Cryoprecipitate and fibrinogen concentrate

INTRODUCTION — Low fibrinogen predisposes to bleeding, and raising the fibrinogen level is indicated in patients with low fibrinogen who have active bleeding or who are at high bleeding risk. Cryoprecipitate and fibrinogen concentrates can provide fibrinogen, but there are differences in composition and possible adverse effects, and both products are not always available in all institutions.

In the past, Cryoprecipitate was used to treat other deficiencies, but these uses are mostly outdated in high-resource settings.

This topic discusses the components of Cryoprecipitate and fibrinogen concentrate, differences between them, dosing, and adverse effects.

Separate topics discuss:

Other plasma products and plasma derivatives:

●Plasma – (See "Clinical use of plasma components".)

●Clotting factor concentrates – (See "Plasma derivatives and recombinant DNA-produced coagulation factors".)

●Pathogen inactivation – (See "Pathogen inactivation of blood products".)

Bleeding disorders:

●Fibrinogen disorders – (See "Disorders of fibrinogen".)

●von Willebrand disease (VWD) – (See "von Willebrand disease (VWD): Treatment of major bleeding and major surgery".)

●DIC – (See "Evaluation and management of disseminated intravascular coagulation (DIC) in adults".)

●Liver disease – (See "Hemostatic abnormalities in patients with liver disease".)

●Uremic bleeding – (See "Uremic platelet dysfunction".)

The choice between Cryoprecipitate and fibrinogen concentrate is discussed in topics on specific indications. (See 'Use in specific settings' below.)

FIBRINOGEN ROLE IN BLOOD CLOTTING — Most of the clotting factors are enzymes or cofactors present in small amounts in the circulation. (See "Overview of hemostasis", section on 'Multicomponent complexes'.)

In contrast, fibrin, the product of cleaved fibrinogen (factor I) at the end of the coagulation cascade, is the major structural component of a clot; it forms a crosslinked meshwork that can span a gap in the vasculature until re-endothelialization occurs. Clots also contain platelets and often red blood cells (RBCs). Fibrin also contributes to wound healing. (See "Disorders of fibrinogen", section on 'Functions in hemostasis and other processes'.)

Because of the structural role in clotting, fibrinogen abundance in the circulation is much greater than other clotting factors (typical concentration, 200 to 400 mg/dL; 5.9 to 11.8 micromol/L [SI units]). (See "Laboratory test reference ranges in adults", section on 'Fibrinogen, plasma'.)

Factor XIII crosslinks fibrin strands once they are assembled in the clot. (See "Overview of hemostasis", section on 'Continuation of the coagulation cascade' and "Rare inherited coagulation disorders", section on 'Factor XIII deficiency (F13D)'.)

PREPARATION AND CONSTITUENTS

Cryoprecipitate (preparation/constituents) — The official name for Cryoprecipitate is Cryoprecipitated antihemophilic factor (AHF), although this is commonly abbreviated "Cryoprecipitate" or "cryo."

It is composed of the insoluble coagulation factors (proteins) that precipitate out of solution after Fresh Frozen Plasma (FFP) or Plasma Frozen Within 24 Hours After Phlebotomy (PF24) is thawed between 1 and 6° C and centrifuged. The insoluble precipitate is resuspended in approximately 15 to 20 mL of plasma and refrozen at -18° C. This process creates one unit of Cryoprecipitate.

At the request of the transfusing facility, most blood suppliers will provide prepooled Cryoprecipitate (one "bag") containing the Cryoprecipitate obtained from 5, 6, 8, or 10 units of FFP, which usually range in volume from 100 to 200 mL. (See 'Cryoprecipitate (dosing and administration)' below.)

