Vague anaemias in old folk

76-year-old Mrs Ann Imeeya

Reason for appointment: Blood results

Please let everything be normal. Mrs Imeeya will be relieved, I can squeeze in a QOF smoking status and catch up 5 precious minutes of my 40 minute late surgery.

You quickly find the FBC, U&E, LFT, TFTs, Lipid and HbA1c done three days ago.

All the results are normal except for the FBC. This shows:

 Units3 days agoReference range
Haemoglobin (HB)g/L105115-165
White Cell Count (WBC)109/L7.84-11
Platelet Count (PLT)109/L188150-450
Red Blood Count (RBC)1012/L3.73.8-5.8
Mean Cell Volume (MCV)fl8180-100
Packed Cell Volume (PCV)/Haematocrit (HCT)L/L0.380.37-0.47
Mean Cell Haemoglobin (MCH)pg2827-32
Mean Cell Haemoglobin Concentration (MCHC)g/L333320-360
Neutrophil Count109/L5.62.0-7.5
Lymphocyte Count109/L1.61.5-4.5
Monocyte Count109/L0.20.2-0.8
Eosinophils Count109/L0.30.0-0.4
Basophils109/L0.10-0.1

You note over the past three years, her Hb (in g/L) has been between 113 and 120. Her last FBC was 7 months ago and was 116 g/L.

You ask yourself:

  • Can I attribute a slowly progressing normocytic anaemia to age?
  • What data do I need to gather in the consultation?
  • What further tests could I do to prove it’s not something sinister? And how far do I go?

Can I attribute a slowly progressing normocytic anaemia to age?

Around 10% of 65+ and more than 20% of those 85+ are anaemic (1).

The usual microcytic/normocytic/macrocytic approach isn’t always as helpful in the elderly, as the MCV tends to drift upwards with age. This may be because of shortened red blood cell survival with ageing, leading to younger red blood cells with larger MCVs (2). So basically we need to consider iron-deficient states even when normocytic.

Combining MCV with red cell distribution width (RDW) is helpful here, as an increased RDW could occur with co-existing microcytosis and macrocytosis, such as iron and B12 deficiency.

A useful approach particularly when there isn’t marked microcytosis/macrocytosis is to consider the likely causes in this age group:

Some clarification around “nutritional deficiency”. Iron deficiency in the elderly is very rarely only from poor oral intake. 1mg a day oral intake is enough for an elderly person to maintain iron stores if there is no blood loss, and the typical Western diet has 15-20mg iron per day. Iron deficiency anaemia in the elderly therefore is assumed to be GI blood loss until proven otherwise. About 40% of iron deficiency anaemias in over 50s are upper GI and 20% lower GI (3).

The “unexplained anaemia of old age” (aka normocytic and ferritin, B12 and folate came back normal) is often because of renal impairment and/or chronic inflammation. In terms of what else to worry about, about 5% of cases myelodysplasia is the cause. Leukaemias are less common, especially without other cells lines affected.

What data do I need to gather in the consultation?

In a 10 minute consultation with an elderly person with normocytic anaemia, there are two main elements to explore. One is diagnostic pointers, and the other is how far the patient would like this to be explored in view of their overall health and goals.

Pointers:

  • Any GI symptoms? Not just direct GI blood loss, but any markers pointing to upper or lower malignancy
  • GU blood loss (it’s not just urology; visible haematuria in a woman over 55 with low Hb is also a suspected endometrial cancer)
  • Diet, especially vegan/vegetarian and/or a “tea and biscuits” diet, as well as ETOH intake
  • Systemic features such as weight loss and night sweats
  • Symptoms of the anaemia itself such as SOB/fatigue
  • Drugs, especially anticoagulants/antiplatelets/DMARDS
  • Examination for abdominal masses, organomegaly and lymph nodes

More likely to investigate/treat:

  • Co-morbidities would benefit (e.g. heart failure)
  • Rapid progression
  • Good level of function
  • Symptomatic

Less likely to investigate/treat:

  • Poor level function
  • Patient preference
  • Likely cause would not benefit from active treatment

What further tests could I do to prove it’s not something sinister? And how far do I go?

So, our group of First5s had a long think about this. We looked at NICE guidelines for FIT testing, myeloma and also considered our experience that when you ask the online haematology advice, we sometimes get asked to do tests that might not always be rationalised to our patient e.g. HIV and Hep C.

We came up with the following approach for otherwise unexplained normocytic anaemia in over 65s for potential intervention:

  • If anaemia is slow and subtle, consider rechecking in 1-6 months depending on rate of decline before doing other tests.

    If other tests are being done:
  • Blood film
  • Ferritin, folate, B12. Ferritin is particularly helpful for distinguishing iron deficiency from chronic inflammation.
  • FIT test (if no PR bleeding; if PR bleeding 2WW unless definitely explained)
  • Coeliac screen
  • U&Es
  • LFTs
  • TFTs (if macrocytic)
  • Myeloma screen -> some debate over how far to go, but we felt that if a full workup was justified, there’s no point doing a half workup. This meant protein electrophoresis and Bence Jones proteins.
  • Reticulocyte count (screening for haemolysis)

If you can’t find anything concerning, a reasonable worst-case scenario is the early stages of a grumbling MDS / some other nasty haem thing. If the patient would consider active treatment if those things were to be discovered, we think it’s worth monitoring so-called unexplained anaemia in the elderly every 3-6 month with safety netting, depending on the rate of progression.

References

(1) Guralnik JM, Eisenstaedt RS, Ferrucci L, Klein HG, Woodman RC. Prevalence of anemia in persons 65 years and older in the United States: evidence for a high rate of unexplained anemia. Blood. 2004; 104 (8): 2263-2268. Available from: doi: 10.1182/blood-2004-05-1812 Available from: https://doi.org/10.1182/blood-2004-05-1812 [Accessed 2/2/2020].

(2) Gamaldo AA, Ferrucci L, Rifkind JM, Zonderman AB. Age-related changes in mean corpuscular volume in adult whites and African Americans. Journal of the American Geriatrics Society. 2011; 59 (9): 1763-1764. Available from: doi: 10.1111/j.1532-5415.2011.03583.x Available from: https://www.ncbi.nlm.nih.gov/pubmed/22136544https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4642713/ .

(3) Gordon SR, Smith RE, Power GC. The role of endoscopy in the evaluation of iron deficiency anemia in patients over the age of 50. The American Journal of Gastroenterology. 1994; 89 (11): 1963-1967.