Anaemia

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Anaemia

• Prof. A. B. Skotnicki M.D. Ph.D.

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Anaemia

• Decreased haemoglobin concentration and/or PCV

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Internal iron exchange.

• Absorption - about 1 mg/d is required from the
  diet in men, 1.4 mg/d in women
• transferrin saturation 20 to 60

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Iron storage and transport
Tissue ferritin
Serum transferin 20 umol/l
Bone Marrow Erythroblasts
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Classification of anaemia

• Morphological
• Based on red cell measurement

• Aetiological
• Based on cause

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Aetiological classification of anaemia
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Morphological classification of anaemia
Acute blood loss Haemolysis Bone marrow
aplasia Bone marrow infiltration
? Fe
? B12 ? fol.ac.
Chronic disease
? MCV ? MCH
? MCV ? MCH
MCV and MCH normal
Macrocytic hyperchromic Megaloblastic anaemia
Microcytic hypochromic anaemia
Normocytic normochromic anaemia
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Anaemia signs and symptoms

• General signs and symptoms universal for all
  anaemias
• Signs and symptoms specific for a particular cause

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General symptoms of anaemia
? O2 carrying capacity of blood TISSUE HYPOXIA
? Hb
Compensatory mechanisms mobilised to contract
hypoxia
Clinical manifestations
Palpitations Tachycardia Heart murmurs
Cardiac overactivity
Cadiorespiratory insufficiency
dyspnoea
Skin vasoconstriction redistribution of blood
flow (brain, heart)
pallor
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Anaemia general signs and symptoms

• CSN
• Headaches
• Tinnitus

Pale skin mucous membranes

• General
• Shortness of breath
• Fatigue
• Weakness
• Susceptibility to infections

• CVS
• Tachycardia
• Functional murmur
• Stenocardiac pain

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Anaemia major types

• Iron deficiency anaemia
• Megaloblastic anaemia
• Haemolytic anaemia
• Aplastic anaemia
• Anaemia of chronic disease

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Normal erythropoiesis
Fe
B12
haemoglobinisation
MCV90 fl
HB
N

MCHC32 g/l
N
E
RBC production
MCH32 pg
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Erythropoiesis in IDA or after bleeding
Fe
B12
haemoglobinisation
MCV70 fl
HB
ltN

MCHC28 g/l
N/gtN
E
RBC production
MCH25 pg
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Iron deficiency anaemia (IDA) - causes
Increased requirement
Inadequate intake

• Chronic blood loss
• GI
• Urinary Tract

Iron malabsorbtion
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IDA causes of chronic blood loss
Haematemesis Haemoptysis

• Gastrointestinal tract bleeding
• Hiatus hernia
• Gastritis haemorrhagica
• Peptic ulcer
• Gastric cancer
• Intestinal polyposis
• Colonic cancer
• Colitis ulcerosa
• Haemorrhoidal varices

• Urinary tract
• bleeding haematura
• Renal disorders
• Inflammation
• Tumour
• Urinary tract
• Calculosis
• Polyps
• Urinary bladder tumours

• Genital tract bleeding
• Menorrhagiae
• Metrorrhagiae
• Uterine myoma

• Melaena

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IDA - signs and symptoms
General signs and symptoms PLUS tissue asiderosis

• Hair
• Fragility, coming out
• Early gray

• Skin
• Dry, cracked
• Cheilitis angularis
• rhagades

• Eyes
• Bluish sclera

• Nails
• Brittle, spoon nails
• Atrophic changes

• Tongue
• Glossitis anaemica

Dysphagia Plummer-Vinson syndrome
Pica
Gastric troubles
Neurovegetative dystonia
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Moderately severe iron deficiency anaemia

• This example of moderately severe iron deficiency
  anaemia shows anisocytosis, anisochromasia,
  hypochromia, microcytosis and poikilocytosis. The
  poikilocytes include several particularly long
  elliptocytes, sometimes referred to as 'pencil
  cells'. Elliptocytes are characteristic of iron
  deficiency but not pathognomonic.

