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Q: medical blood test ( Answered,   1 Comment )
Question  
Subject: medical blood test
Category: Health > Medicine
Asked by: rocky_-ga
List Price: $25.00
Posted: 26 Nov 2006 11:36 PST
Expires: 26 Dec 2006 11:36 PST
Question ID: 785711
This question is very specific and should not be attempted to answer
without verifiable data (and/or) technical paper. I would like data
and model to show the direct relationship between ESR (sed rade) and
Hematocrit(%) in normal healthy sample of patients. There should be a
negative correlation. Statistical data which have low P value and good
fit between two variables (ESR mm/hr) and (%Hematocrit). This would
probabally be a good question for med student who may have access
directly to data from journals. I will be picky regarding answer. I
need to have published data.
Answer  
Subject: Re: medical blood test
Answered By: crabcakes-ga on 26 Nov 2006 20:34 PST
 
Hello Rocky_,

   Google Researchers do not have special access to data, and if we
did, we are not to post information that the customer is not able to
access themselves. I have gathered numerous articles and data for you
using Google Scholar  http://scholar.google.com/   as well as Google
and other search engines. Please check each site for complete
information.


     Normochromic, normocytic anemias can increase the sed rate, but
microcytic anemia, but sickle cell anemia, hemolytic and AIHA, and
anemias that cause poikilocytosis, spherocytes or anisocytosis
generally don?t increase the ESR, and may decrease the reading.
Macrocytosis can increase the ESR.


?Falsely decreased ESR (interfere with rouleaux formation) 
A.	Severe Leukocytosis 
B.	Polycythemia 
C.	Red Blood Cell abnormalities 
1.	Acanthocytosis 
2.	Poikilocytosis 
3.	Anisocytosis 
4.	Spheocytosis 
5.	Sickle cell disease 
6.	Microcytosis (e.g. Iron Deficiency Anemia) 
http://www.fpnotebook.com/HEM117.htm



   ?Anemia and macrocytosis increase the ESR. In anemia, with the
hematocrit reduced, the velocity of the upward flow of plasma is
altered so that red blood cell aggregates fall faster. Macrocytic red
cells with a smaller surface-to-volume ratio also settle more
rapidly.?
http://www.aafp.org/afp/991001ap/1443.html


   ?The requirements for this well-defined process are an electrolyte
and a neutral or negatively charged macromolecule in the solution and
a metabolically active red cell. If these conditions are not met, red
cells either will not aggregate at all or will form amorphous
aggregates. Rouleau formation and sedimentation are inhibited by 4,4'-
diisothiocyanatostilbene-2,2'-disulfonic acid, an inhibitor of anion
transport, but not by ouabain, a cation transport inhibitor. The
kinetics of erythrocyte sedimentation reflects the aforementioned
mechanism: no sedimentation occurs during rouleau formation. Once the
spheres of uniform size are formed, they will settle according to the
Einstein-Stokes equation. In this model, parameters of sedimentation
kinetics are the delay before sedimentation starts, the rate of
sedimentation in the steady state, and the radius of the sedimenting
aggregate.

 The radius can be calculated from the rate of fall of the aggregates
and agrees well with the microscopically observed radius. It is
inversely proportional to the hematocrit, which explains the elevated
sedimentation rates in anemia.?
http://www.bloodjournal.org/cgi/content/abstract/70/5/1572

Try to download the entire article here. (I could not download it, but
I?m hoping you can-for that reason I?m posting the link:
http://www.bloodjournal.org/cgi/reprint/70/5/1572



