FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2113736324> ?p ?o ?g. }

• W2113736324 endingPage "2440" @default.
• W2113736324 startingPage "2437" @default.
• W2113736324 abstract "Antiphospholipid syndrome patients with recurrent miscarriage have an impairment in fibrinolysis demonstrated by prolonged clot lysis time (CLT) that cannot be attributed to differences in thrombin activatable fibrinolysis inhibitor (TAFI) antigen levels. Patients with unexplained recurrent miscarriage have an impairment in fibrinolysis demonstrated by increased CLT, that can be at least partly explained by higher TAFI antigen levels. Antiphospholipid syndrome patients with recurrent miscarriage have an impairment in fibrinolysis demonstrated by prolonged clot lysis time (CLT) that cannot be attributed to differences in thrombin activatable fibrinolysis inhibitor (TAFI) antigen levels. Patients with unexplained recurrent miscarriage have an impairment in fibrinolysis demonstrated by increased CLT, that can be at least partly explained by higher TAFI antigen levels. Normal pregnancy is associated with changes in all aspects of hemostasis, including an increase in concentrations of most clotting factors, a decrease in the concentrations of some of the natural anticoagulants, and a reduction in overall fibrinolytic activity (1Bremme K.A. Haemostatic changes in pregnancy.Best Pract Res Clin Haematol. 2003; 16: 153-168Abstract Full Text Full Text PDF PubMed Scopus (339) Google Scholar, 2Brenner B. Haemostatic changes in pregnancy.Thromb Res. 2004; 114: 409-414Abstract Full Text Full Text PDF PubMed Scopus (427) Google Scholar). These changes help to maintain placental function during pregnancy and to meet the hemostatic challenge of delivery but may predispose the woman to thrombosis and placental vascular complications (1Bremme K.A. Haemostatic changes in pregnancy.Best Pract Res Clin Haematol. 2003; 16: 153-168Abstract Full Text Full Text PDF PubMed Scopus (339) Google Scholar, 2Brenner B. Haemostatic changes in pregnancy.Thromb Res. 2004; 114: 409-414Abstract Full Text Full Text PDF PubMed Scopus (427) Google Scholar). Thus, evidence has been accumulating to suggest that some cases of recurrent miscarriage (RM) are the result of an exaggerated hemostatic response during pregnancy, resulting in thrombosis of the uteroplacental vasculature and subsequent fetal loss (3Preston F.E. Rosendaal F.R. Walker I.D. Briet E. Berntorp E. Conard J. et al.Increased fetal loss in women with heritable thrombophilia.Lancet. 1996; 348: 913-916Abstract Full Text Full Text PDF PubMed Scopus (616) Google Scholar, 4Rai R. Is miscarriage a coagulopathy?.Curr Opin Obstet Gynecol. 2003; 15: 265-268Crossref PubMed Scopus (31) Google Scholar). Although thrombophilias are debated as a cause of early RM, in the recent literature both acquired and genetic thrombotic conditions are considered to be associated with increased RM (3Preston F.E. Rosendaal F.R. Walker I.D. Briet E. Berntorp E. Conard J. et al.Increased fetal loss in women with heritable thrombophilia.Lancet. 1996; 348: 913-916Abstract Full Text Full Text PDF PubMed Scopus (616) Google Scholar, 4Rai R. Is miscarriage a coagulopathy?.Curr Opin Obstet Gynecol. 2003; 15: 265-268Crossref PubMed Scopus (31) Google Scholar, 5Patnaik M.M. Haddad T. Morton C.T. Pregnancy and thrombophilia.Expert Rev Cardiovasc Ther. 2007; 5: 753-765Crossref PubMed Scopus (28) Google Scholar).The antiphospholipid syndrome (APS) is a common acquired prothrombotic condition characterized by vascular thrombosis and pregnancy morbidity in association with persistently positive circulating antiphospholipid (aPL) (6Miyakis S. Lockshin M.D. Atsumi T. Branch D.W. Brey R.L. Cervera R. et al.International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS).J Thromb Haemost. 2006; 4: 295-306Crossref PubMed Scopus (4989) Google Scholar). We previously reported that these antibodies are detected in 10% of patients with RM (7Balasch J. Creus M. Fabregues F. Reverter J.C. Carmona F. Tassies D. et al.Antiphospholipid antibodies and human reproductive failure.Hum Reprod. 