Researchers determined that as many as nine successive capillary blood drops must be collected and tested to achieve results that would be comparable to testing with venous blood

A new study is raising questions about the implications of using fingerprick blood samples for point-of-care tests. Done by researchers at Rice University’s Department of Bioengineering, the study suggests clinicians use measurements with caution when assessing patients’ conditions based on the results of clinical laboratory tests using a single drop of capillary blood collected by fingerstick.

Pathologists and clinical laboratory scientists were quick to call attention to the study, based on the press release Rice University issued. That’s because, for almost 30 years, medical laboratories have struggled to correlate the results for such biomarkers as glucose. It is common for capillary blood specimen collected by finger stick and tested on a point-of-care device to produce different results for the same patient when compared with that of a venous specimen tested on the automated, high-volume analyzes in a central laboratory. The Rice researchers offer useful insights about such variation.

Study of Capillary Blood Specimens May Relate to Issues at Theranos

Another reason this study is attracting attention among medical laboratory professionals is because it has links to the unfolding story of Theranos, the high-profile lab testing company in Palo Alto, California. For two years, Theranos has touted the benefits of its proprietary lab test technology that involves a finger stick collection, a capillary blood specimen, and a four-hour turnaround time for hundreds of different lab tests that it says can be run on its analyzer.

In fact, capillary blood specimens and finger-stick collections have been national news in recent weeks because of disclosures in The Wall Street Journal (WSJ) last month that Theranos has struggled with its proprietary lab testing technology and had quietly been performing much of its clinical lab testing for consumers and patients using venous specimens run on conventional lab testing equipment. Theranos has disputed these claims. For this reason, the Rice study of capillary blood for lab testing purposes may prove to be just as interesting to Wall Street investors as it is to pathologists and medical laboratory scientists.

Rice Study Published in Peer-Reviewed American Journal of Clinical Pathology

The study, “Drop-to-Drop Variation in the Cellular Components of Fingerprick Blood,” was published in the December issue of the American Journal of Clinical Pathology (AJCP). Researchers Meaghan M. Bond and Rebecca Richards-Kortum, PhD, found wide variation for successive drops of fingerprick blood.

“The average coefficient of variation (CV) for successive drops of fingerprick blood was higher by up to 3.4 times for hemoglobin, 5.7 times for WBC count, 3 times for lymphocyte count, 7.7 times for granulocyte count, and 4 times for platelets than in venous controls measured using a hematology analyzer,” they wrote. “The average percent CV for fingerprick blood was up to 5 times higher for hemoglobin than venous blood measured using a point-of-care hemoglobinometer.”

Meaghan Bond

At the Rice University Department of Bioengineering, a research team working on “novel, low-cost” diagnostic test solutions for anemia, platelet, and white blood cells testing “in low-resource settings” were getting discordant results when using capillary blood specimens. This led them to conduct a study on the variability of consecutive blood drop specimens collected from a fingerprick. Pictured above is Meaghan Bond, one of the authors of the study, which was published in the December issue of the American Journal of Clinical Pathology. (Photo copyright: Jeff Fitlow/Rice University.)

In the study, Bond and Richards-Kortum used a hematology analyzer to measure the hemoglobin concentration, total white blood count (WBC), 3-part WBC differential, and platelet count in 6 successive drops of blood collected from 1 fingerprick from 11 donors, and a hemoglobinometer to measure the hemoglobin concentration of 10 drops of fingerprick blood from 7 donors, they wrote.

In a press release about the study, the university said, “Bond and Richards-Kortum found that averaging the results of the droplet tests could produce results that were on par with venous blood tests, but tests on six to nine drops blood were needed to achieve consistent results.” Given that so few donors were used, Bond and Richards-Kortum called their research a pilot study and recommended that researchers do studies with more participants.

Important to Note Drop-to-Drop Variability in Capillary Specimens

“This research is significant because the drop-to-drop variability in capillary specimens collected consecutively from the same patient is important to note,” stated Frederick L. Kiechle, MD, PhD, FCAP, pathologist and Medical Director, Clinical Pathology at Memorial Healthcare System in Hollywood, Fla. Kiechle is a nationally recognized expert in pre-analytical medical laboratory processes and specimen collection and handling. For the College of American Pathologists (CAP), he has chaired the Patient Preparation and Specimen Handling Editorial Board. He has also edited the past six editions of the CAP publication, “So You’re Going to Collect a Blood Specimen.”

