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Year 1 Semester 2 > Haematology > Flashcards

Haematology Flashcards

1
Q

What are the main constituents of coagulation?

A
  • Vessel wall lined by endothelium
  • Platelets - derived from megakaryocytes in marrow
  • Coagulation factors in un-activated state
  • Inhibitors of coagulation
  • Fibrinolytic system and inhibitors
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2
Q

What do endothelial cells do?

A
  • Line blood vessels and form a barrier
  • Produce thrombomodulin and heparin sulphate to inhibit thrombin production
  • Enzymes to degrade platelet granule-derived molecules
  • Prostacyclin and nitric oxide (NO) to reduce platelet adhesion
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3
Q

What are some features of platelets?

A
  • Fragments of megakaryocyte cytoplasm
  • Budded off into lumen of marrow sinusoids
  • Production stimulated by thrombopoetin (TPO) - liver derived
  • Circulate for 5-10 days with ~30% stored in spleen
  • Form a plug when attracted by lowered prostacyclin and by collagen exposure
  • Thromboxane A2 and serotonin from platelets cause vasoconstriction
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4
Q

How do platelets adhere to vessel walls?

A

Via Von Willibrand’s factor and Glycoprotein Ib

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5
Q

How do platelets adhere to each other?

A

Via Glycoprotein IIb-IIIa and fibrinogen

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6
Q

What are the two pathways in the coagulation cascade?

A

Intrinsic and extrinsic

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7
Q

What are some inhibitors of the coagulation cascade?

A
  • Protein C activated by thrombomodulin-thrombin complex and with co-factor -Factor S - Va and VIIIa are degraded
  • Antithrombin (previously antithrombin III) inhibit Xa and IIa
  • Heparin cofactor II inhibits IIa
  • Heparin stimulates antithrombin and heparin cofactor II
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8
Q

How is coagulation measured?

A
  • Full bloods count - includes platelet count/size/granules but is a poor assessment of platelet function - specialised tests of aggregation can be done
  • Ref range 150-400 times 10 to the power of 9 /L
  • Easy bruising and purpura when <30-50 (thrombocytopenia)
  • Risk of major bleeding if <10
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9
Q

How does prothrombin time testing work?

A
  • All coagulation tests are done on citrated plasma - removes Ca2+
  • At 37 degrees thromboplastin (brain extract) and Ca2+ added
  • Measure time till clot forms - extrinsic and common pathway
  • Prolonged by low levels of II, X and VII
  • Warfarin reduces active II, VII, IX and X so a useful measure of dose - expressed as international normalised index
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10
Q

Explain the activated partial thromboplastin test (APTT)

A
  • Ca2+, kaolin and phospholipids added to citrated plasma
  • Measure of intrinsic and common pathway
  • Prolonged in haemophilia and by heparin
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11
Q

What is fibrinogen?

A
  • Final substrate for making fibrin

- Can be measured by clot density or by thrombin time - thrombin and Ca2+ added to citrated plasma

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12
Q

What are some features of haemophilia A and B?

A

-X linked defect in VIII or IX gene
-Commonly a new mutation so no family history (1 in 3)
-Approx 1:5000 of males
Female heterozygotes (carriers) not affected
-Can be very mild - chance finding or issue for surgery
-Severe (<1% VIII level) - frequent bleeds into joints and soft tissues

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13
Q

How is haemophilia treated?

A
  • Historically - no treatment - then fresh frozen plasma
  • Porcine and then recombinant factor replacement
  • Issues of hepatitis B or C and HIV
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14
Q

Describe Von Willebrand disease

A
  • Usually autosomal dominant
  • Defect in platelet adhesion and binding of VIII
  • Up to 1% of population
  • Mild disease - easy bruising, heavy periods
  • Severe disease - similar to haemophilia
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14
Q

Describe Von Willebrand disease

A
  • Usually autosomal dominant
  • Defect in platelet adhesion and binding of VIII
  • Up to 1% of population
  • Mild disease - easy bruising, heavy periods
  • Severe disease - similar to haemophilia
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15
Q

What is disseminated intra-vascular coagulation (DIC)?

