Factor VIII Inhibitors and their Treatment Procedures

Factor VIII Inhibitors and their Treatment Procedures

HRF, INC.

The presence of Factor VIII in the body is essential in the process of blood clotting since it prevents severe blood loss. However, not all people have the Factor VIII in their bodies leading to hemophilia A that often needs immediate medical response. Most of these patients with hemophilia A will need Factor VIII replacements to make them cope up with the body demands.  Hemophilia A is complicated with the chances of the patient acquiring the Factor VIII replacements that render it ineffective in the process. The Factor VIII inhibitors are dangerous to the hemophilia A patients since it increases morbidity as time progresses and also making the treatment procedure even more expensive.

The presence of Hemophilia A in the body raises the need to seek Factor VIII replacement that will be essential in helping the patient. More importantly, Factor VIII helps in creating blood clots in the body that reduces excess bleeding^[1]. The severe blood loss from the body might make one feel weak and complicate the situation even further. The Factor VIII replacement goes a long way in ensuring the patient is safe and free from the fears of undergoing excessive bleeding again. However, the Factor VIII replacement procedure tends to experience some difficulties that complicate the issue even further. The presence of the alloantibodies inhibit the Factor VIII processes in the body even the replacements^[2]. More specifically, the alloantibodies that are the inhibitory antibodies end up making the Factor VIII replacements less effective because of the way it interferes with the clotting Factor infusion into the bloodstream. In the end, the patients that have the Factor VIII inhibitors end up experiencing severe bleeding since the normal procedure cannot undertake any fruitful treatment procedure at that time. The presence of the inhibitors in the body makes the treatment procedures even much expensive as the morbidity also increases since it is more dangerous than the normal hemophilia A that the patient had earlier^[3]. Of the patients with hemophilia A, 36% of them tend to experience the inhibitor formation in their bodies that even make their situation complicated^[4].

The early detection of the Factor VIII inhibitors in the body of the patient often plays an important role since it becomes easier to manage it before it reaches a severe state. Given its increased morbidity, it is fair if its treatment begins at an early stage. Often, the symptoms might begin as lack of response to the fVIII infusion that might also be present in the poor recovery of the patient in the long-run^[5]. At times, shortened half-life, as well as the inadequate response, is some of the signs that show the presence of the inhibitors in the patient. In the process of detecting the presence of the inhibitors, the Bethesda inhibitor assay (BIA) is often effective. The screening often needs to be done during the first 50 treatment days as opposed to after 150 treatment days because the rate of development of the inhibitors at the initial days is faster making the detection a bit easier to undertake as well^[6]. The early detection prevents any further complications since it manages the severity of the inhibitors before it worsens in the end. The patients that are at risk of acquiring the inhibitors include those with more null mutations, nonsense mutations, large deletions as well as those with the intron 22 inversions^[7]. In fact, 68.8% of the patients that have large deletions had even acquired the high-titer inhibitors^[8]. The other Factor VIII mutations showed a less likelihood of getting the inhibitors in comparison to the ones mentioned above.

The treatment of the inhibitor is a bit complicated but close monitoring of the procedure increases the chance of the patient undergoing effective treatment procedures. After it has been detected, the inhibitor is often at the low titer level where it can even respond to the replacement but with some slight change instead^[9]. When the Factor VIII reaches 5 BU/mL, the inhibitor renders it useless and making the bleeding episodes to begin^[10]. In the process, the treatment will need to bypass the ineffective clotting Factor. The current medication that helps in reducing the severity of the include the rfVIIa; Novoseven; Bagsvaerd, NovoNordisk, Denmark that are the recombinant activated Factor 8 while the likes of the Baxter, Deerfield, IL are under the FEIBA VH^[11]. In particular, the rfVIIa aids in the process of creating a cloned human Factor VII gene that will confuse the inhibitors. The generation of the rfVIIa is essential in inducing hemostasis and even facilitating the Factor X that is located on the platelet to bypass the tenase complex^[12]. The two approaches are effective in reducing the impact of the inhibitors that is the severe bleeding that will make it hard for the patients to survive. The failure of the rfVIIa means that the doctors should try FEIBA VH and ascertain whether the patient will respond effectively as expected^[13]. The two approaches are given in different dosages; but, the presence of the doctor will ascertain the level of response and determine any more addition or the extent.

