page167
minor bleeding; the recommendations apply to patients
taking warfarin:
.
Major
bleeding—stop warfarin;
give phytomena-
dione (vitamin K
1
)
5–10 mg by slow intravenous
injection;
give dried prothrombin complex (factors
II,
VII,
IX,
and X—section 2.11) 30–50 units/kg (if
dried prothrombin complex unavailable,
fresh fro-
zen plasma 15 mL/kg can be given but
is
less
effective)
.
INR > 8.0,
no bleeding or
minor
bleeding—stop
warfarin and give phytomenadione (vitamin K
1
)
2.5–5 mg by mouth using the intravenous prepara-
tion orally [unlicensed use],
or
0.5–1 mg by slow
intravenous injection (if complete reversal required
5–10 mg by slow intravenous injection); repeat dose
of
phytomenadione if
INR still
too high after
24
hours;
restart warfarin when INR <5.0
.
INR 5.0–8.0,
no bleeding—stop warfarin;
minor
bleeding—stop warfarin and give phytomenadione
(vitamin K
1
)
1–2.5 mg by mouth using the intra-
venous preparation orally [unlicensed use];
restart
warfarin when INR <5.0
.
Unexpected bleeding at therapeutic levels—always
investigate
possibility
of
underlying
cause
e.g.
unsuspected renal
or gastro-intestinal
tract pathol-
ogy
Hepatic impairment
Warfarin,
acenocoumarol,
and
phenindione should be avoided in severe impairment,
especially if prothrombin time is already prolonged.
Renal
impairment
Warfarin,
acenocoumarol,
and
phenindione should be used with caution in mild to
moderate impairment
and avoided in severe impair-
ment.
Pregnancy
Warfarin,
acenocoumarol,
and phenindi-
one are teratogenic and should not be given in the first
trimester
of
pregnancy.
Women of
child-bearing age
should be warned of
this danger since stopping these
drugs before the sixth week of
gestation may largely
avoid the risk of
fetal
abnormality.
These oral
anticoa-
gulants cross the placenta with risk of
congenital
mal-
formations,
and placental,
fetal,
or neonatal
haemorr-
hage, especially during the last few weeks of pregnancy
and at delivery. Therefore, if at all possible, they should
be avoided in pregnancy, especially in the first and third
trimesters.
Difficult
decisions may have to be made,
particularly in women with prosthetic heart valves, atrial
fibrillation,
or
with
a
history
of
recurrent
venous
thrombosis or pulmonary embolism.
Breast-feeding
With warfarin,
acenocoumarol,
and
phenindione there is a risk of
haemorrhage which is
increased by vitamin-K deficiency.
Warfarin is not pre-
sent in milk in significant amounts, and appears safe, but
phenindione should be avoided;
the manufacturer
of
acenocoumarol
recommends
prophylactic vitamin K
for the infant (consult product literature).
Treatment booklets
Anticoagulant treatment book-
lets should be issued to patients,
and are available for
distribution
to
local
healthcare
professionals
from
Health Authorities and from:
3M Security Printing and Systems Limited
Gorse Street
Chadderton
Oldham,
OL9 9QH
Tel:
0845 610 1112
nhsforms@spsl.uk.com
These booklets
include advice for
patients
on anti-
coagulant treatment,
an alert card to be carried by the
patient at all
times,
and a section for recording of INR
results and dosage information.
Electronic copies and
further advice are also available at
www.npsa.nhs.uk/
nrls/alerts-and-directives/alerts/anticoagulant.
WARFARIN SODIUM
Indications
prophylaxis of embolisation in rheumatic
heart disease and atrial fibrillation;
prophylaxis after
insertion of prosthetic heart valve; prophylaxis and
treatment of venous thrombosis and pulmonary
embolism;
transient ischaemic attacks
Cautions
see notes above; also recent surgery; recent
ischaemic stroke; history of gastro-intestinal bleeding;
peptic ulcer;
concomitant use of drugs that increase
risk of bleeding; bacterial endocarditis (increased risk
of bleeding; use only if warfarin otherwise indicated);
avoid cranberry juice;
interactions: Appendix 1
(coumarins)
Contra-indications
haemorrhagic stroke;
significant
bleeding;
avoid use within 48 hours postpartum
Hepatic impairment
see notes above
Renal impairment
see notes above
Pregnancy
see notes above
Breast-feeding
see notes above
Side-effects
haemorrhage—see notes above;
also
nausea,
vomiting,
diarrhoea,
jaundice,
hepatic dys-
function,
pancreatitis,
pyrexia,
alopecia,
purpura,
rash,
‘purple toes’,
skin necrosis (increased risk in
patients with protein C or protein S deficiency)
Dose
. See notes above
Warfarin
(Non-proprietary) A
Tablets
, warfarin sodium 500 micrograms (white), net
price 28-tab pack = £1.49; 1 mg (brown), 28-tab pack
= 93p; 3 mg (blue), 28-tab pack = 95p; 5 mg (pink), 28-
tab pack = £1.03.
Label:
10, anticoagulant card
Brands include
Marevan
c
Oral suspension
,
warfarin sodium 5 mg/5 mL,
net
price 150 mL = £90.00.
Label:
10,
anticoagulant card
ACENOCOUMAROL
(Nicoumalone)
Indications
see under Warfarin Sodium
Cautions
see under Warfarin Sodium
Contra-indications
see under Warfarin Sodium
Hepatic impairment
see notes above
Renal impairment
see notes above
Pregnancy
see notes above
Breast-feeding
see notes above
Side-effects
see under Warfarin Sodium
Dose
. 4 mg on first day, 4–8 mg on second day; maintenance
dose usually 1–8 mg daily adjusted according to
response
Sinthrome
c
(Alliance) A
Tablets
, acenocoumarol 1 mg, net price 100-tab pack
= £4.27.
Label:
10,
anticoagulant card
BNF 61
2.8.2 Oral anticoagulants
147
2
Cardiovascular system