C H A P T E R 4 8
Drugs affecting blood coagulation
763
cephalosporins. Decreased anticoagulation can occur if
heparin is combined with glyceryl trinitrate.
Warfarin has documented drug–drug interactions
with a vast number of other drugs (Table 48.3). It is a
wise practice never to add or take away a drug from
the regimen of the person receiving warfarin without
careful monitoring and adjustment of the warfarin
dose to prevent serious adverse effects. Because of the
many factors that can affect the therapeutic levels of
warfarin, it is often very difficult to reach a stable level
and maintain that level.
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TABLE 48.2 Review of clotting studies
Test
Measure
Therapeutic range
Uses
Activated partial thromboplastin
time (aPTT)
Partial thromboplastin time (PTT)
Activity of intrinsic
pathway of coagulation
1.5–2.5 times baseline Dose adjustment for heparin,
low-molecular-weight heparins,
bivalirudin
International Normalised Ratio
(INR)
Standardised measure of
prothrombin levels
2–3.5
Warfarin dose adjustment,
fondaparinux dose adjustment
Prothrombin time (PT)
Time required for clotting
to occur; extrinsic
pathway activity
1.3–1.5
Warfarin dose adjustment
Safe medication administration
Injectable vitamin K is used to reverse the effects of warfarin.
Vitamin K promotes the liver synthesis of several clotting
factors. When these pathways have been inhibited by
warfarin, clotting time is increased. If an increased level of
vitamin K is provided, more of these factors are produced,
and the clotting time can be brought back within a normal
range. Because of the way in which vitamin K exerts its
effects on clotting, there is a delay of at least 24 hours from
the time the drug is given until some change can be seen.
This occurs because there is no direct effect on the warfarin,
but rather an increased stimulation of the liver, which must
then produce the clotting factors. The usual dose for the
treatment of anticoagulant-induced prothrombin deficiency
is 2.5 to 10 mg intramuscularly (IM) or SC or, rarely, 25 mg
IM or SC. Oral doses can be used if injection is not feasible.
A prothrombin time (PT) response within 6 to 8 hours after
parenteral doses or 12 to 48 hours after oral doses will
determine the need for a repeat dose. If a response is not
seen and the person is bleeding excessively, fresh-frozen
plasma or an infusion of whole blood may be needed.
Prototype summary: Heparin
Indications:
Prevention and treatment of venous
thrombosis and pulmonary emboli; treatment of
atrial fibrillation with embolisation; diagnosis and
treatment of DIC; prevention of clotting in blood
samples and heparin locksets.
Actions:
Inhibits thrombus and clot production
by blocking the conversion of prothrombin to
thrombin and fibrinogen to fibrin.
Pharmacokinetics:
Route Onset
Peak
Duration
IV Immediate Minutes
2–6 hours
SC 20–60 mins 2–4 hours
8–12 hours
T
1/2
:
30 to 180 minutes; metabolised in the cells and
excreted in urine.
Adverse effects:
Loss of hair, bruising, chills, fever,
osteoporosis, suppression of renal function (with
long-term use).
Safe medication administration
In cases of a heparin overdose, the antidote is protamine
sulfate (generic). This basic protein drug forms stable salts
with heparin as soon as the two drugs come in contact,
immediately reversing heparin’s anticoagulant effects.
Paradoxically, if protamine is given to a person who has not
received heparin, it has anticoagulant effects. The dose is
determined by the amount of heparin that was given and the
time that elapsed since then. A dose of 1 mg IV protamine
neutralises 90 USP of heparin derived from lung tissue or
110 USP of heparin derived from intestinal mucosa. The drug
must be administered very slowly—not to exceed 50 mg
IV in any 10-minute period. Care must be taken to calculate
the amount of heparin that has been given to the person.
Potentially fatal anaphylactic reactions have been reported
with the use of protamine sulfate and so life support
equipment should be readily available when it is used.
Care considerations for
people receiving anticoagulants
Assessment: History and examination
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Assess for any known allergies to these drugs. Also
screen for conditions
that could be exacerbated
by increased bleeding tendencies
, including
haemorrhagic disorders, recent trauma, spinal
puncture, GI ulcers, recent surgery, intrauterine
device placement, tuberculosis, presence of
