Hypoxia alters syncytiotrophoblastic microparticles (STBM)-related coagulation capacities

Introduction: Endothelial dysfunction, defined as vasoconstiction and platelet activation, is thought to be the cause of preeclampsia (PE) symptoms. Especially severe forms of the pregnancy-associated pathology PE is correlated to the release of syncytiotrophoblastic microparticles (STBM), which triggers inflammatory processes on the endothelium. The thrombogenic potential of STBMs, however, are not well characterized.

Aim of the study was to investigate the pro-coagulant activity of STBMs.

Methods: STBMs were derived from placentae perfused under norm- and hypoxic conditions and quantified with our house-“ELSA.” Surface phospholipid-dependent thrombin formation of microparticles was dermined with a commercial ELISA. Rate and absolute platelet aggregation in platelet-rich plasma (PRP), while fibrin production in platelet free plasma, was measured in absence and presence of STBMs using a PAP-4 aggregometer (mölab GmbH, Hilden).

Results: STBM concentration and STBM-induced thrombin formation is stable under normoxic, but is elevated under hypoxic, conditions. STBMs derived from hypoxic placentae increases the rate of fibrinogenesis non-dosis-dependently. Maximum platelet aggregation is stable under normoxic, while highly variable under hypoxic, conditions. STBMs of hypoxic placentae cannot alter the rate of platelet aggregation, while normoxic STBMs adjust the rate according to need.

Conclusion: STBMs expose negatively-charged phospholipids which exert significant pro-coagulant activity as indicated by their prothrombinase activity as well as by the accelerated fibrin formation. Hypoxia negatively affects fibrinogenesis and the platelet aggregation-modulating effects of STBMs, which might be due to a phenotype alteration. All observed resluts may contribute to the impaired microcirculation seen in PE.