Cryoprecipitate contains the following proteins from a unit of FFP; in parentheses are the minimum levels specified by the US Food and Drug Administration (FDA) and Association for the Advancement of Blood & Biotherapies (AABB):

●Fibrinogen (factor I; at least 150 mg)

●Factor VIII (at least 80 international units)

●Factor XIII (at least 50 to 75 international units)

●von Willebrand factor (VWF; at least 100 to 150 international units)

●Fibronectin (concentration not measured)

Cryoprecipitate can only be made from Fresh Frozen Plasma (FFP), which by definition has been frozen within eight hours of whole blood collection, or Plasma Frozen Within 24 Hours After Phlebotomy (PF24). Cryoprecipitate can be stored frozen for up to one year.

Pathogen-reduced Cryoprecipitate (preparation/constituents) — Pathogen-reduced Cryoprecipitate is produced from pathogen-reduced plasma, as discussed separately. (See "Pathogen inactivation of blood products", section on 'Cryoprecipitate'.)

●Europe – A CE Mark is available for pathogen-reduced plasma by amotosalen plus UVA light, methylene blue plus visible light, and riboflavin plus UV light methods. Cryoprecipitate may be manufactured by blood collection facilities from this plasma that meets European Union requirements.

●United States – The US Food and Drug Administration (FDA) has approved amotosalen plus UVA light Pathogen Reduced Cryoprecipitated Fibrinogen Complex (PRCFC) for the treatment and control of bleeding, including massive hemorrhage, associated with fibrinogen deficiency. The advantage of this product is that it has a five-day shelf-life after thawing, compared with four to six hours for standard Cryoprecipitate. However, PRCFC costs more than standard Cryoprecipitate.

Fibrinogen concentrate (preparation/constituents) — Fibrinogen concentrate is prepared from pooled human plasma. The process involves several purification and lyophilization steps that are considered theoretically sufficient to inactivate all bacteria, viruses, and parasites. (See "Plasma derivatives and recombinant DNA-produced coagulation factors", section on 'Fibrinogen'.)

Fibrinogen concentrate contains only fibrinogen; unlike Cryoprecipitate, there are no other coagulation proteins. There are two different products (RiaSTAP, referred to as Haemocomplettan in Israel, and FIBRYGA) with slightly different purification methods [1-3].

Fibrinogen concentrates containing 900 to 1300 mg of fibrinogen are reconstituted by adding sterile saline (typical volume, 50 mL) at the time of administration. Slight differences in the final concentration lead to slightly different dosing calculations. (See 'Fibrinogen concentrate (dosing and administration)' below and "Disorders of fibrinogen", section on 'Fibrinogen concentrate: Dosing and monitoring'.)

DIFFERENCES BETWEEN THEM — For patients with serious bleeding and low fibrinogen, the best source of fibrinogen is the one that is most easily available [4]. In most institutions, only one product is available. Generally, institutions in the United States are more likely to stock Cryoprecipitate, and those in Europe and Canada are more likely to stock fibrinogen concentrates. Clinicians should familiarize themselves with the product(s) available at their institution.

If more than one product is available, the choice between them depends on the relative efficacy, risks, and costs (table 1).

The main differences are as follows:

●Efficacy – Direct comparisons of the relative efficacy of Cryoprecipitate versus fibrinogen concentrates to guide decision making are limited to data from small pilot trials [5]. Specific evidence is presented in separate topic reviews listed below. (See 'Use in specific settings' below.)

●Adverse effects – Both products are generally well-tolerated. However, Cryoprecipitate is a blood component that carries risks of transfusion complications, some of which may be mitigated by pathogen-inactivation and some of which may not, as discussed below. (See 'Cryoprecipitate adverse effects' below and 'Fibrinogen concentrate adverse effects' below.)

●Costs and burdens – Cryoprecipitate may be less expensive than fibrinogen concentrate, even after adjusting for potential product wastage and technologists' salaries to prepare Cryoprecipitate [6]. However, fibrinogen concentrate may be cost-effective and less expensive in some settings, even considering the higher up-front product cost [7].

The risk benefit calculations have led to different practices in different countries.

