In an inpatient with active bleeding, major surgery, trauma, or massive transfusion, when should fibrinogen be measured and how should a fibrinogen level below 150 mg/dL be corrected (including preferred products, dosing, and target levels)?

Fibrinogen Management in Bleeding Inpatients

In actively bleeding inpatients with trauma, major surgery, or massive transfusion, measure fibrinogen immediately upon presentation and repeat frequently, then replace with fibrinogen concentrate 3-4 g (or cryoprecipitate 50 mg/kg) when levels fall below 150 mg/dL (1.5 g/L), targeting levels of 150-200 mg/dL (1.5-2.0 g/L). 1

When to Measure Fibrinogen

Immediate Measurement Indications

• Measure fibrinogen on arrival in all patients with active bleeding, major trauma, major surgery, or anticipated massive transfusion 2, 3
• Fibrinogen is the first coagulation factor to reach critically low levels during massive hemorrhage, often before PT/INR or aPTT become abnormal 2, 4
• Conventional coagulation screens (INR, aPTT) only monitor initiation phase and may appear normal while fibrinogen is critically depleted 2

Repeat Measurement Strategy

• Repeat measurements frequently during ongoing resuscitation, as fibrinogen depletes progressively with blood loss, dilution, and consumption 3, 4
• Consider continuous monitoring with viscoelastic testing (ROTEM/FIBTEM or TEG functional fibrinogen) for real-time assessment, providing results 30-60 minutes faster than laboratory testing 2, 5

Critical Thresholds

Treatment Threshold: <150 mg/dL (1.5 g/L)

• Begin replacement when fibrinogen falls below 150 mg/dL (1.5 g/L) in patients with significant bleeding 1, 3
• Levels below 200 mg/dL (2.0 g/L) have 100% positive predictive value for progression to severe hemorrhage 6, 2
• At fibrinogen levels of 90 mg/dL (0.9 g/L), patients are overtly coagulopathic with severely impaired clot formation 1

Target Level: 150-200 mg/dL (1.5-2.0 g/L)

• Target fibrinogen levels of 150-200 mg/dL (1.5-2.0 g/L) during active bleeding 1, 7
• This target correlates with Maximum Clot Firmness of 7 mm on ROTEM, representing adequate clot strength 1, 2

Replacement Products and Dosing

First-Line: Fibrinogen Concentrate

• Administer 3-4 grams of fibrinogen concentrate as initial dose 1, 6
• This typically raises fibrinogen levels from approximately 140 mg/dL to 240 mg/dL 1
• Fibrinogen concentrate is preferred over cryoprecipitate when available due to standardized dosing, viral inactivation, and rapid reconstitution 1

Alternative: Cryoprecipitate

• Administer 50 mg/kg of cryoprecipitate (approximately 15-20 units in a 70 kg adult) if fibrinogen concentrate unavailable 1, 6
• Each unit of cryoprecipitate contains approximately 200-250 mg of fibrinogen 1

Repeat Dosing

• Guide repeat doses by repeat fibrinogen measurements or viscoelastic monitoring every 30-60 minutes during ongoing bleeding 1
• Continue replacement until bleeding controlled and fibrinogen maintained above 150 mg/dL 1

Measurement Methods

Laboratory Testing: Clauss Method

• The Clauss method is the preferred laboratory technique for measuring fibrinogen concentration 1, 7
• Critical pitfall: Hydroxyethyl starch (HES) and other artificial colloids cause significant overestimation of fibrinogen by Clauss method 1, 2, 7
• Laboratory results typically require 45-90 minutes, delaying treatment decisions 2

Point-of-Care: Viscoelastic Testing

• ROTEM FIBTEM or TEG functional fibrinogen provide superior real-time assessment of fibrinogen's functional contribution to clot formation 1, 2, 5
• FIBTEM Maximum Clot Firmness (MCF) ≤7 mm correlates with fibrinogen approximately 200 mg/dL and indicates need for replacement 1, 2
• Viscoelastic methods avoid the overestimation problem with colloids and provide results in 10-15 minutes 2, 5
• ROTEM FIBTEM shows better correlation with Clauss method (R=0.27-0.94) than TEG functional fibrinogen (R=0-0.9) 5

