Paroxysmal nocturnal hemoglobinuria medical therapy
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Editor-In-Chief: C. Michael Gibson, M.S., M.D. [1]; Associate Editor(s)-in-Chief: Ahmed Elsaiey, MBBCH [2]
Overview
The mainstay of treatment for paroxysmal nocturnal hemoglobinuria is medical therapy. Treatment includes anticomplement therapy which includes Eculizumab which acts on reducing the hemolysis and possible complications of PNH. Other treatment regimens include hematopoietic cell transplantation and treatment of the anemia.
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 Graft-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
- Management of hemolytic anemia in PNH includes the following steps:
- Transfusion support: Packed red blood cell transfusions can be administered to help treat hemolytic anemia in the short-term. This is the most rapid method that raises hemoglobin level. Transfusions were the mainstay of treatment greater than 50 years ago, prior to the develop of effective immunosuppressive therapies. However, it is important to note that transfusions are a temporizing measure until a more long-term or disease-modifying medication can be given.[4]
- Iron supplmentation for patients with low reticulocyte count.
- Folate supplementation to convoy the accelerated erythropoiesis due to blood transfusion.
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.
- ↑ Salama A (2015). "Treatment Options for Primary Autoimmune Hemolytic Anemia: A Short Comprehensive Review". Transfus Med Hemother. 42 (5): 294–301. doi:10.1159/000438731. PMC 4678315. PMID 26696797.