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Cardio - mine > coagulation > Flashcards

coagulation Flashcards

1
Q

what is haemostasis

A

arrest of blood loss from a damaged vessel at the site of injury

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2
Q

what is involved in the sequence of haemostasis

A
  1. vascular wall damage which exposes collagen and tissue factor
  2. primary haemostasis
  3. activation of blood clotting and formation of a stable clot
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3
Q

what is involved in primary haemostasis

A

local vasoconstriction

platelet adhesion, activation, and aggregation by fibrinogen

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4
Q

what do activated platelets release

A

thromboxane A2 (TXA2)

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5
Q

what does TXA2 bind to, what does this cause

A
  1. platelet GPCR TXA2 receptors (TP receptors) which causes mediator release
  2. vascular smooth muscle cell TXA2 receptors causing vasoconstriction
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6
Q

what mediators are released by TXA2 binding

A

5-HT (aka serotonin)

ADP

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7
Q

what does ADP bind to in primary haemostasis, what does this cause

A

platelet GPCR purine receptors (P2Y12)

binding causes: further platelets to be activated, aggregation of platelets into a ‘soft plug’, and exposure of acidic phospholipids on the platelet surface that initiates coagulation of blood and solid clot formation

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8
Q

describe the coagulation cascade

A

X is converted to Xa + Va (together known as prothrombinase) by IXa and VIIIa (together known as tenase). prothrombinase then converts II (prothrombin) to IIa (thrombin). thrombin then cleaves fibrinogen to form fibrin (solid clot)

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9
Q

what is thrombosis

A

pathological haemostasis, a haematological plug in the absence of bleeding

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10
Q

what is an arterial thrombus

A

mainly platelets in a fibrin mesh

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11
Q

what is an arterial thrombus also known as

A

a white thrombus

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12
Q

what does an arterial thrombus form if it detaches

A

an embolus which then lodges in an artery (causing stroke) or other organ

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13
Q

how is an arterial thrombus treated

A

antiplatelet drugs

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14
Q

what is a venous thrombus

A

white head, jelly-like red tail.. fibrin rich

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15
Q

what is a venous thrombus also known as

A

red thrombus

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16
Q

what does a venous thrombus form if it detaches

A

an embolus that usually lodges in the lung

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17
Q

how is a venous thrombus treated

A

anticoagulants

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18
Q

what drug works on factor X

A

warfarin

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19
Q

what drug works on factor II

A

warfarin

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20
Q

what drug works on factor Xa

A

orally active inhibitors

heparin/LWMH/fondaparinux

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21
Q

what drug works on factor IIa

A

orally active inhibitors

heparin/LWMH/fondaparinux

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22
Q

what is warfarin’s mechanism of action

A

inactivates factors II, VII, IX, and X

23
Q

how is warfarin administered

A

orally

24
Q

what is used to treat an warfarin overdose

A

vitamin K (as phytomenadione)

25
Q

what is orally active inhibitor’s mechanism of action

A

directly inhibit thrombin or factor Xa

26
Q

give an example of an orally active inhibitors

A

dabigatran (inhibits thrombin)

rivaroxaban (inhibits factor Xa)

27
Q

what is the mechanism of action of heparin

A

inhibits factors Xa and IIa

28
Q

what is the mechanism of low molecular weight heparin (LWMH)

A

inhibits factor Xa

29
Q

what are the serine proteases in the coagulation cascade

A

VIIa
IXa
Xa

30
Q

what does anti-thrombin III (ATIII) do

A

important inhibitor of coagulation as it neutralised ALL serine protease factors in the coagulation cascade

31
Q

explain the link between heparin and ATIII

A

heparin binds to ATIII which increases its binding affinity especially for factors Xa and IIa which increases their rate of inactivation

32
Q

how does heparin inactivate IIa

A

by binding to ATIII AND factor IIa

33
Q

how does heparin inactivate Xa

A

by binding to ATIII

34
Q

what are anticoagulants used to treat

A

AF
DVT
post-op thrombosis
patients with artificial heart valves

35
Q

give examples of low molecular weight heparin (LMWH)

A

“-parin”

fondaparinux “-pariniux”

36
Q

how is LMWH administered

A

subcutaneously (SC) = injection

37
Q

how is heparin administered

A 
IV = immediate onset of action
SC = onset delayed by 1 hour
38
Q

when is heparin preferred over LMWH, why?

A

renal failure

LMWH is excreted via the kidneys, heparin is not

39
Q

what is given in if a heparin haemorrhage has occurred

A

protamine sulfate IV

40
Q

what are anticoagulants used for

A

venous thrombosis

41
Q

what are antiplatelets used for

A

arterial thrombosis

42
Q

give examples of antiplatelets

A

aspirin
clopidogrel
tirofiban

43
Q

what is the mechanism of action of clopidogrel

A

links to the P2Y12 receptor via disulphide bond producing irreversible inhibition

44
Q

when would clopidogrel be used

A

most often given in patients intolerant to aspirin

45
Q

what is the mechanism of action of aspirin

A

irreversibly blocks cycloxygenase (COX) in platelets preventing TXA2 synthesis

also blocks COX in endothelial cells inhibiting production of antithrombotic prostaglandin I2 (PGI2)

46
Q

what cascade opposes the coagulation cascade

A

fibrinolytic cascade

47
Q

describe the fibrinolytic cascade

A

plasminogen is converted to plasmin via endogenous tissue plasminogen activator (tPA). Plasmin then converts fibrin to fibrin fragments which are involved in clot lysis

48
Q

where do fibrinolytic drugs act

A

act on the conversion on plasminogen to plasmin

49
Q

give examples of fibrinolytic drugs

A

streptokinase
alteplase
duteplase

50
Q

what is streptokinase

A

a protein extracted from strep cultures

51
Q

when is streptokinase contraindicated

A

in a patient with a recent strep infection or an allergy

52
Q

what are alteplase and duteplase

A

recombinant tissue plasminogen activators (rt-PAs)

53
Q

how can haemorrhage caused by alteplase or duteplase be treated

A

oral tranexamic acid which inhibits plasminogen activation

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