ANEMIA
2021-2022
Professor Doctor
Ahmed K Yassin Elmeshhedany
Internist & Clinical Hematologist
MBChB , DM, CABM,
FIBMS(Clinical Hematology.)
FRCP(London)
Hawler Medical University
College of Medicine
Department of Medicine
Objectives
• What is pallor
• Etiology
• Assessing seriousness
• Managements
• Paleness (pallor in Latin) is abnormal loss of
color from normal skin or mucous
membranes due to reduced amount of the
blood in the skin arteries.
• Note: Due to issues in the blood or the
vessels (e.g., vasoconstriction)
Paleness should be distinguished from
other causes of prominent white skin:
• Fair skin.
• Myxedema
• Albinism
• Vitiligo
Paleness does not always mean you
are ill.
• Low environmental temperature
• Skipped meal
• Dehydration
• Exertion or fear
Sudden pallness caused by many
medical conditions
• Motion sickness
• Orthostatic hypotension
• Fainting (vasovagal syncope)
• Dehydration
• Stomach upset
• Acute infection (usually with fever)
•
•
•
•
•
•
Allergy to drugs
Rapid stomach emptying (dumping syndrome)
Migraine
Heat stroke
Hypothermia
Heart failure due to heart attack, arrhythmia, infective
endocarditis or other heart disorder, when the heart can not
efficiently pump the blood into the circulation
• Low blood sugar (hypoglycemia), common in insulindependent diabetics after an exercise, skipped meal or insulin
overdose
• Blood loss due to external or internal bleeding (in car
accidents, shooting or stitch injuries), heavy menstrual
bleeding, surgery
• Shock – a sudden, deep fall of blood pressure – due to
poisoning, severe infection, burns, severe blood loss
• Side effect of medications:
– warfarin, corticosteroids, aspirin and other anti-rheumatic
drugs may cause intestinal bleeding
– iron poisoning
• Drug overdose: amphetamine (speed), cocaine
• Chemical poisoning (pesticides), plant poisoning
(Atropa belladonna)
• Death
Lecture outlines
• What is anemia
• Acute anemia, chronic anemia.
• What is effects of anemia on organs ( skin,
heart, brain, bowel, kidneys,etc)
• What is the effects of anemia on patient and
age groups ( child, adult, heart problem,
neuopsychiatric problem, etc)
Case 1
• M is 2 years old boy referred to you because
of pallor, jaundice, hepatosplenomegally
Case 2
• S is 23 years old girl with recent history of
progressive pallor,
• On history she has joint pain and fever.
• Examination showed jaundice,
hepatosplenomegally.
Case 3
• J is 65 years old male with history of
progressive exertional dyspnea
• Examination showed pallor
• No organomegally
Case 4
• S& I are 22 years old young couple planning
for marriage
• They asked your opinion as accidently the
laboratory evaluation is showing abnormal
indices.
Etiology of anemia
• Blood loss
• Underproduction
• Decrease red cell survival (note: instead of the
usual 120 days, it’s lower, and the bone
marrow cannot compensate)
• Sequestration
The most common worldwide
Pallor and chronic blood loss
(Iron deficiency anemia)
A source of blood loss should be determined. This can be
simple, such as menorrhagia, epistaxis, hemorrhoids, PUD,
etc. or very grave, e.g., malignancy of the GI tract. Hence,
these serious causes should not be missed for a simple
cause. In iron deficiency, the treatment is not an issue, but
determining the etiology is a matter of importance.
Case 1
• You received 65 years old male with
hypochromic microcytic anemia and low
serum ferritin
• Whats your DDX
• How you manage this case
• What therapy will you use, and why
Notes on case 1
• In such a case with this age, even if not anemic but
with low serum ferritin (always means iron deficiency;
A reduced ferritin is the most reliable initial marker to
diagnose iron deficiency without anemia), the first
thing you should consider is malignancy.
• Other causes may include:
• Malnutrition; with a lot of modifications made to
the diet of a person as they get older for health
concerns and teeth hygiene, iron deficiency with
malnutrition can occur.
