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Flashcards in Coagulation/anticoagulation Deck (102)
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1
Q

What are some risk factors for clotting?

A
60+
Active cancer or cancer treatment
Dehydrated 
Obese
History/family history of VTE
HRT or COC
Pregnancy
Critical condition
Surgery
2
Q

What are some risk factors for a bleed?

A
Epidural
Surgery
Active bleeding
Blood disorder
INR >2
Acute stroke
Uncontrolled hypertension
Concurrent use of anticoagulants
3
Q

Long-haul flyers could reduce the risk of blood clts by

A

Wearing compression stockings.

4
Q

People prefer which type of compression stockin?

A

Knee high. (thigh high not liked)

5
Q

When would we use UFH unfractionated heparins instead of LMWH?

A
  1. Impaired renal function

2. If patient has a high risk of bleeding - they have short half-lifes.

6
Q

What is UFH dosing adjusted according to?

A

The APTT: activated partial thromboplastin time, which is a measure of the activity of the intrinsic and common pathways of coagulation.

7
Q

What is the APTT?

A

APTT: activated partial thromboplastin time.

8
Q

Why are UFH preferred instead of LMWH in patients with a high bleed risk?

A

UFH have a shorter half life than LMWH,.

9
Q

The clotting time for APTT lies between

A

27-35 seconds

10
Q

What is the difference between APTT, APTT ratio and INR?

A

APTT is ~30s, APTT ratio = (APTT value)/control value = ~1.5 etc.

It is the same principle as INR.

11
Q

What does the prothrombin time measure?

A

Prothrombin time (PT) is a blood test that measures how long it takes blood to clot. A prothrombin time test can be used to check for bleeding problems. PT is also used to check whether medicine to prevent blood clots is working. A PT test may also be called an INR test.

12
Q

What are the properties of an ideal anticoagulant?

A
  1. Orally active
  2. Rapid (several hours) immediate response.
  3. Wide therapeutic index
  4. Little or no inter-individual or intra-individual variability.
  5. No drug/food interactions.
  6. Predictable PD/PK
  7. No routine monitoring required.
  8. No routine dose adjustment needed.
  9. Highly efficacious in reducing thromboembolic events
  10. Good safety profile.
13
Q

A measure of the common and intrinsic pathways of coagulation.

A

APTT: activated partial thromboplastin time.

14
Q

How do LMWH compare with the ideal qualities for an anticoagulant?

A

Has all of them except oral activity.

  1. SC injection not orally active X
  2. Rapid (several hours) immediate response.
  3. Wide therapeutic index
  4. Little or no inter-individual or intra-individual variability.
  5. No drug/food interactions.
  6. Predictable PD/PK
  7. No routine monitoring required.
  8. No routine dose adjustment needed.
  9. Highly efficacious in reducing thromboembolic events
  10. Good safety profile.
15
Q

LMWH are used to treat

A

DVT/PE & UA

16
Q

LMWH are used for prohylaxis of

A

thrombo-prophylaxis in medical or surgicial situations.

17
Q

How are LMWH heparins dosed?

A

According to patient weight, given SC

18
Q

Give examples of three LMWH

A

Tinzaparin
Dalteparin
Enxaparin

19
Q

What are the differences in license between tinzaparin, dalteparin and enoxaparin?

A

All are licensed for DVT, PE, Prophylaxis.

Tinzaparin is NOT licensed for UCAD while dalteparin and enoxaparin are. (unstable coronary artery disease).

20
Q

What is the VTE treatment dose of Tinzaparin?

A

175ui/kg OD

21
Q

What is the VTE treatment dose of Dalteparin?

A

200iu/kg OD

22
Q

What is the VTE treatment dose of Enoxaparin?

A

1.5mg/kg OD

23
Q

What is the UCAD dose of Dalteparin?

A

120ui/kg BD

24
Q

How frequently is Dalteparin used for UCAD and what dose?

A

BD, 120ui/kg

25
Q

A LMWH which has a VTE treatment dose of 175iu/kg OD.

A

Tinzaparin.

