{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,3,13]],"date-time":"2026-03-13T07:11:04Z","timestamp":1773385864990,"version":"3.50.1"},"reference-count":35,"publisher":"MDPI AG","issue":"18","license":[{"start":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T00:00:00Z","timestamp":1694131200000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["JCM"],"abstract":"<jats:p>Acquired isolated factor VII (FVII) deficiency is a rare but important discovery in patients with plasma cell disorders with significant therapeutic and prognostic implications. The present analysis and review of cases reported in the literature is intended to highlight disease-related characteristics associated with this rare clotting defect, clinical manifestations and outcome, and potential underlying mechanisms, and to provide guidance on how to manage these patients in terms of prophylactic and therapeutic measures. The discovery of acquired FVII deficiency in a patient with multiple myeloma (MM) or monoclonal gammopathy of uncertain significance (MGUS) should prompt an evaluation for AL amyloidosis, particularly for amyloid hepatosplenic involvement, whenever not previously documented. Acquired FVII deficiency in patients with MM and AL amyloidosis is frequently associated with severe bleeding diathesis, also related to a number of concomitant predisposing factors, adversely affecting the outcome. The prompt institution of a rapidly acting therapy is crucial to prevent severe bleeding complications and positively impact outcome. Recombinant activated factor VII (rVIIa) may represent a useful supportive care measure, both in treating active bleeding and in the peri-procedural setting. However, further clinical experience is needed to optimize the therapeutic management of this rare disorder.<\/jats:p>","DOI":"10.3390\/jcm12185837","type":"journal-article","created":{"date-parts":[[2023,9,8]],"date-time":"2023-09-08T07:57:17Z","timestamp":1694159837000},"page":"5837","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":3,"title":["Acquired Isolated Factor VII Deficiency in Plasma Cell Dyscrasias: A Brief Presentation of Two Plasma-Cell-Leukemia-Related Cases and Review of Literature"],"prefix":"10.3390","volume":"12","author":[{"given":"Anna","family":"Furlan","sequence":"first","affiliation":[{"name":"Hematology Unit, Azienda ULSS2 Marca Trevigiana, 31100 Treviso, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Francesca","family":"Sartori","sequence":"additional","affiliation":[{"name":"Hematology Unit, Azienda ULSS2 Marca Trevigiana, 31100 Treviso, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Filippo","family":"Gherlinzoni","sequence":"additional","affiliation":[{"name":"Hematology Unit, Azienda ULSS2 Marca Trevigiana, 31100 Treviso, Italy"}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"1968","published-online":{"date-parts":[[2023,9,8]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"2536","DOI":"10.3324\/haematol.2022.280893","article-title":"Thrombosis in multiple myeloma: Risk stratification, antithrombotic prophylaxis, and management of acute events. A consensus-based position paper from an ad hoc expert panel","volume":"107","author":"Larocca","year":"2022","journal-title":"Haematologica"},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"827","DOI":"10.1056\/NEJM198104023041407","article-title":"Mechanism of Factor X Deficiency in Systemic Amyloidosis","volume":"304","author":"Furie","year":"1981","journal-title":"N. Engl. J. Med."},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"1885","DOI":"10.1182\/blood.V97.6.1885","article-title":"Acquired factor X deficiency in patients with amyloid light-chain amyloidosis: Incidence, bleeding manifestations, and response to high-dose chemotherapy","volume":"97","author":"Choufani","year":"2001","journal-title":"Blood"},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"454","DOI":"10.1046\/j.1365-2141.2000.02183.x","article-title":"Bleeding symptoms and coagulation abnormalities in 337 patients with AL-amyloidosis","volume":"110","author":"Mumford","year":"2000","journal-title":"Br. J. Haematol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"10","DOI":"10.1016\/j.hemonc.2018.05.002","article-title":"Acquired factor X deficiency in light-chain (AL) amyloidosis is rare and associated with advanced disease","volume":"12","author":"Patel","year":"2019","journal-title":"Hematol. Stem Cell Ther."