RE: URGENT: DALE & others w/ info on bruising HELP

[Guest guest]

Have they checked for ITP? My son has ITP (along with the CVID,

Syndrome). The ITP causes the platelet counts to drop (can occur suddenly) and

the IVIG is the treatment.

Just food for thought.

Pam

(TIM - CVID/ITP age 15)

[Guest guest]

I did a quick search of medical literature and found some interesting

things-something about elevated Platelet IgG levels keeps popping up -not

exactly certain what IgG Platelet levels are----but here is an interesting

abstract that may be of no help, but I found the IgG connection interesting.

There are several other abstracts that look interesting, as well. FWIW,

here ya go:

Ann Intern <javascript:AL_get(this,%20'jour',%20'Ann%20Intern%20Med.');>

Med. 1981 Jan;94(1):27-30.

Easy bruising, thrombocytopenia, and elevated platelet immunoglobulin G in

Graves' disease and Hashimoto's thyroiditis.

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Search & itool=pu

bmed_Abstract & term=%22Hymes+K%22%5BAuthor%5D> Hymes K,

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Search & itool=pu

bmed_Abstract & term=%22Blum+M%22%5BAuthor%5D> Blum M,

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Search & itool=pu

bmed_Abstract & term=%22Lackner+H%22%5BAuthor%5D> Lackner H,

<http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?db=pubmed & cmd=Search & itool=pu

bmed_Abstract & term=%22Karpatkin+S%22%5BAuthor%5D> Karpatkin S.

Platelet IgG levels, count, and function and easy bruising or bleeding were

studied in 25 patients with Graves' disease and 12 with Hashimoto's

thyroiditis (normal value for platelet IgG 10.7 +/- 4.5 ng [sD]/10(6)

platelets). Eight of 22 patients with Graves' disease and normal platelet

counts had elevated platelet IgG averaging 38 +/- 4.0 ng (SEM) (range, 24 to

60). Four of 10 patients with Hashimoto's thyroiditis and normal platelet

counts ahd elevated platelet IgG averaging 45 +/- 7.2 ng (range, 27 to 66).

Five patients with thrombocytopenia had platelet counts averaging 53000 +/-

12000/microL (SEM) and elevated platelet IgG averaging 154 +/- 40 ng (range,

27 to 300). Twelve of 15 patients with a history of easy bruising or

bleeding had elevated platelet IgG compared to five of 22 without easy

bruising (p < 0.001). Four of six with elevated platelet IgG had one or more

abnormal in-vitro platelet aggregation measurements (particularly with

epinephrine) compared to none of six with normal platelet IgG levels (p =

0.03). We conclude that elevated platelet IgG is associated with easy

bruising and thrombocytopenia in about half of patients with Graves' disease

or Hashimoto's thyroiditis.

PMID: 6893793 [PubMed - indexed for MEDLINE]

Peace Be With You,

Pattie

Don't let your past dictate who you are now, but let it be a part of who you

will become.

_____

[Guest guest]

I don't know if you are talking about Idiopathic Thrombocytopenic Purpura

looking bruising but, if so, you may want to take a look at:

http://www.emedicine.com/EMERG/topic282.htm

ITP is a decrease in the number of circulating platelets in the absence of

toxic exposure or a disease associated with a low platelet count.

BUT, they also note that systemic symptoms linked to to medications such as

heparin, alcohol, quinidine/quinine, sulfonamides that may cause

thrombocytopenia. Additional problems to be considered include:

Pseudothrombocytopenia (platelet clumping in the presence of

ethylenediaminetetraacetic acid [EDTA]), drug-induced immune thrombocytopenia

(alcohol, heparin, quinine/quinidine, sulfonamides), Infection/sepsis among

others.

This is very upsetting for us all. Let us know what you learn. I have to

leave in 6 min.

[Guest guest]

Tiff n Dayna -

One last thought:

Was there anything, anything at all, that you shared in common (same lots of

heparin, premeds, needles, anything?) -- that may be a potential environment

toxin/contaminant?

btw, if this continues to be a problem you could contact the CDC and request

an investigation.

Running....

Jess

[Guest guest]

Here is the abstract--- for the full text article go to :

http://www.pubmedcentral.com/articlerender.fcgi?artid=425040

Reactions of immunoglobulin G-binding ligands with platelets and

platelet-associated immunoglobulin G.

