Inherited Thrombophilia and Pregnancy Complications: Should We Test?

2018 ◽  
Vol 45 (01) ◽  
pp. 050-060 ◽  
Author(s):  
Mike Makris ◽  
Deepa Arachchillage
Keyword(s):  
Pregnancy Outcome ◽  
Health Care Professionals ◽  
Pregnancy Complications ◽  
Recurrent Miscarriage ◽  
Late Pregnancy ◽  
Inherited Thrombophilia ◽  
Recurrent Miscarriages ◽  
Conflicting Evidence ◽  
Recurrent Pregnancy Losses ◽  
Additional Therapy

AbstractRecurrent miscarriages and pregnancy-related complications cause significant stress to couples looking for successful pregnancy outcome as well as to health care professionals. There is conflicting evidence with respect to the presence and the strength of associations between inherited thrombophilia and these complications. A complete thrombophilia screen is expensive, and no proven effective treatment for women with recurrent miscarriage and inherited thrombophilia is currently available. Based on the concept of microvascular thrombosis of the placenta, women with recurrent miscarriage and placenta-related complications frequently get treated with antithrombotic therapy. In this narrative review, the authors explore the evolving understanding and evidence of inherited thrombophilia in recurrent miscarriages and other pregnancy complications, and whether antithrombotic treatment would modify pregnancy outcome in women with inherited thrombophilia. Finally, they provide some personal recommendations based on available evidence for clinical practice. In summary, inherited thrombophilia testing is not required outside a clinical trial for women with recurrent pregnancy losses or late pregnancy complications. The presence of thrombophilia markers does not generally indicate additional therapy during pregnancy, even if a heritable thrombophilic defect is found in women with recurrent miscarriages or late pregnancy complications.

scholarly journals Anticoagulation in pregnancy complications

Hematology ◽  
2014 ◽  
Vol 2014 (1) ◽  
pp. 393-399 ◽  
Author(s):  
Saskia Middeldorp
Keyword(s):  
Pregnancy Complications ◽  
Recurrent Miscarriage ◽  
Late Pregnancy ◽  
Severe Preeclampsia ◽  
Inherited Thrombophilia ◽  
Increased Risk ◽  
Improve Pregnancy Outcome ◽  
Clinical Trial Evidence ◽  
Unexplained Recurrent Miscarriage ◽  
Trial Evidence

Abstract Women with acquired and inherited thrombophilia are thought to be at increased risk for pregnancy complications, including recurrent pregnancy loss and, depending on the type of thrombophilia, severe preeclampsia. This review discusses the associations between the types of thrombophilia and types of complications, as well as the currently available clinical trial evidence regarding the use of aspirin and heparin to prevent these pregnancy complications. In women with antiphospholipid syndrome, guidelines recommend prescribing aspirin and heparin to women with recurrent miscarriage. The same regimen is suggested for late pregnancy complications by some, but not all, experts. Aspirin or low-molecular-weight heparin to improve pregnancy outcome in women with unexplained recurrent miscarriage has no benefit and should not be prescribed. Whether anticoagulant therapy prevents recurrent miscarriage in women with inherited thrombophilia or in women with severe pregnancy complications remains controversial because of inconsistent results from trials. Aspirin modestly decreases the risk of severe preeclampsia in women at high risk.

Recurrent pregnancy loss

2019 ◽  
Vol 13 (7) ◽  
pp. 402-408
Author(s):  
Priyanka Krishnaswamy ◽  
Rohit Arora
Keyword(s):  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Recurrent Miscarriage ◽  
Second Trimester ◽  
Successful Pregnancy ◽  
Inherited Thrombophilia ◽  
Epidemiological Factors ◽  
Factors Influencing ◽  
Recurrent Pregnancy Losses ◽  
Male Factors