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"377","DOI":"10.1016\/j.mayocp.2020.06.061","article-title":"Coagulation Abnormalities in Light Chain Amyloidosis","volume":"96","author":"Abdallah","year":"2021","journal-title":"Mayo Clin. Proc."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"689","DOI":"10.1046\/j.1365-2141.2002.03545.x","article-title":"Factor VII Deficiency","volume":"118","author":"Perry","year":"2002","journal-title":"Br. J. Haematol."},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"638","DOI":"10.1038\/clpt.1994.80","article-title":"Pharmacokinetics and pharmacodynamics of recombinant factor VIIa","volume":"55","author":"Lindley","year":"1994","journal-title":"Clin. Pharmacol. Ther."},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1182\/blood.V80.1.25.25","article-title":"Measurement of basal levels of factor VIIa in he-mophilia A and B patients","volume":"80","author":"Peter","year":"1992","journal-title":"Blood"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"705","DOI":"10.1177\/1076029615599440","article-title":"Acquired Isolated FVII Deficiency: An Underestimated and Potentially Important Laboratory Finding","volume":"22","author":"Girolami","year":"2016","journal-title":"Clin. Appl. Thromb.\/Hemost."},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"403","DOI":"10.1038\/sj.bmt.1703381","article-title":"Acquired factor VII deficiency in hematopoietic stem cell transplant recipients","volume":"29","author":"Toor","year":"2002","journal-title":"Bone Marrow Transplant."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"314","DOI":"10.2169\/naika.86.314","article-title":"Case of factor VII deficiency with systemic amyloidosis having a unique clinical course such as splenic rupture","volume":"86","author":"Uematsu","year":"1997","journal-title":"Nihon Naika Gakkai Zasshi"},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"553","DOI":"10.1097\/MBC.0000000000000023","article-title":"Clinical analysis of six cases of multiple myeloma first presenting with coagulopathy","volume":"25","author":"Hu","year":"2014","journal-title":"Blood Coagul. Fibrinolysis"},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"7235","DOI":"10.4081\/hr.2018.7235","article-title":"Acquired factor VII deficiency causing severe bleeding disorder secondary to AL amyloidosis of the liver","volume":"10","author":"Nguyen","year":"2018","journal-title":"Hematol. Rep."},{"key":"ref_15","first-page":"29","article-title":"Factor VII Deficiency in Systemic Primary Amyloidosis: A Rare Case","volume":"5","author":"Dursun","year":"2018","journal-title":"Case Rep. Intern. Med."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1177\/0036933019853167","article-title":"Acquired Factor VII deficiency\u2013A rare but important consideration","volume":"64","author":"Zaidi","year":"2019","journal-title":"Scott. Med. J."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"105","DOI":"10.1111\/j.1600-0609.1989.tb00258.x","article-title":"Successful treatment of hemorrhagic syndrome due to an acquired, combined deficiency of factors VII and X in a patient with multiple myeloma and amyloidosis","volume":"42","year":"1989","journal-title":"Eur. J. Haematol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"171","DOI":"10.1002\/ajh.21603","article-title":"Systemic AL amyloidosis with acquired factor X deficiency: A study of perioperative bleeding risk and treatment outcomes in 60 patients","volume":"85","author":"Thompson","year":"2010","journal-title":"Am. J. Hematol."},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"947","DOI":"10.1053\/j.ajkd.2006.03.036","article-title":"Amyloidosis and Bleeding: Pathophysiology, Diagnosis, and Therapy","volume":"47","author":"Sucker","year":"2006","journal-title":"Am. J. Kidney Dis."},{"key":"ref_20","doi-asserted-by":"crossref","unstructured":"Napolitano, M., Siragusa, S., and Mariani, G. (2017). Factor VII Deficiency: Clinical Phenotype, Genotype and Therapy. J. Clin. Med., 6.","DOI":"10.3390\/jcm6040038"},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1050","DOI":"10.1056\/NEJM197911083011907","article-title":"Factor X Deficiency in Primary Amyloidosis: Resolution after Splenectomy","volume":"301","author":"Greipp","year":"1979","journal-title":"N. Engl. J. Med."