• Malabsorption, e.g., due to PPI abuse.
Case 2
• You received 17 years old girl with
hypochromic microcytic anemia and low
serum ferritin
• Whats your DDX
• How you manage this case
• What therapy you will use, why
Prevalence of IDA:
• Iron Deficiency Anaemia is the most common
form of anaemia, with an estimated > 500
million people affected worldwide.
• It is more common in developing countries like
ours.
• It is frequently encountered in Erbil area.
Iron absorption:
• Normal mixed diet contains about 10-20 mg of iron /day. This
present in inorganic or organic forms.
• Dietary sources include: meats especially liver and kidney, egg yolk,
some green vegetables like Peas, lentil and beans. Milk has low iron
content generally.
• Usually only 5-10% of ingested iron is absorbed.
• After ingestion of iron containing foods, Iron is released from protein
complexes by acid and proteolytic enzymes in stomach and SI, and then is
maximally absorbed in duodenum and less so the (note: upper) Jejunum.
• Note: iron absorption is increased when there is iron deficiency or when
there is increased demand for iron; when the iron levels are low or there
is increased demand on iron for cellular processes, the production of
hepcidin (negative regulator of iron absorption) is decreased to allow iron
to enter the plasma to meet iron demand[1].
(note: ferric, ferrous)
Note: A careful history of diet is thus important
Note (extra): iron status and absorption
• At physiological pH, iron exists in the oxidized, ferric (Fe3+) state. To
be absorbed, iron must be in the ferrous (Fe2+) state or bound by a
protein such as heme. The low pH of gastric acid in the proximal
duodenum allows a ferric reductase enzyme, duodenal cytochrome B
(Dcytb), on the brush border of the enterocytes to convert the
insoluble ferric (Fe3+) to absorbable ferrous (Fe2+) ions
Distribution of Body Iron
Plasma (transferrin) (~0.1%)
Myoglobin
(~10%)
Storage iron
(~25%)
Hemoglobin
(~65%)
Causes of Iron Deficiency:
• Blood loss: Most common cause in developed countries; Most likely
from the gastrointestinal tract (hookworm infestation, Duodenal
ulcer, Ca stomach or colon, Crohn's, ulcerative colitis, hemorrhoids,
salicylates). In females, bleeding from genital tract is also quite
common.
• Blood loss could be from simple or very serious causes
• Nutritional: Quite common cause of Iron deficiency in developing and
underdeveloped countries, especially if inadequate intake is coupled
with increased demand (e.g., infancy and pregnancy and
adolescence).
• Inadequate absorption: Malabsorption syndromes e.g. Celiac disease.
Body Iron distribution
Hemoglobin ~65%
Blood loss
Iron Def. Anaemia.
Clinical Findings:
• Clinical features related to underlying pathology, if any.
• Early stages: no significant findings (note: They may present because
they look pale or depressed to family members)
• As anemia progresses:
1. Signs and Symptoms of anemia: Pallor, Fatigue, decrease exercise
capacity, shortness of breath.
2. Mucosal changes in severe IDA:
• Glossitis: smooth red tongue
• koilonychia
3. PICA (craving to eat unusual substances like dirt, clay, ice, salt, hair
or cardboard).
4. No Organomegaly
Glossitis
Koilonychia (Spooning of the nails)
Note: When you see a pale hand on clinical examination, your next step is
to check the nails for koilonychia, evidence of chronic liver disease, and
ask about paresthesia.
Blood Picture in IDA:
1. Hemoglobin: reduced
•
PCV: reduced.
•
MCH, MCV, MCHC all reduced.
2. Leucocytes and platelets usually normal.
3. Red cells on film: Hypochromic, microcytic.
4. Bone marrow aspirate: Non-specific changes. Depleted Iron stores on
Staining the marrow with a stain for iron (Diagnostic). (note: rarely
needed[1])
Blood Film findings in IDA:
Normochromic, normocytic
NORMAL
IDA
Hypochromic, Microcytic
Diagnosis of IDA:
1. Hematological findings
2. Serum Iron and TIBC:
• Serum Iron reduced.
