Talk:Thrombotic thrombocytopenic purpura

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Ideal sources for Wikipedia's health content are defined in the guideline Wikipedia:Identifying reliable sources (medicine) and are typically review articles. Here are links to possibly useful sources of information about Thrombotic thrombocytopenic purpura.

PubMed provides review articles from the past five years (limit to free review articles)
The TRIP database provides clinical publications about evidence-based medicine.
Other potential sources include: Centre for Reviews and Dissemination and CDC

Untitled

Has this page been closed to editing? The Symptoms and diagnosis sections don't appear on the editing page.

In any case someone should add "Schistocytes" as an alternative spelling of "Schizocytes".

Relation with contraception

Both references that were included for the statement that there is a relation between anticonception use and TTP conclude that: a causal relationship between progestogen-only contraceptives and TTP is not established by the data presented. So I don't think it should be included in this article unless new hard evidence becomes available. The first study also had some follow-up letters disputing its claims. The references:

Wysowski DK, Green L (1995). "Serious adverse events in Norplant users reported to the Food and Drug Administration's MedWatch Spontaneous Reporting System". Obstet Gynecol. 85 (4): 538–42. PMID 7898829.
Fraser JL, Millenson M, Malynn ER, Uhl L, Kruskall MS (1996). "Possible association between the Norplant contraceptive system and thrombotic thrombocytopenic purpura". Obstet Gynecol. 87 (5 Pt 2): 860–3. PMID 8677116.{{cite journal}}: CS1 maint: multiple names: authors list (link)

--WS 05:14, 15 January 2006 (UTC)[reply]

While I agree with you that causality has never been proven, I think that the controversy is sufficiently important (and interesting) that it should be mentioned somewhere in the article. Mgmei 05:21, 15 January 2006 (UTC)[reply]

A total of 3 reported cases ever worldwide is hardly even controversial. The reported rate was not even higher than in women who didn't use norplant. It was the authors estimation (no evidence given) that it was underreported and therefore the actual rate could be actually higher. If you really want to add that to the article that's fine with me, but choose your words carefully and certainly don't state it as a fact and also for nothing else than norplant. --WS 05:35, 15 January 2006 (UTC)[reply]

I agree with WS here. Just because TTP is rare does not mean all theoretical links should be farmed out over here. Ticlopidine, now that's a different matter. JFW | T@lk 14:15, 16 January 2006 (UTC)[reply]

Ehlichiosis

CaliforniaLyme (talk · contribs) has inserted material to reflect that Ehlichiosis can cause TTP, or at least a TTP-like picture. The problem is - if it is a microangiopathic haemolytic anaemia due to Ehrlichiosis it is by definition not TTP. I cannot disagree that Ehlichia serology will need to be considered in patients presenting with haemolysis, but that not be mentioned here. Oddly, PMID 14976527 does not even mention red cell fragments as characteristic for TTP, nor do any other of the three case reports available on pubmed that mention TTP as a differential.[1] Reviewing PMID 11927032 yielded those same reports.

Wikipedia needs to be selective in its medical content. It cannot possibly list all diseases, mimics, differential diagnoses and so on. When mentioning diseases as mimics/differentials, a small number of case reports is generally insufficient, however meaningful the association to one particular person.

If this is not agreeable, please leave a message on WP:CLINMED. Perhaps my colleagues disagree with my assessment. JFW | T@lk 22:36, 18 December 2006 (UTC)[reply]

From my talk page: David Ruben ^Talk 02:32, 23 December 2006 (UTC)[reply]

