L M I Volume 5 No. 6

MI L
Volume 5 No. 6
August 2011
This Medicines Information Leaflet is produced locally to encourage prescribing which is cost effective to the NHS. Information will be given on quality improvement issues and the costs to hospital
and community.
Guidelines on when to use and how to monitor Unfractionated Heparin in adults
H
eparin remains the most widely used
parenteral antithrombotic. The general
adoption of low molecular weight heparin
(LMWH) represents a significant therapeutic
advance in terms of ease and convenience of
administration. There may also be some advantages in terms of efficacy and fewer sideeffects. This leaflet gives guidance on when to
use intravenous unfractionated heparin (UFH)
for treatment of thrombosis (it does not address prophylaxis where LMWH is preferred).
tin Time (APTT) is simpler than using
LMWH and relying on anti-Xa levels
3. Very obese patients (more than 120 kg), in
whom dose adjustment of LMWH therapy
is less predictable.
Mode of action
Baseline tests (before treatment)
Heparin is a glycosaminoglycan, extracted
from porcine mucosa and is available as the
sodium or calcium salt. Its anticoagulant properties depend on the presence of a specific
pentasaccharide sequence which binds with
high affinity to antithrombin and potentiates its
activity. Metabolism is by a saturable mechanism, involving binding to endothelial cells and
clearance by the reticuloendothelial system,
and a non-saturable mechanism involving
mainly renal clearance. There is no evidence
that heparin crosses the placenta.
Measure: APTT; Prothrombin Time (PT);
platelet count and potassium.
When to consider using UFH instead of
LMWH
LMWHs have replaced UFH as the preferred
option in most clinical situations. Use of UFH is
only considered in the following situations:
1. Patients who might require their anticoagulation to be stopped rapidly e.g. patients at very high risk of bleeding and
those who may require urgent invasive
procedures (the half-life of UFH is dosedependant, around 45-60 min unless renal
function is severely impaired).
2. Patients in severe renal failure: titration
against the Activated Partial Thromboplas-
Indications for intravenous UFH
If patient’s condition (see above) warrants the
use of UFH rather than LMWH this must be
clearly documented in the patient’s notes together with the indication for use.
Dose
Note: Unfractionated heparin dosing is unpredictable and a high percentage of patients will
still have APTT results outside the desired
range even with careful monitoring. The risks
of this must be taken into account when deciding to use UFH rather than LMWH.
Loading dose: 5000 units heparin
or 75 units/kg (maximum dose of 10,000 units)
Omission of loading dose delays effective anticoagulation.
Maintenance dose: Initially 1400 units heparin per hr or 18 units/kg per hr (maximum dose
of 2500 units per hr), equivalent to infusion
rate of 1.4mL per hr using infusion solution of
1000 units of heparin per mL.
Cardiology: Reduce initial infusion rate (see
below for criteria) to 1000 units per hr (12
units/kg per hr), equivalent to infusion rate of
1mL per hr using infusion solution of 1000
units of heparin per mL :
Patients receiving aspirin and clopidogrel,
Patients post-alteplase (rt-PA, tissue-type plasminogen activator)
Medicines Advisory Committee. Oxford Radcliffe Hospitals
August 2011
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Medicines Information Leaflet
Patients on heparin during intra aortic balloon pump
support
Patients post abciximab (Reopro®)
Note: Patients with prosthetic heart valves requiring
heparinisation prior to surgery - discuss initial heparin dose with Cardiologist.
Table 1: Adjustment of heparin infusion
rate based on APTT using infusion solution
of 1000 units per mL concentration.
Administration
Loading dose: Give as slow IV bolus over 35mins.
Preparation: Use a standardised ready to
administer heparin preparation of 1000 units
per mL (ie undiluted).
Maintenance dose: Give as continuous IV
infusion. Start intravenous infusion at 1400
units per hr =1.4 mL per hr (or 18 units/kg per
hr). Adjust dose according to APTT (see monitoring section below and Table 1). A lower initial infusion rate is used for some cardiology
patients (see above). The infusion rate must
be accurately controlled using a syringe pump.
Preparation:
Use a standardised ready-to-administer heparin preparation of 1000 units per mL. Standard
volume of infusion is 25mL (ie 25,000 units in
25mL undiluted). See heparin injectables
monograph for complete preparation and administration details.
Once prepared the infusion should only be
used for 24 hours and any remaining infusion
solution discarded. The infusion must be monitored at hourly intervals using infusion monitoring chart.
Monitoring APTT
#
The target APTT is 60 – 100 seconds.
Check APTT 4 hrs after start of infusion, and
adjust infusion rate according to Table 1.
Recheck APTT 6 hrs after any change of dose
(4 hrs if greater than 170 or less than 45) or, if
no change required check within 24 h.
Target APTT and infusion rate changes must
be documented appropriately. In general ward
areas all dose and infusion rate changes
must be hand written on the in-patient drug
chart and signed by a doctor.