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Severe iron deficiency anaemia

• Blood film from a patient with severe iron
  deficiency anaemia. The film shows anaemia,
  microcytosis, hypochromia, anisocytosis,
  anisochromasia and poikilocytosis.

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Pallor in iron deficiency anaemia

• The hand of a patient with iron deficiency
  anaemia showing pallor. The hand of a non-anaemic
  person is pictured for comparison. Pallor is a
  non-specific feature of anaemia.

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Pale conjunctiva in iron deficiency anaemia

• The best places to check for pallor that may
  indicate anaemia are the conjunctiva, the nail
  beds and the palms of the hands. This patient
  with iron deficiency anaemia has conjunctival
  pallor.

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Pallor in iron deficiency anaemia

• Pallor in a patient with iron deficiency anaemia.
  The patient's hand is pictured together with the
  hand of a healthy person.(Courtesy of Dr D.
  Samson.)

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Oral changes in iron deficiency anaemia

• Angular cheilosis and atrophic glossitis in iron
  deficiency anaemia. These features are typical of
  moderately severe iron deficiency anaemia and
  indicate the effect of iron deficiency on tissues
  other than the bone marrow.(Courtesy of Dr D.
  Samson.)

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Cheilitis Angularis in IDA
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Koilonychia in iron deficiency anaemia

• Koilonychia or spoon-shaped nails in iron
  deficiency anaemia. Koilonychia has a high degree
  of specificity for iron deficiency but it is a
  relatively uncommon feature, occurring only in
  severe chronic iron deficiency.

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Typical changes in blood count in IDA

• Normal Blood Count
• Hb 14 g/dl
• RBC 4,50 x 1012/l
• PCV 40
• MCV 90 fl
• MCH 30 pg
• Ret 0,5
• WBC 7,5 x 109/l
• Differential normal
• Platelets 400x109/l

• Blood Count in IDA
• Hb 7,5 g/dl
• RBC 4,05 x 1012/l
• PCV 26
• MCV 64 fl
• MCH 18,5 pg
• Ret 2,6
• WBC 7,5 x 109/l
• Differential normal
• Platelets 530x109/l

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Iron deficiency is NOT a diagnosis but a symptom
Iron Deficiency anaemia
Aetiology ?
Clinical laboratory findings
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Iron deficiency anaemia

• 53 old male
• Tiredness
• Hb 7 g/l
• MCV 69 fl
• Serum ferritin 8ug/l
• Occult faecal blood test positive ()
• Colonoscopy

• Carcinoma of the colon

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22 years old patient with ACD (Hodgkins lymphoma)
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Megaloblastic Anaemia

• Abnormal changes in blood cell formation leading
  to macrocytic anaemia and varying degrees of
  pancytopenia as a result of abnormal DNA
  synthesis because of single or combined
  deficiency of folate and/or vitamin B12

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Normal erythropoiesis
Fe
B12
haemoglobinisation
MCV90 fl
HB
N

MCHC32 g/l
N
E
RBC production
MCH32 pg
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Erythropoiesis in B12 deficiency
Fe
B12
haemoglobinisation
MCV100 fl
HB
N

MCHC32 g/l
ltN
E
RBC production
MCH40 pg
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Megaloblastic anaemia - causes
Inadequate intake
Increased requirement
Malabsorbtion

• Disturbed metabolism

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Megaloblastic anaemia - causes

• FOLIC ACID DEFICIENCY
• Inadequate intake unbalanced diet (common in
  alcoholics, teenagers, some infants)
• Increased requirements Pregnancy, Infancy,
  Malignancy, Increased hematopoiesis, Chronic
  exfoliative skin disorders
• Malabsorption Tropical sprue, Nontropical
  sprue, others

