First, every lab should have developed its own reference ranges for all the procedures that are performed there. While everyone's ranges will be close, there will be variations due to collection, storage, transport and preparation techniques, types of instruments used and the specific patients in the population. And, since the ranges that are developed are averages, not a definition of "normal", the best way to look at those values are as a reference, something to compare yourself against others in your situations. The best comparison, however, is against your own previous reports (not helpful if they are your first but you have to start somewhere).
Second, every test has a unique reproducibility, that is, the range of results expected when you repeatedly perform the same test on the same sample. Obviously, you want the answer to be identical but, again, changes in collection, storage, transport, preparation, and instruments do occur so that the object here is to get the reproducibility as close to zero as possible.
So what I'm giving you is a general "sense" of average:
In the US, the reference range for haemoglobin in adult males is between 14.0 - 18.0 g/dL; for adult females it is 12 - 16. The ranges for children vary by age. Typically, for the most common procedure, the reproducibility here is plus or minus 0.1.
In the US, the reference range for platelets is between of 150,000 - 450,000 or 150. - 450. x10 raised to the 9th power per litre or 150. - 450. x 10 raised to the 3rd power per microliter. There are several different methods for platelet counts that are distinct reproducibility - the range can be from +/- 10,000 all the way up to +/-25,000.
In the US, the reference range for total white blood cell counts is between of 4,000 - 11,000 or 4. - 11. x10 raised to the 9th power per litre or 4. - 11. x 10 raised to the 3rd power per microliter. Typically, for the most common procedure, the reproducibility here is plus or minus 500.
Peter - this is the classic example of why you shouldn't be looking at the percentages of cells but looking at the absolute numbers (which you will have to calculate). When total leukocyte counts (your TLC, other people's WBC) are either high or low, the percentages may not accurately reflect the true population of cells because you must count to 100 cells to get a percent. For example - is her monocyte count actually increased or is the percentage skewed because of a decrease in lymphocytes or in neutrophils?
To calculate absolute counts - multiply the TLC by the percentage of the cell line in which you are interested.
In the US, the typical reference range for WBC is between 4 - 11 and the typical reference range for monocyte percentages is 0 -10% so the absolute reference range for monocytes is between 0 and 1.1 In your wife's situation, you multiply 2.8 by 0.23 for an absolute count of 0.6 - well within the reference range.
For her neutrophil count - the absolute count is 1.17 (reference here is between 2.0 - 7.7) For her lymphocyte count - the absolute count is 0.4 (reference here- between 0.8 and 4.4)
So - her monocyte are fine. Her lymphocytes are half what they should be and her neutrophils are about half what they should be.
White blood cell counts are reported in 3 different formats, depending on what country you come from. The good part is that the format doesn't get in the way of the patient number.
In the US - we don't believe in going along with other countries so we still use the oldest method of reporting (sigh). WBC are reported as cells per microliter (µl) or worse (and incorrectly) cells by cubic millimeter (cumm). Because the instrument does care which description is printed on the requisition form, you might see this reported as cells times 10 raised to the 3rd power per microliter. Verbally this sounds like thousands so you husband's WBC would be 77 thousand. In Europe (and most of the world), WBC are reported as number of cells per liter or in this case, 77 times 10 raised to the 6th power per liter. You have noticed that the really important number - the 77 - doesn't change only the "description" does so most folks now just read the number as 77 with a general reference range of 4 to 11.
CD stands for clusters of differentiation; they are chemical structures on the cell membrane that "do" a specific something. For example,you have receptors on every cell for insulin; that would translate into a CD. For lymphocytes, there are certain patterns of CDs that are seen frequently in CLL. Some combination of CD5, CD19, CD20, CD 21, CD23 and CD24 are seen. The more we test for CDs in CLL the more variability we find. There are several other CDs that are also evaluated. I would suggest that you sit down with his physician and have him/her explain the what and why of every test so that you can get a handle of the reasoning behind the decisions.