A
  • Activation of clotting cascade due to trauma, malignancy (eg prostate cancer), sepsis and amniotic fluid embolism
  • Causes depletion of clotting factors and damage due to clot
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16
Q

What blood products are used to help blood clot/prevent bleeding?

A
  • Platelets - derived from blood donation
  • Fresh frozen plasma - 200ml plasma from blood donation - contains coag factors in normal proportions - dose 15ml/kg
  • Cyroprecipitate - pools of 5 donations using precipitate at 4C - concentrated fribrinogen, von Willebrand factor and VIII
  • Specific coag factors eg IX, VIII and fibrinogen
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17
Q

Describe tranexamic acid

A
  • Anti-fibrinolytic drug
  • Oral or IV
  • Inhibits activation of plasminogen to plasmin
  • Uses in trauma/GI bleeding/ post op or delivery
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18
Q

What does warfarin do?

A

Inhibits production of vitamin K in reduced form

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19
Q

What are some positive aspects of warfarin?

A
  • Established for decades
  • Cheap
  • Easily measurable effect
  • Can be reversed with vitamin K or factor concentrate
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20
Q

What are some negative aspects of warfarin?

A
  • Lots of drug interactions to enhance or inhibit effect
  • Slow onset - several days
  • Unpredictable dose need
  • Needs regular blood testing
  • Risk of bleeding
  • Narrow therapeutic window
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21
Q

How can the effects of warfarin be increased?

A
  • Amoxycillin - reduce gut vit K
  • Erythromycin, statins, acute alcohol intake - enzyme inhibition
  • Aspirin, clopidogrel, NSAIDS - increase bleeding risk - platelet function and GI mucosal damage
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22
Q

How can the effects of warfarin be decreased?

A

-Rifampicin, carbamazepine, phenytoin, chronic alcohol intake - enzyme induction

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23
Q

What are some indications for warfarin?

A
  • Deep vein thrombosis (DVT) and pulmonary embolism (PE) - short or long term depending on whether recurrent and/or provoked
  • Prosthetic heart valve replacement
  • Atrial fibrillation to reduce stroke risk
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24
Q

What can be used to determine risk of a stroke?

A

CHA2DS2-VASc score

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25
Q

What are the two types of direct oral anticoagulants (DOACs) and give some examples

A
  • Xa inhibitors e.g apixaban, rivaroxaban, edoxaban

- Direct thrombin inhibitors e.g dabigatran

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26
Q

What would favour warfarin over DOACs?

A
  • Established drug
  • Cheap - but needs monitoring
  • Can be reversed
  • Effect can be easily measured
  • Can be used with poor renal function
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27
Q

What would favour DOACs over warfarin?

A
  • Good trial evidence
  • No monitoring needed
  • Lower bleeding risk
  • As effective for stroke prevention
  • Reversal agents recently available (but expensive)
  • Short half life
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28
Q

Describe heparin

A
  • Naturally occurring anticoagulant
  • Can be extracted from lung and liver
  • Given as IV - unfractionated - half life <1 hour
  • Binds to and activates anti-thrombin so reducing Xa and thrombin generation
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29
Q

What are some adverse effects of heparin?

A
  • Pain at site of injection
  • Increased bleeding risk
  • Osteoporosis with prolonged use
  • Heparin-induced thrombocytopenia - antibody mediated, 5-10 days into treatment
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30
Q

How can aspirin be used to modify platelet function?

A
  • Low doses e.g 75-150mg/day cause irreversible inhibition of COX-1 so less thromboxane A2 production - less aggregation of platelets
  • Typically used after transient ischaemic attack (TIA) or myocardial infarction
  • Some effect in stroke prevention in AF but not as effective as warfarin/DOACs
  • Increase in GI bleeding risk, dyspepsia
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31
Q

Describe clopidogrel

A
  • Inhibit ADP induced platelet aggregation
  • Used with aspirin to prevent recurrent myocardial infarction
  • Used in ischaemic stroke and TIAs
  • Increased risk of dyspepsia and GI bleeding
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32
Q

How long will aspirin and clopidogrel effects last and why?