• COBALAMIN DEFICIENCY.
• Inadequate intake vegetarians (rare)
• Malabsorption Defective release of cobalamin
  from foodGastric achlorhydria, Partial
  gastrectomy, Drugs that block acid secretion
• Inadequate production of intrinsic factor (IF)
  Pernicious anemia Total gastrectomy Congenital
  absence or functional abnormality of IF Disorders
  of terminal ileum
• Competition for cobalamin
• Other

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Megaloblastic anaemia - causes
Cause B12 deficiency Folic acid deficiency
1. Dietary deficiency   2. Malabsorbtion Atrophic gastritis Hipochlorchydria Lack of intrisinc factor Small bowel diseases Post gastrectomy   3. Increased demands Pregnancy   4. Disturbed metabolism anticonvulsives cytostatics rarely         -     - often (alcohol abuse, parenteral nutrition, age)   - - -        
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Megaloblastic anaemia symptoms and signs

• CSN
• Headaches
• Tinnitus

• Visual disturbances
• Optic nerve disturbances
• Psychiatric disturbances
• Irritability
• Sleepiness
• Dementia
• Peripheral neuropathy
• Paresthesia
• Pins and needles
• Unsteady gait
• Reduced Sensation
• Imbalance
• Dysuria
• Reduced heat and cold sensibility

• Glossitis Hunteri
• smooth
• Reddened
• Burning
• Reduced in size
• Loss of appetite
• Loss of taste
• Loss of body weight
• Abdominal pains
• Atrophic gastritis
• Diarrhoea
• Achlorchyrdia

Average age 60 Often - women
Specific PLUS General signs and symptoms
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Blood film in megaloblastic anaemia

• In megaloblastic anaemia the most characteristic
  features in the peripheral blood film are
  hypersegmented neutrophils and macrocytes,
  particularly oval macrocytes arrow. The
  neutrophil shown has six lobes and is therefore
  classified as hypersegmented    

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Haemolytic anaemia

• Decrease in the total number of circulating
  erythrocytes that is caused by premature
  destruction or removal of red cells from the
  circulation

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Haemolytic anaemia

• Classifications of HA according to
• Type of defect
• Site of defect
• Site of haemolisis

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Classification of HA according toType of defect

• Hereditary
• Membrane defect
• Metabolic defect
• Hemoglobinopathies

• Acquired
• Immunologic defect
•  Mechanical defect
• Intravascular coagulopathy
•  March hemoglobinuria
• Infection
• Membrane abnormality

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Classification of HA according toType of defect

• Hereditary
• Membrane defect
• HS
• Hereditary elliptocytosis
• Metabolic defect
• GdPD deficiency
• PK deficiency
• Hemoglobinopathies
• Thalassemias
• Sickle cell diseases
• Other hemoglobinopathies

• Acquired
• Immunologic defect
• Drug-induced hemolysis
• Isoimmune and alloimniune hemolysis (neonatal and
  delayed transfusion reactions)
•  Mechanical defect
• Rapid turbulent flow of blood, tumors,
  hypertension, aortic stenosis, Prosthetic valve
  leaks
• Intravascular coagulopathy
•  March hemoglobinuria
• Infection
• Membrane abnormality (stem cell abnormality)

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Classifications of HA according toSite of defect

• Extracorpuscular factors
• Antibodies (Autoimmune hemolytic anaemia,
  transfusion-related haemolytic reactions,
  Drug-related hemolytic reactions)
• Mechanical or traumatic factors (Prosthetic heart
  valves, High-flow red cell damage, Intravascular
  coagulopathy)
• Infections (Bacterial, Parasitic)
• Cell membrane lipids (Liver disease, Lipid
  disorders)

• Intracorpuscular factors
• Red cell membrane abnormalities (HS and related
  abnormalities PNH)
• Hemoglobinopathies (Thalassemias, Sickle cell
  disease and related hemoglobinopathies,
  Methemoglobinemia, Unstable hemoglobin diseases )
• Enzymopathies (G6PD deficiency Others)

