Elevated Procoagulant Endothelial and Tissue Factor Expressing Microparticles in Women with Recurrent Pregnancy Loss

Patil, Rucha; Ghosh, Kanjaksha; Satoskar, Purnima; Shetty, Shrimati

doi:10.1371/journal.pone.0081407

Cited by 42 publications

(33 citation statements)

References 25 publications

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“…A number of studies have compared the levels of MPs in the blood of patients with primary APS, SLE patients with secondary APS, SLE patients with or without antiphospholipid antibodies (aPL) in the absence of secondary APS, and healthy individuals with or without aPL in the absence of thrombotic events. In general, these studies have reported elevated numbers of EMPs in patients with APS, lending credence to links of EMPs with thrombotic events and pregnancy complications [57][58][59]. However, the precise contribution to thrombosis remains unclear.…”

Section: Anti-phospholipid Syndromementioning

confidence: 85%

Endothelial microparticles: Pathogenic or passive players in endothelial dysfunction in autoimmune rheumatic diseases?

McCarthy

Wilkinson

Parker

et al. 2016

Vascular Pharmacology

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Autoimmune rheumatic diseases are characterised by systemic inflammation and complex immunopathology, with an increased risk of cardiovascular disease, initiated by endothelial dysfunction in a chronic inflammatory environment. Endothelial microparticles (EMPs) are released into the circulation from activated endothelial cells and may therefore, reflect disease severity, vascular and endothelial dysfunction, that could influence disease pathogenesis via autocrine/paracrine signalling. The exact function of EMPs in rheumatic disease remains unknown, and this has initiated research to elucidate EMP composition and function, which may be determined by the mode of endothelial activation and the micro environment. To date, EMPs are thought to play a role in angiogenesis, thrombosis and inflammation by transferring specific proteins and microRNAs (miRs) to target cells. Here, we review the mechanisms underlying the generation and composition of EMPs and the clinical and experimental studies describing the involvement of EMPs in rheumatic diseases, since we have previously shown endothelial dysfunction and an elevated risk of cardiovascular disease are characteristics in systemic lupus erythematosus. We will also discuss the potential of EMPs as future biomarkers of cardiovascular risk in these diseases.

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Section: Anti-phospholipid Syndromementioning

confidence: 85%

Endothelial microparticles: Pathogenic or passive players in endothelial dysfunction in autoimmune rheumatic diseases?

McCarthy

Wilkinson

Parker

et al. 2016

Vascular Pharmacology

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“…A study at our centre has earlier shown elevated cellderived microparticles in women with recurrent pregnancy loss [3] and when these patients were initiated on anticoagulant therapy the microparticle levels gradually reduced and successful pregnancy outcome was achieved in cases where microparticles normalized [4]. As no strong thrombophilia markers were detected in the above patient, cell-derived microparticles were investigated by flow cytometry.…”

Section: Case Reportmentioning

confidence: 99%

Management of pregnancy in dysfibrinogenemia cases

Patil

Mukaddam²,

Ghosh³

et al. 2017

Blood Coagulation &Amp; Fibrinolysis

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Dysfibrinogenemia is a very challenging disorder, and there are no firm guidelines on treatment for pregnant patients with dysfibrinogenemia. A 37-year-old patient with a history of six unexplained recurrent miscarriages was referred for thrombophilia testing. Elevated procoagulant microparticles were found, for which during her seventh pregnancy anticoagulant therapy was initiated. However, she again miscarried and bled excessively. She was then diagnosed with dysfibrinogenemia. DNA sequence analysis revealed a novel homozygous insertion-deletion in exon 7 in FGB. Dysfibrinogenemia is very difficult to diagnose and even after diagnosis, the treatment varies with the patient's symptoms. In this case, anticoagulant therapy failed. With her history of recurrent miscarriages, it is clear that pregnancy without any treatment is not an option. Few reports suggest a combination of intravenous fibrinogen infusions along with anticoagulants in which successful pregnancy outcome was achieved. The present case thus stresses on the need for some treatment guidelines in such cases.

