Amyloidosis is a heterogeneous group of diseases in which misfolding of extracellular protein is the pathogenic factor. This process produces insoluble, toxic protein aggregates that are deposited in tissues in bundles of β-sheet fibrillar protein [1]. The most common cause of amyloidosis is clonal plasma cells in the bone marrow producing immunoglobulins that are amyloidogenic (light chain amyloidosis or AL) [2]. Hemorrhagic events, ranging from mild subcutaneous hemorrhage to life-threatening bleeding, account for a significant proportion of morbidities and mortality in AL. Bleeding tendency is frequently encountered in AL, and while mild subcutaneous hemorrhage is the most common manifestation, life-threatening bleeding has also been reported [3-6]. Acquired hemostatic abnormalities, including coagulation factor deficiencies, hyperfibrinolysis, and platelet dysfunction are the background of bleeding tendency [5, 6]. In particular, acquired deficiency of factor X is the most common coagulation factor deficiency in patients with AL, and it is postulated to occur via the adsorption of factor X to amyloid fibrils [3, 5-8]. We herein report 2 Korean patients with acquired factor X deficiency in association with AL.

Acquired factor deficiency with or without bleeding symptoms is not infrequent in AL, whereas it is rare in other types of amyloidosis. Specific coagulation factor deficiencies in AL have long been recognized and have been explained by the adsorption of coagulation factors to amyloid fibrils. Evidence showing the interaction of amyloidogenic light chains with coagulation factors and anecdotal reports of improved hemostasis after removal of amyloidotic spleen support the fact that coagulation factors bind to the amyloid fibrils [5]. Both isolated coagulation factor deficiency and combined deficiencies have been reported. Factor X deficiency has been described as the most common acquired coagulation factor deficiency, affecting up to one-third of patients with AL. Deficiencies of other coagulation factors such as II, V, VII, and IX have also been reported [5-7]. According to a previous study that evaluated a total of 368 patients with AL, 32 patients had a factor X activity below 50% of normal. Eighteen of these patients (56%) had bleeding complications, which were more severe in the 12 patients with factor X activity below 25% of normal [7]. The 2 patients with acquired factor X deficiency from AL described in the present report had no bleeding symptoms, even with the very low level of factor X activity (5%) in Patient 1. A review of the literature revealed a single case report on acquired factor X deficiency in AL patients in Korea [9]. Kim et al. [9] reported factor X deficiency in a patient with AL and nephrotic syndrome. The patient had mildly decreased factor X activity of 49% (70-120%), prolonged PT of 1.32 INR and upper normal aPTT of 39.4 sec (32-41.2 sec). Despite normal aPTT, mildly prolonged PT, and slightly decreased factor X activity, he had bleeding tendency and symptoms such as petechiae.

Previous studies reported that high-dose chemotherapy followed by autologous stem cell transplantation led to complete remission and normalization of the factor X level [7, 10, 11]. Patient 1 achieved complete remission after chemotherapy and autologous peripheral blood stem cell transplantation. The patient showed improvement of prolonged PT and aPTT (2.51 to 1.77 INR and 75.1 to 52.5 sec, respectively). However, factor X activity was still significantly decreased (12%), and the patient developed bleeding diathesis during the course of treatment. Indeed, it was reported that the baseline factor X level was not predictive of bleeding risk, and optimal management of factor X deficiency in AL is still elusive [12]. The findings in the previously reported patient [9] and the 2 patients described in the present report demonstrate the heterogeneous clinical and laboratory manifestations of factor X deficiency in Korean patients with AL.

To the best of our knowledge, this is only the second report of factor X deficiency in association with AL in Korea. Further prospective studies involving multiple institutions are needed to investigate the epidemiology and clinical implications of acquired factor X deficiency in Korean patients with AL. Appropriate coagulation workup should be conducted in patients with AL with prolonged coagulation times, and further studies are needed to obtain laboratory and clinical data to delineate the frequency and clinical implications of acquired coagulopathy in Korean patients with AL.