– 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%.
– 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
– 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;