ANEMIA 2

Almajd alyazidi
Omcm-15-143
SESSION LEARNING
OUTCOMES
▪ Define and classify anemia
▪ Detect the signs of anemia
▪ Identify the differential diagnosis of microcytic anemia
▪ Identify the differential diagnosis of macrocytic anemia
▪ Identify the differential of hemolytic anemia
▪ Construct a management plan of anemia
CONTENTS
▪ Macrocytic Anemia
▪ Megaloblastic anemia(B12, folate)
▪ Non-megaloblastic anemia- Alcohol, liver disease, hypothyroidism
▪ Normocytic Anemia
▪ Hemolytic Anemia (Spherocytosis, G6PD, Sickle Cell Anemia)
▪ Anemia of chronic disease- malignancy, RA, TB, vasculitis, DM, CRF
▪ Aplastic Anemia
SESSION LEARNING
OBJECTIVE
▪ Understand the pathogenesis of Macrocytic anemia (B12, folate)
▪ Understand the cause of macrocytic anemia and how to recognize it’s symptoms
▪ Plan a management for a patient with macrocytic anemia considering it’s underlaying cause
▪ Understand the pathogenesis of normocytic anemia (Hemolytic anemia ,Aplastic)
▪ Understand the cause of normocytic anemia and how to recognize it’s symptoms and histological
differences.
▪ Plan a management for a patient with normocytic anemia
▪ understand the different types of Hemolytic anemia (spherocytosis, G6DP,Sickle cell anemia)and
their histological, and managemental differences.
▪ Aplastic anemia; the pathogenesis ,causes, and management.
MACROCYTIC ANEMIA
▪ Low Hb
▪ MCV >100fL

▪ Macrocytic Anemia
▪ Megaloblastic anemia- B12, folate
▪ Non-megaloblastic anemia- Alcohol, liver disease, hypothyroidism
 MEGALOBLASTIC ANEMIA

▪ Vitamin B12 and folate both required for DNA synthesis, and their deficiency or impaired
metabolism leads to inadequate biosynthesis of thymidine one of the building blocks of
DNA .
▪ -So the end result is cells with arrested nuclear maturation but normal cytoplasmic
development.
▪ Nuclear maturation is delayed (lags behind Hb synthesis) and as this takes long time, more
Hb will be synthesized causing enlargement of the resultant cell.
MACROCYTIC ANEMIA
▪ Macrocytic anemia is type of anemia in which the Mean corpuscular (Cell) Volume is higher
than 96 femtoliter
▪ (78-96) is the normal range of MCV

▪ Causes of Macrocytic anemia

▪ Megaloblastic : B12 deficiency , Folate deficiency

▪ Non-Megaloblastic : : Alcohol excess, liver disease, hypothyroidism,

 VITAMIN B12
(COBALAMIN)
DEFICIENCY
▪ B12 helps synthesize thymidine, and hence DNA.
▪ Sources:
▪ Liver, kidney, fish, chicken, meats, and dairy products
▪ Absorption takes place by active and passive mechanisms—the
latter being dependent on intrinsic factor, a protein produced by
gastric parietal cells
▪ Body stores of B12 are sufficient for 4yrs.
CAUSES OF B12 DEFICIENCY
▪ Causes
▪ Inadequate dietary intake—e.g. vegans
▪ Malabsorption—coeliac disease, crohns disease
▪ Autoimmune- pernicious anaemia
▪ Drugs—metformin; drugs causing achlorhydria, e.g. PPIs, H2 antagonists
▪ Surgery:; gastrectomy, ileal resection)
PRESENTATION
▪ Incidental finding of macrocytosis
▪ Sore mouth (glossitis, mouth ulcers)
▪ Neuropsychiatric problems
▪ Investigation- CBC, PS, s/B12 and specific ………….
B12 DEFICIENCY SYMPTOMS
 PERNICIOUS ANEMIA
▪ This is an autoimmune condition in which atrophic gastritis leads to a lack of IF secretion from
the parietal cells of the stomach. Dietary B12 therefore remains unbound and consequently
cannot be absorbed by the terminal ileum.
▪ Tests
▪ Parietal cell antibodies: found in 90% with PA
▪ Intrinsic factors IF antibodies: specific for PA,
but have lower sensitivity.
INVESTIGATION
▪ Blood films (peripheral blood smear)
▪ Hyper segmented neutrophils, and microcytes appear under microscope.

