Endothelial Injury Is Common in Antiphospholipid-Positive Patients but Risk of Thrombosis Depends on Platelet Activation.

Abstract

Background: The association between antiphospholipids antibodies (APLA) and thrombosis is controversial. Positive APLA are frequently noted in patients without thrombosis. Many mechanisms have been proposed to explain how APLA might induce thrombosis. A leading hypothesis is that platelet activation is central to thrombosis in APLA positive patients, but endothelial injury is also widely proposed. We aimed to evaluate these two theories by measuring endothelial microparticles (EMP) and platelet microparticles (PMP), which are sensitive markers of endothelial and platelet activation respectively, in patients with positive APLA, with and without thrombosis to determine whether these biomarkers correlate with thombotic risk in this population.Study Subjects and Methods: We studied 80 patients referred to our clinic having positive APLA. Positive IgM or IgG against cardiolipin or β2 glycoprotein I were confirmed at least twice by ELISA. Sixty of them had a history of obstetric complications or thrombosis, including TIA, stroke, myocardial infarction, deep venous thrombosis or pulmonary embolism. The remaining 20 patients had positive APLA without history of thrombosis. We excluded all patients who had a thrombotic event within 90 days prior to obtaining the sample to avoid the possible effect of acute thrombus formation on EMP and PMP. We measured EMP, PMP, and P-selectin expression by flow cytometry. PMP were defined as CD31+/CD42+ particles and EMP were defined as CD62E+ particles <1.5 μm in diameter. We compared EMP and PMP in these two patient groups to determine which markers correlate well with thrombotic events. Due to the non-normal distribution of PMP levels, values were log-transformed before comparison between the 2 groups and are expressed as geometric means.Results: Levels of EMP were significantly higher in patients with thrombosis (681 counts/μL) compared to normal controls (195 counts/μL; p<0.0001). EMP were also higher in patients with positive APLA and no thrombosis (488 counts/μL) than normal controls (p=0.003). EMP were not significantly different between APLA positive patients with vs. without thrombosis (p=0.86). In contrast, levels of PMP were significantly higher in patients with thrombosis (3305 counts/μL) than without thrombosis (1170 counts/μL; p =0.03) or healthy controls (620 counts/μL; p=0.01). No significant differences in PMP were found between patients without thrombosis and normal controls (p=NS). Results of platelet activation marker P-selectin were parallel to those of PMP. After adjusting for age, and risk factors for arterial thrombosis (dyslipidemia, diabetes mellitus, hypertension, and current smoking) the difference in PMP between patients with/without thrombosis persisted (p=0.04).Conclusion: EMP are elevated in patients with positive APLA regardless of whether they had thrombosis or not. However, only APLA positive patients with thrombosis had elevated PMP. These results suggest that endothelial injury is widely present in APLA positive patients, but that risk of thrombosis depends mainly on platelet activation