VKORC1 -1639G>A and CYP2C9*3 are the major genetic predictors of phenprocoumon dose requirement.

PURPOSE: Phenprocoumon, similar to other coumarin-derived anticoagulants, is associated with a large variation in the individual dose requirement to achieve stable anticoagulation. Polymorphisms in the vitamin K epoxide reductase complex subunit 1 (VKORC1) and the liver enzyme cytochrome P450 2C9 (CYP2C9) effectively account for the variability in warfarin and acenocoumarol response but are less well-defined pharmacogenetic predictors in phenprocoumon therapy. METHODS: A retrospective study was performed on 185 outpatients attending anticoagulation clinics in Austria and Germany. These patients were genotyped for the VKORC1 -1639G>A and 3730G>A polymorphisms as well as for the CYP2C9 *2 and *3 polymorphisms using a reverse hybridisation-based teststrip assay. RESULTS: The VKORC1 -1639A allele, which was present at a frequency of 41.4% in the study cohort, significantly reduced the mean weekly phenprocoumon dose by 3 mg (19%) in the heterozygous and by 6.7 mg (43%) in the homozygous state compared to wild-type carriers (15.5 +/- 6.8 mg, p < 0.0001). A stepwise multiple regression analysis revealed that VKORC1 -1639G>A, age and CYP2C9*3 were the major independent determinants of phenprocoumon dose, accounting for 14.2, 9.1 and 4.7% of its variability, respectively (p A genotype had no additional predictive power for individual dose variability. CONCLUSION: Similar to warfarin and acenocoumarol, the VKORC1 -1639G>A polymorphism had the highest impact on the maintenance dose of phenprocoumon. The factor age was the second most important predictor and explained a greater percentage of the variability than CYP2C9 genotype.

Comparison of Two Different Blood Sample Tubes for Platelet Function Analysis with the Multiplate® System.

BACKGROUND: For whole blood aggregation on the Multiplate® system, the use of thrombin inhibitor as anticoagulant is recommended. So far sample tubes containing liquid lepirudin were provided (Dynabyte, Munich, Germany). They are not sterile and have to be stored refrigerated. For better handling now also sterile tubes with dried hirudin, storable at room temperature, are also provided (Dynabyte). The aim of this study was to compare the performance of these both sample tubes on the Multiplate system. PATIENTS AND METHODS: Blood was collected from 30 patients, treated with aspirin and/or clopidogrel, in tubes, and ASPItest, ADPtest and TRAPtest were performed. RESULTS: The correlation between both sample tubes was excellent with ASPItest (r(2) = 0.96), good with ADPtest (r(2) = 0.91) and also satisfying with TRAPtest (r(2) = 0.85). CONCLUSION: Both sample tubes are well qualified for platelet function analysis with the Multiplate system. The new sterile sample tube with dried hirudin may be preferred for better handling.