Fatal bleeding due to acquired factor IX and X deficiency: a rare complication of primary amyloidosis; case report and review of the literature

Amyloid light chain (AL) amyloidosis is a clonal plasma cell disorder, resulting in tissue and organ immunoglobulin deposits. Often multiple organ systems are involved, but occasionally it can impact predominantly one organ. Extensive amyloid involvement of the spleen can present with an acquired factor deficiency associated hemorrhage due to the selective clotting factor adsorption of the amyloid fibrils. Life-threatening bleeding due to deficiencies of individual or combinations of clotting factors is, fortunately, a relatively unusual problem in the context of AL amyloidosis, but presents unique diagnostic and therapeutic challenges. Though publications documenting successful resolution of amyloidosis-associated factor deficiency after splenectomy are scarce (seven cases reviewed in our study), the present lack of robust alternative therapies suggests consideration of splenectomy in the case of refractory bleeding with exhausted conservative measures in the context of biopsy-negative but clinically likely amyloidosis (findings of MGUS, splenomegaly, and unexplained acquired coagulation factor deficiencies). In the absence of tissue diagnosis, other rare causes of factor X deficiency should be considered, including liver disease, certain tumors (spindle cell thymoma, renal/adrenal carcinoma, gastric carcinoma), and mycoplasma pneumonia (a rare association with transient factor X deficiency). The low sensitivity associated with tissue biopsies in splenic predominant amyloidosis may be due to lower amyloid burden in other, more commonly biopsied tissues. As splenectomy itself can be a high-risk procedure, obtaining multiple fat aspirates looking for AL deposition in an effort to obtain tissue proven diagnosis is a prudent and low-risk diagnostic necessity.