Kiechle noted that, in their study, researchers Bond and Richards-Kortum pointed out that high rates of variability from one drop to another raise questions about the reliability of point-of-care testing equipment. But also, Kiechle said, such variability will be important for any medical laboratory using small blood samples taken with a fingerprick, such as Theranos.

Use of Capillary Specimens Collected by Fingerprick at Theranos

Last month, The Wall Street Journal (WSJ) reported that the proprietary lab instrument Theranos has touted as one important piece of its business strategy handled only a small number of tests sold to consumers. This instrument analyzes capillary blood specimens collected by finger sticks and sent to the Theranos lab in what the company calls nanotainers, the WSJ noted.

Also last month, the WSJ quoted officials from Walgreens Boots Alliance Inc. (WBA:NASDAQ), which has Theranos’ blood drawing stations in more than 40 Walgreens stores in Arizona. Walgreens officials said the pharmacy retailer will not open any new such centers until the lab company resolves questions about its technology.

Three Suggestions for Any Company or Lab Using Capillary Blood Specimens

The Bond and Richards-Kortum study may help to explain why diagnostic technology using capillary blood specimens collected via fingerprick may be problematic for some medical laboratory testing purposes. At the end of their AJCP article, the Rice University researchers made three suggestions for any company using such blood samples. The options for clinicians are to:

  • “accept the inaccuracy of fingerprick blood on these devices as a trade-off for easy blood collection;
  • “collect, read, and average multiple fingerprick samples, gaining accuracy but sacrificing cost and time; or,
  • “collect and analyze venous blood.”

In the concluding paragraph of their article, Bond and Richards-Kortum wrote, “In recent years, a large number of devices using tiny volumes of blood have been developed. Our data suggest caution in using the results of these hemoglobin and WBC tests for clinical decision making, such as determining anemia status. (Other studies need to be conducted to assess the drop-to-drop variability for other analytes.)

Research Study Looked at Cellular Components of Capillary Blood Specimens

While acknowledging the importance of the study, Kiechle added that he was not surprised by the results. “This is because of the way the cellular components of blood move through the circulatory system, particularly those cellular components flowing through capillaries, from which clinicians draw finger stick samples,” observed Kiechle.

Pictured above is pathologist Frederick Kiechle, MD, PhD, FCAP, Medical Director, Clinical Pathology at Memorial Healthcare System in Hollywood, Florida. He is recognized nationally for his expertise in pre-analytical clinical laboratory processes and specimen collection and handling. He called the Rice University study into the variability of capillary blood specimens collected by fingerprick as “significant,” particularly because this is the first such study to demonstrate “the drop-to-drop variability in capillary specimens collected consecutively from the same patient.” (Photo copyright: The Dark Report.)

Pictured above is pathologist Frederick Kiechle, MD, PhD, FCAP, Medical Director, Clinical Pathology at Memorial Healthcare System in Hollywood, Florida. He is recognized nationally for his expertise in pre-analytical clinical laboratory processes and specimen collection and handling. He called the Rice University study into the variability of capillary blood specimens collected by fingerprick as “significant,” particularly because this is the first such study to demonstrate “the drop-to-drop variability in capillary specimens collected consecutively from the same patient.” (Photo copyright: The Dark Report.)

“When analyzing the components of blood, what’s important to track are the formed elements, but these are not distributed equally throughout the circulatory system,” he said. “Blood volume consists of plasma volume plus the red-cell volume. Medical laboratories today use red-cell volume when analyzing formed elements because the red cells are about 95% of the formed or cellular components of blood.”

Kiechle cautioned, however, that when compared with the liquid components of blood, the formed components make up only about 10% of blood volume in the human vascular system. “And, it’s even lower in the great veins,” he emphasized. “That’s much different than measuring glucose, for example, which is dissolved in the liquid portion of the blood and hopefully in equilibrium.

Cellular Volume of the Formed Components Are Subject to Lesser Short-term Variations

“When conducting medical laboratory testing, it is important to understand what happens to the cellular components within blood because both the cellular and liquid components pass into and out of the extravascular space and into and out of blood vessels,” Kiechle explained. “That means the cellular volume—the formed components—are subject to lesser short-term variations than the liquid portion of the blood.

