A Review on Hemophilia it’s diagnostic tests and the application of Extending Half Life Products

Manish Kumar Gupta^1*, Krishna Gopal², Anil Ahuja³, Sudheesh Shukla⁴ and Ajay Bilandi⁵

^*Correspondence: Manish Kumar Gupta, Department of Pharmaceutical Chemistry, SGT University, Gurugram Haryana, India, Email:

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Introduction

Mechanism of blood clotting

The process of blood clotting can be defined as a process of producing a clot in order to inhibit bleeding [1]. It is a complex process. The body depends on collaboration of 3

processes so as to inhibit bleeding:

First two processes are involved in primary hemostasis:

• Vasoconstriction: It is defined as body’s first response to the injury caused in vascular wall. Whenever there is an injury, constriction of vessel walls occurs which leads to the decreased flow of blood towards the site of injury.

• Platelet plug: Just at site of damage, platelets collect. They act like a “plug” by acting in unison. In platelets, production of fibrin clot, termed as secondary hemostasis, is initiated [2].

Secondary hemostasis: There is no way for platelets to shield vessel wall from injury. When you have a blood clot, it should form at the wound site. The production of clot depends on different elements known as clotting factors. These elements are denoted from the roman numerals I till XIII. The clotting cascade occurs as these mechanisms interact with one another. When fibrinogen is cleaved into fibrin and a soluble solids, and fibrin, a – anti protein, this leads in a cascading effect Fibrin proteins produce a clot by linking together. Two separate yet interrelated mechanisms are used in the coagulation sequence the intrinsically and extrinsically routes [3].

Extrinsic pathway: External damage activates the extrinsic pathway, causing blood to leak from a vascular system. This pathway performs quicker function than that of intrinsic pathway. It functions with the help of factor VII.

Intrinsic pathway: The intrinsic cascade is triggered via damage within vascular system and may be triggered with the exposed collagen, platelets, hormones or endothelial cells. Since this route is gentler than that of extrinsic route, but this pathway is more significant. Factors XII, XI, IX, and VIII are involved [4].

Common pathway: A general pathway is carried out in which all the pathways combine and complete the clot formation pathway. Factors I, II, V, and X are all included in the general pathway. Factor IX (F-IX) and Factor IX (FIX) , they are both X-linked hereditary bleeding disorders, which are associated with germline abnormalities in F-IX and F-VIII genes, respectively. Factor plasma concentration of 1% or less, 2–5%, and 6–40% may both engage in the internal method of coagulation factors, and afflicted people may have disease that is very mild, moderate, or severe, depending on the amount of factor present. One in every five thousand males is born having haemophilia A, whereas one in every thirty thousand males is born having haemophilia B. Hemorrhage in people with severe hereditary hemorrhagic telangiectasia is rather prevalent. Staphylococcus infections may lead to joint, nerve, or soft tissue haemorrhages for no apparent cause. Deadly hemorrhage outbreaks, like cerebral haemorrhages, may also occur [5]. Factor insufficiency seldom causes unintentional haemorrhage, but trauma or surgery-related haemorrhage is more likely to occur.

A variant of haemophilia called haemophilia the consequences from deficiency of the coagulation factor VIII; whereas another kind called haemophilia B is related to a deficiency of the clotting factors IX. They are often acquired via an X chromosome through one parent. Clotting antibodies may arise in early development because a novel mutation cannot be detected, or they may develop later in life due to haemophilia due to an increase in clotting antibodies. Other manifestations include low factor XI-deficient haemophilia C, and low factor V-deficient parahemophilia. Hemophilia may lead to tumours, autoimmune disorders, and pregnancy complications.

Discussion

Genes Involved in Hemophilia Discussion

The F9 as well as F8 alleles both are present on X chromosome, positioned towards the end of a very long arm (Xq28 for F8 and Xq27 for F9).

The F8 gene is very massive (about 180 kb), with a very complicated structure (twenty six exons), while the gene F9 being much smaller (of about thirty four kb), and has a more straightforward structure (only eight exons). Hundreds of people who have the haemophilia mutations have been discovered. The overwhelming number of mutations revealed underscores the genetic complexity of haemophilia.

Deletions, point mutations, rearrangements/ inversions and insertions are found in the F9 and F8 have all been linked to haemophilia A and B in people who exhibitthese mutations [8]. While these mutations are somewhat prevalent in HA and HB, the frequency varies. in particular, the gross genetic flaws contribute to around 7% of HB cases, but HA has half of its severe instances resulting from rearrangements in the genes, wherein inversion of the 22nd intron is the most common.

References

1. Orlova NA, Kovnir SV, Vorobiev II, et al. Blood clotting factor VIII: From evolution to therapy. Acta Naturae 2013;5(2):19â??39.

   [Crossref], [Google Scholar], [Indexed]  

2. Favaloro EJ, Zafer M, Nair SC, et al. Evaluation of primary in haemostatis in people with neurofibromatosis type 1. Clin Lab Haematol 2004;26(5):341â??345.

