Multidisciplinary Team Management of Congenital Dysfibrinogenemia in Pregnancy: A Case Report

Multidisciplinary Team Management of Congenital Dysfibrinogenemia in Pregnancy: A Case Report | Research Square window.SnipcartSettings = { analytics: { enabled: false } }; (function() { var accessVector = localStorage.getItem('access_vector') || ''; window.dataLayer = window.dataLayer || []; if (accessVector) { window.dataLayer.push({ user: { profile: { profileInfo: { snid: accessVector } } } }); } })(); (function(w,d,s,l,i){w[l]=w[l]||[];w[l].push({'gtm.start':new Date().getTime(),event:'gtm.js'});var f=d.getElementsByTagName(s)[0],j=d.createElement(s),dl=l!='dataLayer'?'&l='+l:'';j.async=true;j.src='https://www.googletagmanager.com/gtm.js?id='+i+dl;f.parentNode.insertBefore(j,f);})(window,document,'script','dataLayer','GTM-K279D39R'); Browse Preprints In Review Journals COVID-19 Preprints AJE Video Bytes Research Tools Research Promotion AJE Professional Editing AJE Rubriq About Preprint Platform In Review Editorial Policies Our Team Advisory Board Help Center Sign In Submit a Preprint Cite Share Download PDF Case Report Multidisciplinary Team Management of Congenital Dysfibrinogenemia in Pregnancy: A Case Report Meng Jie He, Zhou Jun Wei, Fei Wang, Hai Ying Zhang This is a preprint; it has not been peer reviewed by a journal. https://doi.org/ 10.21203/rs.3.rs-6137704/v1 This work is licensed under a CC BY 4.0 License Status: Published Journal Publication published 03 Jul, 2025 Read the published version in BMC Pregnancy and Childbirth → Version 1 posted 25 You are reading this latest preprint version Abstract Background: Congenital dysfibrinogenemia is an autosomal dominant inherited disorder characterized by abnormal fibrinogen. Managing patients with congenital dysfibrinogenemia during pregnancy and perioperative periods is complex, with potential risks of bleeding and thrombosis. Additionally, pregnancy may be associated with adverse events such as recurrent pregnancy loss, stillbirths, placental abruption, and fetal growth restriction. Due to significant individual variability in clinical presentation, there is currently no routine laboratory test to effectively predict bleeding or thrombotic risks, complicating clinical management, especially during pregnancy. Case presentation: A 23-year-old primigravida was diagnosed with congenital dysfibrinogenemia after low fibrinogen levels were detected early in her pregnancy. Family history revealed similar fibrinogen abnormalities in her father and brother. Amniocentesis for fetal genetic testing was performed after a multidisciplinary team evaluated bleeding risks, with no complications during or immediately following the procedure. Genetic testing confirmed congenital dysfibrinogenemia in both the mother and fetus. Throughout the pregnancy, the patient was closely monitored, with no signs of bleeding, thrombosis, or other complications. At 39.3 weeks, following a failed attempt at vaginal delivery, she underwent a cesarean section with fibrinogen replacement therapy. The surgery was uneventful, and there were no significant bleeding or thrombotic events postoperatively. Conclusions: This case emphasizes the critical role of a multidisciplinary team approach in managing congenital dysfibrinogenemia during pregnancy, amniocentesis, and perinatal care. It demonstrates the effectiveness of thorough disease assessment and fibrinogen replacement therapy in preventing bleeding, thereby ensuring positive outcomes for both the mother and fetus. Congenital dysfibrinogenemia Pregnancy Amniocentesis Multidisciplinary team Figures Figure 1 Figure 2 Figure 3 1 Background Fibrinogen plays a central role in hemostasis, contributing to clot formation, platelet aggregation, and fibrinolysis [ 1 , 2 ]. Reduced fibrinogen levels can result from either hereditary or acquired causes. Hereditary fibrinogen deficiencies are less common, while acquired reductions are frequently associated with conditions such as liver dysfunction, thrombotic thrombocytopenic purpura, hemophagocytic syndrome, autoimmune diseases, traumatic blood loss, and certain medications. Distinguishing between hereditary and acquired dysfibrinogenemia often involves genetic analysis, family history, and laboratory evaluations, which help guide clinical decisions, particularly in predicting bleeding or thrombotic risks [ 3 ]. Hereditary fibrinogen defects are rare and can affect either the quantity (hypofibrinogenemia and afibrinogenemia) or the quality (dysfibrinogenemia) of circulating fibrinogen. Pregnant women with congenital dysfibrinogenemia (CD) are at high risk of early pregnancy loss and postpartum hemorrhage [ 4 ]. Women with hypofibrinogenemia or dysfibrinogenemia typically experience milder bleeding but are still at elevated risk during pregnancy or surgery [ 1 , 2 ]. In these cases, fibrinogen replacement therapy (FRT) is considered a key component in the management of CD, especially in pregnancy. Fibrinogen concentrate (human) (FCh) has been used effectively for treating fibrinogen disorders during pregnancy [ 4 ]. Here, we report the case of a pregnant woman with dysfibrinogenemia who experienced bruising following minor trauma. Managed by a multidisciplinary team (MDT), she underwent amniocentesis without complications, received FRT before a cesarean section, and delivered via cesarean with the application of Hayman sutures—a type of uterine compression suture used to control postpartum hemorrhage (PPH). No bleeding or thrombotic events occurred during or after the procedure. 2 Case presentation A 23-year-old pregnant woman, gravida 1, para 0, with a natural pregnancy, was referred at 27.6 weeks' gestation for further evaluation after significantly reduced fibrinogen levels were detected at 10 weeks during her first prenatal visit at 10 weeks' gestation at the local hospital. She reported easy bruising after minor trauma but had no other bleeding symptoms. Menstrual cycles were previously regular, and no vaginal bleeding occurred during pregnancy. Although no specific treatment was provided locally, coagulation status was closely monitored. Coagulation function tests revealed extremely low fibrinogen levels, with a minimum value of 0.41 g/L (reference range: 2.00–4.00 g/L). Family history revealed fibrinogen abnormalities in the patient’s father and brother, both asymptomatic for bleeding or thrombosis. At 27 weeks, she was referred for genetic counseling at our Prenatal Diagnosis Center. The genetics and prenatal diagnosis specialist recommended close monitoring of coagulation function and amniocentesis for family-based exome sequencing. To guide pregnancy management and due to the patient's strong desire to clarify the genetic basis of her and the fetus's condition, she consented to undergo amniocentesis and fetal genetic testing. Upon admission, coagulation tests showed the following: thrombin time (TT) at 37.6 seconds (reference range: 14.0–21.0 s), fibrinogen (Clauss method) (Fib-Clauss) at 0.79 g/L, fibrinogen (PT-derived method) (Fib-PT-derived) at 2.22 g/L, and a Fib-PT-derived/Clauss ratio greater than 1.43. The prolonged TT and an elevated Fib-PT-derived/Clauss ratio are suggestive of CD. Further investigations excluded liver disease, autoimmune conditions, hematologic disorders, disseminated intravascular coagulation (DIC), and drug-related causes. Additional examinations revealed the D-dimer level was 0.86 µg/mL (reference range: 0–3 µg/mL), which fell within the normal range for mid-pregnancy, Doppler ultrasound of the lower limbs, neck, and abdominal large vessels showed no evidence of thrombosis. Moreover, Fetal ultrasound revealed no signs of fetal growth restriction or placental abnormalities. Subsequently, a MDT discussion was held to assess the bleeding and thrombotic risks. Considering the low bleeding risk associated with amniocentesis and the patient's clinical presentation—limited to bruising after minor trauma and fibrinogen levels ranging from 0.79 to 0.86 g/L—she was deemed at low risk for bleeding.amniocentesis