Transcript Microcytic Anemia

APPROACH TO A PATIENT WITH
ANEMIA
Acibadem University
Acibadem Medical Faculty
Department of Pediatrics
Cengiz Canpolat M.D.
Professor of Pediatrics
Division of pediatric Hematology-Oncology
Objectives
• Review basic science of the RBC
• Define Anemia
• Review key aspects of history, physical
and laboratory evaluation
• Review a systematic approach to the
differential diagnosis
• http://www.anemia.org/professionals/
• http://www.anemia.org/patients/bonemarrow-basics/
Bone Marrow
Definitions
• Anemia is defined as the values of
hemoglobin, hematocrit which are more
than 2 standard deviations below the
mean
• RBC counts and RBC indices helps us in
differential diagnosis
RBC-The important players
• Hemoglobin
– reversibly binds and transports oxygen from
lungs to tissues
– 4 globin chains & iron
RBC-The important players (2)
• Iron
– key element in the production of hemoglobin
– absorption is poor
• Vitamin B12
• Folic acid
• Zinc
General Principles
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Anemia is a sign, not a disease.
Anemias are a dynamic process.
Its never normal to be anemic.
The diagnosis of iron deficiency anemia
mandates further work-up.
Differential Diagnosis
• Classification by Pathophysiology
– Blood Loss
– Decreased Production
– Increased Destruction
Blood Loss
• Acute
– Traumatic
– Variety of sources
• Melena, hematemesis, menometrorrhagia
• Chronic
– Occult bleeding
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Fissura
Hemorrhoids
Polyps
menstruation
Decreased Production
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Infectious
Neoplastic
Endocrine
Nutritional Deficiency
Anemia of Chronic Disease
Decreased Production
INFECTIOUS
• Bacterial
– Tuberculosis
• Viral
– HIV
– Parvovirus
– CMV
Decreased Production
NEOPLASTIC
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Leukemia
Lymphoma/solid tm mets
Myeloproliferative Syndromes
Myelodysplasia
Decreased Production
ENDOCRINE
• Thyroid Dysfunction
– Hypothyroidism
• Erythropoietin Deficiency
– Renal Failure
Decreased Production
NUTRITIONAL DEFICIENCY
• Iron
• B12
• Folate
Anemia of chronic disease
* Infections: TB, SBE, osteomyelitis, chronic UTI or
pyelonephritis, fungal infections
* Chronic inflammatory disorders: JRA, SLE,
Sarcoidosis, Collagen Vascular Disease,
* Malignancy: Metastasis, Leukemia, Lymphoma,
INCREASED DESTRUCTION
Hemolytic Anemias
• Immune Mediated
• Non-immune Mediated
Evaluation of the Patient
• HISTORY
– Is the patient bleeding?
• Actively? In past?
– Is there evidence for increased RBC
destruction?
– Is the bone marrow suppressed?
– Is the patient nutritionally deficient? Pica?
Evaluation of the Patient (2)
REVIEW OF SYMPTOMS
CNS Fatique, Depression, Impaired cognitive function
GIS Anorexia, Neausia
CVS Lower skin temperature, Pallor of skin mucous
membranes and conjuctivae
CRS Dyspnea, Tachycardia, Palpitations, Cardiac
enlargement/hypertophy, increased pulse pressure,
Systolic ejection murmur, Risk of cardiac failure
IS
Impaired T-cell and Macrophage function
GUS Menstrual Problems
Evaluation of the Patient (3)
PHYSICAL EXAM
•Stable or Unstable?
-ABCs
-Vitals
•Pallor
•Jaundice / hemolysis
•Lymphadenopathy
•Hepatosplenomegally
•Bony Pain
•Petechiae
•Rectal-? Occult blood
Red Cell Indices
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RBC
Hb
Hct
MCV
MCH
MCHC
RDW
Red Blood Cell
Hemoglobin
Hematocrit
Mean Corpuscular Volume
Mean Corpuscular Hemoglobin
MCH concentration
Red Cell Distribution Width
Red blood cell indices
(RBC), MCH, MCHC, MCV, RDW
– Use of volume-sensitive automated blood cell
counters, such as the Coulter counter. The
red cells pass through a small aperture and
generate a signal directly proportional to their
volume.
