Factor V Leiden (G1691A) and prothrombin gene G20210A mutations as potential risk factors for venous thromboembolism after total hip or total knee replacement surgery.
Patients (n = 1600) from 12 European countries, scheduled for elective orthopaedic hip or knee surgery, were screened for Factor V Leiden and prothrombin gene G20210A mutations, found in 5.5% and 2.9% of the populations, respectively. All patients underwent prophylactic treatment with one of four doses of melagatran and ximelagatran or dalteparin, starting pre-operatively. Bilateral ascending venography was performed on study day 8-11. The patients were subsequently treated according to local routines and followed for 4-6 weeks postoperatively. The composite endpoint of screened deep vein thrombosis (DVT) and symptomatic pulmonary embolism (PE) during prophylaxis did not differ significantly between patients with or without these mutations. Symptomatic venous thromboembolism (VTE) during prophylaxis and follow-up (1.9%) was significantly over-represented among patients with the prothrombin gene G20210A mutation (p = 0.0002). A tendency towards increased risk of VTE was found with the Factor V Leiden mutation (p = 0.09). PE were few, but significantly over-represented in both the Factor V Leiden and prothrombin gene G20210A mutated patients (p = 0.03 and p = 0.05, respectively). However, since 90% of the patients with these genetic risk factors will not suffer a VTE event, a general pre-operative genotyping is, in our opinion, of questionable value.
Wåhlander
K
K
Department of Clinical Chemistry and Transfusion Medicine, Sahlgrenska University Hospital, Göteborg, Sweden. karin.wahlander@astrazeneca.com
Larson
G
G
Lindahl
T L
TL
Andersson
C
C
Frison
L
L
Gustafsson
D
D
Bylock
A
A
Eriksson
B I
BI
D020016:Activated Protein C Resistance / Q000150:complications* / Q000235:genetics; D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000925:Anticoagulants / Q000627:therapeutic use; D019644:Arthroplasty, Replacement, Hip; D019645:Arthroplasty, Replacement, Knee; D001384:Azetidines / Q000627:therapeutic use; D001596:Benzylamines; D004252:DNA Mutational Analysis; D017985:Dalteparin / Q000627:therapeutic use; D004311:Double-Blind Method; D005060:Europe / Q000453:epidemiology; D005165:Factor V / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005998:Glycine / Q000031:analogs & derivatives* / Q000627:therapeutic use; D006801:Humans; D008297:Male; D008875:Middle Aged; D011183:Postoperative Complications / Q000453:epidemiology* / Q000209:etiology / Q000517:prevention & control; D011401:Promoter Regions, Genetic / Q000235:genetics; D011446:Prospective Studies; D011516:Prothrombin / Q000235:genetics*; D011655:Pulmonary Embolism / Q000453:epidemiology / Q000209:etiology / Q000235:genetics / Q000517:prevention & control; D012307:Risk Factors; D019851:Thrombophilia / Q000150:complications* / Q000235:genetics; D020246:Venous Thrombosis / Q000453:epidemiology* / Q000209:etiology / Q000235:genetics / Q000517:prevention & control
D000925:Anticoagulants; D001384:Azetidines; D001596:Benzylamines; C095381:factor V Leiden; C109573:melagatran; C426686:ximelagatran; D005165:Factor V; D011516:Prothrombin; D017985:Dalteparin; D005998:Glycine