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LAB-Results

Question:

What is ANA and ANCA?

Dr. Eric

The ANA is the Anti-Nuclear Antibody test. This is a blood test that is a general screen for autoantibodies. It has a low frequency of positives in PAN patients, but it can sometimes point to other diseases that may resemble PAN.The ANCA is the Anti-Neutrophil Cytoplasmic Antibody test. This blood test is positive in a high percentage of patients with certain types of vasculitis, such as Wegener's Granulomatosis and Churg-Strauss Syndrome. Again, it can help to better define the type of vasculitis.

Question

How does this differ from a biopsy?

Dr. Eric

The ANA and ANCA are blood tests, but the biopsy requires a bit of tissue for analysis. the biopsy must be read by an experienced pathologist who can recognize the characteristic appearance of the cells through the microscope.

Question

If they are forms of diagnosis, which is the preferred method of diagnosis for PAN? ANA, ANCA or biopsy?

Dr. Eric

The biopsy is the definitive method for diagnosis.

Question

Am I correct in thinking that the ESR (SED rate) indicates inflammation that has occurred in the past two weeks and the CRP indicates more recent inflammation?

Dr. Eric

This is correct.

Question

I do hope I don't sound totally thick! I have often thought about writing about these topics however, I never really liked to ask before for fear that I would look totally stupid. Okay so I am stupid (I can accept that now), but I really do want to be able to understand as much as I can. I truly believe that it is only through knowing as much as I can grasp,that I will be able to help Steve more

Dr. Eric

Not at all thick or stupid. Everyone who is affected by these diseases, whether as a patient, a caregiver, or a family member, needs to understand as much as possible about the diseases, how they are diagnosed, how they are treated, and the prognosis. You deserve the answers to ALL of your questions. If your GP or specialist can't (or won't) answer them, your friends here in this group often can.

Knowledge is power. As you note, you need that knowledge to properly help Steve.There are no stupid questions. Never be afraid to ask.

Question

So the meaning to the tests that show I have no antibodies for means that I should have them to help fight off that disease should I come in contact with it? The only other test I think I listed last week was Anti-SSA AB and Anti-SSB AB. Those were 20 also.

Dr. Eric

Mary, All four of those antibodies: Anti-SM, Anti-RNP, Anti-SSA, and Anti-SSB are abnormal autoantibodies. They are only seen in people who have autoimmune diseases. They are not involved in fighting infections. You are not at any risk because you don't have the antibodies. In fact, the PRESENCE of these antibodies would indicate autoimmune disease, so if you are negative for them (and you ARE), it is a very good sign.

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Question

Kevin—20 yr. Old. Microscopic Polyarteritis Nodosa patient, Kidney transplant recipient. Kevin has been doing well until a few days ago. All of a sudden, at routine bloodwork, his creatinine level went up to 1.04. It was holding steady at 1.02. Doc was concerned, sent him in for a biopsy. The level went as high as 1.07, then dropped to 1.04 again right before the biopsy. It seems there is a "film" on the kidney. Doc does not know what it is.

Dr. Eric

Debra, Do you know what the units are for the creatinine values? Most labs in the USA report creatinine in milligrams/deciliter, and the normal values are 0.6-1.2 mg/dl. Outside the USA most labs use micromoles/liter, so the normal range is 53-106. The values that you are stating seem to be in mg/dl, and all would be considered normal, even in a kidney transplant patient. Even if they are in micromoles/liter. (and are 104 instead of 1.04) they are at the upper end of the normal range, and would not be a large concern to me.

Another point: the creatinine assay is not accurate enough to report to two decimal points. I have never seen a result like "1.04". In most labs this would be rounded to "1.0", as would "1.02". "1.07" would be rounded to "1.1", still within normal range.

I've never heard this terminology used in regard to a kidney biopsy. How was the "film" diagnosed? By the pathologist looking at the biopsy? Is the "film" on the outside of the kidney or in the glomeruli (filtration units)?Is your doc a nephrologist? Does she have other patients who have received kidney transplants? How did they decide that it wasn't a virus? What makes them think it may be a flare of PAN?

I know these are a lot of questions, but if you can get this information I can help out more.

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Question

What does "100, 000" Flora mean on a urine test?

Dr. Eric

Mary,
"100,000 Flora" means that the urine sample was contaminated with skin or vaginal bacteria. It has NO clinical significance. The high level of bacteria may also account for an increase in protein (bacteria have protein in their little bodies).As Daniel Dank said, the best way to check for protein (if the doc is concerned about kidney damage) is a 24 hour urine collection. They can do a creatinine clearance on the same 24 hour sample to assess if there is any kidney damage.Aside form the high sed rate, your lab results are NOT unusual, and I would not spend a lot of time and energy worrying about them.