    ?On bivariate analysis, increased Westergren ESR of 62 (4-160)
mm/h correlated inversely with hematocrit (Hct) and serum albumin, and
positively with age, plasma fibrinogen, serum C-reactive protein
(CRP), immunoglobulins A and G,  1-acid-glycoprotein and 
1-antitrypsin. On multivariable analysis, independent predictors of
the ESR were raised CRP (p < 0.0001), low Hct (p < 0.0001), increased
fibrinogen (p < 0.0001) and immunoglobulin A (p = 0.009), and older
age (p = 0.015). The Hct-corrected ESR level [ESR  (Hct/45)] of 38
(4-91) mm/h was independently predicted by CRP (p < 0.0001),
fibrinogen (p < 0.0001), and age (p = 0.001). In the patients with
normal CRP and albumin, the Hct-corrected ESR value was normal (23
mm/h) and lower than that of 59 mm/h in the subjects with elevated CRP
and hypoalbuminemia. Using these cut-off points, the positive and
negative predictive values of the Hct-corrected ESR on the presence of
inflammation were 1.0, and its sensitivity and specificity were 100%.?
http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowFulltext&ProduktNr=0&Ausgabe=227278&ArtikelNr=46107

http://www.thedoctorsdoctor.com/labtests/esr.htm


Purchase the entire above article for $15 USD
http://content.karger.com/ProdukteDB/produkte.asp?Aktion=ShowPDF&ArtikelNr=46107&Ausgabe=227278&ProduktNr=223854&filename=46107.pdf



?There are numerous factors that can elevate the ESR. 
1.Anemia with normal RBC morphology. This effect is mediated by the
change in the ratio of erythrocytes to plasma, which favors rouleaux
formation, independent of the changes in fibrinogen concentration
(less friction to keep the RBCs suspended caused by changes in the
ratio).
2.Elevated serum concentrations of nonfibrinogen proteins: M proteins,
macroglobulins, and RBC agglutinins.
3.Renal failure [2 4]. In stable patients, renal failure is probably
due to elevated serum fibrinogen levels.
4.Heparin [5]. Sodium citrate and EDTA do not affect the ESR.
5.Hypercholesterolemia [6].
6.Extreme obesity, which is probably the result of elevated fibrinogen
levels [7, 8].
7.Pregnancy (testing for which was the first medical use of the ESR) [9].
8.Female sex [10].
9.Advanced age [11, 12]. As a rule of thumb, for men, the upper limit
of the normal ESR is age divided by 2; for women, it is age plus 10,
divided by 2.
10.Technical factors. Tilting the test tube accelerates the ESR. The
RBCs aggregate along the lower side while plasma rises along the upper
side. Consequently, the retarding influence of the plasma is
diminished. An angle of even 3 from the vertical may accelerate the
ESR by as much as 30 points [13].


There are also  numerous factors that can decrease the ESR. 
1.	Morphological abnormalities of the RBCs. Commonly seen
abnormalities of the RBCs can interfere with RBC pellet formation,
thus affecting the ESR. Red cells with an abnormal or irregular shape,
such as sickle cells, hinder rouleaux formation, which decreases the
ESR. Spherocytes, anisocytosis, and poikilocytosis also interfere with
the stacking of erythrocytes, thus decreasing the ESR [14, 15].
2.	Polycythemia. This will have the opposite effect that anemia has on
RBC pellet formation.
http://www.journals.uchicago.edu/CID/journal/issues/v33n4/001294/001294.html


   ?1. In the hematocrit, the percentage of the red cell column
occupied by trapped plasma increases directly with the packed cell
volume; this is due to a corresponding reduction of the effective
radius of centrifugation.
2. When P.C.V. is determined in Wintrobe hematocrit tubes spun at 3000
r.p.m. in a centrifuge of radius 15 cm., the variation in plasma
trapping between one sample and another is much smaller after 55
minutes centrifugation than after 30 minutes. If a 55 minute period is
used, variation is so small, even when pathologic bloods are tested,
that it is satisfactory to use a calibration curve.?
http://www.bloodjournal.org/cgi/content/abstract/7/12/1227

You may try to download the entire article here:
http://www.bloodjournal.org/cgi/reprint/7/12/1227


   ?The major components of blood viscosity are the blood cell mass
(i.e. the hematocrit), the intrinsic resistance of the plasma to flow
(commonly measured by capillary viscometry), and red blood cell
aggregability, which can be estimated through the erythrocyte
sedimentation rate (ESR). A recent meta-analysis of population-based
studies3 calculated that the IHD risk ratios of subjects in the top vs
bottom tertile of the distribution of hematocrit, plasma viscosity,
and ESR were 1.60, 1.57, and 1.33, respectively. Even higher risk
ratios (1.81 for hematocrit and 2.60 for plasma viscosity) were found
in patients with preexisting cardiovascular disease, whereas no data
are available on the prognostic value of ESR in these patients.