was successfully performed on the second day after admission, without the need for FRT before or after the procedure. Postoperatively, only mechanical thromboprophylaxis was applied. The puncture site was closely monitored for any bleeding, and fetal status was rigorously observed, with no abnormalities detected. The patient was discharged without incident on the second day after the procedure. Following discharge, she continued regular prenatal visits, with monthly monitoring of fetal growth and fibrinogen activity. Genetic testing of the amniotic fluid using high-throughput whole-exome sequencing revealed a heterozygous variant in the FGA gene (NM_021871.4: exon2: c.95G > A: p.G32E). The mutation of glycine at position 32 to glutamate (Gly32Glu) was identified and classified, classified as likely pathogenic according to the American College of Medical Genetics and Genomics (ACMG) standards and guidelines [ 5 ]. The sequencing results are shown in Figure_1, inherited from both the mother and maternal grandfather. The patient's family pedigree for CD is shown in Figure_2. At 38.8 weeks of gestation, the patient was admitted for delivery, with a Fib-Clauss level of 0.79 g/L. Another MDT discussion recommended a trial of vaginal delivery, as there were no medical indications for a cesarean section. Following induction with oxytocin, frequent uterine contractions occurred without signs of labor. Due to concerns about non-reassuring fetal status and potential placental abruption, oxytocin was discontinued, and tocolytic agents were administered to suppress uterine contractions. At 39.3 weeks, a cesarean section was performed. To minimize the risk of bleeding associated with cesarean delivery, 3 g of FCh was infused 3 hours prior to surgery, resulting in a Fib-Clauss level of 1.69 g/L 2 hours later. Prophylactic Hayman suturing was applied during the surgery to further reduce bleeding risk. The procedure proceeded without complications, with an estimated blood loss of approximately 300 mL. Postoperatively, carbetocin was administered to promote uterine contractions, and close monitoring for uterine tone and vaginal bleeding was implemented. On postoperative day 3, Fib-Clauss level was rechecked at 1.40 g/L. Given the long half-life of fibrinogen (median 3–5 days), no additional FCh was administered. Based on her personal history, family history, and genetic findings, the patient was classified as having type 3A CD. Standard thromboembolic risk assessment indicated no need for enoxaparin, and mechanical thromboprophylaxis was applied. The patient was discharged on postoperative day 6, with Fib-Clauss level at 1.08 g/L. Placental pathology revealed no thrombus formation or vascular abnormalities. The patient delivered a healthy female infant, with a birth weight of 2890 g, a length of 49 cm, and an Apgar score of 10-10-10. The infant appeared normal at birth, with clear amniotic fluid and no signs of bleeding. Coagulation tests performed at birth revealed a prolonged TT and a low Fib-Clauss level of 0.33 g/L, consistent with CD. The infant developed mild neonatal jaundice but exhibited no signs of bleeding, which was confirmed by cranial and abdominal ultrasounds. Follow-up at 1 month showed no bleeding symptoms in either the mother or the infant. Laboratory values of coagulation function during pregnancy and perioperative management are provided in Figure_3. 3 Discussion and conclusions In this case, the patient's diagnosis of CD, a rare disorder characterized by impaired fibrinogen function, resulting in abnormal clot formation [ 6 ], presented unique clinical challenges, especially in the context of pregnancy. While most patients with CD are asymptomatic, with fibrinogen abnormalities often discovered incidentally during routine physical exams or preoperative screenings [ 6 ]. Genetic testing is considered the gold standard for diagnosis, though it is time-consuming and costly. Coagulation function tests, including normal prothrombin time (PT) and activated partial thromboplastin time (APTT), prolonged TT, significantly decreased Fib-Clauss levels, normal or elevated Fib-PT-derived levels, and a Fib-PT-derived/Clauss ratio greater than 1.43, or a Fib-Clauss/PT-derived ratio less than 0.7 [ 7 , 8 ] are recommended as rapid diagnostic methods in most medical settings. In this case, the patient's family history and laboratory findings strongly suggested CD, which was confirmed through genetic testing. CD has diverse clinical phenotypes, typically without racial differences in presentation. While most patients are asymptomatic, a small proportion experience bleeding or thrombotic events. The most common bleeding phenotype observed in both Europe and China is bruising [ 9 , 10 , 11 ]. Women with CD face a higher risk of pregnancy-related complications such as recurrent pregnancy loss, stillbirth, placental abruption, fetal growth restriction, and postpartum hemorrhage [ 11 ]. Despite this, many patients with CD have uneventful pregnancies, though pregnancy remains a high-risk condition that requires personalized management. Consequently, clinical management during pregnancy and the perinatal period presents significant challenges, necessitating a MDT approach that integrates the patient's personal history, family history, and prior pregnancy history to formulate an individualized management plan and assess risks of adverse pregnancy events [ 12 ]. The patient in this case underwent a multidisciplinary evaluation, including Medical Intensive Care Unit (MICU) where a hematologist was involved, as well as Obstetrics, Clinical Pharmacy, Medical Genetics, and Anesthesiology. The evaluation focused on assessing thrombosis and bleeding risks, as well as managing the pregnancy, amniocentesis, and peripartum period. For patients with a high thrombosis risk, preventive measures should include thromboprophylaxis with low molecular weight heparin (LMWH) throughout the pregnancy [ 6 ]. In Chinese populations, the reported incidence of thrombosis is relatively low, at approximately 3.9% [ 13 , 14 ]. Given the limited reports on invasive procedures in patients with CD, an MDT evaluation was conducted for amniocentesis management, which represents a particularly novel aspect of this case. A comprehensive assessment of bleeding risk was essential. Vaginal bleeding occurs in approximately 2–3% of amniocentesis procedures [ 15 ]. The Royal College of Obstetricians & Gynaecologists (RCOG) guideline [ 16 ] does not list bleeding as a risk. Despite ongoing debate, thromboelastography (TEG) provides valuable insights into coagulation status during pregnancy [ 4 , 8 , 9 , 17 ]. In this case, pre-procedural TEG showed no abnormalities, and MDT discussions concluded that the bleeding risk was low, supporting the safe conduct of the procedure. Amniocentesis was performed successfully and no prophylactic hemostatic agents were used pre-or postoperatively, the patient's hemostasis was achieved without complications. Subsequent whole-exome sequencing identified a pathogenic mutation at the AαGly32Glu site in the FGA gene, confirming the diagnosis of CD. Fibrinogen gene mutations, especially in the Aα chain and thrombin cleavage sites, are strongly linked to thrombosis [ 6 , 18 ]. These mutations reduce plasminogen binding, impair plasminogen activator activation, and increase self-binding propensity [ 18 , 19 ]. Notable mutations include AαArg16Cys, AαSer532Cys, γAsp364Val, BβAla68Thr, and AαArg554Cys [ 6 ]. In this case, the identified mutation has not been linked to increased risk of thrombosis. Accordingly, the case classified as type 3A, which is characterized by a low thrombotic risk. The classification of dysfibrinogenemia is summarized in Table 1 [ 20 ]. Table 1 Classification of Dysfibrinogenemia Type Description ThrombosisRisk Type 3A Dysfibrinogenemic patients either with bleeding phenotype or with thrombotic phenotype not fulfilling criteria for dysfibrinogenemia 3B or asymptomatic individuals Low Type 3B Dysfibrinogenemic patients carriers of a thrombotic fibrinogen