You are using an outdated browser. Please upgrade your browser to improve your experience and security.

Skip to content

Diagnostic Criteria

Multiple diagnostic criteria have been utilized to recognize and diagnose VOD/SOS

Historically, the modified Seattle and Baltimore criteria have been used for diagnosis of VOD/SOS1-3

Modified Seattle criteria1

Presentation by Day 20 post HSCT of at least 2 of the following:

  • Bilirubin >2 mg/dL
  • Hepatomegaly or right upper quadrant pain
  • Weight gain (>2%)

Baltimore criteria4

Presentation of bilirubin ≥2 mg/dL by Day 21 post HSCT and at least 2 of the following: 

  • Painful hepatomegaly
  • Weight gain (>5%)
  • Ascites

However, there are limitations to these criteria1,4,5

  • Criteria do not consider that signs and symptoms of VOD/SOS can occur after the first 21 days post HSCT
  • Criteria do not consider VOD/SOS that presents in the absence of specified signs and symptoms; eg, VOD/SOS without hyperbilirubinemia is not considered in the Baltimore criteria
  • Criteria do not capture recent clinical descriptions of disease
  • Criteria do not include newer imaging capabilities, which may be more sensitive to specific indicators of VOD/SOS
See below for recently published criteria that have been proposed to address these limitations

EBMT diagnostic criteria for VOD/SOS in adults

VOD/SOS that occurs ≤21 days post HSCT4

Baltimore criteriaa: 
Presentation of bilirubin ≥2 mg/dL and at least 2 of the following: 

  • Painful hepatomegaly
  • Weight gain (>5%)
  • Ascites

Late-onset VOD/SOS >21 days post HSCT4

Baltimore criteriaa beyond Day 21 
OR histologically proven VOD/SOS 
OR 2 or more of the following criteria must be present:

  • Bilirubin ≥2 mg/dL (or 34 µmol/L)
  • Painful hepatomegaly
  • Weight gain (>5%)
  • Ascites

AND hemodynamic or/and ultrasound evidence of VOD/SOS (hepatomegaly, ascites, and decrease in velocity or reversal of portal flow)

  1. Defined as classical VOD/SOS in EBMT criteria.4

EBMT diagnostic criteria for VOD/SOS in children6,7

No limitation for time of VOD/SOS onset6

The presence of 2 or more of the following is required6,b:

  • Unexplained consumptive and transfusion-refractory thrombocytopeniac,d
  • Otherwise unexplained weight gain on 3 consecutive days, despite the use of diuretics, or weight gain >5% above baseline value
  • Hepatomegaly above baseline value (best if confirmed by imaging)c,e
  • Ascites above baseline value (best if confirmed by imaging)c,e
  • Rising bilirubin from a baseline value on 3 consecutive days or bilirubin ≥2 mg/dL within 72 hours
 
  • Mahadeo et al recommend use of a structured radiologic reporting template when there is clinical concern for VOD/SOS7

Mahadeo et al endorse pediatric and AYA criteria for VOD/SOS as proposed by EBMT and provide implementation guidance for standardization across centers7

Proposed EBMT criteria have not been prospectively validated in clinical trials6
  1. With the exclusion of other potential differential diagnoses.6
  2. Additional implementation guidance from Mahadeo et al is available for thrombocytopenia, hepatomegaly, and acites.7
  3. ≥1 weight-adjusted platelet substitution/day to maintain institutional transfusion guidelines.6
  4. Suggested: imaging (US, CT, or MRI) immediately before HSCT to determine baseline value for both hepatomegaly and ascites.6

Cairo/Cooke revised diagnostic criteria for VOD/SOS in children and adults5

Any 2 of the following after HSCT5,f:

  • Elevated bilirubin (≥2 mg/dL) or greater than upper institutional limitsg
  • Unexpected weight gain (≥5% compared to baseline weight pre-HSCT)
  • Excessive platelet transfusions consistent with refractory thrombocytopenia post HSCT
  • Hepatomegaly for age or increased size over pre-HSCT
  • Right upper quadrant pain
  • Ascites confirmed by physical exam and/or imaging studies
  • Reversal of portal venous flow (hepatofugal flow) by Doppler ultrasound

