5 Anticoagulants
Anticoagulants are substances used to prevent blood clotting.
The student should be aware of:
factors predisposing to thromboembolism
local protocols for management of thromboembolism
the antagonist for such treatment and its availability
conditions requiring treatment with anticoagulants
maternal and fetal sequelae of such treatment
Heparin antagonist: protamine sulphate
Warfarin antagonist: vitamin K and plasma
BP
Heparin (as sodium or calcium salt)
Proprietary
Heparin Sodium (Wockhardt UK Ltd)
Group
Anticoagulant, parenteral
Uses/indications
Treatment of DVT, pulmonary embolism, thromboembolism – susceptible clients, prophylaxis in LSCS or high risk due to impaired mobility
Type of drug
POM
Presentation
Preloaded syringes, vials or ampoules
Dosage
IV: 5000 units loading dose and then continuous infusion of 15–25 units/kg/hr adjusted by laboratory monitoring (severe PE: loading dose 10 000 units)
S.C.: after LSCS 5000 units b.d. until ambulant during pregnancy: 5–10 000 units b.d. – monitoring required
DVT: 15 000 units b.d.
S.C.: after LSCS 5000 units b.d. until ambulant during pregnancy: 5–10 000 units b.d. – monitoring required
DVT: 15 000 units b.d.
Route of admin
S.C., IV
Contraindications
Haemorrhagic disorders, including heparin-induced thrombocytopenia, cerebral aneurysm, cerebral vascular accident/cerebral haemorrhage, severe hypertension, peptic ulcer, haemophilia, liver disease, major trauma, hypersensitivity, threatened abortion
Side effects
Haemorrhage, including placental sites, thrombocytopenia hypersensitivity, bruising and haematoma formation. Prolonged use is associated with osteoporosis
Interactions
Nil specific
Anticoagulants – concomitant use enhances effects: use caution when transferring to oral anticoagulants
Antihistamines – decreases the anticoagulant effect
Aspirin – antiplatelet effect enhanced by heparin
Diclofenac – increased risk of haemorrhage (with IV diclofenac)
GTN – the excretion of heparin is increased by the GTN decreasing the anticoagulant effect
NSAIDs IV – possible increased risk of bleeding
Anticoagulants – concomitant use enhances effects: use caution when transferring to oral anticoagulants
Antihistamines – decreases the anticoagulant effect
Aspirin – antiplatelet effect enhanced by heparin
Diclofenac – increased risk of haemorrhage (with IV diclofenac)
GTN – the excretion of heparin is increased by the GTN decreasing the anticoagulant effect
NSAIDs IV – possible increased risk of bleeding
Pharmacodynamic properties
A naturally occurring anticoagulant that is synthesized and excreted by mast cells in the body. It acts by forming a complex with antithrombin, catalysing the inhibition of several activated blood coagulation factors and thrombin. This prevents the conversion of fibrinogen to fibrin, which is crucial for clot formation. The onset of action is immediate; and it is most commonly used for the prevention and treatment of venous and arterial thromboembolism
Fetal risk
Available data suggest there is no risk to fetus or neonate
Breastfeeding
Not excreted in breast milk
NB: discontinue use prior to peridural anaesthesia, i.e. 8–12 h; can cause spinal haematoma or permanent paralysis
OVERDOSE
Indicated by haemorrhage; APTT and platelet count should be determined. Minor haemorrhage rarely requires specific treatment; and decreasing or delaying subsequent doses of heparin should be sufficient. Major haemorrhage: the anticoagulant effect is reduced immediately by 1% protamine sulphate, but caution is required as protamine also has an anticoagulant effect. A single dose should never exceed 50 mg
IV injection of protamine can cause a sudden fall in blood pressure, bradycardia, dyspnoea and transitory flushing, but this can be avoided or decreased by slow and careful administration
NB: discontinue use prior to peridural anaesthesia, i.e. 8–12 h; can cause spinal haematoma or permanent paralysis
OVERDOSE