   [Crossref], [Google Scholar], [Indexed]

3. Durachim A, Astuti D. â??Hemostatis [Book]. Teknol Lab MedisKemenkes2018.
4. Volin L, Vesa R, Vahtera E, et al. â??Heme arginate: Effects on hemostatis. Blood 1988;71(3): 625-628.

   [Crossref], [Google Scholar], [Indexed]

5. Feng Y, Li Q, Shi P, et al. Mutation analysis in the F8 gene in 485 families with haemophilia A and prenatal diagnosis in China. Haemophilia 2020;27(1):e88â??e92.

   [Crossref], [Google Scholar], [Indexed]

6. Gouw SC, van den Berg HM, Oldenburg J, et al. F8 gene mutation type and inhibitor development in patients with severe hemophilia A: Systematic review and meta-analysis. Blood 2012;119(12):2922â??2934.

   [Crossref], [Google Scholar], [Indexed]

7. Salviato R, Belvini D, Radossi P, et al. High resolution melting for F9 gene mutation analysis in patients with haemophilia B. Blood Transfusion 2019;17(1):72â??82.

   [Crossref], [Google Scholar], [Indexed]

8. Blood clotting factor VIII: From evolution to therapy
9. Pandey Y, Atwal D, Konda M, et al. Acquired hemophilia A. Proceedings 2020;33(1):71â??74.

   [Crossref], [Google Scholar], [Indexed]

10. Goodeve AC. Hemophilia B: Molecular pathogenesis and mutation analysis. J Thromb Haemost 2015;13(7):1184â??1195.

    [Crossref], [Google Scholar], [Indexed]

11. Van Vulpen LFD, Holstein K, Martinoli C. Joint disease in haemophilia: Pathophysiology, pain and imaging. Haemophilia 2018;24(Suppl 6):44â??49.

    [Crossref], [Google Scholar], [Indexed]

12. Kizilocak H, Young G. Diagnosis and treatment of hemophilia. Clin Adv Hematol Oncol2019;17(6):344â??351.

    [Crossref], [Google Scholar], [Indexed]

13. Chuansumrit A, Sasanakul W, Promsonthi P, et al. Prenatal diagnosis for haemophilia: The Thai experience. Haemophilia 2016;22(6):880â??885.

    [Crossref], [Google Scholar], [Indexed]

14. Awad MA, Eldeen OA, Ibrahim HA. Stability of activated partial thromboplastin time (APTT) test under different storage conditions. Hematology 2006;11(5), 311â??315.

    [Crossref], [Google Scholar], [Indexed]

15. Nagakari K, Emmi M, Iba T. Prothrombin time tests for the monitoring of direct oral anticoagulants and their evaluation as indicators of the reversal effect. Clin Appl Thromb Hem 2017;23(6):677â??684.

    [Crossref], [Google Scholar], [Indexed]

16. Kakkar VV, Nicolaides AN. The 125I fibrinogen test and its uses. Acta Universitatis Carolinae Medica 1972.
17. Burggraf M, Payas A, Kauther MD, et al. Evaluation of clotting factor activities early after severe multiple trauma and their correlation with coagulation tests and clinical data. World J Emerg Surg 2015;10:43.

    [Crossref], [Google Scholar], [Indexed]

18. Crossref
19. Bhardwaj R, Rath G, Goyal AK. Advancement in the treatment of haemophilia. Int J Biol Macromol 2018;118(A):289â??295.

    [Crossref], [Google Scholar], [Indexed]

20. von der Lippe C, Frich JC, Harris A, et al. Treatment of hemophilia: A qualitative study of mothersâ?? perspectives. Pediatr Blood Cancer2017;64(1):121â??127.

    [Crossref], [Google Scholar], [Indexed]

21. Nikisha GN, Menezes GA. Hemophilia and its treatment: Brief review. Int J Pharm Sci Rev Res 2014.

    [Google Scholar]

22. Amiral J, Seghatchian J. Usefulness of chromogenic assays for potency assignment and recovery of plasma-derived FVIII and FIX concentrates or their recombinant long acting therapeutic equivalents with potential application in treated pediatric hemophiliac patients. Transfus Apher Sci 2018;57(3):363â??369.

    [Crossref], [Google Scholar], [Indexed]

23. Clarence DM, Petros N. Hemophilia review [Online]. US Pharm 2020;45(7/8):36.
24. Mishra P, Nayak B, Dey RK. Pegylation in anti-cancer therapy: An overview. Asian Journal of Pharmaceutical Sciences 2016;11(3):337â??348.

    [Crossref], [Google Scholar], [Indexed]

25. Schulte S. Half-life extension through albumin fusion technologies. Thromb Res2009;124(2):S6â??S8.

    [Crossref], [Google Scholar], [Indexed]

26. Grevsen JV, Kirkegaard H, Kruse E, et al.

    [Early achievements of the Danish pharmaceutical industry--8. Lundbeck]. Theriaca 2016. [Google Scholar], [Indexed]