The procoagulant status. Hypercoagulability as a risk factor of primary and secondary infertility

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Abstract

Thrombophilia is a disorder that makes patients susceptible to intravascular thrombosis that may increase the risk of developing a pregnancy on a known pathology. The female patient diagnosed with hypoplastic uterus and hereditary thrombophilia had a favorable evolution under properly administered anticoagulant treatment. The homozygous status for the C677T mutation may lead to an increase in plasma homocysteine levels, especially in pregnant women, being an associated risk factor for thrombosis. The risk of developing intravascular thrombosis requires primary prevention measures by adding D-dimers in the early diagnostic algorithm, being the most accurate marker of hypercoagulability and endogenous fibrinolysis. The corroboration of the hypercoagulability status with the results of genotyping, the frequencies of the minor/major alleles studied, single mononucleotide polymorphisms (SNPs) and the establishment of preventive therapy, aims to prevent intravascular thrombosis and thromboembolic phenomena.

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Most cited references 28

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Increased frequency of genetic thrombophilia in women with complications of pregnancy.

A Eldor, Ayad Jaffa, A Many … (1999)

Obstetrical complications such as severe preeclampsia, abruptio placentae, fetal growth retardation, and stillbirth are associated with intervillous or spiral-artery thrombosis and inadequate placental perfusion. Whether these complications are associated with an increased frequency of thrombophilic mutations is not known. We studied 110 women who had one of the above-mentioned obstetrical complications and 110 women who had one or more normal pregnancies. The women were tested several days after delivery for the mutation of guanine to adenine at nucleotide 1691 [corrected] in the factor V gene (factor V Leiden), the mutation of cytosine to thymine at nucleotide 677 in the gene encoding methylenetetrahydrofolate reductase, and the mutation of guanine to adenine at nucleotide 20210 in the prothrombin gene. Two to three months after delivery the women were tested for deficiency of protein C, protein S, or antithrombin III and for the presence of anticardiolipin antibodies. The mutation at nucleotide 1691 [corrected] in the factor V gene was detected in 22 of the women with obstetrical complications and in 7 of the women with normal pregnancies (20 percent and 6 percent, respectively; P=0.003). Twenty-four women with complications, as compared with nine women without complications, were homozygous for the C677T mutation in the gene encoding methylenetetrahydrofolate reductase (22 percent and 8 percent, respectively; P=0.005). The G20210A mutation in the prothrombin gene was found in 11 women with complications as compared with 3 women without complications (10 percent and 3 percent, respectively; P=0.03). Overall, 57 women with obstetrical complications had a thrombophilic mutation, as compared with 19 women with normal pregnancies (52 percent and 17 percent, respectively; P<0.001). Deficiency of protein S, protein C, or antithrombin III or anticardiolipin antibodies were detected in an additional 14 women with complications, as compared with 1 woman with a normal pregnancy (13 percent and 1 percent, respectively; P<0.001). Women with serious obstetrical complications have an increased incidence of mutations predisposing them to thrombosis and other inherited and acquired forms of thrombophilia.

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Thrombin-activatable fibrinolysis inhibitor (TAFI, plasma procarboxypeptidase B, procarboxypeptidase R, procarboxypeptidase U).

Joost C. M. Meijers, B. Bouma (2003)

Recently, a new inhibitor of fibrinolysis was described, which downregulated fibrinolysis after it was activated by thrombin, and was therefore named TAFI (thrombin-activatable fibrinolysis inhibitor; EC 3.4.17.20). TAFI turned out to be identical to the previously described proteins, procarboxypeptidase U, procarboxypeptidase R, and plasma procarboxypeptidase B. Activated TAFI (TAFIa) downregulates fibrinolysis by the removal of carboxy-terminal lysines from fibrin. These carboxy-terminal lysines are exposed upon limited proteolysis of fibrin by plasmin and act as ligands for the lysine-binding sites of plasminogen and tissue-type plasminogen activator (t-PA). Elimination of these lysines by TAFIa abrogates the fibrin cofactor function of t-PA-mediated plasminogen activation, resulting in a decreased rate of plasmin generation and thus downregulation of fibrinolysis. In this review, the characteristics of TAFI are summarized, with an emphasis on the pathways leading to activation of TAFI and the role of TAFIa in the inhibition of fibrinolysis. However, it cannot be ruled out that TAFI has other, as yet undefined, functions in biology.

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Fibrinolysis in pregnancy: a study of plasminogen activator inhibitors.

