The odd asterisk: not-quite-normal blood tests.

NOTE: These blog posts are written from the perspective of a GP colleague who still seems to accumulate a list of unanswered questions at the end of each day in practice.  Each post describes how I went about trying to answer the specific questions.  These posts are not intended to be used for specific clinical guidance but hopefully provide links to some useful resources which the registrar can explore for themselves.  

I keep a running list of results to chase up and it was getting too long earlier this year.  I did notice that there were a number of haematological results which weren’t too worrying but which weren’t exactly normal and I was meaning to look up whether I should just repeat or do any extra tests – that question of whether that asterisk really is clinically significant. These are some of the basic FBC results that appeared on my expanding list:

  • Iron deficiency (several, at various stages of having had other causes excluded)
  • Persisting mild neutropaenias
  • High haemoglobins (with no obvious cause)

Our local haematology department is usually very helpful if you fax them a question, and they will reply with “Do the following tests x, y and z.  Only contact us if abnormal or if the following red flags occur…” They have recently taken to sending us a helpful one-page cheat sheet-with every fax and have noted the unit was experiencing “high demand in the face of dwindling resources”.

I will just address neutropaenia in this blog.

Around the time that I was following up these patients I noted this How to Treat topic in Australian Doctor in April. This answered most of my questions along with a brief Melbourne Pathology 2013 publication on neutropaenia (which explains some basic facts about neutrophils which I had forgotten) .  This latter article also mooted whether the cut-off point ought to be 1.7 or 1.8 rather than the accepted level of 2 X 109 /L.

The key points in the Ausdoc article were:

  1. monitor mild single cell abnormalities (done). Many will settle down (one eventually did, one didn’t)
  2. If unsure whether referral is needed, ring the local haematology department. (done – or at least letters faxed)

I find that a mildly decreased neutrophil count appears to be very common and often occurs in the context of a viral illness, after which it goes back to normal.  The article noted that in such instances (and in the context of no concerning symptoms or signs) a haematology opinion is rarely needed.

There are also patients who, when you go back through their results, tend to sit on the low end of the normal range all the time, just dipping under every now and then.  Some remain in the mild range and occasionally bounce up to normal.

I had two patients with very similar neutrophil counts varying between 1.3 and 1.7 which produced slightly different responses when I requested advice.  One was offered an appointment in three months and a suggestion of a small list of tests to do first and the other was offered no appointment (because it was “mild” neutropaenia).  A slightly different list of tests was suggested.  Both these lists of tests were slightly different to the ones on the “cheat sheet” from the department. I used these various resources as guidance for which investigations to pursue.  However, in my mind these tests were rather random and it was only on reading the articles that I could put them into some sort of logical clinical and pathological order.  I received a very delayed letter back from the specialist about the patient seen in the clinic and this letter helpfully reiterated all the points that one should consider in such patients and which are mentioned in the articles.

Rationale for history, examination and tests

The purpose is generally to rule out known causes. It can either be approached as common versus rare or in terms of underlying pathologies.  When a haematologist talks of “common” causes, these may still occur fairly rarely in the GP context but it is useful to get a comprehensive overview as presented in these articles – you never know when something rare may turn up in your surgery.  That is the nature of general practice. Some of the common causes may include symptomatic patients whereas the focus of this discussion was the incidental abnormal finding.

Common causes are listed as:

  • benign ethnic (with quite surprisingly significant variation in different populations – read the articles for details)
  • viral
  • incidental asymptomatic
  • severe bacterial
  • auto immune
  • drugs

Rare causes include myelodysplasia/infiltrative pathology and congenital neutropenia.

The causes of neutropenia can also be considered in terms of:

  • infectious – which could include EBV, cytomegalovirus, influenza, hep A, B and C (consider populations at higher risk) and HIV. Malaria is relevant in returned travellers (pancytopenia and fevers)
  • auto-immune – in the context of SLE and RA (Felty’s syndrome) or auto immune neutropenia (usually mild)
  • nutritional – Iron deficiency; severe B12 and folate deficiency is noted as “an important part of the workup” (but anaemia is usually present), iron deficiency; copper deficiency is also mentioned.
  • medications – see the extensive drug list in the Australian Doctor article. These should not be forgotten.
  • myelodysplasia/infiltrative – investigated once common causes are excluded (or if suggestive constitutional symptoms of fevers, sweats, weight loss etc)

Important reminders

  • Don’t forget to take a good history, including family, ethnicity (there are surprising and significant variations), infections, mouth ulcers, medications, travel etc and perform an appropriate examination. Don’t just move onto further investigations without further thinking and merely on the basis of a test done for other reasons.
  • An isolated mild neutropenia in an asymptomatic patient can be monitored with repeat testing in two to three months (but ensure follow-up).
  • Chronic neutropenia (more than three months) warrants further investigations as suggested.
  • Chronic, mild, asymptomatic neutropenia does not usually require review by a haematologist – but it is reasonable to get an opinion to ensure all the appropriate tests have been done.
  • Obviously
    • moderate-to-severe neutropenia (absolute neutrophil count less than 1.0 x 10 /L) warrants further investigation (and probably referral to or liaison with haematology)
    • symptomatic neutropenia (did you remember to ask about symptoms?) requires investigation/referral
  • Severe, persistent and symptomatic neutropenia is followed up by the haematologist and may require other tests and involvement of other specialties
  • but the appropriate degree of investigation of asymptomatic neutropenia remains debatable clinically. Tests suggested include: full blood count, blood film, Hepatitis B and C, HIV, antinuclear antibody, extracted nuclear antibodies, rheumatoid factor, CCP antibodies, ESR, CRP, double stranded DNA, Vitamin B12, folate, iron studies

In my patients the overall theme seemed to be likewise to rule out common causes, especially autoimmune or infectious pathology  or nutritional deficiency initially.  The haematologist also suggested EPG, IEPG and serum free light chains.

The haematology cheat sheet suggested CXR and abdominal US (to exclude splenomegaly). I had not done this, nor did the haematologist suggest this when I liaised with them and it wasn’t done when the patient was seen in the clinic.

The conclusion was that this particular case was idiopathic neutropenia which is OK if it is over 1 and normalises with infection (and other things have been ruled out).  The suggested future management was to follow up 2 monthly (but OK to delay if clinically well) and to consider biopsy if the count was under one, there were other cytopaenias or new features.

The second patient probably warranted monitoring of FBC in two to three months.  Interestingly their neutrophil count had normalised by the time I had done the other tests.  The abnormal levels had been over a shorter time-frame than the first patient,

Both patients had slightly abnormal CD4/CD8 results which need follow up. Reduced T cells with a normal CD4:8 ratio were noted at the clinic in the first patient and an HIV test was ordered.  A repeat of the peripheral blood immunophenotyping at twelve months was advised.  The clinic was asked about the results in the second patient.

Following investigation algorithms and advice can often raise more questions!

It would seem advisable, in the asymptomatic patient, to

  • repeat an abnormal test
  • make sure no important items of history and examination have been missed initially
  • do the suggested basic tests (and perhaps to formulate a list to have at the ready)
  • seek advice
  • and to always ensure follow-up.

I found it useful to read the linked articles to put the question in context and to refresh my knowledge of some of the background clinical and pathological issues.

Cathy Regan

 

 

 

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