A 32-year-old female has been admitted to the ICU following an emergency response call for generalised tonic clonic seizures and obtundation. No past history is available. Non-contrast CT brain scan is normal. The following results are obtained:

Parameter

Patient Value

Adult Normal Range

Sodium 

143 mmol/L

135 – 145

Potassium  

3.0 mmol/L*

3.5 – 5.0

Chloride 

116 mmol/L*

95 – 105

Bicarbonate 

15.0 mmol/L*

22.0 – 26.0 

Glucose 

5.2 mmol/L

3.5 – 6.0

Urea 

12.4 mmol/L*

3.0 – 8.0

Creatinine  

202 μmol/L*

45 – 90 

Magnesium

0.75 mmol/L

0.75 – 0.95

Albumin 

14 g/L*

35 – 50 

Protein 

49 g/L*

60 – 80

Total bilirubin 

35 μmol/L*

< 26

Aspartate aminotransferase (AST) 

58 U/L*

< 35

Alanine aminotransferase (ALT)

50 U/L*

< 35

Alkaline phosphatase (ALP)

145 U/L*

30 – 110

-Glutamyl transferase (GGT)

45 U/L*

< 40

Ionised calcium 

1.90 mmol/L*

1.10 – 1.35

Calcium corrected 

2.90 mmol/L*

2.12 – 2.62

Phosphate 

1.8 mmol/L*

0.8 – 1.5

Creatinine Kinase 

356 U/L*

55 – 170 

Lactate dehydrogenase

450 U/L*

120 – 150

Haemoglobin 

75 g/L*

120 – 160

White Cell Count  

20.0 x 109/L*

4.0 – 11.0

Platelet count 

60 x 109/L*

150 – 350 

  1. List three differentials for the above-mentioned clinical presentation and pathology results.  (30% marks)
  1. List three further pathology tests that would aid your diagnosis.              (30% marks)

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College answer

a)                                                                                                                                         
•    Thrombotic thrombocytopenic purpura 
•    HELLP syndrome 
•    Septic -meningo-encephalitis 
•    Drug - induced 
•    Vasculitis  
•    Malignancy 
 
b) 
•    Blood film for schistocytosis 
•    Blood cultures/lumbar puncture  
•    Vasculitic screen 
•    Serology for pneumococcus/meningococcus 
•    Pregnancy test 
 

Examiners Comments: 
 
Generally, these questions were answered well. Those candidates that failed, missed all or part of the question or misinterpreted what was being asked, reiterating how important it is to read the question and understand what is required before starting to answer. 

 

Discussion

The abnormalities in this set of results are:

  • Acidosis, likely metabolic, with an anion gap of 15 which (even when using a normal value corrected for the shockingly low albumin) give a delta ratio of 0.67, i.e. predominantly a normal anion gap metabolic acidosis.
  • Renal failure, of indeterminate acuity
  • Low albumin and serum protein, which are nonspecific findings in critical illness
  • Raised bilirubin, which in the presence of essentially normal LFTs raises the suspicion of haemolysis
  • Hypercalcemia and hyperphosphataemia, as well as a slightly elevated alkaline phosphatase, suggestive of increased rate of bone resorption
  • Raised CK, which is not sufficiently elevated to suggest rhabdomyolysis
  • Raised LDH, which is a non-specific finding suggestive of cellular injury, but which in the presence of a raised bilirubin could be consistent with haemolysis, and in the presence of hypercalcemia suggests malignancy
  • Anaemia
  • Thrombocytopenia
  • Leukocytosis

So; this mixture of abnormalities has to play along with a history of being young, female and seizury. The differentials therefore need to explain a decreased level of consciousness, renal failure, haematological disturbance with anaemia and theromobocytopenia, and seizures. 

  • TTP
  • Sepsis with DIC
  • Vasculitis with MAHA
  • Intoxication
  • Haematological malignancy

It is hard to say how HELP syndrome could have attracted any marks here, as you're missing the EL. Also, none of the differentials (apart from malignancy) explain the hypercalcemia. Also, malar

Thus, one would order a broadside of tests:

  • Conjugated ad =unconjugated bilirubin levels
  • "Vasculitic screen" including ADAMTS-13 levels
  • Fibrinogen level and coags
  • Blood cultures
  • Lumbar puncture (given that sepsis with DIC could be due to  Neisseria meningitides)

References

References