D Welti, C Genton, Alina Bachmann … (1987)

During pregnancy the plasma concentration of two different inhibitors of plasminogen activators (PAIs) increases. The only one found in the plasma of nonpregnant women (PAI1) is immunologically related to a PAI of endothelial cells; its plasma activity, as deduced from the inhibition of single-chain tissue-type plasminogen activator (t-PA), increased from 3.4 +/- 2.3 U/mL (mean +/- 95% confidence limits) in the plasma of nonpregnant women to 29 +/- 7 U/mL at term, and its antigen level, measured by a radioimmunoassay, increased from 54 +/- 17 ng/mL to 144 +/- 25 ng/mL. In pregnancy plasma a second PAI (PAI 2) related to a PAI found in placenta extracts was observed. Its level, quantified with a radioimmunoassay, increased from below the detection limit (approximately 10 ng/mL) in normal plasma to 260 ng/mL at term. One hour after delivery, PAI 1 activities and antigen decreased sharply, but the PAI 2 antigen levels remained constant. Three days later, the PAI 1 antigen levels had fallen to normal levels, but the PAI 2 antigen levels were still at least eightfold above the nonpregnant values. During pregnancy, the t-PA and prourokinase (u-PA) antigen concentrations increased 50% and 200%, respectively, whereas the plasminogen and alpha 2-antiplasmin levels remained constant. Despite the large variations in the levels of PAs and PAIs, the overall fibrinolytic activity as measured in diluted plasma by a radioiodinated fibrin plate assay did not change significantly. Just after delivery, a great increase in the t-PA antigen levels was observed. Three to five days after delivery most parameters of the fibrinolytic system were normal again. Our results demonstrate that during pregnancy and in the puerperium profound alterations of the fibrinolytic system occur that are characterized by increases in PAs and their inhibitors, but these alterations do not affect the overall fibrinolytic activity.

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Author and article information

Journal

Journal ID (nlm-ta): Rom J Morphol Embryol

Journal ID (iso-abbrev): Rom J Morphol Embryol

Journal ID (publisher-id): RJME

Title: Romanian Journal of Morphology and Embryology

Publisher: Academy of Medical Sciences, Romanian Academy Publishing House, Bucharest

ISSN (Print): 1220-0522

ISSN (Electronic): 2066-8279

Publication date (Print): Jul-Sep 2021

Publication date (Electronic): 06 February 2022

Volume: 62

Issue: 3

Pages: 829-834

Affiliations

[1 ]Department of Hematology, Faculty of Pharmacy, University of Medicine and Pharmacy of Craiova, Romania

[2 ]Department of Legal Medicine, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, Romania

[3 ]Department of Neonatology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, Romania

[4 ]Student, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, Romania

[5 ]Department of Obstetrics and Gynecology, Victor Babeş University of Medicine and Pharmacy, Timişoara, Romania

[6 ]Department of Histology, Faculty of Medicine, University of Medicine and Pharmacy of Craiova, Romania

[7 ]Department of Obstetrics and Gynecology, University of Medicine and Pharmacy of Craiova, Romania

[8 ]Department of Medical Rehabilitation, University of Medicine and Pharmacy of Craiova, Romania

Author notes

Corresponding Author: Liliana Stanca Lecturer, MD, PhD, Department of Legal Medicine Faculty of Medicine University of Medicine and Pharmacy of Craiova 2 Petru Rareş Street 200349 Craiova, Dolj County Romania +40740–197 898 lillystanca@ 123456yahoo.com

Corresponding Author: Mirela Anişoara Siminel Lecturer, MD, PhD, Department of Neonatology Faculty of Medicine University of Medicine and Pharmacy of Craiova 1 Filantropiei Street 200143 Craiova, Dolj County Romania +40251–307 500 +40728–293 390 mirelasiminel@ 123456gmail.com

Article

Publisher ID: 620321829834

DOI: 10.47162/RJME.62.3.21

PMC ID: 9019663

PubMed ID: 35263412

SO-VID: d5b018b6-22ed-48f4-aa40-86fb9af7d0d9

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This is an open-access article distributed under the terms of a Creative Commons Attribution-NonCommercial-ShareAlike 4.0 International Public License, which permits unrestricted use, adaptation, distribution and reproduction in any medium, non-commercially, provided the new creations are licensed under identical terms as the original work and the original work is properly cited.

The procoagulant status. Hypercoagulability as a risk factor of primary and secondary infertility

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Most cited references 28

Increased frequency of genetic thrombophilia in women with complications of pregnancy.

Thrombin-activatable fibrinolysis inhibitor (TAFI, plasma procarboxypeptidase B, procarboxypeptidase R, procarboxypeptidase U).

Fibrinolysis in pregnancy: a study of plasminogen activator inhibitors.

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