In order to give someone stem cells (whether from themselves or someone else), you need to give enough of them for the person to survive. The magic number is 2,000/microliter or 2.0x10^3/µl or 2.0x10^6/L. Less than that the patient has a significantly harder time recovering from the BMT.
When you test cells, some cells are stain more positively than others. So sometimes you want an average "positivity" value which you do by taking all the results and finding the mathematical average. After you do that, you might want to know what the range of positivity was. Remember how the MCV is the mean size of the red cell and the RDW is the range of size? Well in flow cytometry, you need the same types of values- they are just called different things. MFIR are mean fluorescent intensive ratios (your average result divided by a reference cell set's values) and the StD is the standard deviation.
CD19 is a pan B cell marker which means that it should be positive on all B cells, regardless of which type of B cell is present. This gives you the total number of B cells in a sample. Then you want to know WHICH B cell subtypes (subsets) are present.
Ditto for the CD3 which is a pan T cell marker.
Once you know how many of each of these major types of lymphocytes you have, you then want to know about the specific subsets. Fr example, CD4 is found only on cells that are initiators/controllers of the immune response while CD8 is found only on cells that suppress the immune response.
Too many CD4 cells, you get a hyperactive immune response while too many CD8 cells will give you a lessened or absent immune response.
Q. "In other words, for the total lymphocytes, CD19 and CD3 should be 100%? >And are the markers more significant on the CD19 subset when diagnosing for CLL or a variant?"
Well, we are never that perfect but , yes, in principle the combined value should be 100% - more likely 95 - 100%.
Since the most common presentation of CLL is a B cell disorder, the CD19 is expected more often but CLL can also be a T cell problem at which point the CD3 become the item of interest.
> >So the higher the ratio CD4/CD8 the better? When looking at CD4 and CD8 is >intensity more important than percentage? or is it more a combination of the >two? Has too high or too low been defined for those markers? > No, ratios are funny things. Thye don't tell actual numbers just relationships.for example having 3x too many CD4 would give you a ratio of 3:1 but so would having 1/3 as many CD8s and, of course, if the CD4 were increased 9 fold and the CD8 by three fold , you would still have a 2:1 ratio.. The ratio is a convenient shorthand - once you have already established which cell is the "offending" cell? What you want is n acceptable ratio with the absolute numbers within reference range. Check the report sheet. These values should be there.
Intensity is also one of those "grey "things. Yes, you do want cells that are metabolically active (intense) but you don't want them too active or you would be in a constant heightened immune response . One of the most complex things about a flow cytometry report is that it must be looked at as a whole. One can not pull one thread out and look at it alone. Ask your physician to explain how you flow allows for a better understanding of your CBC and current status. He will be able to pull together your signs and symptoms as well as the raw numbers.
Gayle - a primary criteron for a diagnosis of CLL is the having the percentages of lymphocytes (all stages of maturation) greater than 30%. Typically there are less than 20% lymphocytes so you met one important criteria. (What I mentioned was a diagnostic criteria of greater than 30% lymphocytes in the bone marrow - not in the peripheral blood).
Another criterion is the that the cells in question have to have one abnormal ancestor. Typically, if you were to perform a glow cytometry examination on a normal blood sample, you would find that there would be a wide diversity of markers and variable intensity as well, indicating that you had a lot of different cells, each one responding (or not) to a different or varied antigen.
CD5 is a marker for T cells. CD13 is a marker for monocytes and granulocytes. CD19 is a B lymphocytes and some marrow cells called dendritic cells. CD20 is another B cell marker. CD23 is another B cell marker. CD52 is a marker on lymphocytes (both T and B) and granulocytes.
You said = CD19 77.4, CD5 is 95.7, CD19 and 5 coexpression of 77.2, CD19 and 13 is 1.8, CD20 is 82.1, 2+ intensity, CD52 is 99.5, 3+ intensity, CD23 is 79.5."
So most of your cells are B cells (CD19, CD23, CD52). Of those cells, the majority of them appears to have the classic markers for CLL (5 and 19). A small number of abnormal cells appear to be monocytes. This is good in that if the monocytes were heavily involved, there would be additional complications and a greater loss of immune function and a more aggressive disease.
