Anemia

Dr.Basim Almgoter
MBCHB MRCP
 What is Anemia?
 Anemia is defined by reduction in Hb
Concentration, Hct Concentration or RBC
count
 Anaemia ( from Greek word anaimia,
meaning lack of blood)
 WHO criteria is Hb < 13 in men and Hb < 12
in women
 Anemia: Special Cases
 Erythrocytosis
– People who live at high altitude have greater RBC volume
– Smokers have increased HCT – impairs the ability of the
RBCs to deliver O2
 African-American HGBs are 0.5 to 1.0g/dL lower
than Caucasians
 Athletes (increased plasma volume, Fe deficiency,
hemolysis, polycythemia, use of performance
enhancing agents)
 Anemia: History
 Is the patient bleeding?
– NSAIDs, ASA
– Menstrual history, if applicable (include older women)
– Prior intestinal surgery?
– Hx of hemorrhoids, hematochezia, or melena?
 Past medical history of anemia? Family history?
 Alcohol, nutritional questions
 Liver, renal diseases
 Ethnicity
 Environmental/work toxins (ie lead)
 Signs of Anemia
 Tachycardia, tachypnea, orthostasis
 Pallor
 Jaundice
 Murmur
 Koilonychia or “Spoon nails”
 Splenomegaly, lymphadenopathy
 Petechiae, ecchymoses
 Atrophy of tongue papillae
 Heme + stool
 The Four Causes of Anemia
 Decreased red blood cell
production
 Increased red blood cell
destruction
 Red blood cell loss
 Red blood cell sequestration
* Underlying disorder is abnormal production vs. premature loss
 Decreased RBC production
 Deficiency of iron, B12, folate
 Marrow is dysfunctional from
myelodysplasia, tumor infiltration, aplastic
anemia, etc.
 Bone marrow is suppressed by
chemotherapy or radiation
 Low levels of erythropoeitin, thyroid
hormone, or androgens
 Increased RBC destruction
 RBCs live about 100 days
 Acquired: autoimmune hemolytic anemia,
TTP-HUS, DIC, malaria
 Inherited: spherocytosis, sickle cell,
thalassemia
 RBC Loss
 Bleeding!
 Obvious vs occult
 Iatrogenic: venesection e.g. daily CBC,
surgical, hemodialysis
 Retroperitoneal
 Approach to Anemia
CBC
Reticulocyte count
MCV

RI < 2% RI > 2%

Underproduction Increased destruction or loss

MCV
Further work up
Based on history,
Physical, other
MCV < 80 MCV 81 – 99 MCV > 100
Microcytic Normocytic Macrocytic
 Approach to Anemia
 LOOK AT THE SMEAR!!!!
 Convenient to separate
into three classes based on
the size of the RBC
 MCV and RDW
 Microcytosis: < 80 fL
 Normocytosis: 80-100 fL
 Macrocytosis: >100 fL
 CBC, reticulocyte count, Fe,
Ferritin, TIBC, folate, B12,
LDH, CMP, ESR…
 Reticulocytes
 Nucleated RBCs – form in marrow where they
mature for 3 days and then spend 1 day in
circulation (before maturing to RBC)
 Given avg life span of RBC of 100 days, 1% of RBCs
are destroyed each day
 Retics form 1% of circulating RBCs qd
 Nl RBC count is 5 million/uL so marrow makes
50,000 reticulocytes/uL blood qd
– With epo, can increase to 250,000 retics/uL blood qd
(given nl marrow and replete iron, folate, b12)
 Microcytic Anemia
 Iron Deficiency Anemia
 Thallasemia
 Anemia of chronic
disease
 Sideroblastic anemia
 Iron Deficiency Anemia
 The definitive test is serum ferritin
 Low serum ferritin (<12 ug/L)is diagnostic of iron
deficiency
 Although ferritin is an acute phase reactant, it will still be
low in iron deficiency
 Also, high TIBC
– Fe saturation = Fe/TIBC < 10% in Fe deficiency
– If ferritin is indeterminate
 Low serum Fe is not in itself diagnostic, neither is marrow
staining
 Anisocytosis (heterogeneous in shape) and poikilocytosis
(abnormal shape)
 Reactive thrombocytosis
 Investigation

normal

Microcytic hypochromic anemia with:

• Anisocytosis( variation in size)
• Pokiliocytosis (variation in shape)
Iron deficiency
 Investigation

BM Iron stain (Perl’s stain): The gold standard but invasive procedure

Normal IDA: reduced or absent iron stores

(hemosiderin)
 Treatment of IDA

• Treat the underlying cause

• Iron replacement therapy:
Oral :( Ferrous Sulphate OD for 6 months)
Intravenous:( Ferric sucrose OD for 6 months)

Hb should rise 2g/dL every 3 weeks

1. L o s s o f a l l f o u r g e n e s
completely - suppresses α -
chain synthesis is incompatible
with life and leads to death in
utero hydrops fetalis.
 Beta-Thalassemia
 2 genes
 1/2 mutation: Beta-Thal trait, increased
Hgb A2, rarely anemic, mild microcytosis
 2/2 mutation: Beta-Thalassemia disease,
Hgb F, microcytosis, anemia
 Usually found in people of African or
Mediterranean descent but has world-wide
distribution
 Abnormal hemoglobin electrophoresis
Clinical features of beta thalassemia
major:
 Laboratory diagnosis of beta thalassemia major:

1- There is a severe
hypoc hromic mic roc ytic
anaemia, raised reticulocyte
percentage with normoblasts,
target cells and basophilic
stippling in the blood film
Beta - Thalassemia
 β - Thalassaemia minor

•
Hypochromic microcytic blood picture (MCV and
MCH very low) but high red cell count (> 5.5 × 10 12
/L) and mild anaemia (haemoglobin 10 – 12 g/dL).

