The Need for Anticoagulation

Question 1

What is the evidence to suggest we need anticoagulation in VTE?

Answer 1

Barritt et al, 1960:
the FIRST trial for VTE anticoagulation
-RCT of 2 groups:
1. Heparin or VKA
2. No anticoagulation
*Only 35 patients in the trial
The trial was stopped early when 5 patients in the non-coagulated group died from P.E and 5 had recurrences, everyone was moved to the treatment group
This trial quickly showed that anticoagulation was favourable
*BUT it must be noted that there is NO evidence for anticoagulation use in VTE from PLACEBO-CONTROLLED trials so it CANNOT be Level A evidence

Question 2

What anticoagulants do leeds trust use?

Answer 2

Enoxaparin, Fondaparinux, Heparin, Tinzaparin, Warfarin

Question 3

What is a vitamin K antagonist?

Answer 3

Vitamin K is needed to produce FII, FVII, FIX, Protein C and Protein S so VKAs stop their production and reduce clotting.
Upon initiation of treatment with VKAs, LMWH is needed for 5 days to bridge protein S and C deficiency because there are natural anticoagulant factors that are affected first so blood clotting can actually increase
e.g Warfarin

Question 4

What are heparins?

Answer 4

Thrombin and factor X inhibitors
UFH is less useful than LMWH because it is less dose responsive and cannot be reversed. However LMWH cannot be used in renal failure.

Question 5

Evidence for LMWH versus UFH:

Answer 5

Van Dongen, 2004:
9000 patients
LMWH shown to have lower mortality and fewer complications than UFH

Question 6

What are the guidelines for Heparin use?

Answer 6

Patients receive LMWH/UFH whilst awaiting scan results if high clinical probability.
Confirmed VTE receives LMWH/UFH 5 days then switch to Warfarin for 3 months.
Cancer patients receive LMWH for 6 months then must assess pros and cons of treatment continuation.
Pregnant women receive LMWH throughout the pregnancy.

Question 7

What is the evidence for the length of anticoagualtion (i.e minimum of three months):

Answer 7

Sudlow et al, 1992:
400 patients
-RCT 2 groups:
1. 4 weeks anticoagulation
2. 3 months anticoagulation
Failure of VTE resolution was higher in the 4 week group and it also had a higher number of recurrences
So it was established that 3 months was an adequate length of anticoagulation in patients WITHOUT a non-modifiable risk factor such as cancer
*Cancer patients, pregnancy etc were not trialled

Question 8

What are the options for short term management of VTE?

Answer 8

• Compression Stockings (SOX trial with placebo stockings showed these made no difference to risk of post-thrombotic syndrome so are mainly used for VTE prevention rather than treatment)
• Anticoagulation
• Thrombolysis
• IVC filter (for patients in whom anticoagulation is contraindicated e.g GI/cranial haemorrhage)

Question 9

How are cancer patients with VTE treated?

Answer 9

Cancer patients receive 6 months of LMWH/UFH anticoagulation, and at 6 months the treatment is reviewed.
In patients with a seemingly unprovoked DVT and unknown to have cancer, tests to detect cancer must be performed e.g Physical examination, CXR, Abdominal/pelvic CT, mammogram for females, bloods: FBC, LFT, Calcium

Question 10

What is thrombolytic therapy?

Answer 10

Inserting a catheter to inject thrombolytic drugs directly or injecting them systemically (the latter is usually performed in haemodynamically unstable patients in an emergency)
-Can use streptokinase, alterplase, tPA

Question 11

When is thrombolytic therapy used?

Answer 11

Can be used in the haemodynamically unstable but also in symptomatic ileofemoral DVTs IF:

• symptoms are of duration <14 days
• patient has good functional status
• life expectancy >1 year (very expensive)
• only if there is a low risk of bleeding

Question 12

What is the evidence for thrombolysis for DVT?

Answer 12

CaVent Trial, 2012:
-200 patients with mid-thigh level DVT
-an RCT with 2 groups:
1. Catheter directed thrombolysis
2. Standard anticoagulation
More patients in the thrombolysis group had ileofemoral patency at 6 months
Fewer patients in the thrombolysis group developed post-thrombotic syndrome
*So thrombolysis appears a more effective treatment but there is an increased risk of bleeding complications

Question 13

What is a provoked DVT?

Answer 13

Caused by factors that are transient e.g:

• Surgery
• trauma
• significant immobility
• pregnancy
• COCP/HRT

Question 14

What is an unprovoked DVT?

Answer 14

A DVT that occurs with no antecedent major clinical risk factor and no active cancer or history of VTE.
These patients MUST be checked for underlying cancer

Question 15

Active Cancer and VTE:

Answer 15

Active cancer increases the risk of VTE 5-fold

Cancer patients constitue 15-20% of all VTEs

Question 16

Why does VKA treatment need to be monitored?

Answer 16

• VKAs are metabolised by Cytochrome P450 enzymes which are very polymorphic so people have BIG variations in dose response
• Response is also altered with diet, medications and dose
• An International Normalised Ratio is used to check warfarin response
• 1 is normal blood clotting, warfarin aims to be within 2 and 3 (bleeding risk doubles with every increase in ratio)