– Other automated counters measure red
blood cell volume by means of techniques
that measure refracted, diffracted, or
scattered light
Red blood cell indices
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Automated RBC measurement:
–RBC, Hb, MCV
Derived RBC indices:
–Hct = MCVx RBC x 0.1
–MCH = Hb/RBC x 1 000 000
–MCHC = Hb/Hct x 0.1
Laboratory Evaluation
• Initial Testing
– CBC w/ differential (includes RBC indices)
– Reticulocyte count
– Peripheral blood smear
Erythrocyte Development
Reticulocytes
Reticulocytes
Reticulocyte count
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Retic count = % immature RBC
Normal 0.5-1.5% (for non-anemic)
<1% Inadequate production
>=2% Increased production (? adequacy)
Laboratory Evaluation (2)
• Bleeding
– Serial HCT or HGB
• Iron Deficiency
– Iron Studies
• Hemolysis
– Serum LDH, indirect bilirubin, haptoglobin, coombs,
coagulation studies
• Bone Marrow Examination
• Others-directed by clinical indication
– hemoglobin electrophoresis
– B12/folate levels
Differential Diagnosis No 2
• Classification by Morphology
– Normocytic
– Microcytic
– Macrocytic
Microcytic Anemia
• MCV <70
• Reduced iron
availability
• Reduced heme
synthesis
• Reduced globin
production
Iron deficiency is a
common form of
malnutrition that affects
more than 2 billion people
globally.
- Project IDEA (Iron Deficiency
Elimination Action)®, CDC
Iron defficiency
Microcytic Anemia
REDUCED IRON AVAILABILTY
• Iron Deficiency
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Deficient Diet/Absorption
Increased Requirements
Blood Loss
Iron Sequestration
• Anemia of Chronic Disease
– Low serum iron, low TIBC, normal serum ferritin
– MANY!!
• Chronic infection, inflammation, cancer, liver disease
Iron absorbtion (2)
• • The body absorbs iron best from
ingestion of meat (heme-iron pathway)
• • Absorption of iron can be increased by
adjunct ingestion of the following:
– Absorption of iron can be enhanced by
foods high in vitamin C
_ Iron absorption can be blocked by coffee,
tea, egg yolk, milk, fiber and spinach
Microcytic Anemia
REDUCED HEME SYNTHESIS
• Lead poisoning
• Acquired or
congenital
sideroblastic anemia
Characteristic smear finding
``Basophylic stippling``
Sideroblastic Anemias
• Heterogenous grouping of anemias defined by
presence of ringed sideroblasts in the BM
• Etiologies:
– Hereditary (rare), type of porphyria
– Myelodysplasia
– EtOH
– Drugs (INH, Chloramphenicol)
• Tx:
– Trial of pyridoxine for hereditary or INH induced
SA
Sideroblastic anemia
• Accumulation of
mitochondrial iron in
erythroblasts
• Hereditary
• Drugs - INH, lead,
zinc, alcohol,
chloramphenicol,
cycloserine, plavix
• Hypothermia
• Confirm w/ BM Bx
Microcytic Anemia
REDUCED GLOBIN PRODUCTION
• Thalassemias
• Smear Characteristics
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Hypochromia
Microcytosis
Target Cells
Tear Drops
Thalassemias
• Genetic defect in hemoglobin synthesis
–  synthesis of one of the 2 globin chains ( or )
– Imbalance of globin chain synthesis leads to depression of
hemoglobin production and precipitation of excess globin
(toxic)
– “Ineffective erythropoiesis”
– Ranges in severity from asymptomatic to incompatible with
life (hydrops fetalis)
– Found in people of African, Asian, and Mediterranean
heritage
Macrocytic anemia
Macro
RPI >= 2
RPI < 2
Check Occult Blood Loss
Check B12 and folate
No
Coombs’ test
Yes
Macrocytic Anemia
• MCV > 100
• Megaloblastic
Abnormalities in nucleic
acid metabolism
– B12, Folate
• Non-megaloblastic:
Abnormal RBC
maturation
– Myelodysplasia
• Alcohol, liver disease,
hypothryroidism, GIS Ca,
chemotherapy/drugs
Macrocytic: RPI < 2
B12/Folate
B12 Low
Normal
Folate Low
MMA High
MMA
Homocysteine
Normal
Homocysteine
High
Consider
Liver, Renal,
Thyroid,
Alcohol,
Chronic dis.