26
Q

A LMWH which has a VTE treatment dose of 200ui/kg OD.

A

Dalteparin.

UCAD dose 120ui/kg BD

27
Q

What is the UCAD dose of enoxaparin?

A

1mg/kg BD.

28
Q

PT is a measure of which pathway?

A

Extrinsic

29
Q

PT measure what?

A

Time to clot formation which is normally about 12 seconds.

30
Q

How is PT converted into INR?

A

Using an international sensitivity index (ISI) to enable comparisons between different tissue thromboplastins.

31
Q

What is the normal INR?

A

1.0-1.2

32
Q

What is the calculation to work out INR?

A

INR = PT(patient)/PT(mean normal)*ISI

33
Q

How does Warfarin compare to the ideal characteristics of anticoagulants?

A

Orally admin.
Not rapid onset.
Not wide index of action.
Variability in dose response present.
Interactions with food or drugs common: antibiotics.
Unpredictable PD/PK due to patient variability.
Routine monitioring is needed.
Dose adjustment can be frequently needed.
Only highly effective when INR therpeutic levels.
Only good safety profile when therapeutic INR.

34
Q

Why are interactions with warfarin so common? (2)

A

IT is metabolished by the liver cytochrome p450 system - other drugs can interfere with this metabolism.

Warfarin is highly bound to plasma proteins like albumin - other protein bound drugs can have a competitive effect.

35
Q

How can warfarin overdose be treated?

A

Beriplex: NICE recommend prothrombin complex concentrates for emergency reversal of warfarin.

Beriplex P/N contains all the vitamin K- dependent coagulation factors as well as the coagulation inhibitors Protein C and S.

36
Q

Warfarin inhibits the effective synthesis of the vitamin K-dependent clotting factors: II, VII, IX and X, as well as the regulatory factors ______ and ________.

A

Warfarin inhibits the effective synthesis of biologically active forms of the vitamin K-dependent clotting factors: II, VII, IX and X, as well as the regulatory factors protein C, and protein S

37
Q

________ is an innate anticoagulant that, like the procoagulant factors that warfarin inhibits, requires __________ __________ for its activity.

A

Protein C is an innate anticoagulant that, like the procoagulant factors that warfarin inhibits, requires vitamin K-dependent carboxylation for its activity

38
Q

_________ is a vitamin K-dependent anticoagulant protein.

A

Protein S is a vitamin K-dependent anticoagulant protein

39
Q

What does DOAC stand for?

A

Direct Acting (ORAL) AntiCoagulants.

40
Q

What is apixiban?

A

DOAC with less bleeding risk, half-life of 12 hours.

Direct inhibitor of activated factor X (factor Xa)

41
Q

What are the 4 indiciatons for Apixiban use?

A
  1. VTE prevention post knee or hip replacement.
  2. Treatment of DVT and
  3. Prophylaxis of recurrent DVT and PE.
  4. Non-valvular AF
42
Q

What is Dabigatran?

A

Another DOAC.
Orally active.
Direct thrombin inhibitor

43
Q

What are the indications for dabigatran?

A

VTE prevention post knee or hip replacement.
Treatment of DVT and prophylaxis of recurrent DVT and PE.
Stroke prevention in patients with AF

44
Q

Why would you use Apixiban instead of Dabigatran?

A

Less bleed risk.

45
Q

What is edoxaban?

A

Direct inhibitor of activated factor X (Factor Xa) Same as apixiban.

46
Q

What are the indications for the use of Edoxaban? (3)

A

Prevention of stroke and systemic embolism.
Treatment of DVT, PE.
Prevention of recurrent DVT and PE (VTE).

47
Q

Direct thrombin inhibitor

A

Dabigatran

48
Q

DOAC used for prevention of stroke and systemic embolism

A

Edoxaban.

49
Q

What do edoxaban, apixiban and rivaroxaban have in common?

A

All direct inhibitors of activated factor X (Factor Xa)

50
Q

Caution should be taken when using dabigatran in patients with

A

Renal failure.

