Bleeding Episodes Among Patients with Congenital Fibrinogen Disorders, a Study On 12 New Iranian Patients
Background: Congenital fibrinogen disorders (CFDs) comprise about 10% of rare bleeding disorders (RBDs). CFDs are divided into two groups of quantitative (afibrinogenemia and hypofibrinogenemia) with autosomal recessive inheritance pattern, and qualitative (dysfibrinogenemia, hypodysfibrogenemia) disorders, mainly with autosomal dominant inheritance pattern. Sistan and Baluchestan Province in Iran, with its high rate of consanguineous marriages, has a high incidence of RBDs including CFD. In the current study, we report clinical manifestations of patients with CFDs.
Methods: Twelve new Iranian patients from Sistan and Baluchestan Province with different types of CFDs were selected for this study. Diagnosis of CFDs was based on clinical features and familial history followed by laboratory assessment by routine and specific coagulation tests including prothrombin time (PT) and activated partial time tests (APTT), as well as FI activity assay by Clauss method.
Results: Out of 12 patients, 3(25%) had afibrinogenemia, 7(58.3%) had hypofibrinogenemia while 2(16/7%) were suspected of having dysfibrinogenemia. Although umbilical cord bleeding (UCB) 9(75%) was the most common clinical presentation among the study population, this feature was not observed among patients with dysfibrinogenemia. Hematoma (100%) was the most common presentation of patients with dysfibrinogenemia.
Conclusion: Results of this study revealed that some clinical presentations are the diagnostic features of CFDs and can be used for precise and in-time diagnosis CFDs in conjunction with family history and laboratory findings.
Keywords: Fibrinogen Deficiency; Congenital Afibrinogenemia; Blood Coagulation Disorder; Afibrinogenemia
Neerman-Arbez M, De Moerloose P, Bridel C, Honsberger A, Schönbörner A, Rossier C, et al. Mutations in the fibrinogen Aα gene account for the majority of cases of congenital afibrinogenemia. Blood. 2000;96(1):149-152.
Vu D, Neerman-Arbez M. Molecular mechanisms accounting for fibrinogen deficiency: from large deletions to intracellular retention of misfolded proteins. Journal of Thrombosis and Haemostasis. 2007;5(s1):125-131.
Asselta R, Duga S, Tenchini M. The molecular basis of quantitative fibrinogen disorders. Journal of Thrombosis and Haemostasis. 2006;4(10):2115-2129.
Kent WJ, Sugnet CW, Furey TS, Roskin KM, Pringle TH, Zahler AM, et al. The human genome browser at UCSC. Genome research. 2002;12(6):996-1006.
Redman CM, Xia H. Fibrinogen biosynthesis. Annals of the New York Academy of Sciences. 2001;936(1):480-495.
Vu D, Bolton-Maggs PH, Parr JR, Morris MA, De Moerloose P, Neerman-Arbez M. Congenital afibrinogenemia: identification and expression of a missense mutation in FGB impairing fibrinogen secretion. Blood. 2003;102(13):4413-4415.
Acharya S, Dimichele D. Rare inherited disorders of fibrinogen. Haemophilia. 2008;14(6):1151-1158.
Peyvandi F, Duga S, Akhavan S, Mannucci P. Rare coagulation deficiencies. Haemophilia. 2002;8(3):308-321.
Lak M, Keihani M, Elahi F ,Peyvandi F, Mannucci P. Bleeding and thrombosis in 55 patients with inherited afibrinogenaemia. British journal of haematology. 1999;107(1):204-206.
Peyvandi F, Haertel S, Knaub S, Mannucci P. Incidence of bleeding symptoms in 100 patients with inherited afibrinogenemia or hypofibrinogenemia. Journal of Thrombosis and Haemostasis. 2006;4(7):1634-1637.
Hanss M, Biot F. A database for human fibrinogen variants. Annals of the New York Academy of Sciences. 2001;936(1):89-90.
Naderi M, Eshghi P, Cohan N, MIRI-MOGHADDAM E, Yaghmaee M, Karimi M. Successful delivery in patients with FXIII deficiency receiving prophylaxis: report of 17 cases in Iran. Haemophilia.2012;18(5):773-6.
Akbar Dorgalaleh, Shadi Tabibian, Maryam Sadat Hosseini, Yadollah Farshi, Fateme Roshanzamir, Majid Naderi, Ahmad Kazemi, Farhad Zaker, Ali Noroozi Aghideh, Morteza Shamsizadeh .Diagnosis of Factor XIII Deficiency. Hematology.2016;1-28.
Acharya, S. S., Coughlin, A., & Dimichele, D. M. Rare Bleeding Disorder Registry: deficiencies of factors II, V, VII, X, XIII, fibrinogen and dysfibrinogenemias. Journal of Thrombosis and Haemostasis. 2004; 2(2):248-256.
Naderi, M., Eshghi, P., Saneei Moghaddam, E., Alizadeh, S., Dorgalaleh, A., Younesi, M. R., & Khateb, Z. K. Safety of human blood products in rare bleeding disorders in southeast of Iran. Haemophilia.2013; 19(2): e90-e92.
16. Peyvandi, F. Epidemiology and treatment of congenital fibrinogen deficiency. Thrombosis research.2012; 130: S7-S11.
Dorgalaleh A, Naderi M, Hosseini MS, Alizadeh S, Hosseini S, Tabibian S, et al., editors. Factor XIII Deficiency in Iran: A Comprehensive Review of the Literature. Seminars in thrombosis and hemostasis; 2015.
Naderi M, Dorgalaleh A, Alizadeh S, Tabibian S, Hosseini S, Shamsizadeh M, et al. Clinical manifestations and management of life-threatening bleeding in the largest group of patients with severe factor XIII deficiency. International journal of hematology. 2014;100(5):443-9.
Authors who publish with this journal agree to the following terms:
a. Authors retain copyright and grant the journal right of first publication with the work simultaneously licensed under a Creative Commons Attribution License that allows others to share the work with an acknowledgement of the work's authorship and initial publication in this journal.
b. Authors are able to enter into separate, additional contractual arrangements for the non-exclusive distribution of the journal's published version of the work (e.g., post it to an institutional repository or publish it in a book), with an acknowledgement of its initial publication in this journal.
c. Authors are permitted and encouraged to post their work online (e.g., in institutional repositories or on their website) prior to and during the submission process, as it can lead to productive exchanges, as well as earlier and greater citation of published work (See The Effect of Open Access).