1996; 11: 2310-2315Crossref PubMed Scopus (86) Google Scholar) and they have emerged as one of the most common causes of this reproductive complication (8Vinatier D. Dufour P. Cosson M. Houpeau J.L. Antiphospholipid syndrome and recurrent miscarriages.Eur J Obstet Gynecol Reprod Biol. 2001; 96: 37-50Abstract Full Text Full Text PDF PubMed Scopus (93) Google Scholar). A number of mechanisms by which aPL may promote thrombotic events have been proposed, most of which involve the disturbance of the coagulation pathway and the cells that control them (9Mackworth-Young C.G. Antiphospholipid syndrome: multiple mechanisms.Clin Exp Immunol. 2004; 136: 393-401Crossref PubMed Scopus (99) Google Scholar, 10Pierangeli S.S. Chen P.P. Raschi E. Scurati S. Grossi C. Borghi M.O. et al.Antiphospholipid antibodies and the antiphospholipid syndrome: pathogenic mechanisms.Semin Thromb Hemost. 2008; 34: 236-250Crossref PubMed Scopus (182) Google Scholar). Reduced fibrinolytic activity has been described in APS patients and may be responsible for thrombotic events (11Espinosa G. Cervera R. Font J. Shoenfeld Y. Antiphospholipid syndrome: pathogenic mechanisms.Autoimmunity Rev. 2003; 2: 86-93Crossref PubMed Scopus (68) Google Scholar, 12Forastiero R. Martinuzzo M. Prothombotic mechanisms based on the impairment of fibrinolysis in the antiphospholipid syndrome.Lupus. 2008; 17: 872-877Crossref PubMed Scopus (20) Google Scholar).Thrombin activatable fibrinolysis inhibitor (TAFI) is a main inhibitor of fibrinolysis and a known contributing factor in the development of thrombotic events (13Bouma B.N. Meijers J.C. Thombin-activatable fibrinolysis inhibitor (TAFI, plasma procarboxypeptidase B, procarboxypeptidase R, procarboxypectidase U).J Thromb Haemost. 2003; 1: 1566-1574Crossref PubMed Scopus (149) Google Scholar). Several polymorphisms have been identified in the TAFI gene (14Franco R.F. Fagundes M.G. Meijers J.C. Reitsma P.H. Lourenco D. Morelli V. et al.Identification of polymorphisms in the 5'-untranslated region of the TAFI gene: relationship with plasma TAFI levels and risk of venous thrombosis.Haematologica. 2001; 86: 510-517PubMed Google Scholar, 15Henry M. Aubert H. Morange P.E. Nanni I. Alessi M.C. Tiret L. et al.Identification of polymorphisms in the promoter and the 3' region of the TAFI gene: evidence that plasma TAFI antigen levels are strongly genetically controlled.Blood. 2001; 97: 2053-2058Crossref PubMed Scopus (140) Google Scholar). Among TAFI polymorphisms, +505A/G and +1542C/G (15Henry M. Aubert H. Morange P.E. Nanni I. Alessi M.C. Tiret L. et al.Identification of polymorphisms in the promoter and the 3' region of the TAFI gene: evidence that plasma TAFI antigen levels are strongly genetically controlled.Blood. 2001; 97: 2053-2058Crossref PubMed Scopus (140) Google Scholar) have been the most thoroughly studied, and strong associations have been reported between these polymorphisms and plasma concentrations of TAFI (14Franco R.F. Fagundes M.G. Meijers J.C. Reitsma P.H. Lourenco D. Morelli V. et al.Identification of polymorphisms in the 5'-untranslated region of the TAFI gene: relationship with plasma TAFI levels and risk of venous thrombosis.Haematologica. 2001; 86: 510-517PubMed Google Scholar, 15Henry M. Aubert H. Morange P.E. Nanni I. Alessi M.C. Tiret L. et al.Identification of polymorphisms in the promoter and the 3' region of the TAFI gene: evidence that plasma TAFI antigen levels are strongly genetically controlled.Blood. 2001; 97: 2053-2058Crossref PubMed Scopus (140) Google Scholar). Both TAFI levels and TAFI polymorphisms have been related to arterial and venous thrombosis. Routine laboratory assays of fibrinolytic factors provide static data and therefore have been of limited diagnostic use. Overall coagulation assays provide a source of information that assesses changes over time in the balance of the fibrinolytic system (16Curnow J.L. Morel-Kopp M.-C. Roddie C. Aboud M. Ward C.M. Reduced fibrinolysis and increased fibrin generation can be detected in hypercoagulable patients using the overall hemostatic potential assay.J Thromb Haemost. 2006; 5: 528-534Crossref PubMed Scopus (47) Google Scholar). Impaired fibrinolysis increases clot lysis time (CLT) and elevated TAFI antigen levels may contribute to this in part (17Wang W. Boffa M.B. Bajzar L. Walker J.B. Nesheim M.E. A study of the mechanism of fibrinolysis by activated thrombin–activatable fibrinolysis inhibitor.J Biol Chem. 1998; 273: 27176-27181Crossref PubMed Scopus (361) Google Scholar).A few studies have investigated TAFI levels (18Folkeringa N. Korteweg F.J. Veeger N.J.G.M. Middeldorp S. Hamulyak K. Prins M.H. et al.Thrombin activatable fibrinolysis inhibitor (TAFI) is not associated with fetal loss, a retrospective study.Thromb Res. 2009; 123: 511-514Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar, 19Knol H.M. Veeger N.J.G.M. Middeldorp S. Hamulyak K. Van der Meer J. High thrombin–activatable fibrinolysis inhibitor levels may protect against recurrent fetal loss.J Thromb Haemost. 