▪ LFT :(include gamma GT), TFT, serum B12, and serum folate (or red cell folate—a more
reliable indicator of folate status, as serum folate only reflects recent intake).
▪ Bone marrow biopsy
B12 DEFICIENCY
MANAGEMENTS
▪ Dietary cause: then oral B12 can be given after the initial IM course
(50–150mcg/daily, between meals).
▪ Malabsorption :Give hydroxocobalamin (B12) 1mg IM alternate days for 2wks (or,
if CNS signs, until improvement stops), then 1mg IM every 3 months for life.
▪ Improvement is indicated by a transient marked reticulocytotic after 4–5 days.
▪ Confirm response by repeating Full Blood count (FBC) after 8wk.
FOLATE DEFICIENCY
▪ Body stores can last for 4 months.
▪ General Symptoms of anemia, smooth red
tongue.
▪ Maternal folate deficiency causes fetal
neural tube defects
 FOLATE (VITAMIN B9)
DEFICIENCY
▪ Source:
▪ Highest concentrations in liver and yeast but is also in spinach, other green vegetables, and
nuts.
▪ Presentation:
▪ Incidental finding of macrocytosis
▪ Symptoms and signs of anaemia
▪ Always check serum B12 as deficiencies may coexist
FOLATE DEFICIENCY
▪ Causes
▪ Intake; Poor diet: ( poverty, alcoholics, elderly, Alcohol).
▪ Increased demand: (pregnancy or increase cell turnover in hemolysis, malignancy, inflammatory
disease, and renal dialysis).
▪ Malabsorption, (coeliac disease, tropical sprue).
▪ Drugs: anti-epileptics (phenytoin, valproate), methotrexate, trimethoprim
FOLATE DEFICIENCY
MANAGEMENT
▪ Treat underlaying cause.
▪ folic acid 5mg/day PO for 4 months.
▪ Treat for B12 unless the patient is known to have a normal B12 levels.
▪ folic acid 5mg/24h PO in unwell patient (e.g. congestive cardiac failure)
▪ In pregnancy, prophylactic doses of folate (400mcg/day) are given.
NORMOCYTIC ANEMIA

▪ Normocytic Anemia

▪ Hemolytic Anemia (Spherocytosis, G6PD, Sickle Cell Anemia)

▪ Anemia of chronic disease- malignancy, RA, TB, vasculitis, DM, CRF
▪ Aplastic Anemia
NORMOCYTIC ANEMIA
▪ In normocytic anemia the MCV value is (78-96) fL
▪ In can be differentiated into different types depending on it’s reticulocytes count
▪ High Reticulocytes
▪ Hemolytic anemias.
▪ Blood loss
▪ Low reticulocytes
▪ Pancytopenia
▪ Anemia of chronic illness
HEMOLYTIC ANAEMIA
▪ Normal red cells survive 120d
▪ In haemolytic anaemia red cells are destroyed faster than they are produced
▪ Presentation:
▪ May have FH
▪ Dark urine, Jaundice, high unconjugated bilirubin
▪ FBC: ↓ Hb; ↑ reticulocytes
▪ Film shows:
▪ Polychromasia
▪ ± abnormal-shaped cells (e.g. schistocytes)

▪ Can be exacerbated by intercurrent illness, e.g. aplastic crisis with parvovirus

HEREDITARY SPHEROCYTOSIS
▪ Hereditary spherocytosis is an autosomal dominant membranopathy of the RBC causing them
to lose their natural concave shape leading them to get stuck in vessels which leads to the rapid
removal from circulation through extravascular hemolysis.
▪ prevalence: 1:3000
▪ Signs: Splenomegaly, jaundice.
▪ Tests:
▪ Coombs test
▪ Mild if Hb >110g/L and reticulocytes

6%; film, . Increase in Bilirubin (higher chance

of gallstones).
HEREDITARY SPHEROCYTOSIS
CAUSE
▪ caused by genetic changes in five different genes;
▪ Causing the cell to lose it’s shape making easier to get trapped (in spleen sinus capillaries) thus
leading to it’s destruction.
HEREDITARY SPHEROCYTOSIS
MANAGEMENT
▪ Folic acid prophylaxis, 5 mg daily, life long
▪ In severe cases consider splenectomy, which improves but does not normalise red cell
longevity
▪ Potential indications for splenectomy include:
• Moderate to severe haemolysis with complications (anaemia and gallstones)

▪ Acute, severe haemolytic crises  blood transfusion

GLUCOSE-6-PHOSPHATE
DEHYDROGENASE DEFICIENCY
▪ G6PD deficiency is an X-linked. the chief RBC enzyme defect.
▪ affects 100 million (mainly males) in Mediterranean, Africa, Middle/Far East.
▪ Most are asymptomatic, but may get oxidative crises due to decrease in glutathione production.

