Approach to the patients with anemia

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Approach to the patients with anemia

• Hasan Atilla Özkan, MD.

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Anemia

• Definition reduction in the total red blood
  cell mass

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Clinical Presentation

• Mild anemia
• Usually asymptomatik
• Palpitation and dyspnea with exercise
• More pronounced anemia
• Exercise capacity greatly reduce
• Any exertion causes palpitation, dyspnea,
  headache and rapid exhaustion
• Heart failure and angina in patients with
  underlying heart disease

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Clinical Presentation

• Sign and symptoms depends on
• Severity
• Rapidity of onset
• Age of the patient

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Clinical Presentation

• Rapidity of onset is very important
• Acute blood loss may cause vascular collapse
• Patients with chronic blood loss can compansate

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Anemia as a disease?

• Anemia is a sign of an underlying disease

Mechanism (Kinetic Approach)

• Decreased RBC production
• Increased RBC destruction
• Blood loss

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Decreased RBC Production

• Lack of nutrients
• deficiency of iron, B12,or folate, etc
• Bone marrow disorders
• Aplastic anemia, pure RBC aplasia, MDS, tumor
  infiltration, etc
• Bone marrow suppression
• Drugs, chemo, irradiation
• Low levels of trophic hormones
• CRF, hypothrioidism, hypogonadism
• Inflammation

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Clinical evaluation

• Cause of anemia may be suggested from the history
  and physical examination

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History

• Time of the onset of symptoms
• Transfusion history
• Past blood count measurements
• Nutritional habbits
• Alcohol intake
• Weight loss, fever or night sweats
• Picophagia

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Physical examination

• Pallor
• In dark skinned people not reliable
• Conjonktiva, mucous membranes, nail beds and
  palmar creases

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Investigations

• Rule out dilutional
• Peripheral Blood Smear
• What is the reticulocyte count?
• High?
• Acute blood loss (trauma, GI Bleed)
• Low?
• Decreased production
• MCV

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Peripheral Blood Smear (PBS)

• Size
• Colour
• Shape
• Distribution
• Inclusions

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PBS - Shape

• Spherocyte due to loss of membrane
• Hereditary spherocytosis, immune HA
• Elliptocyte
• Herediatry, megaloblastic anemia
• Fragmented cells (schistocytes, helmet cells)
• -split RBC due to traumatic disruption of
  membrane
• MAHA (TTP, DIC, HELLP, prosthetic heart valve)

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PBS Shape

• Sickle cell
• Target cell increased ratio RBC surface/volume
• thalassemia
• Teardrop
• myelofibrosis
• Acanthocyte (spur cells)
• severe liver disease
• Burr cell uremia, artifact

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Spherocyte
http//www.wadsworth.org/chemheme/heme/microscope/
spherocyte.htm
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Schistocyte
http//www.wadsworth.org/chemheme/heme/microscope/
schistocyte.htm
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Sickle Cell
http//www.wadsworth.org/chemheme/heme/microscope/
sicklecell.htm
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Target Cell
http//www.wadsworth.org/chemheme/heme/microscope/
targetcells.htm
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Burr cell
http//www.wadsworth.org/chemheme/heme/microscope/
echinocytes.htm
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PBS Distribution

• Rouleaux formation aggregates of RBC resembling
  stacks of coins
• Artifact
• Paraprotein (multiple myeloma, macroglobinemia)

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Rouleaux formation
http//www.wadsworth.org/chemheme/heme/microscope/
rouleaux.htm
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PBS - Inclusions

• Nucleated RBC immature RBCs
• Extramedullary hematopoiesis, hypoxia, hemolysis
• Heinz bodies denatured and precipitated
  hemoglobin
• G6PD deficiency
• Howell-Jolly bodies small nuclear remnant with
  the colour of a pyknotic nucleus
• splenectomy, hyposplenism
• Basophilic stippling deep blue granulations,
  pathologic aggregation of ribosomes
• Lead intoxication, thalassemia

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Howell Jolly Bodies
http//www.wadsworth.org/chemheme/heme/microscope/
howelljolly.htm
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Basophilic stippling
http//www.wadsworth.org/chemheme/heme/microscope/
basostip.htm
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Back to the Retic count
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You have a low retic count (ret. producing
index) now what?

