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Cryoprecipitate: Composition, Compatibility, and Use

Updated May 2026

Reference summary

Cryoprecipitate is the cold-precipitate fraction of plasma, rich in fibrinogen, Factor VIII, von Willebrand factor, and Factor XIII. It is used in massive haemorrhage, Disseminated Intravascular Coagulation, and acute hypofibrinogenaemia. ABO-matched cryo is preferred but not strictly required. This page summarises clinical use and compatibility preferences. It is not medical advice. Decisions about transfusion are made by the treating clinical team.

What cryoprecipitate is

Cryoprecipitate, often abbreviated cryo, is a blood product manufactured from fresh frozen plasma (FFP). When FFP is thawed slowly at 1 to 6 degrees Celsius, several plasma proteins precipitate out as a cold-insoluble fraction. The cryoprecipitate is collected by centrifugation, refrozen, and stored. The supernatant (the FFP minus cryoprecipitate) becomes a separate product called cryo-poor plasma, used in some specific contexts such as plasma exchange for thrombotic thrombocytopenic purpura.

The cryoprecipitate fraction is enriched in fibrinogen (the soluble protein that polymerises to form fibrin clots), Factor VIII (the clotting factor deficient in haemophilia A), von Willebrand factor (the protein that mediates platelet adhesion and stabilises Factor VIII), Factor XIII (which crosslinks fibrin), and fibronectin. A single unit of cryo is small in volume (10 to 20 mL) and contains roughly 150 mg of fibrinogen, 80 IU of Factor VIII, and 100 IU of von Willebrand factor.

Several single units (typically five to ten in adults) are pooled to create an adult therapeutic dose of about 100 to 200 mL. The pooled product is what reaches the bedside in most modern blood banks. The UK JPAC Transfusion Handbook section on cryoprecipitate covers the manufacturing process and product specification in detail.

Indications for cryoprecipitate

The dominant modern indication is fibrinogen replacement in active bleeding. Massive obstetric haemorrhage (postpartum haemorrhage, placental abruption) and major trauma both consume fibrinogen rapidly, and replacement is needed when plasma fibrinogen falls below about 1.5 to 2.0 g/L (with the higher target in obstetrics, where fibrinogen is normally elevated in pregnancy). Cryoprecipitate or fibrinogen concentrate is given empirically in major obstetric haemorrhage protocols.

Disseminated Intravascular Coagulation (DIC) consumes fibrinogen and other clotting factors throughout the circulation. Cryo is used to support fibrinogen levels in active bleeding from DIC, alongside FFP for the broader factor deficit and platelets for thrombocytopenia. Inherited hypofibrinogenaemia or dysfibrinogenaemia, while rare, is also a cryo indication.

Cryo was historically the mainstay treatment for haemophilia A (Factor VIII deficiency) and severe von Willebrand disease. In modern practice, recombinant Factor VIII concentrate, plasma-derived Factor VIII, and von Willebrand factor concentrate have replaced cryo for these conditions in resource-rich settings. Cryo is still used in low-resource settings where dedicated factor concentrates are unavailable, and in specific perioperative situations.

ABO compatibility for cryoprecipitate

Cryoprecipitate contains a small volume of plasma, so the donor's anti-A and anti-B antibodies are passively transferred along with the clotting factors. The volume is much smaller than for FFP, so the haemolysis risk is correspondingly smaller. ABO-matched cryo is preferred where supply allows, but ABO-incompatible cryo is acceptable in emergencies and in adults.

The AABB Technical Manual notes that cryoprecipitate may be transfused without regard to ABO type in adults, with the caveat that group O cryo from donors with high anti-A and anti-B titres may cause haemolysis if given to non-O recipients in large volumes. Most blood centres screen high-titre donors out of cross-ABO use.

For neonates and infants, where the ratio of transfused antibody to recipient red cell mass is higher, ABO matching is more important and is generally observed. Rh matching is not required for cryoprecipitate because the product contains no red cells.

Dosing and clinical effect

The conventional adult cryo dose is 5 to 10 single units (roughly one pool) and is expected to raise plasma fibrinogen by about 0.5 g/L in an adult of average body weight. Dosing in major haemorrhage is empirical, with serial fibrinogen measurement (POC or laboratory) guiding ongoing replacement.