mutation or suffering from thrombotic events with a first-degree familial thrombotic history (relatives with the same genotype) without any other thrombophilia High Given the elevated risk of obstetric complications in CD, attributable to fibrinogen's critical role in maintaining fetal–maternal circulation and peripartum hemostasis, the patient was placed under MDT management to ensure individualized, risk-adapted care during pregnancy [ 6 , 21 ]. FRT may be warranted in cases of recurrent pregnancy loss or placental insufficiency to maintain fibrinogen levels ≥ 1 g/L [ 6 ], and was reserved for potential vaginal bleeding, targeting fibrinogen levels ≥ 1.5 g/L [ 22 ]. In contrast, routine FRT or anticoagulation is generally unnecessary in uncomplicated pregnancies, where regular monitoring suffices. In this case, the pregnancy was uneventful apart from mild bruising. Although thrombosis-related mutations have been associated with fetal growth restriction and placental abruption [ 20 ], this patient, classified as low thrombotic risk, showed normal fetal growth throughout gestation. The timing of pregnancy termination was primarily based on the mother's and fetus's overall condition. An MDT discussion and obstetric evaluation concluded a favorable pregnancy outcome with no adverse events, initially recommending vaginal delivery. Upon admission, the patient's Fib-Clauss level was 0.79 g/L. Given that natural labor, regional anesthesia, and cesarean section require maintaining fibrinogen ≥ 1.5 g/L [ 20 ]. Additionally, this case underscores the importance of carefully managing the timing, dosage, and duration of FCh infusion, as well as assessing postpartum thrombosis risk. The clinical pharmacist recommended FCh due to its pharmacokinetics, achieving peak fibrinogen levels within 2 hours and improving clot firmness 1 hour post-infusion [ 23 ]. However, FCh infusion may increase the risk of pulmonary embolism [ 24 ] or deep vein thrombosis [ 25 ] in patients with CD. Thus, FCh administration was carefully timed: after labor onset for vaginal delivery and at least 2 hours before cesarean section. The dose was calculated based on the patient's pregnancy weight [ 26 ]. Blood bank communication ensured sufficient blood products for postpartum hemorrhage prevention. As the patient showed no signs of labor, oxytocin was administered, causing severe uterine contractions and concerns of fetal distress or placental abruption. Consequently, vaginal delivery was abandoned in favor of cesarean section. 3 g of FCh was administered 3 hours before the procedure to maintain fibrinogen ≥ 1.5 g/L [ 26 ]. 2 hours after infusion, the fibrinogen level was 1.60 g/L, and epidural anesthesia was chosen in consultation with the anesthesiology department. Despite no significant bleeding during pregnancy, patients with CD are still at higher risk for postpartum hemorrhage. To address this, the obstetrician performed Hayman suturing during surgery, and 100 µg of carbetocin was administered postpartum to reduce bleeding from uterine atony. Given fibrinogen's half-life of 3–4 days, levels returned to pre-infusion values by day 9 [ 23 ]. Postoperatively, the patient experienced no significant bleeding, and no additional FCh was given. Fibrinogen levels on postoperative days 3 and 6 were 1.40 g/L and 1.08 g/L, respectively, in line with guidelines [ 26 ]. Given that the patient was type 3A, a postoperative thrombosis risk assessment was performed according to standard protocols for pregnant women. Her postpartum Venous thromboembolism (VTE) risk score was 2 (2 points for conversion to cesarean section). As her score was below 3, only mechanical prophylaxis was administered. The postoperative course was uneventful, with favorable maternal and neonatal outcomes and no observed complications. In conclusion, this case underscores the importance of personalized management in pregnant patients with CD. A MDT approach, individualized treatment strategies, and appropriate use of FRT contributed to a successful outcome. Additionally, the case provides valuable insights into the management of invasive procedures such as amniocentesis in patients with CD, underscores the essential role of MDT in addressing bleeding and thrombotic risks and in preventing postpartum hemorrhage following cesarean section. This case highlighting promising avenues for future research, including risk stratification through personalized biomarkers, optimization of FRT protocols, and the development of procedural guidelines for CD management in pregnancy, particularly within the context of MDT-led care. Abbreviations ACMG American College of Medical Genetics and Genomics APTT Activated partial thromboplastin time CD Congenital dysfibrinogenemia DIC Disseminated intravascular coagulation FCh Fibrinogen concentrate (human) Fib-Clauss fibrinogen (Clauss method) Fib-PT-derived fibrinogen (PT-derived method) FRT Fibrinogen replacement therapy LMWH Low molecular weight heparin MDT Multidisciplinary team MICU Medical Intensive Care Unit PT Prothrombin time RCOG Royal College of Obstetricians & Gynaecologists TEG Thromboelastography TT Thrombin time VTE Venous thromboembolism Declarations Ethics approval and consent to participate: This study was conducted in accordance with the ethical principles of the Declaration of Helsinki and received formal approval from the Institutional Review Board of the Sichuan Provincial Women's and Children's Hospital, Grant No. 20250326-73. Written informed consent was obtained from the participant for publication of anonymized clinical data and research findings, including any accompanying images or case details. All procedures maintained strict confidentiality in accordance with institutional data protection protocols. Consent for publication: This study was conducted in accordance with the ethical principles of the Declaration of Helsinki and received formal approval from the Institutional Review Board of the Sichuan Provincial Women's and Children's Hospital. Written informed consent was obtained from the participant for publication of anonymized clinical data and research findings, including any accompanying images or case details. Written informed consent has been obtained from the patient to publish this paper. Availability of data and materials: All data generated or analysed during this study are included in this published article. Competing interests: The authors declare no competing interests. Funding: The Fund of Chengdu Medical College(Grant CYJD22-01); The Fund of Chengdu Medical College(Grant CYSZD23-05) Authors' contributions: Meng Jie He: was a major contributor in writing the manuscript and collecting the data; Zhou Jun Wei: was a main contributor in writing the manuscript and collecting the data; Fei Wang: was involved in pharmaceutical care; Hai Ying Zhang: designed the study. All authors read and approved the final manuscript. Acknowledgements: Not applicable. References Acharya SS, Dimichele DM. Rare inherited disorders of fibrinogen. Haemophilia. 2008;14(6):1151–8. de Moerloose P, Neerman-Arbez M. Congenital fibrinogen disorders. Semin Thromb Hemost. 2009;35(4):356–66. Casini A, Neerman-Arbez M, Ariens RA, et al. Dysfibrinogenemia: from molecular anomalies to clinical manifestations and management. J Thromb Haemost. 2015;13(6):909–19. Huang LY, Zhang DL, Fu RF, et al. 