The risk for thromboembolic disease in lupus anticoagulant patients due to pathways involving P-selectin and CD154.
Individuals with lupus anticoagulants (LA) are at risk for thromboembolism (TE). Chronic inflammation is an important characteristic in LA patients which may dispose for TE. Platelets play a key role in inflammation and TE. We therefore investigated gene polymorphisms as well as plasma levels of platelet receptors as predictors of TE in 107 LA patients. We compared 74 patients with a history of thromboembolic disease (TE+), 56 with venous thrombosis (VT), 12 with arterial thrombosis (AT), and six patients who had both, with 33 LA patients without previous thrombosis (TE-). The P-selectin Pro715 allele was slightly more frequent in VT (OR = 3.167,95% CI 0.955-10.503; p = 0.0594), but no patient with AT had this allele (OR = 0.099, 95 % CI 0.001-0.790; p = 0.0238) which therefore may protect from AT. Plasma levels of P-selectin, collected a median of 35 months (range 2-329 months) after the last thrombotic event, were higher in patients withVT (p = 0.0096) than in TE-, but not with AT (p = 0.4713). These high P-selectin levels were not explained by the P-selectin polymorphism. The CA repeat polymorphism in the 3'-noncoding region of CD154 was significantly associated with the development of AT (OR = 4.035,95 % CI 1.329-12.249; p = 0.0138). Plasma levels of CD154 were not significantly different among the subgroups. Thus, the Thr715Pro polymorphism of P-selectin and CA repeats of CD154 are differentiating between the risk for VT and AT. Further, soluble P-selectin is elevated in LA patients with previous VT, but its role to predict VT needs to be evaluated in prospective studies.
Bugert
Peter
P
Institute of Transfusion Medicine and Immunology, German Red Cross Blood Service of Baden-Württemberg, Hessen, University of Heidelberg, Faculty of Clinical Medicine, Mannheim, Germany.
Pabinger
Ingrid
I
Stamer
Kathrin
K
Vormittag
Rainer
R
Skeate
Robert C
RC
Wahi
Monika M
MM
Panzer
Simon
S
D000328:Adult; D023201:CD40 Ligand / Q000097:blood / Q000235:genetics*; D015331:Cohort Studies; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D016015:Logistic Models; D016682:Lupus Coagulation Inhibitor / Q000097:blood*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D008875:Middle Aged; D016017:Odds Ratio; D019007:P-Selectin / Q000097:blood / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D011237:Predictive Value of Tests; D011392:Proline; D018570:Risk Assessment; D012307:Risk Factors; D013912:Threonine; D013923:Thromboembolism / Q000175:diagnosis / Q000209:etiology* / Q000235:genetics / Q000276:immunology; D013927:Thrombosis / Q000209:etiology; D020246:Venous Thrombosis / Q000209:etiology
D016682:Lupus Coagulation Inhibitor; D008562:Membrane Glycoproteins; D019007:P-Selectin; C084882:P-selectin ligand protein; D023201:CD40 Ligand; D013912:Threonine; D011392:Proline