Patient Monitoring
Monitor patient for signs of bleeding. Platelet
counts should be measured on alternate days
from days 4-14 of therapy (see below). Potassium should also be monitored regularly, especially if therapy exceeds 7 days.
APTT (s)
Action
greater
than 170
stop for one hr and reduce infusion rate by 300 units/hr (0.3
mL/hr)
126 - 170
reduce infusion rate by 200
units/hr (0.2 mL/hr)
101 - 125
reduce infusion rate by
100 units/hr (0.1 mL/hr)
60 - 100
no change
45 - 59
increase infusion rate by
200 units/hr (0.2 mL/hr)
Less than
45
give a 5000 unit bolus IV and
increase infusion rate by
300 units/hr (0.3 mL/hr)
#
An APTT of 60 – 100 seconds corresponds to
0.35-0.7 anti-Xa units/mL with the current laboratory
reagent. It will need to be reviewed when the APTT
reagent is changed.
***Before changing the rate of infusion,
check that the initial rate was correct ***
Compatible infusions:
Glucose 5%, Sodium Chloride 0.9%
Heparin is incompatible with a number of medicines including many antibacterials. Contact
Medicines Information (Ext 21505) for further
advice.
Heparin and intramuscular injections
Intramuscular injections should be avoided in
patients receiving anticoagulants, except for
adrenaline for severe anaphylaxis.
Contra-indications
severe liver disease
peptic ulcer
severe / uncontrolled hypertension
known haemorrhagic diathesis
thrombocytopenia
recent cerebral haemorrhage.
injuries to or recent operations to the
eyes/ears or central nervous system.
spinal or epidural anaesthesia
infective endocarditis
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Cautions
concomitant medicines that may enhance
anticoagulant effect e.g. aspirin,
clopidogrel, dipyridamole, iloprost, NSAIDs
hepatic impairment
renal impairment
active tuberculosis
Adverse effects
haemorrhage
thrombocytopenia (see below)
hyperkalaemia (see below)
osteoporosis
alopecia on prolonged use
hypersensitivity reactions (including urticaria, angioedema, and anaphylaxis)
Hyperkalaemia
Inhibition of aldosterone secretion by 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 the CSM has recommended that the potassium concentration
should be measured in patients at risk of hyperkalaemia before starting heparin and monitored regularly thereafter, particularly if heparin
is to be continued for longer than 7 days.
Heparin and surgery
In patients with normal renal function intravenous UFH can be stopped 6 hrs before surgery to allow coagulation to return to normal.
Heparin-induced thrombocytopenia(HIT)
Clinically important HIT is immune-mediated
and does not usually develop until 5–10 days
after starting heparin therapy unless the patient has been exposed to heparin before. HIT
can be complicated by thrombosis. All patients
who are to receive heparin should have a
platelet count on the day of starting treatment.
For patients previously exposed to heparin in
the last 100 days, obtain a platelet count 24
hrs after starting heparin. For all other patients
alternate day platelet counts should be performed from days 4 to 14 of therapy. Signs of
HIT include a 50% reduction of platelet count,
thrombosis, or skin allergy. If HIT is strongly
suspected or confirmed, heparin should be
stopped and an alternative anticoagulant
should be given. Contact the on-call haematology registrar for advice.
Overdose/Reversal
In an emergency the anticoagulant effect of
heparin can be inhibited by protamine sulphate. One mg of protamine sulphate inhibits
the effect of 100 units of heparin – usually the
maximum dose is 50 mg given by slow IV injection (rate not exceeding 5mg per minute)
Switching from UFH to LMWH
If patients are to be switched from intravenous
UFH to subcutaneous LMWH, the UFH infusion should be stopped approximately 4 hours
before the first dose of LMWH is due (providing patient’s renal function is normal and last
APTT result is within range i.e. 60-100).
Safe Medication Practice for prescribing Heparin Infusions
Target APTT should be documented
Heparin should always be prescribed with
‘UNITS’ written in full
Always use standard heparin infusion concentration of 1000 units per 1mL
The prescription must state
 Heparin dose in units for bolus dose
 Heparin infusion rate in mL per hour
 Infusion volume
 Route
 Time for next APTT
Infusion rate changes must be prescribed
by doctor.
Infusion must be changed every 24 hrs
References
Baglin, T., Barrowcliffe, T.W., Cohen, A. & Greaves,
M. (2006) Guidelines on the use and monitoring of
heparin. Br J Haematol, 133, 19-34.
Sweetman SC (Ed). Martindale: The Complete
th
Drug Reference. 35 Ed, Pharmaceutical Press;
London 2007.
th
Trissel L.A. Handbook on injectable Drugs. 10 Edition, American Society of Health-System Pharmacists Inc, Bethesda.
Prepared by: David Keeling, Consultant Haematologist; Jo Coleman, Medicines Safety Pharmacist; Scott Harrison, Lead Pharmacist - anticoagulation. With advice from: Colin Forfar,
Consultant Cardiologist.