Congenital Factor XIII Deficiency with Multiple Benign Breast Tumours and Successful Pregnancy with Substitutive Therapy

Boda, Zoltán; Pfliegler, G; Muszbek, László; Tóth, A; Adány, R; Hársfalvi, Jolán; Papp, Z; I, Tornai; K, Rák

doi:10.1159/000216082

Cited by 12 publications

(24 citation statements)

References 13 publications

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“…This concept is also supported by the fact that substitution therapy with FXIII concentrates permitted normal pregnancies in human patients with FXIII deficiency. [18][19][20] Homozygous fibrinogen-deficient mice also displayed miscarriage 21,22 because of intrauterine bleeding around 10 dG. Again, it is suggested that maternal fibrinogen plays an essential role in the maintenance of pregnancy.…”

Section: Resultsmentioning

confidence: 99%

Factor XIII A subunit-deficient mice developed severe uterine bleeding events and subsequent spontaneous miscarriages

Koseki-Kuno

Yamakawa

Dickneite

et al. 2003

Blood

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IntroductionCoagulation factor XIII (FXIII) is a heterotetramer consisting of A subunits (FXIIIA) and B subunits (FXIIIB). FXIII catalyzes intermolecular cross-linking reactions between fibrin monomers, ␣ 2 -plasmin inhibitor, and fibronectin. These reactions increase the mechanical strength of the fibrin clot and its resistance to proteolytic degradation and enhance the assembly of the extracellular matrix. Accordingly, a deficiency of FXIII results in defective cross-linking reactions of these substrates and is thus associated with a number of diseases. 1 Congenital FXIII deficiency is caused by defects in the F13A or F13B genes, 2 leading to a bleeding tendency and abnormal wound healing in affected patients and spontaneous miscarriage in female patients. [3][4][5] To understand the molecular pathology of these deficiencies, we have identified a number of mutations in the F13A and F13B genes in patients' DNA and have analyzed the molecular mechanisms of FXIII deficiency using in vitro procedures. 6-15 Because it is not possible to understand completely the clinical pathologic mechanisms of this disease in vivo, we performed functional analyses on FXIIIA knockout (KO) mice. Study designFXIIIA KO mice were created by replacing exon VII with a neomycinresistance cassette as described previously. 16 All KO and wild-type CBA mice were housed in a specific pathogen-free facility. Experimental procedures were approved by the Animal Care and Use Committee of Yamagata University and were carried out in accordance with the guidelines of this committee and that of Japanese governmental law.Using tail biopsy DNA, genotyping of the mice was performed by polymerase chain reaction (PCR) with 2 forward primers designed from the neomycin-resistant gene (5Ј-CAC TGC ATT CTA GTT GTG GTT TGT CC-3Ј) and exon VII of the mouse F13A gene (5Ј-GCC AAG GAT GAT GAA GGT GTT CTT-3Ј), respectively, and a common reverse primer from intron G (5Ј-CCC TGA GAC TTA CGG ATG AAG AAG-3Ј).Tissues collected for histologic analyses were placed in 10% neutralbuffered formalin, processed into paraffin, and 3-m sections were prepared and stained with hematoxylin and eosin by standard techniques.The distribution of events between the study groups was analyzed using 4 ϫ 2 contingency tables for individual study groups as well as 2 ϫ 2 tables for a combined group of female wild-type mice and female homozygous FXIIIA KO mice. The 2 test was also carried out by using StatView software (Abacus Concepts, Berkeley, CA). Differences were considered statistically significant at P values less than .05. Results and discussionWestern blot analysis and amine-incorporation enzymatic assay confirmed the complete absence of FXIIIA in the uterus and plasma (where FXIIIA is normally expressed/present) of the homozygous FXIIIA KO mice identified by genotyping (data not shown). Despite the complete loss of FXIIIA, all homozygous FXIIIA KO mice had appeared normal at birth as previously reported. 16 Whereas all 20 of the female homozygous KO mice survived, 3 of 20 male KO mice...