Clinical Algorithm

Step 1: Identify High-Risk Patient

• Active bleeding with trauma, major surgery, or massive transfusion 1, 3

Step 2: Immediate Measurement

• Draw fibrinogen level (Clauss method) AND initiate viscoelastic testing if available 2, 5
• Do not wait for results before starting resuscitation 3

Step 3: Interpret Results

• If fibrinogen <150 mg/dL OR FIBTEM MCF ≤7 mm: Proceed to replacement 1, 2
• If fibrinogen 150-200 mg/dL with ongoing bleeding: Consider replacement and recheck in 30 minutes 1, 3
• If fibrinogen >200 mg/dL: Continue monitoring, no replacement needed unless bleeding worsens 7

Step 4: Administer Replacement

• Give fibrinogen concentrate 3-4 g IV (preferred) 1, 6
• OR cryoprecipitate 50 mg/kg (15-20 units in 70 kg adult) 1, 6

Step 5: Reassess

• Recheck fibrinogen or FIBTEM in 30-60 minutes 1
• Repeat dosing as needed to maintain target 150-200 mg/dL 1

Common Pitfalls and How to Avoid Them

Pitfall 1: Relying Only on PT/INR and aPTT

• PT/INR and aPTT remain normal while fibrinogen is critically depleted because they only assess initiation phase 2
• Solution: Always measure fibrinogen specifically in bleeding patients, not just routine coagulation panel 2, 3

Pitfall 2: Delayed Recognition

• Fibrinogen becomes critically low before other coagulation factors, often while PT/INR still normal 2, 4
• Solution: Measure fibrinogen immediately on presentation, not after other interventions fail 3, 4

Pitfall 3: Colloid Interference

• HES and other artificial colloids cause significant overestimation of fibrinogen by Clauss method 1, 2, 7
• Solution: Use viscoelastic testing (ROTEM/TEG) in patients receiving colloids, or interpret Clauss results cautiously 1, 2

Pitfall 4: Transfusing Platelets Instead of Fibrinogen

• Low clot strength on TEG/ROTEM is often attributed to platelets, but fibrinogen contributes 30% of clot strength and correlates more strongly (R=0.80) than platelet count (R=0.51) 8
• Solution: Use functional fibrinogen assays to differentiate fibrinogen vs platelet contribution before transfusing platelets 8

Pitfall 5: Inadequate Dosing

• Underdosing fibrinogen fails to achieve target levels, prolonging coagulopathy 1
• Solution: Use weight-based dosing (3-4 g or 50 mg/kg) and verify response with repeat measurement 1, 6

Special Populations

Trauma Patients

• Fibrinogen depletion occurs through blood loss, dilution, consumption, hyperfibrinolysis, hypothermia, and acidosis 3, 4
• Early fibrinogen substitution is associated with improved survival in combat-related trauma 1
• Algorithm-based fibrinogen replacement reduces mortality, transfusion needs, and costs 9

Surgical Patients

• Preoperative fibrinogen levels inversely correlate with blood loss and transfusion needs 1
• Best evidence for algorithm-based fibrinogen replacement exists in cardiac surgery, followed by liver transplantation 9
• Intraoperative fibrinogen administration (45 mg/kg) reduces postoperative transfusion requirements 1

Massive Transfusion

• Fibrinogen reaches critical levels during massive blood loss replacement before other factors 1, 4
• Goal-directed fibrinogen replacement reduces allogeneic blood product transfusion 1, 9

Monitoring Response to Treatment

Expected Response

• Fibrinogen concentrate 3-4 g typically increases levels by approximately 100 mg/dL (from 140 to 240 mg/dL) 1
• Peak levels occur immediately after infusion, then decline over 24 hours as part of ongoing consumption and acute phase response 1

Thrombotic Risk

• Fibrinogen levels naturally rise to approximately 700 mg/dL after major surgery and trauma as part of acute phase response 1
• Intraoperative fibrinogen administration results in higher early postoperative levels, but by 24 hours levels are identical to patients without administration 1
• No evidence of increased venous thromboembolism risk from therapeutic fibrinogen replacement 1