Haematology Flashcards
What is the pathology behind transfusion-associated graft vs host disease? Who is at an increased risk?
T-cells in blood products attack the recipient’s tissues.
Increased risk pts include immunosuppressed or previous Hodgkin’s lymphoma.
What is Transfusion associated circulatory overload (TACO)?
Pulmonary oedema due to circulatory excess, occurs in those who cannot cope with the excess fluid after blood transfusion (elderly, young, heart failure).
How can you mitigate the risk of transfusion associated circulatory overload?
Prophylactic furosemide to those at higher risk (elderly, children, heart failure). Also ensure to only give them 1 unit at a time.
What is transfusion associated lung injury (TRALI)?
Non-cardiogenic pulmonary oedema and ARDS as a result in activation of immune cells in the lungs.
Which factors are assessed by the APTTR and the INR?
APTTR: 8, 9, 11,12
INR: 10, 9, 7, 2
What is the ISTH BAT score? What is abnormal?
ISTH ‘bleeding assessment score’ for assessing the severity of potential bleeding disorders.
>3 men and >5 women is abnormal.
What is a mixing study?
Mixing pt plasma with normal plasma (50:50) to see if a problem is corrected.
If it is just a deficiency it will completely correct the problem.
If it is autoimmune due to autoantibody destruction then it won’t correct as the antibodies would destroy it in normal blood too.
What is DIC? What are the lab findings?
Loads of small clots throughout the body meaning clotting factors are used up and the pt is at a significantly increased risk of bleeding.
Secondary to infection, injury, and malignancy.
Labs: elevated D-dimer, increased APTT and PT, low platelets and fibrinogen.
What is HUS? What is it most commonly caused by?
Haemolytic uremic syndrome: haemolytic anaemia (schistocytes), thrombocytopenia (bleeding/bruising), AKI.
Typically caused by diarrhoeal/foodborne illness (E.coli 0157) when they break down and release toxins.
What is Atypical HUS?
Caused by complement deficiencies rather than infection.
What causes intravascular haemolysis?
Something within the vessels causing RBCs to become shredded/fragmented (schistocytes). E.g., mechanical heart valve and the fibrin clots in DIC.
What blood film results might indicate an intravascular haemolysis? What do you see on biochemostry?
Schistocytes and reticulocytes on blood film.
Unconjugated hyperbilirubinaemia, raised LDH, haemoglobinuria (due to free Hb in urine), decreased haptoglobin.
How do you manage a febrile non-haemolytic transfusion reaction?
Stop transfusion, give paracetamol (anti-pyretic), and recommence at a slower rate once stable.
What are the signs of essential thrombocytosis? What is it caused by?
Dizziness, bleeding (including melena), raised platelets, headaches, splenomegaly, erythromelalgia (burning, red, hot skin), livedo reticularis (nettle reddish blue pattern on skin).
Caused by JAK2 V617F mutation.
What is the inheritance pattern of sickle cell anaemia? How can it be diagnosed?
- Autosomal recessive
- A-haemoglobin electrophoresis shows sickling of cells and genetic testing will identify allele
What are the 4 main Crises that someone with sickle cell may present with?
- Aplastic crisis: profound anaemia, likely shows pancytopenia, caused by infections. present with tachycardia and tachypnoea in absence of splenomegaly.
- Acute sequestration crisis: excessive blood trapped in spleen causes reduction in circulating volume.
- Vaso-occlusive crisis: microvascular obstruction due to sickling, inflammation, and vasoconstriction. Cold, dehydrated, and after exercise trigger this. Very painful.
- Chest crisis: presents with tachypnoea, wheeze, and cough, with hypoxia and pulmonary infiltrates on chest X-ray. Unknown cause.
Why do sickle cell pts experience hyposplenism? What is the consequence of this?
Repeated splenic infarctions which can cause reduced splenic function.
