Theme 3: Haematology Flashcards

1
Q

what are the 5 stages of haemostats?

A
  1. vasoconstriction
  2. primary haemostasis
  3. secondary haemostasis
  4. clot retraction and repair
  5. fibrinolysis
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2
Q

what happens when NO production is disrupted by injury to the endothelium?

A

vasoconstriction

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3
Q

what does ADP released from damaged endothelial cells do?

A

ADP acts on platelet P2Y1 and P2Y12 receptors causing platelet activation- they form pseudopodia and release the contents of their granules

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4
Q

where is von willebrand factor found and what does it bind to in primary heamostasis?

A

vWF is found on exposed collagen and binds to glycoprotein 1b on platelets

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5
Q

what platelet glycoprotein does collagen bind directly to?

A

GPVI

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6
Q

what does cyclooxyrgenase-1 (cox-1) released by activated platelets do?

A

converts arachidonic acid to thromboxane A2 which activates more platelets

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7
Q

how do platelets bind to each other?

A

the GPIIb/ GPIIIa molecules on platelets bind to each other via a molecule of fibrin

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8
Q

what is the trigger for the extrinsic pathway of the coagulation cascade?

A

tissue factor

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9
Q

which coagulation factor is involved in the extrinsic pathway?

A

factor VII which then activates factor x in the common pathway

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10
Q

what is the trigger for the intrinsic pathway of the coagulation cascade?

A

negatively charged collagen in the sub-endothelium of blood vessels

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11
Q

which coagulation factors are involved in the intrinsic pathway?

A

twelve, eleven, nine, eight then ten in the common pathway

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12
Q

what activates factor XIII and what is its function?

A

thrombin (factor IIa) activates factor XIII which then stabilises the clot by cross linking fibrin

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13
Q

what is the function of fibrin?

A

fibrin forms a sticky mesh which traps platelets and RBCS into the plug stabilising it

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14
Q

how is plasminogen activated and what does it do?

A

plasminogen is activated to plasmin by tissue plasminogen activator (tPA) and urokinase.
plasmin degrades fibrin into fibrin degradation products (FDP) such as D dimer

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15
Q

how does sodium citrate act as an anticoagulant?

A

sodium citrate binds to calcium which stops the coagulation cascade. its effects can be reversed by adding calcium

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16
Q

which pathway does the prothrombin time measure?

A

the extrinsic pathway

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17
Q

which pathway does the activated partial thromboplastin time measure?

A

the intrinsic pathway

18
Q

what is the INR?

A

the international normalised ratio is a measure derived from PT which allows standardisation of PT so it can be compared between different labs- used to measure the affects of warfarin

19
Q

what is a D dimer test used for?

A

it is used to detect the presence of fibrin clots e.g DVT or PE

20
Q

what are the different categories of platelet disorders?

A

quantitative- to do with platelet number e.g thrombocytopenia/ thombocytosis
qualitative- to do with platelet function. can be hereditary or aquired ( drugs, liver/renal failure)

21
Q

what can cause thrombocytopenia?

A

decreased synthesis- BM failure, aplastic anaemia, leukaemia
increased consumption- infection, disseminated intravascular coagulation
increased destruction- idiopathic thrombocytopenia purpura (ITP), splenomegaly

22
Q

how does glazmans thrombasthenia cause abnormal platelet function?

A

abnormality in GPIIb/IIIa (fibrinogen receptor)- platelets can’t bind to one another

23
Q

how does Bernard-soulier syndrome cause abnormal platelet function?

A

abnormality in GPIb (vWF receptor)- platelets do not bind to the injury site

24
Q

what is the pathogenesis of haemophilia A/B?

A

there is a genetic variant in factor VIII (A) or factor IX (B)

25
what is the pathogenesis of acquired haemophilia?
autoantibodies against a coagulation factor (usually factor VIII) are formed is either idiopathic or associates with malignancy, autoimmune disease or drugs
26
what are the favourable conditions for coagulation?
virchows triad: - stasis of blood flow- venous stasis, AF - endothelial injury- e.g atheroma - hypercoagulability
27
what are the symptoms of DVT?
pain, swelling, warmth, erythema, shiny skin
28
where is a venous thromboembolism usually lodge?
a pulmonary artery- pulmonary embolism
29
what are the signs and symptoms of pulmonary embolism
symptoms- breathlessness, chest pain, haemoptysis, syncope | signs- tachycardia, tachypnoea, signs of pleural effusion, signs of right heart strain
30
what can cause hyper coagulability?
cancer- especially pancreas, lung, brain, gastric antiphospholipid syndrome oestrogen- post-partum, COCP hereditary thrombophilia factor V leiden mutation antithrombin III deficiency protein C/S deficiency (normally degrade coagulation factors)
31
what can arterial thrombosis cause?
myocardial infarction actue limb ischamia acute mesenteric (gut) ischaemia stroke
32
what is the mechanism of action of heparin and low molecular weight heparin?
heparin- activates antithrombin III which inhibits thrombin clotting factors IX, Xa and XIII LMWH- inactivates factor Xa via action of antibrombin III. cannot inactivate thrombin as it is not large enough to bind to ATIII and thrombin at the same time
33
what are the side effects of heparin?
bleeding hypersensitivity heparin- induced thrombocytopenia
34
what is the clinical use of heparin?
treatment of established VTE prevention of post-operative VTE used to initiate coagulation therapy until an oral anticoagulant takes effect
35
what is the mechanism of action of warfarin?
vitamin K antagonist | inhibits the activation of vitamin K dependant clotting factors (VII, IX, X, II)
36
what is the clinical use of wrafarin?
prevent the recurrence or progression of venous thrombosis or PE prevent arterial thromboembolism in patients with AF or cardiac disease (mechanical heart valves)
37
what is the mechanism of action of rivaroxaban?
selective factor Xa inhibitor- binds to and inhibits both free and bound Xa
38
what is the mechanism of action of dibigatran?
direct thrombin inhibitor- competitive reversible inhibitor of thrombin
39
what is the mechanism of action of aspirin as an anti-platelet drug?
aspirin irreversible inhibits COX-1 and therefore inhibits the synthesis of thromboxane A2 (which promotes platelet aggregation)
40
what is the mechanism of action of altepase?
recombinant tissue plasminogen activator- activates the conversion of plasminogen to plasmin which breaks down fibrin and degrades clots