Direct oral anticoagulants (DOACs) - Factor Xa and Thrombin inhibitors Flashcards
Do anticoagulants act on primary or secondary haemostasis?
- secondary haemostasis
What is the purpose of the coagulation cascade?
1 - accentuate primary haemostasis
2 - convert fibrinogen into fibrin
3 - inhibit platelets activation in primary haemostasis
2 - convert fibrinogen into fibrin
- fibrinogen = factor 1
- fibrin = 1a
- fibrin are monomers that form crosslinks and a strong clot
The coagulation cascade has 3 parts, intrinsic, extrinsic and common pathways. How is the intrinsic pathway started?
1 - factor XII (12) comes into contacts with collagen or activated platelets
2 - factor X (10) binds with fibrin
3 - factor XII (12) binds von willebrand factor
4 - factor XII (12) binds inactive platelets
1 - factor XII (12) comes into contacts with collagen or activated platelets
- platelets are activated from primary haemostasis
In secondary coagulation the extrinsic pathway is started when damaged endothelial cells release factor III (tissue factor III) which binds with the active factor VIIa (7a) and Ca2+. This then forms the VIIa-TF complex on the smooth muscle of blood vessels. The VIIa-TF complex then cleaves what factor?
1 - factor II (2 or prothrombin)
2 - factor X forming Xa
3 - factor VIII (8)
4 - factor V (5)
2 - factor X forming Xa
Once factor Xa has become active due to the extrinsic pathway, what factor does Xa (10a) and Ca2+ bind with that will then go onto form the prothrombinase complex?
1 - factor II (2 or prothrombin)
2 - factor I (1)
3 - factor VIII (8)
4 - factor V (5)
4 - factor V (5)
Once the prothrombinase complex has been formed by active factors X (10) and V (5), what does this then cleave in the extrinsic pathway?
1 - factor II (2 or prothrombin)
2 - factor I (1)
3 - factor VIII (8)
4 - factor XII (12)
1 - factor II (2 or prothrombin)
- prothrombin becomes thrombin (IIa)
Which pathway of the coagulation cascade doe the prothrombin time (PT), which is essentially the time it takes to form a clot measures?
1 - common
2 - extrinsic
3 - intrinsic
2 - extrinsic pathway
- essentially this is the time it takes to form a clot
- tissue factor (III), Ca2+ and factor VII (7) form complex and active factor X (10)
- factor X (10) binds factor V (5) and Ca2+ and cleaves prothrombin into thrombin, which is where the name prothrombin time comes from
What is the normal value for prothrombin time (PT), which is essentially the time it takes to form a clot?
1 - 0.1 - 1.4 secs
2 - 1-4 secs
3 - 10-14 secs
4 - 15-20 secs
3 - 10-14 secs
In the coagulation cascade, activated partial thromboplastin time (aPTT) is a measure of which aspect of the coagulation cascade?
1 - common
2 - extrinsic
3 - intrinsic
3 - intrinsic
- time it takes the intrinsic and common pathway to form a clot following the addition of calcium and phospholipid emulsion in-vitro
In the coagulation cascade, activated partial thromboplastin time (aPTT) is a measure of the intrinsic and common pathway to form a clot following the addition of calcium and phospholipid emulsion. What is the normal time for this?
1 - 0.1 - 1.4 secs
2 - 1-4 secs
3 - 10-14 secs
4 - 27-41 secs
4 - 27-41 secs
What is the international normalised ratio (INR)?
1 - measure of aPTT compared to age and gender matched aPTT
2 - measure of AP
3 - measure of PT as a ratio to a standardised or control PT
3 - measure of PT as a ratio to a standardised or control PT
- PT is a measure of how long it takes clot to form
- measures extrinsic pathway
The international normalised ratio (INR) is a measure of PT as a ratio to a standardised or control PT. What is a normal value for INR?
1 - 0.1 - 1.4 secs
2 - 1-1.3 secs
3 - 10-14 secs
4 - 27-41 secs
2 - 1-1.3 secs
Once the intrinsic pathway has begun by factor XII (12) binding with activated platelets or collagen, what then happens in the intrinsic pathway?
1 - factor XII (12) then becomes factor X (10)
2 - activated platelets activate factor XI
3 - factor XII (12) becomes factor XIIa (12a) and activates factor XI (11), then IX (9) and then X (10)
4 - collagen activates factor XI (11)
3 - factor XII (12) becomes factor XIIa (12a) and activates factor XI (11), then IX (9) and then X (10)
In the intrinsic pathway, which factor activates the common pathway?
1 - factor XIIa (12a)
2 - factor XIa (11a)
3 - factor IX (9)
4 - factor Xa (10a)
4 - factor Xa (10a)
- Xa (10a) then activates factor II (2) called thrombin
- factor II (2) called thrombin then activates factor I (1) which builds the fibrin mesh
Once the common pathway has been activates by factor Xa (10) it activates factor II (2 thrombin) which activates factor Ia (1a, called fibrin) which begins building fibrin. Which 4 other cofactors is factor IIa (2a thrombin) able to also activate?
1 - Ia (1a), IIIa (3a), IVa (4a) and V (5a)
2 - XIa (11a), IIIa (3a), IVa (4a) and VIIa (7a)
3 - IIIa (3a), IVa (4a), Va (5a) and XIIa (12a)
4 - Va (5a), VIIIa (8a), IXa (9a) and XIIIa (13a)
4 - Va (5a), VIIIa (8a), IXa (9a) and XIIIa (13a)
- Va (5a) acts as a cofactor for factor Xa (10a)
- VIIIa (8a) acts as a cofactor for factor IXa (9a)
- IXa (9a)
- XIIIa (13a) helps factor I (1a) called fibrin form crosslinks and a stronger clot