51
Q

Direct thrombin inhibitor that can be used for stroke prevention in patients with AF

A

Dabigatran

52
Q

Dabigatran has interactions with what drugs?

A

Verapamil and quinine/quinidine.

53
Q

What is Rivaroxaban, how does it work?

A

DOAC

A direct inhibitor of activated Factor X (Factor Xa)

54
Q

What is Rivaroxaban licensed to treat?

A
  1. VTE prevention post knee or hip replacement.
  2. Treatment of DVT and prophylaxis of recurrent DVT and PE.
  3. Stroke prevention in patients with AF.
55
Q

How should Rivaroxaban be taken and why?

A

With food: increased BA.

56
Q

What are the limits of the DOACs?

A

Limited reversibility - what if an accident with severe bleeding occurs? how do we restore coagulation?

Although one of the benefits is that we do not have to monitor the patients as much - we also do not know if the patients are taking them correctly.

57
Q

What does the baseline monitoring for DOACs consist of?

A
  1. Prothrombin time
  2. Liver function
  3. Renal Function
  4. BP
58
Q

What DOACs can be used for VTE prevention in hip and knee replacement?

A

Dabigatran
Rivaroxaban
Apixaban.
NOT Edoxaban.

59
Q

What DOACS can be used for the prevention of non-valvular AF?

A
Dabigatran
Rivaroxaban
Apixaban
Edoxaban
ALL of them.
60
Q

What DOACS can be used for the treatment of DVT?

A

ALL of them
Dabigatran
Rivaroxaban
Edoxaban

61
Q

What DOAC cannot be used for VTE prophylaxis in hip and knee replacement?

A

Edoxaban.

62
Q

How should patients be swapped from warfarin to xarelto (Rivaroxaban)?

A

When the INR is < 2.5.

63
Q

Why should INR values not be used to measure the anticoagulant activity of Rivaroxaban?

A

Not valid.

64
Q

How should patients be swapped from warfarin to Apixaban?

A

When INR < 2.0

65
Q

When should patients be swapped from warfarin onto Edoxaban?

A

INR: <2.5

66
Q

How is an overdose of dabigatran treated?

A

Activated charcoal within 1-2 hours

67
Q

How is rivaroxaban overdose treated?

A

Activated charcoal reduces absorption if used within 2-4 hours of ingestion.

68
Q

How is apixaban overdose treated?

A

Activated charcoal up to 3 hours post ingestion.

69
Q

How can bleeding be managed with DOACs?

A

Stop the drug.
Fluid replacement to ensure good urine output.
PCC or rFVII
IV tranexamic acid
Haemodialysis - not for FXa inhibitors as they are highly protein bound. Only for Dabigatran.

70
Q

What is Idarucizumab?

A

Fully humanised monoclonal antibody fragment which has a highly specific binding affinity with dabigatran therefore reversing any anticoagulant activity of dabigatran and its metabolites.

SO EXPENSIVE: 5g = £2,400.

71
Q

Andexanet Alpha is being developed for reversal of the actions of which DOACs?

A

Rivaroxaban
Apixaban
Edoxaban
All factor Xa inhibitors.

72
Q

Aripazine is being developed for the reversal of the anticoagulant effect of

A

All DOACs, oral factor Xa inhibitors, fondaparinux, LMWHs and unfractionated heparins.

73
Q

How does Andexanet Alpha work?

A

Factor Xa decoy that binds the direct factor Xa inhibitors rivaroxaban, apixaban and edoxaban.

74
Q

What is Ciraparantag?

A

Small synthetic water-soluble molecule that binds to a wide range of anticoagulants from binding to their endogenous targets.

75
Q

What are the most important contra-indications for DOACs?

A
A lesion or condition, if considered a significant risk factor for major bleeding. This may include:
GI ulcers. 
Varices
Haemorrhage
Brain/Spinal/Eye surgery.

Treatment with other anticoagulant agents.

76
Q

What is betrixaban?

A

Pipeline. Oral, once-daily Factor Xa inhibitor, an important validated target in the blood coagulation pathway, to prevent life-threatening thrombosis.

