Paroxysmal nocturnal hemoglobinuria medical therapy: Difference between revisions

Jump to navigation Jump to search
← Older edit
VisualWikitext
Anmol Pitliya (talk | contribs)
Bureaucrats, bureaucrats, nocaptcha, Administrators, Widget editors
9,217 edits
No edit summary
Aelsaiey (talk | contribs)
nocaptcha, smwadministrator, Administrators
4,616 edits
No edit summary
 
(8 intermediate revisions by 2 users not shown)
Line 1: Line 1:
__NOTOC__
__NOTOC__
{{Paroxysmal nocturnal hemoglobinuria}}
{{Paroxysmal nocturnal hemoglobinuria}}
{{CMG}}; {{AE}}
{{CMG}}; {{AE}} {{AEL}}  


==Overview==
==Overview==
There is no treatment for [disease name]; the mainstay of therapy is supportive care.
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.  


OR
==Medical Therapy==
 
* The mainstay of treatment for PNH is medical therapy.  
Supportive therapy for [disease name] includes [therapy 1], [therapy 2], and [therapy 3].
* Treatment of PNH includes the following:
 
** Anti-complement therapy
OR
** Hematopoietic cell transplantation
 
** Treatment of the anemia
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
=== 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


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==
*Pharmacologic medical therapy is recommended among patients with [disease subclass 1], [disease subclass 2], and [disease subclass 3].
*Pharmacologic medical therapies for [disease name] include (either) [therapy 1], [therapy 2], and/or [therapy 3].
*Empiric therapy for [disease name] depends on [disease factor 1] and [disease factor 2].
*Patients with [disease subclass 1] are treated with [therapy 1], whereas patients with [disease subclass 2] are treated with [therapy 2].
===Disease Name===


* '''1 Stage 1 - Name of stage'''
=== Hematopoietic cell transplantation ===
** 1.1 '''Specific Organ system involved 1'''
* Hematopoietic stem cell transplantation is an important curative therapy for paroxysmal nocturnal hemoglobinuria.  
*** 1.1.1 '''Adult'''
* Stem cell transplantation is usually reserved for the severely affected patients and is indicated for the following type of patients:<ref name="pmid28013015">{{cite journal| author=DeZern AE, Zahurak M, Symons H, Cooke K, Jones RJ, Brodsky RA| title=Alternative Donor Transplantation with High-Dose Post-Transplantation Cyclophosphamide for Refractory Severe Aplastic Anemia. | journal=Biol Blood Marrow Transplant | year= 2017 | volume= 23 | issue= 3 | pages= 498-504 | pmid=28013015 | doi=10.1016/j.bbmt.2016.12.628 | pmc=5373094 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=28013015  }}</ref>
**** Preferred regimen (1): [[drug name]] 100 mg PO q12h for 10-21 days '''(Contraindications/specific instructions)''' 
** Patients with severe aplastic anemia who are HLA matched donor.
**** Preferred regimen (2): [[drug name]] 500 mg PO q8h for 14-21 days
** Patients with myelodysplastic syndromes
**** Preferred regimen (3): [[drug name]] 500 mg q12h for 14-21 days
** Patients who are unresponsive to the anti complement therapy (eculizumab)  
**** Alternative regimen (1): [[drug name]] 500 mg PO q6h for 7–10 days 
* Transplantation related issues:<ref name="pmid22689687">{{cite journal| author=Peffault de Latour R, Schrezenmeier H, Bacigalupo A, Blaise D, de Souza CA, Vigouroux S et al.| title=Allogeneic stem cell transplantation in paroxysmal nocturnal hemoglobinuria. | journal=Haematologica | year= 2012 | volume= 97 | issue= 11 | pages= 1666-73 | pmid=22689687 | doi=10.3324/haematol.2012.062828 | pmc=3487438 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=22689687 }}</ref><ref name="pmid16051736">{{cite journal| author=Parker C, Omine M, Richards S, Nishimura J, Bessler M, Ware R et al.| title=Diagnosis and management of paroxysmal nocturnal hemoglobinuria. | journal=Blood | year= 2005 | volume= 106 | issue= 12 | pages= 3699-709 | pmid=16051736 | doi=10.1182/blood-2005-04-1717 | pmc=1895106 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=16051736  }}</ref>
**** Alternative regimen (2): [[drug name]] 500 mg PO q12h for 14–21 days
** Acute Graft-Versus-Host Disease (GVHD) occurs in almost third of the PNH patients treated with transplant.  
**** Alternative regimen (3): [[drug name]] 500 mg PO q6h for 14–21 days
** Survival rate of the PNH patients treated with transplantation is from 50% to 60%.
*** 1.1.2 '''Pediatric'''
**** 1.1.2.1 (Specific population e.g. '''children < 8 years of age''')
***** Preferred regimen (1): [[drug name]] 50 mg/kg PO per day q8h (maximum, 500 mg per dose) 
***** Preferred regimen (2): [[drug name]] 30 mg/kg PO per day in 2 divided doses (maximum, 500 mg per dose)
***** Alternative regimen (1): [[drug name]]10 mg/kg PO q6h (maximum, 500 mg per day)
***** Alternative regimen (2): [[drug name]] 7.5 mg/kg PO q12h (maximum, 500 mg per dose)
***** Alternative regimen (3): [[drug name]] 12.5 mg/kg PO q6h (maximum, 500 mg per dose)
****1.1.2.2 (Specific population e.g. ''''''children < 8 years of age'''''')
***** Preferred regimen (1): [[drug name]] 4 mg/kg/day PO q12h（maximum, 100 mg per dose）
***** Alternative regimen (1): [[drug name]] 10 mg/kg PO q6h (maximum, 500 mg per day)
***** Alternative regimen (2): [[drug name]] 7.5 mg/kg PO q12h (maximum, 500 mg per dose)  
***** Alternative regimen (3): [[drug name]] 12.5 mg/kg PO q6h (maximum, 500 mg per dose)
** 1.2 '''Specific Organ system involved 2'''
*** 1.2.1 '''Adult'''
**** Preferred regimen (1): [[drug name]] 500 mg PO q8h
*** 1.2.2  '''Pediatric'''
**** Preferred regimen (1): [[drug name]] 50 mg/kg/day PO q8h (maximum, 500 mg per dose)


