Warfarin toxicity

Presented by: Dr.Somaia Janah

 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.

Warfarin

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).

*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.

Monitoring

*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 24- 36 hours .

Monitoring of INRINR 3.5

INR2-3

*Recurrent DVT*Recurrent pulmonary

embolism.(3* )Mechanical MV

*DVT*Pulmonary embolism

*Atrial fibrillation *DCM

*Mural thrombus *before & after

Cardioversion.*mechanical AV (3)

*Post MI (2.5) *Antiphospholipid syndrome

Warfarin toxicity

is common and usually results from dose changes or drug

interactions.

Presentations of warfarin toxicity

Major bleeding e.g. : * : 1) hemorrhage

*GI hemorrhage*intracranial bleeding

*retroperitoneal bleeding

*Minor bleeding e.g. : * mucous membranes * subconjunctival hemorrhage * hematuria *epistaxis, and ecchymoses

Follow))Presentations of warfarin toxicity

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 .

Follow))Presentations of warfarin toxicity

: 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.

Follow))Presentations of warfarin toxicity

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.

Follow))Presentations of warfarin toxicity

:5)Drug interactionsHere some medications affect INR:

INR Depression INR Elevationrifampicin amiodarone

secobarbital ciprofloxacin

carbamazepine Metronidazole , fluconazole

phenytoin Clarithromycin . erythromycin

Phenobarbital fluvastatin , lovastatin

primidone fluvoxamine

Cigarette smoking isoniazide

phenylbutazone

Natural Products That Can Alter the Anticoagulant Effect of Warfarin

Decreased Anticoagulant Effect

Increased Anticoagulant Effect 

Alfalfa Asafetida , Clove Oil

Ginseng Garlic ,Ginger

Ginseng ,Anise

INR reversal protocol

Overdose of warfarin

INR <5No

significant bleeding

INR 5-9 No

significant bleeding

*Hold the dose of warfarin

*Resume warfarin at lower dose when INR therapeutic

INR >9With 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 INRD/C warfarin.

**FFP

15ml/kg +/- use of profilnine SD 25-50

U/kg r FVIIa

40µg/kg

Thank you