Prof.

Dr Mohamed Hamdy

Anemia
BY
Prof.Dr/Mohamed Hamdy
professor of internal medicine and Hematology
Ain Shams university

Prof.Dr Mohamed Hamdy

 Prof.Dr Mohamed Hamdy
Objectives of the lecture
At the end of the lecture the student should be
able to :
• Define anemia
• Describe common clinical picture of anemia.
• Understand how to recognize pallor (to be applied in clinical sessions).
• List the RBC indices and how to calculate them and their impotence.
• Classify anemia according to MCV.
• List the causes of iron deficiency anemia
• Order the investigation for cases of anemia in general and in iron deficiency anemia
• Describe the treatment lines for iron deficiency anemia
• Compare Iron deficiency anemia with other causes of microcytic anemia
• Define Macrocytic anemia and list different causes
• Describe causes, clinical picture ,investigation ,and treatment for folic acid deficiency
• Describe causes, clinical picture ,investigation ,and treatment for vitamin B12 deficiency
• Define pernicious anemia as a special kind of B12 deficiency anemia
• Describe causes, clinical picture ,investigation ,and treatment for aplastic anemia

Prof.Dr Mohamed Hamdy

 Prof.Dr Mohamed Hamdy

Roadmap
• Different anemia can come at different ages , different sex association ,
with symptoms and signs or with routine CBC in asymptomatic patient.
• Anemias are 2 categories (hypoproliferative or hyperproliferative)
• Anemia are 3 categories according to RBC size (micro-Macro-normo/cytic)
• How to make studying anemia easy
• general S/s of anemia
• General investigation for groups of anemia
• Special S/S of each anemia
• Special investigation for subtypes of anemia
• Treatment is easy
• Treat the cause e.g iron in IDA
• Blood transfusion if failed

Prof.Dr Mohamed Hamdy

 Prof.Dr Mohamed Hamdy

Definition and general causes:

Definition(remember anemia is a laboratory diagnosis)
• low hemoglobin (Hb) concentration due either to a low red cell mass or increased plasma
volume.(the later is not true anaemia)
• A low Hb is <13.5g/dL for men and <11.5g/dL for women.

Causes
• Reduced production of RBCS .(hypo…)
• Increased destruction/loss of RBCS.(hyper….)

These will often be distinguishable by history, examination, and inspection of the blood film.

Prof.Dr Mohamed Hamdy

 Prof.Dr Mohamed Hamdy

Clinical picture
Symptoms: Signs:
1. General symptoms of any anemia : 1. General signs of any anemia:
• fatigue • pallor (not a reliable sign).
• palpitations • hyper dynamic circulation (compensatory).
• angina if has CAD. • Tachycardia.
• dyspnea • ejection-systolic murmur over apex and
• headache, tinnitus ,faintness. aortic valve.
• cardiac enlargement and later, heart
• anorexia. failure.(high COP HF)

• retinal hemorrhage (rarely) .

2-symptoms specific to the etiology 2-Signs specific to the etiology

and subtype of anemia. and subtype of anemia.
Prof.Dr Mohamed Hamdy
 Prof.Dr Mohamed Hamdy

Conjunctival pallor, the classic sign of anemia

Prof.Dr Mohamed Hamdy

 Prof.Dr Mohamed Hamdy

CBC and anemia , RBC indices

• Hematocrit(HCT) measures the proportion of whole blood volume that
consists of packed red blood cells.
• Mean corpuscular volume (MCV) is a measurement of the average size of
red blood cells =HCT/No of RBC= normal 90 FL
• Mean corpuscular hemoglobin (MCH) is the average amount of
hemoglobin inside each red blood cell=Hgb/no of RBC=30 Pg
• Mean corpuscular hemoglobin concentration (MCHC) is a calculated
measurement of how concentrated hemoglobin is within red blood cells.
• Red cell distribution width (RDW) is a measurement of the variation in the
size of your red blood cells.

Prof.Dr Mohamed Hamdy

 Prof.Dr Mohamed Hamdy
Types of Anemia(many many many classifications)
Classification according to the mean cell volume (MCV). (Normal MCV is 76–96 FL / single RBC)

I- Low MCV (microcytic): • III- High MCV (macrocytic):

1. Iron-deficiency anemia (IDA). 1. B12 or folate deficiency
2. Thalassemia .
2. Alcohol excess
3. Sideroblastic anemia.
3. liver disease.
II- Normal MCV (normocytic): 4. Reticulocytosis (e.g. with hemolysis).
1. Acute blood loss. 5. Drugs: antifolate (e.g phenytoin) ,
2. Anemia of chronic disease (or decrease Cytotoxic, (e.g. hydroxycarbamide).
MCV). 6. Myelodysplastic syndromes or Marrow
3. Bone marrow failure. infiltration.
4. Renal failure.
5. Pregnancy. IV-(Normal or increase MCV).
Hypothyroidism
Hemolysis
Prof.Dr Mohamed Hamdy
 Prof.Dr Mohamed Hamdy

