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?
As someone who's lived with health professionals my whole life ... if you're smart and have a background in science or engineering, you're only about two or three questions away from stumping health-care providers.
The level of understanding required to build a thing is very different from the level of understanding required to patch a somewhat broken system.
The volume of venous blood for everyday blood test is indeed well known, and has been established decades ago. Take a look at your test tubes then next time you have your blood drawn. The required volumes are always clearly indicated.
This study is about novel tests based on minute volumes of blood. These are not routine in medical practice.
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."
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?
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
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.
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...
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?
I wouldn't put it that bluntly. This study focused on large molecule biomarkers for the most part. There are HUGE number of possible smaller blood based biomarkers that could very likely be normal in finger-prick blood.
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.
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?
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.
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.
Metrics behind the primary purpose of blood circulation, oxygen/CO2 and energy delivery (to which you allude), aren't the parameters they found fluctuated:
>single fingerpricks on multiple subjects varied substantially on results for basic health measures like hemoglobin, white blood cell counts and platelet counts.
It would be interesting to see what sort of variance they observed.
I'm fairly sure there is an implied "(collected at the same point of the body)" after "every drop of a person's blood". In which case your argument, while elegant, is beside the point.
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.
This study doesn't address genetics. Rather it is measure amounts of soluble blood proteins.
For all intents and purposes, your DNA is the same in every cell. We know this because we can pool DNA from multiple cells and sequence them. We see orders of magnitude more variation from sequencing error than true intra-isolate nucleotide variation.
Yes epigenetics exists, and it influences our development and habits, but it's not going to change the content of your DNA.
[+] [-] danso|10 years ago|reply
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|10 years ago|reply
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.
[+] [-] JabavuAdams|10 years ago|reply
The level of understanding required to build a thing is very different from the level of understanding required to patch a somewhat broken system.
[+] [-] ufo|10 years ago|reply
[+] [-] paviva|10 years ago|reply
This study is about novel tests based on minute volumes of blood. These are not routine in medical practice.
[+] [-] teekert|10 years ago|reply
[+] [-] tomkinstinch|10 years ago|reply
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...
[+] [-] mmmBacon|10 years ago|reply
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?
[+] [-] ttandon|10 years ago|reply
[1]http://www.hindawi.com/journals/isrn/2012/508649/ [2]http://www.ncbi.nlm.nih.gov/pubmed/23294266 [3]http://journals.plos.org/plosone/article?id=10.1371/journal....
[+] [-] kbenson|10 years ago|reply
[+] [-] _lex|10 years ago|reply
[+] [-] zitterbewegung|10 years ago|reply
[+] [-] IanCal|10 years ago|reply
[+] [-] c-slice|10 years ago|reply
[+] [-] jerryhuang100|10 years ago|reply
[+] [-] JabavuAdams|10 years ago|reply
[+] [-] dsr_|10 years ago|reply
[+] [-] seibelj|10 years ago|reply
[+] [-] semi-extrinsic|10 years ago|reply
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.
[+] [-] adevine|10 years ago|reply
[+] [-] unknown|10 years ago|reply
[deleted]
[+] [-] DINKDINK|10 years ago|reply
>single fingerpricks on multiple subjects varied substantially on results for basic health measures like hemoglobin, white blood cell counts and platelet counts.
It would be interesting to see what sort of variance they observed.
[+] [-] semi-extrinsic|10 years ago|reply
[+] [-] zkhalique|10 years ago|reply
[+] [-] searine|10 years ago|reply
For all intents and purposes, your DNA is the same in every cell. We know this because we can pool DNA from multiple cells and sequence them. We see orders of magnitude more variation from sequencing error than true intra-isolate nucleotide variation.
Yes epigenetics exists, and it influences our development and habits, but it's not going to change the content of your DNA.
[+] [-] tosseraccount|10 years ago|reply
[+] [-] privong|10 years ago|reply