Miscarriage is defined as the spontaneous loss of a pregnancy before the fetus reaches viability; it includes all pregnancy losses from the time of conception until 24 weeks of gestation. Early miscarriages are common, occurring in 10–20% of all pregnancies, with 2% of second-trimester pregnancies being miscarried before 24 weeks of gestation. Recurrent miscarriage, defined as the loss of three or more consecutive pregnancies, affects 1% of couples trying to conceive with the chance of having two consecutive miscarriages being 5%. Clinical studies show that 3 in 4 women will have a successful pregnancy with supportive care alone. Therefore, couples should be given reassurance about their chances of a successful pregnancy in the future. In this review we look at the epidemiological factors influencing rates of miscarriage, acquired and inherited thrombophilia, genetic, anatomical, endocrine, immune, infective and male factors for recurrent miscarriage. Despite these potential causes, the majority (around 50%) of recurrent pregnancy losses remain unexplained.

scholarly journals Association of inherited thrombophilia gene polymorphism with sporadic and recurrent miscarriages

2021 ◽  
Vol 29 ◽  
pp. 168-173
Author(s):  
L. B. Chorna ◽  
H.V. Makukh ◽  
D.V. Zastavna ◽  
Ya.Yu. Zaganyach ◽  
O.I. Kolodiy ◽  
...  
Keyword(s):  
Gene Polymorphism ◽  
Recurrent Miscarriage ◽  
Significant Risk ◽  
Fold Increase ◽  
Mthfr Gene ◽  
Control Group ◽  
Inherited Thrombophilia ◽  
Recurrent Miscarriages ◽  
Group I ◽  
Pai 1

Aim. Despite numerous scientific studies of possible causes of miscarriage, their etiology remains unclear in approximately 50% of cases. Investigate the prevalence of thrombophilia associated gene polymorphism FGB 455G/A, FII 20210 G/A, FV 1691G/A, ITGA2 807C/T, PAI-1 5G/4G and MTHFR 677C/T in women with sporadic and recurrent miscarriages. Methods. Group I included 35 women with sporadic miscarriage (SM), group II consisted of 57 women with recurrent miscarriage (RM) and 55 women of control group. Genetic testing was performed by PCR-RFLP. Results. In group I of women with SM the 455GA genotype of the FGB gene was more common and its presence in the genotype increases the risk of SM by 4 times and the presence of the 455A allele by 2 times. The Leiden mutation increases the risk of SM by 5 times. In II group of women with RM, the frequency of the 455 AA genotype of the FGB gene was more prevalent and the risk of RM was increased 2.5 times. It is shown that the risk of RM increases 4 times in the presence of the Leiden mutation. The 4G allele of the PAI-1 5G/4G polymorphism leads to a 2-fold increase in the risk of RM, and the presence of the 677TT genotype of the MTHFR gene increases the risk of RM by 3 times. Conclusions. Genetic factors of inherited thrombophilia alleles 455A of the FGB gene, 1691A of the FV gene, 4G of the PAI-1 gene and 677T of the MTHFR gene are alleles of significant risk of reproductive losses both sporadic and, to a greater extent, recurrent. Keywords: sporadic miscarriage, recurrent.miscarriage, inherited thrombophilia, genetic polymorphism.

scholarly journals POS0737 LOW PRECONCEPTIONAL COMPLEMENT LEVEL IS RELATED WITH ADVERSE OBSTETRIC OUTCOME IN A MULTICENTRIC COHORT OF PREGNANCY IN PATIENTS WITH APS AND APL POSITIVITY

2021 ◽  
Vol 80 (Suppl 1) ◽  
pp. 619.2-620
Author(s):  
D. Lini ◽  
C. Nalli ◽  
L. Andreoli ◽  
F. Crisafulli ◽  
M. Fredi ◽  
...  
Keyword(s):  
Pregnancy Outcome ◽  
Complement Activation ◽  
Pregnancy Complications ◽  
Antiphospholipid Antibodies ◽  
Pregnancy Loss ◽  
Adverse Pregnancy Outcome ◽  
Obstetric Outcome ◽  
Complement Level ◽  
Increased Risk ◽  
Adverse Pregnancy