* 2 '''Stage 2 - Name of stage'''
=== Treatment of the anemia ===
** 2.1 '''Specific Organ system involved 1 '''
* Management of hemolytic anemia in PNH includes the following steps:  
**: '''Note (1):'''
** '''[[Blood transfusion|Transfusion support]]''': [[Packed red blood cell transfusion|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 therapy|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.<ref name="pmid26696797">{{cite journal| author=Salama A| title=Treatment Options for Primary Autoimmune Hemolytic Anemia: A Short Comprehensive Review. | journal=Transfus Med Hemother | year= 2015 | volume= 42 | issue= 5 | pages= 294-301 | pmid=26696797 | doi=10.1159/000438731 | pmc=4678315 | url=https://www.ncbi.nlm.nih.gov/entrez/eutils/elink.fcgi?dbfrom=pubmed&tool=sumsearch.org/cite&retmode=ref&cmd=prlinks&id=26696797 }}</ref>
**: '''Note (2)''':
** Iron supplmentation for patients with low reticulocyte count.  
**: '''Note (3):'''
** Folate supplementation to convoy the accelerated erythropoiesis due to blood transfusion.  
*** 2.1.1 '''Adult'''
**** Parenteral regimen
***** Preferred regimen (1): [[drug name]] 2 g IV q24h for 14 (14–21) days
***** Alternative regimen (1): [[drug name]] 2 g IV q8h for 14 (14–21) days
***** Alternative regimen (2): [[drug name]] 18–24 MU/day IV q4h for 14 (14–21) days
**** Oral regimen
***** Preferred regimen (1): [[drug name]] 500 mg PO q8h for 14 (14–21) days
***** Preferred regimen (2): [[drug name]] 100 mg PO q12h for 14 (14–21) days
***** Preferred regimen (3): [[drug name]] 500 mg PO q12h for 14 (14–21) days
***** Alternative regimen (1): [[drug name]] 500 mg PO q6h for 7–10 days 
***** Alternative regimen (2): [[drug name]] 500 mg PO q12h for 14–21 days
***** Alternative regimen (3):[[drug name]] 500 mg PO q6h for 14–21 days
*** 2.1.2 '''Pediatric'''
**** Parenteral regimen
***** Preferred regimen (1): [[drug name]] 50–75 mg/kg IV q24h for 14 (14–21) days (maximum, 2 g)
***** Alternative regimen (1): [[drug name]] 150–200 mg/kg/day IV q6–8h for 14 (14–21) days (maximum, 6 g per day)
***** Alternative regimen (2):  [[drug name]] 200,000–400,000 U/kg/day IV q4h for 14 (14–21) days (maximum, 18–24 million U per day) ''''''(Contraindications/specific instructions)''''''
**** Oral regimen
***** Preferred regimen (1):  [[drug name]] 50 mg/kg/day PO q8h for 14 (14–21) days  (maximum, 500 mg per dose)
***** Preferred regimen (2): [[drug name]] '''(for children aged ≥ 8 years)''' 4 mg/kg/day PO q12h for 14 (14–21) days (maximum, 100 mg per dose)
***** Preferred regimen (3): [[drug name]] 30 mg/kg/day PO q12h for 14 (14–21) days  (maximum, 500 mg per dose)
***** Alternative regimen (1): [[drug name]] 10 mg/kg PO q6h 7–10 days  (maximum, 500 mg per day)
***** Alternative regimen (2): [[drug name]] 7.5 mg/kg PO q12h for 14–21 days  (maximum, 500 mg per dose)
***** Alternative regimen (3): [[drug name]] 12.5 mg/kg PO q6h for 14–21 days  (maximum,500 mg per dose)
** 2.2  '<nowiki/>'''''Other Organ system involved 2''''''
**: '''Note (1):'''
**: '''Note (2)''':
**: '''Note (3):'''
*** 2.2.1 '''Adult'''
**** Parenteral regimen
***** Preferred regimen (1): [[drug name]] 2 g IV q24h for 14 (14–21) days
***** Alternative regimen (1): [[drug name]] 2 g IV q8h for 14 (14–21) days
***** Alternative regimen (2): [[drug name]] 18–24 MU/day IV q4h for 14 (14–21) days
**** Oral regimen
***** Preferred regimen (1): [[drug name]] 500 mg PO q8h for 14 (14–21) days
***** Preferred regimen (2): [[drug name]] 100 mg PO q12h for 14 (14–21) days
***** Preferred regimen (3): [[drug name]] 500 mg PO q12h for 14 (14–21) days
***** Alternative regimen (1): [[drug name]] 500 mg PO q6h for 7–10 days 
***** Alternative regimen (2): [[drug name]] 500 mg PO q12h for 14–21 days
***** Alternative regimen (3):[[drug name]] 500 mg PO q6h for 14–21 days
*** 2.2.2 '''Pediatric'''
**** Parenteral regimen
***** Preferred regimen (1): [[drug name]] 50–75 mg/kg IV q24h for 14 (14–21) days (maximum, 2 g)
***** Alternative regimen (1): [[drug name]] 150–200 mg/kg/day IV q6–8h for 14 (14–21) days (maximum, 6 g per day)
***** Alternative regimen (2):  [[drug name]] 200,000–400,000 U/kg/day IV q4h for 14 (14–21) days (maximum, 18–24 million U per day)
**** Oral regimen
***** Preferred regimen (1): [[drug name]] 50 mg/kg/day PO q8h for 14 (14–21) days  (maximum, 500 mg per dose)
***** Preferred regimen (2): [[drug name]] 4 mg/kg/day PO q12h for 14 (14–21) days (maximum, 100 mg per dose)
***** Preferred regimen (3): [[drug name]] 30 mg/kg/day PO q12h for 14 (14–21) days  (maximum, 500 mg per dose)
***** Alternative regimen (1):  [[drug name]] 10 mg/kg PO q6h 7–10 days  (maximum, 500 mg per day)
***** Alternative regimen (2): [[drug name]] 7.5 mg/kg PO q12h for 14–21 days  (maximum, 500 mg per dose)
***** Alternative regimen (3): [[drug name]] 12.5 mg/kg PO q6h for 14–21 days  (maximum,500 mg per dose)