• Whats the MCV?

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Causes of a Microcytic Anemia

• Iron Deficiency
• Thalassemia
• Anemia of Chronic Disease
• Lead Poisoning
• Sideroblastic

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So whats the next step?

• Check Iron studies

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Iron Studies

• Gold Standard?
• Bone marrow aspirate
• Lab studies?
• Ferritin
• Serum iron
• Total Iron Binding Capacity
• Transferrin Saturation
• Soluble transferrin receptor
• Hgb content of reticulocytes

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Ferritin

• Hepatocytes are main site of storage
• Also an acute phase reactant, elevates in
  inflammatory disease, liver disease, neoplasm,
  hyperthyroidism
• Single most important blood test for iron stores

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Serum iron

• Varies significantly daily
• A measure of all non-heme Fe in blood
• Virtually all serum iron is bound to transferrin
• Only a trace of serum Fe is free or complexed in
  ferritin

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TIBC

• High specificity for decreased iron, low
  sensitivity
• Measure of total measure of total amount of
  transferrin present in blood

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Saturation

• Serum Fe
• TIBC
• As a percentage or proportion
• lt 15

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Iron Deficiency Anemia

• Most common cause of anemia
• Etiology
• Increased demand (eg pregnancy)
• Decreased supply (diet, absorption)
• Increased loss

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Iron Deficiency Anemia

• Incrased loss
• Hemorrhage
• Obvious menorrhagia
• Occult PUD, ASA, GI cancer
• Intravascular hemolysis
• Hemoglobinuria
• Cardiac valve RBC fragmentation

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• Iron deficiency in males ALWAYS warrants a GI
  work up!!!

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Iron Deficiency Anemia

• Treatment
• Treat underlying cause
• Fe p.o.
• If malabsorption can give parenteral forms
  (biggest risk is anaphylaxis, though reduced with
  Venofer)
• Reticulocyte count increases after one week

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But what if those iron studies were normal?

• Check the RBC count

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If the RBC count is

• High
• (and there also happens to be a family history of
  anemia)
• Thalassemia
• Low
• AOCD
• Sideroblastic anemia

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Thalassemia

• Defects in the production of the Hb a or ß
  leading to microcytosis
• Recall
• 4 a genes, located on chr 16, two on each chr
• 2 ß genes, located on chr 11
• Fetal Hb (HbF) switches to adult forms HbA and
  HbA2 at 3-6 months of life
• HbA 97 of adult hemoglobin

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ß Thalassemia

• Defect in single gene Minor
• Defect in both genes Major
• Common among people of Mediterranean decent

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ß Thalassemia Minor

• Symptoms
• Mild or no anemia
• Possible palpable spleen
• Peripheral Blood
• Microcytosis hypochromia
• Target cells

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ß Thalassemia Minor

• Hb electrophoresis
• HbA2 slightly increased (gt4) above normal
  (1.5-3.5)
• otherwise non specific
• Treatment
• Not necessary
• Genetic counselling

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ß Thalassemia Major

• Ineffective chain synthesis leading to
  ineffective erythropoiesis and hemolysis of RBCs
• Increase in HbF
• Electrophoresis
• HgA 0-10 (normal gt95)
• HgF (90-100)

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ß Thalassemia Major

• Symptoms
• Initial presentation at 3-6 months due to
  replacement of HbF by HgA
• Severe anemia develops in the first year of life
• Jaundice
• Stunted growth and development (hypogonadal dwarf)

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ß Thalassemia Major

• Symptoms
• Gross HSM (extramedullary hematopoiesis)
• Bony changes
• Skull XR hair on end appearance
• Pathological fractures common
• Hb catabolism (gallstones)
• Death from
• Untreated anemia
• Infections
• hemochromatosis

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Hair-on-end appearance
http//radiology.rsnajnls.org/content/vol221/issue
2/images/large/r01nv03g1x.jpeg
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Anemia of Chronic Disease