▪ Free radicals which are not regulated by

glutathione damage hemoglobin which
cause it to attach to the inner border of the
RBC forming the Heinz bodies and
reducing the flexibility of the cells.
 GLUCOSE-6-PHOSPHATE
DEHYDROGENASE DEFICIENCY
▪ precipitated by drugs (e.g. primaquine,
sulfonamides, aspirin),.
▪ exposure to Vicia faba (broad beans/favism).
GLUCOSE-6-PHOSPHATE DEHYDROGENASE
DEFICIENCY INVESTIGATION AND
MANAGEMENT
▪ Tests:
▪ Film: bite- and blister-cells
▪ Enzyme assay (>8wks after crisis as young RBCs may have enough enzyme so results normal).

▪ Managements
▪ Avoid precipitants (e.g. henna)
▪ treat any underlying infection
▪ transfuse if severe attacks
SICKLE CELL ANEMIA
▪ Sickle-cell anemia is an autosomal recessive disorder in which production of abnormal
hemoglobin results in Vaso-occlusive crises.
▪ It is most commonly seen in people of African origin, and arises from an amino acid
substitution in the gene coding for the Beta chain;
▪ Glu change into Val at position 6, which leads to production of HbS rather than HbA
▪ (HbA2 and HbF are still produced).

▪ Homozygotes (SS) have sickle-cell anemia (HbSS), and hetero zygotes (HbAS) have sickle-
cell trait, which causes no disability (and protects from falciparum malaria). Heterozygotes may
still, however, experience symptomatic sickling in hypoxia,( e.g. in unpressurized aircraft or
anesthesia).
SICKLE CELL ANEMIA
PATHOGENESIS
▪ HbS polymerizes when deoxygenated, causing RBCS to deform, producing sickle cells, which
are fragile and hemolyze, and also block small vessels.
SICKLE CELL ANEMIA
PATHOGENESIS
SICKLE CELL ANEMIA
INVESTIGATIONS
▪ Patients with HBS usually show the following in investigations
▪ Hemolysis is variable. Hb ≈ 60–90g/L.
▪ Increase in reticulocytes 10–20%.
▪ Increase in bilirubin.

▪ In films it shows ▪ Features of hyposplenism(decrease spleen function)

from a young age.
▪ Spot sickling test- HbS can be demonstrated by
exposing red cells to a reducing agent such as
sodium dithionite;
▪ Haemoglobin electrophoresis is the definitive
diagnosis
CLINICAL FEATURES
▪ Irreversibly sickled cells have a shortened survival and plug vessels in the microcirculation
▪ This results in a number of acute syndromes, termed ‘crises’, and chronic organ damage:

1 Painful vaso-occlusive crisis:

▪ Plugging of small vessels in the bone produces acute severe bone pain
▪ This affects areas of active marrow:
▪ Children: the hands and feet (so-called dactylitis)
▪ Adults: the femora, humeri, ribs, pelvis and vertebrae
▪ Patients usually have a systemic response with tachycardia, sweating and a fever
2 Sequestration crisis:
▪ Thrombosis of the venous outflow from an organ causes loss of function and acute painful enlargement
▪ In children  spleen
▪ Massive splenic enlargement  severe anaemia  circulatory collapse and death
▪ Recurrent sickling in the spleen in childhood  infarction and adults may have no functional spleen
▪ In adults, the liver may undergo sequestration with severe pain due to capsular stretching
▪ Priapism is a complication seen in affected men

3 Aplastic crisis:
▪ Infection of adult sicklers with human parvovirus B19  severe but self-limiting red cell aplasia  profound anaemia 
heart failure
▪ Reticulocyte count is low