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Also discoverable on Platform About Our Team In Review Editorial Policies Advisory Board Help Center Resources Author Services Accessibility API Access RSS feed Manage Cookie Preferences © Research Square 2026 | ISSN 2693-5015 (online) Privacy Policy Terms of Service Do Not Sell My Personal Information {"props":{"pageProps":{"initialData":{"identity":"rs-6137704","acceptedTermsAndConditions":true,"allowDirectSubmit":false,"archivedVersions":[],"articleType":"Case Report","associatedPublications":[],"authors":[{"id":443562613,"identity":"4b880e42-1fcd-4842-90ec-95e0cd938bfb","order_by":0,"name":"Meng Jie He","email":"","orcid":"","institution":"Maternal and Child Health Hospital of Sichuan Province","correspondingAuthor":false,"prefix":"","firstName":"Meng","middleName":"Jie","lastName":"He","suffix":""},{"id":443562616,"identity":"81839f1b-3e70-476d-96cf-ba7741fbb33a","order_by":1,"name":"Zhou Jun Wei","email":"","orcid":"","institution":"Maternal and Child Health Hospital of Sichuan Province","correspondingAuthor":false,"prefix":"","firstName":"Zhou","middleName":"Jun","lastName":"Wei","suffix":""},{"id":443562617,"identity":"6a8b93e0-4db0-4b4b-95bf-79631c48f314","order_by":2,"name":"Fei Wang","email":"","orcid":"","institution":"Maternal and Child Health Hospital of Sichuan Province","correspondingAuthor":false,"prefix":"","firstName":"Fei","middleName":"","lastName":"Wang","suffix":""},{"id":443562618,"identity":"1d569ce8-70b7-4502-87b4-44f40d4fd5be","order_by":3,"name":"Hai Ying Zhang","email":"data:image/png;base64,iVBORw0KGgoAAAANSUhEUgAAAZAAAAAyAQMAAABI0h/eAAAABlBMVEX///8AAABVwtN+AAAACXBIWXMAAA7EAAAOxAGVKw4bAAAAxElEQVRIiWNgGAWjYDACZgaGA4wNDHL8zMyHH5CkxViynS3NgHibgFoSN5znUZAgSrXBcR7Dgz93HGbcfJiHwYChxiaasJbDPAYHJM8cZjY7zHvgAcOxtNwGorQYth1mMzvMl2DA2HCYSC2JbYd5jJt5DCSI13Kw7bCEATOxWiQPsxUcbGxLN5A4DAzkBGL8wnf+8OaPP9us6/v7Dx9+8KHGhrAWhQMcoAhshvASCCkHAfkG9gdAqo4YtaNgFIyCUTBSAQBSuEQReXyhQwAAAABJRU5ErkJggg==","orcid":"","institution":"Maternal and Child Health Hospital of Sichuan Province","correspondingAuthor":true,"prefix":"","firstName":"Hai","middleName":"Ying","lastName":"Zhang","suffix":""}],"badges":[],"createdAt":"2025-03-02 06:38:08","currentVersionCode":1,"declarations":"","doi":"10.21203/rs.3.rs-6137704/v1","doiUrl":"https://doi.org/10.21203/rs.3.rs-6137704/v1","draftVersion":[],"editorialEvents":[{"content":"https://doi.org/10.1186/s12884-025-07834-3","type":"published","date":"2025-07-03T15:57:52+00:00"}],"editorialNote":"","failedWorkflow":false,"files":[{"id":81010558,"identity":"8684942c-b484-41d9-b557-f52f2c665e24","added_by":"auto","created_at":"2025-04-21 08:18:32","extension":"png","order_by":1,"title":"Figure 1","display":"","copyAsset":false,"role":"figure","size":473122,"visible":true,"origin":"","legend":"\u003cp\u003eSanger sequencing results of the mutation site of the FGA gene in the family pedigree\u003c/p\u003e","description":"","filename":"floatimage1.png","url":"https://assets-eu.researchsquare.com/files/rs-6137704/v1/135aa7a72ab591ae6369b90f.png"},{"id":81010561,"identity":"46f19d61-c4c9-4770-aba1-b38c5464c823","added_by":"auto","created_at":"2025-04-21 08:18:32","extension":"png","order_by":2,"title":"Figure 2","display":"","copyAsset":false,"role":"figure","size":27686,"visible":true,"origin":"","legend":"\u003cp\u003eGenealogy of Hereditary Abnormal Fibrinogenemia\u003c/p\u003e","description":"","filename":"floatimage2.png","url":"https://assets-eu.researchsquare.com/files/rs-6137704/v1/b6149573f1137cd3b4502bb4.png"},{"id":81013225,"identity":"e522dc62-9a17-47e7-9d89-f2dea177c517","added_by":"auto","created_at":"2025-04-21 08:34:32","extension":"png","order_by":3,"title":"Figure 3","display":"","copyAsset":false,"role":"figure","size":61285,"visible":true,"origin":"","legend":"\u003cp\u003eLaboratory Values of Coagulation Function during pregnancy and perioperative period\u003c/p\u003e","description":"","filename":"floatimage3.png","url":"https://assets-eu.researchsquare.com/files/rs-6137704/v1/2e3b2e3fa3f5b00250e91a3b.png"},{"id":86179127,"identity":"6c66d7f8-ca80-46ea-9e99-39d2cf35787e","added_by":"auto","created_at":"2025-07-07 16:16:06","extension":"pdf","order_by":0,"title":"","display":"","copyAsset":false,"role":"manuscript-pdf","size":977149,"visible":true,"origin":"","legend":"","description":"","filename":"manuscript.pdf","url":"https://assets-eu.researchsquare.com/files/rs-6137704/v1/c4590075-7fcd-4120-ba1f-b55babf83f4a.pdf"}],"financialInterests":"No competing interests reported.","formattedTitle":"Multidisciplinary Team Management of Congenital Dysfibrinogenemia in Pregnancy: A Case Report","fulltext":[{"header":"1 Background","content":"\u003cp\u003eFibrinogen plays a central role in hemostasis, contributing to clot formation, platelet aggregation, and fibrinolysis [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. Reduced fibrinogen levels can result from either hereditary or acquired causes. Hereditary fibrinogen deficiencies are less common, while acquired reductions are frequently associated with conditions such as liver dysfunction, thrombotic thrombocytopenic purpura, hemophagocytic syndrome, autoimmune diseases, traumatic blood loss, and certain medications. Distinguishing between hereditary and acquired dysfibrinogenemia often involves genetic analysis, family history, and laboratory evaluations, which help guide clinical decisions, particularly in predicting bleeding or thrombotic risks [\u003cspan citationid=\"CR3\" class=\"CitationRef\"\u003e3\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHereditary fibrinogen defects are rare and can affect either the quantity (hypofibrinogenemia and afibrinogenemia) or the quality (dysfibrinogenemia) of circulating fibrinogen. Pregnant women with congenital dysfibrinogenemia (CD) are at high risk of early pregnancy loss and postpartum hemorrhage [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e]. Women with hypofibrinogenemia or dysfibrinogenemia typically experience milder bleeding but are still at elevated risk during pregnancy or surgery [\u003cspan citationid=\"CR1\" class=\"CitationRef\"\u003e1\u003c/span\u003e, \u003cspan citationid=\"CR2\" class=\"CitationRef\"\u003e2\u003c/span\u003e]. In these cases, fibrinogen replacement therapy (FRT) is considered a key component in the management of CD, especially in pregnancy. Fibrinogen concentrate (human) (FCh) has been used effectively for treating fibrinogen disorders during pregnancy [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eHere, we report the case of a pregnant woman with dysfibrinogenemia who experienced bruising following minor trauma. Managed by a multidisciplinary team (MDT), she underwent amniocentesis without complications, received FRT before a cesarean section, and delivered via cesarean with the application of Hayman sutures\u0026mdash;a type of uterine compression suture used to control postpartum hemorrhage (PPH). No bleeding or thrombotic events occurred during or after the procedure.\u003c/p\u003e"},{"header":"2 Case presentation","content":"\u003cp\u003eA 23-year-old pregnant woman, gravida 1, para 0, with a natural pregnancy, was referred at 27.6 weeks' gestation for further evaluation after significantly reduced fibrinogen levels were detected at 10 weeks during her first prenatal visit at 10 weeks' gestation at the local hospital. She reported easy bruising after minor trauma but had no other bleeding symptoms. Menstrual cycles were previously regular, and no vaginal bleeding occurred during pregnancy. Although no specific treatment was provided locally, coagulation status was closely monitored. Coagulation function tests revealed extremely low fibrinogen levels, with a minimum value of 0.41 g/L (reference range: 2.00\u0026ndash;4.00 g/L). Family history revealed fibrinogen abnormalities in the patient\u0026rsquo;s father and brother, both asymptomatic for bleeding or thrombosis.\u003c/p\u003e \u003cp\u003eAt 27 weeks, she was referred for genetic counseling at our Prenatal Diagnosis Center. The genetics and prenatal diagnosis specialist recommended close monitoring of coagulation function and amniocentesis for family-based exome sequencing. To guide pregnancy management and due to the patient's strong desire to clarify the genetic basis of her and the fetus's condition, she consented to undergo amniocentesis and fetal genetic testing.