Haematology Flashcards
What is TORCH screen? (1)
Screen for infective agents that cause congenital intrauterine infections that may damage the growing foetus. Toxoplasmosis Other- Varicella zoster, syphilis Rubella CMV Herpes simplex
A child who is 12 hours old is noticed to have microcephaly, cataracts, hepatomegaly, splenomegaly, a petechial rash and jaundice. What is the most likely diagnosis? (1)
TORCH infection
Why do term infants have high levels of Hb (140-210g/L) at birth? (1)
Levels of HbF are high to compensate for low oxygen concentration in the foetus.
Name 4 causes of anaemia in a child. (4)
Impaired red cell production- iron deficiency*, folic acid deficiency, CRF, leukaemia, aplastic anaemia Increased haemolysis- hereditary spherocytosis, G6PD deficiency, sickle cell Blood loss (rare)- von Willebrand disease
What is hereditary spherocytosis? (1)
Autosomal dominant caused by mutations in genes for proteins of red cell membrane.
RBCs are spherical and less deformable than normal RBCs so are destroyed by the spleen.
Name 4 features of hereditary spherocytosis. (4)
What investigation will diagnose? (1)
What management is required? (2)
(Clue: JAPGAS)
Jaundice, Anaemia, Pigment Gallstones, Aplastic crisis, Splenomegaly
Blood film
Folic acid for increase RBC production and consider splenectomy for poor growth or bad anaemia
How does Glucose-6-phosphate dehydrogenase deficiency cause anaemia? (1)
Why are men more affected? (1)
Which ethnicities are more commonly affected? (3)
G6PD is essential enzyme for preventing oxidative damage/haemolysis to RBCs.
X-linked. Affects central africa, middle east, far east and mediterranean origins more commonly.
What is the normal composition of HbF and HbA? (2)
Therefore why do β-thallesaemias and sickle cell disease not present until after 6 months of age? (1)
What is the pattern of inheritance in the thallesaemias? (1)
HbF has 2 α and 2 γ components, whereas HbA has α and 2 β chains.
Because in these 2 diseases only β-chains are affected and as HbF is predominant until about 6 months of age, they do not show symptoms until HbA takes over.
Autosomal recessive
A 6 month old child is brought to the GP with yellowing of the sclera, anaemia and splenomegaly. The child’s parents are from the Caribbean. What is the most likely diagnosis? (1)
What is the amino acid change that causes the production of HbS? (1)
Sickle cell disease.
Glutamine to Valine in the β-haemoglobin chain.
What is the difference between sickle cell anaemia and sickle cell trait? (2)
Sickle cell anaemia is HbSS (homozygous HbS) the sickle mutation in both genes means they have NO HbA. (But may prodcue some HbF to compensate)
Sickle cell trait are heterozygous HbS and HbA. They are therefore asymptomatic but able to pass the HbS gene on.
What is the problem with irreversibly sickle shaped RBC’s? (2)
The cells have a reduced lifespan and may become trapped in the microcirculation => blood vessel occlusion => ischaemia of organ or bone
Why are children with sickle cell disease at increased risk of infection? (1)
Which organisms pose a greater threat? (1)
Hyposlenism occurs secondary to chronic sickling and microinfarction of the spleen in infancy.
More at risk from encapsulated organisms eg pneumococci or Haemophilis influenzae.
What is a common example of a vaso-occlusive crises in infant with sickle cell disease? (2)
Hand-foot syndrome in which there is dactylitis with swelling and pain of the finger or feet from vaso-occlusion.
Name 3 things that can precipitate a vaso-occlusive episode in SCD? (3)
Exposure to cold, dehydration, excessive exercise, stress, hypoxia or infection.
What infection can cause an aplastic crises in SCD? (1)
Parvovirus infection causes complete but temporary cessation of RBC production => acute anaemia
Name 4 long term complications associated with sickle cell disease. (4)
Short stature and delayed puberty.
Stroke
Adenotonsilar hypertrophy => sleep apnoea => nocturnal hypoxaemia => vaso-occlusive crises or stroke
Cardiomegaly <= increased bile pigment production
Leg ulcers
How can children with SCD be protected from encapsulated viruses? (2)
Why are they more prone to infections? (1)
What medication can help prevent anaemia? (1)
Immunisations against pneumococcus, HiB and meningococcus and daily oral penicillin prophylactically.
Functional asplenia
Chronic haemolytic anaemia causes increased demand of folic acid.
How are acute vaso-occlusive crises treat? (4)
Analgesia for pain
IV fluids for dehydration
Oxygen is desaturated
Antibiotics if infection
Exchange transfusion for acute chest syndrome, stroke and priapism.
