Haematology Anaemia Flashcards
WHO definition of anaemia
Anaemia is a condition in which the number of red blood cells (and consequently their oxygen-carrying capacity) is insufficient to meet the body’s physiological need
Anemia Varies by
Age – older lower hb Gender – more in males Altitude – higher hb from hypoxic dribe Smoking behaviour Stage of pregnancy – haemodilute (although RBC is raised despite increased fluid)
Most useful parameter when assessing anaemia
Mean cell volume (MCV) is the most useful parameter when considering the cause of anaemia
Hb (g/L)
F:115-155
M:130-170
RBC volumes
F:3.8-5.3
M:4.5-6.0
Haematocrit ranges
F:0.37-0.45
M:0.40-0.52
MCV ranges
F:83-96
M:83-96
Mean cell haemoglobin
F:27-32
M:27-32
MCV <83 fL
Microcytic
MCV 83-96 fL
Normocytic
MCV >96 fL
Macrocytic
Microcytic
Iron defiency
Thalassemia
Anaemia of chronic disorder
Normocytic
Acute blood loss Haemolysis Anaemia of chronic disorder Bone marrow infiltration Combined haematinic deficiency
Macrocytic
B12/folate deficiency Haemolysis Hypothyroidism Liver disease Alcohol excess Myelodysplasia
Microcytic Anaemia: types
- Iron deficiency (covering this)
- Thalassaemia – covered elsewhere
- Anaemia of chronic disease
Iron deficiency Epi
Most common cause worldwide
Iron deficiency Causes (most common)
- Dietary insufficiency (80% from meat, 20% from vegetables) -
- Physiological (infancy, adolescence, pregnancy)
- Blood loss (GI, mennorhagia)
- Malabsorption e.g. coeliac disease
Iron deficiency Total body iron
4g:
- Hb 3g
- Reticuloendothelial system 1g
Iron deficiency Normal diet
Absorption = loss
Iron deficiency Clinical Features
- Angular stomatitis
- Glossitis
- Koilonchia
- Pharyngeal and oesophageal webs
Iron deficiency Laboratory Features
Microcytic hypochronic anaemia (Greater central pallor)
Low serum ferritin (beware: acute phase protein) *
Absent iron stores in bone marrow (rare late stage)
Further investigations: Physiological
Treat with oral iron
Further investigations: Females: pre-menopausal
Localising GI symptoms or signs
• Treat with oral iron
• Colonoscopy/Barium Enema OGD (Smal bowel study)
Further investigations: Males and post-menopausal women
Investigate:
Colonoscopy/Barium Enema OGD (Smal bowel study)
Normocytic Anaemias: types
- Acute blood loss
- Anaemia of chronic disease – insufficient production
- Bone marrow infiltration
- Combined haemotinic deficiency
- Haemolysis (exam favourite) - augmented destruction
Anaemia of Chronic disease: Definition
Depression of erythropoiesis of multifactorial aetiology seen as a secondary manifestation in a wide variety of disorders:
• Mild to moderate (hb 90-110 g/L)
• Normochromic/microcytic hypochromic
• Serum ferritin normal or increased
Anaemia of Chronic disease: Mechanisms
Main defect is failure of transport of iron from RE system to developing red cells
→ Proteins in liver/spleen/ bone marrow defect and therefore preventing transport to red cells
Anaemia of Chronic disease: Common causes
Chronic infection/inflammation – RA/SLE
Malignancy – nutritionally deficient and malignancy supresses erythropoiesis
Uraemia – high concentrations suppress erythropoiesis (kidney disease double hit)
Endocrine disorders – poorly controlled (hypothyroidism/diabetes)
Anaemia of Chronic disease: Treatment
Correction of underlying causes
Erythropoietin (+iron Iv) – potentially in inflammatory conditions. Floods bone marrow with iron readily available to ue and doesn’t rely on transport from elsewhere.
Haemolytic Anaemia: Definition
Increased destruction of red cells; reduced life span.
Compensation: expansion of erythropoiesis can increase red cell production 7x without anaemia presenting (will see haemolysis)
Decompensating: due to infection, folate deficiency or other stressors – when the anaemia presents
Haemolytic Anaemia:Haemolysis categorisation
Intravascular
Extravascular
Congenital (can be intra or extra vascular)
Acquired (can be intra or extra vascular)
Haemolytic Anaemia: Intravascular
Red cells lyse in circulation, release Hb into plasma (toxic)
Haemolytic Anaemia: Extravascular
Red cells phagocytised by macrophages In liver and spleen – no free Hb in plasma.
