Veno-occlusive Hepatic Disease Workup
- Author: James L Harper, MD; Chief Editor: Jennifer Reikes Willert, MD more...
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- One of the major challenges in the diagnosis of veno-occlusive disease (VOD) is the lack of sensitive laboratory and imaging studies that can accurately assist in diagnosis, which is very important with regard to the prompt start of appropriate treatment. Early diagnosis and subsequent timely treatment significantly affect the risks of morbidity and mortality. However, current diagnostic tools lack the necessary sensitivity.
- The laboratory workup of a patient with possible veno-occlusive disease has several objectives. The first goal, of course, is to confirm the diagnosis, the second goal is to look for a detectable discrete cause, and the third goal is to establish the function of the liver and other end organs.
- Relevant laboratory findings include hyperbilirubinemia, parameters of cholestasis (alkaline phosphatase and γ-glutamyltransferase [GGT]), thrombocytopenia, and abnormal coagulation parameters (especially elevated plasminogen activator inhibitor-1 [PAI-1] levels), as well as decreased antithrombin III (ATIII), protein C, and protein S levels.
- Documentation of increased total and direct bilirubin levels assists in the identification of cholestatic disease.
- GGT, alkaline phosphatase, and transaminase levels should be measured to rule out other causes of hepatic inflammation.
- A CBC count and differential should be obtained to assess engraftment total lymphocyte count, as well as transfusion-refractory thrombocytopenia.
- Coagulation parameters should include prothrombin and activated partial thromboplastin times, fibrinogen levels, fibrin split product levels, D-dimer levels, ATIII levels, protein C levels, and protein S levels to rule out disseminated intravascular coagulation (DIC) and to assess specific veno-occlusive disease–related coagulation factors.
- PAI-1 levels are often abnormally elevated, and ATIII levels are decreased in patients with hepatic veno-occlusive disease; thus, measurement of these factors may be helpful as sensitive markers of veno-occlusive disease. Recent reports suggest that PAI-1 may also be an essential factor in the pathogenesis of veno-occlusive disease.
- Parameters of infection and/or inflammation (eg, C-reactive protein levels) should be obtained to help assess the infectious risk and rule out sepsis.
- Despite the vasculitic basis for this disease, obtaining sedimentation rates is not particularly helpful because they may be nonspecifically elevated in any patient who has undergone transplantation.
- A decrease in the anticoagulant protein levels after transplantation may be a harbinger of early end-organ damage, particularly in patients with preexisting conditions (eg, low anticoagulant protein levels prior to transplantation). Weekly measurements of these anticoagulants during the first 2 weeks after transplantation may allow for early detection of veno-occlusive disease.
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- The diagnostic imaging study of choice is abdominal Doppler ultrasonography. Ultrasonography of the liver reveals engorgement, and the Doppler reveals direction of flow in the veins.
- Other hepatic pathology may be detected (eg, gallbladder thickening, gallstones, lymphadenopathy).
- Ultrasonography is a powerful tool for confirming diagnosis, but typical findings often manifest late in the course or are not always apparent. Thus, ultrasonography should not be relied on to rule out the diagnosis of veno-occlusive disease in the face of other evidence that would support it.
- The diagnostic ultrasonography finding is a reversal of flow in the portal and hepatic veins. Other findings include ascites and hepatomegaly.
- Imaging studies should be used to assess the following:
- Size of liver and spleen
- Free abdominal fluid
- Thickening of the gallbladder wall
- Diameter of the portal vein and liver veins
- Portal venous flow
- Hepatic venous flow
- Loss of the respiration dependent flow modulation
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- Histologic findings include hepatic engorgement and zone 3 inflammation. Occasionally, zone 2 may also be involved.
- Injury to endothelial cells and the terminal hepatic venule is common.
- For more information, see Pathophysiology.
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