 In general, in comparison with the other indices of blood viscosity
(19 studies of haematocrit and six of plasma viscosity,3) ESR has been
somewhat neglected, with two large4,5 and three very small6?8
prospective studies published in the last three decades. One reason
might be that the ESR can only be measured on fresh bloodsamples, and
is confounded by gender, age,hematocrit, as well as the presence of
many acute or chronic illnesses.

 On the other hand, the ESR measurement by the Westergren method is
standardized, accurate, universally available, and cheap. Furthermore,
when red blood cell physical characteristics are taken into account by
adjusting for hematocrit, ESR largely reflects the plasma
concentration of acute phase response proteins resulting in a compound
index of both viscosityand inflammation.?
http://eurheartj.oxfordjournals.org/cgi/content/full/24/7/639


   ?Preparation of blood samples - Venous blood samples were obtained
from healthy adults, age range 28-54 years and of either gender, via
withdrawal into sterile vacuum tubes containing (1.5 mg/ml blood). RBC
were separated from the blood by centrifugation 1,400 g for 10 min and
washed with 10 mM phosphate
buffered saline (PBS; pH=7.4; osmolality 290  3 mOsm/kg). The washed
RBC were then resuspended in PBS at a hematocrit of approximately 5%.
These low-hematocrit RBC suspensions were divided into four aliquots and
exposed to: 1) 0.005% glutaraldehyde (GA; Sigma Chemical Company, St.
Louis, MO, USA) at 25 ?C for 30 min; 2) 1mM hydrogen peroxide (H2O2,
Sigma) at 25 ?C for 30 min; 3) heat treatment at 48 C for 5 minutes. The
remaining aliquot was kept at 25 C for 30 minutes and served as the
control. In some experiments RBC were exposed to GA at concentrations
ranging between 0.005% and 0.02% at 25 C for 30 minutes. Following the
treatment or control periods, the cells were washed three times in PBS and
resuspended in either autologous plasma or PBS at a hematocrit of 40% and
then used for viscosity and aggregation measurements. The washed RBC
were also used for elongation index (EI) measurements by ektacytometry
(see below). All analyses were completed within 5 hours after blood
collection.?
http://www.akdeniz.edu.tr/~baskurt/doc/vis.pdf



    ?Despite the statistically significant association between
haematocrit and coronary heart disease in the general population, the
risk ratio is only slightly elevated above 1?0 and its relevance
remains uncertain. Haematocrit levels are correlated with a number of
standard vascular risk factors (Table 1) and adjustment for the
measured values of these factors in some studies reduces the strength
of the associations between haematocrit and coronary heart disease.
Hence, adjustment for the longterm usual values of those factors (and
other possible confounders) should reduce the risk ratio still further
towards 1?0. It is also possible that the available evidence on
haematocrit and coronary heart disease has been exaggerated somewhat
by publication bias[35].

   Assays for haematocrit are widely available, so other relevant
studies of haematocrit and incident coronary heart disease may well
exist (e.g., in trials of vascular disease prevention) that have not
yet been reported.  Indeed, separate results for coronary heart
disease were not reported in a few long-term prospective studies of
haematocrit and all-cause mortality[36,37], but any bias owing to the
absence of these published studies is not likely to be substantial
since they include less than 5% of the deaths in the available
studies.
Similar considerations apply to the prospective studies of coronary
heart disease and viscosity, even fewer of which are published, with
five of the six publications being reported only since 1996 (Fig. 2).
So, further measurement of these rheological factors (and of various
possible confounders or mediators) in some large studies might
substantially change the present overall results and their
interpretation. With regard to erythrocyte sedimentation rate, few
studies are available and only two reported adjustment for standard
risk factors, while none reported adjustment for fibrinogen.?
http://cardio.bjmu.edu.cn/reference/168.pdf




   ?Moderately elevated ESR occurs with inflammation, but also with
anemia, infection, pregnancy, and old age.?

