-
Current Problems in Clinical... 1984
Comparative Study Review
Topics: Afibrinogenemia; Amino Acid Sequence; Blood Coagulation; Blood Coagulation Tests; Carbohydrates; Factor XIII; Fibrinogen; Fibrinolysin; Fibrinopeptide A; Fibrinopeptide B; Genetic Variation; Humans; Macromolecular Substances; Peptide Fragments; Thrombin; Transglutaminases
PubMed: 6150812
DOI: No ID Found -
Seminars in Thrombosis and Hemostasis 1993
Review
Topics: Fetal Proteins; Fibrinogen; Genetic Variation; Humans; Mutation; Structure-Activity Relationship
PubMed: 8140431
DOI: 10.1055/s-2007-993290 -
Zhonghua Nei Ke Za Zhi Apr 2020
Topics: Afibrinogenemia; Asian People; Humans; Pedigree
PubMed: 32209199
DOI: 10.3760/cma.j.cn112138-20190730-00525 -
Journal of Thrombosis and Haemostasis :... Apr 2023Postpartum hemorrhage (PPH) may be exacerbated by hemostatic impairment. Information about PPH-associated coagulopathy is limited, often resulting in treatment... (Observational Study)
Observational Study
BACKGROUND
Postpartum hemorrhage (PPH) may be exacerbated by hemostatic impairment. Information about PPH-associated coagulopathy is limited, often resulting in treatment strategies based on data derived from trauma studies.
OBJECTIVES
To investigate hemostatic changes associated with PPH.
PATIENTS/METHODS
From a population of 11 279 maternities, 518 (4.6%) women were recruited with PPH ≥ 1000 mL or placental abruption, amniotic fluid embolism, or concealed bleeding. Routine coagulation and viscoelastometric results were collated. Stored plasma samples were used to investigate women with bleeds > 2000 mL or those at increased risk of coagulopathy defined as placenta abruption, amniotic fluid embolism, or need for blood components. Procoagulant factors were assayed and global hemostasis was assessed using thrombin generation. Fibrinolysis was investigated with D-dimer and plasmin/antiplasmin complexes. Dysfibrinogenemia was assessed using the Clauss/antigen ratio.
RESULTS
At 1000 mL blood loss, Clauss fibrinogen was ≤2 g/L in 2.4% of women and 6/27 (22.2%) cases of abruption. Women with very large bleeds (>3000 mL) had evidence of a dilutional coagulopathy, although hemostatic impairment was uncommon. A subgroup of 12 women (1.06/1000 maternities) had a distinct coagulopathy characterized by massive fibrinolysis (plasmin/antiplasmin > 40 000 ng/mL), increased D-dimer, hypofibrinogenemia, dysfibrinogenemia, reduced factor V and factor VIII, and increased activated protein C, termed acute obstetric coagulopathy. It was associated with fetal or neonatal death in 50% of cases and increased maternal morbidity.
CONCLUSIONS
Clinically significant hemostatic impairment is uncommon during PPH, but a subgroup of women have a distinct and severe coagulopathy characterized by hyperfibrinolysis, low fibrinogen, and dysfibrinogenemia associated with poor fetal outcomes.
Topics: Female; Humans; Infant, Newborn; Pregnancy; Afibrinogenemia; Antifibrinolytic Agents; Blood Coagulation Disorders; Cohort Studies; Embolism, Amniotic Fluid; Fibrinogen; Fibrinolysin; Hemostatics; Placenta; Postpartum Hemorrhage
PubMed: 36696216
DOI: 10.1016/j.jtha.2022.11.036 -
Ryoikibetsu Shokogun Shirizu 1998
Review
Topics: Afibrinogenemia; Antineoplastic Agents; Biomarkers; Bone Marrow Transplantation; Fibrinogen; Humans; Liver Diseases; Thrombin Time
PubMed: 9833562
DOI: No ID Found -
Research and Practice in Thrombosis and... Jul 2023Variants of fibrinogen sequences that bind to thrombin's catalytic sites are mostly associated with bleeding phenotypes, while variants with fibrinogen...
BACKGROUND
Variants of fibrinogen sequences that bind to thrombin's catalytic sites are mostly associated with bleeding phenotypes, while variants with fibrinogen nonsubstrate-thrombin-binding sites are commonly believed to cause thrombosis. AαGlu39 and BβAla68 play important roles in fibrin(ogen)-thrombin-nonsubstrate binding. The BβAla68Thr variant has been described in several unrelated families with apparent thrombotic phenotypes.
OBJECTIVES
Homozygous AαGlu39Lys variant (fibrinogen BOE II) was identified in a boy with dysfibrinogenemia who had multiple cerebral hemorrhages. A series of analyses were performed to assess the variant's functions and elucidate underlying bleeding mechanisms.
METHODS
Abnormal fibrinogen was purified from plasma and subjected to Western blot, fibrinogen and fibrin monomer polymerization, clottability, fibrinopeptides release, activated factor (F)XIII (FXIIIa) cross-linking, fibrinolysis, and scanning electron microscopy analyses.
RESULTS
Fibrinogen BOE II weakened the binding capacity of thrombin to fibrinogen and delayed the formation of fibrin clots. The release of fibrinopeptides, polymerization of fibrinogen catalyzed by thrombin, and cross-linking of FXIIIa of fibrinogen BOE II were impaired. In contrast, batroxobin-catalyzed fibrinogen polymerization and desA/desAB fibrin monomer polymerization did not differ from those in normal controls. Fibrin clots formed by fibrinogen BOE II were composed of thicker fibrin fibers and showed a faster fibrinolysis rate.
