Vitamin K antagonist

 

– The VKA act through competitive inhibition of hepatic synthesis of certain clotting factors vitamin K-dependent: prothrombin (II); proconvertin (VII); factor IX; Factor X (X).

– Protein C and Protein S (coagulation inhibitors) are also vitaminic-K-dependent.

– Two families derivatives indandione (fluindione or Previscan) and coumarin (acenocoumarol or Sintrom®; warfarin or Coumadin®).

– Fixing to plasma proteins (albumin) at 90%.

Coagulation

Coagulation

– Biological Monitoring: prothrombin time (PT), which must be between 25 and 35%; INR (TP TP patient of witness)

– Therapeutic areas: INR between 2 and 3 (prevention of arterial embolism in case of ACFA; DVT; pulmonary embolism); INR between 3 and 4.5 -> mechanical heart valve prostheses.

– The thrombotest Owen explores all the vitamin K-dependent factors.

– In case of overdose of Vitamin K antagonist -> PPSB; vitamin K is used in cases of minor accidents.

– Heparin can not be stopped when the INR is within the therapeutic areas

– Potentialisateures VKA:

* Antibiotics (decreased synthesis of vitamin K by intestinal flora); paraffin oil (decreased intestinal absorption of vitamin K)

* Clofibrate sulfonamides and NSAIDs -> move the Vitamin K antagonist bound to albumin (increased free fraction).

* Azole antifungals (fluconazole …) -> inhibit hepatic metabolism of warfarin

* Other: amiodarone; allopurinol (Zyloric) fluoroquinolones; Statins

Warfarin chemical formula Técarfarine

Chemical formula Warfarin / Técarfarine

– By cons enzyme inducers decrease the activity of the VKA (rifampicin, phenobarbital, carbamates, griseofulvin); Other: antacids, laxatives; Questran® (cholestyramine); phenytoin;Carbamazepine (Tegretol)

– Treatment with VKA is preventive; the main indication is the prevention of thromboembolism (venous thrombosis and pulmonary embolism).

– Other information: mitral stenosis; AF (Atrial fibrillation); certain valvular prosthesis;acquired deficiency of antithrombin III, protein C

– Contraindications: any bleeding lesion (active ulcer, digestive and kidney tumors, angioma, intracerebral aneurysm); Hemorrhagic recent stroke; pericarditis; pregnant and lactating women;

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