HAEM: Systemic disease Flashcards
What does a deficiency of FVIII cause?
Haemophilia A –> bleeding disorder
What does a deficiency of protein C cause?
Pro-thrombosis
What is the types of primary haematological disorders. Give examples of each.
1.Germline mutation/inherited
- FIX e.g. FIX deficiency = haemophilia B
- Erythrocytes e.g. beta globin chain deficiency causes beta-thalassaemia
2.Somatic/acquired
- Erythrocytes - JAK2 V617F mutation in polycythaemia vera
- Myeloid/granulocyte - BCR-ABL1 mutation in CML
What is the difference between a primary and secondary haematological disorder?
Secondary are changes in haematological parameters secondary to a non-haematological disease e.g. cyanotic heart disease causing polycythaemia or excess FVIII in inflammatory responses
What does VHL gene mutation cause?
Chuvash polycythaemia causing excess erythrocytes
When are soluble haematological components increased?
in inflammation - this increases thrombosis
When are erythrocytes raised/reduced?
Raised:
- EPO secreting tumour
- Altitude
- Hypoxia
Reduced:
- BM infiltration
- Deficiency disease e.g. B12 or Fe
- Shortened survival in haemolytic anaemia
When are platelets raised/reduced?
Raised:
- bleeding
- inflammation
- splenectomy
Reduced:
- BM infiltration
- Deficiency disease e.g. B12
- Shortened survival e.g. ITP, TTP
When are leukocytes raised/reduced?
Raised:
- Inflammation
- Infection
- Corticosteroids
Reduced:
- BM infiltration
- Deficiency disease e.g. B12
List 4 types of anaemia.
- Iron deficiency
- Autoimmune haemolytic
- Microangiopathic
- Leucoerythroblastic
What are the laboratory findings in Fe deficiency anaemia?
- Microcytic
- hypochronic
- Reduced ferritin
- Reduced TF saturation
- Raised TIBC
Which cancers can cause occult blood loss causing Fe deficiency anaemia?
- GI cancers - gastric, colorectal
- Urinary tract cancers (less common - renal cell carcinoma, bladder
NB: Fe deficiency is bleeding until proven otherwise
- Menorrhagia in pre-menopausal women
- GI blood loss in men and post-menopausal women
What is leucoerythroblastic anaemia? Why is it important?
- Red and white cell precursor anaemia of variable degree
- Usually the first manifestation of a bone marrow malignancy – breakdown in barrier from immature cells leaving the bone marrow
What is the morphology of a leucoerythroblastic anaemia on peripheral blood film?
- Teardrop RBCs – aniso and poikilocytosis
- Nucleated (normal in BM but should lose nucleus before they leave) RBCs (left purple cell)
- Immature myeloid cells (right purple cell)
What are 3 causes of a leucoerythroblastic film?
- Malignant – haematological (leukaemia/lymphoma/myeloma) or non-haematological (metastatic/breast/bronchus/prostate)
- Severe infection e.g. miliary TB or severe fungal infection
- Myelofibrosis
Define haemolytic anaemia.
Shortened RBC survival
What are the common lab features of all haemolytic anaemias? Which liver associated proteins are raised?
- Anaemia – may be compensated
- Reticulocytosis – immature red cell production in an attempt to compensate for some short cell survival
- Unconjugated bilirubin raised i.e. pre-hepatic
- LDH raised – intracellular enzyme released as a result of cell content release due to lysis
- Haptoglobins reduced
How are haemolytic anaemias classified?
- Inherited
- Acquired
Give 3 examples of inherited haemolytic anaemias.
Inherited = defects of the red cell /germline DNA mutation
- Membrane e.g. hereditary spherocytosis
- Cytoplasm/enzyme e.g. G6PD deficiency
- Haemoglobin e.g. SCD (structural) or thalassemia (quantitative)
Give 2 types of acquired haemolytic anaemias.
Acquired = RBC is healthy but is due to defects in the environment where the RBC finds itself
- (1) Immune-mediated (DAT aka Coombs positive)
- (2) Non-immune mediated (DAT -ve)
What are the two types of immune-mediated haemolytic anaemia?
- Warm AIHA - IgG , extravascular haemolysis
- Cold AIHA - IgM (or IgG), intravascular haemolysis