Morphometric and Nanomechanical Features of Platelets from Women with Early Pregnancy Loss Provide New Evidence of the Impact of Inherited Thrombophilia.

Pregnancy is associated with hypercoagulation states and increased thrombotic risk, especially in women with thrombophilia. We combine atomic force microscopy (AFM) and flow cytometry to examine the morphology and nanomechanics of platelets derived from women with early pregnancy loss (EPL) and control pregnant (CP) and non-pregnant (CNP) women. Both control groups exhibit similar morphometric parameters (height and surface roughness) and membrane stiffness of platelets. EPL patients' platelets, on the other hand, are more activated than the control groups, with prominent cytoskeletal rearrangement. In particular, reduced membrane roughness (22.9 ± 6 nm vs. 39.1 ± 8 nm) (p < 0.05) and height (692 ± 128 nm vs. 1090 ± 131 nm) (p < 0.05), strong alteration in the membrane Young modulus, increased production of platelets' microparticles, and higher expression of procoagulant surface markers, as well as increased occurrence of thrombophilia (FVL, FII20210A, PLA1/A2, MTHFR C677T or 4G/5G PAI-1) polymorphisms were found. We suggest that the carriage of thrombophilic mutations triggers structural and nanomechanical abnormalities in platelets, resulting in their increased activation. The activation state of platelets can be well characterized by AFM, and the morphometric and nanomechanical characteristics might serve as a new criterion for evaluation of the cause of miscarriage and offer the prospect of an innovative approach serving for diagnostic purposes.

Rs5918ITGB3 Polymorphism, Smoking, and BMI as Risk Factors for Early Onset and Recurrence of DVT in Young Women.

OBJECTIVE: To evaluate the contribution of rs5918ITGB3 on the incidence and recurrence of deep venous thrombosis (DVT) in women and the relationship with body mass index (BMI) and smoking and to compare with data in men. RESULTS: Rs5918(C) polymorphism in ITGB3 gene was assessed in 224 patients diagnosed with DVT and 216 controls. Thrombophilic genetic variant rs5918(C) was significantly pronounced in women (χ2 =7.565, P = .008) and total patients (χ2 = 9.266, P = .002) but not in men. Women patients (<45 years) who were carriers of rs5918ITGB3 polymorphism had an early onset of DVT (34.5 vs 39.4 years, χ2 = 7.027, P = .008) as analyzed by Kaplan-Meier and a higher risk of the recurrent event (χ2 = 3.405, odds ratio = 2.581, P = .044). The period before recurrent venous thromboembolism event was related to smoking status and BMI in young female who were carriers of rs5918 polymorphism but not in the males. CONCLUSIONS: Carriage of genetic variant rs5918(C) polymorphism in ITGB3 gene in women contributes to higher risk of single and recurrent DVT events at younger age.