Haematological disorders Flashcards
What is haemopoiesis?
The process which maintains lifelong production of haemopoietic (blood) cells
Where is the main site of haemopoiesis in the foetus and in postnatal life?
Fetal - fetal liver
Postnatal - bone marrow
How does HbF (fetal haemoglobin) differ from adult Hb?
HbF has a higher affinity for oxygen than adult Hb
When does HbF stop being present in the blood stream?
After about 1 year HbF is very low in healthy children
How does Hb alter throughout birth and the first stages of life?
Hb concentration is high at birth but falls to its lowest level at 2 months of age
What are the mechanisms of anaemia?
Reduced red cell production (iron deficiency) Increased red cell destruction (haemolysis) Blood loss (relatively uncommon in children)
What are the main causes of reduced red cell production?
Ineffective erythropoiesis (iron deficiency, folic acid deficiency, chronic inflammation (JIA), chronic renal failure) Red cell aplasia (complete absence of red cell production)
What are the main causes of increased red cell destruction?
Red cell membrane disorders
Red cell enzyme disorders
Haemoglobinopathies
Immune
What are the main causes of iron deficiency in children?
Inadequate intake
Malabsorption
Blood loss
How would you diagnose iron deficiency in children?
Microcytic, hypochromic anaemia
Low serum ferritin
If the bilirubin is raised in anaemia what does that tell you about the cause?
It is haemolysis as bilirubin is created from the break down of red blood cells
What are the main diseases causing haemolytic anaemia?
Sickle cell
Beta thalassaemia
G6PD deficiency
How do you manage iron deficiency?
Dietary advice
Supplementary oral iron for several months, a minimum 3 months after Hb has returned to normal
What are the disease consequences of haemolysis?
Anaemia
Hepatomegaly and splenomegaly
Increased blood levels of unconjugated bilirubin
Excess urinary urobilinogen
What are the diagnostic clues to haemolysis?
Raised reticulocyte count
Unconjugated bilirubinaemia and increased urinary urobilinogen
Abnormal appearance of the red cells on a blood film
Positive direct antiglobulin test
Increased red blood cell precursors in the bone marrow
What is G6PD deficiency?
G6PD is the rate-limiting enzyme in the pentose phosphate pathway and is essential for preventing oxidative damage to red cells. Those deficient are susceptible to oxidant-induced haemolysis
How is G6PD deficiency inherited?
It is X-linked so mainly affects males
How does G6PD deficiency present?
Neonatal jaundice within first 3 days
Acute haemolysis precipitated by infection, certain drugs, fava beans and naphthalene in mothballs.
Fever, malaise and dark urine
How do you diagnose G6PD deficiency?
Measuring G6PD activity in red blood cells
How do you manage G6PD deficiency?
The parents should be given advice about the signs of acute haemolysis and provided with a list of drugs, foods and chemicals to avoid
What are haemoglobinopathies?
RBC disorders which cause haemolytic anaemia because of reduced or absent production of HbA (thalassaemia) or because of the production of abnormal Hb (sickle cell)
Which races is sickle cell most common in?
Patients whose parents are black and originate from tropical Africa or the Caribbean but it is also found in the middle east
How does sickle cell disease affect the cell shape?
HbS polymerises within RBCs forming rigid tubular spiral bodies which deform the red cells into a sickle shape.
What does the abnormal sickle cell shape mean practically?
The cells have a reduced lifespan and may be trapped in the microcirculation, resulting in blood vessel occlusion and therefore ischaemia in an organ or bone.
What exacerbates vaso-occlusive crises in sickle cell?
Low oxygen tension, dehydration, undue stress, excessive exercise and cold
What are the clinical features of sickle cell disease?
Anaemia Infection Painful crises Acute anaemia Priapism Splenomegaly Long-term problems
What does the increased risk of infection in sickle cell disease mean practically?
Full immunisation is required
Daily oral penicillin throughout childhood should be given
Daily folic acid
What is the most common painful crisis in sickle cell disease?
Vaso-occlusive crises
How do vaso-occlusive crises present ?
Pain may affect many organs of the body with varying frequency and severity. A common mode of presentation in late infancy is the hand-foot syndrome, dactylics with swelling and pain of the fingers and/or feet from vast-occlusion
What is the most severe painful crisis in sickle cell disease and why?
Acute chest syndrome, it can lead to severe hypoxia and the need for mechanical ventilation and emergency transfusion
What are the crises that can lead to acute anaemia in sickle cell disease?
