Relationship between factor VIII genetic pattern and presence of mild hemophilia, severity of bleeding

Document Type : Original Article

Authors

1 Student Research Committee, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

2 Thalassemia & Hemoglobinopathy Research Center, Health Research Institute, Ahvaz Jundishapur University of Medical Sciences, Ahvaz, Iran.

3 Department of Biostatistics, Faculty of Medical Sciences,Tarbiat Modares University, Tehran, Iran.

Abstract

We aimed to assess mild hemophilia and relationship between blood parameters and genetic pattern and bleeding in patients with mild hemophilia. This cross-sectional descriptive-analytic study was performed on 50-member family was screened for people with mild hemophilia. To detect gene mutations in patients, peripheral blood was taken DNA was extracted to assess DNA variant of factor VIII by the PCR method and finally DNA sequences was determined using the ALFexpress auto read sequencing. The rate and severity of bleeding was evaluated using a special questionnaire. Out of 50 subjects studied, 32 (64.0%) including 16 men and 16 women were carriers for hemophilia, while 18 (36.0%, 13 men and 5 women) were normal for the disease. The mean level of factor VIII was significantly lower in those suffering mild hemophilia as compared to normal people (23.69 ± 4.30 versus 73.39 ± 3.42, p < 0.001). Similarly, the mean PTT was also higher in mild hemophilia group than in healthy group (34.00 ± 1.69 versus 26.95 ± 0.60, p < 0.001). Most cases with mild hemophilia had no bleeding or suffering mild bleeding. There was no significant correlation between severity of bleeding and the level of factor VIII in mild hemophilia. The gene analysis could confirm the genotype of hemophilia in those patients who were homozygous for factor VIII gene. Lowering factor VIII with overexpression of its related gene is dominant in patients with mild hemophilia; however, it may not be associated with the severity of bleeding in such patients.   

Keywords

References

Allan JN1, Friedman KD, DeSancho MT. Life-threatening bleeding in a patient with mild hemophilia A and heterozygosity for von Willebrand disease Type 2N. Int J Hematol. 2014 Dec;100(6):602-6. doi: 10.1007/s12185-014-1662-3. Epub 2014 Sep 12.
Bhoi D1, Kashyap L. Perioperative management of a patient with hemophilia A and crigler-najjar syndrome. J Anaesthesiol Clin Pharmacol. 2013 Oct;29(4):582-4. doi: 10.4103/0970-9185.119177.
Bhopale GM1, Nanda RK. Blood coagulation factor VIII: An overview. J Biosci. 2003 Dec;28(6):783-9.
Biswas A, Ivaskevicius V, Thomas A, Oldenburg J. Coagulation factor XIII deficiency. Diagnosis, prevalence and management of inherited and acquired forms. Hamostaseologie. 2014;34(2):160-6
Castaman G, Eckhardt C, van Velzen A, Linari S, Fijnvandraat K. Emerging issues in diagnosis, biology, and inhibitor risk in mild hemophilia A. In: Seminars in thrombosis and hemostasis: thieme Medical Publishers; 2016. pp. 507-512.
Fijnvandraat K, Cnossen MH, Leebeek FW, Peters M. Diagnosis and management of haemophilia. BMJ. 2012 May 02;344:e2707.
Iorio A, Oliovecchio E, Morfini M, Mannucci P, Directors AoIHC. Italian Registry of Haemophilia and Allied Disorders. Objectives, methodology and data analysis. Haemophilia 2008,14:444-453.
Jensson O, BERNVIL SS, JÖNSÖDTTIR S, Ingerslev J. Mild haemophilia A in Iceland: clinical genetic studies of three families with the same mutation. Journal of internal medicine 1994,235:443-450.
Konkle BA, Huston H, Nakaya Fletcher S. Hemophilia A. In: Adam MP, Ardinger HH, Pagon RA, Wallace SE, Bean LJH, Stephens K, Amemiya A, editors. GeneReviews® [Internet]. Seattle (WA): University of Washington, Seattle; 1993-2018.
Lippi G, Franchini M, Guidi GC. Diagnostic approach to inherited bleeding disorders. Clin Chem Lab Med. 2007;45:2–12. 
Mannucci PM1, Mancuso ME, Santagostino E. How we choose factor VIII to treat hemophilia. Blood. 2012 May 3;119(18):4108-14. doi: 10.1182/blood-2012-01-394411. Epub 2012 Mar 12.
Miesbach W1, Alesci S, Geisen C, Oldenburg J. Association between phenotype and genotype in carriers of haemophilia A. Haemophilia. 2011 Mar;17(2):246-51. doi: 10.1111/j.1365-2516.2010.02426.x. Epub 2010 Dec 1.
Paroskie A1,2, Gailani D1, DeBaun MR2, Sidonio RF Jr3. A cross-sectional study of bleeding phenotype in haemophilia A carriers. Br J Haematol. 2015 Jul;170(2):223-8. doi: 10.1111/bjh.13423. Epub 2015 Apr 1.
Peters R, Harris T.
advances and innovations in haemophilia treatment. Nat Rev Drug Discov. 2018 Jul;17(7):493-508.
POON MC, LUKE KH. Haemophilia care in China: achievements of a decade of World Federation of Hemophilia treatment centre twinning activities. Haemophilia 2008,14:879-888.
Powell JS1. Recombinant factor VIII in the management of hemophilia A: current use and futurepromise. Ther Clin Risk Manag. 2009 Apr;5(2):391-402. Epub 2009 May 20.
Srivastava, A. et al. Guidelines for the management of hemophilia. Haemophilia 19, e1–e47
Walker I, Pai M, Akabutu J, Ritchie DB, Growe G, Poon MC, et al. The Canadian Hemophilia Registry as the basis for a national system for monitoring the use of factor concentrates. Transfusion 1995,35:548-551.
International Journal of Education and Applied Sciences
Volume 3, Issue 3 - Serial Number 3
October 2021
Pages 108-115

Files

Share

How to cite

Statistics