As I dust off my vampire outfit for our Halloween party it seems fitting that I talk about the blood sciences for this spooky edition of the blog.
I have been asked on many occasions “why do microbiology laboratories not highlight on their reports what of this result is normal and what is abnormal?” Essentially microbiology laboratories report the presence or absence of microorganisms or the immune response to those microorganisms. In order to decide if the result is normal or abnormal requires an understanding of what is going on in that specific patient. Most of the time microbiology laboratories don’t have that information available, partly because request forms are not completed and partly the forms don’t actually allow for a detailed clinical history.
I have been asked on many occasions “why do microbiology laboratories not highlight on their reports what of this result is normal and what is abnormal?” Essentially microbiology laboratories report the presence or absence of microorganisms or the immune response to those microorganisms. In order to decide if the result is normal or abnormal requires an understanding of what is going on in that specific patient. Most of the time microbiology laboratories don’t have that information available, partly because request forms are not completed and partly the forms don’t actually allow for a detailed clinical history.
The assessment of the significance of a microbiology result is based around the history and examination of the patient, as well as an understanding of normal flora (see previous blog). The next part of the assessment is the results from our colleagues in the blood sciences, specifically Haematology and Biochemistry. When I’m teaching medical students and junior doctors I spend a lot of time going over these “non-microbiological” results because I think it’s essential that they understand how interlinked and valuable they are when dealing with patients with infections.
In essence, Haematology deals with the constituents of blood whereas Biochemistry deals with the chemicals found in the serum. (I appreciate it is a bit more complicated than this, but where infection is concerned this description is enough).
So what do I look at when assessing a patient with a possible infection and why?
Haematology - Full Blood Count (FBC)
The FBC includes a lot of information, only some of which is of particular interest to a Microbiologist. The first to look at when assessing if a patient has an infection is the total white blood cell (WBC) count. The normal range is 4-11x109/L (or, as I was told the other day, "normal is anything not red on the computer"!) In infection it can go up or down. A raised WBC shows that there is likely to be an acute inflammatory response going on whereas a low WBC shows that the acute response is unable to keep pace with the infection and is often a more worrying sign.
The next part of the FBC to look at is the differential WBC. This is the individual cell types that make up the total WBC and which can give an indication of the type of infecting microorganisms present. Nothing is 100% in medicine but in general if one of the following cell types is raised in a patient with an infection it tends to suggest the specific microorganism type in the table:
In essence, Haematology deals with the constituents of blood whereas Biochemistry deals with the chemicals found in the serum. (I appreciate it is a bit more complicated than this, but where infection is concerned this description is enough).
So what do I look at when assessing a patient with a possible infection and why?
Haematology - Full Blood Count (FBC)
The FBC includes a lot of information, only some of which is of particular interest to a Microbiologist. The first to look at when assessing if a patient has an infection is the total white blood cell (WBC) count. The normal range is 4-11x109/L (or, as I was told the other day, "normal is anything not red on the computer"!) In infection it can go up or down. A raised WBC shows that there is likely to be an acute inflammatory response going on whereas a low WBC shows that the acute response is unable to keep pace with the infection and is often a more worrying sign.
The next part of the FBC to look at is the differential WBC. This is the individual cell types that make up the total WBC and which can give an indication of the type of infecting microorganisms present. Nothing is 100% in medicine but in general if one of the following cell types is raised in a patient with an infection it tends to suggest the specific microorganism type in the table:
Click for larger image
Beware: the WBC within the normal range when one particular cell type is high and another is low; the WBC may appear “normal” but it is in fact abnormal.
The final aspect of the FBC which can help decide if a patient has an infection or not is the platelet count. Platelets are acute phase reactants which go up as part of an inflammatory response. A rising platelet count suggests acute or ongoing inflammation. In contrast, a low platelet count in infection might suggest the onset of Disseminated Intravascular Coagulation (DIC) and is a sign that the patient is very unwell.
Haematology – Clotting and INR
There are a number of ways in which clotting studies can help in the management of patients with infection.
Biochemistry - Urea, Creatinine & Electrolytes (U&Es)
In order to prescribe antibiotics safely it is necessary to know how well the patient’s kidneys are working. In hospital this is done by measuring the creatinine and then calculating the Glomerular Filtration Rate (GFR) using the Cockcoft-Gault equation. In primary care it is routine to assume that the patients renal function is stable and therefore it will be the same as when it was last measured or if it hasn’t been measured, it is probably normal; patients whose infections are so severe as to push them in to acute renal failure tend to be the ones who are sick enough to admit to hospital.
The other way in which U&Es can help is in the assessment of severity of specific infections. Urea is used to assess the severity of community acquired pneumonia as part of the CURB-65 score with the “U” standing for a urea >7mmol/L. A rising creatinine on the other hand is a marker for severe Clostridium difficile associated disease.
Biochemistry - C-Reactive Protein (CRP)
CRP is an acute phase reactant indicating acute inflammation. It is made in the liver. The normal range is always <10mg/L but it does vary between laboratories! From a microbiology perspective a significant value is >200mg/L (for an inflammatory or rheumatology problem the significant value is often less e.g. >100mg/L).
For microbiology, the trend is often more useful than a one off value. A rising CRP may indicate that the patient is getting worse whereas a falling CRP may suggest they are getting better. There are a couple of caveats to that though: the CRP often takes 24-48 hours to respond to treatment so might continue to rise even though the patient is subjectively improving, and a falling CRP can occur if the patient is going in to liver failure and is therefore unable to produce CRP any more (see below).