Increased susceptibility to encapsulated organisms ie, pseudomonas aeruginosa, haemophilus influenza, strep pneumoniae, etc.
A sickle cell pt with >3 painful crisis in 12 months may indicate the need for what medication? How does it work?
Hydroxyurea - increases foetal Hb (has no beta subunit so not susceptible to sickling).
What is the inheritance pattern for Hereditary Haemorrhagic Telangiectasia (Osler-Weber-Rendu syndrome)? What are the complications?
Autosomal dominant ENG and ACVRL1 genes.
Recurrent epistaxis (malformations in nasal mucosa), widespread telangiectasia, AVM malformations.
What is the most common hereditary thrombophilia? What is its inheritance pattern?
Factor V Leiden mutation.
Autosomal dominant.
Why does a Factor V Leiden mutation increase the risk of thromboembolic disease?
Factor V is resistant to degradation by Protein C, increasing thrombin formation and creating a prothrombotic state.
What is the inheritance pattern for G6PD deficiency? What is it?
X-linked.
G6PD (glucose-6 phosphate dehydrogenase) deficiency is an enzyme deficiency increasing susceptibility to the development of haemolytic anaemia.
What are the common triggers of haemolysis in G6PD deficiency pts?
Medications- sulphonylureas, ciprofloxacin, nitrofurantoin.
How might someone in a haemolytic crisis with a background of G6PD deficiency present? What might you see on blood film?
SOB, exhaustion, dark urine, scleral ictus, on a abackground of starting a new medication,
Blood smears showing RBC fragments (schistocytes), bite cells (misshaped RBCs) and heinz bodies (denatured Hb).
What is the inheritance pattern for congenital sideroblastic anaemia? What is it?
X-lined recessive (predominantly affecting males)
Defect in haem synthesis .
What type of anaemia is seen in congenital sideroblastic anaemia?
Microcytic anaemia but normal iron levels.
Inefficient erythropoiesis means the iron isn’t used and becomes deposited in mitochondria and various organs.
What is seen on bone marrow aspiration for congenital sideroblastic anaemia? What do you see on blood film?
BM - Ring sideroblasts (abnormal RBCs).
BF - pappenheimer bodies (basophilic granules of iron).
How may congenital sideroblastic anaemia present?
Fatigue, dyspnoea, palpitations, microcytic anaemia, hepatosplenomegaly.
What causes paroxysmal nocturnal haemoglobinuria (PNH)?
Mutation in the PIGA gene in haematopoietic stem cells causing a haemolytic anaemia.
How do we investigate for paroxysmal nocturnal haemoglobinuria (PNH)?
Flow cytometry for CD55 and CD59.
How does paroxysmal nocturnal haemoglobinuria (PNH) present? What are the complications?
Sx of anaemia, dark urine (@night or in morning), abdominal pain, easy bruising/bleeding.
Cx include dysphagia, erectile dysfunction, thrombosis (hepatic, cerebral, abdominal), pulmonary HeTN.
What is the inheritance pattern for Thalassaemia? How might it present?
Autosomal recessive.
Jaundice, sx of anaemia, facial bone deformities (extreme cases).
What causes Beta-thalassaemia? What are the subtypes? Where is it most common?
- Defect in the beta globin gene of Hb,
- Major: both subunits affected, Minor/trait: 1 affected
- Mediterranean, Middle East, Asia, parts of Africa
What might you see on blood film for someone with beta-thalassaemia?
Hypochromic, microcytic target cells and nucleated RBCs.
How might you detect Beta-Thalassaemia Minor/Trait?
Found incidentally in someone with microcytic anaemia where MCV in much lower than you would expect of Hb level. Can also get a high HbA2.
Alpha thalassaemia is caused by what? What is the consequence?
Defect in the alpha globin gene in Hb,
Can result in death in utero.
What is the mainstay treatment for thalassaemia?
Blood transfusions or stem cell transplants.
What is a complication of using repeated blood transfusions in thalassaemia pts? How would you treat this?
