Sequential Therapy in treating Unresponsive Bleeding in Patients with Hemophilia A

Although scientists have found a way to handle hemophilia complications, the presence of the inhibitors have made it worse to manage the severity. The treatment of the hemophilia patients has seen the two agents that are the recombinant Factor VIIa (rFVIIa) and the activated prothrombin complex concentrates (APCC)^[1]. Unfortunately, the presence of the two agents for the treatment of the hemophilia patients is not enough to control the bleeding that the patients experience. The failure of the two main agents in treating the patients has created a dilemma for the researchers and medical providers that have to find a better solution to handle the issue. In fact, the chances of morbidity and mortality as a result of the excess bleeding are high^[2]. Hence, the medical practitioners should be quick enough to correct the severe bleeding before it reaches some extreme measures that will be detrimental to the patient. For instance, the process of replacing the Factor that is deficient often seems a bit challenging based on the presence of the inhibitors that prevent the success of the treatment. With the replacement therapy being ineffective, there is the need to incorporate prompt measures that will help in handling the issue instead.

The presence of the alloimmune antibody has restrained the activities of the medical practitioners that are focused on making the patients with hemophilia A manage the occasional bleeding. The sequential use of both the APCC and the fFVIIa results in a scenario that the complications arising from the presence of the inhibitors are no longer something to worry about. The conventional Factor replacement cannot provide the expected results that will even reduce the excess bleeding^[3]. Currently, the medical field has two bypassing agents that have the ability to end the bleeding especially, if the patient lacks the inhibitors. However, the use of a single bypassing agent shows no significant impact on the patient that also has the inhibitors that are a challenge to the success of the medication process^[4]. The unsuccessful implementation of monotherapy led to the attempt of the sequential application of the two bypassing agents that showed how it was possible to reduce the impact of severe bleeding in the patients that had previously reported unresponsive pattern in the bleeding.

As long as the patient has unresponsive bleeding because of the presence of the inhibitors, the Sequential bypassing agents have the ability to manage the bleeding. More importantly, the dosage needs to be applied in a systematic way and not in a random way instead. However, the single bypassing agent is more likely to result in refractory bleeding that will be harmful to the patient in this case^[5]. Often, the sequential infusion will rely on the medical officer administering the APCC dose and later even two or one dose of rFVIIa might be used as well. The two doses will have to be administered within a period of 12 hours in order to make sure it is effective as expected^[6]. Messing with the dosage or the time that one is taken before another will reduce its efficiency and enhance the refractory bleeding. The same APCC dose is given at a range of50-100 IU/kg in a day while rFVIIa is administered in a period of two or even three hours but the limit remains 90 µg/kg^[7]. The only thing that can change in the dosage of rFVIIa is the time interval since the medical practitioner will administer the dose based on the response that the patient will have to the dosage given. Before proceeding with the dosage, the medical practitioners should also have enough information on the complete blood count of the patient. The presence of the Factor VIII and the level of antibodies are also essential since the medical practitioner will use all those details to determine the success of the sequential therapy^[8]. As long as the dosage is administered correctly and in the required time interval, the recovery process will not be much of a challenge for the patient and most likely the refractory bleeding will reduce to a large extent as well.

Even if the sequential therapy is effective in reducing the unresponsive bleeding, there is the likelihood of developing thrombosis. The presence of the thrombosis in the blood is often not dangerous. However, the problem arises when one of the blood clots gets off and is released into the bloodstream that will even reach pulmonary circulation system and even remain in the lung^[9]. Its presence in the lungs is life-threatening thereby making it effective to deal with the thrombosis right on time without any hesitance. The thrombosis is more likely to arise from the sequential therapy as it occurs. The medical practitioners will even control the bleeding by administering the antithrombin III as well as the FFP^[10]. Other risks of the medication are the reduced platelet levels as well as fibrinogen and even an increase in the D-dimer levels. More likely, the risks and levels of the complications did not reach the levels that might lead to the disseminated intravascular coagulation (DIC) that is another dangerous complication^[11]. Hence, one should not administer the sequential therapy on his or her own since the expert authority will be essential in the long-run.

