Patient on Direct anti-coagulant therapy (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
The extrinsic pathway is activated when factor VIIa (7a) binds with what on exposed tissue?
1 - von Willebrand factor
2 - tissue factor
3 - tissue plasminogen factor
4 - protein C
2 - tissue factor
- factor VIIa (7a) then activates the factor Xa (10a) and the common pathway
In secondary haemostasis, which factor is often referred to as the accelerator due to its multiple procoagulating functions?
1 - factor IIa (2a)
2 - factor Xa (10a)
3 - factor Va (5a)
4 - factor Ia (1a)
1 - factor IIa (2a)
- also referred to as thrombin
Thrombin (factor IIa (2a) is able to do lots of things involved in coagulation. It does all of the following EXCEpt which one?
1 - binds platelets activating them
2 - activates factor Va (5a)
3 - activates factor VIIIa (8a)
4 - converts fibrinogen (factor I (1) into fibrin (factor Ia (1a))
5 -converts factor XIII (13) into factor XIIIa (13a) that binds with Ca2+ cofactor forming cross bridges between fibrin mesh
6 - activates protein C and S
6 - activates protein C and S
- proteins S and C ensure clotting does not go into overdrive
Factor IIa (2a) also called thrombin is one of the key cofactors in secondary haemostasis. What is the bodies natural molecule that aims to modulate the activation of thrombin?
1 - protein S
2 - protein C
3 - antithrombin (factor IIIa (3a))
4 - factor Va (5a)
3 - antithrombin (factor IIIa (3a))
Factor IIa (2a) also called thrombin is one of the key cofactors in secondary haemostasis. Antithrombin (factor IIIa (3a)) is the bodies naturally produced modulator of thrombin. Which 2 key factors in the common pathway is antithrombin (factor IIIa (3a)) able to bind with and reduce coagulation?
1 - factors Va (5a) and Xa (10a)
2 - factors IIa (2a) and Xa (10a)
3 - factors XIIIa (8a) and Xa (10a)
4 - factors IIa (2a) and XIIIa (13a)
2 - factors IIa (2a) and Xa (10a)
- this essentially inhibits or reduces the activity of the common pathway
- factor Xa converts prothrombin into thrombin (factor IIa (2a))
- remember 2 = 7 = 9, 10, 11, 12
Which factors overall is anti-thrombin (IIIa (3a)) able to bind with and inhibit?
1 - factors 1, 2, 3, 4 and 5
2 - factors 2, 7, 9, 10, 11 and 12
3 - factors 1, 2, 7, 9 and 10
4 - factors 5, 7, 9, 11, 13
2 - factors 2, 7, 9, 10, 11 and 12
- remember 2 = 7 = 9, 10, 11, 12
Which of the following is NOT a DOAC factor Xa inhibitor?
1 - Dalteparin
2 - Edoxaban
3 - Apixaban
4 - Rivaroxaban
1 - Dalteparin
- mechanism is inhibition of factor Xa (10a)
- this is a conjugated heparin
Do anticoagulants that inhibit just factor IIa (2a, aka thrombin) or factor Xa (10a) have a greater affect on the coagulation cascade?
- factor Xa (10a) inhibitors
- no factor Xa (10a) means thrombin is not activated
Which of the following is the DOAC thrombin inhibitor that we need to be aware of?
1 - Dabigatran
2 - Edoxaban
3 - Apixaban
4 - Rivaroxaban
1 - Dabigatran
- all others are factor Xa (10a) inhibitors
DOACs are indicated in all of the following EXCEPT?
1 - PE
2 - DVT
3 - ACS
4 - AF
5 - prevent VTE in hip and knee surgery
3 - ACS
- PE and DVT make up venous thromboembolism
Are DOACs or anti-platelets more affective at preventing clot formation in the arteries?
- anti-platelets
- DOACs are more effective in veins
All of the following are adverse events of DOACs. Which is the key adverse event?
1 - anaemia
2 - GI upset
3 - dizziness
4 - bleeding
5 - elevated liver enzymes
4 - bleeding
- this is key adverse event as we could die from this
Which 2 of the following should DOACs be avoided in where possible?
1 - active clinical bleeding
2 - risk factors for bleeding
3 - renal disease
4 - liver disease
1 - active clinical bleeding
2 - risk factors for bleeding
As DOACs are removed from the body in a number of ways, which 2 of the following conditions should the dose of DOACs be lowered in?
1 - hepatic disease
2 - renal disease
3 - acute coronary syndrome
4 - hypertension
1 - hepatic disease
2 - renal disease
Which 2 of the following are DOAcs contraindicated in?
1 - CKD
2 - pregnancy
3 - hepatic cirrhosis
4 - breast feeding
2 - pregnancy
4 - breast feeding
Which of the following drugs can interact with DOACs and therefore accentuate the risk of bleeding further?
1 - heparin
2 - NSAIDs
3 - anti-platelets
4 - all of the above
4 - all of the above
Which of the following will need to be prescribed DOACs lifelong?
1 - AF
2 - venous thromboembiolism
3 - ACS
4 - knee surgery
1 - AF
Are DOACs typically administered orally or IV?
- orally
Do DOACs need to be taken with food?
- no
- EXCEPT rivaroxaban
Why do patients taking DOACs require an alert card?
1 - incase of toxicity
2 - incase of clinical treatment
3 - drug interactions
2 - incase of clinical treatment
- this is the main reason
- important if accident or surgery is required