• Total Iron binding capacity increased
• S. Iron/TIBC: Transferrin saturation reduced (< 15%).
3. S. Ferritin (< 15ug/L)
• Note: low serum ferritin is diagnostic of iron deficiency[1]
• Note: the most sensitive laboratory test for IDA, however, serum ferritin can be elevated
in inflammation (i.e., it’s an acute phase reactant), and so is not always a reliable test of
iron status if it is within normal limits. Thus, when obtaining a serum ferritin level, the
patient should ideally be free of any infection or disease process, which might lead to
increased inflammation or an immunological response. Therefore, a low serum ferritin is
meaningful for ID, but a normal ferritin is less meaningful and may be reflective of
inflammation[1].
4. Bone marrow Iron: as determined by Prussian blue stain for marrow Iron is
depleted. (Diagnostic).
Iron stain on marrow
Iron is represented by blue granules
Normal Marrow
Normal storage Iron
(note: diagnostic)
Iron deficient marrow
Absent storage iron
Management of IDA:
1.
Check and exclude causes of Iron deficiency especially
pathological blood loss (note: it’s VERY IMPORTANT to
determine a cause before you start treating IDA)
2.
In adults, iron deficiency equal blood loss unless proved
otherwise
3.
Oral Iron therapy: treatment of choice (note: Iron
pills can change the color of stool to a greenish
or grayish black. The patient should be warned)
4.
Parenteral Iron: is only indicated if there is
malabsorption or intolerance to oral iron (note:
parenteral iron can have serious adverse effects)
*
* e.g., continued menorrhagia, hemorrhoids, etc.
Differential diagnosis of IDA
(from other causes of hypochromic Anaemia:
1. Thalassemia: Clinical features, Iron studies, Hb
electrophoresis.
2. Sideroblastic Anaemia: Clinical features, Iron
studies, bone marrow, iron stain.
3. Lead poisoning: History, Iron studies, blood film,
urine lead.
4. Anemia of Chronic disorders: History, Iron
studies.
Anaemia of chronic disorders (note: iron
malutilization):
• A hematological syndrome that accompanies certain nonhematological diseases and is mild to moderate anemia,
variable hypochromia, and hypoferremia despite adequate iron
stores.
• Anaemia is usually normochromic normocytic, but sometimes
hypochromic.
• Severity of anemia is often related to the severity of the
underlying disease.
• Note – laboratory findings:
• MCV is normal or decreased
• Serum iron is low
• TIBC is low or normal
• Transferrin saturation is normal or decreased
• Serum ferritin is high or normal
Causes of Anemia of chronic disorders
1. Chronic infections:
- like T.B., osteomyelitis, chronic
abscess, SBE.
2. Chronic inflammatory disorders:
- like Rheumatoid arthritis, SLE, PAN, etc.
3. Non-hematological malignancy.
4. Chronic Renal failure.
Note: The treatment is to treat the underlying
condition.
CONCLUSION
• IRON DEFICIENCY IS COMMONEST TYPE OF
ANEMIA
• BLOOD LOSS MUST BE EXCLUDED
• ORAL IRON IS BEST
Pallor & jaundice
(Haemolytic anemias)
Case 1
• You are asked to see 15 years old boy with pallor and
jaundice with positive family history (i.e., congenital
disease)
• What is your DDx
• How you can diagnose HS
Note: Thalassemia major usually presents before 2
years. Hereditary spherocytosis can present at any age
from the neonatal period to the ninth decade,
depending on severity.
Case 2
• You received 4 years old boy with 1 day history
of severe pallor, jaundice and black urine
• He has no organomegally but severe
tachycardia and hypotension
• How you manage such patient
• What is your diagnosis
• Favism
Case 3
• MRs H is 35 years old lady with history of SLE
on therapy, recently she developed increasing
pallor
• What is your DDx
• Note: Could be due to autoimmune
hemolysis, menstrual bleeding, druginduced, anemia of chronic disease, etc.
