The risk for thromboembolic disease in lupus anticoagulant patients due to pathways involving P-selectin and CD154

Summary

Individuals with lupus anticoagulants (LA) are at risk for thromboembolism(TE). Chronic inflammation is an important characteristicin LA patients which may dispose for TE. Platelets play akey role in inflammation and TE. We therefore investigated genepolymorphisms as well as plasma levels of platelet receptors aspredictors of TE in 107 LA patients. We compared 74 patientswith a history of thromboembolic disease (TE+),56 with venousthrombosis (VT), 12 with arterial thrombosis (AT), and six patientswho had both, with 33 LA patients without previousthrombosis (TE-).The P-selectin Pro715 allele was slightly morefrequent inVT (OR=3.167,95 % CI 0.955–10.503;p=0.0594),butno patient with AT had this allele (OR=0.099, 95 % CI0.001–0.790; 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, werehigher in patients withVT (p=0.0096) than inTE-,but not withAT(p=0.4713).These high P-selectin levels were not explained bythe P-selectin polymorphism. The CA repeat polymorphism inthe 3’-noncoding region of CD154 was significantly associatedwith the development of AT (OR=4.035, 95 % CI 1.329–12.249;p=0.0138). Plasma levels of CD154 were not significantly differentamong the subgroups. Thus, theThr715Pro polymorphism ofP-selectin and CA repeats of CD154 are differentiating betweenthe risk for VT and AT. Further, soluble P-selectin is elevated inLA patients with previousVT, but its role to predictVT needs to be evaluated in prospective studies.

Keywords

Lupus anticoagulant - thromboembolism - P-selectin - CD154

^* These authors contributed equally to this manuscript.

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