2009; 7: 903-906Crossref PubMed Scopus (11) Google Scholar), TAFI polymorphisms (20Masini S. Ticconi C. Gravina P. Tomassini M. Pietropolli A. Forte V. et al.Thrombin–activatable fibrinolysis inhibitor polymorphisms and recurrent pregnancy loss.Fertil Steril. 2009; 92: 694-702Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar), and overall fibrinolytic capacity (21Gris J.C. Schved J.F. Neveu S. Mares P. Aguilar-Martinez P. Dupaigne D. Impaired fibrinolytic capacity and early recurrent spontaneous abortion.BMJ. 1990; 300: 1500Crossref PubMed Scopus (20) Google Scholar, 22Rai R. Tuddenham E. Backos M. Jivraj S. El'Gaddal S. Choy S. et al.Thromboelastography, whole-blood haemostasis and recurrent miscarriage.Hum Reprod. 2003; 12: 2540-2543Crossref Scopus (75) Google Scholar) in patients with unexplained RM, but to the best of our knowledge there has been no previous report on TAFI or CLT in patients with aPL as the cause of their RM. This case-control study is a retrospective analysis of prospectively collected material to analyze the association between TAFI plasma antigen levels, TAFI polymorphisms, and CLT in APS patients with ≥3 RM (APS group). To this end, two control groups of patients were used: patients with ≥3 unexplained RM (uRM group) and fertile controls (group C).A total of 246 women were prospectively recruited at the Department of Gynecology at the Hospital Clínic of Barcelona from September 2003 to October 2007. All the women included gave informed consent to participate in the study, which was approved by the ethics committee of our hospital. The study group consisted of 63 women aged 27 to 39 years (mean ± standard deviation [SD], 33.4 ± 4.1 years) who had been previously diagnosed with primary APS and had ≥3 consecutive first trimester spontaneous abortions (APS group). The diagnosis of APS was based on the international consensus statement of the classification criteria for definite APS (6Miyakis S. Lockshin M.D. Atsumi T. Branch D.W. Brey R.L. Cervera R. et al.International consensus statement on an update of the classification criteria for definite antiphospholipid syndrome (APS).J Thromb Haemost. 2006; 4: 295-306Crossref PubMed Scopus (4989) Google Scholar). The uRM patients who tested negative for the lupus anticoagulant and anticardiolipin antibodies were checked for the presence of β2 glycoprotein-I antibodies and all were seronegative.The first control group included 119 women aged 27 to 38 years (mean ± SD, 34.8 ± 4.1 years) with ≥3 consecutive first trimester spontaneous abortions of unknown etiology (uRM group). Nine patients in the APS group (14%) and 22 patients in the uRM group (18%) had previous successful pregnancies before RM. All patients were routinely screened according to a diagnostic work-up previously reported elsewhere (7Balasch J. Creus M. Fabregues F. Reverter J.C. Carmona F. Tassies D. et al.Antiphospholipid antibodies and human reproductive failure.Hum Reprod. 1996; 11: 2310-2315Crossref PubMed Scopus (86) Google Scholar, 23Creus M. Calafell J.M. Civico S. Fabregues F. Carmona F. Vanrell J.A. et al.Materno-fetal immunogenetic disparity: the biological basis for in vitro fertilization treatment in patients with unexplained recurrent abortion?.Am J Reprod Immunol. 2003; 50: 420-426Crossref PubMed Scopus (7) Google Scholar) and were found to be normal for known causes of RM (except aPL in patients in the APS group). Fifty-two additional patients were excluded from participation in this study because any abnormality (apart from aPL) in the diagnostic workup for RM was found.The second control group was composed of 64 women (group C) aged 25 to 37 years (mean ± SD, 32.7 ± 3.9 years) who were selected on the basis of clinical health, having at least one healthy child after an uneventful pregnancy, and having no history of pregnancy loss. Controls were frequency matched in 5-year age groups to patients. No other characteristics were considered in this respect.No patient had taken medications known to affect plasma CLT for ≥8 weeks before the study. Blood samples for coagulation and fibrinolysis studies and genotype studies were obtained, stored, and evaluated as previously reported elsewhere (15Henry M. Aubert H. Morange P.E. Nanni I. Alessi M.C. Tiret L. et al.Identification of polymorphisms in the promoter and the 3' region of the TAFI gene: evidence that plasma TAFI antigen levels are strongly genetically controlled.Blood. 