Patient on anti-coagulant therapy (DOACs) - Vitamin K antagonists Flashcards
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
2 - 1-1.3
3 - 10-14
4 - 27-41
2 - 1-1.3
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
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 factors in the coagulation cascade are synthesised in the liver are vitamin K dependent?
1 - 2, 3, 4 and 5
2 - 2, 7, 9 and 10
3 - 2, 4, 6 and 8
4 - 2, 7, 10 and 12
2 - 2, 7, 9 and 10
Warfarin is the core vitamin K antagonist we need to know about. Which factors of the coagulation cascade is Warfarin able to inhibit?
1 - 2, 3, 4 and 5
2 - 2, 7, 9 and 10
3 - 2, 4, 6 and 8
4 - 2, 7, 10 and 12
2 - 2, 7, 9 and 10
- inhibits vitamin K factors II (2), VII (7), IX 9 and X (10) - coagulation
- 1972 was the year of diSCo
- factors 9, 7, 2 and 10
- proteins S and C
Warfarin is able to inhibit the synthesis of factors 2, 7, 9 and 10 in the coagulation cascade. However, what enzyme is Warfarin able to inhibit to cause an anti-coagulability state?
1 - vitamin K hydroquinone
2 - glutamyl carboxylase
3 - vitamin K epoxide reductase
4 - quinone reductase
3 - vitamin K epoxide reductase
- essentially stops the recycling of vitamin K
In addition to inhibiting factors 2, 7, 9 and 10, what 2 other proteins is Warfarin able to inhibit?
1 - albumin
2 - protein S
3 - protein C
4 - fibrinogen
2 - protein S
3 - protein C
- 1972 was the year of diSCo
- factors 9, 7, 2 and 10
- proteins S and C
Warfarin is indicated in all of the following EXCEPT?
1 - PE
2 - DVT
3 - ACS
4 - AF
3 - ACS
- PE and DVT make up venous thromboembolism (VTE)
- DOACs are the generally preferred over Warfarin
In which of the following is Warfarin preferred as the 1st choice medication?
1 - mechanical heart valves
2 - AF
3 - atrial flutter
4 - ACS
1 - mechanical heart valves
Which of the following is the key adverse event of Warfarin?
1 - anaemia
2 - GI upset
3 - dizziness
4 - bleeding
5 - elevated liver enzymes
4 - bleeding
- contraindicated if active bleeding is present
What is the antidote of Warfarin?
1 - naloxone
2 - acetylcysteine
3 - flumazenil
4 - phytomenadione
4 - phytomenadione
- naloxone = opioid antidote
- acetylcysteine = paracetamol overdose on liver
- flumazenil = benzodiazepine overdose
Warfarin is not effective immediately. There is typically a lag between the dose and effect. How long is this typically?
1 - 24h
2 - 24-48h
3 - 3-4 days
4 - 7 days
3 - 3-4 days
Why are warfarins not generally used in patients with liver disease?
1 - blood flow will be impaired
2 - cannot remove warfarin and it can become toxic
3 - coagulation factors will already be depleted
3 - coagulation factors will already be depleted
- this would amplify the anti-coagulation effect of warfarin
Why is warfarin not recommended for women pregnancy in the 1st trimester?
1 - teratogenicity
2 - cross placenta and cause blood thinning in foetus
3 - can be passed through breast milk
4 - increases risk of rhesus positive
1 - teratogenicity
- leads to deformity in babies
Warfarin is metabolised by cytochrome P450 (CYP). Which of the following are CYP inducers, which effectively increasing the risk of clotting?
1 - phenytoin
2 - carbamazepine
3 - rifampicin
4 - all of the above
4 - all of the above
- phenytoin = epilepsy medication
- carbamazepine = anticonvulsant medication
- rifampicin = antibiotic
Warfarin is metabolised by cytochrome P450 (CYP). Which of the following are CYP inhibitor, which effectively increases the risk of bleeding?
1 -fluconazole
2 - macrolids
3 - verapamil
4 - all of the above
4 - all of the above
- fluconazole = anti-fungal medication
- macrolids = antibiotic class
- verapamil = Ca2+ channel blocker
In addition to macrolids and rifampicin, other antibiotics can aaccentuate the effects of warfarin, but not by affecting cytochrome P450 (CYP). How else can other antibiotics affect warfarin efficacy?
1 - inhibit absorption of vitamin K
2 - kill off healthy flora, reducing absorption of vitamin K
3 - increase risk of diarrhoea
2 - kill off healthy flora, reducing absorption of vitamin K
When administering Warfarin, it can initially making clotting worse, generally in the first 36 hours. Why is this the case?
1 - liver becomes hypersensitive to vitamin K
2 - toxicity damages coagulation proteins
3 - warfarin takes a long time to metabolise
4 - inhibits proteins S and C
4 - inhibits proteins S and C
- proteins S and C inhibit Va and VIIIa
- basically means patients may be at increase risk of clot in this 36 hour window
- heparin can be used to help with this
Which of the following needs to be monitored to alter the patients warfarin dose and efficacy?
1 - AP
2 - aPTT
3 - INR
3 - INR
- measures extrinsic pathway
- INR = PT/normal PT
- warfarin effects factor VIIa (7a) first, a measure of the extrinsic pathway through factor VIIa
What is considered a normal INR in patients taking warfarin?
1 - 0.1-1
2 - 1.0-1.3
3 - 2.0-3.0
4 - 5.0-10.0
3 - 2.0-3.0