• How you can confirm the diagnosis
Objectives
• What is hemolytic anemia
• Causes
• Types
• Management
Definition of Hemolytic anemia
• Note: In a healthy individual about 1% of the circulating erythrocytes are
being destroyed (removed) daily due to senescence and new blood
corpuscles are produced by bone marrow.
• Note: With decreased survival/increased destruction, the bone marrow
increases production of RBCs to compensate. The bone marrow can usually
increase RBC production 6-8 fold to keep pace with cell breakdown, thus
giving a compensated hemolytic anemia[1]. Anemia results when bone
marrow production can no longer compensate for the shortened RBC
survival; this condition is termed uncompensated hemolytic anemia.
• Anemia resulting from an increased rate of red cell destruction (decreased
red cell survival)
• Note: can be immune or nonimmune; acquired or congenital
Destruction may be predominantly:
1. Extra-vascular
2. Intra-vascular
General evidence of hemolysis:
• 1. Evidence of RBC and Hb breakdown:
- Increased unconjugated (Indirect) Bilirubin (note: may
cause jaundice)
- Increased urinary Urobilinogen.
- Increased Stool Sterecobilinogen.
- Absent Hb binding protein (Haptaglobin).
• 2. Evidence of increased red cell production:
- Reticulocytosis (An elevation in the number of
reticulocytes – immature RBCs) – blood. (healthy marrow)
(note: normal range is 0.5-1.5%)
- Erythroid hyperplasia – marrow.
General evidence of hemolysis (Cont.):
•3. Evidence of RBC Damage:
- Spherocytes, fragmented red cells.
-Special tests: red cells survival studies.
•4. If intravascular hemolysis:
- Hemoglobinuria.
- Hemoglobinaemia.
- Hemosidrinuria (if prolonged).
Classification of Hemolytic
anemia
Could be broadly classified into:
• Inherited Hemolytic anemias.
• Acquired Hemolytic anemias.
Causes of inherited Hemolytic anemia:
1. Enzymopathies:
• G6PD deficiency.
• Pyruvate kinase deficiency.
2. Membrane defect:
• Hereditary spherocytosis.
• Hereditary Ovalocytosis.
3. Haemoglobinopathies:
• Thalassaemias: quantitative Hbpathies.
• Qualitative Hbpathies: Hb S, C, D, E etc.
Inherited Hemolytic
Anemia
Due to RBC enzyme defects
1. G6PD Deficiency.
2. Pyruvate Kinase Deficiency.
3. Others (very rare).
Glucose 6 Phosphate Dehydrogenase
Deficiency
(G6PD Deficiency)
Definition of G6PD Deficiency
• Sex-linked inherited disorder (note: i.e., it usually
affects males)
• Characterized usually by acute hemolytic episodes
following exposure to oxidant stress (infection,
drugs or fava beans), due to deficiency of RBC
enzyme G6PD.
G6PD Deficiency
• More than 100 million people effected worldwide.
• Quite frequent in Iraq with 6-13% of the population
affected.
• One of the most frequent causes of acute hemolysis
in Erbil region, especially during the fava bean
season.
Favism
• Occurs on consumption
of Fava beans.
• Usually occurs within
24 hours of ingestion.
• Most frequent in spring
(March-May).
• 2/3 of cases occur in
1-6 year old children.
• Males predominate.
Clinical features of favism
• Sudden Pallor
• Jaundice.
• Red or dark urine (note: cola-colored urine)
due to Hemoglobinuria.
• Lasts usually for 2-6 days followed by
spontaneous recovery.
• No organomegaly.
Note: G6PD deficiency can cause neonatal
jaundice (i.e., present at birth)
Hemoglobinuria in favism
Note: Patient should be admitted and urine should be examined every day.
With removal of the offending agent, the urine gradually recovers.
Day
Recovering hemoglobinuria
1
2
3
4
5
6
Blood Film in acute hemolytic episode in
G6PD deficiency.