2001; 97: 2053-2058Crossref PubMed Scopus (140) Google Scholar, 24Brandt J.T. Triplett D.A. Alving B. Scharrer I. Criteria the diagnosis of lupus anticoagulant: an update. Subcommittee on Lupus Anticoagulant/Antiphospholipid Antibody of the Scientific and Standardisation Committee of the ISTH.Thromb Haemost. 1995; 74: 1185-1190Crossref PubMed Scopus (1294) Google Scholar, 25Gils A. Alessi M.C. Browers E. Peeters M. Marx P. Leurs J. et al.Development of a genotype 325-specific proCPU/TAFI ELISA.Arterioscler Thromb Vasc Biol. 2003; 23: 1122-1127Crossref PubMed Scopus (81) Google Scholar, 26Meltzer M.E. Doggen C.J. de Groot P.G. Rosendaal F.R. Lisman T. Reduced plasma fibrinolytic capacity as a potential risk factor for a first myocardial infarction in young men.Br J Haematol. 2009; 145: 121-127Crossref PubMed Scopus (56) Google Scholar, 27Martínez-Zamora M.A. Tassies D. Carmona F. Espinosa G. Cervera R. Reverter J.C. et al.Thrombin activatable fibrinolysis inhibitor (TAFI) and clot lysis time (CLT) in pregnant patients with antiphospholipid syndrome (APS): relationship with pregnancy outcome and thrombosis.Am J Reprod Immunol. 2009; 62: 381-389Crossref PubMed Scopus (9) Google Scholar, 28Levine J.S. Rauch J. Branch D.W. Anti-phospholipid syndrome.N Engl J Med. 2002; 346: 752-763Crossref PubMed Scopus (1310) Google Scholar).Statistical analysis was performed with the SPSS 15.0 for Windows (SPSS, Chicago, IL). Comparison of quantitative variables was performed using analysis of variance (ANOVA) with Bonferroni's post hoc analysis. Comparison of qualitative variables was carried out using the chi-square test. P<.05 was considered statistically significant. Results are presented as mean ± SD.The mean age, number of previous pregnancy losses, and mean gestational age at pregnancy loss were similar in the three groups studied (data not shown). As expected, women in the APS and uRM groups had more previous pregnancies compared with group C (3.9 ± 4, 4.3 ± 17, and 1.4 ± 3, respectively), but no differences were observed between the APS and uRM groups in this respect.Figure 1 shows TAFI antigen levels and CLT values in the three groups studied. The TAFI antigen levels were statistically significantly higher in the uRM group compared with the other two groups. The CLT was statistically significantly longer in the APS and uRM groups compared with group C. The allele distribution of TAFI polymorphisms was similar within the three groups studied; the TAFI antigen levels were found to be as expected considering each allele (14Franco R.F. Fagundes M.G. Meijers J.C. Reitsma P.H. Lourenco D. Morelli V. et al.Identification of polymorphisms in the 5'-untranslated region of the TAFI gene: relationship with plasma TAFI levels and risk of venous thrombosis.Haematologica. 2001; 86: 510-517PubMed Google Scholar, 15Henry M. Aubert H. Morange P.E. Nanni I. Alessi M.C. Tiret L. et al.Identification of polymorphisms in the promoter and the 3' region of the TAFI gene: evidence that plasma TAFI antigen levels are strongly genetically controlled.Blood. 2001; 97: 2053-2058Crossref PubMed Scopus (140) Google Scholar), and were higher in genotypes +1542 GG and +505 AA (data not shown).Although the association of aPL antibodies with pregnancy loss and pregnancy morbidity is widely accepted, its mechanisms remain unknown (28Levine J.S. Rauch J. Branch D.W. Anti-phospholipid syndrome.N Engl J Med. 2002; 346: 752-763Crossref PubMed Scopus (1310) Google Scholar). Impaired fibrinolysis has been one of pathogenic mechanisms proposed (27Martínez-Zamora M.A. Tassies D. Carmona F. Espinosa G. Cervera R. Reverter J.C. et al.Thrombin activatable fibrinolysis inhibitor (TAFI) and clot lysis time (CLT) in pregnant patients with antiphospholipid syndrome (APS): relationship with pregnancy outcome and thrombosis.Am J Reprod Immunol. 2009; 62: 381-389Crossref PubMed Scopus (9) Google Scholar, 29Carmona F. Lazaro I. Reverter J.C. Tassies D. Font J. Cervera R. et al.Impaired factor XIIa-dependent activation of fibrinolysis in treated antiphospholipid syndrome gestations developing late-pregnancy complications.Am J Obstet Gynecol. 