Genetic analysis of a Chinese pedigree affected with Congenital coagulation factor XII deficiency due to a c.1A>G start codon variant of F12 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the clinical characteristics and genetic etiology of a consanguineous Chinese pedigree affected with Congenital coagulation factor XII (XII) deficiency.@*METHODS@#Members of the pedigree who had visited Ruian People's Hospital on July 12, 2021 were selected as the study subjects. Clinical data of the pedigree were reviewed. Peripheral venous blood samples were taken from the subjects. Blood coagulation index and genetic testing were carried out. Candidate variant was verified by Sanger sequencing and bioinformatic analysis.@*RESULTS@#This pedigree has comprised 6 individuals from 3 generations, including the proband, his father, mother, wife, sister and son. The proband was a 51-year-old male with kidney stones. Blood coagulation test showed that his activated partial thromboplastin time (APTT) was significantly prolonged, whilst the FXII activity (FXII:C) and FXII antigen (FXII:Ag) were extremely reduced. The FXII:C and FXII:Ag of proband's father, mother, sister and son have all reduced to about half of the lower limit of reference range. Genetic testing revealed that the proband has harbored homozygous missense variant of c.1A>G (p.Arg2Tyr) of the start codon in exon 1 of the F12 gene. Sanger sequencing confirmed that his father, mother, sister and son were all heterozygous for the variant, whilst his wife was of the wild type. By bioinformatic analysis, the variant has not been included in the HGMD database. Prediction with SIFT online software suggested the variant is harmful. Simulation with Swiss-Pbd Viewer v4.0.1 software suggested that the variant has a great impact on the structure of FXII protein. Based on the Standards and Guidelines for the Interpretation of Sequence Variants: A Joint Consensus Recommendation of the American College of Medical Genetics and Genomics (ACMG), the variant was rated as likely pathogenic.@*CONCLUSION@#The c.1A>G (p.Arg2Tyr) variant of the F12 gene probably underlay the Congenital FXII deficiency in this pedigree. Above finding has further expanded the spectrum of F12 gene variants and provided a reference for clinical diagnosis and genetic counseling for this pedigree.

Analysis of F12 gene variants and molecular mechanisms in patients with coagulation factor Ⅻ deficiency / 中华医学遗传学杂志

OBJECTIVE@#To analyze the sequence of the F12 gene and molecular mechanism for 20 patients with coagulation factor Ⅻ (FⅫ) deficiency.@*METHODS@#The patients were selected from the outpatient department of the Second Hospital of Shanxi Medical University from July 2020 to January 2022. The activity of coagulation factor Ⅷ (FⅧ:C), factor Ⅸ (FⅨ:C), factor Ⅺ (FⅪ:C) and factor Ⅻ (FⅫ:C) were determined by using a one-stage clotting assay. All exons and 5' and 3' UTR of the F12 gene were analyzed by Sanger sequencing to detect the potential variants. Bioinformatic software was used to predict the pathogenicity of the variants, conservation of amino acids, and protein models.@*RESULTS@#The FⅫ:C of the 20 patients has ranged from 0.07% to 20.10%, which was far below the reference values, whilst the other coagulation indexes were all normal. Sanger sequencing has identified genetic variants in 10 patients, including 4 with missense variants [c.820C>T (p.Arg274Cys), c.1561G>A (p.Glu521Lys), c.181T>C (p.Cys61Arg) and c.566.G>C (p.Cys189Ser)], 4 deletional variants c.303_304delCA(p.His101GlnfsX36), 1 insertional variant c.1093_1094insC (p.Lys365GlnfsX69) and 1 nonsense variant c.1763C>A (p.Ser588*). The remaining 10 patients only harbored the 46C/T variant. The heterozygous c.820C>T(p.Arg274Cys) missense variant in patient 1 and the homozygous c.1763C>A (p.Ser588*) nonsense variant in patient 2 were not included in the ClinVar and the Human Gene Mutation Database. Bioinformatic analysis predicted that both variants were pathogenic, and the corresponding amino acids are highly conserved. The protein prediction models suggested that the c.820C>T (p.Arg274Cys) variant may affect the stability of the secondary structure of FⅫ protein by disrupting the original hydrogen bonding force and truncating the side chain, leading to changes in the vital domain. c.1763C>A (p.Ser588*) may produce a truncated C-terminus which may alter the spatial conformation of the protein domain and affect the serine protease cleavage site, resulting in extremely reduced FⅫ:C.@*CONCLUSION@#Among individuals with low low FⅫ:C detected by one-stage clotting assay, 50% have harbored variants of the F12 gene, among which the c.820C>T and c.1763C>A were novel variants underlying the reduced coagulating factor FⅫ.