Indicated by haemorrhage; APTT and platelet count should be determined. Minor haemorrhage rarely requires specific treatment; and decreasing or delaying subsequent doses of heparin should be sufficient. Major haemorrhage: the anticoagulant effect is reduced immediately by 1% protamine sulphate, but caution is required as protamine also has an anticoagulant effect. A single dose should never exceed 50 mg
IV injection of protamine can cause a sudden fall in blood pressure, bradycardia, dyspnoea and transitory flushing, but this can be avoided or decreased by slow and careful administration
BP
Warfarin sodium
Proprietary
Marevan® (Goldshield Group Ltd),
Warfarin sodium (non-proprietary, see BNF for details)
Warfarin sodium (non-proprietary, see BNF for details)
Group
Anticoagulant – oral
Uses/indications
Prophylaxis after prosthetic heart valve surgery, DVT, pulmonary embolism, and transient ischaemic attacks
Type of drug
POM
Presentation
Tablets, white 0.5 mg, brown 1 mg, blue 3 mg, pink 5 mg
Dosage
Refer to pharmacist or BNF; usually 3–10 mg daily
Route of admin
Oral
Contraindications
Pregnancy, but may be used between 16 and 36 weeks’ gestation if heparin not available and risks of thrombosis outweigh the risk to the fetus; peptic ulcer, severe hypertension, bacterial endocarditis, haemorrhage; use within 24 h of surgery or labour – caution if needed
Side effects
Haemorrhage, nausea, transient alopecia, hypersensitivity, fall in haematocrit, purple toes, liver dysfunction, pancreatitis
Interactions
Alcohol – enhanced effects with large alcohol doses
Antacids – cimetidine inhibits the metabolism and enhances the effect of warfarin
Aspirin – increased risk of haemorrhage – antiplatelet effect
Antibiotics – cephalosporins, macrolides, erythromycin and metronidazole, sulphonamides, trimethoprim – possible enhanced coagulant effect
Penicillins – possible alteration of INR
Antidepressants – SSRIs – anticoagulant effect increased
Dextropropoxyphene – anticoagulant effect enhanced
Paracetamol – theoretical increased risk of bleeds with prolonged use
Cholestyramine – enhanced anticoagulant effect
Barbiturates – metabolism of warfarin increased, therefore diminishes the anticoagulant effect
Antiepileptics – carbamazepine and phenobarbital – diminishes the anticoagulant effect
Phenytoin – both enhances and diminishes warfarin’s effect
Sodium valproate – enhanced anticoagulant effect
Oral contraceptive – diminished contraceptive effect
NSAIDs – enhanced anticoagulant effect
Mefenamic acid – enhances anticoagulant effect
Progestogen – antagonism of anticoagulant effect
Antacids – cimetidine inhibits the metabolism and enhances the effect of warfarin
Aspirin – increased risk of haemorrhage – antiplatelet effect
Antibiotics – cephalosporins, macrolides, erythromycin and metronidazole, sulphonamides, trimethoprim – possible enhanced coagulant effect
Penicillins – possible alteration of INR
Antidepressants – SSRIs – anticoagulant effect increased
Dextropropoxyphene – anticoagulant effect enhanced
Paracetamol – theoretical increased risk of bleeds with prolonged use
Cholestyramine – enhanced anticoagulant effect
Barbiturates – metabolism of warfarin increased, therefore diminishes the anticoagulant effect
Antiepileptics – carbamazepine and phenobarbital – diminishes the anticoagulant effect
Phenytoin – both enhances and diminishes warfarin’s effect
Sodium valproate – enhanced anticoagulant effect
Oral contraceptive – diminished contraceptive effect
NSAIDs – enhanced anticoagulant effect
Mefenamic acid – enhances anticoagulant effect
Progestogen – antagonism of anticoagulant effect
Pharmacodynamic properties
Synthetic anticoagulant of the coumarin series. It acts by inhibiting the formation of active clotting factors II, VII, IX and X. An effective prothrombin time (PT) can be achieved in 24–36 h post initial dose, max 36–48 h, and this therapeutic PT is maintained for 48 h after stopping drug
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