2006; 194: 457-465Abstract Full Text Full Text PDF PubMed Scopus (17) Google Scholar). Previous work in recent literature has focused on fibrinolytic defects and RM (18Folkeringa N. Korteweg F.J. Veeger N.J.G.M. Middeldorp S. Hamulyak K. Prins M.H. et al.Thrombin activatable fibrinolysis inhibitor (TAFI) is not associated with fetal loss, a retrospective study.Thromb Res. 2009; 123: 511-514Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar, 19Knol H.M. Veeger N.J.G.M. Middeldorp S. Hamulyak K. Van der Meer J. High thrombin–activatable fibrinolysis inhibitor levels may protect against recurrent fetal loss.J Thromb Haemost. 2009; 7: 903-906Crossref PubMed Scopus (11) Google Scholar, 20Masini S. Ticconi C. Gravina P. Tomassini M. Pietropolli A. Forte V. et al.Thrombin–activatable fibrinolysis inhibitor polymorphisms and recurrent pregnancy loss.Fertil Steril. 2009; 92: 694-702Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar, 21Gris J.C. Schved J.F. Neveu S. Mares P. Aguilar-Martinez P. Dupaigne D. Impaired fibrinolytic capacity and early recurrent spontaneous abortion.BMJ. 1990; 300: 1500Crossref PubMed Scopus (20) Google Scholar, 22Rai R. Tuddenham E. Backos M. Jivraj S. El'Gaddal S. Choy S. et al.Thromboelastography, whole-blood haemostasis and recurrent miscarriage.Hum Reprod. 2003; 12: 2540-2543Crossref Scopus (75) Google Scholar, 30Sotiriadis A. Makrigiannakis A. Stefos T. Paraskevaidis E. Kalantaridou S.N. Fibrinolytic defects and recurrent miscarriage: a systematic review and meta-analysis.Obstet Gynecol. 2007; 109: 1146-1155Crossref PubMed Scopus (50) Google Scholar). Remarkably, there are no eligible studies for TAFI, and data on other factors have either failed to show an association or were quite limited (30Sotiriadis A. Makrigiannakis A. Stefos T. Paraskevaidis E. Kalantaridou S.N. Fibrinolytic defects and recurrent miscarriage: a systematic review and meta-analysis.Obstet Gynecol. 2007; 109: 1146-1155Crossref PubMed Scopus (50) Google Scholar). High TAFI levels in RM patients without aPL have been proposed as a protective factor against miscarriage (18Folkeringa N. Korteweg F.J. Veeger N.J.G.M. Middeldorp S. Hamulyak K. Prins M.H. et al.Thrombin activatable fibrinolysis inhibitor (TAFI) is not associated with fetal loss, a retrospective study.Thromb Res. 2009; 123: 511-514Abstract Full Text Full Text PDF PubMed Scopus (12) Google Scholar, 19Knol H.M. Veeger N.J.G.M. Middeldorp S. Hamulyak K. Van der Meer J. High thrombin–activatable fibrinolysis inhibitor levels may protect against recurrent fetal loss.J Thromb Haemost. 2009; 7: 903-906Crossref PubMed Scopus (11) Google Scholar). This is in contrast with the results of our study in which higher TAFI antigen levels were observed in the uRM group.Discrepancies between the previous reports and our study may be accounted for in several ways. As noted by the investigators themselves, those studies were retrospective, the clinical characteristics of the patients were ill-defined, and systematic research for other causes of RM was not performed; thus, selection bias may have been introduced. Only two previous studies have investigated the overall fibrinolytic capacity of RM patients without aPL, and both reports concluded that impaired fibrinolysis could be a risk factor for thrombosis in future untreated pregnancies (21Gris J.C. Schved J.F. Neveu S. Mares P. Aguilar-Martinez P. Dupaigne D. Impaired fibrinolytic capacity and early recurrent spontaneous abortion.BMJ. 1990; 300: 1500Crossref PubMed Scopus (20) Google Scholar, 22Rai R. Tuddenham E. Backos M. Jivraj S. El'Gaddal S. Choy S. et al.Thromboelastography, whole-blood haemostasis and recurrent miscarriage.Hum Reprod. 2003; 12: 2540-2543Crossref Scopus (75) Google Scholar). This is in keeping with our study, in which longer CLT in the uRM group was found.Genetic factors may explain between 20% and 62% of the variation in TAFI antigen levels, but the relationships among TAFI polymorphisms, TAFI antigen levels, and the risk of thrombotic complications are not well understood (21Gris J.C. Schved J.F. Neveu S. Mares P. Aguilar-Martinez P. Dupaigne D. Impaired fibrinolytic capacity and early recurrent spontaneous abortion.BMJ. 1990; 300: 1500Crossref PubMed Scopus (20) Google Scholar, 22Rai R. Tuddenham E. Backos M. Jivraj S. El'Gaddal S. Choy S. et al.Thromboelastography, whole-blood haemostasis and recurrent miscarriage.Hum Reprod. 