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Section: Resultsmentioning

confidence: 99%

Factor XIII A subunit-deficient mice developed severe uterine bleeding events and subsequent spontaneous miscarriages

Koseki-Kuno

Yamakawa

Dickneite

et al. 2003

Blood

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“…For each pregnancy, the following data were collected: bleeding during pregnancy and gestational age at the time of bleeding, miscarriage and gestational age at time of miscarriage, prophylactic treatment prior to and/or during pregnancy; mode of delivery; gestational age at delivery, presence of antenatal complications; occurrence of postpartum haemorrhage; other postpartum complications; and neonatal outcome. [10,46] included 13 women who were also reported individually as case reports [11,12,16,17,22,24,28,30,[32][33][34][35]. These 13 cases were included only once, making the total number of women in the review 121 women.…”

Section: Data Extractionmentioning

confidence: 99%

“…Menorrhagia (heavy menstrual bleeding, HMB) was reported in 31 (26%) women, making it the second most common bleeding symptom [10][11][12]21,25,28,30,32,33,35,37,38,41,42,44,45]. Umbilical bleeding was the most common bleeding symptom and reported in 33 (27%) women.…”

Section: Gynaecological and Other Bleeding Symptomsmentioning

confidence: 99%

“…The median number of miscarriages was five, (range 1-13). Two miscarriages occurred between 5 and 7 weeks of gestation [14,27]; 14 miscarriages occurred between 8 and 12 weeks of gestation [11,14,16,26]; and 11 miscarriages between 16 and 18 weeks of gestation [11,21,26]. The gestational age in the remaining 100 miscarriages was not reported.…”

Section: Pregnancy Outcomementioning

confidence: 99%

“…Viability status (pregnancy progressed to 24 weeks of gestation or more) was reached in 65 pregnancies and 62 delivered a live babies [10][11][12][14][15][16][17][18]20,21,23,29,32,33,35,37,[43][44][45]. There was one intrauterine death (IUD) at 37 weeks of gestation due to placental abruption [27], and two neonatal deaths after preterm delivery at 25 [26], and 28 weeks gestation [21].…”

Section: Pregnancy Outcomementioning

confidence: 99%

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Congenital factor XIII deficiency in women: a systematic review of literature

Sharief

Kadir

2013

Haemophilia

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Factor XIII (FXIII) deficiency is a rare congenital bleeding disorder. There is a paucity of data in the literature about obstetrics and gynaecological problems in women affected by FXIII deficiency. The aim of this study was to examine gynaecological problems and obstetric complications and outcome in women with congenital FXIII deficiency. An electronic search was performed to identify the published literature on PUBMED, MEDLINE, EMBASE, Journals @OVID and CINAHL Plus databases using the following keywords: 'congenital factor XIII deficiency' AND 'women OR Pregnancy'. A total of 39 relevant articles were found and included in this systematic review; 27 case reports and 12 case series dating from 1964 to 2012. A total of 121 women were identified. Menorrhagia (26%) was the second most common bleeding reported after umbilical bleeding. Ovulation bleeding reported in 8% of women. Among 63 women, 192 pregnancies were reported; of these, 127 (66%) resulted in a miscarriage and 65 (34%) reached viability stage. In 136 pregnancies without prophylactic therapy, 124 (91%) resulted in a miscarriage and 12(9%) progressed to viability stage. Antepartum haemorrhage occurred in 5/65 (8%) pregnancies reaching viability stage while postpartum haemorrhage (PPH) seen in 16 (25%) cases. Women with congenital FXIII deficiency suffer significant bleeding complications. Menorrhagia and ovulation bleeding are common gynaecological problems and more prevalent than reported. Pregnancies in women with FXIII deficiency have a significant risk of miscarriage, placental abruption and PPH if not on prophylaxis treatment.

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Onset and distribution of factor XIII-containing cells in the mesenchyme of chorionic villi during early phase of human placentation

et al. 1994

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Congenital Factor XIII Deficiency with Multiple Benign Breast Tumours and Successful Pregnancy with Substitutive Therapy

Cited by 12 publications

References 13 publications

Factor XIII A subunit-deficient mice developed severe uterine bleeding events and subsequent spontaneous miscarriages

Factor XIII A subunit-deficient mice developed severe uterine bleeding events and subsequent spontaneous miscarriages

Congenital factor XIII deficiency in women: a systematic review of literature

Onset and distribution of factor XIII-containing cells in the mesenchyme of chorionic villi during early phase of human placentation

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