No, it is a human disorder as well, the entry for it in Wikipedia is just plain ridiculous, look at the CDC website for a good one. I keep meaning to update WIki because although it does affect dogs its human pathology is more important. The incidence of human Ehrlichiosis 1000 cases per million as opposed to TTP 3-6 pre million, hence my personal belief that it may be underdiagnosed especially because even in fatal cases it is seronegative half the time and because doctors tend NOT to have heard of it!!!!!!!!!!!! I wish you would have kept that in. I had ehrlichiosis and hemolytic anemia after moving into my house at the base of NIsene Mark State Park which in 2003 San Jose State Entomologists found had not only the highest Lyme MIR in all of California 17.8% in adult ticks but also HIGH levels of the causative agents of both HME and HGE Human Granulytic and Human Monocytic Ehrlichiosis (I had HME) up to 13.3% in ticks. In my house a couple decades ago a 16 year old girl named Wendy Ann Hunter died of "peripheral vascular collapse" and meningitis- I got a copy of her death certificate after her mother stopped by our house when we were having a yard sale and told us about her. "This is the last place I remember my duaghter alive." ALSO our babysitter down the street Juniper was diagnosed TTP with a history of Lyme disease,(the preceding is why I care) but her doctor REFUSED TO TEST HER FOR EHRLICHIOSIS!!!

Safdar N, Love RB, Maki DG.
Severe Ehrlichia chaffeensis infection in a lung transplant recipient: a review of ehrlichiosis in the immunocompromised patient.
Emerg Infect Dis. 2002 Mar;8(3):320-3. Review. PMID 11927032
Modi KS, Dahl DC, Berkseth RO, Schut R, Greeno E.
Human granulocytic ehrlichiosis presenting with acute renal failure and mimicking thrombotic thrombocytopenic purpura. A case report and review.
Am J Nephrol. 1999;19(6):677-81. PMID 10592363
Marty AM, Dumler JS, Imes G, Brusman HP, Smrkovski LL, Frisman DM.
Ehrlichiosis mimicking thrombotic thrombocytopenic purpura. Case report and pathological correlation.
Hum Pathol. 1995 Aug;26(8):920-5. PMID 7635455
Am J Trop Med Hyg. 2001 Nov;65(5):603-9.
Tissue diagnosis of Ehrlichia chaffeensis in patients with fatal ehrlichiosis by use of immunohistochemistry, in situ hybridization, and polymerase chain reaction.
Dawson JE, Paddock CD, Warner CK, Greer PW, Bartlett JH, Ewing SA, Munderloh UG, Zaki SR.
Publication Types:Case Reports PMID 11716122
In the United States, human ehrlichiosis is a complex of emerging tick-borne diseases caused by 3 distinct Ehrlichia species: Ehrlichia chaffeensis, Ehrlichia ewingii, and the human granulocytotropic ehrlichiosis agent. Ehrlichioses are characterized by a mild to severe illness, and approximately 4% of cases are fatal. Because these obligate intracellular bacteria are difficult to resolve with routine histologic techniques, their distribution in tissues has not been well described. To facilitate the visualization and detection of ehrlichiae, immunohistochemistry (IHC), in situ hybridization (ISH), and polymerase chain reaction (PCR) assays were developed by use of tissues from 4 fatal cases of E. chaffeensis infection. Evidence of E. chaffeensis via IHC, ISH, and PCR was documented in all 4 cases. Abundant immunostaining and in situ nucleic acid hybridization were observed in spleen and lymph node from all 4 patients. Significantly, in 2 of these patients, serologic evidence of infection was absent. Use of IHC, ISH, and PCR to visualize and detect Ehrlichia in tissues can facilitate diagnosis of ehrlichial infections.

—Preceding unsigned comment added by CaliforniaLyme (talk • contribs) 15:35, 21 December 2006

You comment above"hence my personal belief that it may be underdiagnosed especially..."', your are entitled to an opinion of course, and as such open-up discussion on an article and what it does or does not cover. However "my personal belief" counts as original research and thus has no place (irrespective whether right or wrong) in an article under WP:No original research guidelines. Instead one must find WP:reliable sources that give such opinions.

Your discussion above focuses on ehrlichiosis in the US, yet wikipedia is not an Amercican health manual but has worldwide perspective.