Background:The role of complement in the antiphospholipid (aPL) related pathology has been widely studied in animal models. Antiphospholipid antibodies can induce fetal loss in experimental animals but mice deficient in specific complement components (C4, C3, C5) appear somehow protected. In addition, in pregnant mice injected with aPL, antibody deposition has been found at decidual level causing focal necrosis, apoptosis and neutrophil infiltrates and supporting aPL pathogenetic potential. On the other hand, human studies did find hypocomplementemia associated to pregnancy complications in patients with obstetric antiphospholipid syndrome (APS). These results, however, are not unanimously confirmed and, in addition, some studies only show increased levels of complement activation products (i.e. Bb) and not decreased levels of C3 and/or C4. A recently study focusing on complement level in early pregnancy and before pregnancy showed a significant correlation with pregnancy complications and loss in a large cohort of primary APS.Objectives:To investigate if the simple detection of low C3 and/or C4 could be considered a risk factor for adverse pregnancy outcome in APS and aPL carriers pregnancies.Methods:We performed a multicentric study including patients from 10 Italian and 1 Russian Centers. Data on pregnancies in women with primary APS (n=434) and asymptomatic carriers with persistently positive aPL but not fulfilling clinical criteria for APS (n=218) were retrospectively collected. Serum C3 and C4 levels were evaluated by nephelometry; hypocomplementemia was defined by local laboratory reference values. Statistical analysis was performed using GraphPad.Results:Preconceptional complement levels and gestational outcome were available for 107 (25%) pregnancies in APS out of 434 and for 196 (90%) pregnancies in aPL carriers women out of 218. In pregnancies with low preconceptional C3 and/or C4, a significantly higher prevalence of pregnancy losses was observed (p=0.019). A subgroup analysis focusing on triple aPL positive patients was also performed. Preconceptional low C3 and/or C4 levels were found to be associated with an increased rate of pregnancy loss (p = 0.027) in this subgroup also. Otherwise, adverse pregnancy outcomes in single or double aPL positive women were not related to preconception complement levels (p = 0.44) (Table 1). Of note, all the pregnancy losses in the triple positive group occurred in patients treated with low dose aspirin and low molecular weight heparin from the time of positive pregnancy test.Conclusion:Our findings confirm that decreased complement levels before pregnancy are associated with increased risk of adverse outcome. This has been seen only in in women with triple aPL positivity, indeed single or double positivity does not show this trend. Complement levels are cheap and easy to be measured therefore they could represent a useful aid to identify patients at increased risk of pregnancy loss. test positivity.References:[1]De Carolis S, et al. Complementemia and obstetric outcome in pregnancy with antiphospholipid syndrome. Lupus (2012) 21:776–8.[2]Kim MY, et al. Complement activation predicts adverse pregnancy outcome in patients with systemic lupus erythematosus and/or antiphospholipid antibodies. Ann Rheum Dis (2018) 77:549–55.[3]Fredi M, et al. Risk Factors for Adverse Maternal and Fetal Outcomes in Women With Confirmed aPL Positivity: Results From a Multicenter Study of 283 Pregnancies. Front Immunol. 2018 May 7;9:864.Triple aPL positivitySingle or double aPL positivityGestational outcomeLow C3/C4 (n=49)Normal C3/C4(n=17)pLow C3/C4 (n=57)Normal C3/C4(n=165)pTerm live birth (>37w)15 (31%)6 (35%)ns34 (60%)110 (67%)nsPreterm live birth (≤37w)22 (45%)11 (65%)ns15 (26%)38 (23%)nsPregnancy losses (abortion and miscarriages)12 (24%)0 (0%)0.0278 (14%) 17 (10%)nsDisclosure of Interests:None declared

scholarly journals Women with a History of Recurrent Pregnancy Loss Are a High-Risk Population for Adverse Obstetrical Outcome: A Retrospective Cohort Study

2021 ◽  
Vol 10 (2) ◽  
pp. 179
Author(s):  
Emma Rasmark Roepke ◽  
Ole Bjarne Christiansen ◽  
Karin Källén ◽  
Stefan R. Hansson
Keyword(s):  
Cohort Study ◽  
Preterm Birth ◽  
Pregnancy Complications ◽  
Pregnancy Loss ◽  
Recurrent Pregnancy Loss ◽  
Placental Abruption ◽  
Late Pregnancy ◽  
High Risk Population ◽  
Risk Population ◽  
Increased Risk

