Anticoagulation Flashcards
Give examples of when anticoagulation is used for primary prevention
Arterial:
- Stroke prevention in patients with AF
Venous:
- Prevention of DVT or PE (i.e VTE) in high risk patients
Give examples of when anticoagulation is used for secondary prevention
Arterial:
- Acute MI, thrombotic/embolic stroke and prevention of recurrence
Venous:
- Treatment of VTE and prevention of recurrence
What are the main hereditary risk factors for venous thromboembolism (VTE)?
Deficiency of anticoagulant
- Antithrombin
- Protein C
- Protein S
Abnormal protein
- Factor V Ledien
- Fibrinogen
Increased procoagulant
- Prothrombin
- Factor VIII
Abnormal metabolism
- Hyperhomocysteinaemia
Putative mechanisms
- Thrombomodulin defects
- Fibrinolytic defects
What should be used in patients with renal failure for venous thromboprophylaxis? (eGFR
Unfractionated Heparin (UFH)
Well’s score for diagnosis of DVT
1 point each for
- Active Cancer
- Paralysis, paresis or recent plaster
- Recently bedridden and/or major surgery
- Localised tenderness along the distribution of the deep vein system
- Entire leg swollen
- Calf swelling 3cm compared to other leg
- Pitting Oedema in the symptomatic leg
- Collateral superficial veins (non-varicose)
-2 points for Alternative diagnosis
More than 2 points = High risk
1-2 points = Moderate risk
Less than 1 point = Low risk
Well’s score for diagnosis of PE
3 points for
- Clinical signs/symptoms of DVT
- Alternative diagnosis deemed less likely than PE
- 5 points each for
- Heart rate higher than 100 bpm
- Immobilisation or surgery in previous 4 weeks
- Previous DVT or PE
1 point each for
- Haemoptysis
- Cancer (or treated in last 6 months)
More than 6 points = High risk
2-6 points = Moderate risk
Less than 2 points = Low risk
Clotting cascade
Look at diagram in lecture
LEARN!!
In relation to Factor Xa and Thrombin inhibition, UFH and LMWH inhibit which better?
LMWH inhibits Factor Xa better than Thrombin
UFH inhibits Thrombin better than Factor Xa
How do Heparins work?
They bind to Lys and Arg on antithrombin and increase it’s activity
Antithrombin inhibits the activity of Thrombin (Factor IIa), Factor Xa, Factor IXa and Factor XIa
What monitoring is needed for UFH?
aPTT and anti-factor Xa assay
What is the aPTT?
Activated Partial Thromboplastin Time (aPTT)
It measures the activity of the intrinsic and common pathways of coagulation.
aPTT normal is around 27-35 seconds
aPTT ratio = APTT/Control
Do no confuse with INR!
What investigations should be carried out before prescribing LMWH?
FBC, INR & APTT
U&Es
LFTs
Heparin-induced thrombocytopenia
Need to monitor platelet count when using UFH or LMWH
Greater than 30% reduction in platelets indicates thrombocytopenia
Mechanism of action of Vitamin K antagonists/Coumarins
Vit K epoxide reductase inhibitors
Inhibits synthesis of clotting factors II, VII, IX, X (2, 7, 9 and 10)
Prevents the gamma-carboxylation of serine proteases which leads to the production of non-carboxylated proteins (known as PIVKAs). This leads to limited thrombin generation.
Also inhibits protein C and protein S which are inhibitors of (Factor Va and Factor IIIa) - they are anticoagulants and therefore warfarin is initially a prothrombotic!
What is Prothrombin Time (PT)
Used to measure time to clot formation
Extrinsic pathway
Used to calculate INR
INR = (patient PT/mean normal PT)^ISI
What monitoring is needed for Warfarin/
PT/INR
Starting warfarin
Check baseline INR, FBC and LFTs
Given alongside a LMWH for at least 5 days and 2 consecutive INR readings in the therapeutic range are needed before stopping the LMWH
Reduce dose in elderly patients and those with impaired liver function
Adjust dose according to interacting medication
Why is the heparin-warfarin overlap necessary?