Iron overload: deposition in joints especially metacarpophalangeal joints, deposition in organs (diabetes, erectile dysfunction, etc), hyperpigmentation.
Mx- desferrioxamine.
What is the pathophysiology of hereditary hemochromatosis? How does this show on biochemistry?
Autosomal recessive mutation in the HFE gene (most commonly C282Y then H63D is next most common)
This causes a dysfunction in iron excretion.
Biochem: increased iron, ferritin and transferrin saturation, with a low total iron binding capacity.
Hereditary hemochromatosis causes what complications?
- Cirrhosis (Jaundice), diabetes,
- Arthritis (joint pain),
- Fatigue,
- Erectile dysfunction,
- Heart failure (dilated cardiomyopathy)
How is hereditary haemochromatosis managed?
Venesection to trigger erythropoiesis to remove iron from sites around the body.
What is the pathophysiology behind Aacute intermittent porphyria? How might it present?
Autosomal dominant disease causing deficiency of the enzyme hydroxymethylbilane (part of the pathway to create heme).
Generalsied sx of abdo pain, N+V, weakness, neurological sx, convulsions, hyponatraemia.
What can trigger acute intermittent porphyria?
Usually starting new drugs e.g., COCP, antidepressants.
How do we investigate for and manage acute intermittent porphyria?
Inx- urine sample (stored in brown bag to protect from changing colour in light) test creatinine, PBG (porphobilinogen), ALA (aminolevulinic acid) , and total porphyrins.
Mx - acute attacks are treated with IV heme arginate
What are the clotting screen findings for Von-Willebrand disease? How is it managed?
Normal platelet, thrombin time and prothrombin time.
Prolonged bleeding time, prolonged APTT.
Mx - desmopressin.
How is APTT corrected when testing for Von-Willebrand Disease?
50:50 mixing with normal plasma
Which autoantibodies are +ve in anti-phospholipid syndrome?
- Anti-beta-2-glycoprotein
- Anti-cardiolipin
- Lupus anticoagulant
How do you manage antiphospholipid syndrome?
- If pregnant: LMWH and low dose aspirin
- Not pregnant: warfarin
What are the components of TTP (thrombotic thrombocytopenic purpura)?
- Purpuric (red/purple spots that do not blanch) rash
- thrombocytopenia
- anaemia
- unconjugated hyperbilirubinemia
- can get a raised LDH.
What causes TTP? What is seen on blood film?
Formation of antibodies against ADAMTS13 protein.
BF - schistocytes (fragmented RBCs).
What is autoimmune haemolytic anaemia? What do you see on blood film?
Antibodies develop against RBCs cause destruction and deformities.
Spherocytes: damage to RBC membrane causes change of shape.
Which antibody develops in cold autoimmune haemolytic anaemia? How do we test for this?
IgM- but this becomes unbound by the time sample reaches lab so you test for C3d.
Which antibody develops in warm autoimmune haemolytic anaemia?
IgG.
ITP (immune thrombocytopenic purpura) is characterised why reduction in circulating what?
Platelets.
What are symptoms/signs of ITP?
Usually post viral infection in children but chronic and relapsing in adults…
- easy or excessive bruising (purpura)
- superficial bleeding into the skin appearing as a rash of pin-point sized reddish purple spots (petechiae) usually on shins
- prolonged bleeding from cuts
- spontaneous mucocutaneous bleeding (nose and gums)
- haematuria and blood in stools
- unusually heavy menstrual flow
How is ITP managed?
Corticosteroids to decrease platelet destruction.
What is Pernicious anaemia? What are the symptoms? What do you seen on blood film?
Vitamin B12 deficiency due to inability to properly absorb B12 from the GIT due to antibodies against IF/parietal cells.
Causes fatigues, pallor, SOB, dizziness, memory loss, confusion, jaundice, atrophy of lingual papillae.