   ?Although a low ESR is not usually important, it can be seen with
polycythemia (a condition where a patient makes too many red blood
cells), with extreme leukocytosis (patient has too many white blood
cells), and with some protein abnormalities. Some changes in red cell
shape (such as sickle cells in sickle cell anemia) also lower the
ESR.?
http://www.labtestsonline.org/understanding/analytes/esr/test.html


   ?Anemia and macrocytosis increase the ESR. In anemia, with the
hematocrit reduced, the velocity of the upward flow of plasma is
altered so that red blood cell aggregates fall faster. Macrocytic red
cells with a smaller surface-to-volume ratio also settle more rapidly.
A decreased ESR is associated with a number of blood diseases in which
red blood cells have an irregular or smaller shape that causes slower
settling.(1,3)?
http://www.findarticles.com/p/articles/mi_m3225/is_5_60/ai_57436944




   ?The role of the surface charge of human red blood cells (RBC's) in
affecting RBC aggregation by macromolecules was studied by comparing
the behavior of normal RBC's with that of RBC's treated with
neuraminidase, which removes the sialic acids from the cell membrane
and reduces the zeta potential. RBC aggregation in dextrans with
different molecular weights (Dx 20, Dx 40, and Dx 80) was quantified
by microscopic observation, measurement of erythrocyte sedimentation
rate, and determination of low-shear viscosity. Dx 20 did not cause
aggregation of normal RBC's, but caused considerable aggregation of
neuraminidase-treated RBC's. Neuraminidase-treated RBC's also showed
stronger aggregation than normal RBC's in Dx 40 and 80.?
http://www.jgp.org/cgi/content/abstract/61/5/638



   ?Abstract. Precise measurements have been made of the rate of
sedimentation of whole blood in which the concentrations of red blood
cells and the plasma proteins have been systematically varied. The
contribution of each factor to the sedimentation process is expressed
in terms of three parameters that describe the sedimentation curve:
the set-up time, and the slopes of the first and second phases of
settling. This analysis affords delineation between the onset and the
degree of aggregation of the red blood cells as contributors to the
usual ESR value, the height of plasma in a 200 nm blood column after
60 min.?
http://www.iop.org/EJ/abstract/0031-9155/39/11/005

Purchase this article for $30 USD
http://www.iop.org/EJ/article/0031-9155/39/11/005/pb941105.pdf


You may find this article of use too: Click on the page numbers found
at the top and bottom of each page, to go from one page to another:
http://www.pubmedcentral.nih.gov/pagerender.fcgi?artid=1371717&pageindex=1


   ?For studies of RBCs suspended in plasma, the hematocrit of the
blood was adjusted to 40  1% via addition of either autologous plasma
or packed RBC; hematocrit values were determined using the
microhematocrit method (14,000  g, 4 min). An appropriate volume of
stock polymer solution in PBS was added to an aliquot of the RBC
suspension to yield the desired plasma polymer concentration; an
equivalent volume of polymer-free PBS was added to the controls. For
studies with RBCs suspended in polymer solutions, RBCs were washed
twice with PBS (1400  g, 6 min), then resuspended in 0.25 to 3.0%
(w/v) polymer in PBS to a final hematocrit of 40  1%. Concentrations
of 0.25 to 1.5% (w/v) were used for medium- to high-molecular weight
polymers, and concentrations of 1.5 and 3.0% (w/v) were used for
low-molecular weight polymers. All experiments were completed within 8
h of venipuncture. Microscopic examination of all RBC suspensions
showed normal discocytic cell morphology.?
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1304934