Blister Cell
Other Laboratory tests in favism:
• Hemoglobin in urine and plasma.
• Increase urine urobilinogen.
• Indirect hyperbilirubinemia.
• Methemoglobin reduction test For G6PD deficiency (Screening test)
• Specific Assay for red cell G6PD
Management of G6PD deficiency:
• Note: The usual treatment for hemolytic anemia in G6PD-deficient
patients is supportive care (e.g., IV fluid) plus removal and avoidance of
further triggers. In severe hemolysis, blood transfusions may be
required; hemodialysis may be needed if acute kidney injury occurs.
• Blood transfusion during the episode may be needed.
• Spontaneous recovery.
• No Cure.
• Patient should avoid Fava beans, certain drugs, e.g. certain antimalarials,
sulphonamides, septrin, aspirin, salazopyrine, Nalidixic acid,
Nitrofurantoin, Naphthelene (mothballs).
• Note: It may be more practical to instruct the patient to tell their
physician they have this issue before they get prescribed the medication
than give the patient a long expanding list of medications
Inherited Hemolytic Anemia
Due to Membrane Defects
1.Hereditary
Spherocytosis.
2. Hereditary Ovalocytosis
(Elliptocytosis)
Hereditary Spherocytosis (HS):
• Definition: Inherited disorder resulting from
an intrinsic defect involving red cell
membrane, leading to RBCs which are
osmotically fragile and spherocytic in shape.
• Usually inherited as Autosomal dominant.
• Not common in Iraq.
Note: Osmotic fragility test, used in the diagnosis of HS
More
hypotonic
(of hemolysis)
Note (extra): osmotic fragility test
• The osmotic fragility test (OFT) is used to measure erythrocyte resistance to hemolysis
while being exposed to varying levels of dilution of a saline solution. When
erythrocytes are exposed to a hypotonic environment, water enters the cell and
causes swelling and eventual lysis. The susceptibility of osmotic lysis of erythrocytes is
a function of surface area to volume ratio (SAVR)
• Osmotic fragility of RBCs is defined as the ease with which the cells burst in hypotonic
solutions and is expressed in terms of the concentration of the saline solution in
which the cells are hemolyzed.
• The classic osmotic fragility test, originally described by Parpart et al (1947), involves a
small amount of fresh blood being added to a series of solutions with tonicity ranging
from 0.1%-0.9%. Results are then plotted against the NaCl concentrations, yielding an
osmotic fragility curve that is then compared to obtained normal control values.
• In a disease such as hereditary spherocytosis, erythrocytes have a smaller ratio of
surface area to volume and are thus more susceptible to osmotic stress; A spherocyte
will burst at higher saline concentrations, as the RBC’s ability to take in water before
stretching the surface membrane is thus more limited than normal, and it is,
therefore, particularly susceptible to osmotic lysis.
• Thus, in this case, the osmotic fragility curve will shift to the right. That is, the lysis will
start at an even lower hypotonic challenge.
Management of HS
• No Cure.
• Aim is to minimize consequences of disease.
• One of the rare absolutes in Medicine is “TRUE UNCOMPLICATED HS
ALWAYS RESPONDS TO SPLENECTOMY”.
• Note: Splenectomy corrects the anemia and normalizes (increases)
the RBC survival in patients with HS, but the morphological
abnormalities persist.
• Note: In general, splenectomy is not indicated in patients with mild
HS. Indications include (symptomatic) anemia and complications such
as gall bladder stones.
• All should receive folate supplements.
Autoimmune HA
• Dropping hemoglobin level
• Evidence of hemolysis
• Evidence of autoimmunity (note: e.g., Direct Coomb’s test positive,
which detects antibody or complement on human RBC membranes.)
