During pregnancy, the maternal hemostatic system undergoes significant changes to support placental angiogenesis, maintain fetal blood flow, and ensure safe delivery. This study investigates the dysregulation of hemostasis in placental insufficiency and explores potential markers for diagnosing and managing this gestational complication. Thromboelastography, coagulation and fibrinolysis functional assays, ELISA, and immunoblotting were employed to assess hemostasis dysregulation in placental dysfunction of two cohorts of pregnant women with placental dysfunction and healthy controls. Thromboelastographic analysis revealed no significant differences in clot lysis indices between the control and placental dysfunction groups, with values remaining within normal ranges, suggesting this method’s limitations for assessing fibrinolysis in pregnancy. The placental dysfunction group demonstrated moderately increased fibrinogen levels and platelet sensitivity to ADP, indicating hemostasis reactiveness. Significantly lower D-dimer levels, decreased plasminogen activator inhibitor activity (total PAI-1 + PAI-2), and increased plasminogen activator activity, driven primarily by uPA in the placental dysfunction group, indicated abnormal fibrinolysis. Immunoblotting confirmed elevated uPA/uPA-PAI complexes and reduced tPA/tPA-PAI complexes, indicating that shutdown of tPA-mediated fibrinolysis and induction of uPA-driven vessel-wall-associated proteolysis are linked to placental dysfunction. Placental dysfunction involves fibrinolytic system dysregulation, marked by decreased PAI and tPA, uPA overproduction, and hypofibrinolysis, contributing to thrombotic risks, impaired placental flow, and complications like fetal growth retardation. PAI/PA ratio and D-dimer levels have diagnostic potential for placental-dysfunction-associated complications.

Protein C (PC) is the main anticoagulant protein of the hemostasis system. It can inhibit the blood clotting cascade before the formation of a thrombus, while its concentration can decrease significantly during strong activation of blood clotting. The PC concentration was found to decrease during systemic lupus erythematosus (SLE) (with a median of 75%) and depended heavily on the inflammation index. It was also associated with the accumulation of soluble fibrin monomeric (SFMCs) (with a median of 7 µg/mL). A low PC level was detected during severe ischemic heart disease (IHD) (with medians of 60 and 63%, respectively). These pathologies also were associated with clotting activation. During abdominal aortic aneurysm (AAA), the PC level in blood plasma before surgery was found to range from 40% to 119%. A decrease in the PC level in the blood plasma of patients with AAA before surgery, lower than 78%, was associated with high blood loss (more than 1.5 L). A decrease in the PC level can lead to an imbalance between coagulation and anticoagulation. Thus, during the treatment of complex pathologies associated with the activation of coagulation, specific attention should be paid not only to classic markers of thrombus formation but also to the state of the anticoagulant link.

Мета дослідження: вивчення стану тромбоцитарної ланки гемостазу у вагітних із плацентарною дисфункцією. Матеріали та методи. Проведено клініко-лабораторний аналіз результатів обстеження 54 пацієнток із плацентарною дисфункцією. До групи контролю увійшли 30 практично здорових жінок із фізіологічним перебігом вагітності. У жінок, включених до дослідження, проводили забір венозної крові для тестування із використанням вакуумних систем у пробірки із 3,8% цитратом натрію. Функціональну активність тромбоцитів вивчали на фотооптичному агрегометрі AP2110 (Солар, Білорусь), тромбоцитограму проводили на гематологічному аналізаторі H18 LIGHT (SFRI SAS, Франція), тромбоеластометричні тести виконані на системі ROTEM delta (Tem Innovations GmbH, Німеччина). Результати. Тромбоцитарний гемостаз має значущий вплив на показник максимальної стійкості до згустків (MCF) за результатами ROTEM у пацієнток із плацентарною дисфункцією. Даний показник може бути ефективним у визначенні гіперреактивності тромбоцитарної ланки у пацієнток із плацентарною дисфункцією. Хоча не виявлено статично значущої різниці між показниками оптичної агрегатометрії індукованої АДФ та колагеном у пацієнток із плацентарною дисфункцією та групою контролю, слід відзначити чітку тенденцію до різкого скорочення lag-періоду колаген-індукованої агрегації тромбоцитів у пацієнток з плацентарною дисфункцією. Висновки. Поряд з пошкодженням ендотелію і коагуляційними змінами порушення у тромбоцитарній ланці гемостазу може відігравати суттєву роль у формуванні тромбофілічного стану у пацієнток із плацентарною дисфункцією. Застосування тесту на основі колаген-індукованої агрегації тромбоцитів може бути перспективним для ефективної діагностики гіперреактивності тромбоцитів. Дослідження тромбоцитарної ланки має стати додатковим елементом лабораторного обстеження з метою вирішення питання щодо необхідності призначення антиагрегантів для профілактики розвитку плацентарної дисфункції.

Background/Objectives: Pregnancy is associated with increased procoagulant conditions, and when combined with obesity, it can elevate the risk of thrombosis. The study aims to assess thrombosis risk markers during pregnancy in relation to obesity. Methods: Somatically healthy women aged 18–42 years with spontaneous pregnancies who did not receive specific antithrombotic treatment were enrolled in the study (n = 97). The participants were divided into groups based on pregestational BMI: the first group consisted of patients who had a BMI ≤ 25 (n = 42), and the second group consisted of patients who were overweight (BMI > 25) and obese (BMI > 30) (n = 55). The control group comprised healthy, non-pregnant, non-obese women (n = 10). Results: Fibrinogen levels, elevated during pregnancy, were higher in the II and III trimesters, with gestational period having a greater influence than BMI. Moderate D-dimer accumulation was observed regardless of obesity, but higher levels were seen in obese women during the III trimester, indicating the dissolution of intravascular fibrin deposits. Soluble fibrin was significantly higher in obese and overweight women during the II trimester and elevated in both groups during the III trimester, correlating with D-dimer accumulation and indicating thrombus formation. A decrease in platelet aggregation ability was observed correlating with D-dimer and soluble fibrin patterns. Conclusions: A significant accumulation of thrombosis risk markers was observed in the III trimester compared to the II, occurring earlier in obese and overweight pregnant women and indicating a higher risk of thrombotic complications in obesity.

This paper describes a novel approach the development of biocompatible polyvinyl chloride (PVC) and polyurethane (PU) polymers, modified with copper (II) ions followed by the immobilisation the thrombin inhibitor argatroban (AG) using dopamine chemistry. The surface loading of the immobilised AG was 6.06 µg cm⁻² on PVC and 6.66 µg cm⁻² on PU, confirmed by FTIR and inhibitor concentration measurements. Both AG/Cu-modified polymers produced NO by catalytically decomposing S-nitrosothiol, reaching NO levels in plasma of 0.59 × 10^–10 $$\text{mol} \, {\text{cm}}^{-2} \, {\text{min}}^{-1}$$mol cm - 2 min - 1 for AG/Cu-PVC and 0.51 × 10^–10 $$\text{mol} \, {\text{cm}}^{-2} \, {\text{min}}^{-1}$$mol cm - 2 min - 1 for AG/Cu-PU, matching endothelial cell-produced physiological levels. This modification improved the haemocompatibility of the polymers through thrombin inhibition and reduced platelet aggregation and adhesion. Additionally, both modified polymers inhibited Staphylococcus aureus adhesion, growth and viability, confirming their acquired antibacterial properties. Antibacterial activity against Escherichia coli was also observed. These results demonstrate that modifying PVC and PU surfaces with copper (II) and AG produced materials with dual antithrombotic and antibacterial functions. Graphical abstract