HOW Collaborative position paper on the management of thrombocytopenia in pregnancy.

Thrombocytopenia in pregnancy is a common occurrence, affecting up to 10% of women by the time of birth. These recommendations aim to provide pragmatic guidance on the investigation, diagnosis and management of thrombocytopenia in pregnancy; including safety of neuraxial anaesthesia and precautions required for birth. Management of neonatal thrombocytopenia is also addressed. The authors are clinicians representing haematology, obstetric medicine, maternal-fetal medicine, and anaesthesia. Each author conducted a detailed literature review then worked collaboratively to produce a series of unanimous recommendations. The recommendation strength is limited by the lack of high-quality clinical trial data, and represents level C evidence.

Comparison of the effects on maternal endothelial cell activation: an in vitro study of anti-hypertensive drugs clinically used in pre-eclampsia.

Endothelial cell dysfunction in pregnancy, which can be induced by placental factors, is the fundamental component of the pathogenesis of pre-eclampsia. The dysfunctional vascular endothelium disrupts the balance of vasodilatory and vasoconstrictive factors, resulting in increasing blood pressure. There is currently no effective treatment for pre-eclampsia and effective control of hypertension may reduce neonatal morbidity and mortality by prolonging gestation, especially in cases of early onset disease. To date methyldopa, labetalol, nifedipine and metoprolol are recommended for controlling blood pressure in pre-eclampsia. All of these drugs have different mechanisms of action. In this in vitro study we investigated whether different types of anti-hypertensive drugs could have different effects on improving maternal endothelial cell dysfunction. Endothelial cells (HMEC-1) were exposed to phorbol-12-myristate-13-acetate (PMA) or pre-eclamptic sera or extracellular vesicles (EVs) derived from pre-eclamptic placentae, in the presence of each of the studied anti-hypertensive drugs (methyldopa, labetalol, nifedipine and metoprolol) or placebo for 24 h. Endothelial cell-surface adhesion molecule (ICAM-1) and monocyte adhesion were measured. The expression of cell-face ICAM-1 by HMEC-1 cells and THP-1 monocyte adherent to HMEC-1 that were exposed to three separate well-known activators of endothelial cells in the presence of four anti-hypertensive drugs was significantly reduced regardless of the dose. However, the effect on the reduction of ICAM-1 expression and monocyte adhesion was not significantly different between the four medications. Our data suggest that the beneficial effect on improving endothelial cell function by these commonly prescribed anti-hypertensive drugs is seemingly independent of the anti-hypertensive mechanisms of the medication.

Antiphospholipid antibodies do not cause retargeting of placental extracellular vesicles in the maternal body.

Antiphospholipid antibodies (aPL) are autoantibodies that cause pregnancy disorders by a poorly defined mechanism that involves the placenta. The human placenta is covered by a single multinucleated cell, the syncytiotrophoblast, which extrudes vast numbers of extracellular vesicles (EVs) into the maternal blood. Extracellular vesicles are tiny packages of cellular material used by cells for remote signalling. In normal pregnancy, placental EVs assist maternal adaptations to pregnancy. We have previously shown that aPL alter the cargo of placental EVs, increasing the load of danger signals. These changes in EV cargo may explain how aPL contribute to the increased risk of recurrent miscarriage, preeclampsia and stillbirths observed in aPL-affected pregnancies. An additional possibility, that aPL alters the targeting of placental EVs to maternal organs to cause maternal maladaptation to pregnancy was investigated in this study.