• Can be primary (note: no underlying etiology demonstrated;
approximately 50% of cases[1]) or secondary
Secondary AIHA
• Autoimmune diseases
• Lymphoproliferative diseases (LPD) (note: e.g., Non-Hodgkin’s
lymphoma)
• Cancer (note: e.g., thymoma, ovarian Ca, prostate Ca)
• Infections
• Drugs
Note:[1]
• Antibiotics (cephalosporins, beta-lactamase inhibitors, cotrimoxazole)
• Antiviral drugs: HAART
• Anti-PD-1 monoclonal antibodies (nivolumab, pembrolizumab)
• Chemotherapy (carboplatin, oxaliplatin)
• Non-steroidal anti-inflammatory drugs (diclofenac)
• Others: methyldopa
Treatment of AIHA
• If Hb less than 10gm/dL
• Start prednisolone 1mg/kg
• When Hb >10gm/dL, start tapering
• If no response, intolerance, contraindication,
non-compliance, do splenectomy
• Note: other immunomodulatory agents
(e.g., rituximab, IVIG, cyclophosphamide,
etc.) may be tried before a splenectomy
conclusion
•
•
•
•
Hemolytic anemia are of diverse etiology
Indirect hyperbilirubinemia, reticulocytosis
Hemolysis can be life threatening sometimes
Folate supplementation is crucial.
Questions?
• How you can differentiate hereditary
spherocytosis from immune hemolytic anemia
MEGALOBLASTIC ANEMIA
Hawler Medical University
College of Medicine
Department: MEDICINE
OBJECTIVES
• REVIEW PREVIOUS LECTURE
• WHAT IS MEGALOBLASTIC ANEMIA
• PATHOPHYSIOLOGY
• CAUSES
• MANEGEMENT
MEGALOBLASTIC ANEMIA
Definition
• Note: a metabolic anemia
• Anemias characterized by distinctive
cytological and functional abnormalities in
blood and marrow due to impaired DNA
synthesis (note: can affect all proliferating
cells)
• It maybe due to:
– Vitamin B12 (cobalamin) deficiency
– Folate deficiency
– Or interference with DNA synthesis
by other mechanisms
; relatively heat-stable
Summary of Absorption of B12
Duodenum
STOMACH
Vit B12
R-binder
Intrinsic Factor
CELLS
of the
Body
Trancobalamin
II
od
stream
Blood stream
TCII
absorbed
Cells of
ileum
This reaction is
extremely important for
normal Synthesis of DNA
This reaction is important
for normal myelination of
neurons.
Blood Picture in Megaloblastic anaemia
Film: Normochromic, Anisocytosis
poikilocytosis, macrocytosis, tear
drop cells
• Variable degree of
anaemia, may reach a
low of 2-3g/dl.
• MCV increased >100
fl, maybe up to 135.
• Low retics.
• Leucocytes may be
reduced, some
neutophils maybe
hypersegmented.
• Platelets may be
reduced.
Blood Film in Megaloblastic anaemia
Hypersegmented Neutrophils
Bone marrow findings in Megaloblastic Anaemia
• Hypercellular marrow.
• Erythroid hyperplasia,
with megaloblastic
maturation.
• Granulopiesis: Giant
forms seen.
• Abnormal
megakaryocyte nuclear
segmentation.
Megaloblasts versus Normoblasts
• Megaloblasts are larger.
• Show a shift towards more immature precursors.
• Nucleo-cytoplasmic maturation dissociation.
• Note: As the DNA doesn't synthesize normally, nuclear maturation is
delayed, while cytoplasmic maturation continues at normal rate, thus
forming a cell with mature cytoplasm with relatively immature, large,
open nucleus, known as a megaloblast.
Early
erythroblasts
Megaloblast
Normoblast
Cobalamin Deficiency
Causes of B12 Deficiency
Impaired Absorption
REDUCED INTAKE
- Unusual;
Gastric
- Pernicious
anaemia.
- Gasterctomy.
INTESTINAL
-Ileal resection
-Blind loop
Syndrome
-Crohn’s dis.
-Celiac Disease
-Strict Vegetarians
Pernicious Anaemia
•
•
•
•
The best known of megaloblastic anaemias due to Cobalamin
deficiency.
Not common in Iraq.
Mostly a disease of the elderly.
