[CIS PIDD] 42 yo man with DGS and refractory ITP

[Verbsky, James]

We have thought about this issue a lot.  We preferred RBC pit assays..but few places do these.  Our blood center is starting this up again.

From what I can tell and the attached paper..Pits and HJB are fairly similar.  The one difference is that a cutoff of 1% of pitted RBCs was used..but a cutoff of 55/10E6 was used for HJ bodies (0.01%).  Thus you have to sample a lot more RBCs to get HJB.  However..they mention an interesting cytometric analysis looking at CD71 negative (mature) RBCs and then doing PI staining to detect the HJ body.

Has anyone used flow to look at splenic function like this?  Might be a better way

James


James W. Verbsky MD/PhD
Associate Professor of Pediatric,s and Medical Microbiology and Genetics
Medical College of Wisconsin
Milwaukee, WI  53211
jverbsky at mcw.edu<mailto:jverbsky at mcw.edu>
414-266-6701 (phone)
414-266-6695 (fax)



From: pagid-bounces at list.clinimmsoc.org [mailto:pagid-bounces at list.clinimmsoc.org] On Behalf Of Church, Joseph
Sent: Wednesday, June 06, 2012 12:20 PM
To: pagid at list.clinimmsoc.org
Subject: Re: [CIS PIDD] 42 yo man with DGS and refractory ITP

From my reading of the literature, the presence of H-J bodies is still the best, routinely available indicator of functinal asplenia.  JC

From: pagid-bounces at list.clinimmsoc.org<mailto:pagid-bounces at list.clinimmsoc.org> [mailto:pagid-bounces at list.clinimmsoc.org]<mailto:[mailto:pagid-bounces at list.clinimmsoc.org]> On Behalf Of Yesim Yilmaz Demirdag
Sent: Wednesday, June 06, 2012 9:58 AM
To: pagid at list.clinimmsoc.org<mailto:pagid at list.clinimmsoc.org>
Subject: Re: [CIS PIDD] 42 yo man with DGS and refractory ITP

he does have Howell-Jolly bodies in 6/10 peripheral smears. Do you think we don't need to look for any residual spleen?
thanks
Y

On Wed, Jun 6, 2012 at 12:37 PM, Church, Joseph <JChurch at chla.usc.edu<mailto:JChurch at chla.usc.edu>> wrote:
If the patient is asplenic he should have Howell-Jolly bodies on routine blood smear.  Joe Church

From: pagid-bounces at list.clinimmsoc.org<mailto:pagid-bounces at list.clinimmsoc.org> [mailto:pagid-bounces at list.clinimmsoc.org<mailto:pagid-bounces at list.clinimmsoc.org>] On Behalf Of Yesim Yilmaz Demirdag
Sent: Wednesday, June 06, 2012 8:45 AM
To: pagid at list.clinimmsoc.org<mailto:pagid at list.clinimmsoc.org>
Subject: Re: [CIS PIDD] 42 yo man with DGS and refractory ITP

there is no spleen now, he had them (he had three of them) removed at age 9. We are now checking if there is any residual spleen.
I am not sure about bortezomib in the treatment of ITP, I am checking the literature now, could you explain more?
Y
On Wed, Jun 6, 2012 at 11:37 AM, <stephan.ehl at uniklinik-freiburg.de<mailto:stephan.ehl at uniklinik-freiburg.de>> wrote:

Is the spleen enlarged?
Have you considered bortezomib? SE

________________________________

  Von: Yeşim Yılmaz Demirdağ [dryesimyilmaz at gmail.com<mailto:dryesimyilmaz at gmail.com>]
  Gesendet: 06.06.2012 11:18 AST
  An: pagid at list.clinimmsoc.org<mailto:pagid at list.clinimmsoc.org>
  Betreff: [CIS PIDD] 42 yo man with DGS and refractory ITP

Dear all,
I was asked to see this patient yesterday. I have added a detailed history below. In summary he is a 42 yo caucasian man who was diagnosed with DiGeorge syndrome with 22q11.2 deletion at 5 yrs of age (we don't have any records of cytogenetic or FISH result). His current problem is severe thrombocytopenia resulting in GI bleeding and anemia. He receives platelet transfusion almost every day in the past 1 month or so. He has been on high dose steroids, IVIG (2gr/kg once a wk), he was on rituximab, Nplate, and vincristine between 2009 and 2011.He is being followed by our adult heme-onc folks. They asked me if I have any idea on what to do, I told them that I will ask to "the group".
Apparently the patient does not want to have plasmapheresis which was recommended by the heme-onc.
also, heme-onc is hesitant to use cytoxan or oral promacta because they never used these medications in immune deficient patients before.
What would be the optimal approach to this case? Does anyone have any idea? I would really appreciate any input.
Have a nice day!

