title: Thromboembolic events in patients with severe inherited fibrinogen deficiency.
abstract: Inherited afibrinogenemia and hypofibrinogenemia are rare bleeding disorders characterized by markedly reduced levels of fibrinogen in blood. Thrombotic complications in these disorders have been rarely described. We performed a multicenter retrospective study and reviewed the occurrence of thrombotic complications among patients with inherited fibrinogen deficiency. Cases were identified during a review of medical records of all patients with inherited fibrinogen deficiency followed at three different university hospitals in Israel. Nine patients were included in this study: five were afibrinogenemic and four hypofibrinogenemic. There were seven thrombotic events, mostly venous, that occurred in four out of nine patients (44 %). All thrombotic events occurred in afibrinogenemic patients. Mean age at the time of thrombosis was 45 (range 28-61) years. Thrombophilic evaluation performed was negative in all cases. At the time of thrombosis in five out of seven (71.4 %) events, fibrinogen replacement therapy was concurrently given. Therapeutic approach was different among patients ranging from supportive therapy alone, antiplatelet agents and anticoagulant therapy with the concurrent administration of fibrinogen replacement therapy. This study discloses a high rate of thrombosis in patients with afibrinogenemia. Events were both venous and arterial and may be recurrent. Management is highly problematic due to the precarious balance between bleeding and thrombotic risk in these patients. Fibrinogen replacement therapy should be cautiously used in these patients as most thrombotic events followed the administration of fibrinogen replacement therapy. Larger cohorts are warranted to better characterize the best management strategy in these paradoxical events.
authors.affiliation: Department of Hematology, Hadassah-Hebrew University Medical Center, POB 12000, 91120, Jerusalem, Israel.
authors.forename: Amihai
authors.initials: A
authors.lastname: Rottenstreich
authors.affiliation: Amalia Biron Research Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Avigal
authors.initials: A
authors.lastname: Lask
authors.affiliation: Hematology-Oncology Unit, Bnei Zion Medical Center, Haifa, Israel.|Rappaport Faculty of Medicine, Technion, Haifa, Israel.
authors.forename: Lilliana
authors.initials: L
authors.lastname: Schliamser
authors.affiliation: Amalia Biron Research Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Ariella
authors.initials: A
authors.lastname: Zivelin
authors.affiliation: Amalia Biron Research Institute of Thrombosis and Hemostasis, Sheba Medical Center, Tel Hashomer and Sackler Faculty of Medicine, Tel Aviv University, Tel Aviv, Israel.
authors.forename: Uri
authors.initials: U
authors.lastname: Seligsohn
authors.affiliation: Department of Hematology, Hadassah-Hebrew University Medical Center, POB 12000, 91120, Jerusalem, Israel. ykalish@gmail.com.
authors.forename: Yosef
authors.identifier: http://orcid.org/0000-0001-9533-5775
authors.initials: Y
authors.lastname: Kalish
mesh_terms: D000328:Adult; D000347:Afibrinogenemia / Q000150:complications / Q000151:congenital / Q000188:drug therapy / Q000235:genetics*; D005340:Fibrinogen / Q000009:adverse effects / Q000627:therapeutic use; D006470:Hemorrhage / Q000139:chemically induced; D006801:Humans; D008875:Middle Aged; D012189:Retrospective Studies; D013923:Thromboembolism / Q000209:etiology*; D013927:Thrombosis / Q000209:etiology
chemical_list: D005340:Fibrinogen
keywords: Afibrinogenemia; Deep vein thrombosis; Fibrinogen replacement therapy; Myocardial infarction; Renal vein thrombosis; Thrombosis