A

No reversal agents for aspirin and clopidogrel so effect will last the duration of platelet lifespan - 5-10 days

32
Q

How long will aspirin and clopidogrel effects last and why?

A

No reversal agents for aspirin and clopidogrel so effect will last the duration of platelet lifespan - 5-10 days

33
Q

Describe thrombolytic drugs

A
  • Drugs to increase activation of plasminogen to plasmin
  • Tissue plasminogen activators (tPA) e.g streptokinase and alteplase - used for thrombolysis
  • Cause breakdown of fibrin and fibrinogen
  • Increased risk of bleeding in hours after dose
  • Stenting and clot removal are alternative treatments
34
Q

What are some symptoms of anaemia?

A
  • Short of breath
  • Muscle pain on exertion
  • Dizzy
  • Angina
34
Q

What are some symptoms of anaemia?

A
  • Short of breath
  • Muscle pain on exertion
  • Dizzy
  • Angina
35
Q

What are some clinical signs of anaemia?

A
  • Pallor in skin and conjuctiva
  • Tachycardia
  • Rapid breathing
  • Peripheral oedema if severe anaemia
  • Signs relating to cause of anaemia
35
Q

What are some clinical signs of anaemia?

A
  • Pallor in skin and conjuctiva
  • Tachycardia
  • Rapid breathing
  • Peripheral oedema if severe anaemia
  • Signs relating to cause of anaemia
36
Q

How does the body adapt to anaemia?

A
  • Mild anaemia likely to cause no symptoms unless extreme exertion
  • Cardiac output increases - rate and stroke volume
  • Changes in distribution of blood flow
  • Change in )2 dissociation curve
37
Q

How is anaemia classified?

A
  • Under production or increased loss of red blood cells
  • Congenital or acquired
  • Acute or chronic
  • By mean cell volume - microcytic/normocytic/ macrocytic
38
Q

What does MCV stand for?

A

Mean cell volume

39
Q

What does MHC stand for?

A

Mean cell Hb

40
Q

What does MCHC stand for?

A

Mean cell Hb concentration

41
Q

Describe microcytic

A
  • MCV = 60-80fl
  • Iron deficient
  • Thalassaemia
42
Q

Describe normocytic

A
  • MCV = 80-100fl
  • Blood loss
  • Anaemia of chronic disease
  • Renal impairment
43
Q

Describe macrocytic

A
  • MCV = 100-120fl
  • Megaloblastic anaemia
  • B12/folate deficiency
  • Myelodysplasia
44
Q

Describe iron deficiency anaemia

A
  • Commonest cause of anaemia worldwide
  • Typically reduction in MCV (microcytic) to 65-80, then in Hb, low ferritin, low transferrin saturation with iron
  • Rest of blood count normal - Raised platelets if bleeding
44
Q

Describe iron deficiency anaemia

A
  • Commonest cause of anaemia worldwide
  • Typically reduction in MCV (microcytic) to 65-80, then in Hb, low ferritin, low transferrin saturation with iron
  • Rest of blood count normal - Raised platelets if bleeding
45
Q

What are some causes of Iron deficiency anaemia?

A
  • Poor intake
  • Blood loss e.g menstrual
  • GI tract - haematemesis or melaena e.g peptic ulcer/cancer/angiodysplasia/hookworm
  • Malabsorption - coeliac disease
  • Increased need e.g growth spurt/pregnancy
46
Q

What are some clinical features of iron deficiency?

A
  • Pale
  • Tachycardia
  • Koilonychia
  • Hair loss
  • Pica
  • Glossitis/angular stomatitis
  • Features relating to the cause e.g weight loss/abdominal pain/ bowel change/ heavy periods
47
Q

How can one investigate for iron deficiency?

A
  • Be guided by history - recent and past clinical findings
  • Confirm iron def by lo ferritin and typical FBC
  • Screen for coeliac disease
  • Upper and lower endoscopy for all except pre-menopausal women
  • Consider other imaging/capsule endoscopy
48
Q

How do we orally treat people with iron deficiency?

