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Bedside Snapshot
- Key Clotting Factor: Fibrinogen is substrate for fibrin clot formation; low levels impair hemostasis
- Common in Hemorrhage: Hypofibrinogenemia common in massive hemorrhage, trauma, obstetric hemorrhage, liver failure, DIC
- Target Levels: Typically target >150-200 mg/dL in active major bleeding; higher targets (>200-300 mg/dL) in obstetric hemorrhage or trauma-associated coagulopathy
- Two Main Products: Fibrinogen concentrate (RiaSTAP) offers rapid, predictable dosing without blood typing; cryoprecipitate more widely available but variable content and transfusion risks
- Massive Transfusion Protocols: Used as part of MTPs, often guided by labs (Clauss fibrinogen) or viscoelastic testing (TEG/ROTEM FIBTEM)
- Clinical Pearl: Fibrinogen is often the first coagulation factor to fall critically low in major trauma and OB hemorrhage, so early replacement can improve clot firmness
Brand & Generic Names
- Generic Name: Fibrinogen concentrate (human)
- Brand Names: RiaSTAP (fibrinogen concentrate), and cryoprecipitate (pooled plasma product)
Medication Class
Human plasma-derived fibrinogen replacement; hemostatic agent; coagulation factor concentrate
Pharmacology
Mechanism of Action:
- Fibrinogen (factor I) is a soluble plasma glycoprotein synthesized in the liver and circulating in blood
- During hemostasis, thrombin cleaves fibrinogen into fibrin monomers, which polymerize and cross-link (via factor XIII) to form a stable fibrin clot
- Adequate fibrinogen levels are essential for clot strength and stability; low fibrinogen impairs clot formation and firmness
- Fibrinogen concentrate provides purified human fibrinogen; cryoprecipitate also provides von Willebrand factor, factor VIII, and factor XIII, which may be advantageous
Pharmacokinetics:
- Onset: Rapid increase in plasma fibrinogen levels within minutes to hours after IV administration
- Half-life: Approximately 3-4 days for fibrinogen; shorter in consumptive coagulopathy
- Dosing: Fibrinogen concentrate dosed in grams (typically 3-4 g for adults); cryoprecipitate dosed in units (typically 10 units for adults, each containing ~200-250 mg fibrinogen)
Dosing & Administration
Available Forms:
- Fibrinogen concentrate (RiaSTAP): Lyophilized vials with standardized 1 g amounts, reconstituted with sterile water and given IV
- Cryoprecipitate: Frozen plasma product, each unit typically contains 200-250 mg fibrinogen, plus vWF, factor VIII, factor XIII; ABO-compatible transfusion preferred but not always required in emergency
Dosing for Hypofibrinogenemia and Bleeding (Adult):
| Indication / Scenario | Fibrinogen Concentrate (RiaSTAP) | Cryoprecipitate | Target Fibrinogen Level |
|---|---|---|---|
| Major trauma / surgery | 3-4 g IV | 10 units IV | >150-200 mg/dL |
| Postpartum hemorrhage | 2-4 g IV | 10-15 units IV | >200-300 mg/dL per OB MTP protocols |
| Congenital fibrinogen deficiency | 50-100 mg/kg IV | 1 unit per 5-10 kg | Target hemostasis; individualized |
| DIC / liver failure with bleeding | 2-4 g IV | 10 units IV | >100-150 mg/dL; ongoing consumption may require repeated dosing |
| Empiric in massive transfusion | 3-4 g IV per protocol | 10 units IV per MTP | Combined with FFP and platelets as per protocol |
| Pediatric | 30-60 mg/kg IV | 1 unit per 5-10 kg | Individualized; consult pediatrics/hematology |
Concentrate vs Cryoprecipitate: Fibrinogen concentrate provides fast, standardized correction without volume and delays of cryoprecipitate; cryo more available but variable fibrinogen content.
Contraindications
Contraindications:
- Hypersensitivity to fibrinogen or human plasma products
- None absolute in life-threatening hemorrhage (benefits typically outweigh risks)
Major Precautions:
- Thrombosis risk: fibrinogen replacement may increase risk of VTE or arterial thrombosis, particularly in patients with underlying thrombotic tendencies
- Transmission of infectious agents: though rare with modern screening, any plasma-derived product carries theoretical risk
- Anaphylaxis or allergic reactions rare but possible
Adverse Effects
Common:
- Generally well-tolerated in acute bleeding settings
- Infusion-related reactions (fever, chills) more common with cryoprecipitate
Serious:
- Thrombotic events (VTE, MI, stroke) especially with overcorrection or underlying prothrombotic state
- Anaphylaxis or severe allergic reactions (rare)
- Transmission of infections (very rare with modern processing)
Monitoring
Laboratory Monitoring:
- Fibrinogen level (Clauss assay) before and after replacement
- Viscoelastic testing (TEG FIBTEM or ROTEM) for real-time assessment of clot firmness
- Coagulation panel (PT/INR, aPTT), hemoglobin, platelet count as part of massive transfusion monitoring
Clinical Monitoring:
- Cessation or control of bleeding
- Signs of thrombosis (chest pain, limb swelling, neurological changes)
- Transfusion reactions (fever, chills, hypotension)
Indications / Clinical Uses (ICU/Hemorrhage Focus)
- Trauma-associated coagulopathy: Major trauma with hypofibrinogenemia and active bleeding
- Massive hemorrhage: Any massive transfusion setting where fibrinogen levels fall below target
- Postpartum hemorrhage: Obstetric hemorrhage with hypofibrinogenemia (targets often higher, >200-300 mg/dL)
- Congenital fibrinogen deficiency: Afibrinogenemia or severe hypofibrinogenemia with bleeding or surgery
- DIC or liver failure with bleeding: Consumptive or synthetic hypofibrinogenemia with active hemorrhage
Clinical Pearls
First Factor to Fall: Fibrinogen is often the first coagulation factor to fall critically low in major trauma and OB hemorrhage, so early replacement can improve clot firmness.
Concentrate Advantages: Fibrinogen concentrate provides fast, standardized correction without volume and delays of cryoprecipitate; useful in massive transfusion protocols.
Viscoelastic Testing: Viscoelastic tests (low FIBTEM amplitudes on TEG/ROTEM) can identify fibrinogen deficiency even before lab fibrinogen results return, allowing earlier intervention.
MTP Integration: Work with hematology and transfusion medicine to build fibrinogen targets into massive transfusion protocols for your institution.
References
- 1. Lexicomp. (2024). Fibrinogen concentrate (human): Drug information. Wolters Kluwer.
- 2. Spahn, D. R., Bouillon, B., Cerny, V., et al. (2019). The European guideline on management of major bleeding and coagulopathy following trauma: Fifth edition. Critical Care, 23(1), 98. https://doi.org/10.1186/s13054-019-2347-3