19.3 Sinusoidal Obstructive Syndrome (Veno-Occlusive Disease)

CPHON TCO V.D.4 is sinusoidal obstructive syndrome (SOS), still widely called hepatic veno-occlusive disease (VOD). The HSCT chapter named the triad and defibrotide; this page is the emergency algorithm. Endothelial injury in hepatic sinusoids traps cells and debris, sinusoids obstruct, and the liver becomes a tender, congested, portal-hypertensive organ. It is not acute graft-versus-host disease (GVHD) until you have walked the timing and the exam, and it is not a laboratory-only diagnosis you wait on until the bilirubin looks official.

A 4-year-old on day +11 after allogeneic hematopoietic stem cell transplantation (HSCT) with busulfan conditioning, a 9-year-old who received gemtuzumab before transplant, and a teenager with prior inotuzumab for relapsed ALL who now has a rising bilirubin and a tight abdomen are the pictures.

Who is at risk and what you see

Classic timing is the early post-HSCT window (often within the first three weeks, though late SOS exists). High-yield exposures:

• Busulfan myeloablative conditioning
• Total body irradiation (TBI)
• Gemtuzumab (anti-CD33 antibody-drug conjugate)
• Inotuzumab (anti-CD22 antibody-drug conjugate)
• Prior liver injury, second transplant, and very young age on some pathways

What you see: tender hepatomegaly (right-upper-quadrant pain, a liver edge you can feel, a child who guards when you examine), weight gain and ascites from sinusoidal hypertension and third-spacing, and jaundice with a rising bilirubin. Rapid overnight kilograms, a growing abdominal girth, and a child who will not stand because the belly is tight are more useful than waiting for scleral icterus to be obvious in a dim room.

Walk the 4-year-old. Busulfan, day +11, two kilograms up since yesterday, liver tender, bilirubin climbing, urine output slipping. This is SOS/VOD until the team says otherwise. Daily weights, abdominal girth, and a right-upper-quadrant exam are not optional if there is time after meds.

Baltimore and Seattle criteria: name the frameworks

Seattle and Baltimore criteria are known clinical frameworks used in transplant programs to recognize SOS/VOD (combinations of bilirubin rise, hepatomegaly or right-upper-quadrant pain, ascites, and weight gain). You may name them. Do not treat their milligram-per-deciliter or percent-weight cutoffs as if ONCC published them on the CPHON outline. Items test whether you recognize the tender liver plus weight gain plus jaundice cluster after a risk exposure and act, not whether you can recite an adult 1980s table from memory.

Ultrasound with Doppler supports the picture: reversed or reduced portal venous flow, increased hepatic-artery resistance, gallbladder-wall thickening, and ascites. Imaging is supportive, not a license to ignore the exam while you wait for a perfect Doppler sentence. A negative ultrasound does not magically make a tender, gaining, jaundiced day-+12 child fine.

Defibrotide and the fluid-kidney tension

Defibrotide is the disease-specific therapy used for VOD/SOS. It is not a diuretic and not ursodiol. Once the team diagnoses SOS, the nursing job is to get defibrotide started as ordered, watch for bleeding (the drug has antithrombotic endothelial effects), and keep invasive procedures to a minimum.

Supportive care is a tension, not a slogan:

• Fluid restriction limits third-spacing into ascites and pulmonary edema.
• Renal perfusion still needs enough intravascular volume. The kidney is downstream of abdominal tamponade from ascites and of hepatorenal physiology. Oliguria is a same-hour call, not proof that restriction is working.

Use concentrated medications, daily (or twice-daily) weights, strict intake and output, and abdominal girth. Albumin and diuretics appear on some pathways; they are team tools, not a reflex furosemide race that empties the tank. Avoid hepatotoxins when alternatives exist: extra acetaminophen, unnecessary herbal products, and stacking cholestatic drugs. Calcineurin inhibitors for GVHD prophylaxis are not casually stopped—that is a transplant-team decision because GVHD kills too.

Ursodiol (ursodeoxycholic acid) is used for prophylaxis in some centers. It is center practice, not a universal ONCC-mandated start-on-admission rule. Know that it exists; do not fail an item because a stem asked about prophylaxis rather than treatment. Treatment of established SOS is defibrotide plus supportive care, not more ursodiol as the rescue.

Distinguishing look-alikes

Hepatic GVHD is usually later than classic SOS, more purely cholestatic, and often travels with skin and gut GVHD. Day +12 tender hepatomegaly and three kilograms of ascites is SOS until proven otherwise; day +45 jaundice with a new rash and watery diarrhea is GVHD until proven otherwise. They can overlap. Do not give high-dose steroids as the only move for an early tender liver without considering SOS, and do not give defibrotide for every late bilirubin bump without looking at skin and stool.

Infection: viral hepatitis (including adenovirus, cytomegalovirus, hepatitis viruses), cholangitis, and disseminated fungal disease can raise bilirubin and make the liver tender. Culture, polymerase-chain-reaction panels the team uses, and imaging still belong in the workup.

Drug cholestasis: parenteral nutrition, azole antifungals, and other hepatically cleared drugs cause cholestasis without the rapid weight-gain and ascites packing of SOS. Timing, drugs, and Doppler help. Stopping a hepatotoxin is reasonable; calling every azole bump VOD is not.

A 9-year-old who received gemtuzumab, then TBI-based allogeneic HSCT, who gains 1.5 kg overnight with a tender liver is an SOS page, not a wait-for-Monday hepatology consult. A teenager whose only finding on day +50 is a slow bilirubin rise after a new azole, with a soft nontender abdomen and a gut-skin GVHD rash, is not automatically a defibrotide start.

Teach families that the liver's small blood channels were injured by conditioning or by gemtuzumab or inotuzumab, that fluid is leaking into the abdomen, and that defibrotide is the medicine aimed at those vessels. Daily weights are treatment, not nagging.

That is TCO V.D.4: name busulfan, TBI, gemtuzumab, and inotuzumab as risk, recognize tender hepatomegaly plus weight gain plus jaundice, use Baltimore and Seattle as named frameworks without treating cutoffs as ONCC numbers, start defibrotide, balance restriction against the kidney, avoid hepatotoxins, know ursodiol prophylaxis exists in some centers, obtain Doppler ultrasound, and tell hepatic GVHD, infection, and drug cholestasis apart.