Analysis of a Chinese pedigree affected with Hereditary coagulation factor Ⅻ deficiency due to compound heterozygous variants of F12 gene / 中华医学遗传学杂志

OBJECTIVE@#To analyze the clinical phenotypes and genetic variants of a Chinese pedigree affected with Hereditary coagulation factor Ⅻ (FⅫ) deficiency.@*METHODS@#A pedigree presented at the First Affiliated Hospital of Air Force Medical University on December 24,2021 was selected as the study subject. Activated partial thromboplastin time (APTT) and coagulation factor Ⅻ activity (FⅫ:C) were determine by a clotting method, and FⅫ antigen was detected with an ELISA assay. Following the extraction of genomic DNA, all exons and flanking regions of the F12 gene were subjected to Sanger sequencing. Clustalx-2.1-win, PROVEAN and Swiss-PDB Viewer software was used to analyze the conservation of amino acids at the variant sites, impact of of the variants on the amino acid substitutions and the protein structure.@*RESULTS@#The APTT of the proband has prolonged to 70.2 s. Her FⅫ:C and FⅫ:Ag have decreased to 12% and 13%, respectively. DNA sequencing revealed that the proband has harbored c.346G>A (p.Gly97Ser) and c.1583C>A (p.Ser509Tyr) heterozygous compound missense variants in exons 5 and 13 of the F12 gene, respectively. Her father and sister were heterozygous carriers for the c.346G>A (p.Gly97Ser) variant, whilst her mother and brother were heterozygous for the c.1583C>A (p.Ser509Tyr) variant.@*CONCLUSION@#The c.346G>A (p.Gly97Ser) and c.1583C>A (p.Ser509Tyr) compound heterozygous variants of the F12 gene probably underlay the pathogenesis of hereditary coagulation FⅫ deficiency in this pedigree.

Analysis of a Chinese pedigree affected with Hereditary FⅫ deficiency due to compound heterozygous variants of F12 gene / 中华医学遗传学杂志

