemolysis due to Mechanical RBC damage

Answer 7

-Cardiac valve prostheses: more in mechanical than bioprosthetic valves
-Microangiopathic hemolytic anemia:
*Occurs following partial microvascular obstruction
*Seen in: DIC, malignant hypertension, TTPHUS, SLE and disseminated cancer
-March hemoglobinuria

Question 8

Malaria

Answer 8

– Intracellular red cell parasite that causes hemolysis of variable severity

Question 9

Anemias of Impaired RBC Production

Answer 9

• Failure of proliferation and/or maturation of committed RBC precursors
• Failure of stem cells(aplastic anemia )
• Unknown/multiple mechanisms(anemias of chronic disease)

Question 10

Failure of proliferation and/or maturation of committed RBC precursors

Answer 10

– Defective DNA synthesis – Megaloblastic anemias
– Defective Heme synthesis – Iron deficiency anemia
– Defective Globin synthesis – Thalassemias

Question 11

Causes of megaloblastic anemia are:

Answer 11

• Vitamin B12 deficiency (cobalamin)
• Folic acid deficiency (Folate)

Question 12

Pathogenesis of megaloblastic anemia:

Answer 12

• Vitamins B12 and folate are both co-enzymes, necessary for the synthesis of thymidine, one of the four bases in DNA
• Deficiency results in inadequate DNA synthesis→ defective nuclear maturation, with relatively normal RNA and protein synthesis→nuclear/cytoplasmic asynchrony

Question 13

Peripheral blood film-Megaloblastic Anemias

Answer 13

• Patients may have pancytopenia
• RBCs are macrocytic (MCV >100 fl), with increased reticulocyte count
• Neutrophils are hypersegmented (with ≥5

Question 14

Megoblastic bone marrow

Answer 14

-Hypercellular (but ineffective) hematopoiesis
-Megaloblastic changes: large red cell and white cell precursors, large megakaryocytes, with large immature nuclei or increased
nuclear lobes

Question 15

Causes of vitamin B12 Deficiency:

Answer 15

-Decreased Intake
-impaired GI absorption (pernicious anemia)
-genetic disorders affecting vitamin B12

Question 16

Pernicious anemia

Answer 16

• Is an autoimmune disease where there is destruction of the gastric mucosa particularly parietal cells→failure of IF production→failure of B12 absorption→B12 deficiency→megaloblastic anemia
-Histologically:chronicatrophicgastritis

Question 17

B12 Deficiency anemia- clinical features

Answer 17

-symptoms of anemia
-mild jaundice
-beefy tongue : due to megaloblastic changes in the oropharyngeal epithelium
-paraparesis, sensory ataxia, lower limb paresthesia

Question 18

B12 Deficiency anemia- lab findings

Answer 18

• CBC: Low Hb with high MCV, pancytopenia
• Peripheral blood film and bone marrow examination show features of megaloblastic anemia, with low reticulocyte counts

• Other lab investigations:
– Serum B12 and Folate levels: Low B12 with normal folate – Serum homocysteine level: Elevated
– Serum methylmalonic acid: Elevated
– Serum antibodies to IF(very specific)
-Schilling test – inability to absorb an oral dose of B12

Question 19

Causes of Folic acid Deficiency:

Answer 19

1. Decreased intake
   – Diet inadequate for green vegetables (e.g. alcoholics)
2. Impaired gastrointestinal absorption
3. Increased requirements
   – Pregnancy
   – Infancy
   – disseminatedcancer
   – Drugs:e.g.methotrexate,Trimethoprim

Question 20

Clinical features of Folic acid Deficiency:

Answer 20

-Are like B12 deficiency but no CNS involvement

Question 21

Folate deficiency anemia : lab findings

Answer 21

• CBC: Low Hb with high MCV, pancytopenia
• Peripheral blood film and bone marrow examination
shows features of megaloblastic anemia with low reticulocyte counts
• Other lab investigations:
– Serum Folate and B12 levels: Low folate with normal B12 – Serum homocysteine level: Elevated
– Serum methylmalonic acid: Normal
– Red cell folate level: Low (v. specific & not affected by diet)