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
Protein C is an innate anticoagulant that, like the procoagulant factors that warfarin inhibits, requires vitamin K-dependent carboxylation for its activity
Protein S is a vitamin K-dependent anticoagulant protein
Since warfarin initially decreases protein C and protein S levels faster than the coagulation factors, it can paradoxically increase the blood’s tendency to coagulate when treatment is first begun
What is the major risk of INR being too high?
Intracranial bleed and other major bleeding
What are the main reasons for the search for alternatives to VKAs?
Poor TTR (Time in the Therapeutic Range)
Drug interactions common
INR monitoring is not practical
Side effects (hair loss, skin rash)
VKA resistance
Renal Impairment
What is the main problem with a poor TTR for warfarin?
the ability to prevent strokes falls significantly
If the patient has a TTR below 40% then the risk of stroke is actually higher than patients not on warfarin!
Bleed risks of NOACs
Rivaroxaban has a similar bleed risk to warfarin.
Dabigatran and Apixaban both have a lower bleed risk than warfarin.
Practical considerations with Dabigatran
Large capsule (difficult to swallow) Cannot go in a dosette box Cannot go down an NGT or PEG Does have a reversibility agent
Practical considerations with Rivaroxaban
Small tablet
Can go in a dosette box
Can go down an NGT or PEG
Lack of reversibility
Practical considerations with Apixaban
Small tablet
Can go in a dosette box
Can go down an NGT or PEG
Lack of reversibility
Advantages of NOACs
Oral Reproducible pharmacokinetics Rapid onset No INR monitoring required Licensed and NICE approved
Unresolved issues with NOACs
No published comparisons with each other
Limited duration of follow up data
Short half life means missed doses are more significant
Lack of reversibility (except dabigatran)
Which NOAC if high risk of bleeding?
Dabigatran (lower dose aka 110) or Apixaban
- Lowest incidence of bleeding
Which NOAC if previous GI bleeding or high risk of GI bleeding?
Apixaban
- Lowest incidence of GI bleeds
Which NOAC if high risk of ischemic stroke, low bleeding risk?
Dabigatran (150)
- Considered to give best reduction of ischemic stroke
Which NOAC if previous stroke?
Apixaban or Dabigatran (150)
- Greatest reduction of stroke
Which NOAC if CAD, previous MI or high-risk for ACS/MI?
Rivaroxaban
- As it has positive effects in ACS
Which NOAC if renal impairment?
Rivaroxaban or Apixaban
- As they are less dependent on renal function
Which NOAC if GI upset/disorders?
Rivaroxaban or Apixaban
- As no reported GI effects
Which NOAC if want a once daily formulation?
Rivaroxaban
Which choice of anticoagulant would you use if looking at CrCl?
less than 15 = Warfarin
15-30 = Rivaroxaban or apixaban
Which anticoagulant would you choose if the patient’s weight was very low or high?
Warfarin
Which anticoagulant would you choose in children?
Warfarin
Which anticoagulant would you choose if the patient had a prosthetic heart valve?
Warfarin
Which anticoagulant would you choose if the patient had a high GI bleed risk?
Warfarin or Apixaban
Which anticoagulant would you choose if the patient had a previous MI?
Warfarin or Xa inhibitor
What is D-Dimer?
A fibrin breakdown product that is present in the blood after a blood clot is broken down by fibrinolysis
Can be used to help diagnose thrombosis
What are the main contraindications for fibrinolysis in acute MI?
Recent haemorrhage Trauma Surgery Coagulation defects Peptic ulceration Severe hypertension Acute pulmonary disease esp cavitation Acute pancreatitis Severe liver disease Previous allergic reaction
What are the prothrombotic risk factors for an increased risk of venous thrombosis?
Age Obesity Varicose veins Family history of VTE Thrombophilias Thrombotic states
NOAC monitoring
Renal function
Liver function
BP
Prothrombin time
LMWH monitoring
Platelet counts
Potassium (hyperkalaemia)
UFH monitoring
INR
APTT
Platelet count
Potassium (hyperkalaemia)
Warfarin monitoring
Baseline INR
FBCs
LFTs
How do you initiate long-term warfarin or a NOAC after LMWH treatment in hospital for a DVT?
Take LMWH and warfarin overlapping for a minimum of 5 days, then wait until INR in therapeutic range for two days, then stop LMWH
Stop LMWH before initiating NOAC. 5 days of LMWH then 150mg BD of dabigatran.
