Haemostasis Flashcards

1
Q

Summarise the mechanisms of normal haemostasis

A

Vessel constriction
Platelet plug formation
Plug stabilisation with fibrin
Dissolution of clot

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2
Q

What clotting factors are synthesised by the vascular endothelium?

A

PGI2
Thrombomodulin
vWF
Plasminogen activators

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3
Q

How many platelets are produced by each megakaryocte?

A

about 4000

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4
Q

What is the lifespan of a platelet?

A

10 days

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5
Q

Where are 1/3 of platelets stored?

A

Spleen

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6
Q

What receptors are present on the platelet surface?

A

Thrombin

Glycoprotein

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7
Q

Recall the types of granule present in platelets and the composition of each type

A

Dense: ADP, ATP, serotonin, Ca++
Alpha: vWF and Factor V
Glycogen

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8
Q

Describe the cytoskeleton of platelets

A

Actomyosin, microtubules

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9
Q

Recall the 2 mechanisms by which a platelet can adhere to the endothelium

A

Direct binding to Gp1a

Binding to Gp1b which binds vWF

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10
Q

What happens when a platelet adheres to the endothelium?

A

GpIIa and GpIIb activated on platelet surface
ADP and TXA2 are released
Thrombin activates coagulation

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11
Q

How are the platelets aggregated when the plug forms?

A

Fibrinogen AND Ca++ connects platelets via GpIIa and GpIIb

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12
Q

Recall the mechanism of PG metabolism that leads to PGI2 and TXA2 production

A
  1. Membrane phospholipid converted to arachdionic acid via phospholipase
  2. Conversion to endoperoxidases (eg PGH2) via COX1
  3. Converted to PGI2/ TXA2 via synthetases
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13
Q

Where are most coagulation factors synthesised?

A

Liver

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14
Q

Where is vWF synthesised?

A

Vascular endothelium

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15
Q

What clotting factors are synthesised in megakaryocytes?

A

Factor V and vWF

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16
Q

Recall the successive activation of factors in the coagulation cascade

A
12
11
9
10
prothrombin
fibrinogen
17
Q

Which coagulation factors are activated by tissue factor? What is the cofactor in each case?

A

9 (8a)

10 (calcium)

18
Q

Recall the mechanism of fibrinolysis

A

Plasminogen and tPA simultaneously encounter a fibrin clot
Plasminogen converted to plasmin
Plasmin degrades fibrin producing FDP

19
Q

What is an elevated FDP indicative of?

20
Q

What are the main inhibitory mechanisms in the clotting cascade?

A

Antithrombin III

Protein C with protein S

21
Q

Where in the coagulation cascade does anti-thrombin have inhibitory action?

A

9a
10a
thrombin

22
Q

What is the other name for factor IIa?

23
Q

What is a normal platelet count?

A

150-400 x 10^9

24
Q

What platelet count would cause common spontaneous bleeding?

A

<40 x 10^9

25
Recall 3 clinical features of AI thrombocytopenia
Purpura Multiple bruises Eccymoses
26
What are the 3 main tests for coagulation?
APTT (activated partial thromboplastin time) PT (prothrombin time) TCT (thrombin clotting time)
27
Describe the function and use of APTT
Initiates coagulation through factor XII therefore detects abnormalities in intrinsic and common pathways
28
What abnormalities can be detected by PT
Extrinsic and common pathway faults
29
What test is used to test for haemophilia?
TCT
30
What coagulation test is used to monitor heparin therapy?
APTT
31
What coagulation test is used to monitor warfarin therapy?
PT
32
Which enzyme is inhibited by warfarin and why does this inhibit coagulant?
Vit K epoxide | clotting factors are reacted with vit K in liver
33
Recall the mechanism of action of heparin
Accelerates antithrombin action
34
Recall the 3 classes of antiplatelet agent
ADP receptor agonists COX antagonist GpIIa/GpIIb antagonists