The links above I agree confirm that the condition may superficial appear somewhat similar in some cases, but this makes it a differential in certain cases, not all cases of apparent TTP. Also it is not a cause of TTP itsef. PMID 11927032 states "with features of thrombotic thrombocytopenic purpura" this is not stating that TTP is caused by ehrlichiosis, just that it has some appearances that appear similar - i.e. separate condition which might coexist on a list of differentials for a given clinical presentation, but they are not being equated as the same. PMID 10592363 discusses "Ehrlichiosis mimicking TTP" and likewise in title of PMID 7635455, so making this a differential in certain circumstances, but not cause.

In conclusion I think any mention of Ehrlichia is something that ought to be outside of main testing section, and in perhaps a subsection dealing exclusively with the local issues (on a global scale) found in some parts of the US. David Ruben ^Talk 02:32, 23 December 2006 (UTC)[reply]

I see CaliforniaLyme has created Ehrlichiosis Induced TTP Mimic. this is wrongly capitalised, poorly phrased title that also is inappropriate as its own article (info should be under the article Ehrlichiosis). See Talk:Ehrlichiosis#Merge from Ehrlichiosis Induced TTP Mimic for discussion. David Ruben ^Talk 02:53, 23 December 2006 (UTC)[reply]

Duplicate information

Somebody added a "history" section which basically attempted to cover all pathological aspects as well. Much of that was duplicate with other sections. I have moved it here; if there is anything that the article does not presently cover it can be moved back. For one thing, it makes numerical claims without reliable sources. JFW | T@lk 09:49, 14 January 2007 (UTC)[reply]

This life-threatening condition may have positive outcomes if recognized early and if medical intervention is initiated early. With the introduction of plasma exchange, the survival rate has improved from approximately 3% prior to the 1960s to 82%. Early plasma exchange initiation has beneficial outcomes.

TTP was once thought to have the same mechanism of disease as hemolytic-uremic syndrome (HUS), the other major thrombotic microangiopathy. However, more recent findings suggest that TTP is a different entity than HUS. They are closely related disorders and are characterized by microvascular lesions with platelet aggregation. HUS is more common in children and is caused by strains of enterohemorrhagic Escherichia coli, especially E coli O157:H7 carrying the Shigalike toxin. HUS is characterized by prominent renal involvement. TTP is associated with pregnancy; diseases such as HIV, cancer, bacterial infection, and vasculitis; bone marrow transplantation; stem cell transplantation; and drugs.

In most cases of familial TTP and acquired idiopathic TTP, the endothelial cells secrete and release the ultralarge (UL) von Willebrand factor (ULVWF) multimers. The sheer stress of fluid and platelet thrombi in the microcirculation should enhance proteolysis of ULVWF. The agitated endothelial cells are the main source of ULVWF multimers in the bloodstream where they bind to specific surface platelet receptors. In 1982, Moake et al showed that the ULVWF multimers were unusually large in patients with chronic relapsing TTP. ULVWF multimers entangle with platelets adhering to the subendothelium. Two independent research groups reported a lack of ULVWF-cleaving protease activity in the blood of patients with TTP. The lack of ULVWF-cleaving protease activity was suggested to be due to the presence of antibodies or a severe deficiency of ULVWF-cleaving protease.

The ULVWF multimers are cleaved by ADAMTS-13 as they are secreted from endothelial cells. Failure to degrade the ULVWF multimers is believed to cause the familial and acquired idiopathic types of TTP. The ULVWF-cleaving protease, ADAMTS-13, is inhibited by the production of autoantibodies in acquired idiopathic TTP and ADAMTS-13 gene mutations in familial TTP causing inactivity or decreased activity of ADAMTS-13. Furlan et al found in their investigation, including retrospective analysis of plasma samples, that an autoimmune mechanism may be responsible in patients with acquired deficiency of the ULVWF-cleaving protease, whereas patients with the familial form have complete protease deficiency. In TTP, insufficiency of ADAMTS-13 may be the key component in the pathogenesis of ULVWF multimer–induced platelet thrombosis.