Correction of ESR
  The erythrocyte sedimentation rate (ESR) may be affected by
variation in hematocrit, MCHC and serum protein. It is important to
correct for these factors to ensure an accurate interpretation.
corrected ESR in mm in 1 hour =
= ((((1.5 * (ESR)) + (1.9905 * C)) / ((100 / (hematocrit as whole
number)) - 1)) - (1.327 * C))
where: 
? C = (((MCHC in g/dL) - (total protein in g/dL)) / 25)
Limitations:
? Anisocytosis or poikilocytosis may interfere with rouleaux formation
and cause large variations in the sedimentation rate.
http://www.medal.org/visitor/www%5CActive%5Cch3%5Cch3.01%5Cch3.01.02.aspx


    ?The erythrocyte sedimentation rate of undiluted blood samples
from 576 patients was measured simultaneously with and without manual
hematocrit adjustment to 0.35 to identify an approximate expression of
the area under the curve and a formula for calculating the Sigma ESR.
The Sigma ESR formula was based on the sum of 2 unadjusted
sedimentation levels, at 30 and 60 minutes, together with the
hematocrit value and the hemoglobin concentration. Sigma ESR values in
274 healthy subjects showed a gaussian distribution, no difference
between men and women, and no significant increase with age. In
recent-onset arthritis or disk-related lumbosciatic syndrome, Sigma
ESR seemed to be a more reliable marker of inflammation than the
Westergren ESR and C-reactive protein.?
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=15491977&dopt=Abstract


  ?Increased Westergren ESR in HD patients is associated with
activated acute-phase response, anemia, and aging. The Hct-corrected
ESR values of 23 and 59 mm/h precisely select the HD patients with
severe inflammation from those without.?
http://cat.inist.fr/?aModele=afficheN&cpsidt=14113445



    I was once  involved in correlation studies comparing Westergren
ESR values to Ves-Matic sed rates. Once we arrived at similar results
as the abstract below, we implemented the Ves-Matic in our hospital.

?VES-matic ESR
The VES-matic family of systems contains several modifications of the
Westergren method. One mL of whole blood is collected into a special
tube containing enough sodium citrate to both anticoagulate and dilute
the blood in the 4:1 modified Westergren ratio. The tube is placed on
a reader where it is held at an angle of 18 off vertical to
accelerate sedimentation. An infrared reader determines the endpoint
after 20 minutes.

The VES-matic ESR results correlate well with the modified Westergren
results and offer advantages of improved timeliness and less specimen
handling. Drawbacks include the need for specialized equipment and
specimen tubes.?
http://www.api-pt.com/pdfs/2006Bcoag.pdf


   ?The zeta sedimentation ratio (ZSR) is a measurement similar to the
determination of the erythrocyte sedimentation rate (ESR) but
possesses sevaral advantages. It is unaffected by anemia and responds
in a linear manner to increase in fibrinogen and/or gamma globulin.
The normal range is identical for males and females. A blood sample,
contained within a vertically oriented capillary tube, is subjected to
four cycles of dispersion and compaction. At the conclusion of this
process, the hematocrit of the blood in the red cell-containing
portion of the capillary tube is measured. This hematocrit, a measure
of the closeness with which red cells will approach each other under a
standardized stress, is the ZSR.?
http://intl.bloodjournal.org/cgi/content/abstract/40/4/550





   ?Moreover, the aggregation of the settling cells result in
decreasing the internal energy of the sample, reducing its surface
tension and drop flattering correspondently, that also increases its
transparency As the change of the sample transparency is in direct
relation to the cells sedimentation process, the change of the light
flow intensity during settling is the desired criterion characterizing
the given process. The process of the cells sedimentation in drop
sample ends in 15-20 min. In this case the value of the photoflow
registered changes (according to the cells sedimentation rate) by a
factor of 1.2-2.5. Based on the experimental results one can conclude
that the use of the given method for the ESR index registration is
very promising.?
http://ieeexplore.ieee.org/xpl/freeabs_all.jsp?arnumber=1213759


   ?The basic principle of the ESR is that when anticoagulated blood
is placed in a vertical column the RBCs normally settle quite slowly.
This occurs for 2 main reasons: (1) RBCs repel each other due to the
negative charges on their surfaces, or zeta potential, and (2) the
large surface-area-to-volume ratio of normal RBCs resists settling.
The aggregation of RBCs into rouleaux, which happens slowly under
normal conditions, markedly accelerates sedimentation by decreasing
the surface-area-to-volume ratio. Conditions that promote the
formation of rouleaux produce an elevated ESR.?