Recurrent pregnancy loss (RPL), defined as three or more consecutive miscarriages, is hypothesized to share some of the same pathogenic factors as placenta-associated disorders. It has been hypothesized that a defect implantation causes pregnancy loss, while a partially impaired implantation may lead to late pregnancy complications. The aim of this retrospective register-based cohort study was to study the association between RPL and such disorders including pre-eclampsia, stillbirth, small for gestational age (SGA) birth, preterm birth and placental abruption. Women registered with childbirth(s) in the Swedish Medical Birth Register (MFR) were included in the cohort. Pregnancies of women diagnosed with RPL (exposed) in the National Patient Register (NPR), were compared with pregnancies of women without RPL (unexposed/reference). Obstetrical outcomes, in the first pregnancy subsequent to the diagnosis of RPL (n = 4971), were compared with outcomes in reference-pregnancies (n = 57,410). Associations between RPL and placental dysfunctional disorders were estimated by odds ratios (AORs) adjusting for confounders, with logistic regression. RPL women had an increased risk for pre-eclampsia (AOR 1.45; 95% CI; 1.24–1.69), stillbirth <37 gestational weeks (GWs) (AOR 1.92; 95% CI; 1.22–3.02), SGA birth (AOR 1.97; 95% CI; 1.42–2.74), preterm birth (AOR 1.46; 95% CI; 1.20–1.77), and placental abruption <37 GWs (AOR 2.47; 95% CI; 1.62–3.76) compared with pregnancies by women without RPL. Women with RPL had an increased risk of pregnancy complications associated with placental dysfunction. This risk population is, therefore, in need of improved antenatal surveillance.

Antiphosphatidylserine/prothrombin Antibodies in Antiphospholipid Syndrome with Intrauterine Growth Restriction and Preeclampsia

2018 ◽  
Vol 45 (9) ◽  
pp. 1263-1272 ◽  
Author(s):  
Valentina Canti ◽  
Stefania Del Rosso ◽  
Marta Tonello ◽  
Roberta Lucianò ◽  
Ariela Hoxha ◽  
...  
Keyword(s):  
Antiphospholipid Syndrome ◽  
Lupus Erythematosus ◽  
Pregnancy Complications ◽  
Intrauterine Growth Restriction ◽  
Late Pregnancy ◽  
Additional Treatment ◽  
Growth Restriction ◽  
Intrauterine Fetal Death ◽  
Thrombotic Risk ◽  
Intrauterine Growth

Objective.Antibodies that recognize the phosphatidylserine/prothrombin complex (antiphosphatidylserine/prothrombin antibodies; aPS/PT) might reveal enhanced thrombotic risk in patients with systemic lupus erythematosus. Little is known about their association with pregnancy complications in the antiphospholipid syndrome (APS).Methods.We enrolled 55 patients with APS who were seeking pregnancy in 2 Italian hospitals. Antiphospholipid antibodies (aPL), including anticardiolipin antibodies, anti-β2-glycoprotein I antibodies, lupus-like anticoagulant, and aPS/PT antibodies were assessed, and the patients were prospectively followed for 24 months.Results.There were 65% (36/55) of the APS patients who had aPS/PT antibodies. Forty-seven pregnancies were followed, including 33 of aPS/PT+ patients. Forty-one of the 47 patients (87%) who initiated a pregnancy eventually gave birth to a child. The pregnancy duration and the mean newborn weight at delivery were significantly lower in aPS/PT+ than in aPS/PT− patients (33.1 ± 4.7 vs 36.2 ± 3.4 wks of gestation, respectively, and 2058 ± 964 g vs 2784 ± 746 g, respectively, p < 0.05). Late pregnancy complications, including intrauterine fetal death, preterm delivery, preeclampsia, and intrauterine growth restriction (IUGR), were more frequent in aPS/PT+ patients, independent of the therapy. Titers of aPS/PT IgG were significantly inversely correlated with the neonatal weight at delivery. Vascular injury, as reflected by thrombosis, fibrinoid necrosis, ischemic and hemorrhagic areas, and presence of chorangiomas characterized the IUGR placentas in the presence of aPS/PT.Conclusion.The aPS/PT antibodies might represent markers of aPL-related pregnancy complications, IUGR/preeclampsia in particular, and could help identify beforehand patients who may require additional treatment.