A
  • Oral-replacement with sufficient iron for long enough period e.g ferrous sulphate 200mg, 2 or 3 per day, 65mg elemental iron per dose
  • Side effects: nausea/abdominal pain/constipation - dose related - may improve if changed to ferrous gluconate or fumarate
  • Typically patients need 3 months of iron after correction of anaemia to build up iron stores
  • Treat underlying cause
  • Rise in Hb generally 10g/l per week if not bleeding
49
Q

What parenteral treatments are used for people with iron deficiency?

A
  • Intramuscular - not used now - painful, multiple doses, stains skin
  • Intravenous - ferric carboxymaltose (ferinject) - over 15-30mins, often need 2 doses - iron dextran (cosmofer) - over 4-6 hours after a test dose
  • All IV iron preparation can cause flu like symptoms and a small risk of hypersensitivity reaction or anaphylaxis
50
Q

Describe B12 deficiency

A
  • Typically a macrocytic anaemia - MCV 100-120 and later a pancytopenia, often bilirubin and LDH raised
  • Can also cause peripheral neuropathy - demyelination and posterior column damage
  • B12 result can be falsely low in pregnancy/oral contraceptive/ on metformin
  • Pernicious anaemia - gastric atrophy and auto antibodies to parietal cells and intrinsic factor preventing absorption
  • Strict vegan or terminal ileal disease also possible
51
Q

How is B12 deficiency treated?

A
  • Hydroxocobalamin 1 mg IM alternate days for 5 doses then 3 monthly if confirmed ongoing need e.g pernicious anaemia
  • Cyanocobalamin available orally but not available on prescription
51
Q

How is B12 deficiency treated?

A
  • Hydroxocobalamin 1 mg IM alternate days for 5 doses then 3 monthly if confirmed ongoing need e.g pernicious anaemia
  • Cyanocobalamin available orally but not available on prescription
52
Q

Describe folate deficiency

A
  • Blood count and film appearance same as B12 deficiency
  • Limited stores of folate so deficiency can develop in weeks
  • Causes - poor intake, increased use e.g pregnancy/haemolysis, malabsorption, drugs e.g anti-epileptics or trimethoprim
  • Replacement with oral folic acid 5mg per day
  • Pre-conception folic acid reduces neural tube defects
53
Q

Describe anaemia due to blood loss

A
  • Hb immediately after blood loss will be normal
  • Drop after fluid replacement
  • Each 500ml loss gives approximate drop of Hb by 10-15 g/l
  • Reticulocyte response within hours/days
  • May need blood transfusion to replace loss e.g trauma/GI bleed/ around delivery
54
Q

Describe anaemia of chronic disease

A

-Typically a normocytic anaemia associated with chronic inflammatory disease
-Plentiful iron stores but poor transfer to RBC due to hepcidin and cytokines
-History of chronic disease, inflammatory marker increased e.g CRP/ESR/plasma viscosity
Will respond to treatment of underlying disease

54
Q

Describe anaemia of chronic disease

A

-Typically a normocytic anaemia associated with chronic inflammatory disease
-Plentiful iron stores but poor transfer to RBC due to hepcidin and cytokines
-History of chronic disease, inflammatory marker increased e.g CRP/ESR/plasma viscosity
Will respond to treatment of underlying disease

55
Q

Describe anaemia of renal failure

A
  • Drop in Hb once creatinine clearance drops below 20-30 ml/min chronically
  • Mainly due to lack of erythropoietin
  • Contribution from blood loss at dialysis, inflammatory disease
  • Responds well to erythropoietin e.g weekly or alternate weeks
56
Q

Describe haemolysis related anaemia

A
  • Increased RBC destruction, marrow can increase production 5-10 fold
  • Can be acute or chronic, congenital or acquired
  • Issues to do with RBC membranes, RBC enzymes and globin chains in Hb
57
Q

Describe anaemia due to abnormal haemoglobin

A
  • Haemoglobinopathy e.g sickle cell disease - single cell mutation causing Hb polymerisation in hypoxic cells in homozygotes
  • Shortened RBC survival, reduced production
  • Chronic anaemia and bone/liver/lung/ brain crisis ie acute infarction
  • Treated by supportive care, hydroxycarbamide to increase HbF production
58
Q

