Pathology - Blood Cells

Question 1

How are the causes of anaemia classified

Answer 1

1) Anaemia of blood loss
- acute or chronic blood loss

2) Anaemia of increased destruction (haemolytic anaemia)
- hereditary spherocytosis, G6PD, sickle cell disease, thalassemia, immunohaemolytic

3) Anaemia of decreased production
- megaloblastic anaemia, anaemia of chronic disease, aplastic anaemia, iron deficiency anaemia

Question 2

Describe the pathogenesis of iron deficiency anaemia and the symptoms

Answer 2

cause: decreased intake, malabsorption, increased demand (pregnancy), chronic blood loss (gi tract, menorrhagia)
film: hypochromic, microcytic anaemia, low serum iron and ferritin and transferrin saturation, high TIBC
symptoms: fatigue, weakness, dyspnea, angina, melena, menorrhagia

specific features: koilonychia, alopecia, glossitis, pharyngeal web, pica

Question 3

What anaemias are more common in specific ethnic groups

Answer 3

G6PD, SCD & thalassemia (african, mediterranean, middle eastern, south asian)
hereditary spherocytosis (northern european)
pernicious anaemia (scandanavian)

Question 4

Describe common features of haemolytic anaemia, classify and provide causes

Answer 4

features: premature RBC destruction, elevated EPO, increased bilirubin

1) Extravascular: occurs in macrophages of the spleen
2) Intravascular: occurs within blood vessels

causes: mechanical injury (cardiac valves), transfusion reaction, parasites (malaria), toxins (clostridial enzymes)

Question 5

What is sickle cell disease and what are the pathological manifestations and precipitants for crisis

Answer 5

hereditary autosomal recessive disorder causing abnormal sickle substitute for the normal beta globin monomer

• adult normally has 2 alpha and 2 beta chains, in sickle cell there are 2 alpha, 1 beta and 1 sickle chain
• when deoxygenated, HbS changes shape and deforms Hb

manifestations: haemolysis, microvascular occlusions (pain and ischaemia), splenic enlargement, aplastic crisis
precipitants: hypoxia, dehydration, drop in pH

Question 6

What is another classification of haemolytic anaemias

Answer 6

1) inherited genetic defects: spherocytosis, G6PD, thalassaemia, sickle cell disease
2) antibody mediated destruction: transfusion reactions
3) mechanical trauma: cardiac valves, DIC
4) infections of RBC: malaria
5) toxic: envenomation

Question 7

What are the manifestations of intravascular haemolysis

Answer 7

anaemia
hemoglobinaemia
hemoglobinuria
unconjugated hyperbilirubinaemia
reduced serum haptoglobin

Question 8

What is the pathogenesis of pernicious anaemia and clinical manifestations

Answer 8

pathogenesis: caused by autoimmune gastritis and loss of intrinsic factor production

• gastric injury initiated by auto-reactive T cells
• parietal cells in stomach are replaced by mucus secreting goblet cells
• loss of secretion of intrinsic factor needed for absorption of vitamin b12 in distal ileum

manifestations: insidious onset
- megaloblastic anaemia, thrombocytopenia, weakness, pallor, mild jaundice, atrophic glossitis, spastic paresis

Question 9

What is haemophilia A and why do they bleed

Answer 9

• most common hereditary disease associated with life-threatening bleeding, due to mutations in factor 8
• x-linked recessive disorder, so bleeding occurs in males and homozygous females
• factor 8 is a co-factor for factor 9 in activating factor 10
• causes reduced amount of factor 8 and thus prolonged PTT (intrinsic pathway defect)
• extrinsic pathway remains intact but not sufficient to provide a stable clot

Question 10

What is the association between clinical severity and factor 8 levels

Answer 10

<1% severe
2-5% moderate
>6-50% mild

Question 11

What are causes of thrombocytopenia

Answer 11

1) decreased production: due to ineffective megakaryopoiesis (HIV) or marrow disease (aplastic anaemia)
2) decreased survival: due to increased consumption (DIC) or immune destruction (SLE)
3) sequestration: hypersplenism
4) dilutional: due to massive transfusions

Question 12

What is the pathogenesis of immune thrombocytopenic purpura?

Answer 12

• increased bleeding caused by autoantibodies formation against platelets, leading to platelet destruction by macrophages in the spleen and liver
• triggers: post viral infection, drugs, HIV

Question 13

What are the haematological, clinical effects and types of von willebrand disease

Answer 13

• function: stabilising VIII, platelet adhesion & aggregation
• haematological: increased bleeding time with prolonged aPTT, normal PT, normal platelets, reduced ristocetin-induced platelet aggregation
• clinical: spontaneous bleeding from mucous membranes, increased bleeding from wounds, menorrhagia

types:

1) type 1 (partial quantitative deficiency) = autosomal dominant, reduced level of vWF, mild severity
2) type 2 (qualitative defects) = autosomal dominant, defect in vWF, mild severity
3) type 3 (complete quantitative deficiency) = autosomal recessive, marked reduction in vWF function, rare and severe