In the three versions for staging of CLL, the best prognosis is for a person with a normal hemoglobin (you have that) and a normal platelet count (you have that) and no disease in the lymph nodes. Within that best prognosis, a stable White cell count give an even better prognosis.
Absolute counts are calculated by taking the total white blood cell count and multiplying it by the percent of the specific cell line you are interested in. The percentages are derived from 1) a microscopic examination of blood performed manually in which some hundreds of cells (varies by need) are differentiated from each other (the procedure is called a differential or diff) or 2)a machine scored differentiation based on cell patterns. Again, reference ranges do vary but granulocytes (polys, segs, neutrophils) are usually 50-70%; lymphocytes 20-40%; monocytes 0-8%; eosinophils 0-2% and basophiles 0-1%. SO, a percentage of 50 % granulocytes in a total white count of 4,000 equals an absolute granulocyte count of 2,000.
Remember that statistics (which is what most of the mumbo-jumbo up above really is) work only on populations, not on individuals. You need to compare yourself to you; not a scale.
Petechiae are small pinpoint haemorrhages most easily seen in the skin and mucous membranes. They occur most often due to low platelet numbers or inadequate platelet quality. The nose bleed might have been connected to the platelets.
Many blood tests are taken from capillary punctures so it is hard to surmise hat might have been done. The logical answer is aCBC if you also got a white cell count out of it. Most infections do increase WBC counts but some can suppress them. Since you didn't say what your count was before this test (but implied that it was high), it's impossible to explain it. Most viral infections cause an increase in lymphocytes, typically those called reactive lymphocytes since they are responding to the viral antigens in a process known as specific immune defence; and since your symptoms are those typically seen in viral disease (throat swollen neck glands etc), it is logical to assume that. For most people, taking antibiotics for a viral disease is a major no-no since it has helped to create the degree of bacterial resistance that is such a problem these days. But, since you are somewhat immunocompromised to start off with, a family doc might just be nervous enough to try and cover all bases.
An RDW is measure of the change in size of the individual red blood cells (anisocytosis). Since red cells range from 1 day old to 120 days old, they tend to get smaller and rounder during the aging process so that the rdw will never be 1(every cell the exact same size). Lower RDW's can come from a variety of sources, most commonly a poor sample collection and capillary punctures are notorious for sample problems. It is possible that's the explanation. Another possibility is that the cells are reacting to your CLL and are starting out less large than usual so there is a lesser change during aging.
The MCH is a measure of the amount of haemoglobin present in each red cell. Persons with difficulties in haemoglobin metabolism (iron deficiency or chronic inflammation for examples) have lesser amounts of haemoglobin in the cells. A normal MCH usually indicates that hemoglobin metabolism is adequate.
Question: What's more important: WBC count, absolute lymphs %, or peripheral blood lymph%?
Answer: They are equally important. The absolute lymphocyte count is calculated by multiplying the lymphocyte percentage by the total white blood cell count. Absolute counts are used to determine if the percentages reflect real changes in the numbers of cells. For example, a normal percentage of lymphocytes in an adult is roughly between 20 and 45 %. An absolute count would be between 800 - 5,000. So, a differential report with a granulocyte value of 90% and a lymphocyte value of 2% might suggest that 1)the granulocytes are elevated OR 2) the lymphocytes are depressed. The only way to tell is to do absolute counts . Say the white count were high - say 50,000, the absolute count of lymphocytes would be 1,000 or within acceptable limits, therefore the problem is with the granulocytes. Another example: same differential but a white count of 3,000. In this case, the granulocytes are within acceptable limits but the lymphocytes are low.
Question: What is the significance of normal hemoglobin yet an above normal MCH and below normal RDW?
Answer: The MCH reflects the average amount of hemoglobin in each red cell. Again, numbers can play games here. The same amount of hemoglobin can be high in a small cell, ok in a normally sized cell or low in a large cell. If you cells are smaller than they should be but still contain the correct number of molecules of hemoglobin, then this number is going to appear high.