The ESR may be elevated by other conditions that decrease the zeta
potential or the RBC surface-area-tovolume ratio. The zeta potential
is reduced by other plasma proteins, including immunoglobulins, as
well as cholesterol, phospholipids, and some medications. By creating
more space between RBCs, anemia reduces the effect of the zeta
potential to slow sedimentation. Decreases in the
surface-area-to-volume ratio, as in macrocytosis, also increase the
ESR.
The ESR may be decreased by conditions that interfere with the
formation of rouleaux or increase the RBC surface-area-to-volume
ratio. Rouleaux formation is hindered by spherocytosis, sickle cell
disease, microcytosis, marked variation in RBC size (anisocytosis),
and some drugs. Polycythemia decreases the compactness of rouleaux
formation. The surface-area-to-volume ratio is increased in some
thalassemias and hemoglobinopathies.?
http://www.api-pt.com/pdfs/2006Bcoag.pdf



Factors affecting Sed Rate
http://www.medal.org/visitor/www%5CActive%5Cch3%5Cch3.01%5Cch3.01.03.aspx#ref

You  may be interested in this article:
http://www.mechatronics.nl/technics/esr/the_erythrocyte_sedimentation_rate_by_c_saadeh_md.pdf



I hope this has answered your question. Please request an Answer
Clarification abd allow me to respond, before you rate, if anything is
unclear.

Regards, Crabcakes

Search Terms
=============
Zeta potential + ESR + anemia 
RBC zeta potential + ESR + hematocrit
RBC indices affect  + ESR
Sed rate + low H&H
ESR + erythrocytopenia
ESR + decreased RBC
ESR + RBC
RBC aggregation + indices

Request for Answer Clarification by rocky_-ga on 28 Nov 2006 07:28 PST
Hi Crabcakes-ga,

Thanks for the work you did, it was helful. Between us both we have
covered several areas. The addtional clarification again comes back to
the actual data correlation between Hct and Esr. Since there is very
little of this actual data plotted and supplied it would be nice to
see low values of ESR 0-1mm/hr as it relates to polycythemia.
Possible in a case study. 

Thanks ! 
Greg

Clarification of Answer by crabcakes-ga on 29 Nov 2006 11:23 PST
Hi again Rocky,

   I think I am not really understanding your question. First you were
asking about ESR and anemias, and now you want ESR and polycythemia.

   The more I think about it, how do you propose plotting ESR results
amongst patients? I have found no such thing, except the ones I post
here. I am not through searching however, but I am leaning towards
thinking such a graph would not exist.

   Here are sample graphs that I have found.

Plotting of ESRs post arthroplasty and lumbar disc surgery:
http://www.uphs.upenn.edu/ortho/oj/2002/html/PICS/p15f1.gif

Additional charts and tables:
http://www.uphs.upenn.edu/ortho/oj/2002/html/oj15sp02p13.html

In HLA-B27 disease
http://www.kickas.org/medical/14.shtml

ESR + corticosteroids
http://webeye.ophth.uiowa.edu/DEPT/AION/fig10.htm


Thyroid + ESR
http://www.medscape.com/viewarticle/436470_3

ESR + CD71
http://bmc.ub.uni-potsdam.de/ar403/F4.htm


Check back often as the notification system does not work.

Regards, Crabcakes
Comments  
Subject: Re: medical blood test
From: pinkfreud-ga on 26 Nov 2006 12:15 PST
 
This article might be of interest:

http://archopht.ama-assn.org/cgi/content/abstract/105/7/965

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