Blood test results, reference ranges, normals and abnormals

We are all very familiar with blood tests, ranging from routine full blood counts and urea and electrolytes to far more esoteric and unusual tests, and we are also familiar with tests having normal or abnormal results and the critical role such results can play in the investigation and management of many medical conditions. Blood test results often also play a pivotal role in clinical negligence cases and it is vitally important in many cases to analyse the results, understand their role and identify the relevance of a normal or abnormal result.

Many patients can now access their blood results from their healthcare provider on the internet. However, there are some important things to be aware of when considering a blood test result and they are not always straightforward to interpret correctly. First, whilst it may sound obvious, an abnormal result does not necessarily indicate ill-health and all results must be interpreted within the context of the whole presentation of the patient. Secondly, again, it may sound obvious, but a normal result does not necessarily indicate health. Results vary from patient to patient, are often influenced by factors such as gender and age, and, furthermore, they can vary according to the patient’s status such as whether they have been fasting, have just exercised, have recently drunk some coffee, etc. Again, context is key. Thirdly, it is necessary to be aware of the “reference range” of the particular laboratory performing the test because not all laboratories have the same ranges. This is because different laboratories use different types of equipment and methods for testing, which can produce different results. There is no “one size fits all”.

And what is a reference range? It is the range of values for a test that is considered to be normal based on a group of healthy individuals, ranging from the lower limit of normal (LLN) to the upper limit of normal (ULN). A range is determined primarily by studying a defined reference population and identifying for any given test where the boundaries of “normal” lie within that population: “normal” is considered to be the middle 95% of the reference population. Therefore, any result that falls in the bottom 2.5% or the top 2.5% will be considered to be “abnormal” i.e., 5% of the reference population are considered to have abnormal results. These numbers are calculated statistically on the basis of two standard deviations from the mean in a normal distribution curve.

When interpreting blood results, it is crucially important to keep them in context. It can be all too easy to look at a marginally abnormal result, consider it to be effectively normal and not consider it further. This may be an erroneous approach. It may be wise to repeat it. An abnormal result does not need to be significantly abnormal for it to be relevant or important. It may be just as erroneous to view a result or a series of results falling within the normal range as not being worthy of further consideration for the very reason that they lie within the normal range. A single result can be misleading and, if in the normal range, it may be falsely reassuring.

I shall give a fairly common practical example in the form of sepsis. In fact, specifically in the form of intra-abdominal sepsis developing following abdominal surgery, often resulting from a bowel leak occurring during or soon after surgery (usually a bowel perforation or an anastomotic leak). I have worked on many such clinical negligence cases over the years, with severe complications having then arisen due to a delay in suspicion, diagnosis, investigation and/or treatment of the resulting post-operative sepsis. Intra-abdominal sepsis can be, and in my experience often is, subtle and initially indolent, so it is necessary for the clinician to be alive to changes in symptoms, minor physiological changes and small changes in blood results. I have used this example as I have noticed a few recurring problems that seem to arise in these cases.

A common theme is the failure by clinicians to pay sufficient attention to the patient’s blood results such as white cell counts (WBC/WCC), white cell count differentials (neutrophils and lymphocytes, in particular) and non-specific inflammatory markers such as CRP (C-Reactive Protein), ESR (Erythrocyte Sedimentation Rate), platelets, etc. Sometimes there is a rather too eager explaining away of any such abnormalities as being due to some cause other than sepsis, such as just having had surgery or some pre-existing comorbidity. This is in particular when the results are only marginally abnormal and not considered to be sufficiently abnormal to be of any relevance. Changes in WCC, CRP and other blood results in intra-abdominal sepsis are often subtle, certainly initially, and it is easy to overlook or ignore as irrelevant such changes.

Blood results also have to be taken in the context of the patient’s whole presentation and in combination with physiological parameters, such as respiratory rate, temperature, heart rate and blood pressure and the same principles apply to changes in such parameters; it is not unusual to see subtle abnormal changes in these parameters also be ignored or go unnoticed, especially when compared to the patient’s pre-operative pre-morbid baseline values.

As said above, many patients will not show overt signs of intra-abdominal sepsis until pretty fulminant peritonitis and septicaemia have developed, by which time much damage may already have been done, so a keen eye and a low threshold of suspicion are critical but often found wanting. This is in particular when only junior doctors are involved in the patient’s management; the experience of a senior doctor or consultant may be crucial. All too often a patient is not considered in the round, namely factoring in together their symptoms, signs, physiological parameters and blood results as opposed to looking at each in isolation. I should perhaps observe at this point that the fact that a body of surgeons would have failed to consider sepsis on the basis of subtle changes in blood results and physiological parameters so as to raise a Bolam defence may not necessarily be a sufficient defence, as such failure may be deemed to be Bolitho illogical and, in my view, given the importance of diagnosing sepsis early, it often should be.

I should also add that I have a particular bugbear with WCC differentials, which I have seen time and time again ignored even when markedly abnormal when, in fact, those abnormal values add significant weight to the need for the consideration of evolving sepsis. I have been faced repeatedly with the assertion that many surgeons do not consider WCC differentials, and it is Bolam reasonable not to do so; the obvious response is that it is Bolitho illogical not to do so given the context and also the existence of medical literature which supports the importance of WCC differentials in intra-abdominal as well as other causes of sepsis.

In addition, a not unusual error is the failure to take into consideration a “trend” in blood test results even though the results are within the “normal” reference range. This can also be important because the subtle nature of evolving intra-abdominal sepsis can mean that “abnormal” changes in blood results may not actually occur until fulminant septicaemia exists as noted above. In such cases, it is not uncommon for there to have been a prior “trend” in a test result, albeit that trend arises within the normal range. Again, WCC is a good example, as I have seen on a number of occasions the WCC gradually rise from low normal to high normal but be ignored (or the trend not be noticed) because each result was still “normal”, before then suddenly becoming very abnormal when fulminant septicaemia had developed.

I am aware that there is some judicial support for the concept of needing to be alive to a “trend” within a normal range, albeit in the context of clinical observations rather than blood test results. In William Shortall v Mid Essex Hospital Services NHS Trust [2014] EWHC 246 (QB), HHJ Nicholas Cooke QC stated [at 83]: “In a situation such as this [a post-colonic resection anastomotic leak case], changes within what are to be regarded in most circumstances as ‘normal ranges’ are both diagnostically and evidentially significant” and, further [at 115]: “Post-operative care needed to acknowledge the insidious and subtle clinical presentation of anastomotic leak and it does not appear here to have done so sufficiently. I have already stressed the need for attention to be paid to clinical signs within normal ranges in such a context”. I concur with this view and believe it is just as applicable to blood test results as it is to clinical observations.

Severe sepsis will often result in a low WCC, but as the drop in count passes from abnormally high to abnormally low it passes through the normal range and a result taken at that moment in time can easily be misinterpreted as a “normal” result.

The above are just a few basic points arising from the example of intra-abdominal sepsis. The importance of careful consideration of blood results and an understanding of what normal and abnormal really means in the context of the whole patient can be crucial and cannot be overstated; mistakes are still all too often made because of a lack of sufficiently careful attention to such results, potentially with a devastating outcome. Intra-abdominal sepsis is but one example of many.

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