The coagulation system Flashcards

1
Q

T or F: haemophilia is a genetic disease in which platelet function is impaired?

A

F, is a problem with factor 8 or 9

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2
Q

Vit K deficiency at birth? risks?

A

severe bleeding in the brain

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3
Q

Thrombosis definition

A

formation of an abnormal thrombus
vessel wall generally intact
Venous: red cells and fibrin
Arterial: platelet rich, occlusive

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4
Q

Physiological haemostasis

A

BV wall disrupted
Form a thrombus to heal the defect
Platelet rich, generally size limited

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5
Q

Haemostats breakdown

A
  • Following vessel injury vessel vasoconstrictor
  • Exposure of collagen in sub endothelial tissue
  • Platelets adhered to collagen via circulating von-hillenbrand factor, binds platelet receptor GP1b to collagen
  • Platelet morphology changes from disc to spiny sphere
  • Shape change associated with release action involves the release of vasoconstricting amines (serotonin) and ADP –> further activation and aggregation
  • Aggregation mediated by fibrinogen, binding platelets together via intergrin and alpha(IIb)beta(3) receptor which is activated during platelet shape change process
  • Prostaglandin pathways in the platelet convert arachidonic acid to thromboxane A2 –> potent vasoconstrictor and aggregator
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6
Q

purpose of the coagulation pathway

A

formation of fibrin (by activation of thrombin) around platelet plug to stabilise clot

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7
Q

the 2 ways to activate the coagulation pathway

A
  1. contact activation on a changed surface

2. protein tissue factor

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8
Q

The coagulation pathway breakdown

A

Tissue factor - only expressed on sub endothelial tissues e.g. fibroblasts and smooth muscle - exposed following trauma
- Factor VII activated by binding to TF and trace amounts of other clotting factors
- VIIa, activates IX and X, this is rapid, this process is also rapidly inhibited by tissue factor pathway inhibiting factor (TFPI)
- Said initial burst of activation was to produce a small amount of Xa, then quickly stop it to prevent widespread coagulation
- Factor Xa slowly converts a small amount of prothrombin –> thrombin
Thrombin (amplifies coagulation pathway to produce more thrombin), activates V, VIII, XI, cofactors dramatically speed up coagulation
VIIa + IXa + calcium + phospholipid = tens complex
Tenase complex converts X to Xa
Xa + Va + calcium + phospholipid = prothrombinase complex
prothrombinase complex converts prothrombin to thrombin
Thrombin:
- Converts fibrinogen to fibrin
- XI –> XIa, which converts IX to IXa

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9
Q

What is the modern theory of coagulation?

A
  1. initial burst of factor VIIa activity with production small amounts Xa and thrombin
    Thrombin feedback activates factors V and VIII, accelerate thrombin generation, accelerate thrombin generation
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10
Q

bonus of the role of phospholipids?

A

from endothelium of activated platelets keeps coagulation localised

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11
Q

Fibrin clot formation

A

Fibrinogen composed of alpha, beta and gamma strands
Thrombin cleaves small fragments of alpha and beta chains so the chains can polymerise to long fibrin strands, stabilised by XIIIa (activated by thrombin)

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12
Q

Other methods of coagulation

A

contact with negatively charges surface, little role in physiology but significant in APTT clotting test
When in glad tube factor XII spontaneously activates which i turn activates factors XI and IX (a good test for determining deficiencies of factors XII, XI, IX, and VII)

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13
Q

What are the contact factors?

A

XII, XI, high molecular weight kininogen and prekallikerin

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14
Q

What are the thrombin sensitive factors?

A

fibrinogen V, VIII and XIII

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15
Q

What are the Vitamin K dependant factors

A

II, VII, IX,X have Gla domain, binds to phospholipid via an interaction with series of glutamic acid residues, need to be gamma carboxylated, which can only be done by Vit K, Vit K inhibited by warfarin,

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16
Q

Natural inhibitors of coagulation

A

proteins prevent uncontrolled coagulation

  • Antithrombin, inhibits thrombin also Xa, IXa, and XIa
  • Protein C activated by thrombin (assisted by thrombomodulin)
  • Protein S a cofactor of protein C
17
Q

Fibrinolytics

A

Activated when any clot forms, to digest clot
Fibrinolytic cascade, converts plasminogen –> plasmin
catalysed by tPA (tissue plasminogen activator) and uPA (urokinase like plasminogen activator)

18
Q

inhibitors of fibrinolysis

A

Antiplasmin binds to plasmin
Thrombin activates TAFI (thrombin activated fibrinolysis inhibitor), when thesis activated by thrombin, it removes lysine residues from fibrin, prevents plasminogen binding to the clot, inhibits fibrinolysis.

19
Q

vit K extra notes

A
Deficiency = bleeding 
get vit k from diet and bowel bacteria 
new born bleeding inside the brain associated with fit K deficiency and the trauma of birth = hemorrhagic disease of newborn 
vit K suplements at birth 
reversal of warfarin = 12 -24 hours
20
Q

Is contact activation important

A

Factor XII deficiency not associated with bleeding
Factor XI deficiency mild
Some mammals do not have factor XII

21
Q

Is the bleeding abnormal

A
start with a bleeding history 
- more important than lab test 
family history 
trauma / surgery - if didn't bleed a lot thats significant 
Menstruation 
Pregnancy 
Bruising or joint bleeds 
Epistaxis 
New borns: umbilical bleeding 
Bleeding in other sites