When should cryoprecipitate (cryoprecipitated antihemophilic factor) be administered?

When to Give Cryoprecipitate

Administer cryoprecipitate when fibrinogen levels fall below 1.5 g/L in major hemorrhage (or below 2.0 g/L in obstetric hemorrhage), or empirically when fibrinogen cannot be measured timely in massively bleeding patients. 1, 2

Primary Indications Based on Fibrinogen Levels

Major Hemorrhage and Massive Transfusion

• Give cryoprecipitate to maintain fibrinogen >1.5 g/L during major hemorrhage, including trauma, cardiac surgical bleeding, and massive transfusion scenarios 1, 2
• The American Society of Anesthesiologists recommends administration when fibrinogen concentration is <80-100 mg/dL (0.8-1.0 g/L) in the presence of excessive bleeding 2
• Use as an adjunct in massively transfused patients when fibrinogen levels cannot be measured in a timely fashion 2

Obstetric Hemorrhage

• Maintain fibrinogen >2.0 g/L in active obstetric hemorrhage, which is a higher threshold than other bleeding scenarios 1, 2
• This reflects the increased fibrinogen demands and consumption in obstetric coagulopathy 1

Disseminated Intravascular Coagulation (DIC)

• Administer cryoprecipitate when DIC is present with fibrinogen <1.0 g/L 1, 2
• This lower threshold reflects the balance between bleeding risk and the pathophysiology of DIC 1

Advanced Liver Disease

• Give cryoprecipitate to maintain fibrinogen >1.0 g/L in advanced liver disease with bleeding 1, 2
• Also indicated in combined liver and renal failure with active bleeding 1, 2

Specific Clinical Scenarios

Bleeding Associated with Thrombolytic Therapy

• Cryoprecipitate is indicated for bleeding complications during or after thrombolytic therapy 1, 2
• If cryoprecipitate is unavailable for urgent INR reversal, administer 10 units IV when four-factor prothrombin complex concentrate (PCC) is not available 3

Von Willebrand Disease

• Use cryoprecipitate only as a last resort in von Willebrand disease types 1 and 2A if desmopressin or VWF/FVIII concentrate are unavailable or ineffective 2
• For types 2B, 2M, 2N, and 3, use cryoprecipitate only if specific VWF/FVIII concentrate is not available 2

Congenital Fibrinogen Deficiencies

• Administer for patients with congenital fibrinogen deficiencies, ideally with hematology consultation 2

Fibrinolysis Detection

• Give cryoprecipitate when thromboelastography (TEG/ROTEM) or other tests indicate fibrinolysis 2

Important Thresholds and Caveats

When NOT to Give Cryoprecipitate

• Transfusion is rarely indicated if fibrinogen >150 mg/dL (1.5 g/L) in nonpregnant patients 2
• Do not use for routine volume replacement 1
• Limited role in mild-moderate coagulation abnormalities in non-bleeding critically ill patients before invasive procedures 1

Dosing Considerations

• Standard adult dose is two pools (10 units total), providing approximately 4 g of fibrinogen 4, 2
• Alternative weight-based dosing of 50 mg/kg (approximately 15-20 units in a 70-kg adult) may be used in major trauma per European guidelines 4
• Each pool contains 5 units with at least 2 g fibrinogen 1, 4

Administration Requirements

• Transfuse using a standard blood giving set with a 170-200 μm filter 1, 4, 2
• Must be used within 4 hours once thawed and cannot be refrigerated again 1, 4, 2
• Should be ABO compatible when possible 3

Evidence Limitations and Clinical Context

Recent Trial Data

• The CRYOSTAT-2 trial (2023) found that early empirical high-dose cryoprecipitate (6 g fibrinogen) did not reduce 28-day mortality in unselected trauma patients with major hemorrhage compared to standard care 5, 6
• This suggests that targeted administration based on measured fibrinogen levels may be more appropriate than empirical early use in all bleeding trauma patients 5, 6
• The trial had significant overlap in timing between groups, limiting intervention separation 6

Safety Monitoring

• Monitor for adverse reactions including anemia (14.3%), acute kidney injury (8.0%), and thrombocytopenia (5.5%) 4
• Watch for volume overload, particularly in patients with cardiac or renal impairment 4
• Risk of transfusion-related acute lung injury (TRALI) and transmission of blood-borne pathogens exists, though cryoprecipitate for those born after 1996 undergoes viral inactivation 1, 3

Alternative Therapies

• Fibrinogen concentrate (3-4 g IV) may be used instead, offering advantages of standardized dosing, viral inactivation, and no cross-matching requirement 4
• Fresh frozen plasma (FFP) at 15 ml/kg contains approximately 2 g fibrinogen in four units, compared to 4 g in two pools of cryoprecipitate 1