Hemorrhagic events, safety and genetic factors among orally anticoagulated patients – Preliminary results

Aims: Over 60 000 patients receive per os anticoagulant treatment in Hungary. Attributable to the narrow therapeutic range and frequent hemorrhagic adverse events the use of coumarins represent elevated risk for gastrointestinal bleeding.

Methods: Among patients arriving for prothrombin laboratory control were questionnaires fulfilled regarding clinical data and side effects of per os anticoagulant treatment. As polymorphisms in CYP2C9 and VKORC1 genes play an important role in coumarin pharmacogenetics, genetic testing was also performed.

Results: A total of 59 adult patients (39 male, 20 female) were examined in the study. From that 54 subjects are of Caucasian origin and 5 subjects enrolled themselves to the Roma ethnic population. Their average age was 67 (SD±12) years. Indications for per os anticoagulant treatment were the followings: 22 atrial fibrillation, 21 pulmonary embolism, 16 deep vein thrombosis, 6 stroke, 8 mechanical heart valve, 5 dilatative cardiomyopathy. 55 patients took acenocoumarol and 4 patients warfarin for 6 years in average. Acenocoumarol dose was 11mg daily in average. Hemorrhagic events appeared by 42 patients, including 3 major gastrointestinal bleeding. Average INR was: 3,00 (SD±1,2). For the CYP2C9*2 SNP 3 patients were homozygous mutant, and 12 patients were heterozygous carriers. Regarding the CYP2C9*3 polymorphism all patients were normal. 12 patients disposed of VKORC1 *2*2 haplotype with decreased need for coumarines. VKORC1 *3*3 haplotype represented in 10, and *4*4 haplotype in 3 patients.

Conclusions: Per os anticoagulation lead to elevated risk for hemorrhagic events despite regular prothrombin control, mainly by the initiation of the therapy. Genetic factors are proposed to take into consideration while determinating anticoagulant dose, and genetic testing can be used routinely to obtain efficient drug therapy and to lower the risk of therapeutic failure.