Hematology Notes for Final State Exam Internal
1. Iron-deficient anemia
Iron deficiency anemia (IDA) – the most common form of anemia worldwide and can be
caused by: inadequate intake, decreased absorption (atrophic gastritis, IBD) increased
demand e.g. pregnancy or increased loss due to GI bleeding or menorrhagia.
Prolonged deficiency depletes iron stores in the body à decreased erythropoiesis and anemia
Epidemio + Etiology
• Most common form of anemia worldwide, highest prevalence in children up to 5 years
of age, young women of childbearing age due to menstruation, and pregnant women.
• The most common cause of IDA can be divided by age group and pathophysiological
mechanism:
o Infants – exclusive intake of non fortified cows milk or exclusive breastfeeding
after 6 months of age
o Children – malnutrition, excessive intake of cows milk, Meckel diverticulum
o Adolescence – menarche, menstruation
o Adults – menorrhagia or pregnancy, peptic ulcer disease
o Adults over 50 – colon polyps, carcinoma, hookworm infections
• Based on underling mechanism
o Iron losses
§ Bleeding – GIT – due to gastrointestinal malignancy, hookworm, peptic
ulcer disease, increased risk with NSAIDs, menorrhagia, hemorrhagic
diathesis, Meckel diverticulum, dialysis dependent renal failure,
frequent blood donation.
o Decreased iron intake
§ Chronic undernutrition, cereal based diet, strict vegan diet
o Decreased iron absorption
§ Achlorhydria, hypochloridria, IBD, celiac, surgical resection of the
duodenum, bariatric surgery
o Increased demand
§ Pregnancy, lactation, growth spurt, EPO therapy
Pathophysiology:
• Iron deficiency à decreased binding of iron to protoporphyrin (last reaction in heme
synthesis) à decreased production of hemoglobin.
Clinical Features
• Signs and symptoms of anemia
o Fatigue, lethargy, pallor
o Cardiac – tachycardia, angina, dyspnea on exertion, pedal edema,
cardiomyopathy in severe cases
o Brittle nails, koilonychia (spoon like nail deformity) hair loss
o Pica, dysphagia
o Angular chelitis – inflammation and fissuring of the corners of the mouth
o Atrophic glossitis – erythrematous, edematous, painful tongue, loss of tongue
papilla.
, o IDA can also be associated with Plummer-Vinson Syndrome
§ Triad of iron deficiency anemia, prostcricoid dysphagia, and upper
esophageal webs
• Thin membrane of normal esophgeal tissue, protrude into the
esophagus causing symptoms of dysphagia, odonyphagia and
food impaction
• Acquired esophageal webs are more common that congenital
webs and are mainly observed in PVS
• Associated with increased risk of esophgeal squamous cell
carcinoma and glossitis
Diagnosis
• Routine blood studies – CBC, to check Hb and Hct
• Iron studies – to confirm the diagnosis
• Empiric iron therapy can be initiated if the patients history points to a clear explanation
of iron deficiency anemia e.g. history of bleeding or multiple blood donations
• Advanced studies – HB decreased, MCV decreased (typically microcytic) can also be
normal and normocytic
• MCH is also typically decreased – hypochromic can also be normal (normocytic)
• Normal or decreased reticulocyte count
• RDW is increased usually
• On a peripheral blood smear – anisocytosis, hypochromasia
• Therefore it is normally a microcytic hypochromic anemia, or normocytic normochromic
anemia
• The best initial test is ferritin – normally it is decreased <45, iron is decreased, transferrin
is normally increased, TIBC is also increased, transferrin saturation is usually
decreased
• Bone marrow biopsy can also be done, is the gold standard but is only indicated in
patients with suspected IDA and unclear iron studies.
Treatment
• Treat the underlying condition – whether bleeding, malabsorption, parasites
• Dietary modifications, iron therapy – oral or parenteral
• Ganzoni formula – formula used to calculate the total iron deficit in patients with iron
deficiency anemia
o Total iron deficit in mg = subject weight in kg x (target Hb in g/dl – current Hb
in g/dl) x2.4 + iron stores in Mg
• RBC transfusion can also be done in severe cases
DDx
• Normocytic anemia
o Acute blood loss anemia
o Occult bleeding
o Anemia of chronic disease
o Hemolytic anemia
o Chronic kidney disease
o Aplastic anemia
,• Microcytic Anemia
o Thalassemia – lab studies
show hemolysis – decreased
haptoglobin, increased
indirect bilirubin, increased
reticulocytes, confirmed on Hb
electrophoresis
o Sideroblastic anemia –
serum ferritin lebels and
transferrin levels are normal or
increased
Anemia of chronic disease –
usually a normocytic
normochromic anemia with
decreased serum iron but
normal or increased iron
stores. The most important
protein in anemia of chronic
disease is hepcidin produced
by the liver, induced by
cytokines esp IL-6, hepcidin
binds to ferroportin on
membrane of iron exporing
cells and inhibits the transfer
of the iron into the blood,
therefore the iron stays
trapped within the cells in the
form of ferritin, hence ferritin
levels are normal or high in
ACD.