\u003c/p\u003e \u003cp\u003eUpon admission, coagulation tests showed the following: thrombin time (TT) at 37.6 seconds (reference range: 14.0\u0026ndash;21.0 s), fibrinogen (Clauss method) (Fib-Clauss) at 0.79 g/L, fibrinogen (PT-derived method) (Fib-PT-derived) at 2.22 g/L, and a Fib-PT-derived/Clauss ratio greater than 1.43. The prolonged TT and an elevated Fib-PT-derived/Clauss ratio are suggestive of CD. Further investigations excluded liver disease, autoimmune conditions, hematologic disorders, disseminated intravascular coagulation (DIC), and drug-related causes. Additional examinations revealed the D-dimer level was 0.86 \u0026micro;g/mL (reference range: 0\u0026ndash;3 \u0026micro;g/mL), which fell within the normal range for mid-pregnancy, Doppler ultrasound of the lower limbs, neck, and abdominal large vessels showed no evidence of thrombosis. Moreover, Fetal ultrasound revealed no signs of fetal growth restriction or placental abnormalities.\u003c/p\u003e \u003cp\u003eSubsequently, a MDT discussion was held to assess the bleeding and thrombotic risks. Considering the low bleeding risk associated with amniocentesis and the patient's clinical presentation\u0026mdash;limited to bruising after minor trauma and fibrinogen levels ranging from 0.79 to 0.86 g/L\u0026mdash;she was deemed at low risk for bleeding.amniocentesis was successfully performed on the second day after admission, without the need for FRT before or after the procedure. Postoperatively, only mechanical thromboprophylaxis was applied. The puncture site was closely monitored for any bleeding, and fetal status was rigorously observed, with no abnormalities detected. The patient was discharged without incident on the second day after the procedure. Following discharge, she continued regular prenatal visits, with monthly monitoring of fetal growth and fibrinogen activity. Genetic testing of the amniotic fluid using high-throughput whole-exome sequencing revealed a heterozygous variant in the FGA gene (NM_021871.4: exon2: c.95G\u0026thinsp;\u0026gt;\u0026thinsp;A: p.G32E). The mutation of glycine at position 32 to glutamate (Gly32Glu) was identified and classified, classified as likely pathogenic according to the American College of Medical Genetics and Genomics (ACMG) standards and guidelines [\u003cspan citationid=\"CR5\" class=\"CitationRef\"\u003e5\u003c/span\u003e]. The sequencing results are shown in Figure_1, inherited from both the mother and maternal grandfather. The patient's family pedigree for CD is shown in Figure_2.\u003c/p\u003e \u003cp\u003eAt 38.8 weeks of gestation, the patient was admitted for delivery, with a Fib-Clauss level of 0.79 g/L. Another MDT discussion recommended a trial of vaginal delivery, as there were no medical indications for a cesarean section. Following induction with oxytocin, frequent uterine contractions occurred without signs of labor. Due to concerns about non-reassuring fetal status and potential placental abruption, oxytocin was discontinued, and tocolytic agents were administered to suppress uterine contractions. At 39.3 weeks, a cesarean section was performed. To minimize the risk of bleeding associated with cesarean delivery, 3 g of FCh was infused 3 hours prior to surgery, resulting in a Fib-Clauss level of 1.69 g/L 2 hours later. Prophylactic Hayman suturing was applied during the surgery to further reduce bleeding risk. The procedure proceeded without complications, with an estimated blood loss of approximately 300 mL. Postoperatively, carbetocin was administered to promote uterine contractions, and close monitoring for uterine tone and vaginal bleeding was implemented. On postoperative day 3, Fib-Clauss level was rechecked at 1.40 g/L. Given the long half-life of fibrinogen (median 3\u0026ndash;5 days), no additional FCh was administered. Based on her personal history, family history, and genetic findings, the patient was classified as having type 3A CD. Standard thromboembolic risk assessment indicated no need for enoxaparin, and mechanical thromboprophylaxis was applied. The patient was discharged on postoperative day 6, with Fib-Clauss level at 1.08 g/L. Placental pathology revealed no thrombus formation or vascular abnormalities.\u003c/p\u003e \u003cp\u003eThe patient delivered a healthy female infant, with a birth weight of 2890 g, a length of 49 cm, and an Apgar score of 10-10-10. The infant appeared normal at birth, with clear amniotic fluid and no signs of bleeding. Coagulation tests performed at birth revealed a prolonged TT and a low Fib-Clauss level of 0.33 g/L, consistent with CD. The infant developed mild neonatal jaundice but exhibited no signs of bleeding, which was confirmed by cranial and abdominal ultrasounds. Follow-up at 1 month showed no bleeding symptoms in either the mother or the infant. Laboratory values of coagulation function during pregnancy and perioperative management are provided in Figure_3.\u003c/p\u003e "},{"header":"3 Discussion and conclusions","content":"\u003cp\u003eIn this case, the patient's diagnosis of CD, a rare disorder characterized by impaired fibrinogen function, resulting in abnormal clot formation [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], presented unique clinical challenges, especially in the context of pregnancy. While most patients with CD are asymptomatic, with fibrinogen abnormalities often discovered incidentally during routine physical exams or preoperative screenings [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. Genetic testing is considered the gold standard for diagnosis, though it is time-consuming and costly. Coagulation function tests, including normal prothrombin time (PT) and activated partial thromboplastin time (APTT), prolonged TT, significantly decreased Fib-Clauss levels, normal or elevated Fib-PT-derived levels, and a Fib-PT-derived/Clauss ratio greater than 1.43, or a Fib-Clauss/PT-derived ratio less than 0.7 [\u003cspan citationid=\"CR7\" class=\"CitationRef\"\u003e7\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e] are recommended as rapid diagnostic methods in most medical settings. In this case, the patient's family history and laboratory findings strongly suggested CD, which was confirmed through genetic testing.\u003c/p\u003e \u003cp\u003eCD has diverse clinical phenotypes, typically without racial differences in presentation. While most patients are asymptomatic, a small proportion experience bleeding or thrombotic events. The most common bleeding phenotype observed in both Europe and China is bruising [\u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR10\" class=\"CitationRef\"\u003e10\u003c/span\u003e, \u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Women with CD face a higher risk of pregnancy-related complications such as recurrent pregnancy loss, stillbirth, placental abruption, fetal growth restriction, and postpartum hemorrhage [\u003cspan citationid=\"CR11\" class=\"CitationRef\"\u003e11\u003c/span\u003e]. Despite this, many patients with CD have uneventful pregnancies, though pregnancy remains a high-risk condition that requires personalized management. Consequently, clinical management during pregnancy and the perinatal period presents significant challenges, necessitating a MDT approach that integrates the patient's personal history, family history, and prior pregnancy history to formulate an individualized management plan and assess risks of adverse pregnancy events [\u003cspan citationid=\"CR12\" class=\"CitationRef\"\u003e12\u003c/span\u003e]. The patient in this case underwent a multidisciplinary evaluation, including Medical Intensive Care Unit (MICU) where a hematologist was involved, as well as Obstetrics, Clinical Pharmacy, Medical Genetics, and Anesthesiology. The evaluation focused on assessing thrombosis and bleeding risks, as well as managing the pregnancy, amniocentesis, and peripartum period. For patients with a high thrombosis risk, preventive measures should include thromboprophylaxis with low molecular weight heparin (LMWH) throughout the pregnancy [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In Chinese populations, the reported incidence of thrombosis is relatively low, at approximately 3.9% [\u003cspan citationid=\"CR13\" class=\"CitationRef\"\u003e13\u003c/span\u003e, \u003cspan citationid=\"CR14\" class=\"CitationRef\"\u003e14\u003c/span\u003e].