Yesim Demirdag, MD
West Virginia University, Morgantown, WV


Detailed medical history:
He was originally diagnosed with ITP at the age of 3, treated with steroids and IVIG.
He eventually underwent splenectomy age 9.  At that time he had 3 spleens which were all removed.
But his thrombocytopenia persisted even after splenectomy.
Somewhere in his mid teens, between the ages of 15 to 18, his thrombocytopenia resolved.
He was followed with observation and had no complication until 2009 when he was again found to have severe thrombocytopenia.  He was admitted to the hospital and subsequently had workup, including a bone marrow biopsy which was normal at that time (normal megacaryocytes).  He has undergone treatment with immunoglobulin, high-dose steroids, rituximab and Nplate, as well as vincristine.  His vincristine was given in 2011 through early 2012.  He has received rituximab for several courses and Nplate on several different course therapies, including 2009, 2010 and again in 2012.  He has received IVIG (2gr/kg) on countless occasions.  However, he recently essentially became dependent upon platelet transfusions.  He also has a remote history of hemolytic anemia, although he has had no blood transfusions until very recently in his course.  Currently, at this time his platelets have been less than 10,000 since March 2012.  He has been receiving platelets now on an almost continuous basis for the last month or so.  He has persistent bleeding, in fact, was recently admitted with GI bleeding as well as persistent nose bleeding. He received 2 units of blood approximately a week ago and has had evidence of anemia since the fall of 2011.  Also, he has had leukocytosis with a white count between 20,000 and 30,000 for most of 2011 and 2012 as well (ALC between 2500-9500).  He has elevated CD8 counts (7211 cells/ul), CD4 counts 1400 cells/ul.Platelet autoantibody was positive (reacts w glycoprotein Ib/IX, IIb/IIa, Ia/IIa). CMV DNA is positive (1600 copies/ml).

He currently has complaints of nose bleeding, bright red blood per rectum, fatigue, malaise, generalized bone pain, more severe in his low back and knees, present now for approximately 2-3 years, treated with pain medication, weight gain of over 100-pounds, fluid retention, swelling in his legs, petechiae, easy bruising, headaches, lightheadedness and dizziness, episodes of passing out, diarrhea and depression and tearfulness.

PAST MEDICAL HISTORY:
1.  Chronic ITP as above.
2.  History of splenectomy at age 9.
3.  Hemolytic anemia at age 5.
4.  A report by his mother of being born without a thymus.
5.  History of congenital hypoparathyroidism treated by Dr. Chideckel.
6.  History of hypocalcemia.
7.  History of Hashimoto's thyroiditis in 2008-2009, treatment unclear.
8.  History of pneumonia for multiple episodes.
9.  History of chronic mastoiditis, status post ear surgery.
10. History of possible interstitial lung disease secondary to Nplate in 2010, requiring oxygen at that time.
11.  History of cataract surgery in 2009 with lens replacements.
12.  History per mother of probable DiGeorge syndrome diagnosed at NIH at age 5.
13.  Diabetes mellitus secondary to steroids.
14.  Hypertension.
15.  Intermittent elevated creatinine.
16.  Anxiety disorder.
17.  History of sleep apnea.

CURRENT MEDICATIONS:
1.  Calcitriol daily.
2.  Calcium 3 times daily
3.  Chlorhexidine as needed.
4.  Nexium 40 mg daily.
5.  Folic acid daily.
6.  Synthroid 100 mcg daily.
7.  Clark's solution as needed.
8.  Metoprolol/hydrochlorothiazide 100/25 daily.
9.  Oxycodone as needed.
10.  MiraLax as needed.
11.  Prednisone 120 mg daily.  Currently I have asked him to increase it down to 60 mg daily.
14:  Topamax 25 mg twice daily


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