==References==
==References==

Latest revision as of 06:47, 20 October 2020

Paroxysmal nocturnal hemoglobinuria Microchapters

Home

Patient Information

Overview

Historical Perspective

Classification

Pathophysiology

Causes

Differentiating Paroxysmal nocturnal hemoglobinuria from other Diseases

Epidemiology and Demographics

Risk Factors

Screening

Natural History, Complications and Prognosis

Diagnosis

Diagnostic Study of Choice

History and Symptoms

Physical Examination

Laboratory Findings

Electrocardiogram

X Ray

CT

MRI

Echocardiography or Ultrasound

Other Imaging Findings

Other Diagnostic Studies

Treatment

Medical Therapy

Surgery

Primary Prevention

Secondary Prevention

Cost-Effectiveness of Therapy

Future or Investigational Therapies

Case Studies

Case #1

Paroxysmal nocturnal hemoglobinuria medical therapy On the Web

Most recent articles

Most cited articles

Review articles

CME Programs

Powerpoint slides

Images

American Roentgen Ray Society Images of Paroxysmal nocturnal hemoglobinuria medical therapy

All Images
X-rays
Echo & Ultrasound
CT Images
MRI

Ongoing Trials at Clinical Trials.gov

US National Guidelines Clearinghouse

NICE Guidance

FDA on Paroxysmal nocturnal hemoglobinuria medical therapy

CDC on Paroxysmal nocturnal hemoglobinuria medical therapy

Paroxysmal nocturnal hemoglobinuria medical therapy in the news

Blogs on Paroxysmal nocturnal hemoglobinuria medical therapy

Directions to Hospitals Treating Paroxysmal nocturnal hemoglobinuria

Risk calculators and risk factors for Paroxysmal nocturnal hemoglobinuria medical therapy

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

  1. ↑ 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.
  2. ↑ 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.
  3. ↑ 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.
  4. ↑ 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.

Template:WH Template:WS

Retrieved from "https://www.wikidoc.org/index.php?title=Paroxysmal_nocturnal_hemoglobinuria_medical_therapy&oldid=1670069"