If repeated hospitalisation for painful vaso-occlusive episodes or chest syndrome, then hydroxyurea can be tried to stimulate increased production of HbF.
A 10/40 african lady attends clinic, her partner has SCD (HbSS) and she wishes to know if her child may be affected. What diagnostic test can give the answer and when can it be performed? (1)
What is the risk of miscarriage from this test? (1)
Chorionic villus sampling (CVS) between 10 and 13/40 (end of first trimester).
Miscarriage risk is 1%.
Why do patients affected by β-thalessaemias require lifelong monthly blood transfusions? (2)
Due to defect in gene coding for β- haemoglobin chains, they are unable to make any HbA (thalessaemia major) or very small amount of HbA or large amount of HbF (thalessaemia intermedia). Therefore they suffer from severe anaemia which is transfusion dependant.
Why does β-thalessaemia cause maxillary overgrowth and skull bossing if untreated? (2)
Without transfusions, extramedullary haematopoiesis occurs. This results in heaptosplenomegaly and bone marrow expansion in an attempt to compensate for haemolysis.
Name 4 complications of long term blood transfusions in children such as those performed in patients with β-thalessaemia. (4)
Iron deposition - (most important) - cardiomyopathy, liver cirrhosis, diabetes, skin hyperpigmentation, delayed growth.
Antibody formation
Infection - Hepatitis A, B, C; HIV; Malaria
Venous access- can be traumatic for children.
What is aplastic anaemia? (1)
Bone marrow failure - reduction or absence of all 3 lineages in bone marrow leading to peripheral blood pancytopenia. (RBCs, WBC,s and platelets)
What is the clinical presentation of bone marrow failure? (3)
Clue: think of what cells are affected.
RBCs- anaemia
WBC’s- infection
Thrombocytopenia- bruising and bleeding
What are the 4 steps of haemostasis? (4)
Vasoconstriction
Platelet plug formation
Clot formation - fibrin mesh
Dissolution of clot by plasmin
What is haemophilia? (1)
X-linked recessive inherited coagulation disorder characterised by recurrent spontaneous bleeding into joints and muscles.
What is the difference between petechiae, purpura and ecchymosis? (1)
All are terms used to describe various sizes of non-blanching red/purple spots caused by bleeding under the skin.
Petechiae are less than 3-4mm (pinprick)
Purpura are less than 1cm
Ecchymosis are more than 1cm and may be caused by bleeding deeper under the skin.
What is the pattern of distribution of Henoch-Schonlein purpura? (2)
Buttocks and extensor surfaces of arms and legs.
Also associated swollen, painful knees and ankles, abdominal pain and haematuria.
What is HSP? (1)
Henoch-schonlein purpura is a IGA-mediated autoimmune hypersensitivity vasculitis of childhood.
What are the naturally occurring anticoagulants? (3)
Protein C
Protein S
Anti-thrombin
What is DIC? (2)
What are the most common causes? (2)
What are the typical clinical features? (3)
Disseminated Intravascular Coagulation
Coagulation pathway activation leading to diffuse fibrin deposition in the microvasculature.
Severe sepsis or shock due to circulatory collapse
Extensive tissue damage due to burns or trauma.
Clinical features of bruising, purpura and haemorrhage.
What WBC would you expect to be raised in worm infestation? (1)
Eosinophils - allergic response to worms (helminths)
Which WBC would be most raised in a viral infection?(1)
Which WBC would be most raised in a bacterial infection? (1)
Lymphocytes in viraL
Neutrophils in bacteria
What is pernicious anaemia? (2)
Autoimmune condition in which there is loss of parietal cells => loss of intrinsic factor production => Vit B12 malabsorption.
Repeated blood transfusions cause iron overload and depositions of iron in various organs. How can this be prevented? (1)
Iron chelation with desferrioxamine.
What is megaloblastic anaemia? (2)
What are the main causes? (2)
Type of macrocytic anaemia characterised by presence in the bone marrow of developing RBC’s with delayed nuclear maturation in relation to that of the cytoplasm. (megaloblasts)
Vitamin B12 and folate deficiency which are required for DNA synthesis.
Name 4 causes of vitamin B12 deficiency. (4)
Low intake - vegans
Impaired absorption -
Stomach: pernicious anaemia, gastrectomy
Small bowel: Coelaiac disease, resection of terminal ileum, ileal diseas eg Crohns, tropical sprue
Name 3 difference in cervical lymphadenopathy between normal physiological and pathological causes. (3)
Physiological - soft, mobile, tender, often linked to infection
Pathological - hard, fixed, non-tender, progressive enlargement
Name 3 causes of pathological cervical lymphadenopathy in a child. (3)
ALL, Hodgkin’s, non-Hodgkin’s lymphoma
What is haemophilia?(1)
How is it inherited? (1)
Deficiency in Factor VIII causing prolonged bleeding, and deep bleeding into muscles and joints.
