Acquired factor VII deficiency causing severe bleeding disorder secondary to AL amyloidosis of the liver

Abstract

A 52 year-old male presented with neck pain after undergoing thyroidectomy for a goiter three weeks prior which was complicated by a neck hematoma requiring evacuation. Computed tomography (CT) scan showed a neck hematoma requiring evacuation and he received desmopressin with cessation of bleeding. Coagulation studies were normal. He returned eighteen months later with severe oral mucosal bleeding after a dental procedure and required transfusions with red blood cells, platelets, and fresh frozen plasma (FFP) in addition to desmopressin, Humate-P, aminocaproic acid, and surgical packing. A comprehensive bleeding diathesis workup was normal. He was readmitted six months later due to abdominal pain and distention and found to have massive hepatosplenomegaly on CT. A new coagulopathy workup revealed prolonged INR to 1.5, corrected prothrombin time mixing study, and a low factor VII level (29%), suggesting acquired factor VII deficiency. A transjugular liver biopsy revealed extensive involvement by ALamyloidosis- Kappa type. He then developed a large right retroperitoneal hematoma which required multiple transfusions with FFP, cryoprecipitate, aminocaproic acid, and vitamin K with slight success. Hemorrhage was subsequently stabilized with recombinant factor VIIa administered every four hours which corresponded with correction of factor VII levels and PT and eventual cessation hemorrhage. Acquired factor VII deficiency causing severe coagulopathy was attributed to hepatic amyloidosis ALkappa subtype. We started treatment with bortezomib, dexamethasone, and cyclophosphamide, however, the patient succumbed to uncontrolled hemorrhage. Acquired factor VII deficiency is extremely rare and to our knowledge, this is the only known case of factor VII deficiency secondary to amyloidosis involving the liver.

Spontaneous hemorrhage after external ventricular drain placement in the setting of low factor VII secondary to liver cirrhosis

“…[ 9 , 16 , 26 , 27 ] Because several hemostatic factors are produced in the liver, liver dysfunction can result in several clotting factor deficiencies including II, V, VII, IX, X, XI, Protein C, and Protein S.[ 10 , 28 ] Factor VII levels tend to decrease earlier than the other Vitamin K-dependent factors due to its extremely short half-life. [ 17 ] These lead to elevated PT and INR. Elevations in INR may not actually correlate with bleeding risk, and attempts to normalize INR with IV Vitamin K or fresh frozen plasma may not be sufficient to mitigate bleeding risk.…”

Acquired Isolated Factor VII Deficiency in Plasma Cell Dyscrasias: A Brief Presentation of Two Plasma-Cell-Leukemia-Related Cases and Review of Literature

“…Seven cases of acquired isolated FVII deficiency associated with plasma cell disorders (MM/PCL and/or AL amyloidosis) are reported in the literature [ 12 , 13 , 14 , 15 , 16 ], including the two personal cases here described, and one patient with combined FVII and FX deficiency [ 17 ]. The analysis also includes a patient taken from our case records with AL amyloidosis and isolated PT prolongation, whose abnormality resolved immediately after splenectomy for splenic rupture, but who was not specifically tested for FVII activity.…”

“…The use of recombinant activated factor VII (rFVIIa) has been reported to be of value in patients with plasma cell disorders and acquired FVII deficiency who are actively bleeding [ 14 , 16 ]. rFVIIa is indicated for use in the congenital deficiency of factor VII and acquired hemophilia, and patients with acquired inhibitors to hemophilia A and B replacement products [ 27 ].…”

“…The choice of the therapeutic regimen should favor combinations with limited hematological toxicity, since thrombocytopenia may exacerbate the bleeding tendency. The failure to attain a hematologic response and, thus, to prevent new amyloid deposition in tissues translated into persistent and uncontrolled bleeding diathesis with fatal outcomes in two cases, including our personal case of pPCL [ 14 ]. On the other hand, in patients responsive to specific treatment, the time for FVII to recover to normal levels was reported to be 30–46 days, concomitant with therapeutic response [ 13 , 16 ] in two patients diagnosed with MM, and with no reported significant hepatosplenomegaly or documented amyloidosis.…”

Acute Myelogenous Leukemia With Trisomy 8 and Concomitant Acquired Factor VII Deficiency

“…1 Acquired factor VII deficiency has been reported in 31 cases and has been described associated with malignancy, infections, sepsis, postoperatively, aplastic anemia, amyloidosis, autoantibodies to factor VII, and in association with bone marrow transplantation. 2-8 There are only 2 prior reported cases of acquired factor VII deficiency in association with AML described in the literature. 2,3 We report the third case of AML associated with acquired factor VII deficiency and the second case of AML associated with trisomy 8 cytogenetic abnormality.…”