Describe thalassaemia

A
  • Inbalance of globin chain production
  • Beta thalassaemia - as Hb F (2 alpha 2 gamma chains) declines after birth - progressive anaemia
  • Supportive care, transfusion, stem cell transplant
  • Progressive iron overload
  • Antenatal screen for Hb-opathy and thalassaemia
58
Q

Describe thalassaemia

A
  • Inbalance of globin chain production
  • Beta thalassaemia - as Hb F (2 alpha 2 gamma chains) declines after birth - progressive anaemia
  • Supportive care, transfusion, stem cell transplant
  • Progressive iron overload
  • Antenatal screen for Hb-opathy and thalassaemia
59
Q

Describe anaemia due to myeloma

A
  • B cell malignancy of mature plasma cells - produce monoclonal immunoglobin or light chains
  • Presents as chance finding, anaemia, renal failure, hypercalcaemia, bone pain or fracture
  • Treatment - supportive care, chemotherapy, radiotherapy
60
Q

Describe anaemia due to marrow failure

A
  • Myelodysplastic disorders - progressive decline in Hb, neutrophils, platelets, macrocytosis. Tendency to progress to acute leukaemia. Treated by supportive care, chemotherapy or stem cell transplant
  • Aplastic anaemia - pancytopenia. Expected result post chemotherapy but can be drug induced e.g NSAIDs, chloramphenicol or idiopathic. Treated by supportive care, anti-thymocyte globulin, stem cell transplant
60
Q

Describe anaemia due to marrow failure

A
  • Myelodysplastic disorders - progressive decline in Hb, neutrophils, platelets, macrocytosis. Tendency to progress to acute leukaemia. Treated by supportive care, chemotherapy or stem cell transplant
  • Aplastic anaemia - pancytopenia. Expected result post chemotherapy but can be drug induced e.g NSAIDs, chloramphenicol or idiopathic. Treated by supportive care, anti-thymocyte globulin, stem cell transplant
61
Q

Where are red cell antigens found?

A

Red cell antigens are present on the surface of red blood cells

62
Q

What naturally occurring antibodies to people with type O antigens have?

A

Anti-A and Anti-B

63
Q

What naturally occurring antibodies to people with type A antigens have?

A

Anti-B

64
Q

What naturally occurring antibodies do people with type B antigens have?

A

Anti-A

65
Q

What naturally occurring antibodies do people with type AB antigens have?

A

None

66
Q

What is the frequency of each type of antigen group in the UK?

A
  • O = 46%
  • A = 42%
  • B = 9%
  • AB = 3%
67
Q

Describe rhesus system

A
  • Antigens: c, C, D, e, E
  • Coded for on chromosome 1 and inherited as a triplet
  • Rhesus negative implies D negative
  • No naturally occurring antibodies but can develop in response to pregnancy or transfusion
68
Q

How can haemolytic disease develop in a newborn?

A
  • Foetal red cells carrying antigens from the father transfer to maternal circulation
  • Mother produces IgG antibodies
  • Antibodies cross the placenta causing anaemia, jaundice, brain damage or foetal death
68
Q

How can haemolytic disease develop in a newborn?

A
  • Foetal red cells carrying antigens from the father transfer to maternal circulation
  • Mother produces IgG antibodies
  • Antibodies cross the placenta causing anaemia, jaundice, brain damage or foetal death
69
Q

Describe the process of cross-matching blood

A
  • Donor blood is checked for ABO, rhesus D and often other antigens and the bag is labelled. Also microbiology screening - HIV, hepatitis etc
  • Recipient’s blood is checked for ABO and rhesus D group and the plasma screened for antibodies against a panel of red cell antigens
  • Recipient’s plasma is mixed with donor red cells to check for agglutination
70
Q

What are some transfusion reactions?

A
  • Acute haemolytic reaction usually due to miss-matched blood, ABO most serious
  • Delayed haemolytic reactions (new antibodies formed during transfusion)
  • Urticaria or anaphylaxis
  • Febrile reactions

Year 1 Semester 2 (26 decks)

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