  OR

Any 1 of the following after HSCT5,f:

  • Hepatic biopsy consistent with VOD/SOS
  • Unexplained elevated portal venous wedge pressure

Though it is not recommended, a liver biopsy or direct portal wedge pressure measurements can be used when making a diagnosis of VOD/SOS, if necessary5

Proposed Cairo/Cooke criteria have not been prospectively validated in clinical trials5
  1. Probably or definitely secondary to VOD/SOS and not other etiologies.5
  2. In patients with an already elevated bilirubin prior to HSCT conditioning, this criterion should not be utilized in the diagnostic criteria.5

Recent advances in making early and accurate diagnosis of VOD/SOS5

Left Scroll ArrowRight Scroll Arrow
 EBMT4
Adult 		EBMT6,7 Corbacioglu/Mahadeo Pediatric & AYA Cairo/Cooke5
Age agnostic 
 ≤21 days post HSCT>21 days post HSCT  
No time constraint to diagnose VOD/SOS 
 
 
 
Allows for cases of anicteric VOD/SOS 
 
 
 
Includes refractoriness
to excessive platelet transfusions		  
 
 
Includes abdominal ultrasound (hepatomegaly and/or ascites) 
 
 
 
Includes Doppler ultrasound imaging (reversal of portal venous flow) 
 
 
 
Hemodynamic stability/
hepatic wedge pressure		 
 
 
 

h

Biopsy 
 

h

 
 

h

VOD/SOS is a clinical diagnosis1
  1. While not recommended, if conducted and diagnostic, this allows for a VOD/SOS diagnosis independent of any other findings.4,5
Be prepared by knowing the signs of renal and pulmonary dysfunction 

AYA=adolescent and young adult; CT=computed tomography; EBMT=European Society for Blood and Marrow Transplantation; HSCT=hematopoietic stem-cell transplantation; MRI=magnetic resonance imaging; SD=standard deviation; SOS=sinusoidal obstruction syndrome; US=ultrasonography; VOD=veno-occlusive disease.

References: 1. Carreras E. Early complications after HSCT. In: Apperley J, Carreras E, Gluckman E, et al, eds. The EBMT Handbook. 6th ed. Paris, France: European School of Haematology; 2012:176-195. 2. Jones RJ, Lee KS, Beschorner WE, et al. Venoocclusive disease of the liver following bone marrow transplantation. Transplantation. 1987;44(6):7778-783. 3. McDonald GB, Sharma P, Matthews DE, at al. Venoocclusive disease of the liver after bone marrow transplantation: diagnosis, incidence, and predisposing factors. Hepatology. 1984;4(1):116-122. 4. Mohty M, Malard F, Abecassis 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 Transplant. 2016;51(7):906-912. 5. Cairo MS, Cooke KR, Lazarus HM, et al. Modified diagnostic criteria, grading classification and newly elucidated pathophysiology of hepatic SOS/VOD after haematopoietic cell transplantation. Br J Haematol. 2020;190(6):822-836. 6. Corbacioglu S, Carreras E, Ansari M, et al. Diagnosis and severity criteria for sinusoidal obstruction syndrome/veno-occlusive disease in pediatric patients: a new classification from the European Society for Blood and Marrow Transplantation. Bone Marrow Transplant. 2018;53(2):138-145. 7. Mahadeo KM, Bajwa R, Abdel-Azim H, et al; Pediatric Acute Lung Injury and Sepsis Investigators (PALISI) Network; Pediatric Diseases Working Party of the European Society for Blood and Marrow Transplantation. Diagnosis, grading, and treatment recommendations for children, adolescents, and young adults with sinusoidal obstructive syndrome: an international expert position statement. Lancet Haematol. 2020;7(1):e61-e72.