Clinical and molecular characterization of Iranian patients with congenital fibrinogen disorders

Mohsenian, Samin; Seidizadeh, Omid; Mirakhorli, Mojgan; Jazebi, Mohammad; Azarkeivan, Azita

doi:10.1016/j.transci.2021.103203

Cited by 7 publications

(16 citation statements)

References 36 publications

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“…Out of 164 patients with a pre‐existing diagnosis of CFD, 21 a total number of 100 patients had complete laboratory and clinical data and could be included in this study. The mean (±SD) age of the study population at the time of diagnosis ( n = 100) was 18.5 (±15.9) that 46 were adults and 54 children.…”

Section: Resultsmentioning

confidence: 99%

Diagnostic utility of bleeding assessment tools in congenital fibrinogen deficiencies

et al. 2023

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Background:The assessment of clinical history is crucial before referring a patient for further laboratory testing. Bleeding assessment tools (BAT) are developed to standardize clinical evaluation. A small number of patients with congenital fibrinogen deficiencies (CFDs) have been evaluated with these tools without definitive results. Aims:We compared the adequacy of the ISTH-BAT and the European network of rare bleeding disorders bleeding score system (EN-RBD-BSS) to identify patients with CFDs. The correlation between the two BATs and fibrinogen levels and patient clinical grade severity was further analyzed. Methods: We included 100 Iranian patients with CFDs. Routine coagulation and fibrinogen-specific tests (fibrinogen antigen [Fg:Ag] and activity [Fg:C]) were performed. The ISTH-BAT and EN-RBD-BSS were used to assess the bleeding score (BS) of all patients. Results:The ISTH-BAT and EN-RBD-BSS median (range) were 4 (0-16) and 2.21 (−1.49 to 6.71), with a statistically significant moderate correlation between the two systems (r = .597, P < .001). In patients with quantitative deficiencies (afibrinogenemia and hypofibrinogenemia), the correlation between Fg:C and the ISTH-BAT was moderately negative (r = −.4, P < .001), while the correlation between Fg:C and the EN-RBD-BSS was weakly negative (r = −.38, P < .001). Overall, 70% and 72% of patients with fibrinogen deficiencies were correctly identified by both the ISTH-BAT and EN-RBD-BSS, respectively. Conclusion:These results suggest that in addition to the ISTH-BAT, the EN-RBD-BSS may also be useful in identifying CFD patients. We found a significant level of sensitivity for detecting fibrinogen deficiency in the two BATs, and bleeding severity classification correctly identified severity grades in almost two-thirds of patients.

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Section: Resultsmentioning

confidence: 99%

Diagnostic utility of bleeding assessment tools in congenital fibrinogen deficiencies

et al. 2023

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“… 34 In addition, in our recent study, the incidence rate of umbilical cord bleeding and cutaneous bleeding was almost the same (47%). 27 Due to the wide variety of bleeding manifestations in patients with CFD, it is difficult to determine which symptoms are the most frequent. 27 , 35 Nonetheless, women with hypofibrinogenemia and dysfibrinogenemia are more prone to suffer from obstetric complications.…”

Section: Discussionmentioning

confidence: 99%

“…In most dysfibrinogenemic cases, the disease is caused by heterozygous missense mutations in FGA and FGG ; hypodysfibrinogenemic patients are heterozygous or combined heterozygous, and their causative mutations are mainly located in FGG . 27 Despite the relative rarity of CFD, the number of cases reported so far is substantial. 14 , 25 , 27 Nonetheless, combining the results obtained from laboratory phenotype, genotype, and clinical analyses is warranted to yield valuable information on the development and course of these diseases as well as for the choice of the appropriate treatment.…”

Section: Introductionmentioning

confidence: 99%

“… 27 Despite the relative rarity of CFD, the number of cases reported so far is substantial. 14 , 25 , 27 Nonetheless, combining the results obtained from laboratory phenotype, genotype, and clinical analyses is warranted to yield valuable information on the development and course of these diseases as well as for the choice of the appropriate treatment. Therefore, the establishment of international collaborations and registries are key steps that help to improve patient management.…”

Section: Introductionmentioning

confidence: 99%

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Congenital fibrinogen disorders: a retrospective clinical and genetic analysis of the Prospective Rare Bleeding Disorders Database