ROTEM and TEG (viscoelastic point-of-care tests) have replaced laboratory fibrinogen as the rapid trigger in many trauma and obstetric protocols. The NICE DG13 viscoelastic testing guidance covers the role of these tests in major bleeding management.

Once thawed, cryo must be used within 4 hours (open product) or 6 hours (closed pool), so it is thawed only when needed. The pre-thaw turnaround time of 20 to 40 minutes is a clinical bottleneck in unanticipated massive bleeding, which is one reason that fibrinogen concentrate (immediately reconstitutable) is preferred in some major haemorrhage protocols.

The move toward fibrinogen concentrate

Fibrinogen concentrate is a virally inactivated, freeze-dried, standardised-dose product manufactured from pooled human plasma. It can be reconstituted in minutes with sterile water and administered as a small-volume infusion. The standardised dose makes fibrinogen replacement more precise than the 30 percent unit-to-unit variability of cryoprecipitate.

UK obstetric haemorrhage guidelines and several European trauma protocols increasingly use fibrinogen concentrate as the first-line fibrinogen replacement product, with cryoprecipitate reserved for when concentrate is unavailable. The US has moved more slowly because fibrinogen concentrate is more expensive and not licensed in all clinical contexts.

The Cochrane review of fibrinogen replacement in major haemorrhage covers the comparative evidence. Both products lower bleeding-related mortality in the right populations; the choice is more about supply chain, logistics, and cost than clinical efficacy.

Donating to support cryo supply

There is no specific cryoprecipitate donation pathway. Cryo is manufactured from FFP, which is itself sourced from whole blood donations and from plasmapheresis donors. Donating whole blood or plasma supports both FFP and cryo manufacturing.

See our who can donate page for general eligibility, our donation types page for the comparison across products, and our plasma compatibility page for the upstream FFP rules.

Frequently asked questions

What is cryoprecipitate made of?
Cryoprecipitate (cryo) is the cold-precipitate fraction of fresh frozen plasma. When FFP is thawed at 1-6 degrees Celsius, fibrinogen, Factor VIII, von Willebrand factor, Factor XIII, and fibronectin precipitate out and are concentrated. The product is small in volume (about 10-20 mL per single unit) and is pooled into adult therapeutic doses.
When is cryoprecipitate used?
Main indications are massive haemorrhage with low fibrinogen (target above 1.5-2.0 g/L in obstetric and trauma settings), Disseminated Intravascular Coagulation (DIC), and bleeding in patients with hypofibrinogenaemia. Historically used for haemophilia A and von Willebrand disease, but now largely replaced by recombinant Factor VIII and von Willebrand concentrates for those conditions.
Does cryoprecipitate need ABO matching?
ABO-matched cryo is preferred but ABO-incompatible cryo is acceptable, especially in adult emergencies. The volume of plasma in a cryo dose is small, so the risk of haemolysis from passive antibody transfer is lower than for plasma. The AABB and JPAC both list cryo as a product where ABO compatibility is preferred but not strict.
Why is fibrinogen concentrate replacing cryoprecipitate in some settings?
Fibrinogen concentrate is a virally inactivated, standardised-dose product. It allows precise fibrinogen replacement without the variability of pooled cryo. The UK and many European centres are increasingly using fibrinogen concentrate in obstetric haemorrhage and trauma. The US is moving more slowly. The Cochrane review of fibrinogen replacement in massive haemorrhage covers the comparative evidence.
How much cryoprecipitate is in an adult dose?
An adult therapeutic dose is typically 5 to 10 single units, pooled into about 100-200 mL. This is expected to raise plasma fibrinogen by about 0.5 g/L in an adult of average size. Dosing is guided by serial fibrinogen measurement in major haemorrhage.
Can I donate cryoprecipitate specifically?
Cryoprecipitate is manufactured from plasma, so plasma donors and whole blood donors both contribute to the cryo supply. There is no separate cryo donation pathway in routine donor centres. Specialised plasmapheresis donations contribute to broader plasma manufacturing including cryo and immunoglobulins.
What is the difference between cryoprecipitate and FFP?
Fresh frozen plasma (FFP) contains all soluble plasma proteins, including all clotting factors, in their natural concentration. Cryoprecipitate is a fractionated product enriched in fibrinogen, Factor VIII, vWF, and Factor XIII. Cryo is preferred when fibrinogen replacement is the priority; FFP is preferred when broader factor replacement is needed.

Sources

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Updated 2026-04-27