2003; 12: 2540-2543Crossref Scopus (75) Google Scholar). We found no differences between groups in the distribution of alleles of the two investigated. This is in contrast with the report by Masini et al. (20Masini S. Ticconi C. Gravina P. Tomassini M. Pietropolli A. Forte V. et al.Thrombin–activatable fibrinolysis inhibitor polymorphisms and recurrent pregnancy loss.Fertil Steril. 2009; 92: 694-702Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar) that concluded that some single nucleotide polymorphisms could be associated with a reduced risk of RM. However, as stressed by the investigators (20Masini S. Ticconi C. Gravina P. Tomassini M. Pietropolli A. Forte V. et al.Thrombin–activatable fibrinolysis inhibitor polymorphisms and recurrent pregnancy loss.Fertil Steril. 2009; 92: 694-702Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar), further investigation is needed to also evaluate TAFI antigen levels and CLT in patients with RM to better understand the actual role of TAFI antigen levels in RM. We examined this issue and, in addition, included only patients with ≥3 miscarriages of unknown etiology whereas Masini et al. (20Masini S. Ticconi C. Gravina P. Tomassini M. Pietropolli A. Forte V. et al.Thrombin–activatable fibrinolysis inhibitor polymorphisms and recurrent pregnancy loss.Fertil Steril. 2009; 92: 694-702Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar) included patients with ≥2 abortions and as many as 45% of patients had at least one definite cause of RM detected in the diagnostic work-up.Our results show increased TAFI antigen levels in uRM patients compared with fertile controls, thereby adding further evidence to support the previous work favoring a role of TAFI antigen levels in RM (20Masini S. Ticconi C. Gravina P. Tomassini M. Pietropolli A. Forte V. et al.Thrombin–activatable fibrinolysis inhibitor polymorphisms and recurrent pregnancy loss.Fertil Steril. 2009; 92: 694-702Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar). Notwithstanding, our study found that increased CLT was associated with higher TAFI antigen levels in the uRM but not the APS group. Similarly, we have reported impaired fibrinolysis to be associated with normal TAFI antigen levels in APS pregnant patients with late obstetric complications (27Martínez-Zamora M.A. Tassies D. Carmona F. Espinosa G. Cervera R. Reverter J.C. et al.Thrombin activatable fibrinolysis inhibitor (TAFI) and clot lysis time (CLT) in pregnant patients with antiphospholipid syndrome (APS): relationship with pregnancy outcome and thrombosis.Am J Reprod Immunol. 2009; 62: 381-389Crossref PubMed Scopus (9) Google Scholar). These findings can be explained on the basis that the contribution of TAFI antigen levels to CLT is limited, despite an association between these two parameters (31Lisman T. deGroot P.G. Meijers J.C.M. Rosendaal F.R. Reduced plasma fibrinolytic potential is a risk for venous thrombosis.Blood. 2005; 105: 1102-1105Crossref PubMed Scopus (214) Google Scholar). On the other hand, it should be emphasized that the pathogenesis of pregnancy complications in APS is multifactorial (10Pierangeli S.S. Chen P.P. Raschi E. Scurati S. Grossi C. Borghi M.O. et al.Antiphospholipid antibodies and the antiphospholipid syndrome: pathogenic mechanisms.Semin Thromb Hemost. 2008; 34: 236-250Crossref PubMed Scopus (182) Google Scholar, 11Espinosa G. Cervera R. Font J. Shoenfeld Y. Antiphospholipid syndrome: pathogenic mechanisms.Autoimmunity Rev. 2003; 2: 86-93Crossref PubMed Scopus (68) Google Scholar, 12Forastiero R. Martinuzzo M. Prothombotic mechanisms based on the impairment of fibrinolysis in the antiphospholipid syndrome.Lupus. 2008; 17: 872-877Crossref PubMed Scopus (20) Google Scholar), and that disruption of fibrinolysis is just one of multiple pathophysiologic mechanisms for thrombotic events in pregnant patients.Our study has two possible limitations. The one is that the sample size was decided arbitrarily but in keeping with a recent study investigating TAFI polymorphisms in RM patients without the APS (20Masini S. Ticconi C. Gravina P. Tomassini M. Pietropolli A. Forte V. et al.Thrombin–activatable fibrinolysis inhibitor polymorphisms and recurrent pregnancy loss.Fertil Steril. 