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“…The method for MP analysis (standardized by participating in the International Society of Thrombosis and Hemostasis workshop) was carried out as described earlier [3]. The PMP levels were found to be 305, 315, and 552 MP/μl plasma in the first, second, and third trimester and 732 MP/μl post-delivery and the total AnnexinV binding MPs were found to be 1473, 1866, and 2756 MP/μl plasma in the first, second, and third trimester and 1895 MP/μl post-delivery.…”

Section: Dear Editormentioning

confidence: 99%

Decrease in circulating percentage platelet microparticles during pregnancy—a different perspective

2015

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Dear Editor,We read with interest the study done by Wong et al. [1] in which the authors analyzed circulating maternal platelet microparticles (PMPs) and trophoblast microparticles (MP) during pregnancy to investigate whether pregnancy, labor, or delivery is associated with changes in maternal MPs with regards to origin and composition. The authors found that the percentage PMPs in laboring healthy women was 8.5 % in the third trimester before delivery and 20.5 % after delivery. The %PMPs in nonpregnant healthy controls was also to be 18 % similar to the percentage post-delivery. However, they concluded that labor and delivery are associated with an increase in platelet activation and thus the increase in %PMPs.We analyzed the %PMPs out of the total AnnexinV binding MPs by flow cytometry in 25 healthy pregnant women with one live child and no history of major illness [2]. The method for MP analysis (standardized by participating in the International Society of Thrombosis and Hemostasis workshop) was carried out as described earlier [3]. The PMP levels were found to be 305, 315, and 552 MP/μl plasma in the first, second, and third trimester and 732 MP/μl post-delivery and the total AnnexinV binding MPs were found to be 1473, 1866, and 2756 MP/μl plasma in the first, second, and third trimester and 1895 MP/μl post-delivery. Thus, the mean %PMPs was found to be 20.7, 17, and 20 % in the first, second, and third trimester and 32 % postdelivery.Thus, if we analyze the data from another angle focusing on the %PMPs instead of the actual levels, is it possible that rather than an increase in platelet activation and %PMPs during labor and delivery, it is actually a decrease of %PMPs during pregnancy which normalizes post-delivery? One possible reason for the decrease during pregnancy is their consumption in fibrin clots which occurs at the placental beds, thus trapping the MPs and thus their removal from circulation.There is evidence of fibrin deposits in placental vasculature in women with bad obstetric history, and PMPs have been shown to adhere to fibrin. Few studies also suggest the consumption of PMPs in fibrin deposits [4,5]. Pregnancy itself is a hypercoagulable state [6], and this condition along with the fact that PMPs apart from being thrombogenic also have the antigen profile of platelets which bind to many factors, may be promoting this consumption of PMPs.The authors have given only %PMPs but have not mentioned the absolute total and platelet MP counts despite of mentioning that MP were measured by adding AccuCount TM fluorescent beads. Also, they have detected platelets under light microscopy only after freeze-thawing. This should have been done prior to freezing as platelets may lyse in the freeze thaw cycle and produce more MPs; distorting the results. Information regarding the platelet counts at different points of sampling would have been useful for their association with the PMPs. With the above information, a clearer idea with respect to the PMP levels during pregnancy would have been established.

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Elevated Procoagulant Endothelial and Tissue Factor Expressing Microparticles in Women with Recurrent Pregnancy Loss

Cited by 42 publications

References 25 publications

Endothelial microparticles: Pathogenic or passive players in endothelial dysfunction in autoimmune rheumatic diseases?

Endothelial microparticles: Pathogenic or passive players in endothelial dysfunction in autoimmune rheumatic diseases?

Management of pregnancy in dysfibrinogenemia cases

Decrease in circulating percentage platelet microparticles during pregnancy—a different perspective

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