The frequency of anticardiolipin antibodies and genetic mutations associated with hypercoagulability among patients with Wegener's granulomatosis with and without history of a thrombotic event.
OBJECTIVE
Venous thrombotic events (VTE), including both deep venous thrombosis and pulmonary emboli, are now recognized as an important complication of Wegener's granulomatosis (WG), but the mechanism(s) of this occurrence is unclear. The frequency of anticardiolipin antibodies (aCL), anti-beta2-glycoprotein antibodies (anti-beta2-GP), and several genetic hypercoagulable factors were examined in a large cohort of patients with WG.


METHODS
One hundred eighty patients with active WG had serum and DNA samples collected upon entry into a clinical trial. Of the 180 patients, 29 patients had VTE -- 13 before trial entry, 16 during trial. aCL (IgG, IgM, and IgA) and anti-beta2-GP (IgG and IgM) were evaluated in 176 patients. Factor V Leiden (FVL), the prothrombin gene mutation (G20210A, PGM), and methylenetetrahydrofolate reductase (MTHFR) gene mutation were tested in the 29 patients with thrombotic events, and 36 patients without.


RESULTS
aCL occurred with increased frequencies in patients with WG when compared to the general population (1%-5%): 12% had aCL and 3% had anti-beta2-GP. There was no difference in the prevalences of aCL or anti-beta2-GP based on clotting status. The prevalence of the genetic hypercoagulable factors examined in patients with WG was comparable to the reported rates in the general population.


CONCLUSIONS
Although the incidence of clinically significant VTE is increased in patients with WG, this increased risk is not explained by increased prevalences of aCL, anti-beta2-GP, FVL, or mutations in PGM or MTHFR. These observations suggest a need to search for new genetic or acquired prothrombotic abnormalities to account for the increased thrombotic event rate in patients with active WG.
Sebastian
Jodi K
JK
Boston University School of Medicine, Boston, Massachusetts 02118, USA.
Voetsch
Barbara
B
Stone
John H
JH
Romay-Penabad
Zurina
Z
Lo
Grace H
GH
Allen
Nancy B
NB
Davis
John C
JC
Hoffman
Gary S
GS
McCune
W Joseph
WJ
St Clair
E William
EW
Specks
Ulrich
U
Spiera
Robert
R
Loscalzo
Joseph
J
Pierangeli
Silvia
S
Merkel
Peter A
PA
D017153:Antibodies, Anticardiolipin / Q000097:blood*; D005260:Female; D020022:Genetic Predisposition to Disease; D014890:Granulomatosis with Polyangiitis / Q000097:blood* / Q000150:complications / Q000235:genetics*; D006801:Humans; D008297:Male; D009154:Mutation; D011655:Pulmonary Embolism / Q000097:blood* / Q000235:genetics; D012307:Risk Factors; D019851:Thrombophilia / Q000097:blood / Q000235:genetics*; D020246:Venous Thrombosis / Q000097:blood* / Q000235:genetics
D017153:Antibodies, Anticardiolipin