When is cryoprecipitate (cryo precipitate) recommended for use in patients?

Cryoprecipitate: Clinical Indications and Administration

Primary Indication

Cryoprecipitate is recommended for treating acquired hypofibrinogenemia in patients with clinically significant bleeding when fibrinogen levels fall below 1.5 g/L (or below 2.0 g/L in obstetric hemorrhage). 1, 2

Specific Clinical Indications

Major Hemorrhage Settings

• Major trauma with active bleeding: Administer cryoprecipitate when fibrinogen drops below 1.5 g/L during massive transfusion 1, 2
• Obstetric hemorrhage: Maintain fibrinogen above 2.0 g/L (higher threshold than other bleeding scenarios) 1, 2
• Cardiac surgical bleeding: Use when fibrinogen is depleted during massive blood loss 1, 2
• Massive transfusion protocols: Fibrinogen is the first coagulation factor to critically decrease during massive blood loss replacement 1

Other Bleeding Scenarios

• Disseminated intravascular coagulation (DIC): Administer when fibrinogen falls below 1.0 g/L 1, 2
• Advanced liver disease with bleeding: Maintain fibrinogen above 1.0 g/L 1, 2
• Combined liver and renal failure with active bleeding 1, 2
• Bleeding associated with thrombolytic therapy 1, 2

Prophylactic Use (Limited)

• Pre-procedure in high-risk patients: Consider when fibrinogen is below 1.0 g/L and there is significant bleeding risk, factoring in personal/family bleeding history and the invasiveness of the planned procedure 1

Congenital Disorders (When Specific Products Unavailable)

• Congenital fibrinogen deficiencies: Use when fibrinogen concentrate is not available 1, 2
• Von Willebrand disease (types 1 and 2A): Only if no response to or availability of desmopressin or VWF/FVIII concentrate 2
• Von Willebrand disease (types 2B, 2M, 2N, and 3): If specific VWF/FVIII concentrate is unavailable 2

When NOT to Use Cryoprecipitate

• Fibrinogen above 1.5 g/L in non-pregnant patients: Transfusion is rarely indicated above this threshold 2
• Routine volume replacement: Should never be used solely for circulatory volume expansion 1
• Prophylactic correction of coagulation tests in stable, non-bleeding critically ill patients: Abnormal PT/APTT are poor predictors of bleeding in hemodynamically stable patients 1

Dosing and Administration

Standard Adult Dosing

• Initial dose: Two pools of cryoprecipitate (each pool contains 5 units = approximately 2 g fibrinogen total per pool, so 4 g total) 1, 2, 3
• Alternative dosing: 50 mg/kg, which equals approximately 15-20 single donor units in a 70 kg adult 1
• Each single unit contains: 400-450 mg of fibrinogen 1, 3

Administration Technique

• Transfuse using: Standard blood giving set with 170-200 μm filter 1, 2, 3
• Infusion rate: 10-20 mL/kg/hour 3
• Time limit after thawing: Must be used within 4 hours at ambient temperature; do not refrigerate once thawed 1, 3

Monitoring and Repeat Dosing

• Monitor fibrinogen levels: Guide repeat doses by laboratory assessment to maintain target levels 1
• Target levels during active bleeding: Maintain fibrinogen >1.5 g/L (general), >2.0 g/L (obstetric hemorrhage), >1.0 g/L (DIC, advanced liver disease) 1, 2

Important Clinical Considerations

Evidence Quality and Recent Trials

The CRYOSTAT-2 trial (2023), the largest randomized controlled trial to date with 1,604 trauma patients, found that early empirical high-dose cryoprecipitate (6 g fibrinogen equivalent) did not improve 28-day mortality compared to standard care (26.1% vs 25.3%, p=0.74) 4. This suggests that routine early empirical administration without documented hypofibrinogenemia is not beneficial. The key takeaway: cryoprecipitate should be administered based on documented low fibrinogen levels, not empirically in all bleeding patients.

Thromboelastometry Guidance

• Viscoelastic monitoring: Can guide cryoprecipitate administration when functional fibrinogen deficit is demonstrated, even before laboratory fibrinogen results are available 1
• Maximum clot firmness (MCF) of 7 mm: Correlates with fibrinogen level of approximately 2 g/L in trauma patients 1

Safety Profile

• Common adverse reactions: Anemia (14.3%), acute kidney injury (8.0%), thrombocytopenia (5.5%) 5
• Volume overload risk: Particularly in patients with cardiac or renal impairment; monitor carefully 5
• Allergic reactions and anaphylaxis: Can occur unpredictably 1
• Thrombotic events: No increased incidence compared to standard care (12.7% vs 12.9%) 4
• Pathogen transmission risk: Cryoprecipitate is a pooled product without pathogen inactivation in most countries (except for patients born after 1996 in the UK, where methylene blue viral inactivation is used) 1, 6

Cryoprecipitate vs Fibrinogen Concentrate

• Clinical equivalence: A recent large trial found fibrinogen concentrate was non-inferior to cryoprecipitate in cardiac surgery patients with bleeding and hypofibrinogenemia 1
• Availability: Many European countries have moved to fibrinogen concentrate as first-line therapy; in the UK and US, cryoprecipitate remains standard of care 1, 7, 8
• Advantages of cryoprecipitate: Contains factor VIII, factor XIII, von Willebrand factor, and fibronectin in addition to fibrinogen 1, 6, 9
• Advantages of fibrinogen concentrate: Pathogen-inactivated, standardized fibrinogen content, longer shelf life, no need for cross-matching 1, 6

Blood Group Compatibility

• Donor and recipient blood groups should match for cryoprecipitate transfusion 1
• If blood group unknown: ABO non-identical plasma with low-titre anti-A or anti-B activity is acceptable 1
• Group O components: Should only be given to group O recipients 1