Anticoagulation
Heparin
LMW = low molecular weight. UF = unfractionated.
Features:
Parental administration (not oral). A glycosaminoglycan (naturally
occurring).
Unfractionated means a mixture of chain lengths whereas LMW
has a uniform smaller chain length.
Mechanism:
↑Activity
of plasma antithrombin. Inhibits active clotting factors esp IIa and
Xa. LMW has more anti-Xa activity than UF.
Comparison of Unfractionated vs. Fractionated
|
|
Unfractionated
|
Low Molecular Weight
|
|
Route
|
IV
|
Subcutaneous
|
|
Bioavailability
|
Poor, unpredictable
|
Good, predictable
|
|
Monitoring
|
aPTT ratio
|
Not needed
|
|
Metabolism
|
Complex
|
Simple
|
|
Half-life
|
1-2h
|
4-6h
|
|
Indications
|
Rapid onset/offset: surgery
|
Initially for DVT/PE, ACS, warfarin unsuitable
|
Adverse Reactions
Interactions:
-
↑Risk bleeding: Aspirin, NSAIDs, Clopidogrel
-
↑Risk hyperkalaemia: ACEIs
Cautions:
Renal failure, coagulopathy (eg liver disease)
Side Effects:
(UF > LMW)
-
Bleeding: contraindicated in risky individuals
-
Heparin induced thrombocytopenia
-
Skin reactions
-
Hyperkalaemia
-
Osteoporosis
Monitoring
UF:
Inhibition of IIa (common) causes ↑aPTT and ↑PT. But aPTT best.
Expressed as: aPTT ratio = Patient's aPTT/normal aPTT
LMW:
At
therapeutic levels neither aPTT or PT will be prolonged, so measure
with anti-Xa assay (very rarely needed).
Administration of UF
Therapeutic
range: 1.5-2.5 (but ↑ needed in arterial thrombosis). Giving:
-
IV bolus 5000 IU
-
IV infusion 15,000 IU over 12 h
-
Check aPTT ratio: 4 h after started and after every dose
change, daily if
infusion rate stable. Check patients platelet count 4 days after start
(heparin-induced-thrombocytopenia)
Administration of LMW
Empirical Prophylaxis eg. clexane. Can monitor with assay, but most
don't need.
Over coagulation treatment
:
-
Mild/mod: stop heparin
-
Life threatening: Stop heparin. Give protamine antidote
Warfarin
The only oral anticoagulant. 100% bio-availability, metabolized by
liver. But variation in pharmacokinetics/pharmacodynamics, ↓therapeutic
window, and half life only 36 hours: means close monitoring required.
Mechanism:
Inhibits recycling of vit K (needed for factors 2, 7, 9, 10).
Doses:
Typically 1-10 mg po once daily
Indications
Long term antithrombotic:
-
DVT/PE
-
Prevention of thrombosis with: AF, prosthetic valves,
peripheral
vascular disease, cerebrovascular disease, IHD
Interactions
(Assume all drugs will!)
Causes overcoagulation
with:
amiodarone, PPI, statin, fluconzole
Causes undercoagulation
with:
barbiturates, carbamezepine,
cholestyramine
Causes ↑bleeding with:
Antiplatelet agents
Adverse Reactions
-
Bleeding
-
Rarely: thrombosis if protein C/S deficient (paradoxically!
these are
also vit k dependent), fetal warfarin syndrome
Cautions
Previous coagulopathy including liver disease, renal failure
Monitoring
Depletes factors in common pathway therefore PT and aPPT affected. But
PT used to monitor.
INR
=
Patient's PT/normal PT
Target INR usually 2-3 (3-4 in: prosthetic hrt valve, or DVT/PE during
anticoagulation)
Loading
-
Loading dose 5-10 mg po day 1
-
Measure INR next day
-
Subsequent doses determined from dosing schedule (a chart
which tells
you what to do)
-
Measure INR until stable
-
For treatment of venous/arterial thrombosis do not
discontinue heparin until
> 48 h after reaching therapeutic INR
Treatment of overcoagulation
Causes serious morbidity and mortality. Reasons: poor
patient understanding,
drift in dose-response.
-
Life threatening: stop warfarin, 5mg vit K (slow IV),
beriplex
(synthetic vit K) (alternative is FFP)
-
Mild/asx: stop warfarin and restart when INR < 5
-
INR 3-8 and no bleed: stop warfarin for 1-2 d
-
Bleeding at their INR: investigate underlying cause
Surgery and warfarin
Principles: therapeutic INR may cause surgical bleeding, risk depends
on INR and procedure, short term cessation of warfarin is not risky
-
Routine INR check 1 w before (to make sure INR is
therapeutic)
-
Omit warfarin 2-3 d before
-
Check INR evening before
-
Consider 1 mg vit k if INR still > 2-5 (?)
-
Most procedures ok w INR < 2
-
Restart warfarin 2-3 d after surgery
Surgery and thrombotic
risky patient:
Give UF heparin, and admit 3d before.
Consider rescheduling surgery