OBJECTIVE@#To explore the laboratory phenotype and molecular pathogenesis in a Chinese pedigree affected with Hereditary coagulation factor Ⅻ (FⅫ) deficiency.@*METHODS@#A male proband admitted to Ningbo No.2 Hospital on July 17, 2021 due to chronic gastritis and members of his pedigree (7 individuals from three generations) were selected as the study subjects. Prothrombin time (PT), activated partial thromboplastin time (APTT), FⅧ activity (FⅧ: C), FⅨ activity (FⅨ: C), FⅪ activity (FⅪ: C), FⅫ activity (FⅫ: C), and FⅫ antigen (FⅫ: Ag) were determined. All of the exons, exon-intronic boundaries, as well as the 5'- and 3'-untranslated regions of the F12 gene were subjected to Sanger sequencing. Candidate variants were verified by cloning sequencing. The effect of candidate variants on the protein function was analyzed by bioinformatics software.@*RESULTS@#The proband, a 47-year-old male, had significantly prolonged APTT (180.0 s) and decreased FⅫ:C and FⅫ:Ag levels (< 1%). His father, mother, brother and two sons also showed certain degrees of reduction. Genetic testing revealed that the proband has harbored compound heterozygous variants of the F12 gene, namely c.1092_1093insC (p.Lys365Glnfs*69) in exon 10 and c.1792_1796delGTCTA (p.Val579Hisfs*32) in exon 14. His mother and elder son were heterozygous for the c.1092_1093ins variant, whilst his father, brother, and younger son were heterozygous for the c.1792_1796delGTCTA variant. Analysis of the promoter region of exon 1 also showed that the proband and both sons had harbored a 46T/T polymorphism, whilst other family members were 46C/T. Bioinformatic analysis suggested that the p.Val579 is a highly conserved site. Protein model analysis showed that, with the p.Val579Hisfs*32 variant, a benzene ring was added and the hydrogen bond of surrounding amino acids was changed. Based on the guidelines from the American College of Medical Genetics and Genomics, the c.1792_1796delGTCTA was classified as a pathogenic variant (PVS1+PM2_Supporting+PM4).@*CONCLUSION@#The c.1092_1093insC (p.Lys365Glnfs*69) and c.1792_1796delGTCTA (p.Val579Hisfs*32) compound heterozygous variants of the F12 gene probably underlay the decreased FXII levels in this pedigree. Above finding has also enriched the mutational spectrum for FⅫ deficiency.

Identification of compound heterozygous variants of F12 gene in a pedigree affected with inherited coagulation factor XII deficiency / 中华医学遗传学杂志

OBJECTIVE@#To explore the molecular pathogenesis for a pedigree affected with hereditary coagulation factor XII (FXII) deficiency.@*METHODS@#Potential variant of the F12 gene was analyzed by PCR and Sanger sequencing. Expression plasmids were constructed by site-directed mutagenesis based on the wild-type and transiently transfected into 293T cells. FXII:C and FXII:Ag of the expression products were determined in the supernatant and cell lysate. Western blotting was used to verify the identify of the protein.@*RESULTS@#Gene sequencing revealed that the proband has carried 46TT genetype and heterozygous p.Glu502Lys variants in exon 13, and a heterozygous p.Gly542Ser variant in exon 14 of the F12 gene. Transfection experiment suggested that the FXII:C and FXII:Ag of p.Glu502Lys variant in the supernatant were 28% and 24%, compared with the wild-type (100%) and FXII:Ag of cell lysates was 39% compared to the wild-type (100%). The FXII:C and FXII:Ag of p. Gly542Ser variant in the supernatant were 32% and 17% and the FXII:Ag of cell lysates was 59%.@*CONCLUSION@#The 46TT genetype, p.Glu502Lys and p.Gly542Ser variants of the F12 gene probably underlie the low FXII level in the proband. As shown by in vitro experiment, the p.Glu502Lys and p.Gly542Ser variants can both inhibit the synthesis and secrection of the FXII protein.

Phenotypic and genetic analysis of two pedigrees affected with hereditary coagulation FXII deficiency / 中华医学遗传学杂志

OBJECTIVE@#To carry out phenotypic and genotypic analysis for two Chinese pedigrees affected with coagulation factor XII (F XII) deficiency.@*METHODS@#Plasma prothrombin time (PT), activated partial thromboplastin time (APTT), fibrinogen (FIB), thrombin time (TT), and blood coagulation factor VIII, IX, XI, XII activity (FVIII:C, FIX:C, FXI:C, FXII:C) were determined with one stage clotting assay on a STAGO coagulation analyzer. FXII antigen was determined with an enzyme linked immunosorbent assay (ELISA). The 14 exons and their flanking sequences of the F12 gene were subjected to PCR amplification and Sanger sequencing. The conservation and structure of mutant protein were analyzed with MegAlign software and PYMOL software.@*RESULTS@#The APTT of the probands was significantly prolonged, while their FXII:C and FXII:Ag were significantly reduced. Genetic analysis of the proband has revealed three novel mutations in the F12 gene, including g.5972G>A splice site mutation in intron 5, g.8810_8814delGTCTA in exon 14, and g.6259G>A (p.Pro182Leu) in exon 7. In addition, a previously known mutation IVS13-1G>A has been found.@*CONCLUSION@#Four mutations have been identified in the two Chinese pedigrees, among which three were novel. Above mutations probably played a role in the defect of FXII in the two pedigrees.

