Platelet Anti Body Tests Negative

So went back and saw what my platlet antibody tests are and found out all the Antibody tests are negative.

So basically why are my platlet count low?

Is this a production problem.


Platelet AB Direct IgM - Negative,

Platelet AB Direct IgG - Negative

Double Strand DNA IgG - Negative

Platelet AB Indirect - Negative

Just did a quick internet search and found this web site: I have copy and pasted a section from the article.

emedicine.medscape.com/article/202158-workup

"Assays for platelet antigen–specific antibodies, platelet-associated immunoglobulin, or other antiplatelet antibodies are available in some medical centers and certain mail-in reference laboratories. The reliability of the results of a platelet antibody test is highly specific to the laboratory used. A negative antiplatelet antibody assay result does not exclude the diagnosis of ITP. [40] The authors do not recommend this test as part of the routine evaluation. Testing for antiplatelet antibodies is not required to diagnose ITP."

Jay:

It could be a production problem. It could also be that you have antibodies that have not yet been discovered. Those tests are considered to be unreliable.

As Winnifred stated, the tests are not necessary to diagnose ITP. I think I mentioned that my antibody tests showed a high presence of antibodies. Knowing that didn't make any difference in treatment methods. Having negatives shouldn't make a difference either.

I am negative on all the antibody tests. I clearly have a spleen working overtime to kill the platelets given the results of my indium test. I think the medical field knows so little about how ItP works. Whether a production problem or destruction problem, the course of illness or symptoms or treatment all seems the same (in my non medical opinion).

Hello Emily,

This episode adds to my suspicion that the main issue is with the production and not destruction.


Spleen destroys platelets of ITP and non ITP patients alike.

Theory is ITP has a higher rate of destruction but there is no proof of this thing, there is no tests to prove the hypothesis.
When you do splenectomy on a patient with ITP and non ITP the paltelet counts go up no matter what.

Prednisone, IVIG and Rituximab has never been tested non ITP patients to see whether it behaves the same manner. If it does then it is mostly a production issue.


This is why nplate and promacta are game changers which try to provide insight into platlet production factors.

jayinchicago wrote:
Theory is ITP has a higher rate of destruction but there is no proof of this thing, there is no tests to prove the hypothesis.
When you do splenectomy on a patient with ITP and non ITP the paltelet counts go up no matter what.

There is a test to prove platelet destruction, but you'd have to go to the UK. It's called the Indium Labeled Platelet Scan. The test takes three days and shows whether platelets are being destroyed in the spleen or the liver. It also proves how quickly destruction is taking place.

Jay, counts do not always go up after a splenectomy.

Jay do you have an evidence base to support your assertion?

Jay, what you are asserting is very different from everything I've "learned" over the years (both from conversations with doctors and from reading/researching).

My understanding is that ITP is low platelets not explained by any other condition, and typically in isolation (no other abnormal lab results). It might involve both destruction and inadequate production.

My ITP/low platelet count responds with a quick rise when WinRho is given, so you'd think that this indicates I have a destruction problem, but my super-smart hematologist said way back in 2009-ish that new treatments needed to focus on production because that avenue hadn't been explored yet and because it might be a useful way to overcome/keep pace with destruction. I'm not treating these days, but if I needed to NPlate and Promacta might be appropriate for me.

So...that's my understanding of the definition of ITP. I'm not saying you're wrong, just that I've been led to believe something different over the years.

My indium scan took just over 24 hours

Megakaryocyte development and platelet production

williams.medicine.wisc.edu/thrombopoiesis.pdf


Goes through the process of platlet production, lists all the issues with production.


A) Inherited thrombocytopenia due to disruptions of signalling molecules or transcription factors. Thrombocytopenia of different severities
can result from varied inherited genetic mutations. This schema demonstrates the human mutations that are known to occur in the thrombopoietin
(TPO) receptor c-Mpl or in transcription factor genes in megakaryocyte progenitor cells. The translated aberrant proteins have different disrupte
d
functions which result in diseases characterised by thrombocytopenia and reduced platelet function. ( Enhanced megakaryocyte proliferation an
d
thrombocytosis due to aberrations of signalling molecules or transcription factors. Familial thrombocytosis can result from different inherited
genetic
mutations. This schema demonstrates the human mutations that are known to occur in TPO, its receptor c-Mpl, in the signalling molecule JAK2 or in
the transcription factor GATA-1, in megakaryocyte progenitor cells. The translated aberrant proteins have different disrupted functions that res
ult in
diseases characterised by enhanced megakaryocyte progenitor proliferation and platelet productio