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Question

I managed to get email through to Dr. Frederick Tam about the article he published on Sept. 7 entitled "Urinary monocyte chemoattractant protein-1 (MCP) is a marker of renal vasculitis".

Dr. Eric - would it be possible to do this test at a hospital lab at this point? It surely would be much easier than a biopsy!
Myrna

Dr. Eric

Myrna,

I would like to see a copy of the paper, if you can Email it to me.It is unlikely that this test is available in a routine hospital lab right now. It usually takes a couple of years from the research lab through additional lab studies and FDA approval for a new lab test to get to the hospital lab. During this process we find out what an abnormal test really means, whether we see abnormal tests in healthy individuals, and whether all patients with a given condition show an abnormal test. All of these facts are necessary for proper interpretation of the test results. It is also important that insurance companies get an understanding of the test and its usefulness, so that they will pay for it.In the meantime, perhaps Dr. Tam can run the test on you in his research lab, and send the results to your doctor.

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Question

Can you explain SED Rate and ESR?

Dr. Eric

Here is the piece I wrote about ESR (Sed Rate) before:

What is the Sed Rate?

The Erythrocyte Sedimentation Rate (ESR or Sed Rate) is a very simple test that the lab can run on a fresh blood sample. The test is run by putting a few milliliters of whole, anticoagulated blood into a long slender tube. The tube is then placed in a rack and allowed to stand for 60 minutes. After the 60 minute incubation, the distance that the erythrocytes (red blood cells, or RBC) have settled is measured. Almost everyone¹s blood will show some settling during the 60 minute period.

What is a normal Sed Rate? The normal values for the Sed Rate are usually accepted to be 0-15 mm/hr for males, and 0-20 mm/hr for females. However, age can also cause a slight increase in ESR, so some labs use these formulas: [(age divided by 2)=normal ESR] for males and [(age+10) divided by 2=normal ESR] for females.

What causes an elevated Sed Rate?

The rate at which the blood cells settle is actually a very intricate set of interactions between the cells and the proteins in the blood plasma.

The proteins in the plasma increase the viscosity of the plasma, so the more proteins, the slower the Sed Rate. During inflammatory reactions, many plasma proteins move out of the blood stream to the tissues that are inflamed. The lower levels of plasma proteins lead to an increased Sed Rate. Anemia can also cause the Sed Rate to increase, because if there are fewer red blood cells in the whole blood, they will settle faster.

Some labs use a correction factor to correct the Sed Rate for severely anemic patients

What does an elevated Sed Rate mean?

Elevation of the Sed Rate usually indicates that an inflammatory process is happening somewhere in the body. The Sed Rate does not indicate any specific disease process, nor does it indicate the prognosis for the patient. Multiple Sed Rates measured during and after the inflammatory process may be helpful in predicting remission from the inflammation. The ESR is elevated in a lot of different conditions.

What other test might be abnormal when the Sed Rate is elevated?

Often the C-Reactive Protein (CRP) is also elevated. (I¹ll write a separate page on CRP.) Some labs are looking at a test that measures plasma viscosity The advantage of the viscosity test is that it is not subject to interference from anemia or age.I'll try attaching this as a Word document, but I'm not sure the PAN Group allows attachments. If anyone would like this as a Word document, just let me know.

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Question

How many times do we have to say it? SED rate isn't always high. But haptoglobin is high in 100% of connective tissue disease patients. How many rheumys know that, let's do a pop quiz. The worse I feel, the higher haptoglobin gets. Why can't haptoglobin just be used as an indicator? When SED rate is normal.

Dr. Eric

Elisabeth, Unfortunately, even the haptoglobin isn't 100% in connective tissue diseases, and it can be elevated in other conditions, too.

Another useful lab test is quantitative complement levels, but these are also non-specific to any disease. They are usually LOWER in connective tissue disease, but I've also seen patients who were in the normal range, in spite of raging active disease, so they aren't 100% either.

The key is for the doc to order a group of tests, have them done in a competent laboratory, and then interpret them in the context of the patient's signs, symptoms, and other clinical findings.

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Question

Could you give us more detail about the SED Rate and the CRP

Dr. Eric

basically the sed rate is a test to diagnose inflammation, but not the most trusted one in the world, since there are many factors than can change the reading. We read those by the amount of red cells that fall over a period of time, in which many things can happen to alter results.

For those who aren't familiar with how these lab tests work, the sed rate is an OLD test that is really very simple to set up, but sometimes difficult to interpret.

