DOI: http://dx.doi.org/10.18203/2320-6012.ijrms20212258

The key complications of hemophilia and recent advancements in their management: an update

Afrisya Adlina Mohd Azhar, Alicia Ann Raj, Filzah Izam, Muhmammad Danial Mokhtar, Nur Asfarina Izzati Aziz Zakaria, Kishore Gopal Banerjee

Abstract


Hemophilia A is an X-linked recessive disorder which is due to factor VIII deficiency. It is a life-threatening coagulation disorder leading to complications including hemophilic-arthropathy, development of inhibitors, transfusion-related infections and profound psychosocial impact on the life of the patients. The aim of this study is to analyze the challenges in complications and the latest advancements in managing those complications. A thorough and systemic literature review was done to fulfill the objective of this study. The emergence of hemophilic arthropathy due to repeated symptoms of hemarthrosis is the most frequent complication found in haemophiliacs. Another critical complication, mainly seen in resource-poor settings is the development of lethal and severe bleeding episodes including episodes of intracranial hemorrhage. The development of inhibitors is another major challenge which often adds profoundly to the financial burden faced by hemophilia patients. Another major challenge is acquiring various transfusion-transmitted infections which was particularly more common few decades back. Studies also have revealed that there are myriads of significant psychosocial effects affecting the quality of life of hemophiliacs. Emerging treatments such as gene therapy, non-clotting factor concentrate products and extended half-life therapy can usher a new era in the management and the quality of life in hemophilia patients.


Keywords


Hemophilia, Bleeding disorders, Factor VIII, Complications, Inhibitors, Prophylaxis, Management, Arthropathy, Psychosocial

Full Text:

PDF

References


Shaikh MF, Shaikh FA. COVID-19 and mental health: Our reactions to its actions. Neurosci Res Notes. 2020;3(2):1-3.

Nance D, Fletcher SN, Bolgiano DC, Thompson AR, Josephson NC, Konkle BA. Factor VIII mutation and desmopressin-responsiveness in 62 patients with mild haemophilia A. Haemophilia. 2013;19(5):720-6.

Blanchette VS, Key NS, Ljung LR, Manco JMJ, Berg HM, Srivastava A. Definitions in hemophilia: Communication from the SSC of the ISTH. J Thromb Haemost. 2014;12(11):1935-9.

Witkop M, Guelcher C, Forsyth A, Hawk S, Curtis R, Kelley L, et al. Treatment outcomes, quality of life, and impact of hemophilia on young adults (aged 18-30 years) with hemophilia. Am J Hematol. 2015;90:3-10.

Perrin GQ, Herzog RW, Markusic DM. Update on clinical gene therapy for hemophilia. Blood. 2019;133(5):407-14.

Sharif Ishak SIZ, Chin YS, Mohd TMN, Chan YM, Mohd SZ. Effectiveness of a school-based intervention on knowledge, attitude and practice on healthy lifestyle and body composition in Malaysian adolescents. BMC Pediatr. 2020;20(1):1-12.

Rodriguez MEC. Hemophilic arthropathy: current treatment challenges and future prospects. Expert Opin Orphan Drugs. 2018;6(8):477-83.

Wyseure T, Mosnier LO, Drygalski A. Advances and challenges in hemophilic arthropathy. Semin Hematol. 2016;53(1):10-9.

Lobet S, Hermans C, Lambert C. Optimal management of hemophilic arthropathy and hematomas. J Blood Med. 2014;207.

Pulles AE, Mastbergen SC, Schutgens REG, Lafeber FPJG, Vulpen LFD. Pathophysiology of hemophilic arthropathy and potential targets for therapy. Pharmacol Res. 2017;115:192-9.

Leslie R, Catherine M. Modern management of haemophilic arthropathy. Br J Haematol. 2007;136(6):777-87.

Ljung R, Auerswald G, Benson G, Dolan G, Duffy A, Hermans C, et al. Inhibitors in haemophilia A and B: Management of bleeds, inhibitor eradication and strategies for difficult-to-treat patients. Eur J Haematol. 2019;102(2):111-22.

Srivastava A, Brewer AK, Mauser BEP, Key NS, Kitchen S, Llinas A, et al. Guidelines for the management of hemophilia. Haemophilia. 2013;19(1):1-47.

Lewis KB, Hughes RJ, Epstein MS, Josephson NC, Kempton CL, Kessler CM, et al. Phenotypes of allo- and autoimmune antibody responses to FVIII characterized by surface plasmon resonance. PLoS One. 2013;8(5):61120.

Gouw SC, Berg HM, Fischer K, Auerswald G, Carcao M, Chalmers E, et al. Intensity of factor VIII treatment and inhibitor development in children with severe hemophilia A: The RODIN study. Blood. 2013;121(20):4046-55.

Santagostino E, Mancuso ME, Rocino A, Mancuso G, Mazzucconi MG, Tagliaferri A, et al. Environmental risk factors for inhibitor development in children with haemophilia A: A case-control study. Br J Haematol. 2005;130(3):422-7.

Rocino A, Franchini M, Coppola A. Treatment and Prevention of Bleeds in Haemophilia Patients with Inhibitors to Factor VIII/IX. J Clin Med. 2017;6(4):46.