77
Q

What is the coagulation cascade made up of?

A

3 pathways.
Intrinsic
Extrinsic
Final common.

78
Q

What is the intrinsic pathway?

A

Factor XII is activated by contact with ‘damaged’ surface which ultimately leads to the activation of factor X.

79
Q

What is the extrinsic pathway?

A

The activation of ‘tissue factor’ - Factor VII is released from damaged cells + calcium ions which causes the activation of factor X.

80
Q

What is the final common pathway?

A

Activated Factor 10 from both the intrinsic and extrinsic pathway helps to convert prothrombin into thrombin which in turn converts fibrinogen to activated fibrin.

81
Q

Activated ___________ from both the intrinsic and extrinsic pathway helps to convert __________ into __________ which in turn converts _______ to activated _____.

A

Activated Factor 10 from both the intrinsic and extrinsic pathway helps to convert prothrombin into thrombin which in turn converts fibrinogen to activated fibrin.

82
Q

What is the MOA of heparins?

A

Activates antithrombin which induces inactivation of thrombin.

Potentiates naturally occurring inhibitors of activated factor 10. (Xa)

83
Q

What monitoring for UFH? [5]

A
  1. Weight
  2. Renal function
  3. FBC: due to heparin induced thrombocytopenia - on initiation and again if the treatment lasts more tha 4 days.
  4. U+Es: risk of hyperkalaemia (all heparins)
  5. APTT

NB. Osteoporosis risk is high with UFHs.

84
Q

Monitoring for heparins?

A
  1. Weight
  2. Renal function
  3. FBC but greater risk of HIT in UFH.
  4. Hyperkaleamia so U+Es.
  5. Use antifactor Xa in special circumstances if pregnant, low weight, children, renal failure to measure the efficacy and if dose is correct - and for HIGH weight.
85
Q

HIT type _ is more common.

A

HIT Type 2, entails platelet counts falling and thombosis.

86
Q

UFH –> FBC when?

A

Intiation and again if treatment lasts more than 4 days.

87
Q

What is warfarin?

A

Vit-K-epoxide-reductase inhibitor - transient risk of increased clot change on initiation due to decreasing innate anticoagulants protein S and C.

Bridging with heparins occurs to overcome this.

88
Q

Warfarin side effects:

A

Skin rashes, alopecia, bleeding, bruising.

Anticoagulant book for all!

89
Q

Apixaban has less bleed risk in

A

Elderly.

90
Q

Rivaroxaban works by

A

Inhibiting Activated Xa.

Taken once daily with food.

Has a positive impact on ACS.

91
Q

Dabigatran works by

A

Directly inhibiting thrombin - reversible via idacruziamb.

Not for renally impaired. 80% renal clearance.

92
Q

Anticoagulation for someone <40kg

A

Warfarin
and children.
NOT pregnancy -> LMWH

93
Q

Anticoagulation for heart valve mechanical?

A

Warfarin

94
Q

eGFR <40 anticoagulants

A

Apixaban, rivaroxaban not DABIGATRAN

95
Q

Which doac not for renally impaired?

A

Dabigatran

96
Q

Warfarin has many drug-drug interactions because:

A

Protein bound and CYP450

97
Q

How does a warfarin to rivaroxaban switch occur?

A

Stop warfarin, wait until INR below 2.5 (5-6days) then start rivaroxaban at BNF dose.

98
Q

What is the largest risk factor for VTE that is not hereditary?

A

COC

99
Q

UFH doses are based on weight/renal function but adjusted according to

A

APTT

100
Q

Protoamine sulphate

A

Reversal agent for heparins, LMWH, UFHs etc.

101
Q

Anticoagulation in pregnancy

A

LMWH - based off pre-pregnancy or early pregnancy weight.

102
Q

If a patient who is pregnant has a history of DVT in a previous pregnancy, how is this managed?

A

Start anti-embolism stockins as soon as pregnancy confirmed.

Start prophylaxis dose LMWH 4 weeks before time of previous DVT in pregnancy occured.