Generic Prescribing, Generic Substitution, and Therapeutic Substitution

PEDIATRICS ◽  
1987 ◽  
Vol 79 (5) ◽  
pp. 835-835
Author(s):  
Keyword(s):  
Health Care ◽  
Health Care Professionals ◽  
Generic Substitution ◽  
Drug Product ◽  
Therapeutic Substitution ◽  
General Acceptance ◽  
Conflicting Evidence ◽  
Therapeutic Category ◽  
Generic Prescribing ◽  
The Cost

Pressures generated by a constellation of professional consumer, legislative, and health care provider vider groups in this era of increasing health care costs have led to enactment of generic substitution laws in 50 states. The general acceptance of this concept, despite conflicting evidence that it has reduced the cost of prescription items to the consumer, has led to the concept of therapeutic substitution. Considerable confusion exists among health care professionals regarding the precise meaning of these concepts. Generic prescribing is the prescribing of a drug by a physician using the generic name. This leaves the choice of brand to the dispensing pharmacist. Generic substitution is a pharmacist-initiated act by which a different brand or an unbranded drug product is dispensed instead of a drug brand that was prescribed by the physician. This means substituting the same chemical entity in the same dosage form for one marketed by a different company. Therapeutic substitution is a pharmacist-initiated act by which a pharmaceutical or therapeutic alternate for the physician-prescribed drug is dispensed without consulting the physician. This denotes replacement of the prescribed drug with a chemically different drug within the same therapeutic category, eg, hydrochlorothiazide for furosemide; ranitidine for cimetidine; chloramphenicol for erythromycin. In 1976, the AAP Committee on Drugs published a commentary in Pediatrics (1976;57:275-277) on generic prescribing and concluded that "the lack of data on bioavailability and bioequivalence in children precludes blanket support of generic prescribing for infants and children." The Committee recently reviewed this issue and concluded that the situation has changed little during the past decade.

scholarly journals Chromosomal abnormalities in recurrent miscarriages by conventional karyotyping analysis

2018 ◽  
Vol 18 (2) ◽  
pp. 265-276 ◽  
Author(s):  
Alessandra Bernadete Trovó de Marqui
Keyword(s):  
Genetic Counseling ◽  
Chromosomal Abnormality ◽  
Pregnancy Loss ◽  
Chromosomal Abnormalities ◽  
Recurrent Miscarriage ◽  
Virtual Library ◽  
Reciprocal Translocations ◽  
Recurrent Miscarriages ◽  
Monosomy X ◽  
Products Of Conception

Abstract Objectives: to describe the prevalence and types of chromosomal abnormalities in couples with recurrent miscarriage and products of conception. Methods: electronic searches were performed in the PubMed/Medline database and in the Portal Regional da Biblioteca Virtual em Saúde/BVS (Regional Website of the Virtual Library in Health/BVS) using the descriptors “chromosomal abnormalities and abortions and prevalence”. After applying the inclusion and exclusion criterias, 17 studies were selected. Results: 11 studies were conducted in couples with recurrent miscarriage and six in products of conception. The main results of the couples with recurrent miscarriage were: the frequency of chromosomal abnormalities which varied from 1.23% to 12% and there was a predominance alteration of the chromosomal structures (reciprocal translocations, followed by Robertsonian). In products of conception, the results observed were: the frequency of chromosomal abnormality was above 50% in approximately 70% of the studies; there was a predominance alteration of the numerical chromosomal (trisomy - chromosomes 16, 18, 21 and 22, followed by polyploidy and monosomy X). Conclusions: in summary, cytogenetic alterations represent an importante cause of pregnancy loss and its detection can help couples with genetic counseling. Therefore, the value of knowledge on the prevalence of cytogenetic abnormalities in miscarriage samples is unquestionable, once it is permitted a proper genetic counseling for the couple.

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