Angiolella LS, Cortesi PA, Rocino A, Coppola A, Hassan HJ, Giampaolo A, et al. The socioeconomic burden of patients affected by hemophilia with inhibitors. Eur J Haematol. 2018;101(4):435-56.

Shima M, Hanabusa H, Taki M, Matsushita T, Sato T, Fukutake K, et al. Factor VIII–Mimetic Function of Humanized Bispecific Antibody in Hemophilia A. N Engl J Med. 2016;374(21):2044-53.

Oldenburg J, Mahlangu JN, Kim B, Schmitt C, Callaghan MU, Young G, et al. Emicizumab Prophylaxis in Hemophilia A with Inhibitors. N Engl J Med. 2017;377(9):809-18.

Mousavi SH, Khairkhah N, Bahri TD, Anvar A, Saraji AA, Behnava B, et al. First Report of Prevalence of Blood-Borne Viruses (HBV, HCV, HIV, HTLV-1 and Parvovirus B19) Among Hemophilia Patients in Afghanistan. Sci Rep. 2019;9(1):6-11.

Zhubi B, Mekaj Y, Baruti Z, Bunjaku I, Belegu M. Transfusion-transmitted infections in haemophilia patients. Bosn J Basic Med Sci. 2009;9(4):271-7.

Elnajeh M, Ghazi HF, Abdalqader MA, Baobaid MF. Knowledge, attitude and practice towards blood donation and its associated factors among university students in Shah Alam, Malaysia. Int J Community Med Public Heal. 2017;4(7):2230.

Ghosh K. Management of haemophilia and its complications in developing countries. Clin Lab Haematol. 2004;26(4):243-51.

Urmila KV, Sarin SM, Mohmad MTP. Prevalence of transfusion transmitted infections in children with inherited coagulation disorders. Int J Contemp Pediatr. 2018;5(5):1740.

Junaid M, Siddique AN, Masood MT, Alam I, Waqas M, Saba, et al. Detection and prevalence of hepatitis B, C and HIV viral infections among hemophilia patients in Peshawar, Pakistan. J Entomol Zool Stud. 2017;5(2):180-4.

Ljung RCR, Chambost H, Stain AM, Dimichele D. Haemophilia in the first years of life. Haemophilia. 2008;14(3):188-95.

Majid Z, Tahir F, Qadar LT, Shaikh MY, Mahmood Shah SM. Hemophilia A with a Rare Presentation of Hemarthrosis and Arthropathy Involving Multiple Joints in a Young Male Child. Cureus. 2019;11(4):4524.

Mansouritorghabeh H. Clinical and laboratory approaches to hemophilia A. Iran J Med Sci. 2015;40(3):194-205.

Franchini M, Mannucci PM. Hemophilia A in the third millennium. Blood Rev. 2013;27(4):179-84.

Anderst JD, Carpenter SL, Presley R, Berkoff MC, Wheeler AP, Sidonio RF, et al. Relevance of Abusive Head Trauma to Intracranial Hemorrhages and Bleeding Disorders. Pediatrics. 2018;141(5):20173485.

Cutter S, Molter D, Dunn S, Hunter S, Peltier S, Haugstad K, et al. Impact of mild to severe hemophilia on education and work by US men, women, and caregivers of children with hemophilia B: The Bridging Hemophilia B Experiences, Results and Opportunities into Solutions (B-HERO-S) study. Eur J Haematol. 2017;98:18-24.

Baumann K, Hernandez G, Witkop M, Peltier S, Dunn S, Cutter S, et al. Impact of mild to severe hemophilia on engagement in recreational activities by US men, women, and children with hemophilia B: The Bridging Hemophilia B Experiences, Results and Opportunities into Solutions (B-HERO-S) study. Eur J Haematol. 2017;98:25-34.

Pinto P, Paredes A, Pedras S, Costa P, Crato M, Fernandes S, et al. Sociodemographic, Clinical, and Psychosocial Characteristics of People with Hemophilia in Portugal: Findings from the First National Survey. TH Open. 2018;2(1):54-67.

Buckner TW, Sidonio R, Witkop M, Guelcher C, Cutter S, Iyer NN, et al. Correlations between patient-reported outcomes and self-reported characteristics in adults with hemophilia B and caregivers of children with hemophilia B: analysis of the B-HERO-S study. Patient Relat Outcome Meas. 2019;10:299-314.

Witkop M, Guelcher C, Forsyth A, Quon D, Hawk S, Curtis R, et al. Challenges in transition to adulthood for young adult patients with hemophilia: Quantifying the psychosocial issues and developing solutions. Am J Hematol. 2015;90:1-2.

Ganasegeran K, Rajendran AK, Dubai SAR. Psycho-socioeconomic factors affecting complementary and alternative medicine use among selected rural communities in Malaysia: A cross-sectional study. PLoS One. 2014;9(11):2-7.

Shbool G, Vakiti A. Acquired Hemophilia A Presenting as Intramuscular Hematoma. J Investig Med High Impact Case Reports. 2018;6.

Mahlangu J, Cerquiera M, Srivastava A. Emerging therapies for haemophilia- Global perspective. Haemophilia. 2018;24:15-21.

Rangarajan S, Walsh L, Lester W, Perry D, Madan B, Laffan M, et al. AAV5–Factor VIII Gene Transfer in Severe Hemophilia A. N Engl J Med. 2017;377(26):2519-30.