Autoantibodies to Factor XII and Kininogen-Dependent Antiphosphatidylethanolamine Antibodies in Patients with Recurrent Pregnancy Loss Augment Platelet Aggregation

Problem: Numerous studies have suggested that factor XII (FXII) deficiency, autoantibodies to FXII (anti-FXII), and antiphosphatidylethanolamine antibodies (aPE) are associated with recurrent pregnancy loss (RPL). aPE in RPL patients recognize the LDC27 peptide of kininogen domain 3. Anti-FXII in RPL patients recognizes the heavy chain of FXII, especially the amino-terminal sequences IPP30 peptide. Previous studies suggested that LDC27 and IPP30 are the responsible sites competing for the same binding site on platelets and inhibiting augmentation of thrombin-induced platelet aggregation. Our aim was to study the influence of antibodies to LDC27 and IPP30 on platelet aggregation.

Methods Of Study: In fifteen healthy volunteers, platelet aggregation induced by γ-thrombin in the presence or absence of antibodies to LDC27 and IPP30 was measured. Sixteen RPL patients who were positive for anti-FXII were measured for spontaneous small platelet aggregate (SSPA) formation.

Results And Conclusions: Antibodies to LDC27 and IPP30 markedly increased aggregation of normal platelets stimulated by γ-thrombin. Augmentation of SSPA formation was more frequent in the patients with RPL who were positive for anti-FXII than in the control group (P = 0.003). This study strongly supports the hypothesis that aPE and anti-FXII may cause RPL due to disruption of the normal antithrombotic effects of kininogens and FXII.