\u003c/p\u003e \u003cp\u003eGiven the limited reports on invasive procedures in patients with CD, an MDT evaluation was conducted for amniocentesis management, which represents a particularly novel aspect of this case. A comprehensive assessment of bleeding risk was essential. Vaginal bleeding occurs in approximately 2\u0026ndash;3% of amniocentesis procedures [\u003cspan citationid=\"CR15\" class=\"CitationRef\"\u003e15\u003c/span\u003e]. The Royal College of Obstetricians \u0026amp; Gynaecologists (RCOG) guideline [\u003cspan citationid=\"CR16\" class=\"CitationRef\"\u003e16\u003c/span\u003e] does not list bleeding as a risk. Despite ongoing debate, thromboelastography (TEG) provides valuable insights into coagulation status during pregnancy [\u003cspan citationid=\"CR4\" class=\"CitationRef\"\u003e4\u003c/span\u003e, \u003cspan citationid=\"CR8\" class=\"CitationRef\"\u003e8\u003c/span\u003e, \u003cspan citationid=\"CR9\" class=\"CitationRef\"\u003e9\u003c/span\u003e, \u003cspan citationid=\"CR17\" class=\"CitationRef\"\u003e17\u003c/span\u003e]. In this case, pre-procedural TEG showed no abnormalities, and MDT discussions concluded that the bleeding risk was low, supporting the safe conduct of the procedure. Amniocentesis was performed successfully and no prophylactic hemostatic agents were used pre-or postoperatively, the patient's hemostasis was achieved without complications.\u003c/p\u003e \u003cp\u003eSubsequent whole-exome sequencing identified a pathogenic mutation at the AαGly32Glu site in the FGA gene, confirming the diagnosis of CD. Fibrinogen gene mutations, especially in the Aα chain and thrombin cleavage sites, are strongly linked to thrombosis [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e]. These mutations reduce plasminogen binding, impair plasminogen activator activation, and increase self-binding propensity [\u003cspan citationid=\"CR18\" class=\"CitationRef\"\u003e18\u003c/span\u003e, \u003cspan citationid=\"CR19\" class=\"CitationRef\"\u003e19\u003c/span\u003e]. Notable mutations include AαArg16Cys, AαSer532Cys, γAsp364Val, BβAla68Thr, and AαArg554Cys [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e]. In this case, the identified mutation has not been linked to increased risk of thrombosis. Accordingly, the case classified as type 3A, which is characterized by a low thrombotic risk. The classification of dysfibrinogenemia is summarized in Table\u0026nbsp;\u003cspan refid=\"Tab1\" class=\"InternalRef\"\u003e1\u003c/span\u003e [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e].\u003c/p\u003e \u003cp\u003e \u003cdiv class=\"gridtable\"\u003e\u003ctable float=\"Yes\" id=\"Tab1\" border=\"1\"\u003e \u003ccaption language=\"En\"\u003e \u003cdiv class=\"CaptionNumber\"\u003eTable 1\u003c/div\u003e \u003cdiv class=\"CaptionContent\"\u003e \u003cp\u003eClassification of Dysfibrinogenemia\u003c/p\u003e \u003c/div\u003e \u003c/caption\u003e \u003ccolgroup cols=\"3\"\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c1\" colnum=\"1\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c2\" colnum=\"2\"\u003e\u003c/div\u003e \u003cdiv align=\"left\" class=\"colspec\" colname=\"c3\" colnum=\"3\"\u003e\u003c/div\u003e \u003cthead\u003e \u003ctr\u003e \u003cth align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDescription\u003c/p\u003e \u003c/th\u003e \u003cth align=\"left\" colname=\"c3\"\u003e \u003cp\u003eThrombosisRisk\u003c/p\u003e \u003c/th\u003e \u003c/tr\u003e \u003c/thead\u003e \u003ctbody\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType 3A\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDysfibrinogenemic patients either with bleeding phenotype or with thrombotic phenotype not fulfilling criteria for dysfibrinogenemia 3B or asymptomatic individuals\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eLow\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003ctr\u003e \u003ctd align=\"left\" colname=\"c1\"\u003e \u003cp\u003eType 3B\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c2\"\u003e \u003cp\u003eDysfibrinogenemic patients carriers of a thrombotic fibrinogen mutation or suffering from thrombotic events with a first-degree familial thrombotic history (relatives with the same genotype) without any other thrombophilia\u003c/p\u003e \u003c/td\u003e \u003ctd align=\"left\" colname=\"c3\"\u003e \u003cp\u003eHigh\u003c/p\u003e \u003c/td\u003e \u003c/tr\u003e \u003c/tbody\u003e \u003c/colgroup\u003e \u003c/table\u003e\u003c/div\u003e \u003c/p\u003e \u003cp\u003eGiven the elevated risk of obstetric complications in CD, attributable to fibrinogen's critical role in maintaining fetal\u0026ndash;maternal circulation and peripartum hemostasis, the patient was placed under MDT management to ensure individualized, risk-adapted care during pregnancy [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e, \u003cspan citationid=\"CR21\" class=\"CitationRef\"\u003e21\u003c/span\u003e]. FRT may be warranted in cases of recurrent pregnancy loss or placental insufficiency to maintain fibrinogen levels\u0026thinsp;\u0026ge;\u0026thinsp;1 g/L [\u003cspan citationid=\"CR6\" class=\"CitationRef\"\u003e6\u003c/span\u003e], and was reserved for potential vaginal bleeding, targeting fibrinogen levels\u0026thinsp;\u0026ge;\u0026thinsp;1.5 g/L [\u003cspan citationid=\"CR22\" class=\"CitationRef\"\u003e22\u003c/span\u003e]. In contrast, routine FRT or anticoagulation is generally unnecessary in uncomplicated pregnancies, where regular monitoring suffices. In this case, the pregnancy was uneventful apart from mild bruising. Although thrombosis-related mutations have been associated with fetal growth restriction and placental abruption [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e], this patient, classified as low thrombotic risk, showed normal fetal growth throughout gestation.\u003c/p\u003e \u003cp\u003eThe timing of pregnancy termination was primarily based on the mother's and fetus's overall condition. An MDT discussion and obstetric evaluation concluded a favorable pregnancy outcome with no adverse events, initially recommending vaginal delivery. Upon admission, the patient's Fib-Clauss level was 0.79 g/L. Given that natural labor, regional anesthesia, and cesarean section require maintaining fibrinogen\u0026thinsp;\u0026ge;\u0026thinsp;1.5 g/L [\u003cspan citationid=\"CR20\" class=\"CitationRef\"\u003e20\u003c/span\u003e]. Additionally, this case underscores the importance of carefully managing the timing, dosage, and duration of FCh infusion, as well as assessing postpartum thrombosis risk. The clinical pharmacist recommended FCh due to its pharmacokinetics, achieving peak fibrinogen levels within 2 hours and improving clot firmness 1 hour post-infusion [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. However, FCh infusion may increase the risk of pulmonary embolism [\u003cspan citationid=\"CR24\" class=\"CitationRef\"\u003e24\u003c/span\u003e] or deep vein thrombosis [\u003cspan citationid=\"CR25\" class=\"CitationRef\"\u003e25\u003c/span\u003e] in patients with CD. Thus, FCh administration was carefully timed: after labor onset for vaginal delivery and at least 2 hours before cesarean section. The dose was calculated based on the patient's pregnancy weight [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Blood bank communication ensured sufficient blood products for postpartum hemorrhage prevention. As the patient showed no signs of labor, oxytocin was administered, causing severe uterine contractions and concerns of fetal distress or placental abruption. Consequently, vaginal delivery was abandoned in favor of cesarean section. 3 g of FCh was administered 3 hours before the procedure to maintain fibrinogen\u0026thinsp;\u0026ge;\u0026thinsp;1.5 g/L [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. 