A 56-year-old male presents with one-month history of weight loss and shortness of breath.

The results of his blood tests are as follows:

Parameter

Patient Value

Normal Adult Range

Haemoglobin

128g/L*

135 - 180

White Cell Count

6.1 x 109/L

4.0 - 11.0

Platelets

35 x 10l;l/L*

150 - 400

Prothrombin time

23.3 sec*

12.0 - 16.5

International normalised ratio

2.0*

0.9 - 1.3

Activated partial thrombop lastin time

45.7 sec*

27.0 - 38.5

Fibrinoqen

0.7 q/L*

2.0 - 4.0

Total Protein

39 a/L*

60 - 80

Albumin

24 q/L*

35 - 50

Total Bilirubin

215 umol/L*

< 20

Alanine  aminotransferase

202 U/L*

< 40

Alkaline phosphatase

243 U/L*

30 - 110

y-Glutamvl transferase

394 U/L*

< 60

Ferritin

120000 ua/L*

30 - 620

Iron

15 µmol/L

9 - 30

Transferrin

13 µmol/L*

23 - 43

Transferrin saturation

58%*

14 - 45

a) Give the diagnosis indicated by these results. (20% marks)

b) Give three possible underlying causes. (15% marks)

[Click here to toggle visibility of the answers]

College answer

a)    Haemophagocytic lymphohistiocytosis (HLH)                     
 
b)    Viral infection e.g. EBV, HSV, HINI influenza                          
Lymphoma 
Malignancy 
Immune deficiency states 
Rheumatological disorders 
Other infection – bacterial and fungal less likely 
 

Discussion

a)

The only thing ever to produce a serum ferritin level of 120, 000? Surely, the college wanted to hear "haemophagocytic syndrome", but there are a variety of possibilites:

  • Malignancy
  • Iron overload syndromes
    • Hereditary haemochromatosis
  • Adult-onset Still's disease
  • Systemic juvenile idiopathic arthritis
  • Haemophagocytic lymphohistiocytosis
  • Chronic inflammatory rheumatological diseases
  • Chronically transfused disease states
    • Sickle cell
    • Thalassaemia
  • Acute inflammatory states:
    • Sepsis
  • Chronic inflammatory states:
    • Chronic advanced liver disease (mainly alcohol-related)
    • Chronic renal failure
    • HIV

b)

Causes of haemophagocytic syndrome:

Congenital:

  • familial HLH (FHLH)
  • Chediak-Higashi syndrome (CHS 1)
  • Griscelli syndrome (GS 2)
  • X-linked proliferative syndrome (XLP)
  • The UpToDate article has whole pages listing obscure-sounding loci of mutation.

Acquired causes

  • Infectious
    • EBV
    • CMV
    • HIV
    • Leishmania
  • Neoplastic
    • Lymphoma, especially T and NK-cell
  • Autoimmune
    • SLE
    • Kawasaki disease

References

References

Moore Jr, Charles, Michelle Ormseth, and Howard Fuchs. "Causes and significance of markedly elevated serum ferritin levels in an academic medical center." JCR: Journal of Clinical Rheumatology 19.6 (2013): 324-328.

Lee, Mark H., and Robert T. Means. "Extremely elevated serum ferritin levels in a university hospital: associated diseases and clinical significance." The American journal of medicine 98.6 (1995): 566-571.

Hearnshaw, Sarah, Nick Paul Thompson, and Andrew McGill. "The epidemiology of hyperferritinaemia." World journal of gastroenterology 12.36 (2006): 5866. - ! WARNING ! this link will download the whole September issue, with the potential to fatally clog your internet hole.

Janka, Gritta E. "Hemophagocytic syndromes." Blood reviews 21.5 (2007): 245-253.