W F Rosse, D V Devine, and R Ware

Abstract

Immunoglobulin G (IgG) bound to platelets is usually detected by one of two

general methods: binding of labeled anti-IgG or consumption of anti-IgG. The

latter method gives, in general, values 5-10-fold greater than the former

under the same conditions. To investigate these discrepancies, we have

compared the detection of platelet-bound IgG by a labeled anti-IgG binding

assay and by a quantitative antiglobulin consumption test using the same

antibodies. The interaction of 125I-labeled monoclonal anti-IgG or

polyclonal anti-IgG with washed and IgG-coated platelets was studied. The

binding of these ligands to washed normal platelets was largely (50-80%)

nonspecific; the binding was not saturable and was only partially

inhibitable by excess unlabeled anti-IgG. The binding of anti-IgG to

platelets coated with anti-PIA1, a platelet-specific IgG antibody, appeared

to be saturable and inhibitable; the dissociation constant (KD) of this

IgG-anti-IgG reaction was 4.9 X 10(-9) for monoclonal and 1.4 X 10(-7) for

polyclonal anti-IgG. The ratio of sites present on the membrane (determined

by 131I-labeled anti-PIA1) to the number of binding sites for anti-IgG

determined by Scatchard analysis was 0.53 for monoclonal anti-IgG and 1.3

for polyclonal anti-IgG. The binding of monoclonal anti-IgG to

platelet-bound immune complexes or IgG aggregates appeared to be complex.

131I-Labeled IgG was affixed to platelets and was detected by three tests:

direct binding of radiolabeled monoclonal anti-IgG and quantitative

antiglobulin consumption (QAC) tests, which were quantitated either by

measuring directly the amount of radiolabeled anti-IgG consumed from fluid

phase (direct QAC), or indirectly by reference to a calibration curve

relating the consumption of anti-IgG by known amounts of fluid-phase,

non-immune IgG (indirect QAC). The amount of platelet-bound IgG detected by

the direct binding of 125I-labeled monoclonal anti-IgG and by the direct QAC

approximated that known to be bound to the platelet. The results of the

indirect QAC test were 10-fold greater. The discrepancy appears to be due to

the fact that there is a difference between the IgG-anti-IgG interaction

when IgG is bound to a platelet and when it is in solution or bound to

plastic nonspecifically or specifically. This difference results in a

falsely high value for platelet-bound IgG when fluid-phase or plastic-bound

IgG is used to calibrate the antiglobulin consumption test.

Peace Be With You,

Pattie

Don't let your past dictate who you are now, but let it be a part of who you

will become.

_____

[Guest guest]

Hays wrote:

> Hey guys,

> We are really having an issue with our son bruising a few days prior

>

, I don't believe it's going to turn out to be IVIG related. I

think that because it starts a couple of days before IVIG -- that that

rules it out. What you may instead be seeing is a condition that the

IVIG is actually helping. In other words -- it shows up as the IVIG is

out of the system (2 or 3 days before infusion) and then clears up 3-5

after the IVIG gets into the system. While IVIG is not totally clear of

the body for 3 months, it's activity is usually very diminished in the

last week before treatment.

But, I do know that your IVIG provider has experts and researchers on

board to help you. There should be an 800 number on your product

information sheet or go on line and find it. I highly recommend your

doctor calling the Consulting Immunology Program which is at

1-877-666-0866. It's free to doctors and is run by the Immune

Deficiency Foundation. They've probably got more expertise than any

single group in the US.

There are a lot of blood platelet issues that I have never researched,

but a lot of them are actually treated with IVIG.

Best wishes as you continue to seek answers.

In His service,

dale

[Guest guest]

For the full text article of the abstract below:

http://www.pubmedcentral.com/articlerender.fcgi?artid=296872

Platelet alpha-granule fibrinogen, albumin, and immunoglobulin G are not

synthesized by rat and mouse megakaryocytes.

P Handagama, D A Rappolee, Z Werb, J Levin, and D F Bainton

Department of Pathology, University of California, San Francisco 94143.

Small right arrow pointing to:This article has been

<http://www.pubmedcentral.com/tocrender.fcgi?action=cited & artid=296872>

cited by other articles in PMC.

Abstract

It has been assumed that endogenous synthesis by the platelet precursor

cell, the bone marrow megakaryocyte, is the major source of platelet

alpha-granule protein. To test this hypothesis, we used mRNA phenotyping to

detect in megakaryocytes the presence of mRNA transcripts specific for

various proteins. Our results indicate that megakaryocytes synthesize

platelet factor 4, a protein relatively specific for platelets, but do not

express mRNA transcripts for the fibrinogen, albumin, or IgG found in

alpha-granules. We have previously shown that megakaryocytes endocytose

circulating proteins, including fibrinogen, albumin, and IgG, and

incorporate them into alpha-granules. Thus, platelets appear to contain a

unique type of secretory granule whose contents originate by both endogenous

synthesis and endocytosis from plasma. Under basal conditions, the source of

alpha-granule fibrinogen is plasma.

