# LIST OF ABBREVIATIONS
Fibrinogen replacement in the setting of acquired hypofibrinogenemia plays an important role in management of massive bleeding post cardiac surgery, trauma and obstetrical hemorrhage among others. However, there continues to be a lack of evidence firmly guiding fibrinogen replacement product choice as well as ongoing uncertainties as to the optimal target and dose.
Fibrinogen concentrate (FC), plasma (including both frozen plasma (FP) and fresh frozen plasma (FFP)), and cryoprecipitate are currently used to treat acquired hypofibrinogenemia.
There are two FC products currently available in Canada: RiaSTAP (CSL Behring) and FIBRYGA (Octapharma) (1,2). Both are licensed for treatment of acute bleeding episodes and perioperative prophylaxis in adult and pediatric patients with congenital afibrinogenemia and hypofibrinogenemia. FIBRYGA is also licensed as a complementary therapy during the management of uncontrolled severe bleeding in patients with acquired fibrinogen deficiency during surgical interventions (2). The use of fibrinogen concentrates in acquired hypofibrinogenemia is supported by studies, including a high-quality randomized trial in bleeding patients undergoing cardiovascular surgery (3).
According to data provided by the manufacturers, in addition to fibrinogen, fibrinogen concentrates contain trace amounts of the other substances, such as FXIII and fibronectin. These substances are not listed as active ingredients in the product monograph and the concentrations in the final product may vary. As such, their clinical relevance, if any, is unknown. Furthermore, both fibrinogen concentrates appear to have similar efficacy in improving clot firmness in a dilutional hypofibrinogenemia model in vitro (4).
The major difference between these products is related to the product storage: FIBRYGA is stored at room temperature for up to 36 months whereas RiaSTAP is stored in a refrigerator for up to 60 months (1,2).
Plasma is indicated for replacement of multiple clotting factor deficiencies and should not be used solely for fibrinogen replacement. FP and FFP are considered equivalent in terms of clinical effectiveness. The additional risks of plasma transfusion include transfusion associated circulatory overload (TACO), transfusion related acute lung injury (TRALI) and allergic reactions.
Cryoprecipitate is prepared from slowly thawed FP and is indicated for replacement of fibrinogen in patients with congenital and acquired fibrinogen deficiency (quantitative or qualitative) in the setting of bleeding or an increased risk of bleeding (ex. impending major surgery).
Currently, there is no evidence of superiority of one fibrinogen replacement source over the others in terms of clinical effectiveness. However, fibrinogen concentrate is pathogen inactivated and has a preferred safety profile in terms of transmissible disease risk as compared to frozen plasma and cryoprecipitate. Furthermore, fibrinogen concentrate offers many logistical advantages, including a more precise fibrinogen dose, simpler preparation (without need for thawing and with capability for bedside reconstitution), and efficiency of administration.

# SECTION 2.0: FIBRINOGEN CONCENTRATE DOSING
Fibrinogen content of the above-mentioned products is as follows (1,2,5-7):
- FC = 0.9 -1. In a bleeding obstetrical patient with acquired hypofibrinogenemia, fibrinogen replacement is indicated when fibrinogen level is less than 2.0 g/L (8,9). In a massively bleeding or preoperative patient with acquired hypofibrinogenemia, fibrinogen should be replaced when the level is less than 1.5 g/L (10-12).
Options for fibrinogen replacement in adult patients with acquired hypofibrinogenemia include the following:  FC: 2-4 g  Cryoprecipitate: 10 units (1 unit/10 kg)  FP or FFP: 3-4 units (10-15 mL/kg)
In neonates and pediatric patients, it is recommended to consult with the product monograph and a specialist with expertise in managing pediatric/neonatal coagulopathy prior to administration of fibrinogen concentrates. In published studies (13)(14) of acquired hypofibrinogenemia in neonatal or pediatric populations, fibrinogen concentrate dosing has ranged between 30-60 mg/kg.
Following administration of a fibrinogen replacement therapy, repeat bloodwork should be completed within 60 minutes to assess the degree of fibrinogen increment. The expected increment is approximately 0.5-1.0 g/L (3,7,14).