When you have your blood drawn, they usually take more than one tube of blood. Some of the tubes allow the blood to clot, so that we can separate the clot from the serum, since many lab tests are based on serum. Other tubes contain anticoagulants to keep the blood from clotting. The sed rate uses some of this anticoagulated blood. Some of the blood is placed in a tall thin tube and placed in a vertical position for a period of time. The blood cells, which are more dense than the liquid portion, will settle as the tube stands. After the incubation period, the distance the cells have settled is measured in millimeters, and this is the sed (sedimentation) rate. This test is subject to a lot of outside interference. If the tube isn't perfectly vertical, if the lab bench vibrates, even the room temperature, can affect the sedimentation of the cells.

Patient factors that can affect the test include inflammation, anemia, drugs, and stress, all of which are seen in PAN and other autoimmune diseases. So what good is the test? It actually can give the physician a tool for tracking the progression of inflammation if all of the other factors are kept relatively constant. Like most lab tests, a single value is not as meaningful as multiple values over time.

The CRP is a more consultive test marker for inflammation. It has been used for heart patients for as a part of a profile for years. So I would feel pretty good if I had a negative CRP level. It is much more accurate test. The CRP (C-Reactive Protein) is a more quantitative and sensitive test. It is measured on serum, using an instrument that detects very low levels of certain proteins. CRP levels move up and down much more quickly than sed rates during inflammation, and they are not as subject to interference. We often use CRP levels to assess post-op inflammation. Just the stress of surgery will cause an elevated CRP, so we measure the level right after surgery to get a "base-line" value. Then we re-check the level every day for 3 to 5 days after surgery. If there is no inflammation from infection, the levels will drop progressively. If there is an infection the levels will stay high or even increase.

In PAN patients, the value of the test is in several measurements over time to monitor the rise or fall of levels. Eric

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Question

I don't know how serious a high sed rate is if you don't have significant symptoms. My guess is that it still means inflammation (infection or autoimmune activity) is going on somewhere. I would think an MD would want to follow up on it.

Dr. Eric

A high sed rate almost always indicates an inflammatory process. It is certainly something that the doctor should analyze, and follow up if he/she can't identify an obvious cause for the elevated test.

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What do you think of what Mary's new rheumie told her? He said if sed rate's up but CRP isn't, then that suggests cancer -- e.g. lymphoma.

I'd never heard this, but I sure don't know enough. I'm in the same situation -- ESR is up and CRP is normal. I thought they just measured inflammation at different points in time (more or less).It scared me a little. Especially since I'm at risk for cancer at least 3 ways: Sjogren's (lymphoma). Ulcerative colitis (colon ca). Radiation to head (thyroid cancer). Plus common variable immune deficiency with T-cell dysfunction. Plus the lovely immune suppressant meds. The risk from any one of them is small. But the combination, plus reading what this MD said, concerned me. When it comes to labs and their implications, you often know more than the MDs (in my opinion, anyway!).

Thanks!

Linda

Dr. Eric

Linda,

My feeling is that either the physician is badly informed, or Mary misunderstood. The Sed Rate is elevated in MANY conditions. It isn't diagnostic of *anything*, and there is no "either-or" relationship. Similarly, the CRP can be elevated by MANY conditions. There is some overlap of elevated Sed Rates and CRP tests, but there is no strict inter-relationship. It is wrong to say that if the Sed Rate is elevated and the CRP is low it indicates ___________ . There is no medical condition that can be used to fill in this blank.

Both the Sed Rate and the CRP indicate inflammatory conditions. The Sed Rate tends to rise faster and fall sooner than the CRP. Neither test is diagnostic of any medical condition. Both tests MUST be interpreted along with symptoms, clinical findings and all of the other laboratory tests.I think Mary need to get further clarification from her doctor.

Regards,
Eric

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Question

Is this why they do an "enzyme" test when my husband is brought into hospital with heart problems? He's had by passes and wears a stent. There have been other angiograms as well. Always they wait for the "ensyme" tests to come back from lab b/4 doing anything else.

Dr. Eric

Exactly right. There are lots of enzymes in active tissues, because the enzymes help convert nutrients (sugars) into energy, which the tissues need for proper function. A very active tissue, like heart muscle, has a lot of active enzymes, so any damage to the heart muscle releases these enzymes into the bloodstream.The two major enzymes found in heart muscle are LDH, which we've already discussed, and Creatine Phospho Kinase, also known as CPK, CK, CK-BB, CK-MB, and CK-MM.

The last three abbreviations are CK Isoenzymes (just like the LDH Isoenzymes). The CK-BB, also called CPK-1, is found primarily in brain and lung. CK-MB, also called CPK-2, is found in heart muscle; and CK-MM, also known as CPK-3, is found in skeletal muscle.

