Question 13.2

Created on Mon, 10/12/2015 - 19:25
Last updated on Sat, 01/13/2018 - 20:10
Pass rate: 66%
Highest mark: 9.3

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The following data refer to a 34-year-old male admitted to ICU twenty days after an allogeneic stem cell transplant for acute myeloid leukaemia. Over the last few days he had been complaining of right upper quadrant abdominal pain, and observed to have gained several kilos in weight.

Venous Biochemistry
Parameter Patient Value Normal Adult Range
Sodium 142 mmol/L 135 – 145
Potassium 4.8 mmol/L* 3.5 – 4.5
Chloride 97 mmol/L 95 – 105
Bicarbonate 22 mmol/L 22 – 26
Urea 11.2 mmol/L* 2.9 – 8.2
Creatinine 134 μmol/L* 70 – 120
Calcium 2.13 mmol/L 2.10 – 2.55
Phosphate 1.21 mmol/L 0.65 – 1.45
Total bilirubin 342 μmol/L* 0 – 25
Aspartate aminotransferase (AST) 175 U/L* < 40
Gamma glutamyl transferase (GGT) 123 U/L* < 40
Alanine aminotransferase (ALT) 87 U/L* < 40

a)  Give the most likely diagnosis. (15% marks)

b)  How would you confirm this? (15% marks)

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College Answer

a)
Veno-occlusive disease of the liver (sinusoidal obstruction syndrome)

b)
Liver USS showing ascites and reversal of portal vein flow

Discussion

Let us dissect the results systematically.

The electrolytes look deceptively normal. However, an exam candidate accustomed to playing these games will recognise the presented panel as an invitation to calculate the anion gap. If one does this, one will discover that it is raised.

 (142 + 4.8) - (97 + 22) = 27.8

There does not seem to be much of a metabolic acidosis associated with this, which is a little weird (delta ratio is very high, which could suggest that there is some sort of pre-existing metabolic alkalosis present). 

The ure and creatinine are raised, but not to a significant degree. Certainly not by a degree that might explain this weight gain with renal-related fluid overload.

The calcium and phosphate are trivially deranged; the normal phosphate suggests that the accumulation of retained non-volatile acids of renal failure is probably not responsible for the high anion gap.

Liver enzymes are deranged. ALT AST and GGT are all elevated, and even though alkaline phosphatase is not reported one can generally comment that there is non-specific liver injury occurring (i.e. the right upper quadrant pain is probably not acute cholecystitis, but rather the feeling of a swollen liver distending its capsule). The liver injury also suggests that lactate could explain the raised anion gap. 

In summary:

  • High anion gap, probably due to lactate
  • Renal impairment
  • Liver injury
  • Oedema

None of these are parfticularly specific and you'd be struggling to narrow your list of differentials, but the college helpfully threw in the story about a recent bone marrow transplant. That's a giveaway. In the pattern recognition algorithm of the exam candidate,  liver injury + BMT = VOD. Veno-occlusive disease tends to occur in the first three weeks after the transplant, and typically manifests with weight gain and a painful liver. The major clinical criteria for diagnosis (Seattle criteria and Baltimore criteria) usually also demand ascites, hepatomegaly and a bilirubin level (which we were not supplied with; it would have to be over 34 mmol/L).

Diagnosis does not require ultrasound, but it is usually ordered in this context. The BCSH/BSBMT guidelines (2013) concluded that "the main role of ultrasound is to exclude the presence of other diagnoses" because the ultrasound findings which are usually associated with VOD are insufficiently sensitive and specific. In any case, here they are:

  • Ultrasound-confirmed ascites
  • Ultrasound-confirmed hepatomegaly
  • Splenomegaly
  • Attenuated or reversed hepatic venous flow
  • Thickened gallbladder wall
  • Ultrasound evidence of increasing hepatic artery  vascular resistance (there is a "hepatic artery vascular resistance index",  which is helpful in the diagnosis if it is greater than 0.75.)

References

Mohty, M., et al. "Revised diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients: a new classification from the European Society for Blood and Marrow Transplantation." Bone marrow transplantation 51.7 (2016): 906-912.

Baron, Frédéric, Manuel Deprez, and Yves Beguin. "The veno-occlusive disease of the liver." Haematologica 82.6 (1997): 718-725.

Dignan, Fiona L., et al. "BCSH/BSBMT guideline: diagnosis and management of veno‐occlusive disease (sinusoidal obstruction syndrome) following haematopoietic stem cell transplantation." British journal of haematology 163.4 (2013): 444-457.

Richardson, Paul G., et al. "Defibrotide for the treatment of severe hepatic veno-occlusive disease and multiorgan failure after stem cell transplantation: a multicenter, randomized, dose-finding trial." Biology of Blood and Marrow Transplantation 16.7 (2010): 1005-1017.

Couriel, Daniel, et al. "Acute graft‐versus‐host disease: Pathophysiology, clinical manifestations, and management." Cancer 101.9 (2004): 1936-1946.

Ljungman, Per, Paul Griffiths, and Carlos Paya. "Definitions of cytomegalovirus infection and disease in transplant recipients." Clinical Infectious Diseases 34.8 (2002): 1094-1097.

Bearman, Scott I. "The syndrome of hepatic veno-occlusive disease after marrow transplantation." Blood 85.11 (1995): 3005-3020.

Coppell, Jason A., et al. "Hepatic veno-occlusive disease following stem cell transplantation: incidence, clinical course, and outcome." Biology of Blood and Marrow Transplantation 16.2 (2010): 157-168.

Mcdonald, George B., et al. "Venocclusive disease of the liver after bone marrow transplantation: diagnosis, incidence, and predisposing factors."Hepatology 4.1 (1984): 116-122.

Jones, Richard J., et al. "Venoocclusive disease of the liver following bone marrow transplantation." Transplantation 44.6 (1987): 778-783.

Kumar, Ashish, Praveen Sharma, and Shiv Kumar Sarin. "Hepatic venous pressure gradient measurement: time to learn." Indian J Gastroenterol 27.2 (2008): 74-80.

Cheuk, D. K., et al. "Interventions for prophylaxis of hepatic veno-occlusive disease in people undergoing haematopoietic stem cell transplantation." The Cochrane database of systematic reviews 5 (2015): CD009311-CD009311.

Mohty, M., et al. "Revised diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in adult patients: a new classification from the European Society for Blood and Marrow Transplantation." Bone marrow transplantation 51.7 (2016): 906-912.