Iron Deficiency Anaemia (IDA) (microcytic)

• Causes:
1. Blood loss (the most common cause), e.g. menorrhagia or
gastrointestinal (GI) bleeding. In the tropics, hookworm
(GI blood loss) is a common cause.
2. Decrease intake may cause IDA in babies or children (but
rarely in adults).
3. Malabsorption (e.g. coeliac disease) is a cause of
refractory IDA.
4. Increase demand e.g. infancy, adolescence, pregnancy and
lactation.
Prof.Dr Mohamed Hamdy
 Prof.Dr Mohamed Hamdy

Iron Deficiency Anaemia (IDA) (microcytic)

• Symptoms:
1. General Symptoms of anemia and symptoms of the cause
of iron deficiency
2. Symptoms of the iron deficiency (dysphagia, pica, loss of
concentration)
• Signs:
1. Koilonychia
2. atrophic glossitis, angular cheilosis
3. rarely, post-cricoid webs (Plummer–Vinson syndrome).

Prof.Dr Mohamed Hamdy

 Prof.Dr Mohamed Hamdy

Koilonychia: spoon-shaped nails angular cheilosis: (=stomatitis):=ulceration at the side of the mouth.
Also a feature of vitamin B12 and B2 (riboflavin) deficiency, and glucagonoma

Atrophic glossitis: red glazed tongue

esophageal web : Plummer Vinson Prof.Dr
syndromeMohamed Hamdy
 Prof.Dr Mohamed Hamdy

Iron Deficiency Anemia (investigation)

Investigations for any microcytic:
1. CBC: Decrease (MCV, MCH, and MCHC).
2. Blood film: microcytic, hypochromic anemia with
anisocytosis and poikilocytosis.
3. iron study :Decrease serum ferritin, decrease serum
iron with increase total iron binding capacity (TIBC).
4. stool microscopy for ova if relevant travel history.
5. Gastroscopy and colonoscopy, especially in elderly
males.

Prof.Dr Mohamed Hamdy

 Prof.Dr Mohamed Hamdy

Iron Deficiency Anemia (treatment by oral iron)

• Treatment plan: Oral iron, e.g. ferrous sulfate 200mg.
• Treat the cause and correct anemia.
• Replenish the stores >>elevate ferritin level.
• Prophylaxis during illness and pregnancy.
Side effects:
nausea, abdominal discomfort, diarrhoea or constipation, black stools.
Follow up
Hb should rise by 1g/dL/week, with a modest reticulocytosis.
Continue for at least 3 months after Hb normalizes to replenish stores.
IV iron indication
oral route is impossible or ineffective.
inadequate mobilization of iron stores in response to erythropoietin therapy.(renal failure)
Prof.Dr Mohamed Hamdy
 Prof.Dr Mohamed Hamdy

Sideroblastic Anemia (microcytic)

Is a type of microcytic anemia not responding to iron.
This condition is characterized by ineffective erythropoiesis, leading to
increased iron absorption, iron loading in marrow ± hemosiderosis.
Causes:
• Congenital (rare, x-linked)
• 2nd to myelodysplastic/myeloproliferative diseases.
• Iatrogenic: chemotherapy, anti-TB drugs, irradiation, alcohol or lead excess.
Investigations:
Serum ferritin : increased
CBC: microcytic hypochromic anemia
Treatment:
1. Remove the cause.
2. Pyridoxine
3. Repeated transfusion in severe anaemia
Prof.Dr Mohamed Hamdy
 Prof.Dr Mohamed Hamdy

Anaemia of chronic disease (normocytic or microcytic)

Causes:
chronic infection, vasculitis, rheumatoid, malignancy, renal failure.
Investigations:
Ferritin normal or increased.
Check blood film, B12, folate, TSH, and tests for hemolysis.
Treatment:
1. Treating the underlying disease.
2. Erythropoietin may be helpful. Also effective in improving quality of
life in malignant disease.
3. IV iron can safely overcome the functional iron deficiency.

Prof.Dr Mohamed Hamdy

 Prof.Dr Mohamed Hamdy

(macrocytic anemia)

Prof.Dr Mohamed Hamdy

 Prof.Dr Mohamed Hamdy

Macrocytic Anaemia
Macrocytosis (MCV >96fL) is common, and may not always be accompanied by
anemia (e.g. in alcohol excess).
megaloblast :is a cell with delayed nuclear maturation with normal plasma maturation
Causes of Macrocytosis (MCV >96fL) :
• Megaloblastic: (blood film shows megaloblast)
• B12 and folate deficiency: both are required for DNA synthesis.
• cytotoxic drugs.
• Non-megaloblastic: (blood film shows no megaloblast)
• Alcohol excess.
• reticulocytotic (e.g. in hemolysis)
• liver disease, hypothyroidism, pregnancy.
• hematological disease: Myelodysplasia, myeloma, myeloproliferative disorders, aplastic
anemia.

