page166
.
Prophylaxis of
venous thromboembolism in medi-
cal
patients,
by
subcutaneous
injection,
2.5 mg
once daily;
CHILD
under 17 years not recommended
.
Treatment
of
superficial-vein thrombosis,
by sub-
cutaneous injection,
ADULT
body-weight over 50 kg,
2.5 mg once daily for at least 30 days (max. 45 days
if high risk of thromboembolic complications); treat-
ment
should be stopped 24 hours before surgery
and restarted at least 6 hours post operatively;
CHILD
under 17 years not recommended
.
Unstable
angina
and non-ST-segment
elevation
myocardial
infarction,
by subcutaneous injection,
2.5 mg once daily for up to 8 days (or until hospital
discharge if
sooner);
treatment should be stopped
24 hours before coronary artery bypass graft sur-
gery (where possible) and restarted 48 hours post
operatively;
CHILD
under 17 years not recommended
.
ST-segment
elevation myocardial
infarction,
initi-
ally
by intravenous injection or infusion, 2.5 mg for
first
day,
thereafter
by
subcutaneous
injection
2.5 mg once daily for up to 8 days (or until hospital
discharge if
sooner);
treatment should be stopped
24 hours before coronary artery bypass graft sur-
gery (where possible) and restarted 48 hours post
operatively;
CHILD
under 17 years not recommended
.
Treatment
of
deep-vein thrombosis and of
pulm-
onary embolism,
by subcutaneous injection,
ADULT
body-weight
under
50 kg,
5 mg every 24 hours;
body-weight
50–100 kg,
7.5 mg every 24 hours;
body-weight
over
100 kg,
10 mg every 24 hours;
continue until adequate oral anticoagulation estab-
lished;
CHILD
under 17 years not recommended
Arixtra
c
(GSK) T A
Injection
,
fondaparinux sodium 5 mg/mL,
net price
0.3-mL (1.5-mg) prefilled syringe = £6.28; 0.5-mL (2.5-
mg) prefilled syringe = £6.28
Injection
,
fondaparinux sodium 12.5 mg/mL,
net
price 0.4-mL (5-mg) prefilled syringe = £11.66, 0.6-mL
(7.5-mg) prefilled syringe = £11.66,
0.8-mL (10-mg)
prefilled syringe = £11.66
2.8.2
Oral anticoagulants
Coumarins and phenindione
The oral anticoagulants warfarin, acenocoumarol and
phenindione,
antagonise the effects of
vitamin K,
and
take at least 48 to 72 hours for the anticoagulant effect
to develop fully;
warfarin is the drug of
choice.
If
an
immediate effect
is
required,
unfractionated or
low
molecular weight heparin must be given concomitantly.
Uses
Indications for these oral anticoagulants include
deep-vein
thrombosis
,
pulmonary
embolism
,
atrial
fibrillation
in those who are at
risk of
embolisation
(see
also section 2.3.1),
and
mechanical
prosthetic
heart
valves
(to prevent
emboli
developing on the
valves).
These oral anticoagulants should not be used in cerebral
artery thrombosis or peripheral artery occlusion as first-
line therapy; aspirin is more appropriate for reduction of
risk in transient ischaemic attacks (see p.
151).
Unfrac-
tionated or
a low molecular
weight
heparin (section
2.8.1) is usually preferred for the prophylaxis of venous
thromboembolism in patients undergoing surgery; alter-
natively,
warfarin can be continued in selected patients
currently taking long-term warfarin and who are at high
risk of thromboembolism (seek expert advice).
Dose
The base-line prothrombin time should be deter-
mined but the initial dose should not be delayed whilst
awaiting the result.
For patients who require rapid anticoagulation the usual
adult induction dose of warfarin is 5–10 mg
1
on the first
day;
subsequent
doses depend upon the prothrombin
time,
reported as INR (international
normalised ratio).
For patients who do not require rapid anticoagulation, a
lower loading dose can be used over 3–4 weeks.
The
daily maintenance dose of
warfarin is usually 3–9 mg
(taken at
the same time each day).
The following
indications and target INRs
2
take into account recom-
mendations of the British Society for Haematology
3
:
.
INR 2.5 for treatment of deep-vein thrombosis and
pulmonary embolism (including those associated
with antiphospholipid syndrome or for recurrence
in patients no longer receiving warfarin),
for atrial
fibrillation, cardioversion (higher target values, such
as an INR of 3, can be used for up to 4 weeks before
the procedure to avoid cancellations due to low
INR;
anticoagulation should continue for at least 4
weeks following the procedure), dilated cardiomyo-
pathy,
mural
thrombus,
symptomatic
inherited
thrombophilia,
coronary artery thrombosis (if anti-
coagulated),
and paroxysmal
nocturnal
haemoglo-
binuria;
.
INR 3.5 for
recurrent
deep-vein thrombosis and
pulmonary embolism (in patients currently receiv-
ing warfarin with INR above 2);
.
For mechanical prosthetic heart valves, the recom-
mended target INR depends on the type and loca-
tion of
the valve.
Generally,
a target
INR of
3 is
recommended for mechanical aortic valves, and 3.5
for mechanical mitral valves.
Monitoring
It is essential that the INR be determined
daily or on alternate days in early days of
treatment,
then
at longer intervals (depending on response
4
)
then
up to every 12 weeks.
Haemorrhage
The main adverse effect
of
all
oral
anticoagulants is haemorrhage.
Checking the INR and
omitting doses
when appropriate is
essential;
if
the
anticoagulant
is
stopped but
not
reversed,
the INR
should be measured 2–3 days later to ensure that it is
falling.
The following recommendations are based on
the result
of
the INR and whether
there is major
or
1.
First
dose reduced if
base-line prothrombin time pro-
longed,
if
liver-function tests abnormal,
or
if
patient
in
cardiac failure,
on parenteral
feeding,
less than average
body weight,
elderly,
or
receiving other drugs known to
potentiate oral
anticoagulants.
2.
An INR which is within 0.5 units of
the target
value is
generally satisfactory;
larger
deviations
require dosage
adjustment.
Target
values (rather
than ranges)
are now
recommended.
3.
Guidelines
on
Oral
Anticoagulation
(warfarin):
third
edition—2005 update.
Br J Haematol
2005; 132: 277–285.
4.
Change in patient’s clinical
condition,
particularly asso-
ciated with liver
disease,
intercurrent
illness,
or
drug
administration, necessitates more frequent testing. See also
interactions, Appendix 1 (warfarin). Major changes in diet
(especially involving salads and vegetables) and in alcohol
consumption may also affect warfarin control.
146
2.8.2 Oral anticoagulants
BNF 61
2
Cardiovascular system