Warfarin toxicity
Presented by:
Dr.Somaia Janah
Warfarin
is an anticoagulant normally used in the prevention
of thrombosis , thromboembolism and the formation of
blood clots in the blood vessels and their migration
elsewhere in the body. It was referred to as a "blood
thinner", this is a misnomer, since it does not affect
the viscosity of blood.
Mechanism of action
Warfarin inhibits the vitamin K-dependent
synthesis of biologically active forms of
the calcium dependent clotting factors II , VII, IX
and X, as well as the regulatory factors protein
C, protein S.
Indications of wafarin
• Deep-vein thrombosis.
• Pulmonary embolism
• Atrial fibrillation which is risk
of embolisation.
• Mechanical prosthetic heart
valves (to prevent emboli
developing on the valves).
Monitoring
*It is essential that the INR be determined daily or on alternate
days in early days of treatment, then at longer intervals
(depending on response) then up to every 12 weeks.
*Baseline INR is recommended prior to initiating warfarin
therapy to assess sensitivity.
*An INR within the last 48 hours is acceptable as a current
baseline INR.
*With initial dosing, the INR will usually increase within 2436 hours.
Monitoring of INR
INR
2-3
*DVT
*Pulmonary embolism
*Atrial fibrillation
*DCM
*Mural thrombus
*before & after
Cardioversion.
*mechanical AV (3)
*Post MI (2.5)
*Antiphospholipid syndrome
INR
3.5
*Recurrent DVT
*Recurrent pulmonary
embolism.
*Mechanical MV )3(
Warfarin toxicity
is common and usually results from dose changes or drug
interactions.
Presentations of warfarin toxicity
1) hemorrhage: *Major bleeding e.g. :
*GI hemorrhage
*intracranial bleeding
*retroperitoneal bleeding
*Minor bleeding e.g. :
* mucous membranes
* subconjunctival hemorrhage
* hematuria
*epistaxis, and ecchymoses
Presentations of warfarin toxicity)Follow)
2) Skin necrosis: usually observed between the third and eighth
days of therapy, is a relatively uncommon.
It may require treatment through debridement or amputation of
the affected tissue .
It occurs more frequently in women and in patients with
preexisting protein C deficiency.
Presentations of warfarin toxicity)Follow)
3)Osteoporosis:
The mechanism was thought to be a combination of reduced
intake of vitamin K, which is necessary for bone health, and
inhibition by warfarin of vitamin K-mediated carboxylation of
certain bone proteins, rendering them nonfunctional.
Presentations of warfarin toxicity)Follow)
4)Purple toe syndrome:
It is another rare complication that may occur early during
warfarin treatment (usually within 3 to 8 weeks of
commencement). This condition is thought to result from
small deposits of cholesterol breaking loose and flowing
into the blood vessels in the skin of the feet, which
causes a bluish purple color and may be painful.
It is typically thought to affect the big toe, but it affects
other parts of the feet as well, including the bottom of
the foot (plantar surface). The occurrence of purple toe
syndrome may require discontinuation of warfarin.
Presentations of warfarin toxicity)Follow)
5)Drug interactions:
Here some medications affect INR:
INR Elevation
INR Depression
amiodarone
rifampicin
ciprofloxacin
secobarbital
Metronidazole , fluconazole
carbamazepine
Clarithromycin . erythromycin
phenytoin
fluvastatin , lovastatin
Phenobarbital
fluvoxamine
primidone
isoniazide
Cigarette smoking
phenylbutazone
Natural Products That Can Alter the
Anticoagulant Effect of Warfarin
Increased Anticoagulant
Effect
Decreased Anticoagulant
Effect
Asafetida , Clove Oil
Alfalfa
Garlic ,Ginger
Ginseng
Ginseng ,Anise
INR reversal protocol
Overdose of warfarin
INR <5
No significant
bleeding
Adjust the dose
of warfarin.
INR 5-9
No significant
bleeding
*Hold the dose
of warfarin
*Resume
warfarin at lower
dose when INR
therapeutic
INR >9
With or without
bleeding
*D/C warfarin
*FFP 15ml/kg +/- use
of profilnine SD 25-50
U/kg r FVIIa 40µg/kg
*resume warfarin at
lower dose when INR
therapeutic
Serious bleeding
at any INR
*D/C warfarin .
*FFP 15ml/kg +/use of profilnine SD
25-50 U/kg r FVIIa
40µg/kg
Thank you