CONCLUSION
Defective fibrin(ogen)-thrombin-nonsubstrate binding is not necessarily associated with thrombotic disorders. When the hypercoagulable state created by increased circulating free thrombin is insufficient to compensate for defective hemostasis caused by slowly formed but rapidly lysed clots, the primary concern of thrombin-binding deficiency dysfibrinogenemia appears to be hemorrhage rather than thrombosis.
PubMed: 37601017
DOI: 10.1016/j.rpth.2023.102145 -
Polski Przeglad Chirurgiczny Apr 2020<b>Introduction: </b>Gastrointestinal bleeding is a common disease that surgeons encounter in everyday clinical practice. It is most often easy to diagnose...
<b>Introduction: </b>Gastrointestinal bleeding is a common disease that surgeons encounter in everyday clinical practice. It is most often easy to diagnose and treat. However, rare causes of bleeding can lead to delayed diagnosis and ineffective treatment. Dysfibrinogenemia is a qualitative fibrinogen disorder in which functional fibrinogen level is reduced with normal antigenic level. <br><b> Case report:</b> Herein we present the case of a 59-year-old female with recurrent gastrointestinal bleeds, that turned out to be an unusual manifestation of congenital dysfibrinogenemia. Detailed imaging and endoscopic diagnostics revealed portal hypertension with a non-bleeding 1-cm gastrointestinal stromal tumor and multiple angiodysplastic lesions in close proximity.
Topics: Afibrinogenemia; Female; Fibrinogen; Gastrointestinal Hemorrhage; Humans
PubMed: 32945266
DOI: 10.5604/01.3001.0014.0948 -
Zhongguo Shi Yan Xue Ye Xue Za Zhi Oct 2023To investigate a family with congenital dysfibrinogenemia, and analyze the risk of hemorrhage and thrombosis and blood transfusion strategies.
OBJECTIVE
To investigate a family with congenital dysfibrinogenemia, and analyze the risk of hemorrhage and thrombosis and blood transfusion strategies.
METHODS
Prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin time (TT) of the proband and her family members were detected by automatic coagulometer, fibrinogen (Fg) activity and antigen were detected by Clauss method and PT algorithm respectively. Meanwhile, thromboelastometry was analyzed for proband and her family members. Then, peripheral blood samples of the proband and her family members were collected, and all exons of and and their flanks were amplified by PCR and sequenced to search for gene mutations.
RESULTS
The proband had normal APTT and PT, slightly prolonged TT, reduced level of Fg activity (Clauss method). The Fg of the proband's aunt, son and daughter all decreased to varying degrees. The results of thromboelastogram indicated that Fg function of the proband and her family members (except her son) was basically normal. Gene analysis showed that there were 6233 G/A (p.AαArg35His) heterozygous mutations in exon 2 of gene in the proband, her children and aunt. In addition, 2 polymorphic loci were found in the family, they were gene g.9308A/G (p.AαThr331Ala) and gene g.12628G/A (p.BβArg478Iys) polymorphism, respectively. The proband was injected with 10 units of cryoprecipitate 2 hours before delivery to prevent bleeding, and no obvious bleeding occurred during and after delivery.
CONCLUSION
Heterozygous mutation of 6233G/A (p.AαArg35His) of gene is the biogenetic basis of the disease in this family with congenital dysfibrinogenemia.
Topics: Humans; Child; Female; Fibrinogen; Pedigree; Afibrinogenemia; Mutation; Blood Transfusion
PubMed: 37846702
DOI: 10.19746/j.cnki.issn.1009-2137.2023.05.034 -
Research and Practice in Thrombosis and... Dec 2021Afibrinogenemia and congenital dysfibrinogenemia (CD) are rare conditions with limited information available for appropriate management. Previous case reports have...
Afibrinogenemia and congenital dysfibrinogenemia (CD) are rare conditions with limited information available for appropriate management. Previous case reports have demonstrated the safe and efficacious use of fibrinogen replacement therapy (FRT) as a therapeutic approach to prevent hemorrhage and fetal loss in pregnant women with CD. In this case report, we present a 28-year-old pregnant woman who sought testing for CD given her family history. She denied any current or previous bleeding symptoms. Laboratory testing confirmed the diagnosis of CD. She was treated with FRT and prophylactic anticoagulation starting in her third trimester. She had preterm labor that prompted an urgent cesarean section with FRT support. This case adds to the sparse literature about fibrinogen disorders in pregnancy, and highlights the benefits, safety, and tolerability of FRT and prophylactic anticoagulation in pregnant women with CD. Finally, it emphasizes the importance of a multidisciplinary team approach for an uneventful delivery.
PubMed: 34816075
DOI: 10.1002/rth2.12619 -
Nouvelle Revue Francaise D'hematologie 1991A thrombotic tendency (venous or arterial) has been reported in some cases of dysfibrinogenemia. We report here the mechanism by which these thrombosis may occur. It may...
A thrombotic tendency (venous or arterial) has been reported in some cases of dysfibrinogenemia. We report here the mechanism by which these thrombosis may occur. It may be related either to a defective clot lysis due to a poor reactivity toward fibrinolytic enzymes or to a defective thrombin binding capacity of the abnormal clot. Acquired fibrin clot structure anomalies may also be responsible for a defective thrombolysis.
Topics: Fibrin; Fibrinogens, Abnormal; Fibrinolysis; Humans; Protein Binding; Thrombin; Thrombosis
PubMed: 1818298
DOI: No ID Found