Prof.Dr Mohamed Hamdy

 Prof.Dr Mohamed Hamdy
Macrocytic Anemia (Investigations)
• 1. Blood film:
• Hypersegmented neutrophils in B12 and folate deficiency.
• Target cells if liver disease.
• 2. serum B12, and serum folate B12 and folate deficiency
• red cell folate—a more reliable indicator result in similar blood
• serum folate only reflects recent intake). film and bone marrow
• 3. Other tests: biopsy appearances
• Liver function tests, thyroid function tests.
• 4. Bone marrow biopsy is indicated if the cause is not revealed by the above
tests. It is likely to show one of the following four states:
• A. Megaloblastic marrow.
• B. Normoblastic marrow (e.g. in liver disease, hypothyroidism).
• C. Abnormal erythropoiesis (e.g. sideroblastic anaemia, leukaemia, aplasia).
• D. Increased erythropoiesis (eg haemolysis).
Prof.Dr Mohamed Hamdy
 Prof.Dr Mohamed Hamdy

Normal vs Hypersegmented neutrophils

Hypersegmented neutrophils
• have 6 or more nuclear lobes.
• typically seen in megaloblastic anemia due to vitamin B12 or folic acid deficiency,
• may also be present in myelodysplastic syndromes and rare congenital conditions.
Prof.Dr Mohamed Hamdy
 Prof.Dr Mohamed Hamdy

Folate Deficiency
• Folate is found in green vegetables, nuts, yeast, and liver; it is synthesized by gut bacteria
and absorbed by duodenum/proximal jejunum.
• Body stores can last for 4 months.
• Maternal folate deficiency causes fetal neural tube defects..
• Causes of folate deficiency:
• Poor diet, e.g. poverty, alcoholics, elderly.
• Malabsorption, e.g. coeliac disease, tropical sprue.
• Increased demand, e.g. pregnancy
• increased cell turnover (haemolysis, malignancy, inflammatory disease, and renal dialysis).
• Alcohol.
• Drugs: anti-epileptics (phenytoin, valproate), methotrexate, trimethoprim.

Prof.Dr Mohamed Hamdy

 Prof.Dr Mohamed Hamdy

Folate Deficiency (Treatment)

• treatment of underlying cause, e.g. poor diet, malabsorption.
• Oral folic acid
• 5mg/day for 4 months
• never without B12 as in low B12 states it may precipitate, or
worsen, subacute combined degeneration of the cord.
• In pregnancy, prophylactic doses of folate (400mcg/day) are given
from conception until at least 12wks; this helps prevent spina
bifida, as well as anemia.

Prof.Dr Mohamed Hamdy

 Prof.Dr Mohamed Hamdy

B12 Deficiency and Pernicious Anemia

• B12 is found in meat and dairy products (not in plants). Body stores are sufficient for 4 years.
• intrinsic factor (IF) in the stomach binds B12, enabling it to be absorbed in the terminal ileum.
• Vitamin B12 deficiency may occur in 15% of older people.
• B12 helps synthesize thymidine of DNA, in deficiency RBC production is slow.
• Causes of B12 deficiency:
• Dietary :(e.g. vegans)
• Malabsorption:
• stomach disease →lack of IF (pernicious anemia, post gastrectomy).
• terminal ileum disease → (ileal resection, Crohn’s disease, bacterial overgrowth, tropical
sprue, tapeworms).
• Congenital metabolic errors.
• Gerneral symptoms and signs of anaemia
• Pallor , glossitis (beefy-red sore tongue), Angular cheilosis.
• Lemon tinge sclera: due to combination of pallor (anaemia) and mild jaundice (due to
haemolysis).
Prof.Dr Mohamed Hamdy
 Prof.Dr Mohamed Hamdy

B12 Deficiency (neurological features)

• Neuropsychiatric: Irritability, depression, psychosis, dementia.
• Neurological: subacute combined degeneration of the spinal
cord
• The onset is insidious (subacute) and signs are symmetrical.
(can occur without anemia)
• posterior (dorsal) column loss→ peripheral sensory neuropathy
• Paresthesia ,loss of joint position , loss of vibration and sensory
ataxia
• posterior (dorsal) column loss→ lower motor neuron signs
(occurs early)
• Weakness and absent both knee and ankle jerks (LMN).
• corticospinal tract loss →upper motor neuron signs
(occurs late if untreated)
• Stiffness and weakness , extensor plantars (UMN)
• The spinothalamic tracts are preserved
• pain and temperature sensation may remain intact even if severe.
Prof.Dr Mohamed Hamdy
 Prof.Dr Mohamed Hamdy

• The big, beefy tongue of B12 deficiency glossitis.

