Molecular actions of heparin and their implications in preventing pre‐eclampsia

Abstract

Pre-eclampsia, a hypertensive disorder of pregnancy, continues to be a significant cause of global maternal morbidity. Low-dose aspirin remains the only standard-of-care prophylactic therapy for preventing pre-eclampsia, but is limited in efficacy. Heparin and its derivatives may further enhance the efficacy of aspirin therapy to prevent pre-eclampsia, but the mechanisms mediating this augmentative effect are not known. Although heparin is an anticoagulant agent, it also possesses many anticoagulant-independent properties that may be relevant in the prevention of pre-eclampsia, including effects on placental, vascular and inflammatory function. This review summarizes the non-anticoagulant properties of heparin, and extrapolates how these actions may influence the trajectory of pre-eclampsia pathogenesis as a means of pathway-specific therapy.

A Cut-off Value for Gestational Week at Birth for Better Perinatal Outcomes in Early- and Late-Onset Fetal Growth Restriction

“…We used ultrasonographic measurement below the 10 th percentile as the initiation of FGR and classified patients as early or late onset based on whether it was before and after the 34 th gestational week. In this study, we show that 31.5 (26)(27)(28)(29)(30)(31)(32)(33) and 37 (33)(34)(35)(36)(37)(38)(39)(40) gestational weeks were the median gestational ages in terms of the first diagnosis of early-and late-onset FGRs. Timing of the diagnosis of FGR is reported to be related with neonatal outcomes [31].…”

“…Recent studies report the effect of anti-inflammatory treatment modalities, such as low-dose aspirin in the reduction of FGR and preeclampsia rates [25]. Low-dose, low-molecular-weight heparin is also reported to be effective for preventing preeclampsia owing to anti-inflammatory effects [26].…”

Use of low-molecular-weight heparin in severe paraquat poisoning: a case report

“…It is increasingly recognized that low-molecular-weight heparins (LMWH) have many pharmacological properties beyond their anticoagulant activity [ 21 ] [ 23 ]. As a naturally occurring molecule, endogenous heparin is specifically localized to immune mast cells in humans to physiologically modulate certain inflammatory pathways [ 24 ], for example through inhibition of the complement cascade. The complement system is a pivotal component of the innate immune system in the response against microorganisms, and it is dysregulated by toxic agents such as PQ [ 25 ].…”

“…Complement can be activated by three distinct pathways: the classical, alternative and lectin pathways. The specific heparin–complement protein interactions include inhibition of C1q (initiator of the classical complement pathway), augmentation of factor H (soluble inhibitor of the alternative pathway) and inhibition of the lytic terminal complement complex [ 24 ]. The three pathways converge at the cleavage and activation of C3, generating split products with biological effector functions (C3 opsonins, cytolytic membrane attack complex, and so on).…”

Antithrombotic therapy to prevent recurrent pregnancy loss in antiphospholipid syndrome—What is the evidence?

“…Possible effects on complement activation may be of more importance and it has been hypothesized that the non-anticoagulant effects of heparins on inflammatory processes, vascular function, or placental pathology may play a role in prevention of pre-eclampsia, a disorder strongly associated with antiphospholipid syndrome. 16,17 Moreover, antiphospholipid antibodies appear to affect the production of several chemokines and angiogenic factors by human endometrial endothelial cells, which may contribute to impaired placentation and vascular transformation. 18 The risk of (recurrent) pregnancy complications may differ between women with and without previous complications, women with high and low antiphospholipid antibodies titers, and women with positive and negative LAC.…”