Prevalent factor XII deficiency in cancer patients with isolated aPTT prolongation

No abstract available.

Identification of a novel heterozygous mutation in a pedigree with hereditary coagulation factor XII deficiency / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To identify potential mutation underlying hereditary coagulation factor XII (FXII) deficiency in a pedigree and explore its molecular pathogenesis.</p><p><b>METHODS</b>Activated partial thromboplastin time (APTT), FXII activity (FXII:C) and FXII antigen(FXII:Ag) and other coagulant parameters of the proband and 5 family members were measured. Potential mutations in the 14 exons and intron-exon boundaries of the FXII gene were screened with polymerase chain reaction (PCR) and direct DNA sequencing. Suspected mutations were confirmed with reverse sequencing. Corresponding PCR fragments from other family members were also sequenced.</p><p><b>RESULTS</b>APPT of the proband and his son were significantly prolonged to 121.5 s and 98.5 s, respectively. FXII:C and FXII:Ag of the proband and his son have reduced to 5%, 6.8% and 9%, 12.2%, respectively. Plasma plasminogen activity (PLG:A) in both individuals was slightly higher than the normal reference range. FXII:C of his second daughter and grandson were slightly reduced to 64% and 60%. FXII:C of the other family members were all in the normal range (72%-113%). A heterozygous missense mutation, g.8597G>A, was identified in exon 13 of the FXII gene in the proband, which resulted in an p.Asp538Asn substitution. For the promoter regions of the FXII gene, the genotype of the proband was 46TT. The same mutations and 46T/T were also found in the proband's son but not in other members of the family. The genotypes of the proband's spouse, eldest daughter and grandson were 46CT, and his second daughter was 46TT.</p><p><b>CONCLUSION</b>The heterozygous mutation of g.8597G>A identified in exon 13 of FXII gene is a novel mutation. Heterozygous p.Asp538Asn mutation and 46TT in the FXII gene can cause hereditary FXII deficiency, which was probably responsible for the low FXII concentrations in this pedigree.</p>

Identification of a novel mutation of factor XII gene in a family with coagulation FXII deficiency / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze genetic mutation and molecular pathogenesis in a family affected with inherited coagulation factor XII(FXII) deficiency.</p><p><b>METHODS</b>Activated partial thromboplastin time (APTT), FXII procoagulant activity (FXII:C), FXII antigen (FXII:Ag) and other coagulants were measured. For affected members of the family, exons 1-14 and flanking intronic regions of the FXII gene were amplified with polymerase chain reaction (PCR) and sequenced thereafter. Expression plasmids containing mutant FXII cDNA was constructed and transfected into COS7 cells transiently. Expressions of FXII:Ag and FXII:C were analyzed.</p><p><b>RESULTS</b>The proband has manifested a prolonged APTT of 108.1 s (reference range: 27.0-41.0 s). Her husband has a normal APTT. Other members of the family had slightly increased APTT. The FXII:C and FXII:Ag of the proband have both dropped to about 0.01 (reference range: 0.72-1.13). The FXII:C levels of her husband, son, daughter and grandchild were 0.57, 0.24, 0.14, 0.16, respectively. And the FXII:Ag levels in her husband, son, daughter and grandchild were 0.55, 0.27, 0.15, 0.21, respectively. The proband and her daughter have both carried a heterozygous deletional mutation 6800-6808delAGCTGGGAG (6800-6808del9bp) in exon 9. For the promoter region of the FXII gene, the genotypes of the proband, her son, daughter and grandchild was TT, whilst that of her husband was CT. Expression study has shown that, whilst the mutant FXII protein has accumulated in the cells similar to wild-type protein, its secretion has reduced approximately by half.</p><p><b>CONCLUSION</b>A novel deletional mutation 6800-6808del9bp has been identified in the FXII gene. Although mutant FXII protein can still accumulate in cells, its secretion has become insufficient. The 6800-6808del9bp mutation and 46T/T have both contributed to the pathogenesis of FXII deficiency in the family, but may have not been the sole cause.</p>

