In what state is fibrinogen primarily deficient, such as in cases of significant bleeding, trauma, postpartum hemorrhage, or disseminated intravascular coagulation (DIC)?

Fibrinogen Deficiency in Bleeding States

Fibrinogen is primarily deficient in states of massive bleeding, major trauma, postpartum hemorrhage, and disseminated intravascular coagulation (DIC), where it becomes the first coagulation factor to critically decrease during massive blood loss. 1

Clinical States Associated with Primary Fibrinogen Deficiency

Major Trauma and Massive Bleeding

• During massive blood loss replacement, fibrinogen is the first coagulation factor to critically decrease, making it the primary deficiency in trauma-associated coagulopathy 1
• Coagulopathic civilian trauma patients typically present with fibrinogen concentrations of 0.9 g/L (interquartile range 0.5 to 1.5 g/L) in conjunction with severely impaired clot firmness 1
• In trauma patients, a maximum clot firmness (MCF) of 7 mm on thromboelastometry correlates with a fibrinogen level of approximately 2 g/L 1, 2

Postpartum Hemorrhage

• During postpartum hemorrhage, fibrinogen plasma concentration is the only coagulation parameter independently associated with progression toward severe bleeding, with a level <2 g/L having a positive predictive value of 100% for severe hemorrhage 1
• Fibrinogen levels <200 mg/dL (2 g/L) are associated with severe postpartum hemorrhage, occurring in 5% of cases with 1000 mL of bleeding and 17% with 2500 mL 3
• A high incidence of hypofibrinogenemia occurs in abruptio placentae (43.9%) and pregnancy-induced hypertension (25%) 4
• Pre-delivery fibrinogen levels can predict both adverse maternal outcomes (DIC, massive transfusion requirements) and neonatal outcomes (low Apgar scores, acidosis) in placental abruption 5

Disseminated Intravascular Coagulation (DIC)

• Hypofibrinogenemia is a usual component of complex coagulopathies associated with DIC 1
• In DIC, many clotting factors are consumed, most notably fibrinogen and platelets, resulting in consumptive coagulopathy 6
• Severe hypofibrinogenemia (<1 g/L) that persists despite fresh frozen plasma replacement characterizes decompensated DIC 7

Cardiac Surgery

• In cardiac surgical patients with significant hemorrhage and hypofibrinogenemia, fibrinogen deficiency is defined as plasma fibrinogen level <2.0 g/L by the Clauss method or clot amplitude at 10 minutes <10 mm by thromboelastometry 8

Critical Thresholds for Intervention

Treatment Thresholds

• Treatment with fibrinogen concentrate or cryoprecipitate is recommended when significant bleeding is accompanied by plasma fibrinogen levels <1.5 to 2.0 g/L 1
• The initial dose should be fibrinogen concentrate 3 to 4 g or 50 mg/kg of cryoprecipitate (approximately 15 to 20 single donor units in a 70 kg adult) 1
• For every gram of fibrinogen concentrate administered, expect a 2-mm increase in FIBTEM maximum clot firmness 2

Monitoring Considerations

• Viscoelastic methods (ROTEM/TEG) may be preferable to laboratory fibrinogen measurement for guiding replacement therapy, as they provide real-time functional assessment 1, 2
• Important caveat: The Clauss method significantly overestimates actual fibrinogen concentration in the presence of artificial colloids such as hydroxyethyl starch 1, 2

Physiological Context

• Normal plasma fibrinogen concentration ranges from 2 to 4 g/L 3
• After major surgery and trauma, fibrinogen levels naturally rise to approximately 7 g/L even without intra-operative administration 1
• Pregnancy represents a state of hypercoagulability with elevated baseline fibrinogen, making the threshold for deficiency particularly critical in obstetric hemorrhage 9