Successful perioperative use of prothrombin complex concentrate in the treatment of acquired factor X deficiency in the setting of systemic light‐chain (AL) amyloidosis
Authors: Anya Litvak, Anita Kumar, Richard J. Wong, Larry Smith, Hani Hassou, Gerald Soff
Journal: American Journal of Hematology (2014)

To the Editor: Acquired factor X (fX) deficiency is a rare, but well recognized complication of amyloidosis, first described in 1961 1. The fX deficiency varies from severe (<10%) to mild (<50%), although there is no consensus on the correlation of bleeding risk with degree of fX deficiency 2. fX binds to amyloid fibrils, which may contribute to the deficiency 3. Literature is limited to guide hemostatic therapy. A review of 60 patients from the Mayo Clinic included 112 invasive procedures, 12 of which were complicated by bleeding, with one fatality 2. A range of modalities, including recombinant fVIIa, plasma, aminocaproic acid, and plasma exchange were used for major procedures 2. Individual cases have been reported who received infusions of fX containing products, with poor recovery and short survival of fX 4-6. We report a 52-year-old woman with AL amyloidosis and acquired fX deficiency who received a three-factor prothrombin complex concentrate (PCC, Bebulin®) perioperatively for thyroidectomy, resulting in adequate hemostasis. She initially presented with nephrotic syndrome and IgG/lambda monoclonal gammopathy. She underwent autologous stem cell transplant (ASCT) in 1999. She required renal transplantation in 2004 despite the absence of clear hematologic relapse. She underwent a second ASCT in 2010, after hematologic relapse but remained with measurable, but low disease activity. In 2013, a thyroid nodule was found and biopsy revealed papillary carcinoma. Evaluation of elevated preoperative activated partial thromboplastin time (37.1″) and prothrombin time (14.7″) was significant for fX deficiency (13%). Factors II, V, VII, VIII, and IX were normal. Mixing studies showed no evidence of an inhibitor. She had no history of spontaneous bleeding. Because of the reported poor response to infused fX, 4-6, and the critical site of the surgery, we wanted to determine response to the PCC before thyroidectomy. She received a test dose of 50 IU/kg (5,000 IU). Her fX level increased from 19 to 37%, and persisted above 30% for 22 hr. This was felt to be a sufficient response for her upcoming thyroidectomy. For surgery, PCC 50 IU/kg was administered at 0 hr (preop), 8 hr, and 14 hr, and 25 IU/kg at 42 hr. Surgery was from 4.5 to 7.5 hr after the initial dose of PCC. Adequate hemostasis was achieved during surgery and no major complications occurred. For each PCC infusion (Fig. 1), fX increased by approximately half of the fIX increase, although the fX:fIX ratio in Bebulin® is >1:1. Half-life determination is not possible from our data, but there was no evidence of rapid clearance, as judged by levels persistently above baseline from 14 through 42 hr. This indicates reduced recovery, but preserved survival of infused fX. Factor X and IX levels following prothrombin complex concentrate infusion. Infusions marked with vertical arrows. Time of surgery marked with orange bar. Our patient illustrates that PCC may be successfully used to increase fX levels in amyloidosis, differing from prior reports. 4-6 Her adequate response may be related to her low-level of disease at the time. If one has the opportunity to perform a test dose prior to planned invasive procedure, PCC may be a safe and effective hemostatic therapy for some patients with fX deficiency associated with amyloidosis. Anya Litvak,1 Anita Kumar,1 Richard J. Wong,2 Larry Smith,3 Hani Hassoun,1 and Gerald A. Soff1* 1Department of Medicine, Memorial Sloan-Kettering Cancer Center, Hematology Service, New York, New York 2Department of Surgery, Memorial Sloan-Kettering Cancer Center, Hematology Service, New York, New York 3Department of Laboratory Medicine, Memorial Sloan-Kettering Cancer Center, Hematology Service, New York, New York