2 hours after infusion, the fibrinogen level was 1.60 g/L, and epidural anesthesia was chosen in consultation with the anesthesiology department. Despite no significant bleeding during pregnancy, patients with CD are still at higher risk for postpartum hemorrhage. To address this, the obstetrician performed Hayman suturing during surgery, and 100 \u0026micro;g of carbetocin was administered postpartum to reduce bleeding from uterine atony. Given fibrinogen's half-life of 3\u0026ndash;4 days, levels returned to pre-infusion values by day 9 [\u003cspan citationid=\"CR23\" class=\"CitationRef\"\u003e23\u003c/span\u003e]. Postoperatively, the patient experienced no significant bleeding, and no additional FCh was given. Fibrinogen levels on postoperative days 3 and 6 were 1.40 g/L and 1.08 g/L, respectively, in line with guidelines [\u003cspan citationid=\"CR26\" class=\"CitationRef\"\u003e26\u003c/span\u003e]. Given that the patient was type 3A, a postoperative thrombosis risk assessment was performed according to standard protocols for pregnant women. Her postpartum Venous thromboembolism (VTE) risk score was 2 (2 points for conversion to cesarean section). As her score was below 3, only mechanical prophylaxis was administered. The postoperative course was uneventful, with favorable maternal and neonatal outcomes and no observed complications.\u003c/p\u003e \u003cp\u003eIn conclusion, this case underscores the importance of personalized management in pregnant patients with CD. A MDT approach, individualized treatment strategies, and appropriate use of FRT contributed to a successful outcome. Additionally, the case provides valuable insights into the management of invasive procedures such as amniocentesis in patients with CD, underscores the essential role of MDT in addressing bleeding and thrombotic risks and in preventing postpartum hemorrhage following cesarean section.\u003c/p\u003e \u003cp\u003e \u003cul\u003e \u003cli\u003e \u003cp\u003eThis case highlighting promising avenues for future research, including risk stratification through personalized biomarkers, optimization of FRT protocols, and the development of procedural guidelines for CD management in pregnancy, particularly within the context of MDT-led care.\u003c/p\u003e \u003c/li\u003e \u003c/ul\u003e \u003c/p\u003e"},{"header":"Abbreviations","content":"\u003cp\u003eACMG American College of Medical Genetics and Genomics\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eAPTT Activated partial thromboplastin time\u003c/p\u003e\n\u003cp\u003eCD Congenital dysfibrinogenemia\u003c/p\u003e\n\u003cp\u003eDIC Disseminated intravascular coagulation\u003c/p\u003e\n\u003cp\u003eFCh Fibrinogen concentrate (human)\u003c/p\u003e\n\u003cp\u003eFib-Clauss fibrinogen (Clauss method)\u003c/p\u003e\n\u003cp\u003eFib-PT-derived fibrinogen\u0026nbsp;(PT-derived method)\u003c/p\u003e\n\u003cp\u003eFRT Fibrinogen replacement therapy\u003c/p\u003e\n\u003cp\u003eLMWH Low\u0026nbsp;molecular weight heparin\u003c/p\u003e\n\u003cp\u003eMDT Multidisciplinary team\u0026nbsp;\u003c/p\u003e\n\u003cp\u003eMICU Medical Intensive Care Unit\u003c/p\u003e\n\u003cp\u003ePT Prothrombin time\u003c/p\u003e\n\u003cp\u003eRCOG Royal College of Obstetricians \u0026amp; Gynaecologists\u003c/p\u003e\n\u003cp\u003eTEG Thromboelastography\u003c/p\u003e\n\u003cp\u003eTT Thrombin time\u003c/p\u003e\n\u003cp\u003eVTE Venous thromboembolism\u003c/p\u003e"},{"header":"Declarations","content":"\u003cp\u003e\u003cstrong\u003eEthics approval and consent to participate:\u0026nbsp;\u003c/strong\u003eThis study was conducted in accordance with the ethical principles of the Declaration of Helsinki and received formal approval from the Institutional Review Board of the Sichuan Provincial Women's and Children's Hospital, Grant No. 20250326-73. Written informed consent was obtained from the participant for publication of anonymized clinical data and research findings, including any accompanying images or case details. All procedures maintained strict confidentiality in accordance with institutional data protection protocols.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConsent for publication:\u0026nbsp;\u003c/strong\u003eThis study was conducted in accordance with the ethical principles of the Declaration of Helsinki and received formal approval from the Institutional Review Board of the Sichuan Provincial Women's and Children's Hospital. Written informed consent was obtained from the participant for publication of anonymized clinical data and research findings, including any accompanying images or case details. Written informed consent has been obtained from the patient to publish this paper.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAvailability of data and materials:\u003c/strong\u003e All data generated or analysed during this study are included in this published article.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCompeting interests:\u0026nbsp;\u003c/strong\u003eThe authors declare no competing interests.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eFunding:\u0026nbsp;\u003c/strong\u003eThe Fund of Chengdu Medical College(Grant CYJD22-01); The Fund of Chengdu Medical College(Grant CYSZD23-05)\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAuthors' contributions:\u0026nbsp;\u003c/strong\u003eMeng Jie He: was a major contributor in writing the manuscript and collecting the data; Zhou Jun Wei: was a main contributor in writing the manuscript and collecting the data; Fei Wang: was involved in pharmaceutical care; Hai Ying Zhang: designed the study. All authors read and approved the final manuscript.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eAcknowledgements:\u0026nbsp;\u003c/strong\u003eNot applicable.\u003c/p\u003e"},{"header":"References","content":"\u003col\u003e\u003cli\u003e\u003cspan\u003eAcharya SS, Dimichele DM. Rare inherited disorders of fibrinogen. Haemophilia. 2008;14(6):1151\u0026ndash;8.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ede Moerloose P, Neerman-Arbez M. Congenital fibrinogen disorders. Semin Thromb Hemost. 2009;35(4):356\u0026ndash;66.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCasini A, Neerman-Arbez M, Ariens RA, et al. Dysfibrinogenemia: from molecular anomalies to clinical manifestations and management. J Thromb Haemost. 2015;13(6):909\u0026ndash;19.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHuang LY, Zhang DL, Fu RF, et al. Analysis of gene mutation spectrum and pharmacokinetics of fibrinogen infusion in 146 cases of congenital fibrinogen disorders. Zhonghua Xue Ye Xue Za Zhi. 2021;42(7):555\u0026ndash;62. \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003e10.3760/cma.j.issn.0253-2727.2021.07.005\u003c/span\u003e\u003cspan address=\"10.3760/cma.j.issn.0253-2727.2021.07.005\" targettype=\"DOI\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRichards S, Aziz N, Bale S, et al. Standards and guidelines for the interpretation of sequence variants: a joint consensus recommendation of the American College of Medical Genetics and Genomics and the Association for Molecular Pathology. Genet Med. 2015;17(5):405\u0026ndash;24.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eYan J, Liao L, Deng D, Zhou W, et al. Guideline for diagnosis and management of congenital dysfibrinogenemia. Clin Chim Acta. 2024;561:119680.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eXiang L, Luo M, Yan J, et al. Combined use of Clauss and prothrombin time-derived methods for determining fibrinogen concentrations: Screening for congenital dysfibrinogenemia. J Clin Lab Anal. 2018;32(4):e22322.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCasini A, Undas A, Palla R, et al. Diagnosis and classification of congenital fibrinogen disorders: communication from the SSC of the ISTH. J Thromb Haemost. 2018;16(9):1887\u0026ndash;90.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhou J, Ding Q, Chen Y, et al. Clinical features and molecular basis of 102 Chinese patients with congenital dysfibrinogenemia. Blood Cells Mol Dis. 2015;55(4):308\u0026ndash;15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eShapiro SE, Phillips E, Manning RA, et al. Clinical phenotype, laboratory features and genotype of 35 patients with heritable dysfibrinogenaemia. Br J Haematol. 2013;160(2):220\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCasini A, Blondon M, Lebreton A, et al. Natural history of patients with congenital dysfibrinogenemia. Blood. 