VOD (Veno-occlusive disease) 

• A diagnosis of exclusion
• A post-BM-transplant complication
• A clinical diagnosis based on 4 elements
  • Tender hepatomegaly
  • Fluid retention
  • Elevated liver enzymes (mainly T. bili), jaundice
  • Unresponsiveness to platelets
• Risk factors
  • Unrelated BMT, due to chemo
  • Hi dose chemo (causes endothelial damage)
  • Busulfan in conditioning
  • Increased transaminases before conditioning (hepatitis)
  • Radiation
  • VAL (vincristine, actinomycin, cyclophosphamide)
  • Younger age
  • DNA repair defect (fanconi’s anemia)
• Pathophys
  • Endothelial damage causes leaky capillaries, exposes fibrin, platelets aggregate and clot forms, may occlude vasculature. Hence platelet consumption (refractory to transfusion), and fluid retention. Severe ascites  is due to oncotic, hydrostatic pressure due to secondary hyperaldosteronemia. In late VOD, liver is like ‘cirrhotis’ and water is squeezed out of liver
• PE
  • Weight gain (fluid retention)
  • Coagulopathy
  • Swelling, edema, sacral edema
  • Abdominal distension, ascites, hepatomegaly
  • Icterus
• DDX
  • Renal dz, decreased cardiac fn, chemical hepatitis, sepsis, GVHD
• Labs
  • Hyponatremia (dilutional)
  • Decreased platelets (consumptive process)
  • Coagulopathy (PT/PTT) à biopsy contraindicated
  • Low albumin
  • Liver enzymes: incr T bili, +/- elev transaminases
  • US/doppler shows blood flow reversal in late dz
  • Pathognomonic: elevated hepatic wedge pressure
  • If absolutely necessary, use TIPS approach (transjugular, intrahepatis portosystemic shunt) and bx through IVC (so bleed into circulation, not liver)
• Grading
  • Mild: bili < 5, always recover
  • Moderate: bili 5-15, recovery w/ aggressive management
  • Severe: >15, usually die; transplant mortality 80%
• Rx supportive
  • Restrict fluids. Replace albumin (25%, 1 g/kg, run as fast as poss ie. 45 min- 1hour, to establish high gradient and follow immediately by Lasix)
  • Heparin drip, started automatically, d’c’ed day 30.
  • Fluid management: blood product + Lasix (FFP, platelets, PRBC)
  • Aldactone (for antialdosterone effect, mainly, prevent hepatocyte edema)
  • If prn Lasix doesn’t work, dopamine drip 3 mcg/kg/min (to increase renal perfusion; peripheral vasoconstriction)… consider adding Lasix drip
  • Consider short term burst of solumedrol 2 mg/kg/d
  • Anti-TNF (enbrel), TPA
  • For hepatorenal syndrome, dialysis doesn’t really help – a last resort
  • Difibrotide , to prevent fibrosis (experimental)
• Morbidity and mortality
  • Death usually d/t end-stage liver dz, pulm edema