You get hypersegmented neutrophils and macrocytic RBCs on blood film.
What type of jaundice do you get in haemolytic anaemia?
Unconjugated hyperbilirubinemia.
Increased breakdown of Hb into globin + haem, haem is broken down into iron and unconjugated bilirubin, but liver cannot compensate for increase in breakdown = raised unconjugated bilirubin = jaundice.
What is seen on bone marrow analysis of Aplastic anaemia?
Hypocellular marrow due to pancytopenia.
What happens when you aspirate bone marrow from someone with myelofibrosis?
You get a dry tap due to fibrosis of bone marrow.
What is seen on blood film for myelofibrosis?
- Poikilocytes (teardrop RBCs)
- Leucoerythroblastic ([presence of immature white an red blood cells)
What happens to platelets and white blood cells in someone with myelifibrosis?
Initially high then you get a pancytopenia.
How does myelofibrosis present?
Constitutional sx (fever, weight loss, night sweats),
Sx of anaemia (fatigue, pallor), leukopenia (recurrent infection),
Sx of thrombocytopenia (bleeding/bruising),
Hepatosplenomegaly.
What is the pathophysiology behind amyloidosis? What are the most common affects?
Deposition of insoluble fibrins in organs and blood vessels.
- Kidneys (commonly nephrotic syndrome)
- GIT (malabsorption, chronic diarrhoea)
- neuro (peripheral neuropathy, carpel tunnel)
- joints (rheumatoid arthritis)
What mutation is associated with 60% myelofibrosis patients?
JAK2
What are the types of amyloidosis?
- AA: amyloid A build up (chronic inflammatory disorders)
- AL: light chain deposition (leukaemia)
- Beta 2: beta 2 microglobulin (dialysis)
How do you diagnose amyloidosis?
Tissue biopsy of affected organs - apple green birefringence when stained with congo red.
Smoking can cause a persistent what?
a) neutropenia b) neutrophilia c) thrombophilia
b) neutrophilia
How do you manage idiopathic autoimmune haemolytic anaemia?
Corticosteroids
What are the manifestations of Hereditary spherocytosis? Mx?
Hyperchromic, normocytic, haemolytic anaemia,
Jaundice,
Gallstones,
Splenomegaly.
Mx - folate suplements and for moderate-severe disease splenectomy.
What is Waldenstroms Macroglobulinaemia?
Low grade lymphoma with monoclonal plasmacytoid lymphocytes.
Clinical features include IgM deposition (hyperviscosity, polyneuropathy), organ infiltration (organomegaly), and bone marrow infiltration (pancytopenia).
What is methemoglobinemia? What are the complications?
Accumulation of methaemoglobin (contains Fe3+) instead of normal haemoglobin (contains Fe2+) meaning less effective oxygen binding. You get a low saturation but high PaO2 when you supplement oxygen.
Cx: seizures, coma, cardiorespiratory collapse.
Management of methemoglobinemia?
Oxygen therapy, methylene blue administration (can help o restore the oxygen carrying ability), ascorbic acid supplementation (reduced methemoglonin).
How do you measure Iron when investigating for IDA?
Ferritin <30 = IDA.
What is Transferrin? At what level is it considered raised? What is this suggestive of?
Iron + Protein
Transferrin saturation >45% is raised and suggestive of hemochromatosis.
What is the most common cause of inherited aplastic anaemia?
What type of inherotance?
Fanconi anaemia.
Autosomal recessive.
What antibodies are associated with pernicious anaemia? What % of pernicious anaemias are they present in?
- Anti-parietal cell (high sensitivity, low specificity), present in 70%
- Anti-intrinsic factor (high specificity, low sensitivity), present in 40%
Why is ferritin usually high in anaemia of chronic disease?
Acute phase protein which is raised by underlying inflammation/malignancy that causes these anaemias.
What % blast cells make the difference between myelodysplastic syndrome and AML?
<20% is MDS, >20% is AML.