Gene analysis in four inherited coagulation FⅫ deficiency pedigree / 中华血液学杂志

<p><b>OBJECTIVE</b>To identify the genotype and pathogenesis in four Chinese pedigrees with Factor Ⅻ deficiency.</p><p><b>METHODS</b>Activated partial thromboplastin time (APTT), FⅫ procoagulant activity (FⅫ∶C), FⅫ antigen（FⅫ∶Ag）and other coagulant parameters were detected. The FⅫ deficiency Pedigree members,all exons,boundary introns including the splice junctions of the FⅫ gene were amplified with Polymerase chain reaction (PCR). Expression plasmids were constructed by mutagenesis based on the wild-type and transfected into COS7 cells. FⅫ∶C and FⅫ∶Ag of the expression levels were tested in the supernatant and cell lysate.</p><p><b>RESULTS</b>The four probands presented prolonged APTT with all the values of FⅫ∶C and FⅫ∶Ag were low to 2% and 1%, respectively. There were common 46C/T polymorphism in the promoter regions of FⅫ gene in four pedigrees. Proband A was heterozygous for two mutations, g.5741-5742delCA (His101Gln) and g.7142insertC (Lys346Gln). Proband B was a heterozygous deletion mutation g.6800-6808del9bp. The results of the transfection revealed that FⅫ∶Ag in cell lysates and conditioned media protein FⅫ6800-6808del9bp were 85.6% and 51.9%. The FⅫ∶C in the conditioned media was 56.4%. Proband C was a heterozygous mutation g.8699G>A(Gly542Ser). Proband D was a homozygous mutation 8699G>A, whose parents with consanguineous marriage.</p><p><b>CONCLUSION</b>Four mutations, g.5741-5742delCA, g.7142insertC, g.6800-6808del9bp and g.8699G>A with 46C/T polymorphism in the promoter regions of FⅫ gene, were identified in the four Factor Ⅻ deficiency pedigrees. The two mutations g.5741-5742delCA and g.6800-6808del9bp were first found in China. FⅫ 6800-6808del9bp expressed in vitro suggested that almost normal proteinum synthesis but defect proteinum secretion.</p>

Pronóstico materno y perinatal en el embarazo con deficiencia del factor XII / Maternal and perinatal prognosis in pregnancy with factor XII deficiency

ANTECEDENTES: El déficit de factor XII es una enfermedad poco frecuente, relacionada con trombosis y abortos a repetición. OBJETIVO: Evaluar el resultado materno y perinatal en 25 embarazadas con déficit del factor XII. MÉTODOS: Estudio observacional descriptivo de 25 embarazadas (27 gestaciones) con esta patología desde enero 2005 a junio de 2011. RESULTADOS: La asociación de alteración del factor XII con otras trombofilias hereditarias o adquiridas es frecuente. En 24 mujeres se obtuvieron gestaciones exitosas, con sólo 3 abortos. Hubo 20 partos a término, con recién nacidos con peso y Apgar adecuado. Se registró un caso de restricción de crecimiento intrauterino. No hubo complicaciones médicas. Se utilizaron en todas las embarazadas antiagregantes y/o antitrombóticos como tratamiento. El fármaco utilizado más frecuente fue la heparina de bajo peso molecular, asociada en ocasiones al ácido acetilsalicílico. No hubo complicaciones por el uso de heparina de bajo peso molecular. CONCLUSIONES: El control multidisciplinar del embarazo y el tratamiento individualizado ha conseguido en esta patología buenos resultados maternos y neonatales.

