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1. Anaemia
Oliver Rácz, 2015

2. Repetition of physiology and
biochemistry
•Red cell properties and function
–Number, synthesis, life span, degradation
•Haemoglobin structure and function
–Structure, oxygen affinity and its regulation,
variants, degradation
•Iron metabolism
–See trace element lecture
•Vitamin B
12and folic acid

3. Definition of anaemia
Deficiency in the oxygen-carrying capacity of the
blood due to diminished erythrocyte mass(THEORY)
Low red cell count, Hb, HT(PRACTICAL MEDICINE)
May be due to:
Erythrocyte loss(bleeding, haemolysis)
Decreased erythrocyte production
Bone marrow dysfunction
Low erythropoietin/high hepcidin
Iron deficiency
Vitamin B
12, folic acid deficiency

4. Indicators of anaemia
•MEASURED ON AUTOMATIC ANALYZERS
•Haemoglobin,grams of Hb/liter of whole blood (or g/dL in USA)
•Hematocrit, ratio between cell and plasma volume
•RBC= millions/microliter (= mm
3
) of whole blood (or 10
12
/liter)
•MCV= Mean corpuscular volume (of 1 RBC)
•> 100femtoliterMacrocytes (1 fl = 10
-15
liter)
•80 –100 femtoliter Normocytes
•< 80femtoliter Microcytes
•MCH = Mean corpuscular Hb (norm is 20 pg/cell; pico = 10
-12
)
•RDW =Red blood cell distribution width
–(Standard deviation of red cell volume/mean cell volume) ×100
–Normal value is 11-15%
–If elevated, suggests large variability in sizes of RBCs

5. Normal and decreased values
•Hb (160)
•Women: <120 severe <100
•Men: < 135
•Ht (0,45)
•Women: < 0,36 severe < 0,30
•Men: < 0,41

6. Symptoms of Anaemia ?
•Decreased oxygenation
–Pallor
–Exertional dyspnea
–Dyspnea at rest
–Fatigue
–Decreased mental function
•Decreased circulating volume
–Fatigue
–Muscle cramps
–Postural dizziness
–Syncope
•Disease/condition specific, e.g.
–Jaundice
–Other
FOR LONG TIME
MOSTLY
NOTHING,
HIDDEN BEHIND
THE BASIC
DISEASE
OR
COMPENSATED
NO CYANOSIS

7. Special considerations
•Acute Bleeding
•Drop in Hb& Htmay not be shown until some time after acute
blood loss (even though patient may be hypotensive)
•WHY???
•Later reticulocytosis
•Pregnancy
•In third trimester, RBC and plasma volume are expanded but
there is a bigger expansion of plasma volume than of red cell
mass.
•Lab values show reductions in Hb, Ht, and RBC count, often to
pathological levels, but according to RBC mass this is a
haemodilutionand not anaemia.
•BUT! Real anaemiais also frequent in gravidity
•Volume Depletion
•Patient’s who are severely volume depleted may have
physiological Htresults and do not show anaemicvalues until
rehydrated !!!

8. RBC Life Cycle
•In the bone marrow, erythropoietin enhances the
growth of differentiation of burst forming units-
erythroid (BFU-E) and colony forming units-erythroid
(CFU-E) into reticulocytes.
•Reticulocytes spend ≈ 3 days maturing in the marrow,
and ≈ 1 day maturing in the peripheral blood
(reticulocyte count ≈ 0,5% of RBCs).
•After blood loss or haemolysis increased % of
reticulocytes if bone marrow is OK
•Mature RBCs circulate in the peripheral blood for 120
days. Under steady state conditions, the rate of RBC
production equals the rate of RBC loss.(Around
1/120 ≈ 0,8 % of cells/day. Iron recycling!)

9. Erythrocyte loss -bleeding
•Acute/Haemodynamically significant(not a
haematological problem in general practice)
•Injury (shock!)
•Gastrointestinal (ulcus, oesophagus, polyps…)
•Retroperitoneal
•Hemophilia and other coagulation disorders
•Chronic
•kidney, abnormal menstrual cycle, ulcer disease in the past
•If not treated it can transform to iron deficiency anaemia

10. Haemolysis
•Osmotic –only in test tube (distilled water)
•Mechanical –artificial heart valves (past)
•Streptococcus haemolyticus ?
•ABO or Rh incompatibility
•Malaria, Babesiosis, and many others
•Autoimmune, toxic
•Inherited –Hb S and other Hbpathies,
thalassemia, membranopathies, enzymopathies

