Article
Intracranial bleeding during oral anticoagulation with vitamin K-antagonists – A clinical study on the importance of vitamin K 2,3-epoxide reductase complex, subunit 1 (VKORC1) mutations in the period from 2007 to 2011
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Authors
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N. Steib
- Klinik für Neurochirurgie, Vivantes Klinikum im Friedrichshain, Berlin
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R. Klamroth
- Klinik für Innere Medizin, Vivantes Klinikum im Friedrichshain, Berlin
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J. Oldenburg
- Institut für Experimentelle Hämatologie und Transfusiosmedizin, Universitätsklinikum Bonn
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D. Moskopp
- Klinik für Neurochirurgie, Vivantes Klinikum im Friedrichshain, Berlin
| Published: | June 4, 2012 |
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Outline
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Objective: Patients receiving oral anticoagulation with phenprocoumon have an increased risk for intracranial haemorrhage. An increased sensitivity to phenprocoumon may lead to a higher bleeding risk. The occurrence of genetic variants in the promoter region of the VKORC1 can reduce the activity of VKORC1. The variants can distinguish between patients with a minimized coumarin dose (coumarin sensitivity = VKORC1 *2/*2), increased coumarin dose (coumarin resistance = VKORC1 *1/*1) or with an average coumarin dose (VKORC1 *1/*2). The aim of this study was to evaluate whether the VKORC1 haplotype coumarinsensitive *2/*2 occurs more frequently in patients with intracranial hemorrhage.
Methods: All patients in the period from 2007 to 2011 with an intracranial hemorrhage receiving oral anticoagulation with phenprocoumon admitted to hospital in the participating study centers were included. Data were recorded on the site of intracranial bleeding, INR at admission and co-morbidities. All patients received a venous blood sample for genotyping VKORC1 and CYP2C9.
Results: 104 patients were included. 52 patients had an intracerebral haemorrhage, 46 patients a subdural haematoma, 5 patients had a subarachnoid haemorrhage and 1 patient an epidural haematoma. 49 patients had a previous trauma before admission and 29 patients had an INR above the therapeutic range. 56 patients (54%) had the VKORC1 genotype *1/*2, which is associated with an average phenprocoumon dose. 31 patients (30%) had the VKORC1 genotype *1/*1, which is associated with an increased phenprocoumon dose. 15 patients (14%) were the VKORC1 genotype *2/*2, which is associated with an average decrease by 50 % phenprocoumon dose. The distribution of genotypes corresponds to the distribution in the general population.
Conclusions: In contrast to the results of Schwarz et al NEJM 2008; 358: 999, the VKORC1 *2/*2 -genotype (phenotype: coumarin sensitivity) in patients with intracranial bleeding during oral anticoagulation was not found more frequently in comparison to the normal population. But 7 out of 15 patients with coumarin sensitivity had an INR above the therapeutic range at admission (> 3).