BACKGROUND: The factor XII deficiency is a rare disease related with thrombosis and recurrent pregnancy loss. OBJECTIVE: To evaluate maternal and perinatal outcome in 25 pregnant women with deficiency of factor XII. METHODS: An observational descriptive study of 25 women with factor XII deficiency and pregnancy (27 pregnancies) between January 2005 and March 2011. RESULTS: The association with other inherited or acquired thrombophilia is common. 24 women have achieved successful pregnancies and only 3 miscarriages. There were 20 women with deliveries at term, with appropiate birth weight and Apgar test. There was one case of intrauterine growth restriction. There were no medical complications. The treatment used was antiplatelet and/or antithrombotic agents in all cases. The most used drug was low molecular weight heparin, sometimes associated to acetylsalicylic acid. CONCLUSIONS: A multidisciplinary control of the pregnancy and an individualized treatment has achieved good maternal and neonatal outcomes.

Frequency of bleeding disorders diagnosed at armed forces institute of pathology Rawalpindi

To determine the frequency of bleeding disorders diagnosed at Armed Forces Institute of Pathology, Rawalpindi [AFIP Rwp]. Descriptive study. Department of Hematology, AFIP Rwp from January 2006 to June 2009. A total of 1836 patients of bleeding diathesis were included in the study. Hess test was done to investigate the vascular defects. Bleeding Time [BT] was done to screen platelet function defects. The 'clotting screen' and mixing studies were done to detect coagulation protein defects. Clot solubility test was performed to screen factor XIII deficiency. Out of 1836 patietns of bleeding diathesis 435 [23.7%] were diagnosed as having haemostatic defects. Out of these 435 patients 273 [62.8%] had coagulation factor deficiency, 81 [18.6%] had platelet function defects and 81 [18.6%] had vWF deficiency. Among the 273 coagulation factor deficiency patients, factor VIII deficiency was in 121 [44.3%], factor IX deficiency in 32 [11.7%], factor V deficiency in 18 [6.6%], factor XIII deficiency in 15 [5.5%], factor VII deficiency in 12 [4.4%], factor X deficiency in 9 [3.3%], factor I deficiency in 8 [2.9%] and factor II deficiency was in 3 [1.1%]. Multiple factor deficiency was 55 [20.1%]. No defects of vasculature were identified. Coagulation factor deficiencies, with factor VII deficiency being the commonest are the most frequent bleeding disorders. Platelet function defects and vWF deficiency also comprise significant proportion of the bleeding disorders

Analysis of an hereditary coagulation factor XII deficiency in a consanguineous pedigree / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To analyze genetic mutation and explore its molecular pathogenesis for an hereditary coagulation factor XII(F XII) deficiency in a pedigree featuring consanguineous marriage.</p><p><b>METHODS</b>Activated partial thromboplastin time (APTT), F XII procoagulant activity (F XII:C), F XII antigen (F XII:Ag) and other coagulant parameters were assayed. For the proband and his family members, exons 1-4, introns including the splice junctions of the F XII gene were amplified with polymerase chain reaction (PCR). The PCR product was purified and sequenced. The mutations were confirmed by sequencing the complimentary strand.</p><p><b>RESULTS</b>The proband has featured prolonged APTT at 157.5 s (reference range, 27.0-41.0 s). The APTT of his son has increased slightly at 48.3 s. The remaining members of the family were in normal range. F XII activity and F XII antigen of the proband were significantly decreased (<1%). The F XII activity of his wife, daughter, son and mother was also dropped to about 51%, 21%, 21% and 50%, respectively, and so was the F XII antigen (42%, 32%, 37% and 48%, respectively). Homozygous missense mutation of G→A transition at position 8699 in exon 14 resulting in Gly542Ser was identified in the proband. His mother, son and daughter were heterozygous for Gly542Ser. In the promoter regions of F XII gene, the genotype of the proband and the other members was 46T/T.</p><p><b>CONCLUSION</b>Homozygous missense mutation Gly542Ser was found in a pedigree of hereditary F XII deficiency. The homozygous missense mutation might have resulted from his parents by consanguineous marriage. Gly542Ser and 46T/T have contributed to the pathogenesis of the hereditary factor XII deficiency pedigree.</p>