TTP differs from HUS by having a deficiency in ULVWF-cleaving protease ADAMTS-13 activity not found in HUS, and HUS has sufficient uninhibited protease. The intervention of plasma exchange is ineffective because its role is to remove antibodies and replace VWF-cleaving protease. Differentiating TTP from HUS benefits the patient because plasma exchange is not a benign intervention. This differentiation also saves costs and time. Research is ongoing, but, presently, TTP is suggested to be a different entity than HUS.

ULVWF multimers are abundant and fibrinogen/fibrin is minimal in TTP, whereas fibrinogen/fibrin is abundant in disseminated intravascular coagulation (DIC). The ULVWF multimer is a marker found in the plasma of patients most likely to have a recurrence of TTP.

Other interactions, both transcellular and intercellular, are suggested in TTP, including various combinations of platelets, leukocytes, erythrocytes, and endothelium. These interactions may be the key stimuli in the initiation of cell activity and morphological changes that occur in TTP.

Mouse model

Both ADAMTS13 and VWF are needed for an experimental model of shiga toxin-induced TTP (http://bloodjournal.hematologylibrary.org/cgi/content/abstract/111/7/3452). JFW | T@lk 00:49, 25 March 2008 (UTC)[reply]

Expert Attention Needed?

This article seems a bit confusing. Maybe it needs expert attention...

The DarkArcher was here (talk) 01:47, 24 June 2008 (UTC)[reply]

Yeah, great. You find an expert in TTP ready to make contributions to this article. For the moment you've got to do with me and possibly MastCell (talk · contribs). JFW | T@lk 16:10, 1 July 2008 (UTC)[reply]

I have to say reading this article makes me feel like i know less than i did before i looked it up--02:56, 22 October 2008 (UTC) —Preceding unsigned comment added by Shimonnyman (talk • contribs)

Sadler

Excellent historical review from the great JE Sadler: http://bloodjournal.hematologylibrary.org/cgi/content/abstract/112/1/11 JFW | T@lk 16:10, 1 July 2008 (UTC)[reply]

Management

I don't think the treatment section is going to be any good without working this review into the article: http://content.nejm.org/cgi/content/short/354/18/1927 JFW | T@lk 22:12, 13 July 2008 (UTC)[reply]

Mnemonic

Hey guys, Im new to editing wikipedia articles. I'd like to put in the mnemonic "FATRN" which is a way to remember the pentad of TTP: Fever Anemia (hemolytic) Thrombocytopenia Renal failure Neuro symptoms — Preceding unsigned comment added by 24.203.220.148 (talk • contribs)

We don't usually put mnemonics on Wikipedia, because they are often very local (USA vs UK), have little value for the reader unless that reader happens to be a medical student, and so on. See WP:MEDMOS for more details. In this instance, I'd need a mnemonic to remember the mnemonic! JFW | T@lk 06:29, 28 June 2011 (UTC)[reply]

Delete table?

There is a table in the article about various conditions (but not TTP) and associated coagulation abnormalities - tangentially related, but not really relevant or informative about TTP. I think it should be deleted. Thoughts on this? Wawot1 (talk) 04:38, 6 January 2012 (UTC)[reply]

It's gone. I agree. JFW | T@lk 23:15, 7 January 2012 (UTC)[reply]

Expert

I have an expert who has given this a lot of attentiong- made the changes and added references. I am here to edit the page and I cannot figure out how to fix the reference section and then go on get the footnotes and citations working correctly. Do you have to edit the references within the article itself or can you start with the reference list? — Preceding unsigned comment added by Dr.Lieberman (talk • contribs) 16:56, 3 January 2013 (UTC)[reply]

Citations are placed inline after the material covered by them. Click here for more details.Novangelis (talk) 17:30, 3 January 2013 (UTC)[reply]

I have already directed this user to WP:CITE. Can I also point out that references for medical articles should meet the criteria outlined in WP:MEDRS? Small case series or trials are not suitable as references. JFW | T@lk 20:26, 3 January 2013 (UTC)[reply]

British review

doi:10.1111/bjh.12718, practical aspects of treatment. The UCH service reputedly treats more TTP than any other centre in the world. JFW | T@lk 13:25, 9 January 2014 (UTC)[reply]