Biochemistry - Liver Function Tests (LFTs) and Albumen
The test usually tells you the results for Aspartate Transaminase (AST), Alanine Transaminase (ALT) and Alkaline Phosphatase (ALP) which are all intracellular enzymes. Contrary to what the name suggests this collection of results does not actually tell you too much about how the live is working. If the results are raised they tell you there has been damage caused to liver cells and the enzymes have leaked out. They do not give any indication as to how well the remaining liver cells are working, this done by looking at the INR and Albumen (often requested separately) both of which are affected by protein produce by the liver, i.e. its synthetic function. Microbiologists use the INR and Albumen as measures of “liver function” not LFTs.
In infection, the CRP normally rises above 200mg/L, however a result of <50-100mg/L may still be significant if the liver is not functioning properly. If the INR is raised and the albumin low then it is possible that the patient’s liver is not working properly and this may affect the rest of the other infection related tests. A CRP of 50-100mg/L may be as high as the patient can manage, equivalent to >200mg/L in a patient with normal liver function.
So microbiology doesn’t just involve knowledge about the tests performed in a microbiology laboratory. Whilst it isn’t usually necessary to have a detailed knowledge of the other blood science disciplines it is important that anyone looking after patients with infections have a basic grasp of the tests done in these laboratories and how these relate to managing infections.
The final aspect of the FBC which can help decide if a patient has an infection or not is the platelet count. Platelets are acute phase reactants which go up as part of an inflammatory response. A rising platelet count suggests acute or ongoing inflammation. In contrast, a low platelet count in infection might suggest the onset of Disseminated Intravascular Coagulation (DIC) and is a sign that the patient is very unwell.
Haematology – Clotting and INR
There are a number of ways in which clotting studies can help in the management of patients with infection.
- In severe infections with the onset of DIC, the clotting becomes deranged and the International Normalised Ratio (INR) increases. This is a sign of severity of infection
- Clotting can be used to assess synthetic liver function (see below)
- Clotting can be used to help identify invasive infections with Group A Beta-haemolytic Streptococcus (iGAS). In this circumstance the INR increases because the organism is producing the chemical streptokinase. It can be used to monitor the response to treatment of patients with confirmed iGAS. If the INR remains high or climbs there is ongoing infection and further treatment may be required, e.g. further surgery in necrotising fasciitis
Biochemistry - Urea, Creatinine & Electrolytes (U&Es)
In order to prescribe antibiotics safely it is necessary to know how well the patient’s kidneys are working. In hospital this is done by measuring the creatinine and then calculating the Glomerular Filtration Rate (GFR) using the Cockcoft-Gault equation. In primary care it is routine to assume that the patients renal function is stable and therefore it will be the same as when it was last measured or if it hasn’t been measured, it is probably normal; patients whose infections are so severe as to push them in to acute renal failure tend to be the ones who are sick enough to admit to hospital.
The other way in which U&Es can help is in the assessment of severity of specific infections. Urea is used to assess the severity of community acquired pneumonia as part of the CURB-65 score with the “U” standing for a urea >7mmol/L. A rising creatinine on the other hand is a marker for severe Clostridium difficile associated disease.
Biochemistry - C-Reactive Protein (CRP)
CRP is an acute phase reactant indicating acute inflammation. It is made in the liver. The normal range is always <10mg/L but it does vary between laboratories! From a microbiology perspective a significant value is >200mg/L (for an inflammatory or rheumatology problem the significant value is often less e.g. >100mg/L).
For microbiology, the trend is often more useful than a one off value. A rising CRP may indicate that the patient is getting worse whereas a falling CRP may suggest they are getting better. There are a couple of caveats to that though: the CRP often takes 24-48 hours to respond to treatment so might continue to rise even though the patient is subjectively improving, and a falling CRP can occur if the patient is going in to liver failure and is therefore unable to produce CRP any more (see below).
Biochemistry - Liver Function Tests (LFTs) and Albumen
The test usually tells you the results for Aspartate Transaminase (AST), Alanine Transaminase (ALT) and Alkaline Phosphatase (ALP) which are all intracellular enzymes. Contrary to what the name suggests this collection of results does not actually tell you too much about how the live is working. If the results are raised they tell you there has been damage caused to liver cells and the enzymes have leaked out. They do not give any indication as to how well the remaining liver cells are working, this done by looking at the INR and Albumen (often requested separately) both of which are affected by protein produce by the liver, i.e. its synthetic function. Microbiologists use the INR and Albumen as measures of “liver function” not LFTs.
In infection, the CRP normally rises above 200mg/L, however a result of <50-100mg/L may still be significant if the liver is not functioning properly. If the INR is raised and the albumin low then it is possible that the patient’s liver is not working properly and this may affect the rest of the other infection related tests. A CRP of 50-100mg/L may be as high as the patient can manage, equivalent to >200mg/L in a patient with normal liver function.
So microbiology doesn’t just involve knowledge about the tests performed in a microbiology laboratory. Whilst it isn’t usually necessary to have a detailed knowledge of the other blood science disciplines it is important that anyone looking after patients with infections have a basic grasp of the tests done in these laboratories and how these relate to managing infections.
Happy Halloween!
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