
Not Every Drop of a Person’s Blood Is the Same, a Study Says - hampelm
http://www.nytimes.com/2016/02/23/health/not-every-drop-of-a-persons-blood-is-the-same-a-study-says.html
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danso
Question from an outsider (of medicine and of medical research): Why is this
study _new_? I mean I can understand why it is _news_ (for the mass
media)...but isn't this something that would've have been tested long ago to a
certain degree? At least to a degree in which, today, doctors are content that
a venous draw is a statistically useful amount of blood to derive health
results from? Wouldn't that have to based on some study that purported to find
the minimum volume of blood needed to reliably represent someone's health?

Not only does it seem like a very fundamental question to have already
asked...it doesn't even seem like a very difficult study to _do_. It's not
substantially longitudinal over time -- for every subject, you take several
pinpricks, and run the tests. Or logistically difficult to manage.

So I get why it's news, in terms of Theranos and what not...but this has to
have been something that was studied many times over many decades. Or is the
NYT misinterpreting/signifying the significance, i.e. the Rice scientists
found a previously undetectable kind of difference, but which is, yes,
technically shows that blood drops are different?

~~~
searine
Microfluidics as a field is relatively new (last 10 years or so).

This study is at the "microtiter" scale, which is the scale that companies
such as theranos are trying to take advantage of.

Microfluidics is largely an industrial field rather than academic.

>Not only does it seem like a very fundamental question to have already
asked...it doesn't even seem like a very difficult study to do.

Yeah, well, that's the difference between Silicon Valley and academia.

SV doesn't want to hear about results that invalidate their business model.

~~~
dnautics
> SV doesn't want to hear about results that invalidate their business model.

I promise you that academics not wanting to hear results that invalidate their
models is the rule, not the exception.

~~~
ufo
otoh, academics _love_ hearing results that invalidate other people's models
:)

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tomkinstinch
In general this doesn't seem like huge surprise. Blood is reasonably
homogeneous, but noise becomes an issue when you're looking for anything
present in low concentration (signal close to the noise floor) or when small
differences in concentration matter (signal superimposed on background noise
causes the value change from expected to be close to the magnitude of the
noise).

If noise is too high for a single drop, a venous draw is a much larger volume
and theoretically equivalent to sampling many drops of blood—it's the physical
equivalent to averaging samples to increase the SNR.

The authors note[1] that averaging may not be enough though, and that there
may be an interesting difference inherent to fingerprick blood (possibly
caused by their collection method):

"Our data also suggest that collecting and analyzing more fingerprick blood
does not necessarily bring the measured value closer to those of the donor’s
venous blood (Figures 1D and 2D). For example, donor B’s hemoglobin and WBC
concentration were similar for venous blood and fingerprick in drop 1 but
became less concordant with additional drops, while donor C’s fingerprick
measures came closer to the venous measures with additional drops. These data
may represent true differences between fingerprick and venous blood, or they
may be the result of errors in collection (such as leaving the tourniquet on
for too long during a venous draw). Further research is needed to determine
how common these patterns are."

1\.
[http://ajcp.oxfordjournals.org/content/ajcpath/144/6/885.ful...](http://ajcp.oxfordjournals.org/content/ajcpath/144/6/885.full.pdf)

~~~
mmmBacon
Considering that the body regulates its temperature by controlling blood flow
to the extremities, maybe it's not surprising that venus blood in particular
is not homogeneous. As the body cools blood flow to the hands is reduced.
Venus blood is also impacted by movement, gravity, etc... Since there's no
pulse in the veins, would it not make sense that the heavier constituents of
the blood would remain as the lighter components "drain?"

I wonder if like how red blood cells would settle to the bottom in a test tube
one might expect that there would be differing concentrations of blood
constituents in venus blood in the extremities depending on the elevation,
temperature, perfusion, etc... of the extremity?

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ttandon
As someone working in this field particularly on the product front and
academic front - a major concern I have with this study is the lack of work
done to establish what the clinical significance is in these variations. The
methodology is well controlled enough to indicate that a statistically
significant difference does indeed exist in the variations on the drop-to-drop
level between venous and capillary samples, but what's missing is a detailed
analysis of whether or not these differences would result in clinically
different outcomes - from my work, the range of identifying an anemic,
leukocyte spikes, etc. is large enough that the spikes in deviations in
capillary samples ultimately become inconsequential. Furthermore dozens of
studies [1,2,3 are just a few examples] in the past have found essentially the
opposite outcome. A discussion is necessary - but suggesting that all drop
based diagnostics will forever be inaccurate is both unbased and dangerous
given the growing importance of this field. If anyone has specific questions
feel free to drop me a line at ttandon[at]stanford[dot]edu

[1][http://www.hindawi.com/journals/isrn/2012/508649/](http://www.hindawi.com/journals/isrn/2012/508649/)
[2][http://www.ncbi.nlm.nih.gov/pubmed/23294266](http://www.ncbi.nlm.nih.gov/pubmed/23294266)
[3][http://journals.plos.org/plosone/article?id=10.1371/journal....](http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0043702)

~~~
kbenson
Perhaps that's not the goal of this study? I think there's benefit in knowing
that there is a difference, even if it's just in the ability to get further,
more targeted studied funded now that a fundamental question has been
answered. Now, instead of answering both whether there's a difference, and
whether it affects a specific aspect of blood testing, future studies can
focus more on the second aspect of that. I imagine that makes funding quite a
bit easier to get.

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_lex
Well, that is the end of Theranos. They should just return what money is left
to their investors at this point. This explains why they could never get the
tech right...