Disorders of thrombopoiesis
Disorders of platelets are diverse and can be genetic or acquired.
Inherited disorders usually result from genetic mutations within
genes that encode regulatory proteins, as mentioned above, or
proteins necessary for platelet production, and can have severe
clinical results with profound thrombocytopenia and extended
bleeding times. May-Hegglin anomaly, Sebastian syndrome,
Fechtner syndrome, Alport syndrome, and Epstein syndrome
are related to mutations in the MYH9 non-muscle myosin heavy
chain IIA gene, which encodes the sole myosin isoform expressed
in platelets and neutrophils (Balduini
et al
, 2002). The defect in
myosin causes altered cytoskeletal dynamics resulting in macro-
thrombocytopenia. Bernard–Soulier syndrome is an autosomal
dominant disorder characterised by a prolonged bleeding time,
macrothrombocytopenia, defective prothrombin consumption
and poor platelet adhesion. The dysfunction is due to the absent
or deficient expression of the GPIb/IX/V complex, which forms
the VWF receptor on the platelet surface (Caen & Rosa, 1995).
Several mutations within the genes that encode GPIba, GPV, or
GPIX have been identified (Patel
et al
, 2005). Gray platelet
syndrome is another autosomal dominant disease characterised
by macrothrombocytopenia with absence of
a
-granules. This
abnormality is due to inadequate packaging of VWF and
fibrinogen within the
a
-granules, which fail to mature during
MK differentiation. The clinical and molecular heterogeneity in
this syndrome has been recently reviewe

Jay, back to your original question. The lack of detectable antibodies does not "prove" you have a production problem or that you don't have ITP.

I believe a BMB will tell you if you have PRIMARILY a production problem, which would likely be one of the conditions in the article you pasted above. However, ITP can be treated by increasing production even if it is a condition of primarily destruction.

Hello Tamar,

Being a novice I am just asking questions.

I spoke to me hema regarding this issue.
She told me production is a factor if all three counts are low.
If WBC is low, RBC is low and platlets are low then they immediately do BMB.
If platlets are only low then most likely it is a destruction issue.

Still I believe that Thrombopoetin TPO levels do matter and they need to investigate it better.

In my case during the last 5 years, I was losing weight by increased running, reduced calorie intake and but at the same time was also increasing\maintaining my alcohol intake.

My theory is this put a lot of strain on my liver and could have led to TPO level reduction.

You are fogetting that there are now thought to be two sorts of ITP, antibody mediated and cytotoxic (killer) T-cell mediated. So if antibodies aren't found then you may have the T-cell type.

Here.. try this, jay.

www.ncbi.nlm.nih.gov/pmc/articles/PMC4189678/

jayinchicago wrote:
I spoke to me hema regarding this issue.
She told me production is a factor if all three counts are low.
If WBC is low, RBC is low and platlets are low then they immediately do BMB.
If platlets are only low then most likely it is a destruction issue.

Not true. People with ITP can have production problems because the megakaryocytes that produce platelets are faulty. The megakaryocytes can even show up in the bone marrow biopsy as normal in number and normal in appearance, but something happens when they attempt to produce platelets. It could be a problem with antibodies that interfere with production...that is the theory. Many hemo's are misinformed.

In conclusion, this study highlights that reduced platelet production, as measured by A-IPF, contributes to the thrombocytopenia of ITP, albeit to a greater extent in certain patients than others. Furthermore, the differences in the mechanisms of several treatments to augment or leave unchanged platelet production while increasing the platelet count are well illustrated in these studies. The ability to use A-IPF as an indicator of the thrombopoietic state in real time allows it to provide insight into the mechanisms of treatment effect in patients with ITP and why certain patients may not respond to these treatments. In the future, A-IPF could be used diagnostically (not explored in this study) to identify subgroups of ITP patients with particularly decreased platelet production as a contributing factor to their thrombocytopenia and potentially facilitate individualized treatment selection.

