Talk:Paroxysmal nocturnal hemoglobinuria

I've
I've been diagnosed with PNH but I think that many of my symptoms point to a G6PD deficiency.


 * Well, your haematologist should surely be able to disentangle your haemolysis. Flow cytometry results? JFW | T@lk  14:39, 20 September 2005 (UTC)

Eculizumab
- eculizumab works. Worth putting this in? JFW | T@lk  14:39, 20 September 2005 (UTC)

Work
I'll be expanding this article with the consensus statement in Blood 1 Dec 2005. JFW | T@lk  21:45, 20 December 2005 (UTC)

Acclaim
Excellent article, and is easy to read...great for a second year medical student.


 * I hope it is understandable also to those without a medical background. Feel free to show it to your tutors & encourage them to improve it. It's a wiki! JFW | T@lk  22:07, 8 March 2006 (UTC)

Chromosome 12 mutations underlying clonality
It has been unclear why PNH is a clonal bone marrow disorder. gives data from 2 PNH patients with chromosome 12 abnormalities leading to ectopic expression of HMGA2 in bone marrow. I don't think we should cite this until the findings have been replicated in larger cohorts of PNH patients. JFW | T@lk  05:05, 21 December 2006 (UTC)

Lethal
An anonymous editor insists that PNH is life-threatening. I disagree. Parker et al state clearly that there are subclinical variants of PNH, and obviously these are not life-threatening at all. I have asked to justify further changes of this kind. JFW | T@lk  22:04, 14 February 2007 (UTC)


 * The trolling is getting tiresome. JFW | T@lk  22:37, 22 March 2007 (UTC)

Update
lists a host of symptoms I don't normally associate with PNH. Hoping to get the fulltext to update this article. JFW | T@lk  21:36, 5 April 2007 (UTC)

give classic case scenario for medical students
even if it often doesn't present with classical symptoms you should still give the classic presentation to help with medical students on exams, some are too lazy to go and research it on their own and need such help.


 * The classic presentation is mentioned. JFW | T@lk  12:01, 5 March 2008 (UTC)

Clonality
The following reference was listed to support some of the pathophysiology data:

However, it actually addresses the more unusual point that many healthy people have small PNH clones but that they have polyclonal PIGA mutations as opposed to "real" PNH patients, whose PIGA mutations are monoclonal. We need to reconsider the relevance of this study before reinserting it into the article. JFW | T@lk  12:01, 5 March 2008 (UTC)

Some sources
Argh, I need to give a case presentation on this subject on Friday! Some sources I've found are the following; we could use them to expand the article.
 * Narrative review Ann Intern Med http://www.annals.org/cgi/content/full/148/8/587
 * From the same author: http://asheducationbook.hematologylibrary.org/cgi/content/full/2006/1/24
 * Blinded RCT of eculizumab (NEJM)
 * Thrombosis risk is also reduced in Soliris http://bloodjournal.hematologylibrary.org/cgi/content/full/110/12/4123
 * Recent developments: http://www.blackwell-synergy.com/doi/abs/10.1111/j.1365-2141.2007.06554.x

Wonder how this will go. JFW | T@lk  07:40, 5 May 2008 (UTC)


 * http://books.google.co.uk/books?id=27qcOn07USkC - entire book on PGI & PNH. ISBN 0127729402. JFW |  T@lk  15:39, 6 May 2008 (UTC)

Removed
Animal studies suggest that infusing membrane-targeted CD59 might restore protection against complement-mediated lysis, and is being developed further for use in patients.


 * Animal studies. Yah. JFW | T@lk  16:50, 7 May 2008 (UTC)

Eculizumab again
http://www.blackwell-synergy.com/doi/abs/10.1111/j.1365-2141.2008.07183.x - anaemia and fatigue improve beyond improvement in transfusion requirements. JFW | T@lk  22:25, 22 May 2008 (UTC)


 * "new drug class" article in Lancet about eculizumab. JFW | T@lk  19:48, 25 January 2009 (UTC)


 * just a note re the cost of this drug, which is produced by one company only. A recent CBC new item mentioned that the drug costs perhaps $70 per vial to produce; each vial costs $6,700 in Canada (I assume $Cdn). The company separately negotiates price with each country, with Canada having to pay the highest amount. Given that the drug's development was based on publicly funded research in public universities and hospitals, there's a serious question as to the ethics of the company's exorbitant price structure.184.145.22.3 (talk) 17:18, 17 August 2015 (UTC)
 * Canada has a specific cost max formula. So that would be unusual that it is the most here. Doc James  (talk · contribs · email) 21:24, 17 August 2015 (UTC)

nocturnal?
Just curious why "nocturnal" is part of the disease name. The article doesn't seem to mention any reason why. —Preceding unsigned comment added by 72.130.191.235 (talk) 22:29, 12 February 2009 (UTC)
 * I've added some details. --Arcadian (talk) 01:47, 13 February 2009 (UTC)