~~~
IanCal
I don't know too much detail about theranos, but is that really the case? The
article says they needed to go to 6-9 drops, is that a dealbreaker for what
they wanted to do?

~~~
adevine
Getting 6-9 drops of blood from a finger tip is not easy - you have to ask "Is
it really a benefit over a venous draw if it's much more difficult?" At some
point I think it makes it easier to instead just focus on super-fine needles,
and the need to draw _less_ blood, from venous draws.

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mikecsh
"Super-fine" cause mechanical haemolysis and will give inaccurate results for
many routine blood tests

~~~
jacobolus
For anyone who isn’t a doctor / biologist: “Mechanical hemolysis” means the
needle is bursting red blood cells, leaking their cytoplasm into the blood
plasma.

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jerryhuang100
this is basically the common sense for any one with some proper medical
training. and it's why many clinical scientists and medical practitioners
(read: peers) keep questioning about Theranos from the beginning.

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JabavuAdams
Something that's always perplexed me -- if we're talking about small amounts
of blood, why finger-tips? This is such a sensitive area. Why not a prick on
the elbow or the shoulder?

~~~
dsr_
The skin is thin, easily accessed, and heals quickly.

~~~
vacri
I used to be a neuro tech, and I remember one patient coming in for a carpal
tunnel test. She looked horrific - a gas heater had exploded and sprayed her a
few years before, and all visible skin looked melted - she looked a bit like a
skeletal-muscle model, as the melted skin had pooled in the divots between
muscles. But what really struck me was that the only part of her skin that
didn't look melted was the palms of her hands (and the inside of her fingers).
They'd healed just fine, and the border between healthy palm and melted skin
was like a knife edge.

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seibelj
If it's scientifically proven that a drop of blood can't be accurate, what is
the alternative to going into the vein? Maybe you wipe down the wrist with
alcohol, then put on a cuff link apparatus that simultaneously takes 20 drops
of blood.

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semi-extrinsic
It appears this depends a lot on what you are testing for. Fingerprick tests
for CRP count (basic inflammation test) seem to already be standard practice
in hospitals and health clinics. The test machine is the size of a toaster and
gives the physician direct results in a minute or two.

Also, for blood glucose, which diabetics need to monitor closely, there is
some buzz now around spectrographic (IR/UV) techniques, meaning you don't even
have to puncture the skin. That would be huge. Diabetics actually complain
more about fingerprick tests for glucose than about insulin injections, which
sounds very counter-intuitive to non-diabetics.

What glucose and CRP have in common is that they are small. TFA talks about
tests for white blood cells, platelets or HIV, which are much larger. If you
compare white blood cells to glucose, they have three orders of magnitude
larger radius, so _nine orders of magnitude_ larger volume.

That's like the difference in volume between a raindrop and a blue whale. No
wonder different mechanisms may apply.

~~~
cperciva
_Also, for blood glucose, which diabetics need to monitor closely, there is
some buzz now around spectrographic (IR /UV) techniques, meaning you don't
even have to puncture the skin. That would be huge._

It would be huge, yes. But it has been "five years away from being available"
for about 25 years. Glucose has a much smaller signal than the Hb / HbO2
signal used for pulse oximetry.

 _Diabetics actually complain more about fingerprick tests for glucose than
about insulin injections, which sounds very counter-intuitive to non-
diabetics._

Most non-diabetics think that "injecting insulin" involves hitting a vein.
That would be far more painful. Instead, we inject into subcutaneous tissue;
and the needles we use are absolutely tiny. It's worth noting that it's very
unusual to get any bleeding from an injection site.

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zkhalique
Finally! I wondered how people actually know that the genetic code is the same
in every cell. How would you prove that? What if everyone is a chimera to some
extent? We are just getting started understanding epigenetics.

~~~
tosseraccount
It's not the same. Telomeric regions shrink over time. Viruses inject their
own dna code into the host genomes. Minor damage piles up over the years.

~~~
arosenfeld
Beyond even random changes and telomeres shrinking, VDJ recombination actively
splices genes from B-cells and somatic hypermutation further modifies certain
regions. Sampling two B-cells that share a common ancestor will likely have
some genomic differences.

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privong
For additional takes on this, there was some discussion of this result
yesterday, based on a post of a direct link to the paper:
[https://news.ycombinator.com/item?id=11159526](https://news.ycombinator.com/item?id=11159526)

