What is cryoprecipitate?

What is Cryoprecipitate

Cryoprecipitate is a concentrated plasma product containing factor VIII, von Willebrand factor, fibrinogen, factor XIII, and fibronectin, produced by thawing fresh frozen plasma at 1-6°C and collecting the precipitated proteins. 1

Composition and Content

Cryoprecipitate is manufactured through a specific cold-precipitation process that concentrates high-molecular-weight plasma proteins:

• Each single unit contains 400-450 mg of fibrinogen, while pooled bags of five units contain at least 2 g of fibrinogen 1, 2
• The product is enriched in factor VIII (antihemophilic factor), von Willebrand factor, fibrinogen, factor XIII, and fibronectin 1, 3, 4
• Despite enrichment of certain factors, only 27% of the original plasma fibrinogen ends up in cryoprecipitate, and it contains low levels of factor V, protein S, protein C, antithrombin III, and plasminogen 3
• The von Willebrand factor multimer pattern in cryoprecipitate is indistinguishable from normal pooled plasma 5

Production and Storage

The manufacturing process involves specific temperature-controlled steps:

• Fresh frozen plasma is thawed at 4 ± 2°C, which causes precipitation of the high-molecular-weight proteins 2, 4, 6
• The precipitate is collected and resuspended in a small volume of plasma 2
• Storage occurs at temperatures below -25°C for up to 36 months 2
• Once thawed for administration, it can be kept at ambient temperature for only 4 hours and must never be refrigerated again 1, 2

Available Forms and Dosing

In the UK, cryoprecipitate comes in standardized preparations:

• Primarily available as pooled bags of five units containing 100-200 ml per bag 1
• Also available as single units of 20-40 ml for smaller patients 1
• The standard adult dose is two pools (containing approximately 4 g of fibrinogen total) 1, 7
• Transfusion requires a standard blood giving set with a 170-200 μm filter 1, 2, 7

Primary Clinical Indications

Cryoprecipitate is used primarily for fibrinogen replacement in specific bleeding scenarios:

• Hypofibrinogenemia due to major hemorrhage and massive transfusion, with increased use in major trauma, obstetric hemorrhage, and cardiac surgical bleeding 1, 7
• During major hemorrhage, fibrinogen should be maintained >1.5 g/L, except in active obstetric hemorrhage where >2 g/L should be maintained 1, 7
• Disseminated intravascular coagulation with fibrinogen <1.0 g/L 1, 7
• Advanced liver disease to maintain fibrinogen level >1.0 g/L 1, 7
• Combined liver and renal failure with bleeding 1, 7
• Bleeding associated with thrombolytic therapy 1, 7

Special Populations

For patients born in 1996 or later, specific safety measures apply:

• Cryoprecipitate is made from FFP sourced outside the UK and undergoes viral inactivation with methylene blue 1, 2
• Available as single units for smaller children and pooled units for older children and young adults 1, 2

Historical Context and Current Use

While cryoprecipitate was historically used to treat hemophilia A and von Willebrand disease, the availability of more highly purified coagulation factor concentrates and recombinant protein preparations has superseded its use for these conditions 4, 6, 8. The most common current use is fibrinogen replacement in patients with acquired hypofibrinogenemia and bleeding 8.

Important Limitations

Clinicians should understand what cryoprecipitate cannot provide:

• Cannot be used for replacement of protein C, protein S, or factor V due to low concentrations of these factors 3
• The cryosupernatant (plasma remaining after cryoprecipitate removal) is virtually deficient in ristocetin cofactor activity and lacks higher molecular weight von Willebrand factor multimers 3
• Common adverse reactions include anemia (14.3%), acute kidney injury (8.0%), and thrombocytopenia (5.5%) 9
• Volume overload can occur, particularly in patients with cardiac or renal impairment 9