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Classifications of HA according toSite of
Haemolysis

• Extra vascular hemolysis
• Autoimmune hemolytic anemia
• Red cell membrane defects
• Spur cell anaemia
• Red cell metabolism defect
• Unstable haemoglobin diseases

• Intravascular hemolysis
• Traumatic hemolysis
• Immune hemolysis
• Infections

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Clinical signs and symptoms of haemolytic anaemia

• General signs and symptoms universal for all
  anaemia
• Signs and symptoms specific haemolysis
• Jaundice
• Increased billirubin (unbound)
• Increased reticulocitosis

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Example of blood film in HA

• Microangiopathic haemolytic anaemia
• Blood film showing the features of
  microangiopathic haemolytic anaemia in haemolytic
  uraemic syndrome. There are schistocytes
  including one microspherocyte

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Aplastic anaemia

• Acellular or hypocellular marrow that causes bone
  marrow failure and lower level of cell
  production, leading to pancytopenia.
• Etiology
• Idiopathic
• Secondary

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Causes of Secondary Aplastic Anaemia

• Drugs and toxins
• Chloramphenicol
• Cancer chmotherapy
• Chemicals
• Infections
• Viral hepatitis
• CMV
• Infectious mononucleosis
• Parvovirus 19

• Proleukaemic and leukaemic conditions
• Paroxysmal nocturnal haemoglobinuria
• Genetic or constitutional conditions

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Bone marrow in AA

• Normal Bone marrow

• Bone marrow in AA

Residual haemopoesis
Fat cells
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Signs and symptoms of AA

• The results of pancytopenia
• Anaemia (general signs)
• Thrombocytopenia (bleeding tendency)
• Granulocytopenia (infections)

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Normal bone marrow (right) and in aplastic
anaemia (left) trephine biopsies
AA
normal
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Anaemia of chronic disease (ACD)

• Common type of anaemia that occurs in patients
  who present with any of several chronic
  inflammatory and malignant diseases

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Anaemia of chronic disease (ACD)

• Anaemia of chronic disease
• caused by a defect in incorporation of iron into
  haemoglobin as a consequence of infection,
  inflammation or malignant disease.
• Bone marrow iron stores are usually normal or
  increased. The anaemia is initially normocytic
  and normochromic but when it becomes severe is
  hypochromic and microcytic.

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Signs and symptoms of ACD

• General signs and symptoms of anaemia
• Blood film as in IDA
• No tissue asiderosis

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ACD IDA clinical laboratory differences
Feature ACD IDA
Severity
Tissue asiderosis -
Chronic disorder
? ESR fever ?WBC ?PLT pain lymph nodes ? -

Serum iron ? ??
Serum ferritin ? ?
Serum transferin ? ?
TIBC ? ?
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Signs and symptoms in anaemia
Anaemia Signs and symptoms
Aplastic Marrow failure
Iron deficiency Tissue asiderosis
B12 follic acid deficiency Neuro gastrointestinal
Chronic disease Without tissue asiderosis
Haemolytic Haemolysis
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Anaemia of chronic disease -bone marrow
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Comparison of blood films in anaemias
Normal
Macrocytic
IDA
Haemolytic
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Fe, TIBC and UIBC
TIBC 60 umol/l
UIBC
Fe 20 umol/l
NORMAL
Fe overload
IDA, pregnancy
Infections cancers
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Oral iron absorbtion test
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MCV in anaemia
Microcytic (MCVltN) Normocytic (MCVN) Macrocytic (MCVgtN)
Iron deficiency FeltN, FerritinltN, TIBCgtN Aplastic Reticulocytes lt N B12 ltN
Chronic disease FegtN, Ferritin,gtN Haemolytic Reticulocytes gt N Folic acid ltN
Talasemia Fe gtN, Ferritin gtN Acute blood loss Reticulocytes gt N