Consider
Bone Marrow
Bx
Macrocytic: RPI < 2
Megaloblastic Anemia
B12
• Inadequate
absorption
• Synthesized by
bacteria
• Meat, fish, dairy
(strict vegans)
• Absorbed as B12-IF
complex in ileum
(gastrectomy)
• Ca++ and pH
dependant (PPI)
Folate
• Inadequate intake
• Synthesized by
plants and microorganism
• Green leafy vege’s
• Fruits
• Absorbed in jejunum
Macrocytic: RPI < 2
Megaloblastic Anemia
Smear
• Macro-ovalocytic
• Polychromasia
• Hypersegmented neutrophil
Other Labs
• Homocysteine – Folate def.
• Methylmalonic A – B12 def.
• Intrinsic Factor Ab test – very
specific for pernicious anemia but
only 50%sensitve
• Parietal cell AB test – quite
sensitive (90%) but not Spesific
• Schilling test
Macrocytic: RPI < 2
Non-megaloblastic
• Consider Liver,
Renal, Endocrine
(thyroid), alcohol,
drugs
• Consider anemia of
chronic disease
• Myelodysplastic
• Myeloproliferative Leukemia, Lymphoma,
Multiple Myeloma
• Get Bone
Marrow
Biopsy
Macrocytic: RPI < 2 continues
Aplastic Anemia
• Fanconi anemia – congenital
• Direct stem cell destruction – external
radiation
• Drugs - chloramphenicol, gold, sulfonamides,
felbamate
• Other Toxins - Solvents, degreasing agents,
pesticides
• Viral infection - parvovirus B19, HIV, other
• Idiopathic
Macrocytic: RPI >= 2
Occult Blood Loss?
Yes
Investigate source
No
Check for Hemolysis
Peripheral smear
Coombs’ (DAT)
Macrocytic: RPI >= 2
Hemolytic Anemia
Other Lab Characteristics
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RBC morphology
Serum haptoglobin
Serum LDH
Unconjugated bilirubin
Hemoglobinuria
Hemosiderinuria
Macrocytic: RPI >= 2
Hemolytic Anemia
Coombs’ (DAT)
Positive
Immune Hemolysis
Drug related Hemolysis
Transfusion, Infection, Cancer
Negative
Hemoglobinopathy, G6PD, PK,
Spherocytosis, Eliptocytosis,
PNH, TTP, DIC
Normocytic Anemia
Hyperproliferative (RPI >= 2)
• Use same flow chart as macrocytic
hyperproliferative
Occult Blood Loss?
Yes
Investigate source
No
Check for Hemolysis
Peripheral smear
Coombs’ (DAT)
Normocytic Anemia
Hypoproliferative (RPI < 2)
1. Get iron panel (ferritin)/B12/folate
- some clue from RBC indices to check
early disease, high RDW, peripheral smear.
2. Consider liver, renal, drugs, toxin, endocrine
(thyroid), and anemia of chronic disease.
3. Get BM bx
- Leukopenia, thrombocytopenia, CRI < 0.1
- Aplastic anemia/pancytopenia
- Abnormal (immature) cells on smear
Elliptocytes/ovalocytes
• Abnormal
cytoskeletal proteins
• Hereditary
elliptocytosis
Howell Jolly body
Nuclear remnant - DNA
• hemolytic anemia
• absent or hypofunction
spleen
Schistocyte/helmet cells
• Fragmented
(mechanical or
phagocytosis)
• DIC
• TTP
• HUS
• Vasculitis
• prosthetic heart valve
• severe burns
Sickle cells
• Molecular
aggregation of
Hgb-S
• SS, SC,
S-thallassemia
• Rarely S-trait
Spherocyte
• There is an absent
central pallor, red
cells look smaller
Hereditary
spherocytosis
Stomatocyte
Mouth like membrane
defects
• Smear artifact
• Hereditary
stomatocytosis
• Liver disease
TTP-HUS / DIC
Target cells
• Hemoglobinopathies
• Thalassemia
• Liver disease
Tear drop cells
• Smear artifact
• Myelofibrosis
• Promyeloblastic
leukemia
• Space occupying
lesions of marrow