2009; 92: 694-702Abstract Full Text Full Text PDF PubMed Scopus (26) Google Scholar). However, our study included a sufficient number of patients to avoid chance findings (type 1 error) and to avoid missing the detection of a true difference (type 2 error) when comparing CLT in APS and uRM groups with controls, as well as when TAFI antigen levels were compared between the APS versus uRM groups and the uRM versus C groups. On the other hand, considering the differences in CLT values and TAFI antigen levels observed in our study, a sample size of 436 and 914 patients per group would be necessary to provide 80% statistical power for avoiding a type 2 error, and a 5% chance of making a type 1 error when comparing CLT values between APS and uRM groups and TAFI antigen levels between APS and C groups, respectively.In addition, a common drawback to most studies on potential etiologic factors in uRM patients is that the most common cause of miscarriage is aneuploidy. The study of products of conception is mandatory to rule out the possibility that patients had aneuploidy pregnancies. Cytogenetic analysis of miscarriages was not available for the specific purposes of our investigation. However, the rationale for abortus tissue karyotyping is that if the abortus is aneuploid the physician may conclude that a maternal cause of pregnancy loss is excluded. Moreover, an abnormal abortus karyotype is a legitimate explanation for the loss that may provide a source of comfort to the couple. However, as stressed by the American College of Obstetricians and Gynecologists (32American College of Obstetricians and GynecologistsManagement of recurrent early pregnancy loss. ACOG Practice Bulletin.Int J Gynecol Obstet. 2002; 78: 179-190Abstract Full Text PDF PubMed Scopus (187) Google Scholar), no published evidence supports these hypotheses, and definite recommendations for routinely obtaining abortus karyotypes cannot be made. In addition, maternally rather than fetally caused RM is primarily observed in young women (≤35 years) (33Christiansen O.B. Steffensen R. Nielsen H.S. Varming K. Multifactorial etiology of recurrent miscarriage and its scientific and clinical implications.Gynecol Obstet Invest. 2008; 66: 257-267Crossref PubMed Scopus (126) Google Scholar), and as many as 81% and 87% of the women in our APS and uRM groups, respectively, were younger than 35 years.Patients with RM associated with APS and uRM patients have an impairment in fibrinolysis demonstrated by prolonged CLT. These fibrinolytic changes can be partially attributed to differences in TAFI antigen levels in uRM patients but not in APS patients. To the best of our knowledge, this has not been previously reported. Therefore, further studies are warranted to confirm or refute our findings. Normal pregnancy is associated with changes in all aspects of hemostasis, including an increase in concentrations of most clotting factors, a decrease in the concentrations of some of the natural anticoagulants, and a reduction in overall fibrinolytic activity (1Bremme K.A. Haemostatic changes in pregnancy.Best Pract Res Clin Haematol. 2003; 16: 153-168Abstract Full Text Full Text PDF PubMed Scopus (339) Google Scholar, 2Brenner B. Haemostatic changes in pregnancy.Thromb Res. 2004; 114: 409-414Abstract Full Text Full Text PDF PubMed Scopus (427) Google Scholar). These changes help to maintain placental function during pregnancy and to meet the hemostatic challenge of delivery but may predispose the woman to thrombosis and placental vascular complications (1Bremme K.A. Haemostatic changes in pregnanc" @default.
• W2113736324 created "2016-06-24" @default.
• W2113736324 creator A5001454539 @default.
• W2113736324 creator A5021585513 @default.
• W2113736324 creator A5024010641 @default.
• W2113736324 creator A5037913108 @default.
• W2113736324 creator A5052172239 @default.
• W2113736324 creator A5062318976 @default.
• W2113736324 creator A5088523647 @default.
• W2113736324 date "2010-11-01" @default.
• W2113736324 modified "2023-10-14" @default.
• W2113736324 title "Thrombin activatable fibrinolysis inhibitor and clot lysis time in women with recurrent miscarriage associated with the antiphospholipid syndrome" @default.
• W2113736324 cites W1595015178 @default.
• W2113736324 cites W1980151434 @default.
• W2113736324 cites W1986551667 @default.
• W2113736324 cites W1988427772 @default.
• W2113736324 cites W1988933965 @default.
• W2113736324 cites W1990276742 @default.