• Infection
• Malignancy
• Inflammatory and rheumatologic disease

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Anemia of Chronic Disease

• Often have a mild hemolytic component
• Epo levels high/N but still low for the degree of
  anemia
• Diagnosis of exclusion
• biochemically R/O Fe deficiency

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Anemia of Chronic Disease

• PBS
• If mild normocytic, normochromic
• Moderate microcytic, normochromic
• Severe microcytic, hypochromic
• Bone Marrow
• Normal or increased Fe stores
• Decreased normal sideroblasts

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Megaloblastic Anemia

• B12 Deficiency
• Folate deficiency
• Drug induced
• MTX
• Folate analogue
• Purine/pyrimidine analogues

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Macrocytic Anemia

• Subdivided by whether or not there is impairment
  of DNA synthesis
• Megaloblastic
• Large nucleated RBC precursor
• Failure of DNA synthesis resulting in
  asynchronous maturation of RBC nucleus and
  cytoplasm
• Non-megaloblastic
• Large RBC
• Membrane abnormality with abnormal cholesterol
  metabolism

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Vitamin B12

• Binds to Intrinsic Factor (IF) secreted by
  gastric parietal cells
• IF stabilizes B12 as it passes through bowel
• Absorbed by terminal ileum
• Total body stores sufficient for 3-4 years

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Vitamin B12 deficiency

• Diet (rare)
• Gastric
• mucosal atrophy of PA
• Post gastrectomy
• Intestinal absorption
• Malabsorption (Crohns, celiac sprue)
• Stagnant bowel
• Fish tapeworm
• Resection of ileum

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Pernicious Anemia

• Auto-antibodies against gastric parietal cells
  leading to achlorhydria and no IF
• Maybe associated with other Autoimmune diseases

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Symptoms of Pernicious Anemia

• Neurological
• Cerebral (common, reversible)
• Confusion
• Delirium
• Dementia
• Cranial nerves
• Optic atrophy (rare)

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Symptoms of Pernicious Anemia

• Neurological
• Cord (irreversible damage)
• Subacute combined degeneration
• Posterior columns
• Pyramidal tracts
• Peripheral neuropathy (variable reversibility)
• Usually symmetrical
• Affecting lower limbs more than upper

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Pernicious Anemia

• PBS
• Macrocytes
• Hypersegmented neutrophils
• Bone Marrow
• Distinguishes between megaloblastic and
  myelodysplastic
• Hypercellular
• Failure of nuclear maturation

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Pernicious Anemia

• Labs
• MCVgt120
• Low retic count relative to the degree of anemia
• Low B12

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Pernicious Anemia

• Treatment
• Vitamin B12 1000µg/day IM 5 days
• Vitamin B12 1000µg/week IM 5 weeks
• Vitamin B12 1000µg/month IM

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Folate Deficiency

• Folate stores are depleted in 3-6 months
• Symptoms
• Mildly jaundiced
• Glossitis and angular stomatitis
• Deficiancy at time of conception and early
  pregnancy linked to neural tube defect (NTD)

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Folate Deficiency

• Etiology
• Diet (most common cause)
• Drugs/chemicals
• EtOH
• Anticonvulsants
• MTX

• Increased demand
• Pregnancy
• Prematurity
• Hemolysis
• Psoriasis
• Intestinal (malabsorption)

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And finally

• Normocytic Anemia

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Normocytic Anemia Algorithm
Check Creatinine
Pancytopenia?
Low Anemia of Renal Failure
Check SPEP
Yes Aplastic Anemia Myelophthisis
Normal Anemia of chronic disease Sideroblastic
Anemia (confirm with bone marrow)
Abnormal M-spike Multiple Myeloma
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To summarize
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Microcytic Anemia Algorithm
Check Iron studies
Low ferritin High RDW Iron deficiency Anemia
Check RBC count
High RBC Low RDW Family History Thalassemia
Anemia of Chronic Disease Sideroblastic
Anemia (Check Bone Marrow)
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Macrocytic Anemia Algorithm
Check B12, Folate, TSH
H/O EtOH? Liver dis?
Low B12/Folate deficiency, hypothyroidism
Check medications
Yes Alcohol Use Liver Disease
Myelodysplastic syndrome (Check Bone Marrow)
Drug Effects