wipe or not to wipe, that is the question!

A Short Early History of Capillary Blood Microsampling 

During the early 1960’s, Dr Robbert Guthrie, a physician based at Buffalo Children’s Hospital, pioneered dry blood spot (DBS) testing for certain inborn errors of metabolism. 

Motivated by seeing the devastating effects of the disease on his niece,  Dr Gutherie realised that if caught early and intervention with a diet deplete of phenylaniline (PKU), then the disease  could be managed.

This kickstarted the birth of neonatal screening, where today many inborn errors of metabolism are detected, monitored and managed before disease progression.  To explore PKU in greater detail and learn about the latest therapeutic developments, visit this blog. 

Around the same at the same time that Dr. Guthrie was achieving significant progress in early PKU detection using DBS, scientist at the clinical diagnostics company Ames were making big strides in capillary blood glucose monitoring. In 1965, the company launched Dextrotix where a large drop of blood was applied to a test strip left for 60 seconds to allow a glucose oxidase reaction to  then washed off to reveal a colour change if glucose was detected. 

This was the first time capillary blood was employed for diabetes control and monitoring.    Furthermore, around the middle of the 20th century (possibly earlier), capillary blood was also being used for measuring haemoglobin using a gravimetric method employing a copper sulphate solution for analysis.   

Benefits And Concerns around Capillary Blood Collection 

Since these early examples, the applications employing blood microsampling have become increasingly diverse and widespread. These include, measuring drug levels for, therapeutic drug monitoring, drugs of abuse testing and PK studies. 

Furthermore, biomarkers, antibodies and environmental exposure makers are being increasingly measured using microsampling.  Moreover, capillary blood collection has also been increasingly utilised for omics research. 

In addition, the recent development of volumetric collection devices such as the Mitra device, offer a much easier way to collect capillary blood, as well allowing for processing more accurate and streamlined analysis in laboratories.  

There are huge benefits to capillary blood microsampling compared to standard blood collection.  It is more convenient, as samples can be collected practically anywhere (including sampling by astronauts in space!) and less painful. 

Furthermore, dried microsamples are often more stable compared to liquid samples - often allowing for inexpensive shipping in ambient conditions. 

However, there are drawbacks too, these include, haematocrit effects especially when working with dried blood samples, although devices like Mitra solve some of these issues. 

Furthermore, there have been concerns around how the sample is collected especially when a healthcare professional is not present to assist or supervise. 

Thankfully efforts are made to ensure that instructions are clear and so sample collection integrity less of a concern evidenced by the weight of successful studies published in the literature.  

The First Drop of Blood 

It is generally considered by institutions, such as the world health organisation (WHO), that the first drop of blood should be wiped away when sampling.  There are a number of reasons for this.   

1. The first is concerns around interstitial fluid mixing with the blood diluting or contaminating the sample leading to positive or negative biases in data. For example, this has been shown to be an issue with measuring haemoglobin concentration.  
2. The next is contamination of the skin and skin fragments.  In the area of lead testing for example, researchers at INSPIQ in Canada, lead found on the skin contributed to a false positives in data.  One solution which worked reasonably well,  was to thoroughly wash the hands before sampling with soap and water.  However, wiping the first drop and sampling a subsequent drop would also be sensible approach, to further help eliminate any surface contamination. 
3. Related to point 2, is the impact of using alcohols swabs to decontaminate / sanitise the sampling area. The issue with alcohol is that it impacts the surface tension of the blood, preventing the formation of a blood bolus.  Wiping away the first drop helps to remove any alcohol which could mix with the first drop.  Anecdotally, it is commonly  observed that the second drop of blood often forms a better bolus than the first drop regardless of the cleansing method.   

When Wiping The First Drop of Blood Not Possible? 

There are two main reasons why wiping the first drop is not possible. 

1. When a subject is known not to bleed very easily, then collecting the first drop may only be the practical option, although he sample may not be of good enough quality for analysis.  Thankfully, using the right type of high-flow lancet, the vast majority of subjects are able to deliver a sufficient quantity for sampling. 
2. The second is due to sampler design; certain samplers (such as upper arm devices) come with integrated lancets.  As a result, the sampler collects as soon as the blood begins to flow, this risks biases in data due to reasons described in the previous section (‘The First Drop of Blood’) of this blog. 

What are the Recommended Guidelines and Instructions? 

These are a plethora of published guidelines which all recommend wiping away at least the first drop of blood below are three examples of such recommendations. 

In a document entitled “WHO Guidelines on Drawing Blood: Best Practices in Phlebotomy” published in 2010 by the World Health Organisation state the following. “Wipe away the first drop of blood because it may be contaminated with tissue fluid or debris (sloughing skin)”. 

Instructions published by the Centres of Disease Control and Prevention (CDC) state “Apply slight pressure to start blood flow. Blot the first drop of blood on a gauze pad without touching the finger and discard the gauze in appropriate container.” 

Health guidelines from Western Australia recommend wiping the first drop as it may be diluted by interstitial fluid, and specifically advise wiping away the first 2-3 drops for haemoglobin testing. 

Conclusion 

The fast pace of analytical and informatics development means we are increasingly able to analyse a lot more with a lot less blood.  This allows us to access more remote populations and allows vulnerable people to send samples from home. 

However, we need to be aware that conducting remote sampling has its own risks, and analytical result can be only as good as integrity of the collected sample. 

Collecting a good quality blood sample, is crucial and so following recommendations by authorities such as the WHO and CDC, should be adhered to when developing instructions for capillary blood collection.