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  • Lichy, Christoph  (2)
  • 2005-2009  (2)
  • 1
    In: Cerebrovascular Diseases, S. Karger AG, Vol. 28, No. 5 ( 2009), p. 468-471
    Abstract: 〈 i 〉 Background: 〈 /i 〉 For many conditions causing transient ischemic attack or minor stroke, secondary prevention with early initiation of oral anticoagulation is indicated. The individual response to coumarins is known to vary widely and is not well predicted by clinical variables. Patients’ discharge from hospital care is often delayed only because the therapeutic target range has not been reached yet. A feasible tool to guide coumarin dosing and thereby safely shortening time in hospital is required. 〈 i 〉 Methods: 〈 /i 〉 We established a polymerase chain reaction technique for rapid genotyping of the vitamin K epoxide reductase complex (VKORC1), which is the pharmaceutical target of the coumarins. C283 + 837C – 〉 T (rs2359612) genotypes were determined in 49 patients who underwent de novo oral anticoagulation with phenprocoumon for cerebrovascular disease. Other variables potentially affecting phenprocoumon sensitivity were systematically evaluated. 〈 i 〉 Results: 〈 /i 〉 Of 49 genotyped patients, 47 were treated in hospital until an international normalized ratio (INR) of 2–3 was reached. The time and the cumulative dose of phenprocoumon necessary to achieve the target INR both were strongly dependent on the individual C283 + 837C – 〉 T genotype (Kruskal-Wallis test p = 0.0002, and p 〈 0.0001, respectively). Carriers of the TT genotype reached an INR of 2–3 after a mean time of 3.2 days (n = 5), CT carriers after 4.4 days (n = 27), and CC carriers after 6.5 days (n = 15). No other variable, including body weight, was significantly correlated with the treatment response. 〈 i 〉 Conclusion: 〈 /i 〉 In patients with cerebrovascular disease, genotyping for VKORC1 alone can strongly predict the individual response to de novo phenprocoumon treatment. The size of the pharmacogenetic test’s potential effect on a more efficient use of hospital capacities remains to be shown by a controlled interventional study.
    Type of Medium: Online Resource
    ISSN: 1015-9770 , 1421-9786
    Language: English
    Publisher: S. Karger AG
    Publication Date: 2009
    detail.hit.zdb_id: 1482069-9
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  • 2
    In: Stroke, Ovid Technologies (Wolters Kluwer Health), Vol. 40, No. 11 ( 2009-11), p. 3547-3551
    Abstract: Background and Purpose— Thrombolysis in patients using oral anticoagulants (OAC) and in patients for whom information on OAC status is not available is frequently delayed because the standard coagulation analysis procedure in central laboratories (CL) is time-consuming. By using point-of-care (POC) coagumeters, international normalized ratio (INR) values can be measured immediately at the bedside. The accuracy and effectiveness of POC devices for emergency management in acute ischemic stroke has not been tested. Methods— In phase 1, the reliability of emergency INR POC measurements in comparison to CL was determined. In phase 2, patients with ischemic stroke admitted within the time frame for systemic thrombolysis and who were either using OAC or for whom information on OAC status was not available were enrolled. Patients received thrombolysis if POC INR was ≤1.5. Precision and time gain was recorded for INR as measured by POC vs CL. Results— In phase 1 (n=113), Bland-Altman analysis showed close agreement between POC and CL, and Pearson correlation was highly significant ( r =0.98; P 〈 0.01). In phase 2, 48 patients were included, of whom 70.8% were using OAC; 23 patients received thrombolysis. After subtracting the time needed for the diagnostic work-up, the net time gain was 28±12 minutes (mean±SD). Conclusions— Measuring INR by POC in an emergency setting is sufficiently precise in OAC acute stroke patients and substantially reduces the time interval until INR values are available and therefore may hasten the initiation of thrombolysis.
    Type of Medium: Online Resource
    ISSN: 0039-2499 , 1524-4628
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    Language: English
    Publisher: Ovid Technologies (Wolters Kluwer Health)
    Publication Date: 2009
    detail.hit.zdb_id: 1467823-8
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