Direct oral anticoagulants (DOACs) - Factor Xa and Thrombin inhibitors Flashcards

1
Q

Do anticoagulants act on primary or secondary haemostasis?

A
  • secondary haemostasis
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2
Q

What is the purpose of the coagulation cascade?

1 - accentuate primary haemostasis
2 - convert fibrinogen into fibrin
3 - inhibit platelets activation in primary haemostasis

A

2 - convert fibrinogen into fibrin

  • fibrinogen = factor 1
  • fibrin = 1a
  • fibrin are monomers that form crosslinks and a strong clot
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3
Q

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

A

1 - factor XII (12) comes into contacts with collagen or activated platelets

  • platelets are activated from primary haemostasis
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4
Q

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)

A

2 - factor X forming Xa

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5
Q

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)

A

4 - factor V (5)

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6
Q

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)

A

1 - factor II (2 or prothrombin)
- prothrombin becomes thrombin (IIa)

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7
Q

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

A

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
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8
Q

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

A

3 - 10-14 secs

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9
Q

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

A

3 - intrinsic

  • time it takes the intrinsic and common pathway to form a clot following the addition of calcium and phospholipid emulsion in-vitro
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10
Q

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

A

4 - 27-41 secs

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11
Q

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

A

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
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12
Q

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

A

2 - 1-1.3 secs

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13
Q

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)

A

3 - factor XII (12) becomes factor XIIa (12a) and activates factor XI (11), then IX (9) and then X (10)

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14
Q

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)

A

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
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15
Q

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)

A

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
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16
Q

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

A

2 - tissue factor

  • factor VIIa (7a) then activates the factor Xa (10a) and the common pathway
17
Q

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)

A

1 - factor IIa (2a)
- also referred to as thrombin

18
Q

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

A

6 - activates protein C and S

  • proteins S and C ensure clotting does not go into overdrive
19
Q

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)

A

3 - antithrombin (factor IIIa (3a))

20
Q

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)

A

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
21
Q

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

A

2 - factors 2, 7, 9, 10, 11 and 12

  • remember 2 = 7 = 9, 10, 11, 12
22
Q

Which of the following is NOT a DOAC factor Xa inhibitor?

1 - Dalteparin
2 - Edoxaban
3 - Apixaban
4 - Rivaroxaban

A

1 - Dalteparin

  • mechanism is inhibition of factor Xa (10a)
  • this is a conjugated heparin
23
Q

Do anticoagulants that inhibit just factor IIa (2a, aka thrombin) or factor Xa (10a) have a greater affect on the coagulation cascade?

A
  • factor Xa (10a) inhibitors
  • no factor Xa (10a) means thrombin is not activated
24
Q

Which of the following is the DOAC thrombin inhibitor that we need to be aware of?

1 - Dabigatran
2 - Edoxaban
3 - Apixaban
4 - Rivaroxaban

A

1 - Dabigatran

  • all others are factor Xa (10a) inhibitors
25
Q

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

A

3 - ACS

  • PE and DVT make up venous thromboembolism
26
Q

Are DOACs or anti-platelets more affective at preventing clot formation in the arteries?

A
  • anti-platelets
  • DOACs are more effective in veins
27
Q

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

A

4 - bleeding

  • this is key adverse event as we could die from this
28
Q

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

A

1 - active clinical bleeding
2 - risk factors for bleeding

29
Q

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

A

1 - hepatic disease
2 - renal disease

30
Q

Which 2 of the following are DOAcs contraindicated in?

1 - CKD
2 - pregnancy
3 - hepatic cirrhosis
4 - breast feeding

A

2 - pregnancy
4 - breast feeding

31
Q

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

A

4 - all of the above

32
Q

Which of the following will need to be prescribed DOACs lifelong?

1 - AF
2 - venous thromboembiolism
3 - ACS
4 - knee surgery

A

1 - AF

33
Q

Are DOACs typically administered orally or IV?

A
  • orally
34
Q

Do DOACs need to be taken with food?

A
  • no
  • EXCEPT rivaroxaban
35
Q

Why do patients taking DOACs require an alert card?

1 - incase of toxicity
2 - incase of clinical treatment
3 - drug interactions

A

2 - incase of clinical treatment

  • this is the main reason
  • important if accident or surgery is required