Heparin and aspirin attenuate placental apoptosis in vitro: Implications for early pregnancy failure

Bose, Patrick; Black, Simon; Kadyrov, Mamed; Weissenborn, U.; Neulen, Joseph; Regan, Lesley; Huppertz, Berthold

doi:10.1016/j.ajog.2004.09.029

Cited by 156 publications

(88 citation statements)

References 24 publications

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“…Therefore, these reports extend previous observations that defective trophoblast proliferation and invasion is a key pathological feature in placenta of patients with antiphospholipid syndrome (APS) [2,3]. Of considerable interest is that these effects could be attenuated in vitro by heparin and aspirin, drugs commonly used for the treatment of APS in pregnancy [22].…”

Section: Preeclampsia: An Immune Disorder?supporting

confidence: 69%

“…It is interesting that recent in vitro or murine studies are starting to elucidate the pathways by which heparin acts under these conditions [22,27]. Although the use of other anti-inflammatory agents and anti-TNFα strategies is being discussed [28], no clinical studies reporting on the efficacy of such planned approaches exist.…”

Section: Therapeutic Possibilitiesmentioning

confidence: 99%

See 1 more Smart Citation

Disturbances in placental immunology: ready for therapeutic interventions?

Hahn

Gupta

Troeger

et al. 2006

Springer Semin Immun

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Recent studies have provided new insight into aberrations in the immunological interplay between mother and fetus and their potential role in the development of recurrent fetal loss and preeclampsia. The action of anti-phospholipid antibodies in recurrent fetal loss is now proposed to involve the complement system, neutrophil activation and the production of TNFα by immune bystander cells. A clear involvement of the immune system is emerging in preeclampsia, involving mainly the innate arm, especially neutrophils. The activation of peripheral neutrophils by placentally released inflammatory debris triggers the induction of neutrophil extracellular traps (NETs), which may lead to an occlusion of the intervillous space, thereby further promoting a condition of placental hypoxia. It has, hence, been suggested that new therapeutic strategies be developed, including the possible use of TNFα antagonists in cases of recurrent miscarriage. These strategies need to be addressed with caution due to the possible induction of fetal congenital abnormalities.

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Section: Preeclampsia: An Immune Disorder?supporting

confidence: 69%

Section: Therapeutic Possibilitiesmentioning

confidence: 99%

Disturbances in placental immunology: ready for therapeutic interventions?

Hahn

Gupta

Troeger

et al. 2006

Springer Semin Immun

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show abstract

“…Thus, pathophysiology other than placental thrombosis may influence pregnancy outcome. Antiphospholipid antibodies have a variety of effects on the trophoblast, including inhibition of trophoblastic function and differentiation, induction of syncytiotrophoblast apoptosis, and activation of complement pathways at the maternal-fetal interface resulting in a local inflammatory response [55].…”

Section: Acquired Thrombophilic Conditionsmentioning

confidence: 99%

“…In vitro studies have shown that the effect of antiphospholipid antibodies on trophoblast function and complement activation [9,55] may be reversed by heparin and both low-dose aspirin and low molecular weight heparin have been recommended for the cases of obstetric APS. Unfortunately, 30% of the cases continue to experience pregnancy loss in spite of treatment with no obvious cause and no effective treatment [46].…”

Section: Acquired Thrombophilic Conditionsmentioning

confidence: 99%

Recurrent Miscarriage: A Review

Barrenetxea¹

2017

RMGO

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pregnancy events [2]. Clinical miscarriages may be subdivided into early clinical pregnancy losses (before gestational week 12) and late clinical pregnancy losses (gestational weeks 12 to 21). The term miscarriage is preferred rather than abortion both by patients and physicians, although "spontaneous abortion" is still used in scientific literature [3,4].For more than 30 years, controversy has existed on the number of miscarriages required to define RM and when diagnostic testing is warranted [5] EpidemiologyEarly pregnancy loss is perhaps the most common obstetric complication, occurring in over two-thirds of human conceptions. Approximately 15 -20% of all clinically recognized pregnancies will end in a miscarriage [4,9,10]. However, prospective cohort studies using sensitive and specific daily urinary hCG assays in women trying to conceive have demonstrated that only around one-third of conceptions progress to a live birth. Most of the losses occur before the clinical recognition of pregnancy as implantation failures. An estimated 30% of human conceptions are lost prior to implantation and a further 30% following implantation but before the missed menstrual period, that is in the third or fourth week of gestation. These are often termed preclinical losses [11].The risk of sporadic miscarriage between 6 and 12 weeks of gestation in women less than 35 years of age is 9% to 12%. The risk increases with age. In women older than 40 years of age, the sporadic miscarriage rate approaches 50%. Late losses between 12 and 22 weeks occur less frequently and constitute around 4% of pregnancy outcomes [4,9].Compared to sporadic miscarriage the prevalence of RM is considerably lower irrespective of whether biochemical losses are included or not. Approximately 1% of all women trying to conceive have recurrent miscarriage, defined as three previous miscarriages; when recurrent miscarriage is defined as two previous miscarriages, the proportion rises to 3% [12,13]. EtiologyMultiple potential etiologies for RM have been described (Table 1). As a consequence, several recommendations have been published regarding the evaluation and management of RM [3].The potential etiologies of RM can be divided into embryologically driven causes (mainly due to an abnormal embryonic karyotype) and maternally driven causes which affect the endometrium and/or placental development [14,15]. Thus, studies that focus on RM have Barrenetxea G, et al., J Reprod Med Gynecol Obstet 2017 AbstractHuman reproduction is characterized by its inefficiency. The loss of pregnancy at any stage can be a devastating experience and particular sensitivity is required in assessing and counseling couples with Recurrent Miscarriage (RM). Recurrent Miscarriage (RM) represents a clinical challenge for physicians not only because there are multiple possible etiologies, but also because the diagnostic testing is costly and time consuming. Despite several well-known etiologic factors, the cause of RM cannot be determined in almost 50% of cases. Multiple potential etiolo...

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“…(10) This "nonprothrombotic theory" is supported by the observation that both heparin and aspirin attenuate trophoblast apoptosis in vitro. (11) The fact that it is not biologically plausible that an assumed thrombotic component in women with inherited thrombophilia plays a role until 10 to 12 weeks of gestation, when the placental vasculature has been developed, leaves unexplained why the vast majority of women with recurrent miscarriage have early losses. For the common forms of inherited thrombophilia, experimental models to study trophoblast differentiation and early placentation are lacking.…”

mentioning

confidence: 99%

Low-molecular-weight heparins have no place in recurrent miscarriage: Debate – For the motion

Middeldorp

2011

Thrombosis Research

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Heparin and aspirin attenuate placental apoptosis in vitro: Implications for early pregnancy failure

Cited by 156 publications

References 24 publications

Disturbances in placental immunology: ready for therapeutic interventions?

Disturbances in placental immunology: ready for therapeutic interventions?

Recurrent Miscarriage: A Review

Low-molecular-weight heparins have no place in recurrent miscarriage: Debate – For the motion

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