•
A raised Hb A 2 (> 3.5%) confirms the diagnosis.
 Sickle cell disease

 African background
 Abnormal hemoglobin causes change in RBC shape,
resulting in constant RBC destruction by the
spleen, functional asplenia, susceptible to
infection
 Arterial occlusion leads to infarcts, pain crises,
acute chest syndrome, stroke, MI
 Keep hydrated, treat pain, take infection seriously
 Also sickle-C and sickle--thalassemia
 Sideroblastic Anemia

 Failure of synthesis of
porphyrin ring
Hereditary
 Acquired (INH, EtOH, B6
deficiency, Lead)
 Smear: sideroblasts and
basophilic stippling
 Macrocytic Anemia (MCV>100)
 Drug Induced (hydroxyurea, AZT, MTX,
chemotherapy, anticonvulsants)
 B12 / folate deficiency
 Myelodysplastic syndrome
 Liver disease
 Alcohol abuse
 Reticulocytes
 Hypothyroidism
 Folate and B12
 Serum folate usually sufficient, but if folate level
is normal but folate deficiency is suspected, check
serum homocysteine (elevated because of impaired
folate dependent conversion of homocysteine to
methionine) or RBC-folate.
 B12 can be spuriously low– a more sensitive and
specific test is serum methylmalonic acid level,
will be increased if B12 is low.
 Classically check Schilling Test for B12 deficiency
(parietal cell antibody or Intrinsic Factor antibody)
B12 and Folate Deficiency
 Myelodysplastic Syndrome
 Primary bone marrow
disorder, often found
in elderly
 Macrocytosis, anemia
 Pseudo-Pelger-Huet
abnormality– the
bilobed nucleus
Normochromic
normocytic anemia is a
form of anemia in which the
average size and hemoglobin
content of the red blood cells
are within normal limits.
 Normocytic Anemia
 Large and complicated group of disorders!
 Hemolytic anemias
 Anemia of chronic disease
 Bone marrow disorder
 Nutritional (early Fe, B12, folate deficiency)
 Renal insufficiency
 Nutritional Anemias
 Iron deficiency and B12/folate deficiency
can present with normocytic anemia– esp.
if both deficiencies are concurrent.
 Check iron studies and B12, folate levels.
 Anemia of Renal Insufficiency
 Unremarkable peripheral blood smear
 Inappropriately normal erythropoietin level
 Anemia usually severe and symptomatic
when Cr > 3.0
 Mild to moderate anemia found in Cr 1.5-3.0
 Tx: Epogen or similar, Fe (oral, IV) if iron
stores are found to be low
Hemolytic Anemia
 Definitionn:

- Haemolytic anaemias are defined as those anaemias that result from an

increase in the rate of red cell destruction.
Classification of haemolytic anemia:
According to the underlying cause :
Evaluation of Hemolysis
 LDH: increases
 Indirect bilirubin increases
(increased Hgb catabolism)
 Haptoglobin decreases
 Reticulocyte count increases
 Urine hemosiderin test =
present in intravascular,
absent in extravascular
hemolysis!
 Coombs test:
– (+) = autoimmune hemolytic
anemia
– (-) consider PNH (abnormal GPI
protein, send flow for CD55 and
CD59)
Hereditary haemololytic anemia due
to membrane defects
Hemolytic Anemia: Spherocytosis
 Definitin:

It is a heterogeneous disorder due to red cell membrane

structural abnormalities result in spherical shaped poorly
formed red cells.
 Clinical Features:

- The inheritance is autosomal dominant.

- The anaemia can present at any age.
- Jaundice is typically fluctuating.
- splenomegaly occurs in most patients.
- Pigment gallstones are frequent.
- Aplastic crises
Hereditary haemololytic anemia due
to defective red cell metabolism
More hemolytic anemias
 Clinical feature of haemolytic anemia:

- Pallor of the mucous membranes

- fluctuating jaundice
- splenomegaly.
- Dark color urine ?????.
- Pigment (bilirubin) gallstones.
- Ulcers around the ankle.
- Aplastic crises.
 Laboratory findings in haemolytic
anemia:

1. Features of increased red cell breakdown:

2. Features of increased red cell production:
3. Damaged red cells:
 Anemia of Chronic Disease
 Thought to be a cytokine mediated process which
inhibits red blood cell production or interferes
with action of erythropoietin
– Therefore, the disease needs to be inflammatory
 Decreased iron utilization/mobilization
 Seen with rheumatologic diseases, chronic
infections, malignancy
 Indices: Low Fe, Low TIBC, Nl/increased Ferritin
 May be seen in conjunction with Fe-deficiency
Anemia due to Primary Bone Marrow
Disorder
 Myelodysplastic syndrome
 Bone marrow infiltration:
nucleated red blood cells
found in circulation
 Might see “rouleaux”
formation in multiple
myeloma
 WBC, plts often abnormal
 Bone marrow biopsy
 Anemia: Treatments
 “Transfusion triggers”
– CAD: Hgb > 10
– All pts: Hgb > 7.0
 Iron supplementation
 Erythropoietin analogs
 B12, folate
Helmet vs. Teardrop Cells