''The "nocturnal" refers to the tendency of the intravascular hemolysis to occur at night. It has been suggested that this may be because the condition is exacerbated by acidosis, and during sleep the blood becomes more acidic, which in turn is caused by the mild hypoxia of sleep. Another theory is that the hemolysis does not increase at night, but that the urine produced after sleep is more concentrated, which makes the blood more apparent. ''

This is all very nice but the sources are hardly WP:MEDRS and I have therefore moved this here until we find a better source for it. JFW | T@lk  23:49, 7 March 2010 (UTC) I would actually support the inclusion of this text as it is offering two quite possible theories as to why the nocturnal feature of the haemoglobinurea is noted. I was actually thought this in college and i believe it was in either Immunology by Janis Kuby or Immunobiology by Abbas and Litmann. Also decreased breathing rate of sleep or rest will invariably result in pH lowering of the blood, this is fairly basic physiology and should need no citation, the more concentrated urine due to lack of fluid intake during sleep is also fairly self evident Jimmy joe joeseph (talk) 15:33, 17 October 2010 (UTC)

Mesenteric Ischemia?
Seems like occlusion of the Inferior Mesenteric Vein should cause Ischemic Colitis, not Mesenteric Ischemia, right? —Preceding unsigned comment added by 24.18.205.173 (talk) 19:38, 29 June 2010 (UTC)

inherited disorder?
the article describes when an aquired gene mutatition occurs to for the specific enzyme involved that when absent removes whatever protection the red cells with lineage from that stem cell have against the complement system. what i would be intrested to know is why this condition occurs at all when a typical adult has around 1000 pleuripotential stem cells 999 of which could be unaffected and producing normal red cells, is this particular gene/locus more vunerable than others in normal stem cells that it affects a significant number of them, or does anyone know of reasearch questioning whether there could be a genetic suseptability to this mutation. or could the pathogenisis be explained more clearly to explain how this mutation is typicaly aquired by a significant number of stem cells.

or is there a growth advantage or resistance to apoptosis to thee abnormal causitive stem cell 87.198.229.90 (talk) 18:14, 21 September 2010 (UTC)

ok ive sort of answered my own question here, according to Dunn et al. in 1999 "the basis of this relation is unknown". Ann Intern Med September 21, 1999 131:401-408 im assuming it is still unknown now 87.198.229.90 (talk) 18:44, 21 September 2010 (UTC)


 * It is still unknown how GPI mutations are acquired in those with conditions such as aplastic anaemia, where resistance to complement-mediated destruction is obviously a survival advantage. It is not known to exist as an inherited condition, although of course inherited GPI mutations will lead to a very similar phenotype. Perhaps it's lethal if present during embryogenesis. JFW &#124; T@lk  07:53, 12 April 2012 (UTC)
 * Most recent hypothesis that I have seen (reviewed nicely by Parker in Curr Opin Hematol, 2012) use the incredibly high co-incidence of aplastic anemia with PNH to explain that most PNH is probably the result of mutated heme-stem cells gaining a competitive advantage in the setting of immune-mediated aplastic anemia. In other words, a significant proportion of PNH pts probably have underlying aplastic anemia, with "breakthough" mutant-PIGA stem cells providing a resistant and imperfect source of hematopoiesis. I will have to read a bit more before adding about this to the article. Dr G (talk) 04:54, 17 September 2014 (UTC)

Thrombosis
Review in JTH about thrombosis in PNH: 10.1111/j.1538-7836.2011.04562.x JFW &#124; T@lk  07:54, 12 April 2012 (UTC)


 * And Blood 10.1182/blood-2012-09-31138. You'd think PNH is common. JFW &#124;  T@lk  18:55, 12 December 2013 (UTC)

Strange edits
An anonymous editor has been alluding to the possibility that PNH may be inherited rather than acquired, as well as mentioning prolonged survival (30 years). Neither of these facts are sourceable to Parker, and no attempt has been made to provide an alternative source. I have left a message on the IP's talk page, seeing that it appears fixed. JFW &#124; T@lk  18:18, 15 April 2012 (UTC)

RA101495
I'm not sure if there's a convention regarding how far a drug needs to be in clinical trials for it to be mentioned here, but it's probably worth mentioning that RA101495 recently passed Phase 2 and is a subcutaneous treatment that worked for patients with an inadequate response to eculizumab. It got >95% C5 inhibition at only 0.3 mg/kg. https://www.businesswire.com/news/home/20180212005448/en/Ra-Pharmaceuticals-Announces-Completion-Dosing-Phase-2 129.10.29.29 (talk) 02:22, 20 March 2018 (UTC)