In conclusion, the Factor VIII inhibitors are dangerous to a patient with hemophilia A since it increases morbidity making it fair to detect it early enough and undertake the required treatment procedures. Its severity is evident in the way that it makes the Factor VIII ineffective and increases the bleeding episodes that the patient will undergo. In the end, severe blood loss will complicate the treatment procedures making it easier to lose the patient. The hemophilia A patients with null mutations, nonsense mutations, large deletions and the intron 22 inversions are the ones that are affected by the complications. The treatment procedure is often effective when it begins at an early stage making it easier to manage the severity before it extends to the extreme level. The presence of the rfVIIa and FEIBA VH treatment is essential in ensuring that the patient’s health is achieved and the victim can no longer report any of those critical complications.

HRF, INC. has been providing specialty plasma products, including Factor VIII for over 30 years. Both donors and recipients have been benefiting HRF, INC.’s exceptional quality control and distribution. In fact, while the company is based in the United States,  HRF, Inc. has clients in dozens of countries, including  Spain, England, France to name just a few.

 

 

 

 

 

Bibliography

Ehrenforth, S., W. Kreuz, R. Linde, M. Funk, T. Güngor, B. Krackhardt, B. Kornhuber, and I. Scharrer. “Incidence of development of Factor VIII and Factor IX inhibitors in haemophiliacs.” The Lancet 339, no. 8793 (1992): 594-598.

Ishiguro, A. “[Immune mechanisms involved in the development and eradication of anti-Factor VIII alloantibodies in hemophilia].” Nihon Rinsho Men’eki Gakkai kaishi= Japanese journal of clinical immunology 34, no. 6 (2010): 476-484.

Kempton, Christine L., and Gilbert C. White. “How we treat a hemophilia A patient with a Factor VIII inhibitor.” Blood 113, no. 1 (2009): 11-17.

Ma, Alice D., and Daniel Carrizosa. “Acquired Factor VIII inhibitors: pathophysiology and treatment.” ASH Education Program Book 2006, no. 1 (2006): 432-437.

Polyanskaya, T., V. Zorenko, E. Karpov, M. Sampiev, G. Mishin, and D. Vasiliev. “Experience of recombinant activated Factor VII usage during surgery in patients with haemophilia with inhibitors.” Haemophilia 18, no. 6 (2012): 997-1002.

Witmer, Char, and Guy Young. “Factor VIII inhibitors in hemophilia A: rationale and latest evidence.” Therapeutic advances in hematology (2012): 2040620712464509.

 

^[1] Ma, Alice D., and Daniel Carrizosa. “Acquired Factor VIII inhibitors: pathophysiology and treatment.” ASH Education Program Book 2006, no. 1 (2006): 432-437.

^[2] Ibid, 1.

^[3] Witmer, Char, and Guy Young. “Factor VIII inhibitors in hemophilia A: rationale and latest evidence.” Therapeutic advances in hematology (2012): 2040620712464509.

^[4] Ibid, 3.

^[5] Kempton, Christine L., and Gilbert C. White. “How we treat a hemophilia A patient with a Factor VIII inhibitor.” Blood 113, no. 1 (2009): 11-17.

^[6] Ibid, 5.

^[7] Ibid, 5.

^[8] Ibid,5.

^[9] Ehrenforth, S., W. Kreuz, R. Linde, M. Funk, T. Güngor, B. Krackhardt, B. Kornhuber, and I. Scharrer. “Incidence of development of Factor VIII and Factor IX inhibitors in haemophiliacs.” The Lancet 339, no. 8793 (1992): 594-598.

^[10] Polyanskaya, T., V. Zorenko, E. Karpov, M. Sampiev, G. Mishin, and D. Vasiliev. “Experience of recombinant activated Factor VII usage during surgery in patients with haemophilia with inhibitors.” Haemophilia 18, no. 6 (2012): 997-1002.

^[11] Ibid, 5.

^[12] Ishiguro, A. “[Immune mechanisms involved in the development and eradication of anti-Factor VIII alloantibodies in hemophilia].” Nihon Rinsho Men’eki Gakkai kaishi= Japanese journal of clinical immunology 34, no. 6 (2010): 476-484.

^[13] Ibid, 5.