X-linked recessive
A child has repeated bruising and epistaxis that stops with pressure. He has also had episodes of malaena and purpura. You suspect a bleeding disorder.
What are the three main groups of bleeding disorder and name one example for each? (3)
Which type do you think is most likely and why? (1)
Vascular - HSP, Scurvy, Ehler-Danlos
Platelets - ITP, von Willebrand disease, leukaemia, aspirin use
Coagulation problems - Haemophilia, haemorrhagic disease of the newborn
Vascular or platelet disorder is most likely as bleeding stops with pressure.
What is von Willebrand disease? (1)
What is von Willebrand factor? (1)
Autosomal dominant bleeding disorder with reduced or without von Willebrand factor.
vWf is secreted by endothelium and platelets to facilitate platelet adhesion.
Name 3 causes of microcytic anaemia? (3)
Low MCV <80 fL
Iron deficiency
Anaemia of chronic disease
Thalassaemia
Sideroblastic anaemia
Name causes of a normocytic anaemia. (4)
Acute blood loss Anaemia of chronic disease Combined deficiency (e.g. iron and folate deficiency) Marrow infiltration/fibrosis Endocrine disease Haemolytic anaemia
Name 3 causes of macrocytic anaemia. (3)
High MCV >90 fL
Megaloblastic: vit B12 deficiency, folate deficiency
Normoblastic: alcohol, liver disease, hypothyroidism, azathioprine
What is transferrin? (1)
The protein the iron is bound to in the plasma.
Most of the iron in the body s incorporated into reticulocytes and red blood cells.
Where is the rest of the iron stores? (2)
Stored as ferritin and haemosiderin in hepatocytes, skeletal muscle and reticuloendothelial macrophages.
Name 3 causes of iron deficient anaemia. (3)
Blood loss (usually from uterus or GI tract)
Increased demands such as growth or pregnancy
Decreased absorption e.g. small bowel disease or post-gastrectomy
Poor dietary intake
What is poikilocytosis? (1)
Variation in shape of red blood cells seen in iron deficient anaemia
Dr French measures Mrs Smith’s ferritin levels.
What is she checking? (1)
When would ferritin levels be inappropriately normal? (1)
Iron stores
Ferritin is also acute phase reactant so may have normal levels in inflammatory or malignancy, even when iron deficient.
What is anaemia of chronic disease? (2)
Either normocytic, normochromic or microcytic.
Characteristic lab findings indicate low iron, low total iron binding capacity and normal/increased ferritin.
What is sideroblastic anaemia? (1)
Rare disorder of haem synthesis characterised by a refractory anaemia with hypo chromic cells in the blood and ring sideroblasts in the bone marrow.
It can be inherited or acquired.
How is it determined whether a macrocytic anaemia is megaloblastic or normoblastic? (1)
What is a megaloblast? (1)
What is the underlying cause? (1)
Bone marrow findings
Megaloblast is developing RBC with delayed nuclear maturation relative to that of the cytoplasm.
Caused by defective DNA synthesis, (usually folate or B12 deficiency)
Describe the normal process of vitamin B12 absorption. (4)
Only dietary sour is dairy and meat products.
- B12 is released from protein complexes by gastrin and pepsin
- Pancreatic enzyme allow free B12
- Free B12 binds to intrinsic factor (from parietal cells)
- Absorbed in the terminal ileum
- Stores in liver sufficient to last 2 years
What is pernicious anaemia? (2)
Autoimmune condition causing atrophic gastritis with loss of parietal cells and so intrinsic factor.
Causing vitamin B12 malabsorption.
What neurological symptoms can occur with deficiency of vitamin B12? (2)
Polyneuropathy - symmetrical damage to the peripheral nerves and posterior and lateral columns of the spinal cord
(subacute combined degeneration of the cord)
Presenting with progressive weakness, ataxia and paraplegia.
Name 3 causes of folate deficiency. (3)
Poor intake: old age, poverty,alcohol excess, anorexia
Malabsorption: coeliac, crohn’s tropical sprue
Drugs: phenytoin, trimethoprim, sulfasalazine, methotrexate
Excess utilisation: pregnancy, lactation and prematurity; chronic haemolytic anaemia, malignant and inflammatory disease, renal dialysis
