Paroxysmal nocturnal hemoglobinuria medical therapy: Difference between revisions
| Line 49: | Line 49: | ||
* The mainstay of treatment for PNH is medical therapy. | * The mainstay of treatment for PNH is medical therapy. | ||
* Treatment of PNH includes the following: | * Treatment of PNH includes the following: | ||
** Anti-complement therapy | ** Anti-complement therapy | ||
** Hematopoietic cell transplantation | ** Hematopoietic cell transplantation | ||
** Treatment of the anemia | |||
=== Anti-complement therapy === | |||
* Most of the symptoms and signs of PNH is related to the deficiency of the CD55/CD59 which lead to complement induced hemolysis. Hereby, the anti-complement therapy is considered the mainstay of treatment for PNH. | |||
* The anti-complement therapy includes '''Eculizumab''' which acts on reducing the hemolysis, reducing the risk of thrombosis, and decreasing the need for blood transfusion. | |||
* '''Eculizumab:''' | |||
** A monoclonal antibody against the complement tends to decrease the intravascular hemolysis due to complement attacking the RBCs. | |||
** Eculizumab acts via binding the C5 component of the complement system preventing its conversion to C5b and eventually no formation of the membrane attack complex (MAC) and no hemolysis takes place. | |||
** Dosage: | |||
*** Preferred regimen (1): Eculizumab 600 mg IV once a week for four weeks. Then 900 mg IV once a week every two weeks. | |||
** Adverse effects: | |||
*** Eculizumab is associated with increase risk of Neisseria infections as it inhibits the complement system (especially MAC) which is important in the elimination process of the Neisseria species from the body. | |||
*** In order to prevent this serious side effects of Eculizumab, patients should receive meningococcal vaccines for two weeks before starting treatment with Eculizumab. Moreover, daily prophylaxis with oral antimicrobial should be prescribed. | |||
* Other anti-complement therapies not approved yet: | |||
** C5 inhibitors as Ravulizumab | |||
** C1 esterase inhibitor | |||
** Factor D inhibition | |||
* | * | ||
| Line 65: | Line 80: | ||
** Acute Gravt-Versus-Host Disease (GVHD) occurs in almost third of the PNH patients treated with transplant. | ** Acute Gravt-Versus-Host Disease (GVHD) occurs in almost third of the PNH patients treated with transplant. | ||
** Survival rate of the PNH patients treated with transplantation is from 50% to 60%. | ** Survival rate of the PNH patients treated with transplantation is from 50% to 60%. | ||
=== Treatment of the anemia === | |||
==References== | ==References== | ||
Revision as of 02:21, 22 August 2018
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief:
Overview
There is no treatment for [disease name]; the mainstay of therapy is supportive care.
OR
Supportive therapy for [disease name] includes [therapy 1], [therapy 2], and [therapy 3].
OR
The majority of cases of [disease name] are self-limited and require only supportive care.
OR
[Disease name] is a medical emergency and requires prompt treatment.
OR
The mainstay of treatment for [disease name] is [therapy].
OR The optimal therapy for [malignancy name] depends on the stage at diagnosis.
OR
[Therapy] is recommended among all patients who develop [disease name].
OR
Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].
OR
Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].
OR
Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].
OR
Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].
Medical Therapy
- The mainstay of treatment for PNH is medical therapy.
- Treatment of PNH includes the following:
- Anti-complement therapy
- Hematopoietic cell transplantation
- Treatment of the anemia
Anti-complement therapy
- Most of the symptoms and signs of PNH is related to the deficiency of the CD55/CD59 which lead to complement induced hemolysis. Hereby, the anti-complement therapy is considered the mainstay of treatment for PNH.
- The anti-complement therapy includes Eculizumab which acts on reducing the hemolysis, reducing the risk of thrombosis, and decreasing the need for blood transfusion.
- Eculizumab:
- A monoclonal antibody against the complement tends to decrease the intravascular hemolysis due to complement attacking the RBCs.
- Eculizumab acts via binding the C5 component of the complement system preventing its conversion to C5b and eventually no formation of the membrane attack complex (MAC) and no hemolysis takes place.
- Dosage:
- Preferred regimen (1): Eculizumab 600 mg IV once a week for four weeks. Then 900 mg IV once a week every two weeks.
- Adverse effects:
- Eculizumab is associated with increase risk of Neisseria infections as it inhibits the complement system (especially MAC) which is important in the elimination process of the Neisseria species from the body.
- In order to prevent this serious side effects of Eculizumab, patients should receive meningococcal vaccines for two weeks before starting treatment with Eculizumab. Moreover, daily prophylaxis with oral antimicrobial should be prescribed.
- Other anti-complement therapies not approved yet:
- C5 inhibitors as Ravulizumab
- C1 esterase inhibitor
- Factor D inhibition
Hematopoietic cell transplantation
- Hematopoietic stem cell transplantation is an important curative therapy for paroxysmal nocturnal hemoglobinuria.
- Stem cell transplantation is usually reserved for the severely affected patients and is indicated for the following type of patients:[1]
- Patients with severe aplastic anemia who are HLA matched donor.
- Patients with myelodysplastic syndromes
- Patients who are unresponsive to the anti complement therapy (eculizumab)
- Transplantation related issues:[2][3]
- Acute Gravt-Versus-Host Disease (GVHD) occurs in almost third of the PNH patients treated with transplant.
- Survival rate of the PNH patients treated with transplantation is from 50% to 60%.
Treatment of the anemia
References
- ↑ DeZern AE, Zahurak M, Symons H, Cooke K, Jones RJ, Brodsky RA (2017). "Alternative Donor Transplantation with High-Dose Post-Transplantation Cyclophosphamide for Refractory Severe Aplastic Anemia". Biol Blood Marrow Transplant. 23 (3): 498–504. doi:10.1016/j.bbmt.2016.12.628. PMC 5373094. PMID 28013015.
- ↑ Peffault de Latour R, Schrezenmeier H, Bacigalupo A, Blaise D, de Souza CA, Vigouroux S; et al. (2012). "Allogeneic stem cell transplantation in paroxysmal nocturnal hemoglobinuria". Haematologica. 97 (11): 1666–73. doi:10.3324/haematol.2012.062828. PMC 3487438. PMID 22689687.
- ↑ Parker C, Omine M, Richards S, Nishimura J, Bessler M, Ware R; et al. (2005). "Diagnosis and management of paroxysmal nocturnal hemoglobinuria". Blood. 106 (12): 3699–709. doi:10.1182/blood-2005-04-1717. PMC 1895106. PMID 16051736.