4 Acute Chest Syndrome- chest pain SOB

SICKLE CELL ANEMIA
MANAGEMENT
▪ Patients should be managed by a hematologist, aiming to prevent crises and treat complications
early.
▪ GPs should:
▪ Treat patients as if hyposplenic—give Hib, meningitis C, pneumococcal + annual influenza vaccination ±
prophylactic antibiotics
▪ Advise patients to avoid cold and maintain adequate hydration;
▪ warn about the dangers of anesthetics.
▪ Treat infection early—be alert for aplastic crisis following parvovirus.
▪ Give analgesia for painful crises (including opioids if needed, but avoid pethidine as may cause cerebral
irritation/ fits)– admit if severe
▪ Admit if significant crisis of any sort (e.g. stroke, dyspnea, acute abdomen, aplastic anemia)
▪ Refer for early management of long-term complications (e.g. renal failure, epilepsy)
SICKLE CELL ANEMIA
MANAGEMENT
▪ Hydroxycarbamide if frequent crises (increase production of fetal hemoglobin, HbF). Dose
example: 20mg/kg/d if eGFR >60mL/min.
▪ Splenic infarction prophylaxis, in terms of antibiotics and immunization, should be given.
▪ Febrile children risk septicemia: repeated admission may be avoided by early rescue out-patient
antibiotics, e.g. ceftriaxone (e.g. 2 doses, 50mg/kg IV on day 0 and 1).
▪ Consider admission if Hb 30 ≈ 109 /L, T° >40°C, severe pain, dehydration, lung infiltration.
Seek expert advice.
▪ Bone marrow transplant can be curative but remains controversial.
▪ Prevention through Genetic counselling and prenatal tests.
APLASTIC ANEMIA
▪ Is a disorder in which the bone marrow stop producing cells ,This is a rare (~5 cases per million/year)
stem cell disorder that leads to pancytopenia.
▪ Myeloid stem cells destruction which are the precursor to RBC,WBC and platelets
▪ Presents with features of anemia as well as;
▪ Decreased Hb
▪ Recurrent infection
▪ Decreased WCC
▪ Bleeding due to decreased platelets clotting (petechiae/bruising)
▪ Lack of reticulocytes
▪ Causes: Most cases are autoimmune, triggered by drugs,(chloramphenicol, benzenes, streptomycin)
viruses (e.g. parvovirus, hepatitis, Epstein Barr virus), or irradiation. May also be inherited, (e.g. Fanconi
anemia/syndrome)
▪ Tests: Bone marrow biopsy is diagnostic. Treatment: Mainly supportive in asymptomatic patients.
Transfuse blood
APLASTIC ANEMIA
MANAGEMENT
▪ Supportive :
▪ immunosuppression with ciclosporin and antithymocyte globulin
▪ Transfusions.

▪ Definitive :
▪ The treatment of choice in young patients with severe disease is
allogeneic marrow transplantation from an HLA-matched.
CASES
▪ A 35 year old male with fatigue, light headedness, paraesthesia in his hands and feet. And he
have history of Crohn disease and ileocecal resection. Vitals are normal, the patient is pale and
you notice that his tongue is big and beefy. Lab investigation shows : Hb of 9.8/dl and MCV of
106.

▪ What is the most likely diagnosis?

▪ What is the most likely cause of the anemia in this patient?
▪ The management/treatment of such case?
CASES
▪ Which of the following is not a normocytic anaemia?

A. Sickle cell anemia

B. Aplastic anemia
C. Hereditary Spherocytosis
D. G6PD
E. All of the above
F. None of the above
CASES
▪ Identify the type of anemia.

A B C
 Low Hb
TAILS:
-T: Thalassemia. Megaloblastic:
-Folate deficiency.
-A: Anemia of chronic
-B12 deficiency.
diseases (1/3 of cases).
-I: Iron deficiency. Non-Megaloblastic:
MCV -Liver diseases,
-L: Lead poisoning.
-Alcoholism,
-S: Sidroblastic
- Hypothyroidism.
Anemia.
Low (<78) Normal (78-96) High (>96)

Microcytic Anemia Normocytic Anemia Macrocytic Anemia

High Reticulocytes Low

No
Hemolysis Blood Loss Pancytopenia
Pancytopenia
Hemolytic anemia GI, GU,… Aplastic anemia Anemia of chronic
diseases
REFERENCES
▪ Oxford handbook of general practice 5th edition
▪ Oxford handbook of clinical medicine 10th edition
▪ https://www.researchgate.net

▪ Videos
▪ https://www.youtube.com/watch?v=mOrRJBqm744&ab_channel=NinjaNerd
▪ https://www.youtube.com/watch?v=XZZuksIDkCw&ab_channel=daf189