• Other causes of glossitis: iron (or Zn) deficiency, pellagra, contact dermatitis/specific food intolerances,
Crohn’s disease, drugs (minocycline, clarithromycin, some ACE-i), TB of the tongue.
• Glossitis may be the presenting feature of coeliac disease or alcoholism.

Prof.Dr Mohamed Hamdy

 Prof.Dr Mohamed Hamdy
Pernicious Anaemia(megaloblastic)
• autoimmune condition →atrophic gastritis → decreased IF secretion from the stomach parietal cells.
• Dietary B12 therefore remains unbound and cannot be absorbed by the terminal ileum.
• Incidence:
• 1:1000; Female:Male≈1.6:1; usually >40yrs; higher incidence if blood group A.
• Associations:
• autoimmune diseases: thyroid disease vitiligo, Addison’s disease, hypoparathyroidism.
• Carcinoma of stomach → upper GI endoscopy.
• Investigations:
1. CBC: decreased Hb, increased MCV, leucopenia and thrombocytopenia if severe, reticulocytes may be
decreased
2. Blood film: hypersegmented neutrophils.
3. serum B12. Decreased
4. Bone marrow : megaloblasts.
5. Specific tests for pernicious anemia:
• Parietal cell antibodies: found in 90% with pernicious anemia, but also in 3–10% without.
• Intrinsic factor antibodies: specific for pernicious anaemia, but lower sensitivity.
• Shilling test : no longer done
Prof.Dr Mohamed Hamdy
 Prof.Dr Mohamed Hamdy

Treatment of B12 Deficiency

1.Treat the cause if possible.
2. If due to malabsorption, give hydroxocobalamin (B12) 1mg IM
alternate days for 2wks then 1mg IM every 3 months for life.
3. If the cause is dietary, then oral B12 can be given after the initial IM
course (50–150mcg/daily, between meals).
• N.B. Improvement is indicated by a transient marked reticulocytosis
after 4–5 days.
• Prognosis:
Supplementation usually improves peripheral neuropathy within the first
3–6 months, but has little effect on cord signs. Patients do best if treated
as soon as possible after the onset of symptoms.
Prof.Dr Mohamed Hamdy
 Prof.Dr Mohamed Hamdy
Aplastic anemia
• Definition:
• Pancytopenia with marrow hypocellularity (Aplasia) of bone marrow.
• Severe aplastic anemia is a life threatening syndrome .
• Etiology:
• Inherited: fanconi anemia
• Acquired: more common
• Idiopathic:65%
• Drugs: Cytotoxics ,anticonvulsant ,sulphonamides and chloramphenicol.
• Radiation.
• Chemicals e.g: Benzene and pesticides.
• Viruses: Hepatitis A , Herpes simplex , EBV, Parvovirus.
• Immune: SLE, RA.

Prof.Dr Mohamed Hamdy

 Prof.Dr Mohamed Hamdy
Aplastic anemia(cont.)
• Clinical Features:
• Low RBC(Anemia):fatigue, shortness of breath , chest pain , dizziness, pallor.
• Low WBC(Leukopenia): fever, infections, flu- like illness.
• Low platelets(thrombocytopenia):red spots , prolonged bleeding , easy bruising.
• Hematological finding:
• Pancytopenia WBC ˂ 2.0,Hb˂ 10, plt.˂100 .
• BM biopsy : hypocellular, increased fat spaces.
• Treatment
• Withdrawal of etiological agents.
• Supportive.
• Restoration of marrow activity:
• Bone marrow transplant.
• Immunosuppressive treatment.
• Androgen.
• Growth factors.
Prof.Dr Mohamed Hamdy
 Prof.Dr Mohamed Hamdy
Symptoms of Anemia

Normal or High Hemoglobin/Hematocrit

Check other
Causes of symptoms
e.g. Cardiac Low
RBC indices
Pulmonary

MCV < 80 MCV=80-96 MCV > 98

MCHC < 32

History of acute blood loss B12 and folate levels

Serum iron and Total Auto immune Hemolytic anemia
Iron binding capacity Anemia of chronic Diseases
of Ferritin Anemia of infection

Low Iron Normal High Iron Low B12 Low folate High or Normal

IDA, chronic Hb BM exam PA, GI Folate MPD

diseases, Renal electrophoresis For problems malnutrition Liver Disease
diseases for Thala. Sideroblastic Severe GI problems
anemia malnutrition. Liver
Prof.Dr Mohamed Hamdy disease