Clinical Significance of Coagulation Screening Tests and Platelet Counts in Children Undergoing Endoscopy / 대한소아소화기영양학회지

PURPOSE: The aim of this study was to assess the benefits of routine pre-endoscopy coagulation screening tests and platelet counts in Korean children. METHODS: Between March 2004 and December 2009, children who underwent gastrointestinal endoscopy for the evaluation of various gastrointestinal symptoms were included. All of the subjects included in the study also underwent routine coagulation screening and platelet count determinations prior to endoscopy and biopsy. The clinical records and laboratory tests were retrospectively reviewed in all patients. RESULTS: One hundred sixty-two of 1,476 (11%) patients who underwent endoscopy had abnormal results on pre-screening coagulation tests. Fourteen patients underwent coagulation factor assays due to abnormal clotting results in consecutive tests or due to clinical evidence of a bleeding tendency. Seven patients were diagnosed with factor XII deficiency, one patient was diagnosed with von Willebrand disease, one patient had von Willebrand disease and factor XII deficiency, and one patient was presumed to have mild hemophilia. The remaining 4 patients had normal results with the factor assays. The results of platelet counts were normal with the exception of 1 patient. No patient had significant bleeding during the endoscopic procedures, despite abnormal pre-endoscopic coagulation tests. CONCLUSION: Routine coagulation screening tests and platelet counts revealed abnormal results in some patients. Most of the patients with abnormal clotting were shown to have a factor XII deficiency, which had no significant associated bleeding tendencies; the other patients were diagnosed with hemophilia or von Willebrand disease. Therefore, although abnormal pre-endoscopic coagulation is not always related to significant bleeding complications, pre-endoscopic coagulation screening may be useful in some children in predicting the risk of bleeding tendency during endoscopic procedures.

Factor XII deficiency and habitual abortion: the Haegman connection

To evaluate the role of factor XII deficiency in cases of habitual abortions. A case control study was conducted on 50 women with history of three or more consecutive first-trimester abortions [group A] of unexplained nature from outpatient clinic of Shatby Maternity University Hospital, and 25 healthy women with no history of recurrent miscarriage, thrombotic disease or adverse pregnancy outcomes [group B]. Blood sample was taken from each patient to assay the following parameters: protein S [PS], protein C [PC], antithrombin III [ATIII], and coagulation factor XII [FXII]. The subsequent miscarriage rate with abnormal FXII is significantly higher than that with normal FXII. However, there were no statistically significant differences in the subsequent miscarriage rates between normal and abnormal PC, PS and ATIII values. Factor XII deficiency might play a role in recurrent miscarriages

A Study of Factor XII Deficiency in Recurrent Spontaneous Abortion / 대한불임학회지

OBJECTIVE: To evaluate factor XII deficiency in patients with recurrent spontaneous abortion and its relation to aPTT. MATERIAL AND METHOD: Factor XII was analyzed by clotting method. RESULTS: Of 70 patients with recurrent spontaneous abortion, there were 35 cases of factor XII deficiency. Among them, there were only 3 cases of prolonged aPTT. CONCLUSIONS: It is still unclear whether factor XII deficiency is related to recurrent spontaneous abortion. Molecular approaches should be used to understand further the causal relationship. But based on this result, in the workup of patients with recurrent spontaneous abortion, factor XII should be included. aPTT is not likely to represent the abnormality of factor XII.