Characterized by stomach atrophy, loss of intrinsic factor and
Hydrochloric acid.
Pernicious Anaemia
• Mostly autoimmune in nature.
• Characterized classically by a combination of
Megaloblastic anaemia, Glossitis and
Neuropathy (Subacute Combined
Degeneration of the Cord/SCDC).
Note: A patient just feeling like he’s
“getting old”
Presentation:
• Symptomless in some
• Symptoms of anemia
• Anorexia.
• Weight loss
• Diarrhea or constipation
• St. Bruising
• Infections (impaired Bactericidal
function of phagocytes)
Pallor with Tinge of Jaundice
-All rapidly growing DNA
synthesizing tissues are
affected.
-Gonads are affected and
infertility is common.
-Recurrent fetal loss.
GLOSSITIS
Clinical features of cobalamin Deficiency.
Neurological Manifestations
Begins with Paresthesia in feet
and fingers due to early peripheral
neuropathy, with disturbance of
sense of vibration and
proprioception.
If untreated, there is
progression to spastic ataxia
resulting from demyelination of
the lateral and posterior
columns of spinal cord.
Brain maybe affected, with
Subacute Combined Degeneration of the Cord
TIP: IF not Managed early enough, then
changes cannot be reversed by treatment
perversion of taste, smell and vision;
dementia and psychological
disturbances may occur
Note: Vitamin B12 deficiency is a cause
of reversible dementia that must be ruled
out in the evaluation of neurocognitive
decline.
Folate Deficiency
Causes of Folate Deficiency
Reduced Intake
Frequent in
infants and
ELDERLY
Excess
utilization
Impaired
Absorption
Prematurity,
pregnancy,
lactation,
Hemolysis,
Malignancy
Malabsorption,
Celiac dis,
Lymphoma,
regional
enteritis,
jejunal
resection
DRUGS
Methotrexate,
Anticonvulsants,
Hydroxyurea,
ARA-c.
Clinical features of Folate deficiency
• Exactly the same as those of
cobalamin Deficiency (B12), except
for the absence of neurological
manifestations.
• The hematological findings on blood
picture and bone marrow exam are
also indistinguishable.
Further Diagnostic evaluation of
Megaloblastic anaemias
• Serum B12 and folate.(should be done
before transfusions or initiating
therapy).
• Search and exclude causes for B12
and folate, e.g. gastrectomy, crohn’s
disease, intake of certain drugs,
intestinal surgery, vegetarians,
patients with increase folate demands
e.g. multiple pregnancy, hemolysis
etc.
Differential Diagnosis of macrocytic anemia
Other than megaloblastic anemia, macrocytosis
maybe seen in the following conditions:
1. Infancy (physiological).
2. Alcoholism.
3. Liver disease.
4. Reticulocytosis (following acute blood hemolysis, or
hemolysis).
5. Aplastic anemia.
6. Acquired Sideroblastic anemia.
7. Leukemia and pre-leukemia.
8. Myxoedema.
Management:
In cobalamin deficiency:
• Hydroxocobalamin by injection.
• Should never give folate on its own in cobalamin deficient because
although response will be seen, aggravation or induction of
neurological complications may be induced.
• Note: B12 given first and if there is no response, folate is started, but
don’t start with folate alone if you’re not sure which is deficient [Dr.
Ahmad]
In folate deficiency:
• Folic acid orally
• The length of therapy is dependent on the underlying pathology.
Assessment of therapy response:
• The patient will feel better rapidly after starting
therapy.
• Reticulocytes will increase within 3-5 days reaching
a peak in 7-10 days.
• Hb will increase at a rate of 1 g/dl per week.
• Leucocytes and platelets will return to normal counts
within days.
• The marrow will start changing from megaloblastic
to normoblastic within 12 hours, and this process
will be complete within 2-3 days.
Conclusions
• Megaloblastic hemopoiesis either due to B12
or folate deficiency
• Neurological deficit is a sign of B12 deficiency
• B12 only from animal origin
Question
• How long after gastrectomy a patient
can develop B12 deficiency.