Fatal Bleeding Due to Acquired Factor IX and X Deficiency: A Rare Complication of Hepatic AL Amyloidosis

Abstract

Purpose: Systemic AL amyloidosis is a disorder of progressive extracellular deposition of insoluble fibrils derived from λ/κ Ig light chains within various organs. Hepatic deposition (clinically silent) occurs in half of cases and liver is rarely the dominant organ. Often, bleeding in AL amyloidosis is multifactorial, including vessel fragility from amyloid infiltration, hyper fibrinolysis, platelet dysfunction and uremia. We report a case of amyloidosis with uncontrolled hemorrhage due to a severe acquired combined factors IX and X deficiency. Methods: A previously healthy 62-year-old man presented with acute abdominal pain with history of vague abdominal discomfort, fatigue, bruisability and microscopic hematuria for two months, but no findings to suggest nephrolithiasis or cancer were identified on imaging and cystoscopy. He was hemodynamically stable, exam was notable for some bruising, abdominal distention and tenderness, but no guarding or heptosplenomegaly. Results: Labs including CBC, electrolytes, LFTs, fibrinogen, thrombin time and D-dimer were normal. PT, INR, and PTT were elevated, but mixing studies were normal. Coagulation factor IX and X levels were noted to be deficient. Free λ light chain was elevated, corresponding to a monoclonal IgG λ band in the γ region, while free κ light chain and β2 microglobulin were normal. With the absence of personal and family history of liver disease, bleeding disorder and subsequent rise in alkaline phosphatase without biliary obstruction, it was concerning for an intrinsic liver disease. With acquired combined factor deficiency in the setting of MGUS, amyloidosis was considered. Liver biopsy was deferred given the concern for increased bleeding risk and hepatic rupture. He died of GI and intra-peritoneal bleeding, despite multiple transfusions including factors, FIEBA. Autopsy showed massive deposition of amyloid within liver and spleen, due to plasma cell dyscrasia with monotypic λ staining plasma cells in bone marrow accounting for 15% of nucleated cell forms. Conclusion: Delayed diagnosis is common in AL amyloidosis due to nonspecific clinical presentations, as in our case. Hepatic amyloidosis carries a poor prognosis, but has no specific effective treatment. Liver transplantation may be a life-saving procedure in selected cases of rapidly progressing hepatic amyloidosis.Figure: Liver section showing sinusoids distended by pink staining amyloid.