In conclusion, even if the single bypassing therapy fails to reduce the unresponsive bleeding in the patients with hemophilia A, the sequential bypassing therapy is successful in controlling the bleeding in the patients. The single bypassing therapy is ineffective in controlling the amount of bleeding in the patients that are also affected by hemophilia A. The only effective way to stop the bleeding is through the use of sequential bypassing therapy that succeeds in managing the excessive bleeding that might arise without the control of the medication. However, the sequential process should not be undertaken without the presence of the medical practitioners since they are the ones aware of the right amount to administer to such patients since their recovery is the utmost objective. However, the use of the sequential therapy tends to expose the patient to the risk of thrombosis. In order to avoid the complications of thrombosis also arising, it is advisable if the patients have expert supervision while using the therapy or even seeks medical advice when something suspicious occurs after the therapy.

 

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Bibliography

Berntorp, Erik. “Differential response to bypassing agents complicates treatment in patients with haemophilia and inhibitors.” Haemophilia 15, no. 1 (2009): 3-10.

Gringeri, A., K. Fischer, A. Karafoulidou, R. Klamroth, M. F. LÓPEZ‐FERNÁNDEZ, and E. Mancuso. “Sequential combined bypassing therapy is safe and effective in the treatment of unresponsive bleeding in adults and children with haemophilia and inhibitors.” Haemophilia 17, no. 4 (2011): 630-635.

Han, Myung Hee, and Young Shil Park. “Sequential therapy with activated prothrombin complex concentrates and recombinant activated Factor VII to treat unresponsive bleeding in patients with hemophilia and inhibitors: a single center experience.” Blood research 48, no. 4 (2013): 282-286.

Hayashi, T., I. Tanaka, M. Shima, K. Yoshida, K. Fukuda, Y. Sakurai, T. Matsumoto, J. C. Giddings, and A. Yoshioka. “Unresponsiveness to Factor VIII inhibitor bypassing agents during haemostatic treatment for life‐threatening massive bleeding in a patient with haemophilia A and a high responding inhibitor.” Haemophilia 10, no. 4 (2004): 397-400.

Martinowitz, U., T. Livnat, A. Zivelin, and G. Kenet. “Concomitant infusion of low doses of rFVIIa and FEIBA in haemophilia patients with inhibitors.” Haemophilia 15, no. 4 (2009): 904-910.

Valentino, L. A. “The benefits of prophylactic treatment with APCC in patients with haemophilia and high‐titre inhibitors: a retrospective case series.” Haemophilia 15, no. 3 (2009): 733-742.

 

^[1] Gringeri, A., K. Fischer, A. Karafoulidou, R. Klamroth, M. F. LÓPEZ‐FERNÁNDEZ, and E. Mancuso. “Sequential combined bypassing therapy is safe and effective in the treatment of unresponsive bleeding in adults and children with haemophilia and inhibitors.” Haemophilia 17, no. 4 (2011): 630-635.

^[2] Ibid, 1.

^[3] Ibid, 1.

^[4] Hayashi, T., I. Tanaka, M. Shima, K. Yoshida, K. Fukuda, Y. Sakurai, T. Matsumoto, J. C. Giddings, and A. Yoshioka. “Unresponsiveness to Factor VIII inhibitor bypassing agents during haemostatic treatment for life‐threatening massive bleeding in a patient with haemophilia A and a high responding inhibitor.” Haemophilia 10, no. 4 (2004): 397-400.

^[5] Ibid, 4.

^[6] Berntorp, Erik. “Differential response to bypassing agents complicates treatment in patients with haemophilia and inhibitors.” Haemophilia 15, no. 1 (2009): 3-10.

 

^[7] Ibid, 6.

^[8] Martinowitz, U., T. Livnat, A. Zivelin, and G. Kenet. “Concomitant infusion of low doses of rFVIIa and FEIBA in haemophilia patients with inhibitors.” Haemophilia 15, no. 4 (2009): 904-910.

^[9] Valentino, L. A. “The benefits of prophylactic treatment with APCC in patients with haemophilia and high‐titre inhibitors: a retrospective case series.” Haemophilia 15, no. 3 (2009): 733-742.

^[10] Han, Myung Hee, and Young Shil Park. “Sequential therapy with activated prothrombin complex concentrates and recombinant activated Factor VII to treat unresponsive bleeding in patients with hemophilia and inhibitors: a single center experience.” Blood research 48, no. 4 (2013): 282-286.

 

^[11] Ibid, 9.