Question 22

Causes of iron Deficiency:

Answer 22

1. Dietary deficiency
   – commonest cause of IDA in developing countries
2. Impaired absorption
3. Increased requirements
   – growing infants/children, premenopausal women, pregnancy
4. Chronic blood loss
   – commonest cause of IDA in the Western world (mainly due to chronic GI blood loss)

Question 23

Hepcidin

Answer 23

a peptide synthesized in the liver in response to high levels of liver iron stores, inhibits iron uptake from duodenal mucosal cells into the
bloodstream

Question 24

Storage Iron:

Answer 24

– Ferritin: which is an iron-protein complex
– Hemosiderin: partly degraded aggregates of ferritin

Question 25

Iron Transport:

Answer 25

• Iron is transported in the plasma bound to a protein called Transferrin
• The capacity of the transferrin to bind iron is referred to as Total Iron Binding Capacity (TIBC)
• Normally 33% of the transferrin is satur

Question 26

Symptoms of IDA

Answer 26

-symptoms of anemia
-pica and ice craving

Question 27

Signs of IDA

Answer 27

• Pallor
• Dry or rough skin
• Atrophic glossitis, with loss of tongue papillae
• Angular cheilitis
• Koilonychia (spoon shaped nails)

Question 28

Lab findings of IDA

Answer 28

• CBC: Low Hb, low MCV, low MCH and High RDW
• Peripheral Blood smear: – Microcytic hypochromic
anemia
– In severe cases “poikilocytosis” and “pencil cells”
• Reticulocytes count: Low

Question 29

IDA : serum iron studies

Answer 29

-low ferritin
-low serum iron
-high TIBC
-low transferrin

Question 30

Anemia of Chronic Disease (ACD)

Answer 30

mainly seen in patients with:
–Chronic bacterial infections:
• e.g. lung abscess, osteomyelitis, endocarditis
–Chronic immune disorders: • e.g. Rheumatoid Arthritis
–Malignant tumors:
• e.g. lymphomas, lung or breast cance

Question 31

Pathogenesis of Anemia of chronic disease

Answer 31

• There is impairment of iron utilization and reduction in RBC production
• During inflammation, there is increased production of hepcidin and decreased production of erythropoietin→decrease transfer of iron from the BM storage pool (macrophages) to RBC precursors→decrease erythropoiesis, with inappropriately low erythropoietin

Question 32

Lab findings of ACD

Answer 32

• Clinical history: chronic medical condition
• CBC: Low Hb, low/normal MCV
• Peripheral Blood smear:
– Normocytic normochromic anemia, but sometimes hypochromic microcytic
• Erythropoietin (EPO) levels: Inappropriately low
• Bone marrow examination for iron stores
– There are normal or increased levels of stainable iron (Prussian blue stain).

Question 33

Serum iron studies:ACD

Answer 33

Ferritin : normal/increased
Serum iron : reduced
Transferrin saturation: normal
TIBC : reduced

Question 34

Aplastic Anemia

Answer 34

-Is a disorder characterized by a defect in the multipotent hematopoietic stem cells (HSCs) leading to bone marrow failure and pancytopenia

Question 35

Causes of aplastic anemia

Answer 35

1) genetic causes / idiopathic
2) acquired : drugs (dose related or Idiosyncratic e.g. chloramphenicol, chlorpromazine, phenytoin) /irradiation / viral infections /

Question 36

Clinical features of Aplastic Anemia:

Answer 36

• Recurrent infections
– due to Leukopenia
• Mucosal hemorrhage or menorrhagia
– due to thrombocytopenia
• Characteristically No Organomegaly

Question 37

Aplastic anemia general investigations

Answer 37

Pancytopenia (↓Hb, WBC, platelet)
PB: Normocytic hypochromic
Low reticulocytes count BM: Hypocellular( only fat cells, few lymphocytes, plasma cell