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Haemorrhage
If
haemorrhage occurs it
is usually
sufficient to withdraw unfractionated or low molecular
weight heparin, but if rapid reversal of the effects of the
heparin is required, protamine sulphate (section 2.8.3) is
a specific antidote (but only partially reverses the effects
of low molecular weight heparins).
HEPARIN
Indications
see under Dose
Cautions
see notes above; also elderly; concomitant
use of drugs that increase risk of bleeding;
interac-
tions:
Appendix 1 (heparin)
Heparin-induced thrombocytopenia
Clinically important
heparin-induced thrombocytopenia is immune-mediated and
does not usually develop until after 5–10 days;
it can be
complicated by thrombosis.
Platelet counts should be mea-
sured just before treatment with unfractionated or low
molecular weight heparin, and regular monitoring of platelet
counts is recommended if given for longer than 4 days. Signs
of heparin-induced thrombocytopenia include a 50% reduc-
tion of platelet count, thrombosis, or skin allergy. If heparin-
induced thrombocytopenia is strongly suspected or con-
firmed, the heparin should be stopped and an alternative
anticoagulant, such as lepirudin or danaparoid, should be
given. Ensure platelet counts return to normal range in those
who require warfarin
Hyperkalaemia
Inhibition
of
aldosterone
secretion
by
unfractionated or low molecular weight heparin can result
in hyperkalaemia;
patients with diabetes mellitus, chronic
renal failure,
acidosis,
raised plasma potassium or those
taking potassium-sparing drugs seem to be more susceptible.
The risk appears to increase with duration of therapy,
and
plasma-potassium concentration should be measured in
patients at risk of hyperkalaemia before starting the heparin
and monitored regularly thereafter, particularly if treatment
is to be continued for longer than 7 days
Contra-indications
haemophilia and other haemor-
rhagic disorders, thrombocytopenia (including history
of heparin-induced thrombocytopenia),
recent cere-
bral haemorrhage,
severe hypertension;
peptic ulcer;
after major trauma or recent surgery to eye or ner-
vous system;
acute bacterial endocarditis;
spinal or
epidural anaesthesia with treatment doses of unfrac-
tionated or low molecular weight heparin;
hyper-
sensitivity to unfractionated or low molecular weight
heparin
Hepatic impairment
risk of bleeding increased—
reduce dose or avoid in severe impairment (including
oesophageal varices)
Renal impairment
risk of bleeding increased in severe
impairment—dose may need to be reduced
Pregnancy
does not cross the placenta;
maternal
osteoporosis reported after prolonged use;
multidose
vials may contain benzyl alcohol—some manufac-
turers advise avoid; see also notes above
Breast-feeding
not excreted into milk due to high
molecular weight
Side-effects
haemorrhage (see notes above),
throm-
bocytopenia (see Cautions),
rarely
rebound hyper-
lipidaemia following unfractionated heparin with-
drawal, priapism,
hyperkalaemia (see Cautions),
osteoporosis (risk lower with low molecular weight
heparins),
alopecia on prolonged use, injection-site
reactions,
skin necrosis,
and hypersensitivity reac-
tions (including urticaria, angioedema,
and anaphy-
laxis)
Dose
. Treatment of deep-vein thrombosis,
pulmonary
embolism,
unstable angina,
and acute peripheral
arterial occlusion,
by intravenous injection,
loading
dose of 5000 units
or
75 units/kg (10 000 units in
severe pulmonary embolism), followed by continuous
intravenous infusion of 18 units/kg/hour
or
treat-
ment of deep-vein thrombosis,
by subcutaneous
injection
of 15 000 units every 12 hours (laboratory
monitoring essential—preferably on a daily basis, and
dose adjusted accordingly);
CHILD
under 18 years
see
BNF for Children
. Prophylaxis in surgery (see also notes above),
by
subcutaneous injection,
5000 units 2 hours before
surgery,
then every 8–12 hours (monitoring not
needed);
during pregnancy (with monitoring), 5000–
10 000 units every 12 hours (important: prevention of
prosthetic heart-valve thrombosis in pregnancy calls
for specialist management)
. Haemodialysis by intravenous injection initially
1000–5000 units, followed by continuous intravenous
infusion of 250–1000 units/hour
. Myocardial infarction,
see section 2.10.1
. Prevention of clotting in extracorporeal circuits,
consult product literature
Doses
above
reflect
the
guidelines
of
the
British
Society for Haematology;
for doses of
the low mole-
cular weight heparins,
see below
Heparin Sodium
(Non-proprietary) A
Injection
, heparin sodium 1000 units/mL, net price 1-
mL amp = 99p, 5-mL amp = £2.50, 5-mL vial = £2.50,
10-mL amp = £4.31, 20-mL amp = £7.09; 5000 units/
mL, 1-mL amp = £1.94, 5-mL amp = £5.06, 5-mL vial
= £5.64; 25 000 units/mL, 0.2-mL amp = £2.49, 1-mL
amp = £5.13,
5-mL vial = £11.11
Excipients
may include benzyl alcohol (avoid in neonates,
see Excipi-
ents, p.
2)
Heparin Calcium
(Non-proprietary) A
Injection
, heparin calcium 25 000 units/mL, net price
0.2-mL amp = £2.61
Low molecular weight heparins
Low
molecular
weight
heparins
(bemiparin,
dalteparin,
enoxaparin,
and tinzaparin)
are usually
preferred over unfractionated heparin in the
prevention
of venous thromboembolism because they are as effec-
tive and they have a lower
risk of
heparin-induced
thrombocytopenia;
see Prophylaxis of
Venous Throm-
boembolism, p.
140. The standard prophylactic regimen
does not require monitoring.
The duration of action of
low molecular weight
heparins is longer
than that
of
unfractionated heparin and
once-daily subcutaneous
administration is possible for some indications,
making
them convenient to use.
Low molecular
weight
heparins are also used in the
treatment
of
deep-vein thrombosis,
pulmonary embo-
lism (see also Treatment, above), myocardial infarction
(section 2.10.1),
unstable coronary artery disease (sec-
tion 2.10.1) and for the prevention of clotting in extra-
corporeal circuits.
Dalteparin is also licensed for the extended treatment
and prophylaxis of venous thromboembolism in patients
with solid tumours;
treatment
is recommended for
a
duration of 6 months.
Routine monitoring of
anti-Factor
Xa activity is
not
usually required during treatment
with low molecular
weight
heparins,
but
may be necessary in patients at
BNF 61
2.8.1 Parenteral anticoagulants
141
2
Cardiovascular system