From bloodjournal on-line:

Part of the activating cross-linked immunoglobulin G is internalized by

human platelets to sites not accessible for enzymatic digestion

MO Spycher and UE Nydegger

The differential uptake of tritium-labeled immunoglobulin G (IgG) cross-

linked with bisdiazonium-benzidine (BDB) (3H-BDB-IgG) by washed, pooled

human platelets to sites inaccessible to pronase digestion was tested. Up to

52% of the 3H-BDB-IgG associated with platelets at 37 degrees C resisted

pronase treatment, whereas only 23% of the cross-linked IgG associated with

platelets at 4 degrees C, or at 37 degrees C but in the presence of

deoxyglucose/antimycin A, remained refractory to pronase. This effect was

not due to platelet agglutination. Pronase resistance reached a maximum

after a 60-minute incubation period at 37 degrees C. With increasing

3H-BDB-IgG input, both the total cross-linked IgG associated with platelets

and the fraction resistant to pronase digestion approached saturation at 4

degrees C, but not at 37 degrees C. The proportion of 3H-BDB-IgG bound to

platelets at 4 degrees C that was resistant to pronase treatment increased

by 13% within five minutes of warming the platelets to 37 degrees C.

Pretreatment of platelets with 10 mmol/L acetylsalicylic acid (or 10 mumol/L

prostaglandin E1) prior to the addition of 3H-BDB-IgG led to a 74% (95%)

inhibition of the 3H-BDB-IgG-induced 14C-serotonin release, but to only a

44% (49%) inhibition of pronase-digestible bound ligand. In contrast,

pretreatment with 10 mumol/L cytochalasin B led to a mere 17% reduction of

14C-serotonin release, whereas acquisition of resistance to pronase

digestion by the bound 3H-BDB-IgG was inhibited by 90%. Incubation of

platelets at 37 degrees C with 3H-BDB-IgG and removal of unbound material

prior to the addition of prostaglandin E1 or deoxyglucose/antimycin A had

little effect on the susceptibility of platelet-associated 3H-BDB-IgG to

pronase, whereas the addition of cytochalasin B to 3H-BDB-IgG-treated

platelets resulted in greatly increased susceptibility of the

platelet-associated ligand to pronase. Thus, after binding, 3H-BDB-IgG

becomes transferred in an energy- dependent process to pronase-resistant

cellular sites, most likely to the open canalicular system.

Volume 67, Issue 1, pp. 12-18, 01/01/1986

Copyright C 1986 by The American Society of Hematology

Peace Be With You,

Pattie

Don't let your past dictate who you are now, but let it be a part of who you

will become.

_____

[Guest guest]

And that is the strange part, isn't it!???? I wonder if the IVIG would

mask ITP? This is one thing I had mentioned, too. If a child developed

ITP while on IVIG, would you pick up on it unless you did the platelet tests

before the next infusion? If the numbers are normal and the function tests

are fine, then what else could there be? Could it be that there is a

mechanism by which the body somehow synthesizes the platelet IgG (which I

assume is in IgG preparations) and causes the problem.but when the infusion

is first given, there is enough of the other " parts " of the IgG to fight off

the problem/possible ITP caused from the overload of platelet IgG.but as it

gets closer to the infusion time, the IgG that is circulating in the blood

is diminished, while the synthesized platelet IgG is still in the

platelets?/ I think platelets only have a life of 7-8 days in the

bloodstream, though... Unless it takes some amount of time for the

platelets to synthesize the IgG from the plasma into the new platelets

being created at the time the IVIG is given. I don't know how long it takes

for a platelet to be created-only that they live in the blood for 7-8 days

once mature. See the article abstracts that I just sent--- one says that

platelets " Thus, platelets appear to contain a unique type of secretory

granule whose contents originate by both endogenous synthesis and

endocytosis from plasma. Under basal conditions, the source of alpha-granule

fibrinogen is plasma. " And IgG comes from plasma.

I would talk to the experts, if you can. See what studies there are and

talk to the researchers directly. They always seem willing to talk to

folks-at least in my experience.

I probably sound ling a lunatic--

Peace Be With You,

Pattie

Don't let your past dictate who you are now, but let it be a part of who you

will become.

_____

There are a lot of blood platelet issues that I have never researched,

but a lot of them are actually treated with IVIG.

Best wishes as you continue to seek answers.

In His service,

dale

_____