Case Presentation: A 32 year old female with Systemic Lupus Erythematosus (malar rash, discoid lupus erythematosus, alopecia) presented with sepsis following a trans-jugular liver biopsy, which was obtained due to chronic transaminitis, thrombocytopenia, hypoalbuminemia, and imaging findings suggestive of early cirrhosis. Liver biopsy showed sinusoidal dilatation without evidence of cirrhosis. Initial work up was notable for E. coli bacteremia, peritonitis, and nephrotic range proteinuria in the setting of elevated double stranded DNA and hypocomplementemia concerning for lupus nephritis. Abdominal imaging revealed a large, nearly occlusive portal vein thrombosis (PVT) with cavernous transformation not seen on abdominal MRI three months prior. An upper endoscopy was performed to evaluate for varices prior to anticoagulation initiation. Friable gastric mucosa with stigmata of bleeding was observed; thus, anticoagulation was deferred as an inpatient given high bleeding risk. Initial hypercoagulable workup revealed a factor VIII level 312% above normal range. Screening for Antiphospholipid Syndrome performed one year prior to presentation was normal.
Discussion: Portal vein thrombosis is not commonly associated with factor VIII elevation, particularly in the setting of a lupus flare. This case is compelling because the patient lacked microscopic evidence of cirrhosis, a known predisposing factor for PVT. Although lupus anticoagulant, anticardiolipin, and beta-2 glycoprotein I are well-established markers of hypercoagulability in lupus patients, factor VIII is a less frequently evaluated marker. Factor VIII is principally produced in liver sinusoidal endothelial cells (LSECs) and circulates in the blood in its inactive form bound to von Willebrand factor (vWF). Upon activation, factor VIII dissociates from vWF and participates in the coagulation cascade to generate a clot. Factor VIII is a pro-thrombotic marker that is associated with a more than 6-fold increased risk of venous thrombosis when levels exceed the 90th percentile. In addition, this appears to be a dose related association. Although factor VIII elevation is seen within the context of systemic inflammation, several studies have suggested that this rise is independent of an acute phase reaction. In this case, it is possible that her sinusoidal dilatation may have contributed to a significantly elevated factor VIII level given its synthesis in LSECs. Anticoagulation for PVT is not well studied in the absence of cirrhosis. However, there is data to support anticoagulation as a means of preventing recurrent thrombosis in patients with underlying pro-thrombotic pathology and reducing known complications associated with PVT, including gut ischemia and portal hypertension.
Conclusions: In patients with cirrhosis, PVT is a common complication that often correlates with the degree of underlying liver disease. However, in cases of PVT without cirrhosis, the etiology is established less than 75% of the time. Elevated factor VIII should be considered in this population.