www.bloodjournal.org/content/117/21/5723?sso-checked=true

In the 1950s and 1960s the studies of Harrington et al1 and Shulman et al2 showed that many ITP patients had plasma antibodies capable of destroying platelets in vivo. Following these studies, it was concluded that platelet destruction was the sole mechanism causing thrombocytopenia in patients with chronic ITP. However, autologous platelet survival studies in the 1980s, showing that most ITP patients had normal or decreased platelet turnover, suggested that platelet production in chronic ITP may also be impaired.3-6 This hypothesis is supported by early morphologic studies of ITP bone marrow showing normal or increased numbers of megakaryocytes with a shift to younger forms that lacked evidence of cytoplasmic granularity or platelet formation and manifested degenerative changes in the nucleus and cytoplasm. Subsequent studies, using electron microscopy, showed 50% to 75% of ITP megakaryocytes had extensive damage consisting primarily of abnormalities of the demarcation membrane system. In some cases, damaged cells showed attached monocytes, which appeared to phagocytose megakaryocyte fragments.15 It is not surprising that ITP autoantibody might affect platelet production because it has been well shown that the common ITP autoantigens, GPIIb-IIIa and GPIb-IX, are expressed on the surfaces of megakaryocytes7 and that ITP autoantibody binds to megakaryocytes.16,17

Attempts to use megakaryocyte colony formation to study thrombopoiesis in ITP have given contradictory results. Some groups, culturing ITP bone marrow, have found increased numbers of megakaryocyte colony-forming units (CFU-Ms),18,19 whereas others have found decreased numbers of CFU-Ms.20 Similarly, one group21 reported that ITP plasma did not affect CFU-M formation by normal cells, yet another group18 noted increased CFU-M formation in the presence of ITP serum.

www.bloodjournal.org/content/103/4/1364.long?sso-checked=true

jayinchicago wrote: So went back and saw what my platlet antibody tests are and found out all the Antibody tests are negative.

So basically why are my platlet count low?

Antibodies to thrombopoietin and antibodies to the thrombopoietin receptors also play a major role in ITP, perhaps greater than the role of antibodies to platelets alone, a new study shows. When all antibodies were examined, they accounted for 100% of the cases of active ITP.
I have posted the study separately:

pdsa.org/forum-sp-534/6-general-itp-discussion/29523-antibodies-to-tpo-receptor-platelets-cause-itp.html

I saw a study at the beginning of my diagnosis that talked about a test for your level, but apparently it is not available for your average person. I tried to get it in england also. I asked dr provan and he confirmed it was not available.

My consultant too (UK) told me no test available only 3 weeks ago

Just found my notes: It was called "Quest Test 16336". Angers me when the medical community has the ability to get information, but because of whatever reason, regulatory, financial....we cannot access that information.

The test exists in the US, but whether insurance will pay for it is another matter.

Here is Quest Diagnostics' info on the TPO test:

www.questdiagnostics.com/testcenter/BUOrderInfo.action?tc=16336&labCode=SKB
Thrombopoietin (TPO) Test Code 16336 CPT Code 83520
This test was performed using a kit that has not been cleared or approved by the FDA. The analytical performance characteristics of this test have been determined by Quest Diagnostics. This test should not be used for diagnosis without confirmation by other medically established means.

Performing Laboratory: Quest Diagnostics Nichols Institute-San Juan Capistrano, CA
Clinical Significance: This test will be used to measure serum TPO level in patients with thrombocytopenia of unknown cause. ITP (Idiopathic Thrombocytopenia purpura) is a common cause of thrombocytopenia.

Probably because it's not FDA approved. :huh:

Sandi wrote: Probably because it's not FDA approved. :huh:

That seems reasonable, but insurance companies pay for unapproved stuff all the time. Heck, Rituxan is not FDA approved for ITP.

Ellen has two artificial hips paid for by BCBS that were in development and not FDA approved at the time. But it took a surgeon to convince them that it would save them money to use that prosthesis.

Right, you have to fight for a treatment if it's not FDA approved. Been there. A test might be different though because they could argue that there is no benefit derived to the patient other than knowledge.

Someday these other antibody tests might be routine, but they probably aren't now because there isn't anything they can do with the information yet. Just a guess.

I told the doctor I would pay out of pocket for the test, but the labs said they could not perform the test. Second hemo said the same thing.

I dunno. Seems like Quest may be working with some company or research group to establish a formal and FDA approved test for the future. That is, 'it's under development'.

Quest probably sees the test as revenue generating in the future, else they wouldn't be providing it for someone.