, 2. Vitamin B12 and folic-deficient anemia
Megaloblastic anemia is the resulting type of anemia that occurs when there is a deficiency
of vitamin B12 or folic acid.
Folate is needed as a substrate for and B12 is an important co-factor to help the generation
of methionine from homocysteine. This reation à tetrahydrofolate which is converted à
thiamine monophosphate for incorporation into DNA.
• Deficiency of either folate or b12 à cells with arrested nuclear maturation, but normal
cytoplasmic development à nucleocytoplasmic asynchrony
• All proliferating cells have megaloblastosis (huge cells)
• The high proliferating rate of the cells and rapid turnover à hypercellular bone marrow
• Hemolysis within the marrow leads to increased LDH and bilirubin in the blood but there
is no reticulocytosis (present in other types of hemolysis)
• Iron stores are typically raiased, and immature granulocyte precurosors are seen as
giant metamyelocytes with large sausage shaped nuclei.
• Mature neutrophils are hypersegmented nuclei with 6 or more nuclear lobes
• Vitamin B12 deficiency is associated with neurological deficits, but folate is not – the
most characteristic neurological deficits come from focal demyelination affecting the
spinal cord, peripheral nerves and optic nerves and cerebrum.
Clinical Features of Megaloblastic Anemia:
• Malaise (90%), breathlessness, paresthesia, sore mouth, weight loss, impotence, poor
memory, depression, personality change, hallucinations, smooth tongue, angular
cheliosis, vitligio, skin pigmentation, heart failure and pyrexia.
Investigations:
• Hemoglobin – often decreased
• MCV – increased, commonly >120
• Erythrocyte count – low
• Blood film à oval macrocytes, poikilocytosis, red cell fragmentation, neutrophil
hypersegmentation
• Leukocytes are low or normal, so are platelets, reticulocytes are low
• Bone marrow is with increased cellularity, megaloblastic changes, giant
metamyelocytes, dysplastic megakaryocytes, increased ironstores and pathological
non ring sideroblasts.
• Ferritin is increased
• LDH is also increased
B12 deficiency is most often due to:
• Dietary deficiency – vegan diet
• Gastric pathology (gastrectomy)
• Pernicious anemia – organ specific autoimmune disorder where the gastric mucosa is
atrophic with loss of parietal cells à intrinsic factor deficiency without intrinsic factor,
less than 1% of b12 intake can be absorbed, the finding of anti-intrinsic factor
antibodies in the context of B12 deficiency confirms the diagnosis.
• Pancreatic insufficiency or small bowel pathology
1. Iron-deficient anemia
Iron deficiency anemia (IDA) – the most common form of anemia worldwide and can be
caused by: inadequate intake, decreased absorption (atrophic gastritis, IBD) increased
demand e.g. pregnancy or increased loss due to GI bleeding or menorrhagia.
Prolonged deficiency depletes iron stores in the body à decreased erythropoiesis and anemia
Epidemio + Etiology
• Most common form of anemia worldwide, highest prevalence in children up to 5 years
of age, young women of childbearing age due to menstruation, and pregnant women.
• The most common cause of IDA can be divided by age group and pathophysiological
mechanism:
o Infants – exclusive intake of non fortified cows milk or exclusive breastfeeding
after 6 months of age
o Children – malnutrition, excessive intake of cows milk, Meckel diverticulum
o Adolescence – menarche, menstruation
o Adults – menorrhagia or pregnancy, peptic ulcer disease
o Adults over 50 – colon polyps, carcinoma, hookworm infections
• Based on underling mechanism
o Iron losses
§ Bleeding – GIT – due to gastrointestinal malignancy, hookworm, peptic
ulcer disease, increased risk with NSAIDs, menorrhagia, hemorrhagic
diathesis, Meckel diverticulum, dialysis dependent renal failure,
frequent blood donation.
o Decreased iron intake
§ Chronic undernutrition, cereal based diet, strict vegan diet
o Decreased iron absorption
§ Achlorhydria, hypochloridria, IBD, celiac, surgical resection of the
duodenum, bariatric surgery
o Increased demand
§ Pregnancy, lactation, growth spurt, EPO therapy
Pathophysiology:
• Iron deficiency à decreased binding of iron to protoporphyrin (last reaction in heme
synthesis) à decreased production of hemoglobin.
Clinical Features
• Signs and symptoms of anemia
o Fatigue, lethargy, pallor
o Cardiac – tachycardia, angina, dyspnea on exertion, pedal edema,
cardiomyopathy in severe cases
o Brittle nails, koilonychia (spoon like nail deformity) hair loss
o Pica, dysphagia
o Angular chelitis – inflammation and fissuring of the corners of the mouth
o Atrophic glossitis – erythrematous, edematous, painful tongue, loss of tongue
papilla.