11. Some forms of haemolytic
anaemia
•Hereditary spherocytosis
•Glucose-6-phosphate dehydrogenase
(G6PD) Deficiency
•Most common enzyme defect in
erythrocytes
•X-linked
•Brisk haemolysis when patients
exposed to oxidative stress from
drugs, infections or toxins.
•Thrombotic Thrombocytopenic
Purpura (TTP)
•Thrombocytopenia and
microangiopathic haemolytic
Anaemia, fever, renal insufficiency,
neurologic symptoms
•Schistocytes on smear
•Haemolytic Uremic Syndrome
•Thrombocytopenia, Microangiopathic
haemolytic Anaemia, renal
insufficiency
•Autoimmune Haemolytic Anaemia
–Warm-antibody mediated
•IgG antibody binds to erythrocyte
surface
•most common
•Diagnosed by POSITIVE Coomb’s
Test (detectgs IgG or complement on
the cell surgace)
•Can be caused drugs
•Treated with corticosteroids or
splenectomy if refractory
–Cold agglutinin Disease
•IgM antibodies bind to erythrocyte
surface
•Does not respond to corticosteroids,
but usually mild.
•Infections
–Malaria
–Babesiosis
–Sepsis
•Trauma
–Includes some snake, insect bites

12. BABESIOSIS

13. Anaemia due to
Low erythropoietin
•Kidney Disease(including diabetic
nephropathy)
–Normocytic
–Low reticulocyte count
–Target Hb for patients on dialysis: 110 -120 g/L
•Administer erythropoietin
•Good iron stores should be maintained
–Peripheral smear in uraemic patients frequently
show echinocytes

14. Aplastic anaemia
(bone marrow dysfunction)
•Radiation
•Toxic substances
•Drug side effects
•Leukaemias

15. Iron deficiency
•Iron Deficiency
–Can result from:
–Pregnancy/lactation
–Normal growth
–Blood loss
–Intravascular haemolysis
–Gastric bypass
–Malabsorption
»Iron is absorbed in proximal small bowel; decreased abosrption in
celiac disease, inflammatory bowel disease
–May manifest as „pica“
•Tendency to eat ice, clay, starch, crunchy materials
–May have pallor, koilonychia of the nails, beeturia
–Peripheral smear shows microcytic, hypochromic red cells
with marked anisopoikilocytosis.

16. Koilonychia

17. Laboratory findings
•Serum Iron
•LOW
•Total Iron Binding Capacity (TIBC)
•HIGH
•Soluble transferrin receptors
•HIGH
•Serum Ferritin
•LOW
•Can be “falsely”normal in inflammatory states

18. Cobalamin deficiency
•Macrocytic Anaemia (megaloblastic, in the past “pernicious”
•Lab Values
–Cobalamin level < 200 pg/mL
–Elevated serum methylmalonic acid
–Elevated serum homocysteine
•Vit B12 binds to intrinsic factor in the small bowel in order to be
absorbed –the pernicious form was an autoimmune condition
blocking intrinsic factor
•Vit. B12 is needed for DNA synthesis
–The anaemia is only the tip of an “iceberg”
•Deficiency can result in cardiac and neuropsychiatric symptoms
–Spastic ataxia, psychosis, loss of vibratory sense, dementia
–Dilated cardiomyiopathy
•Smear shows macrocytosis and hypersegmentation of
polymorphonuclear cells, with possible basophilic stippling.

19. Folate deficiency
•
–Macrocytic Anaemia and a lot of other consequences (spina bifida)
–Lab Values
–Low folate
–Increased serum homocystine
–NORMAL methylmalonic acid
–Often occurs with decreased oral intake, increased utilization, or
impaired absorption of folate
–Folate is normally absorbed in duodenum and proximal jejunum –
deficiency found in celiac disease, regional enteritis, amyloidosis
–Deficiency frequently in alcoholics, because enzyme required for
deglutamation of folate is inhibited by alcohol.
–Deficiency often found in pregnant women, persons with
desquamating skin disorders, patients with sickle cell Anaemia
(and other conditions associated with rapid cell division and turnover)
–Smear shows macrocytosis with hypersegmented neutrophils
–BE CAREFUL WITH FOLATE OVERDOSE

20. Anaemia of „chronic disease“
•Usually normocytic, normochromic(but can
become hypochromic, microcytic over time)
•Occurs in people with inflammatory conditions
such as collage vascular disease, malignancy or
chronic infections
•Iron replacement is not necessary
•May benefit from erythropoietin supplementation.
•HEPCIDIN BLOCKS RESORBTION –IRON IS A
GROWTH FACTOR OF BACTERIA

21. The anaemia of chronic disease
the hepcidin story
•Hepcidin –a 25 aminoacid peptide from liver
discovered in 2001
•Ferroportin –a very specific transmembrane iron
export system
•Hepcidin injection: Serum Fe decrease by
blocking the Fe export from cells storing iron
•Hepcidin deficiency: High serum Fe –iron
overload.
•Inflammation –hepcidin elevated to block iron for
microbes

22. Normal peripheral „smear“

23. Echinocytes (“burr cells”)

24. Iron deficiency anaemia
MICROCYTIC

25. Megaloblasts and hypersegmented
neutrophil

26. Spherocytosis

27. TTP / HUS –microangiopathic
haemolysis with schistocytes

28. Malaria

29. Babesiosis

30. Sickle Cell Anaemia