Haematology 1 Flashcards
What is the composition of haemoglobin?
Metalloprotein
Heme:
Ferrous + Protoporphyrin IX
Globin:
2 alpha chains
2 beta chains
2,3 DPG in central pocket
1Hb = 4O2
Where is haemoglobin produced before birth?
Yolk sack until about 6 weeks post conception
Liver from 6 weeks until 6 weeks after birth.
Liver and spleen from 15 weeks until 6 weeks after birth
Bone marrow takes over after this
When is anaemia diagnosed?
<12 - 13g/dl
Or more than 2 standard deviation below the mean of normal range in an age and sex-matched representative population
What causes hypoproliferative anaemias?
Primary bone marrow pathologies (Red cell aplasia, aplastic, anaemia, fanconi anaemia)
Inadequate supply of ingredients (Iron, folate, B12, erythropoeitin deficiency)
Cytokine dysregulation
What are the types of hypoproliferative anaemias?
Based on the average size of cells and MCV
Microcytic
Macrocytic
Normocytic
What is the most common cause of microcytic anaemia?
Iron deficiency
What causes iron deficiency?
Blood loss
Decreased GI absorption
Increased iron requirement (pregnancy or exogenous EPO)
What are the clinical symptoms of iron deficiency anaemia?
Dizziness, fatigue, pallor, SOB, rapid HR
Glossitis
Angular cheilitis
Koilonychia
Pica
How is iron deficiency diagnosed?
Ferritin (BEST TEST)
Low serum iron
High TIBC (Total iron bondind capacity reflected by transferrin)
How is iron deficiency anaemia treated?
Find the cause
Oral or IV iron replacement
What causes normocytic normochromic anaemia?
Anaemia of chronic disease most common
Anaemia of renal failure
Hypothyroidism
Acute blood loss
What does hepicidin do?
It blocks import of iron from the vilus cells and from the macrophages.
What causes anaemia of chronic disease?
Impaired absorption of iron from the GI tract
Mediated by hepcidin
What chronic diseases cause anaemia of chronic disease?
Infective endocarditis
systemic lupus erythematous
Vasculitis
Cancer
How is anaemia of chronic disease treated?
Treat the underlying cause
Exogenous EPO
What causes macrocytic anaemia?
B12 and folate deficiency
Alcoholic liver disease
Myelodysplasia
Reticulocytosis
Hypothyroidism
Medication induced
What causes B12 deficiency?
Very rarely due to dietary deficiency
Deficiency is usually caused by malabsorption caused by: Pernicious anaemia, partial gasterectomy, Crohn’s, ileal resection
How does folate deficiency relate to B12 deficiency?
Both take years to develop
Folate deficiency is caused by poor intake and high demand. B12 is caused by disease more often.
Symptoms of folate are similar to B12 minus the neurological components
What is the major sign of hyperproliferative anaemia?
High reticulocyte index
What are the types of hyperproliferative anaemias?
Hereditary (Defects in RBC metabolism, defects in haemoglobin)
Acquired (Immune mediated (Direct coombs+) or non immune mediated (directed coombs -)
How is the direct coombs test done?
Blood sample taken from a patient with immune mediated haemolytic anaemia
Patient’s washed RBCs are incubated with antihuman antibodies
RBCs agglutinate caused by links between the RBCs with antibodies attached
What are the types of haemolytic anaemias?
Caused by environmental factors (acquired)
Caused by membrane defects (acquired)
Defects of cell interior (congenital)
What antibodies are involved in autoimmune haemolytic anaemia?
Mostly IgG (warm (reacts at body temperature))
IgM reacts at room temperature. IgM activates complement
What happens to RBCs attacked by antibodies in haemolytic anaemia?
They get taken up by the spleen to form spherocytes and then destroyed.
What is Thrombotic thromboctopaenic purpura (TTP)?
A form of acquired non-immune haemolytic anaemia
What causes TTP?
Can be sporadic: Deficiency in ADAMTS13 (remodels vWF) this is congenital and RARE. Acquired ADAMTS13 can also occur.
Allo-HCT caused by endothelial damage
Medications: Immune mediated (quinine, antimicrobials, gemcitabin, oxaliplatin, proteasome inhibitors) or toxicity/VEGF inibitors.
What toxic agents can be causative of thrombocytopaenic purpura?
immunosuppressive agents (Esp calcineurin inhibitors and drugs of abuse)
How does TTP present clinically?
Thrombocytopaenia
Macroangiopathic haemolytic anaemia
Renal failure
Neurological symptoms
What are the laboratory findings associated with TTP?
Schistocytes
Normal PT, PTT, fibrinogen and D-dimer
Elevated LDH
How is TTP treated?
Plasmapheresis with infusion of FFP (once started continue daily until the symptoms resolve. 20% relapse immediately after treatment)
What is the mortality of TTP like?
10 - 15% which is down from 100%
What are the clinical features of paroxysmal nocturnal haemolytic anaemia?
Haemolytic anaemia
Thrombosis
Impaired bone marrow function
What causes paroxysmal nocturnal haemolytic anaemia?
Defective PIG-A gene leading to loss of protective proteins of RBCs
What are the clinical features of paroxysmal nocturnal haemolytic anaemia?
Haemolytic anaemia
Thrombosis
Impaired bone marrow function
What are some common hereditary anaemias?
Hereditary spherocytosis (defect in membrane proteins)
G6PD deficiency (Over 300 types all are X-linked)
Haemoglobinopathies (Thalassemia (Most common and 2 types alpha/beta) and sickle cell anaemia)
What causes hereditary spherocytosis?
Defect in membrane proteins
What are the signs of G6PD deficiency?
Denatured HgB leading to the formation of Heinz bodies
What are the most common haemoglobinopathies?
Thalassemia
What are the conditions associated with alpha thalassemia?
Silent carrier if there is one deleted gene
Trait is seen in 2 deleted genes
Hb H disease in 3 deleted genes
Hydrops fetalis in 4 deleted genes
What are the characteristic blood cells of alpha thalassemia?
Target cells
What are the types of beta thalassemia? How are they characterized?
Minor: Beta globin deletion, asymptomatic, microcytosis, mild anaemia, splenomegaly, and target cells
Major: Homozygous B gene deletion, rarely survive childhood, hepatosplenomegaly, iron overload, progressive pulmonary HTN, marked expansion of the marrow
What causes sickle cell anaemia?
Autosomal recessive trait caused by Vernon substitution of GAG -> GTG resulting in glutamine to valine change in Hb (becomes HbS)
What are the orofacial features associated with sickle cell anaemia?
Hyperplasia of bone
Hair on end appearance
Osteomyelitis
Parasthesia
Can be asymptomatic
Can result in pulpal necrosis
What kind of anaemia does G6PD deficiency cause?
Normocytic anaemia
What kind of anaemia does sickle cell anaemia cause
Normocytic anaemia
What kind of anaemia does aplastic anaemia cause?
Normocytic anaemia
