From What’s Your Diagnosis? on page 4
Trichrome (Figure A) and reticulin (Figure B) stains of the liver biopsy revealed centrilobular hepatocyte dropout, fibrosis, and narrowing of the central veins by a combination of fibrous tissue and reticulin fibers. These features were diagnostic of veno-oc- clusive disease (VOD, also known as sinusoidal
obstructive syndrome). The treatment team considered
compassionate use of defibrotide, but it was not given because of the remoteness of the initial insult and improving
liver function by then. The patient subsequently enrolled in
hospice owing to her other comorbidities and died.
Hepatic VOD occurs most commonly in patients undergoing hematopoietic stem cell transplant (HSCT).
As with this patient, refractory thrombocytopenia and
coagulopathy in the setting of concomitant liver failure
and recent exposure to chemotherapy usually precludes
liver biopsy; thus, VOD is often diagnosed clinically. The
modified Seattle diagnostic criteria defines VOD as the
otherwise unexplained occurrence of two or more of the
following within 20 days of HSCT: serum total bilirubin
greater than 2 mg/dL, hepatomegaly with right upper
quadrant pain, and sudden weight gain due to fluid accumulation (greater than 2% of baseline body weight).1
VOD is thought to begin with injury to the hepatic ve-
nous endothelium and induction of a procoagulant state.
Treatments for VOD, such as defibrotide, tPA, and heparin,
attempt to reverse this localized hypercoagulability. In
phase I/II trials, defibrotide, which stimulates fibrinolysis
by increasing endogenous tPA production and decreasing
PA-I activity, showed more than 100 day postHSCT survival
rates of 46% with the added advantage of minimal system-
ic anticoagulant effects. 2
Less commonly, VOD occurs after exposure to chemotherapeutic agents in nontransplant settings, ingestion of alkaloid
toxins, and high-dose abdominal radiation therapy. Additional
risk factors include exposure to multiple chemotherapeutic
agents, particularly busulfan and cyclophosphamide, preexisting liver disease, decreased carbon monoxide diffusing capacity, advanced age, and female gender. Bairey et al3 reported
the case of a 49-year-old woman with newly diagnosed acute
monoblastic leukemia who developed severe VOD after induction chemotherapy with idarubicin, cytarabine, and etoposide,
and improved with defibrotide therapy. These cases illustrate
VOD as an important etiology, albeit uncommon, of hepatic
dysfunction in a non-HSCT patient and should be considered
particularly in individuals with known risk factors. A liver
biopsy is useful to diagnose VOD in cases that are not easily
identified based on clinical features alone. n
The authors acknowledge the contributions of John Hart,
M.D., in the Department of Pathology at the University of
Chicago Medicine. A.E.M. and S.S. contributed equally to
1. Coppell, J.A., et al. Biol Blood Marrow Transplant. 2010;16:157-68.
2. Richardson, P.G., et al. Biol Blood Marrow Transplant. 2010;16:1005-17.
3. Bairey, O., et al. Am J Hematol. 2002;69:281-4.