“In addition, the human blood mass is distributed unequally throughout the body,” continued Kiechle. “As much as 70% of it is in veins, 20% is in arteries and the remaining 10% is in capillaries, which, by definition, are narrow vessels and which can constrict the flow of larger components.

“On top of that, many factors can affect the distribution of cellular elements within blood,” he added. “Infections, for instance, can cause cellular elements to be distributed unequally in the capillaries compared with how the components of blood are distributed in the big arteries and veins,” he concluded.

Capillary Blood Specimen Study Focused on Cellular Components of Whole Blood

Pathologists, clinical chemists, and medical technologists will recognize that Kiechle was careful to comment on the fact that the testing done on capillary specimens in the Rice University study was limited specifically to the cellular components of whole blood. The focus of the work at Rice was on these blood components.

Lead researcher Richards-Kortum stated, “Students in my lab are developing novel, low-cost platforms for anemia, platelet and white blood cell testing in low-resource settings, and one of my students, Meaghan Bond, noticed there was wide variation in some of the benchmark tests that she was performing on hospital-grade blood analyzers.” The work was done with funding from the Bill and Melinda Gates Foundation through the Grand Challenges in Global Health Initiative.

What remains unaddressed in this study is how variability in successive capillary blood drops collected from the same patient may affect the results of lab tests designed to measure biomarkers in plasma and serum.

Issues Involving Use of Capillary Specimens When Testing Hospital Inpatients

This remains a serious issue, particularly for testing done on hospital inpatients who may be in emergency rooms, in recovery following surgery, or in critical care units, for example. As noted earlier, since the advent of more sophisticated point-of-care instruments in the 1980s, pathologists directing hospital laboratories have found it challenging to achieve a consistent correlation between lab test results for a single patient from a POC test performed with a capillary blood specimen compared with results from the same test performed in the central lab on an automated analyzer using a venous blood specimen.

For this reason, pathologists and clinical lab executives have been curious about the claims of Theranos that it can perform hundreds of tests using only a capillary blood specimen and its proprietary analyzers. It is also explains why, despite years of optimistic press releases issued by biotech companies announcing that they have breakthrough test technology that uses fingerstick specimens and miniaturized smart-phone-based devices to perform diagnostic tests, almost none of these devices have been successfully reviewed by the FDA and are available for clinical testing purposes today.

Will Labs Study and Publish Findings about Variability of Capillary Blood Specimens?

Therefore, given the widespread frustration across the diagnostic industry with the ability to correlate results on a single patient from tests conducted with capillary blood, and with venous blood, the findings of the Rice University study on variability in successively collected capillary blood specimens may encourage other clinical lab organizations to conduct similar studies, possibly involving larger numbers of patients. This will need to happen if the widely-recognized issues associated with the use of capillary blood for many types of clinical laboratory tests are to be understood and resolved.

—Joseph Burns and Robert L. Michel

Related Information:

Blood Test Results Vary From Drop to Drop in Fingerprick Tests 

So You’re Going to Collect a Blood Specimen: An Introduction to Phlebotomy
Editor: Frederick L. Kiechle, MD, PhD; Co-Editors: Dorothy M. (Adcock) Funk, MD, Rebecca Rosser, CLS, MT(ASCP)DLM Deborah Sesok-Pizzini, MD, MBA

Drop-to-Drop Variation in the Cellular Components of
Fingerprick Blood; Implications for Point of Care Diagnostic Testing

Rice Lab Shows Contents of Blood Can Vary From Drop to Drop

Blood Test Results Vary from Drop to Drop in Fingerprick Tests

Two FDA Inspection Reports Show Theranos’ Blood-Collection ‘Nanotainer’ Was an Uncleared Class II Medical Device

FDA Says Theranos Shipping Unapproved Medical Device

FDA Cites Theranos Over Unapproved Medical Device, Complaint Handling

Theranos Facts (from Theranos website)

Crisis of the Week: Theranos Reacts to Blood Test Stories

Hot Startup Theranos Has Struggled with Its Blood-Test Technology

Theranos CEO: Company Is in a ‘Pause Period’

Walgreens Scrutinizes Theranos Testing

Theranos’ Finger-Stick Blood Testing Gets FDA Approval

Theranos Receives CLIA Waiver, Paving the Way for Greater Accessibility of Health Information at the Time and Place It Matters