• W2113736324 cites W1994709901 @default.
• W2113736324 cites W1997351227 @default.
• W2113736324 cites W2006049280 @default.
• W2113736324 cites W2011784685 @default.
• W2113736324 cites W2013629064 @default.
• W2113736324 cites W2016116321 @default.
• W2113736324 cites W2024804378 @default.
• W2113736324 cites W2027816304 @default.
• W2113736324 cites W2051175919 @default.
• W2113736324 cites W2054330426 @default.
• W2113736324 cites W2054650295 @default.
• W2113736324 cites W2055335489 @default.
• W2113736324 cites W2059863454 @default.
• W2113736324 cites W2073273161 @default.
• W2113736324 cites W2074735065 @default.
• W2113736324 cites W2077087361 @default.
• W2113736324 cites W2093618402 @default.
• W2113736324 cites W2118814376 @default.
• W2113736324 cites W2155963930 @default.
• W2113736324 cites W2156703397 @default.
• W2113736324 cites W2165177633 @default.
• W2113736324 cites W2167655122 @default.
• W2113736324 cites W3021852519 @default.
• W2113736324 cites W4296981399 @default.
• W2113736324 doi "https://doi.org/10.1016/j.fertnstert.2010.02.032" @default.
• W2113736324 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/20378110" @default.
• W2113736324 hasPublicationYear "2010" @default.
• W2113736324 type Work @default.
• W2113736324 sameAs 2113736324 @default.
• W2113736324 citedByCount "10" @default.
• W2113736324 countsByYear W21137363242012 @default.
• W2113736324 countsByYear W21137363242013 @default.
• W2113736324 countsByYear W21137363242014 @default.
• W2113736324 countsByYear W21137363242016 @default.
• W2113736324 countsByYear W21137363242021 @default.
• W2113736324 crossrefType "journal-article" @default.
• W2113736324 hasAuthorship W2113736324A5001454539 @default.
• W2113736324 hasAuthorship W2113736324A5021585513 @default.
• W2113736324 hasAuthorship W2113736324A5024010641 @default.
• W2113736324 hasAuthorship W2113736324A5037913108 @default.
• W2113736324 hasAuthorship W2113736324A5052172239 @default.
• W2113736324 hasAuthorship W2113736324A5062318976 @default.
• W2113736324 hasAuthorship W2113736324A5088523647 @default.
• W2113736324 hasBestOaLocation W21137363241 @default.
• W2113736324 hasConcept C126322002 @default.
• W2113736324 hasConcept C2776825266 @default.
• W2113736324 hasConcept C2776874634 @default.
• W2113736324 hasConcept C2777292125 @default.
• W2113736324 hasConcept C2779234561 @default.
• W2113736324 hasConcept C2779245376 @default.
• W2113736324 hasConcept C2780625311 @default.
• W2113736324 hasConcept C2780868729 @default.
• W2113736324 hasConcept C54355233 @default.
• W2113736324 hasConcept C71924100 @default.
• W2113736324 hasConcept C86803240 @default.
• W2113736324 hasConcept C89560881 @default.
• W2113736324 hasConceptScore W2113736324C126322002 @default.
• W2113736324 hasConceptScore W2113736324C2776825266 @default.
• W2113736324 hasConceptScore W2113736324C2776874634 @default.
• W2113736324 hasConceptScore W2113736324C2777292125 @default.
• W2113736324 hasConceptScore W2113736324C2779234561 @default.
• W2113736324 hasConceptScore W2113736324C2779245376 @default.
• W2113736324 hasConceptScore W2113736324C2780625311 @default.
• W2113736324 hasConceptScore W2113736324C2780868729 @default.
• W2113736324 hasConceptScore W2113736324C54355233 @default.
• W2113736324 hasConceptScore W2113736324C71924100 @default.
• W2113736324 hasConceptScore W2113736324C86803240 @default.
• W2113736324 hasConceptScore W2113736324C89560881 @default.
• W2113736324 hasIssue "6" @default.
• W2113736324 hasLocation W21137363241 @default.
• W2113736324 hasLocation W21137363242 @default.
• W2113736324 hasOpenAccess W2113736324 @default.
• W2113736324 hasPrimaryLocation W21137363241 @default.
• W2113736324 hasRelatedWork W115642794 @default.
• W2113736324 hasRelatedWork W2003410007 @default.
• W2113736324 hasRelatedWork W2023372748 @default.
• W2113736324 hasRelatedWork W2032016313 @default.
• W2113736324 hasRelatedWork W2050550374 @default.
• W2113736324 hasRelatedWork W2068559293 @default.
• W2113736324 hasRelatedWork W2098272040 @default.

• next