2015;125(3):553\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCasini A, de Moerloose P. How I treat dysfibrinogenemia. Blood. 2021;138(21):2021\u0026ndash;30.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHanss MM, Ffrench PO, Mornex JF, et al. Two novel fibrinogen variants found in patients with pulmonary embolism and their families. J Thromb Haemost. 2003;1(6):1251\u0026ndash;7.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eHaverkate M, Samama M. Familial dysfibrinogenemia and thrombophilia. Report on a study of the SSC subcommittee on fibrinogen. Thromb Haemost. 1995;73(1):151\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eJindal A, Sharma M, Karena ZV et al. Amniocentesis. 2023 Aug 14. In: StatPearls. Available from: \u003cspan class=\"ExternalRef\"\u003e\u003cspan class=\"RefSource\"\u003ehttps://www.ncbi.nlm.nih.gov/books/NBK559247/\u003c/span\u003e\u003cspan address=\"https://www.ncbi.nlm.nih.gov/books/NBK559247/\" targettype=\"URL\" class=\"RefTarget\"\u003e\u003c/span\u003e\u003c/span\u003e. Treasure Island (FL): StatPearls Publishing; Accessed 28 Feb 2025.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eNavaratnam K, Alfirevic Z. Royal College of Obstetricians and Gynaecologists. Amniocentesis and chorionic villus sampling. Green-top Guideline 8 BJOG. 2022;129(1):e1\u0026ndash;15.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePeyvandi F, Palla R, Menegatti M, et al. Coagulation factor activity and clinical bleeding severity in rare bleeding disorders: results from the European Network of Rare Bleeding Disorders. J Thromb Haemost. 2012;10(4):615\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eTarumi T, Martincic D, Thomas A, et al. Familial thrombophilia associated with fibrinogen paris V: Dusart syndrome. Blood. 2000;96(3):1191\u0026ndash;3.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCollet JP, Soria J, Mirshahi M, et al. Dusart syndrome: a new concept of the relationship between fibrin clot architecture and fibrin clot degradability: hypofibrinolysis related to an abnormal clot structure. Blood. 1993;82(8):2462\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eCasini A, Abdul Kadir R, Abdelwahab M, et al. Management of pregnancy and delivery in congenital fibrinogen disorders: communication from the ISTH SSC Subcommittee on Factor XIII and Fibrinogen. J Thromb Haemost. 2024;22(5):1516\u0026ndash;21.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eValiton V, Hugon-Rodin J, Fontana P, et al. Obstetrical and postpartum complications in women with hereditary fibrinogen disorders: A systematic literature review. Haemophilia. 2019;25(5):747\u0026ndash;54.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003ePeterson W, Liederman Z, Baker J, et al. Hemorrhagic, thrombotic and obstetric complications of congenital dysfibrinogenemia in a previously asymptomatic woman. Thromb Res. 2020;196:127\u0026ndash;9.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eRoss C, Rangarajan S, Karimi M, et al. Pharmacokinetics, clot strength and safety of a new fibrinogen concentrate: randomized comparison with active control in congenital fibrinogen deficiency. J Thromb Haemost. 2018;16(2):253\u0026ndash;61.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eZhou J, Zhu P, Zhang X. A Chinese family with congenital dysfibrinogenemia carries a heterozygous missense mutation in FGA: Concerning the genetic abnormality and clinical treatment. Pak J Med Sci. 2017;33(4):968\u0026ndash;72.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMeng D, Zhang R, Ji C, et al. A low-dose therapy of fibrinogen supplement during perioperative period of total knee arthroplasty in an asymptomatic man with congenital dysfibrinogenemia: A case report. Med (Baltim). 2022;101(46):e31644.\u003c/span\u003e\u003c/li\u003e \u003cli\u003e\u003cspan\u003eMumford AD, Ackroyd S, Alikhan R, et al. Guideline for the diagnosis and management of the rare coagulation disorders: a United Kingdom Haemophilia Centre Doctors' Organization guideline on behalf of the British Committee for Standards in Haematology. Br J Haematol. 2014;167(3):304\u0026ndash;26.\u003c/span\u003e\u003c/li\u003e\u003c/ol\u003e"}],"fulltextSource":"","fullText":"","funders":[],"hasAdminPriorityOnWorkflow":false,"hasManuscriptDocX":true,"hasOptedInToPreprint":true,"hasPassedJournalQc":"","hasAnyPriority":false,"hideJournal":false,"highlight":"","institution":"","isAcceptedByJournal":true,"isAuthorSuppliedPdf":false,"isDeskRejected":"","isHiddenFromSearch":false,"isInQc":false,"isInWorkflow":false,"isPdf":false,"isPdfUpToDate":true,"isWithdrawnOrRetracted":false,"journal":{"display":true,"email":"[email protected]","identity":"bmc-pregnancy-and-childbirth","isNatureJournal":false,"hasQc":true,"allowDirectSubmit":false,"externalIdentity":"prch","sideBox":"Learn more about [BMC Pregnancy and Childbirth](http://bmcpregnancychildbirth.biomedcentral.com/)","snPcode":"","submissionUrl":"https://www.editorialmanager.com/prch/default.aspx","title":"BMC Pregnancy and Childbirth","twitterHandle":"@BMC_series","acdcEnabled":true,"dfaEnabled":false,"editorialSystem":"em","reportingPortfolio":"BMC Series","inReviewEnabled":true,"inReviewRevisionsEnabled":true},"keywords":"Congenital dysfibrinogenemia, Pregnancy, Amniocentesis, Multidisciplinary team","lastPublishedDoi":"10.21203/rs.3.rs-6137704/v1","lastPublishedDoiUrl":"https://doi.org/10.21203/rs.3.rs-6137704/v1","license":{"name":"CC BY 4.0","url":"https://creativecommons.org/licenses/by/4.0/"},"manuscriptAbstract":"\u003cp\u003e\u003cstrong\u003eBackground: \u003c/strong\u003eCongenital dysfibrinogenemia is an autosomal dominant inherited disorder characterized by abnormal fibrinogen. Managing patients with congenital dysfibrinogenemia during pregnancy and perioperative periods is complex, with potential risks of bleeding and thrombosis. Additionally, pregnancy may be associated with adverse events such as recurrent pregnancy loss, stillbirths, placental abruption, and fetal growth restriction. Due to significant individual variability in clinical presentation, there is currently no routine laboratory test to effectively predict bleeding or thrombotic risks, complicating clinical management, especially during pregnancy.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eCase presentation:\u003c/strong\u003e A 23-year-old primigravida was diagnosed with congenital dysfibrinogenemia after low fibrinogen levels were detected early in her pregnancy. Family history revealed similar fibrinogen abnormalities in her father and brother. Amniocentesis for fetal genetic testing was performed after a multidisciplinary team evaluated bleeding risks, with no complications during or immediately following the procedure. Genetic testing confirmed congenital dysfibrinogenemia in both the mother and fetus. Throughout the pregnancy, the patient was closely monitored, with no signs of bleeding, thrombosis, or other complications. At 39.3 weeks, following a failed attempt at vaginal delivery, she underwent a cesarean section with fibrinogen replacement therapy. The surgery was uneventful, and there were no significant bleeding or thrombotic events postoperatively.\u003c/p\u003e\n\u003cp\u003e\u003cstrong\u003eConclusions: \u003c/strong\u003eThis case emphasizes the critical role of a multidisciplinary team approach in managing congenital dysfibrinogenemia during pregnancy, amniocentesis, and perinatal care. It demonstrates the effectiveness of thorough disease assessment and fibrinogen replacement therapy in preventing bleeding, thereby ensuring positive outcomes for both the mother and fetus.\u003c/p\u003e","manuscriptTitle":"Multidisciplinary Team Management of Congenital Dysfibrinogenemia in Pregnancy: A Case Report","msid":"","msnumber":"","nonDraftVersions":[{"code":1,"date":"2025-04-21 08:18:27","doi":"10.21203/rs.3.rs-6137704/v1","editorialEvents":[{"type":"communityComments","content":0},{"type":"decision","content":"Revision 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