We used to think that it was impossible to get a low RDW (that's how much we know). The RDW is a mathematical expression of the differences in red cell sizes. All red cells start out on the big side and gradually, as they age their expected 120 days in the peripheral blood, get smaller. Simplistically, think of each day's worth of cells as having their "own size", so you can appreciate that the RDW number should not be a perfect "1". Now, it seems that, with a number of disease states, the cells start out smaller than they should be so there is less "daily change" and thus, a resultant smaller RDW.
Laboratories talk about accuracy as in "if the test should be positive, it is positive and if the test should be negative, it is negative. Most procedures should be in the 90% and higher range. What you are talking about is what we call precision. If I were to use the same specimen and test it 10 different times using the same instrument or method, then what is the acceptable "range" of answers for those 10 tests.
Sometimes the actual range doesn't mean so much/ For example, repeat testing for a pregnancy test might range from strongly to markedly strongly positive. Bottom line - you are pregnant - period.
In the case of WBC counts, all instruments have a precision range of +/- 2% (a maximum of 2,000 cells if the WBC count is between 0 and 100). Above 100, the instruments require that you manually dilute the sample and that can introduce some imprecision. If the dilution is a 1:2, then the range should be +/- 4.%. If the dilution is 1:4, then the range will increase to +/- 10% (the more diluted, the greater the potential for error).
So - if your WBC is 380,000, then the laboratory would be using a 1:4 dilution and the acceptable range would be between 360 and 395.
T here are several ways in which WBC counts are expressed. Originally, WBC values were gotten by counting the number of cells in a cubic millimeter (math purists -d o not scream). These turned out to be thousands - as in 5,000 or 5K . Later, it occurred to people that there is no such things as a cubic millimeter but that there is microliter. Since the only thing that changed was an incorrect term to a correct one, people still "talked" about thousands of cells. The rest of the planet (excepting the US) decided about 30 years ago to all go to a standard system of measurement (SI. units) so that everyone would be able to understand everyone else's values. In this system, the volume of blood from which one counts the WBC is the Liter.
Fortunately, all that moving around can be easily accommodated in writing since 5,000/cu mm equals 5,000/µl which can be written in scientific language as 5.0x10 to the 3rd/µl or 5.0x10 to the 9th/L. The problem is that people don't "speak" 5 point zer times ten to the ninth per liter. In the US, they cheat and say 5 thousand.
So your husband's values can be either 11.2 K or eleven thousand, 2 hundred or 11.2x10 to the ninth power per liter. You must not be getting the complete requisition form. I believe that all accreditation agencies require reference ranges to be printed next to the value column. Althought all labs will have their own unique ranges, in the US, a good "sense" of these values is 4 - 11 K or 4.0 - 11.0 times ten to the 9th per liter or 4-11 times ten to the 3rd per microliter.
Yvonne - a 1000 WBC is extraordinarily high. In fact, it is higher than I personally have ever seen. My first reaction is that your father's physician is simply not treating him as he believes that at 79, it is a little value. If he were my father, I would insist of changing physicians today - not tomorrow today - and get him seen by a competent hematologist
When red cells leave the bone marrow, they contain some left over RNA in the form of a network (reticulum). This reticulum is typically gotten rid on within 1 day after leaving the marrow. These cells are called reticulocytes and obviously can be separated from "regular" red cells by the presence of the reticulum. COunting them give s pretty good idea of the capability of the marrow to respond to stress such as decreased oxygen in the blood or shortened lifespan of the red cells, etc. If you have a steady state red cell population, then the number of red cells that you lose every day should be replaced by the same number of cells. So if cells live 110 - 120 days, then you should lose/replace approximately 1/110th or for the sake of ease 1% of the red cell population every day.
Although every laboratory will have their own reference ranges, on average a reticulocyte count should be between 1-3%. This percentage is calculated by counting 1000 cells and discriminating between those with reticulum and those which do not have any reticulum. Parallel to the absolute white cell counts, you can calculate the absolute reticulocyte count by multiplying the total red cell cont by the reticulocyte percentage. So - if your red cell count was 4.5x10^9/liter and you have a 2% reticulocyte count, then your absolute reticulocyte count is 50x10^3 or 50,000 or .50x10^6/microliter.
