{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,13]],"date-time":"2026-10-13T20:28:16Z","timestamp":1791923296387,"version":"4.3.4"},"reference-count":38,"publisher":"Georg Thieme Verlag KG","issue":"02","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Semin Thromb Hemost"],"published-print":{"date-parts":[[2025,3]]},"abstract":"<jats:title>Abstract<\/jats:title><jats:p>Rare bleeding disorders (RBDs) represent 3 to 5% of congenital bleeding disorders and are primarily inherited in an autosomal recessive manner, with increased prevalence in consanguineous populations. Clinically, RBDs can be accompanied by mild to severe bleeding episodes, often assessed using bleeding assessment tools (BATs) such as the International Society on Thrombosis and Hemostasis (ISTH)-BAT. However, the correlation between bleeding severity and coagulation factor activity levels remains inconsistent. This systematic review investigates this relationship to enhance understanding and improve management strategies for patients with RBD. This review adhered to Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines and was registered with the International Prospective Register for Systematic Reviews (PROSPERO) (CRD42024504537). Using the PICO (Population, Intervention, Comparator, and Outcomes) framework, the study focused on RBD patients to explore the correlation between coagulation factor activity levels and bleeding severity. A comprehensive search was conducted across PubMed, Scopus, and Web of Science until April 1, 2024, with data extracted on bleeding severity, phenotype, and coagulation factor activity levels. The analysis highlights complex and often inconsistent relationships between coagulation factor levels and the severity of bleeding. In cases of fibrinogen deficiency, three out of four studies (n\u2009=\u200973 of 111 cases, 66%) demonstrated a moderate to strong correlation between fibrinogen levels and bleeding severity. In prothrombin deficiency, one of two studies (n\u2009=\u200916 of 29 cases, 55%) found a strong correlation between FII levels and bleeding severity. Four of six studies (n\u2009=\u2009106 of 139 cases, 76%) in FV deficiency found a weak or no correlation between factor activity and bleeding severity. In combined FV and FVIII deficiency, two of three studies (n\u2009=\u200926 of 60 cases, 43%) found a significant correlation between factor activity and bleeding severity. In FVII deficiency, four (of nine) studies with a study population of 325 patients (65%) found a weak correlation between factor activity and severity of bleeding. Almost all studies (five of six studies, n\u2009=\u2009114 of 118 patients, 97%) in FX deficiency revealed a strong correlation between FX levels and bleeding severity. In FXI deficiency, most studies (five of seven studies, n\u2009=\u2009254 patients, 93%) found a weak or no correlation between factor activity and bleeding severity or symptoms. For FXIII deficiency, there was a moderate to strong correlation between FXIII activity and bleeding severity in all three studies (n\u2009=\u200961 patients). In conclusion, despite current controversies, this review highlights a moderate or strong correlation between factor activity and bleeding severity in fibrinogen, FX, and FXIII deficiencies, but no correlation or weak correlation for FV, FVII, and FXI deficiencies. Further prospective studies with standardized BATs on a large number of patients are needed to better understand these relationships and optimize patient management.<\/jats:p>","DOI":"10.1055\/s-0044-1800832","type":"journal-article","created":{"date-parts":[[2024,12,6]],"date-time":"2024-12-06T01:03:02Z","timestamp":1733446982000},"page":"180-195","source":"Crossref","is-referenced-by-count":8,"title":["Correlation between Phenotype and Coagulation Factor Activity Level in Rare Bleeding Disorders: A Systematic Review"],"prefix":"10.1055","volume":"51","author":[{"given":"Behnaz","family":"Tavasoli","sequence":"additional","affiliation":[{"name":"Department of Hematology and Blood Transfusion, School of Allied Medicine, Bushehr University of Medical Sciences, Bushehr, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alireza","family":"Zangooie","sequence":"additional","affiliation":[{"name":"Student Research Committee, Birjand University of Medical Sciences, Birjand, Iran"},{"name":"Cellular and Molecular Research Center, Birjand University of Medical Sciences, Birjand, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Seyed Mehrab","family":"Safdari","sequence":"additional","affiliation":[{"name":"Department of Hematology and Blood Banking, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Taraneh","family":"Hoseinnezhad","sequence":"additional","affiliation":[{"name":"Department of Hematology and Blood Transfusion, School of Allied Medicine, Bushehr University of Medical Sciences, Bushehr, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashkan","family":"Shabannezhad","sequence":"additional","affiliation":[{"name":"Department of Hematology and Blood Banking, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Amirreza","family":"Alikhani","sequence":"additional","affiliation":[{"name":"Department of Hematology and Blood Banking, School of Allied Medical Sciences, Iran University of Medical Sciences, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zahra","family":"Salehi","sequence":"additional","affiliation":[{"name":"Hematology, Oncology and Stem Cell Transplantation Research Center, Research Institute for Oncology, Hematology and Cell Therapy, Tehran University of Medical Sciences, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Akbar","family":"Dorgalaleh","sequence":"additional","affiliation":[{"name":"Hamin Pazhuhan Tis Institute, Tehran, Iran"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"194","published-online":{"date-parts":[[2024,12,5]]},"reference":[{"key":"ref1","doi-asserted-by":"crossref","first-page":"101029","DOI":"10.1016\/j.blre.2022.101029","article-title":"Molecular basis of rare congenital bleeding disorders","volume":"59","author":"A Dorgalaleh","year":"2023","journal-title":"Blood Rev"},{"issue":"08","key":"ref2","doi-asserted-by":"crossref","first-page":"811","DOI":"10.1080\/17474086.2020.1796622","article-title":"Pharmacological management of rare coagulation factor deficiencies besides hemophilia","volume":"13","author":"A Dorgalaleh","year":"2020","journal-title":"Expert Rev Hematol"},{"issue":"03","key":"ref3","first-page":"250","article-title":"Phenotype report on patients with congenital Factor V deficiency in Southern Iran: recent ten years' experience","volume":"34","author":"M M Safarpour","year":"2017","journal-title":"Turk J 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