title: Severe Thrombotic Complications in Congenital Afibrinogenemia: A Pathophysiological and Management Dilemma.
abstract: Congenital afibrinogenemia (CA) is a disease characterized by a complex pathophysiology, involving both the procoagulant and fibrinolytic systems, as well as platelet activity. Although hemorrhagic diathesis represents the most frequent clinical presentation of this disorder, severe thrombotic events can occur. It is not yet clear if these events are strictly related to the disease itself or to the fibrinogen replacement therapy. Different hypotheses on the pathophysiological mechanisms have been proposed. It is well known that fibrinogen/fibrin has a role in the downregulation of thrombin generation in plasma. In the absence of circulating fibrinogen, this "antithrombin" activity is missing and plasma thrombin levels rise; this excess of thrombin could promote clotting of the infused fibrinogen, initiating the thrombotic process. Furthermore, the observation of impaired plasmin generation in the plasma of CA patients has raised the hypothesis of a fibrinolytic system deficiency. We report the case of a CA male patient who at the age of 36 years experienced an arterial thrombosis in his left lower limb. Despite an aggressive medical treatment with low-molecular-weight heparin, fibrinolytic and antiplatelet agents, the arterial thrombosis progressed to the obstruction of the whole left arterial district and the patient underwent the amputation of the left lower limb. This case demonstrates the complexity of pathophysiology and clinical management of a "so-called" bleeding disorder as CA.
authors.affiliation: Hematology Division, Department of Cellular Biotechnology and Hematology, Sapienza University of Rome, Rome, Italy.
authors.forename: Cristina
authors.initials: C
authors.lastname: Santoro
authors.affiliation: Hematology Division, Department of Cellular Biotechnology and Hematology, Sapienza University of Rome, Rome, Italy.
authors.forename: Fulvio
authors.initials: F
authors.lastname: Massaro
authors.affiliation: Department of Vascular Surgery, Sapienza University of Rome, Rome, Italy.
authors.forename: Salvatore
authors.initials: S
authors.lastname: Venosi
authors.affiliation: Hematology Division, Department of Cellular Biotechnology and Hematology, Sapienza University of Rome, Rome, Italy.
authors.forename: Saveria
authors.initials: S
authors.lastname: Capria
authors.affiliation: Hematology Division, Department of Cellular Biotechnology and Hematology, Sapienza University of Rome, Rome, Italy.
authors.forename: Erminia
authors.initials: E
authors.lastname: Baldacci
authors.affiliation: Hematology Division, Department of Cellular Biotechnology and Hematology, Sapienza University of Rome, Rome, Italy.
authors.forename: Roberto
authors.initials: R
authors.lastname: Foà
authors.affiliation: Hematology Division, Department of Cellular Biotechnology and Hematology, Sapienza University of Rome, Rome, Italy.
authors.forename: Maria Gabriella
authors.initials: MG
authors.lastname: Mazzucconi
mesh_terms: D000347:Afibrinogenemia / Q000097:blood / Q000150:complications / Q000188:drug therapy; D005260:Female; D005343:Fibrinolytic Agents / Q000627:therapeutic use*; D006801:Humans; D008297:Male; D010975:Platelet Aggregation Inhibitors / Q000627:therapeutic use*; D012720:Severity of Illness Index; D013917:Thrombin / Q000378:metabolism; D013927:Thrombosis / Q000097:blood / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology
chemical_list: D005343:Fibrinolytic Agents; D010975:Platelet Aggregation Inhibitors; D013917:Thrombin