So - a 3.3% reticulocyte is slightly high. I am assuming that the 130.9 has a thousands or x10^3 after it. If that is true, then this supports the reticulocyte percent as high. This could be because 1. your red cells are dying off too fast/being lost due to bleeding so your marrow is trying to compensate by making more red cells. 2. your oxygen level is too low and your marrow is trying to make more red cells that are capable of increasing the oxygen content. 3. something else.
Neutrophils need to be able to move out of the peripheral blood and into the tissue if they are to combat bacteria, etc. So, they are capable of "attaching" themselves onto the walls of the blood vessels so that they can squeeze themselves out of the blood into the tissues. This attachment is called margination.
So polys can be in the blood or off to the side. Prednisone knocks them off the margination and it looks as if your WBC count has gone up. Other situations increase the margination so it looks as if the W C count has gone down
Well, some people are just lucky in that they have a condition known as chronic neutropenia. Others can have it as a result of low grade inflammation that stimulates the polys to stick. Other can have it as a medication side effect. Given CLL's ability to provoke lots of different reactions in people, it could very well be just one of "those" things that CLL people have to deal with. As long as Charlie isn't becoming infected or have slow wound healing ,etc., then he has enough functional - although uncountable - granulocytes and you need not worry.
PS - there is an absolutely horrid test to prove that the cells are sticking to the vessels. You take a WBC count, then hook the person to an IV of epinephrine for at leat 15 minutes - yup that is a prolonged panic reaction - and then take another WBC count to see if the cells have "dropped" off into the circulation (which they will do with enough epinephrine. Then you keep the epinephrine going and about 1 hour later, draw another specimen to check the marrow reserve of polys. Not a pretty experience and not one I would suggest!
Phlebotomists are supposed to follow the NCCLS standards for phlebotomy which dictate 1. the phlebotomist must be wearing gloves to lessen the chance of blood borne pathogens (both to the patient and the phlebotomist)
2. unless otherwise stated/requested, a 70% isopropyl alcohol swab is used in a unidirection (typically downward although concentrate circles is also used) motion and allowed to air dry. At NO time after that swab is used is the phlebotomist to touch the proposed venipuncture site. 70% isopropyl alcohol is NOT an antiseptic; it is a cleaning agent only. Antiseptics include iodine and all its varieties and, for those who have iodine reactions, benzalkonium chloride can be used. Most of the time, these antiseptics are used for blood culture collection, bood alchol collection and highly specific tests for which alchol is a contaminant.
3. At no time should the skin be dried using a piece of gauze. All liquid cleanser/antiseptics must be allowed to air dry.
There are federal regulations concerning the correct "safety" techniques for blood drawing. These mandate that the phebotomist 1. Wash their hands between each and every patient 2. put on a fresh set of gloves prior to the procedure itself (yes you can touch the patient before the actual draw if you have no gloves on but never once the procedure has begun (as in the tourniquet is in place). 3. At no time can you rip a hole in the glove 4. use gloves only in areas that are so designated and never use gloves in areas or or equipment (phones, etc.) not designated.
Yes, you do go through a lot of gloved that way but you also reduce the chance of transferring an infection from one person to another to close to zero.
In addition to these regulations, the NCCLS has published a set of standards for the correct procedure for a phlebotomy. I'm sorry that I can't print them here as they are copyrighted and you have to pay a hefty fee to purchase a set of these guidelines. But they are so accepted that failure to follow them is considered a "malpractic-able" event. These include (but are not limited to) the correct way to 1. use the alcohol pad or other antiseptic 2. find the vein - no slapping, rubbing, or hand pumping. 3. use of proper order of draw - that is, which color stopped tube to draw first, second, etc.
Touching the site of the phlebotomy after the swab has been used in stupid and wrong since you just contaminated the very area you just tried to de-contaminate!