Impact of CYP2C9 and VKORC1 genetic polymorphisms upon warfarin dose requirements in Egyptian patients with acute coronary syndrome.

Warfarin is the most widely prescribed anticoagulant drugs. Cytochrome P450-2C9 (CYP2C9) and vitamin K epoxide reductase-oxidaxe complex subunit 1 (VKORC1) contribute significantly to the variability of warfarin dose requirements among patients. We investigated the impact of CYP2C9 and VKORC1 polymorphisms on the variability of warfarin dosage requirements in Egyptian patients with acute coronary syndrome and their association with other nongenetic factors. Eighty participants with acute coronary syndrome were enrolled in this cross-sectional study. Associations between CYP2C9 and VKORC1 gene variants together with daily warfarin dose, demographic data, clinical status of patients and time to target international normalized ratio were assessed. Mean warfarin dose among patients with wild-type CYP2C91/1 genotype was significantly higher than heterozygous CYP2C91/2 and CYP2C91/3 variants (P ≤ 0.001). Patients with wild VKORC1 (G/G) genotype were treated with significantly higher daily warfarin dosages than homozygous (A/A) and heterozygous (G/A) genotypes. Patients carrying VKORC1 (G/G) genotype in combination with the CYP2C91/1 type alleles had the highest daily warfarin dosage, whereas the lowest daily warfarin dosage to achieve the required clinical effect was found among patients having CYP2C91/2 and CYP2C91/3 genotypes combined with VKORC1 (A/A) genotype (P ≤ 0.001). Regression analysis revealed that age, height, CYP2C9 and VKORC1 genotypes were significantly associated with warfarin dose. Genetic polymorphisms in VKORC1, CYP2C9 along with age and height are determinants of warfarin dose requirements in Egyptian population acute coronary syndrome. Higher warfarin loading dose is required for both wild CYP2C9 and VKORC1 gene variants which may contribute to warfarin-resistant cases.

Comprehensive study on laboratory biomarkers for prediction and diagnosis of deep venous thrombosis.

Deep venous thrombosis (DVT) is based upon clinical suspicion in patients at risk and confirmatory duplex imaging of the deep venous system of the affected extremity. The aim of the present study was to determine different cutoff points of D-dimer, P-selectin and microparticles that could be used in early diagnosis and prediction of impending DVT in symptomatic patients with normal duplex ultrasound. Three groups of individuals were examined: 50 healthy volunteers (Group I); 75 patients with positive duplex ultrasound for DVT (Group II) and 75 symptomatic patients, but with negative duplex ultrasound for DVT (Group III). D-dimer was measured by immunoturbidimetric assay, P-selectin by flow cytometry and microparticles by ELISA. D-dimer, P-selectin and microparticles levels were significantly higher in Group II and III patients when compared with Group I individuals. Using receiver-operating characteristic curves, we determined that cutoff levels of 0.92 mg/l for D-dimer, 17.8% for P-selectin and 16.5 nmol/l for microparticles can accurately rule out DVT. New cutoff levels were estimated for the three studied biomarkers that differentiated the group of DVT-negative duplex patients without thrombosis from those patients of the same group who developed thrombosis being 2.81 mg/l for D-dimer, 30.2% for P-selectin and 26 nmol/l for microparticles. D-dimer, P-selectin and microparticles can be used to diagnose and detect impending DVT, thus identifying patients at high risk that could benefit from early anticoagulant therapy without the need for imaging studies.