},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"597","DOI":"10.1001\/archinte.1983.00350030211041","article-title":"Resolution of factor X deficiency in primary amyloidosis following splenectomy","volume":"143","author":"Rosenstein","year":"1983","journal-title":"Arch. Intern. Med."},{"key":"ref_23","doi-asserted-by":"crossref","first-page":"400","DOI":"10.1016\/j.bbmt.2015.09.024","article-title":"Hepatic Veno-Occlusive Disease after Hematopoietic Stem Cell Transplantation: Risk Factors and Stratification, Prophylaxis, and Treatment","volume":"22","author":"Dalle","year":"2016","journal-title":"Biol. Blood Marrow Transplant."},{"key":"ref_24","doi-asserted-by":"crossref","first-page":"51","DOI":"10.1159\/000217434","article-title":"Acquired Isolated Factor VII Deficiency during Sepsis","volume":"27","author":"Biron","year":"1997","journal-title":"Pathophysiol. Haemost. Thromb."},{"key":"ref_25","first-page":"411","article-title":"Surgery for Scoliosis in Congenital Factor VII Deficiency","volume":"136","author":"Greene","year":"1982","journal-title":"Am. J. Dis. Child."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"79","DOI":"10.1016\/0090-3019(94)90255-0","article-title":"Uncomplicated stereotactic and open neurosurgical procedures in patients with factor VII deficiency","volume":"42","author":"Doran","year":"1994","journal-title":"Surg. Neurol."},{"key":"ref_27","unstructured":"European Medicines Agency (2023, August 04). NovoSeven, Available online: https:\/\/www.ema.europa.eu\/en\/medicines\/human\/EPAR\/novoseven."},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"347","DOI":"10.1097\/00001721-200406000-00010","article-title":"Acquired isolated factor VII deficiency associated with severe bleeding and successful treatment with recombinant FVIIa (NovoSeven)","volume":"15","author":"Mullighan","year":"2004","journal-title":"Blood Coagul. Fibrinolysis"},{"key":"ref_29","doi-asserted-by":"crossref","first-page":"1930","DOI":"10.1016\/S0016-5085(97)70013-1","article-title":"Recombinant factor VIIa corrects prothrombin time in cirrhotic patients: A preliminary study","volume":"113","author":"Bernstein","year":"1997","journal-title":"Gastroenterology"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"1074","DOI":"10.1046\/j.1365-2141.2001.02667.x","article-title":"Recombinant human factor VIIa in the management of amyloid-associated factor X deficiency","volume":"112","author":"Boggio","year":"2001","journal-title":"Br. J. Haematol."},{"key":"ref_31","first-page":"585","article-title":"Use of prothrombin complex concentrate for prophylaxis of bleeding in acquired factor X deficiency associated with light-chain amyloidosis","volume":"14","author":"Veneri","year":"2016","journal-title":"Blood Transfus."},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"358","DOI":"10.1016\/j.gassur.2003.10.014","article-title":"Successful perioperative management of factor X deficiency associated with primary amyloidosis","volume":"8","author":"Takabe","year":"2004","journal-title":"J. Gastrointest. Surg."},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"2632","DOI":"10.1182\/blood.2020009039","article-title":"Phase 1a\/b study of monoclonal antibody CAEL-101 (11-1F4) in patients with AL amyloidosis","volume":"138","author":"Edwards","year":"2021","journal-title":"Blood"},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"46","DOI":"10.1056\/NEJMoa2028631","article-title":"Daratumumab-Based Treatment for Immunoglobulin Light-Chain Amyloidosis","volume":"385","author":"Kastritis","year":"2021","journal-title":"N. Engl. J. Med."},{"key":"ref_35","doi-asserted-by":"crossref","unstructured":"Palladini, G., Milani, P., Malavasi, F., and Merlini, G. (2021). Daratumumab in the Treatment of Light-Chain (AL) Amyloidosis. Cells, 10.","DOI":"10.3390\/cells10030545"}],"container-title":["Journal of Clinical Medicine"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/18\/5837\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,10]],"date-time":"2025-10-10T20:47:13Z","timestamp":1760129233000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/2077-0383\/12\/18\/5837"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2023,9,8]]},"references-count":35,"journal-issue":{"issue":"18","published-online":{"date-parts":[[2023,9]]}},"alternative-id":["jcm12185837"],"URL":"https:\/\/doi.org\/10.3390\/jcm12185837","relation":{},"ISSN":["2077-0383"],"issn-type":[{"value":"2077-0383","type":"electronic"}],"subject":[],"published":{"date-parts":[[2023,9,8]]}}}