So when your hubby is having chest pain, and the docs are waiting for the "Enzyme Tests", they are waiting for the LDH and CPK. If those are abnormal, they will look at the Isoenzyme tests to see why the enzymes are elevated.

And all this work is done by some of the best scientists in the world, the Clinical Laboratory Scientists who no one ever sees. Most people think lab work is done by the doctor, a nurse, or a machine. None of these is true! Laboratory Medicine is a specialty, just like surgery or rheumatology, but since we specialists in Lab Medicine hide in the basement of the hospital, we don't get the good press.

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Question

My doctor said , "you don't have sarcoidosis, or lupus and maybe not even Vasculitis. All of your tests have been good.

Bloodwork good for all of the above." And sed rate of 59 is fine. When I explained that it's been 86 without pred and cytoxan she argued with me and repeated that all the blood tests they have been taking was fine. She also told me I was probably wasting my time seeing a new rheumy since he would just repeat more blood work and ANA and ANCA's and others would still come back the same. Then she had the audacity to tell the resident if we listened to every patient that comes in here and their requests we would be going crazy.

I am too tired and sick to fight with anyone anymore.

Dr. Eric

At this point I would have asked her what tests she looks for to be abnormal so that she can make a diagnosis of vasculitis. One of the biggest problems in the diagnosis of vasculitis is the fact that there is *NO* laboratory test that is diagnostic for the condition (other than a biopsy, and even that can give falsely negative results if done wrong.)

In what universe did this person get her medical training? A sed rate of 59 is *ALWAYS* abnormal. It may not be related to vasculitis, but it is not "fine." If she looks at every lab test like she does the sed rate, no wonder she thinks that "all your lab tests are good."

Yes, I've often said that practicing medicine would be a lot easier if we didn't have to deal with all the sick people. Did this person have a duck under her arm, or did she quack for herself? One of the characteristics of chronic disease is that we become sick and tired of being sick and tired. Mary, it seems to me that you need a whole new team of doctors. Is it possible for you to get to Johns Hopkins in Baltimore, or Boston University Medical Center? There are some excellent vasculitis specialists at both of those institutions.

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Question

Bruce recently posted an article about cytokines and how they increase with AI disease.... Is there any way to use these cytokines as a marker for diagnosis of some diseases? I've noticed that they almost never do lab test for IL-6 ect... Why is that?

Dr. Eric

First of all, there are no FDA-approved tests for cytokines that are available, and almost all tests run in a routine clinical laboratory have to be FDA-approved.The work that Bruce has reported is still at the research stage. The results are very promising, and based on studies like the ones that have been published we can start looking at larger groups of patients and additional disease groups. I have long felt that cytokines could be valuable markers for diseases activity, but the assays haven't been accurate enough to show any trends until recently.

Another problem with cytokines is that they can be influenced by MANY inflammatory processes, so they may turn out to be not much better than the sed rate and CRP in monitoring disease.We're still looking for the holy grail... the single, simple lab test that tells us if the patient has vasculitis, and which type of vasculitis it is.

Regards,
Eric

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Question

What is CEA and what kind of test is it? Does it screen for tumors?

Dr. Eric

Crystal,CEA is Carcino-Embyonic Antigen. This is a protein that is produced by certain tumor cells, especially intestinal tumors. The test is NOT a screening test for tumors, but it is usually run on patients after the diagnosis of an intestinal tumor is made. This gives a baseline level of CEA before surgery. After surgery, we monitor the patient with repeated tests of the CEA levels over a several month period. If the surgery got all of the tumor, the levels should drop to zero and stay there. If the levels drop, but then begin to rise again, it usually indicates that there is a recurrence of the tumor.I want to emphasize that this is a monitoring test, not a screening test.

Some people who don't have tumors will run a slightly elevated level of CEA from time to time. A single CEA value is really meaningless.

Why did they do the CEA on him? Have they done these in the past? Does he have a history of intestinal polyps, or other problems in the gut?

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Question

What exactly is cryoglobulemia? I am getting mixed research about microscopic polyangiitis. The nephrologist diagnosed this, but I am ANCA negative. Is this possible?
Myrna

Dr. Eric

Myrna,
About 20% of people with microscopic polyangiitis (MPA) are ANCA negative, so it is entirely possible that you have MPA and are ANCA negative.Another aspect is that the ANCA test is a relatively new test for many labs, and some labs do a better job than others, so I would look at how long the lab has done the ANCA, what method they are using, and how they have performed on proficiency tests for ANCA. Now, if you can get that information, let me know how you did it, because I have trouble getting it, even when I inspect other labs!


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