Mohsenian,

Palla,

Menegatti

et al. 2024

Blood Advances

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Congenital fibrinogen deficiency (CFD) is a rare bleeding disorder caused by mutations in FGA, FGB and FGG. We sought to comprehensively characterize patients with CFD using PRO-RBDD (Prospective Rare Bleeding Disorders Database). Clinical phenotypes, laboratory and genetic features were investigated using retrospective data from the PRO-RBDD. Patients were classified from asymptomatic to grade III based on their bleeding severity. In addition, FGA, FGB and FGG were sequenced to find causative variants. A total of 166 CFD cases from 16 countries were included, of whom 123 (30 afibrinogenemia, 33 hypofibrinogenemia, 55 dysfibrinogenemia, 5 hypodysfibrinogenemia) were well characterized. Considering the previously established factor activity and antigen level thresholds, bleeding severity was correctly identified in 58% of cases. The rate of thrombotic events among afibrinogenemic and hypofibrinogenemic patients were relatively similar (11% and 10%) and surprisingly higher than in dysfibrinogenemic cases. The rate of spontaneous abortions among 68 pregnancies was 31%, including 86% in dysfibrinogenemic women and 14% with hypofibrinogenemia. 86 patients received treatment (69 on-demand and/or 17 on prophylaxis), fibrinogen concentrates being the most frequently used product. Genetic analysis was available for 91 cases and 41 distinct variants were identified. Hotspot variants (FGG, p.Arg301Cys/His and FGA, p.Arg35Cys/His) were present in 51% of dysfibrinogenemia. Obstetric complications were commonly observed in dysfibrinogenemia. This large multicenter study provided a comprehensive insight into the clinical, laboratory and genetics of patients with CFDs. We conclude that bleeding severity grades were in agreement with the established factor activity threshold in nearly half of the cases with quantitative defects.

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“…Congenital dysfibrinogenemia (CD), a rare autosomal dominant inheritance disease, manifests heterogeneous clinical features, making it impossible to estimate the prevalence of CD, like congenital afibrinogenemia, and there is no correlation between the genotype and the phenotype. [1][2][3] Among heterogeneous clinical symptoms, the bleeding phenotype is more frequent than thrombosis and asymptomatic, but the phenotype at diagnosis can only represent situation at the moment. [4,5] In supplement therapy, different variants respond differently to fibrinogen concentrate (FC).…”

Section: Introductionmentioning

confidence: 99%

A low-dose therapy of fibrinogen supplement during perioperative period of total knee arthroplasty in an asymptomatic man with congenital dysfibrinogenemia: A case report

Meng

Zhang

et al. 2022

Medicine

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Rationale: Congenital dysfibrinogenemia (CD) is a rare coagulation system disease that is often treated without unified management. Individualized treatment thereof presents clinicians with great challenges.Patient concerns: A patient who was about to undergo total knee arthroplasty was found to have CD.Diagnoses: Coagulation screening revealed low fibrinogen, prolonged thrombin time, minor prolonged prothrombin time, and normal activated partial thromboplastin time were detected during admission, but no abnormal personal and family history findings were observed. Therefore, CD and hypofibrinogenemia were suspected. The gene sequencing confirmed the diagnosis of CD. Interventions:The patient received plenty and low level of fibrinogen concentrate during 2 perioperative periods, respectively.Outcomes: Successful clinical outcomes were obtained using different treatment strategies.Lessons: In contrast to prior case reports, this case illustrates the feasibility of low dosing of fibrinogen supplements within an asymptomatic patient in a selective operation. Changes in the level of fibrinogen and fibrin degradation product are of great importance for individualized treatment after supplementation.Abbreviations: CD = congenital dysfibrinogenemia, CH = congenital hypofibrinogenemia, DVT = deep vein thrombosis, FC = fibrinogen concentrate, LMWH = low molecular weight heparin, TKA = total knee arthroplasty, TXA = tranexamic acid.

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Clinical and molecular characterization of Iranian patients with congenital fibrinogen disorders

Cited by 7 publications

References 36 publications

Diagnostic utility of bleeding assessment tools in congenital fibrinogen deficiencies

Diagnostic utility of bleeding assessment tools in congenital fibrinogen deficiencies

Congenital fibrinogen disorders: a retrospective clinical and genetic analysis of the Prospective Rare Bleeding Disorders Database

A low-dose therapy of fibrinogen supplement during perioperative period of total knee arthroplasty in an asymptomatic man with congenital dysfibrinogenemia: A case report

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