Haemolytic crises
Aplastic crises
Sequestration crises
What are the long term complications of sickle cell disease?
Short stature and delayed puberty Stroke and cognitive problems Adenotonsillar hypertrophy Cardiac enlargement Heart failure Renal dysfunction Pigment gallstones Leg ulcers Psychosocial problems
How do you treat painful crises in sickle cell disease?
Oral or IV analgesics
Good hydration
How can you treat the chronic complications of sickle cell?
Hydroxyurea
People from which areas are at more risk of beta thalassaemia?
Indian subcontinent, Mediterranean and Middle East
What are the two main types of beta thalassaemia?
B-thalassaemia major
B-thalassaemia intermedia
What are the clinical features of beta thalassaemia?
Severe anaemia (transfusion dependent age 3-6 months) Failure to thrive Extramedullary haemopoiesis (prevented by regular transfusions)
How do you treat beta thalassaemia?
Lifelong monthly RBC transfusions
What are the complications of lifelong monthly RBC transfusions?
Chronic iron overload, leading to: cardiac failure liver cirrhosis diabetes infertility growth failure
How are the complications of RBC transfusions treated in B-thalassaemia?
Additional iron chelate with SC desferrioxamine OR
oral iron chelator drug such as deferasirox
What is the only cure for B-thalassaemia?
Bone marrow transplant
How can you distinguish between anaemia and B-thalassaemia trait?
Measuring serum ferritin, which is low in iron deficiency but not in B-thalasseamia trait
What is a haemolytic disease of the newborn example?
Rhesus disease
What are the main causes of blood loss in neonates?
Feto-maternal haemorrhage
Twin-to-twin transfusion syndrome
Blood loss around the time of delivery
What are the main causes of anaemia of prematurity?
Inadequate erythropoietin production
Reduced red cell lifespan
Frequent blood sampling whilst in hospital
Iron and folic acid deficiency (age 2-3 months)
What are the five main components of normal haemostasis?
Coagulation factors Coagulation inhibitors Fibrinolysis Platelets Blood vessels
What is the endpoint of the coagulation cascade?
The generation of thrombin
What is haemophilia?
X-linked recessive disorder
Excessive bleeding in a variety of different severities, the severity usually stays constant within the family
How would you treat haemophilia?
Recombinant Factor (whichever is causing type A or B) concentrate
What should be avoided in all haemophilia patients?
Intramuscular infections, aspirin and NSAIDs
What are the two major roles of von Willebrand factor?
Facilitates platelet adhesion to damaged endothelium
Acts as the carrier protein for VFIII:C; protecting it from inactivation and clearance
How is von Willebrand disease inherited?
Usually autosomal dominant
What are the clinical features of von Willebrand disease?
Bruising
Excessive, prolonged bleeding after surgery
Mucosal bleeding such as epistaxis and menorrhagia
How does von Willebrand disease differ from Haemophilia?
In contrast to Haemophilia, spontaneous soft tissue bleeding such as large haematomas and haemarthroses are uncommon
How can von Willebrand disease be treated?
DDVAP
What are the main causes of acquired disorders of coagulation?
Haemorrhagic disease of the newborn due to vit K deficiency
Liver disease
Immune thrombocytopenia
DIC
What are the clinical features of thrombocytopenia?
Bruising
Petechiae
Purpura
Mucosal Bleeding (epistaxis, gum bleeding)
What causes immune thrombocytopenia ?
Destruction of circulating platelets by anti-platelet IgG autoantibodies
What age and after what does ITP present?
Ages 2-10 years, 1-2 weeks after viral infection
What is a serious but rare complication of ITP?
Intracranial bleeding
How is ITP diagnosed?
It is a diagnosis of exclusion
How do you treat ITP?
In most cases, the disease is acute, benign and self-limiting, usually remitting spontaneously within 6-8 weeks
What is chronic ITP?
Low platelet count after 6 months, treatment is usually still supportive
What is DIC?
Coagulation pathway activation leading to diffuse fibrin deposition in the microvasculature and consumption of coagulation factors
What are the predominant clinical features of DIC?
Bruising, purpura and haemorrhage
What are some investigation results that may suggest DIC?
Thrombocytopaenia Prolonged prothrombin time Prolonged APTT Low fibrinogen Raised fibrinogen degradation products D-dimers Marked reduction in the naturally occurring anticoagulants - Proteins C and S and antithrombin
How do you treat DIC?
TREAT CAUSE
Supportive: FFP, cryo and platelets