, o IDA can also be associated with Plummer-Vinson Syndrome
§ Triad of iron deficiency anemia, prostcricoid dysphagia, and upper
esophageal webs
• Thin membrane of normal esophgeal tissue, protrude into the
esophagus causing symptoms of dysphagia, odonyphagia and
food impaction
• Acquired esophageal webs are more common that congenital
webs and are mainly observed in PVS
• Associated with increased risk of esophgeal squamous cell
carcinoma and glossitis
Diagnosis
• Routine blood studies – CBC, to check Hb and Hct
• Iron studies – to confirm the diagnosis
• Empiric iron therapy can be initiated if the patients history points to a clear explanation
of iron deficiency anemia e.g. history of bleeding or multiple blood donations
• Advanced studies – HB decreased, MCV decreased (typically microcytic) can also be
normal and normocytic
• MCH is also typically decreased – hypochromic can also be normal (normocytic)
• Normal or decreased reticulocyte count
• RDW is increased usually
• On a peripheral blood smear – anisocytosis, hypochromasia
• Therefore it is normally a microcytic hypochromic anemia, or normocytic normochromic
anemia
• The best initial test is ferritin – normally it is decreased <45, iron is decreased, transferrin
is normally increased, TIBC is also increased, transferrin saturation is usually
decreased
• Bone marrow biopsy can also be done, is the gold standard but is only indicated in
patients with suspected IDA and unclear iron studies.
Treatment
• Treat the underlying condition – whether bleeding, malabsorption, parasites
• Dietary modifications, iron therapy – oral or parenteral
• Ganzoni formula – formula used to calculate the total iron deficit in patients with iron
deficiency anemia
o Total iron deficit in mg = subject weight in kg x (target Hb in g/dl – current Hb
in g/dl) x2.4 + iron stores in Mg
• RBC transfusion can also be done in severe cases
DDx
• Normocytic anemia
o Acute blood loss anemia
o Occult bleeding
o Anemia of chronic disease
o Hemolytic anemia
o Chronic kidney disease
o Aplastic anemia
,• Microcytic Anemia
o Thalassemia – lab studies
show hemolysis – decreased
haptoglobin, increased
indirect bilirubin, increased
reticulocytes, confirmed on Hb
electrophoresis
o Sideroblastic anemia –
serum ferritin lebels and
transferrin levels are normal or
increased
Anemia of chronic disease –
usually a normocytic
normochromic anemia with
decreased serum iron but
normal or increased iron
stores. The most important
protein in anemia of chronic
disease is hepcidin produced
by the liver, induced by
cytokines esp IL-6, hepcidin
binds to ferroportin on
membrane of iron exporing
cells and inhibits the transfer
of the iron into the blood,
therefore the iron stays
trapped within the cells in the
form of ferritin, hence ferritin
levels are normal or high in
ACD.
, 2. Vitamin B12 and folic-deficient anemia
Megaloblastic anemia is the resulting type of anemia that occurs when there is a deficiency
of vitamin B12 or folic acid.
Folate is needed as a substrate for and B12 is an important co-factor to help the generation
of methionine from homocysteine. This reation à tetrahydrofolate which is converted à
thiamine monophosphate for incorporation into DNA.
• Deficiency of either folate or b12 à cells with arrested nuclear maturation, but normal
cytoplasmic development à nucleocytoplasmic asynchrony
• All proliferating cells have megaloblastosis (huge cells)
• The high proliferating rate of the cells and rapid turnover à hypercellular bone marrow
• Hemolysis within the marrow leads to increased LDH and bilirubin in the blood but there
is no reticulocytosis (present in other types of hemolysis)
• Iron stores are typically raiased, and immature granulocyte precurosors are seen as
giant metamyelocytes with large sausage shaped nuclei.
• Mature neutrophils are hypersegmented nuclei with 6 or more nuclear lobes
• Vitamin B12 deficiency is associated with neurological deficits, but folate is not – the
most characteristic neurological deficits come from focal demyelination affecting the
spinal cord, peripheral nerves and optic nerves and cerebrum.
Clinical Features of Megaloblastic Anemia:
• Malaise (90%), breathlessness, paresthesia, sore mouth, weight loss, impotence, poor
memory, depression, personality change, hallucinations, smooth tongue, angular
cheliosis, vitligio, skin pigmentation, heart failure and pyrexia.
Investigations:
• Hemoglobin – often decreased
• MCV – increased, commonly >120
• Erythrocyte count – low
• Blood film à oval macrocytes, poikilocytosis, red cell fragmentation, neutrophil
hypersegmentation
• Leukocytes are low or normal, so are platelets, reticulocytes are low
• Bone marrow is with increased cellularity, megaloblastic changes, giant
metamyelocytes, dysplastic megakaryocytes, increased ironstores and pathological
non ring sideroblasts.
• Ferritin is increased
• LDH is also increased
B12 deficiency is most often due to:
• Dietary deficiency – vegan diet
• Gastric pathology (gastrectomy)
• Pernicious anemia – organ specific autoimmune disorder where the gastric mucosa is
atrophic with loss of parietal cells à intrinsic factor deficiency without intrinsic factor,
less than 1% of b12 intake can be absorbed, the finding of anti-intrinsic factor
antibodies in the context of B12 deficiency confirms the diagnosis.
• Pancreatic insufficiency or small bowel pathology