Haemolytic Anaemia: Congenital (present during childhood)
- Abnormal haemoglobulin e.g. sickle cell anaemia, thalassemia (contributes to anaemia)
- Abnormal membrane e.g. hereditary spherocytosis – circular cells destroyed faster
- Metabolic defect e.g. enzyme deficiency in glycolytic deficiency in glycolytic pathway (e.g. G6PD) or pentose phosphate shunt (e.g. pyruvate kinase
Haemolytic Anaemia: Acquired
- Immune e.g. autoimmune haemolytic anaemia (auto antigens on RBCs), incompatible blood transfusion
- Traumatic: cardiac valve replacement (abnormal flow), microangiopathic haemolytic anaemia (MAHA) – intravascular *
- Infection e.g. malaria, mycoplasma pneumonia
- Drugs/chemicals through a variety of mechanisms (penicillin- causes immune response)
Haemolytic Anaemia: Clinical features
- Anaemia
- Jaundice
- Splenomegaly – common in RE (extravascular)
- Skeletal abnormalities (chronic haemolytic conditions – bone marrow) - thalessaemia
- Gallstones – intravascular due to increased excretion
- Haemoglobinuria – overwhelmed capacity
Haemolytic Anaemia: Laboratory findings
- Anaemia
- Reticulocytosis – (Immature - large) up-regulated bone marrow action
- Unconjugated hyperbilirubinaemia
- Elevated LDH – marker of cell breakdown
- Absent/reduced haptoglobins – chaperone products of Hb in plasma
- Polychromasia, spherocytes, fragments of sickle cells – depending on cause
- Hyperplastic bone marrow
Autoimmune Haemolytic anaemia two types
Warm AIHI
Cold AIHI
Warm AIHA
IgG autoantibodies active at 37oCq
Warm AIHA Type
Extravascular Haemolysis – RBC with autoantigens taken up by macrophages and destroyed in spleen
Warm AIHA Causes
Idiopathic or Associated with Lymphoma
CLL
SLE
Drugs
Warm AIHI Treatment
Steroids: suppression of immune system
Rituximab (anti CD20 on B cells): suppression of immune system
Splenectomy: remove site where destruction is occuring
Fix causes: Chemotherapy for CLL/Lymphoma
Cold AIHA:
IgM autoantibodies active at <30oC – cross linking
Cold AIHA: Type of Haemolysis
RBC agglutination
Intravascular haemolysis in extremities (temp lower and poor ciruclation)
Cold AIHA: Causes
Idiopathic or associated with lymphoma
Mycoplasma and infectious mononucleosis (glandular fever)
Cold AIHA: Treatment
Keep Warm
Steroids
Rituximab
Chlorambucil
Macrocytic Anaemias: types
- Folate deficiency (most common)
- Vitamin B12 deficiency (Most common)
- Myelodysplasia (common in elderly)
- Hypothyroidism (macrocytes but normal Hb)
- Alcohol excess
- Liver disease (macrocytes but normal Hb)
- (Haemolysis)
Macrocytic definition
Red cells in peripheral blood are large. Erythropoiesis may or may not be megaloblastic.
Megaloblastic –
It is an assessment of bone marrow
• Red cell precursors are abnormally large because of impaired DNA synthesis. The cell continues to grow but does not divide, as it is incapable of replicating DNA.
• RNA synthesis of replicating DNA. RNA synthesis and translation not affected.
Vitamin B12 Deficiency: Type
Megaloblastic anaemia
Vitamin B12 Deficiency:Daily requirement of vitamin B12
1-2 ug.
Vitamin B12 Deficiency: Body stores
2-3 mg; mainly in the liver
Vitamin B12 Deficiency: Synthesised by
Micro-organisms: only present naturally in animal produce
Vitamin B12 Deficiency: Absorption
Combines with intrinsic factor secreted by gastric parietal cells and absorbed in terminal ileum.
Vitamin B12 Deficiency: Causes
Dietary: veganisms, rare
IF deficiency:
• Pernicious anaemia (Ab against parietal or IF)
• Gastrectomy
• Congenital
Intestinal malabsorption – disease in terminal ileum e.g. Crohns, blind loops and small bowel diverticulae.
Vitamin B12 Deficiency: Clinical features
Anaemia
Jaundice
Glossitis
Neurological deficit
Vitamin B12 Deficiency: Laboratory findings
- Anaemia, neutropenia, thrombocytopenia
- Lower serum vitamin B12
- Antibodies against peripheral cells or IF
- Megaloblastic change in bone marrow
- Features of Haemolysis
Vitamin B12 Deficiency: Historical B12 test
B12 absorption test – schilling test
Folic Acid deficiency: Anaemia Type
Megaloblastic anaemia
Folic Acid deficiency: Daily requirement
100-200 ug
Folic Acid deficiency: Body stores
10-15 mg (low therefore easier to require)
Folic Acid deficiency: Dietary sources
Green vegetables
Liver
Nuts
Cereal
Folic Acid deficiency: Absorbed in
Jejunum
Folic Acid deficiency: Close link with
Vitamin B12
Folic Acid deficiency: Causes
- Dietary – common in elderly, poor diet related to alcohol misuse
- Increased utilisation – e.g. in pregnancy, malignancy, haematological disorders with rapid ell turnover
- Malabsorption e.g. coeliac disease
- Drugs e.g. anticonvulsants
- Excessive loss e.g. renal dialysis
Folic Acid deficiency: Clinical Featured
Similar to Vitamin B12 Deficiency but neurological problems don’t occur
Folic Acid deficiency:Lab features
Peripheral blood and bone marrow features identical to Vitamin B12 Deficiency
Folic Acid deficiency:Diagosis made by
Measuring low serum (and sometimes red cel) folate levels.
Folic Acid deficiency:Treatment
- Address underlying causes
- Vitamin B12 replacement as IM injection most common – 3x per week for 2 weeks then maintenance phase( patients usually have malabsorption therefore bypass)
- Oral folic acid replacement
Folic Acid deficiency: Care:
Risk subacute combined degeneration of the cord (with permanent neurological sequel) if folic acid replace in absence of Vitamin B12. Replace B before F.