●United States – The use of Cryoprecipitate has increased in the United States, likely due to increased hemostasis testing and hypofibrinogenemia management of coagulopathic patients [8-10].

●Europe and Canada – The use of fibrinogen concentrates has increased in European countries and Canada, based on the lower risk of complications (viral infection, allergic transfusion reactions, transfusion-related acute lung injury [TRALI]). These safety concerns (particularly transmission of pathogens) have led many European countries and Canada to discontinue the use of Cryoprecipitate and rely solely on commercial fibrinogen concentrates for fibrinogen replacement [4,11-15].

●Resource-limited settings – The use of Cryoprecipitate is much less common in resource-limited settings than in North America or Europe, and there is almost no use of fibrinogen concentrates in these settings.

Based on their strong safety profiles and ease of use, fibrinogen concentrates may supplant Cryoprecipitate for fibrinogen replacement worldwide [9,16-19]. However, since the licensed indication for fibrinogen concentrates is restricted to inherited fibrinogen disorders in some countries, including the United States, Cryoprecipitate is still widely used as a source of fibrinogen for acquired hypofibrinogenemia [20].

USE IN SPECIFIC SETTINGS — Fibrinogen replacement is appropriate in settings with low or dysfunctional fibrinogen and bleeding or high risk of bleeding. Transfusion medicine personnel and/or individuals with hemostasis expertise can help to determine whether these products are indicated for specific patients.

The following sections list common settings in which fibrinogen replacement is used, with indications, choice of product, and supporting evidence discussed in the linked topics.

Congenital fibrinogen disorders — (See "Disorders of fibrinogen", section on 'Management'.)

Cardiac surgery — Acquired hypofibrinogenemia often occurs in cardiac surgery and is associated with excessive bleeding, especially when the fibrinogen levels are below 200 mg/dL [21,22]. Hypofibrinogenemia is a clear indication for administering a fibrinogen product. Details of the indications for fibrinogen replacement, choice of product, and supporting evidence are presented separately. (See "Achieving hemostasis after cardiac surgery with cardiopulmonary bypass".)

Postpartum hemorrhage — Postpartum hemorrhage (PPH: blood loss >500 mL or >1000 mL following delivery, depending on the definition used) can have many causes. Fibrinogen <200 mg/dL is associated with increased risk of severe PPH. Reference ranges for fibrinogen during the third trimester of pregnancy are generally >300 mg/dL. (See "Normal reference ranges for laboratory values in pregnancy", section on 'Reference intervals in pregnancy'.)

Details of the indications for fibrinogen replacement, choice of product, and supporting evidence are presented separately. (See "Overview of postpartum hemorrhage", section on 'Early recognition, assessment, and intervention' and "Postpartum hemorrhage: Medical and minimally invasive management", section on 'Correct clotting factor deficiencies'.)

Trauma — Cryoprecipitate may be used to treat critically low fibrinogen levels in trauma patients; some institutions may include a source of fibrinogen in their massive transfusion protocols.

However, empiric Cryoprecipitate as a general therapy for critical traumatic bleeding does not appear to be effective in improving outcomes. In a 2023 randomized trial in which 1604 trauma patients were assigned to a standard massive transfusion protocol with or without 3 pools of Cryoprecipitate (6 grams fibrinogen equivalent) as early as possible, mortality at 28 days was not statistically different between the no Cryoprecipitate controls and the Cryoprecipitate group (26 percent in controls versus 25 percent with Cryoprecipitate) [23]. There was no difference in safety outcomes or thromboembolic events (13 percent in both groups).

Additional details of massive transfusion and hemostatic support for trauma patients are presented separately. (See "Massive blood transfusion" and "Ongoing assessment, monitoring, and resuscitation of the severely injured patient", section on 'Transfusion' and "Initial management of moderate to severe hemorrhage in the adult trauma patient", section on 'Transfusion'.)

Inherited fibrinogen disorders — Pathogenic variants in one of the three genes that encode fibrinogen (FGA, FGB, FGG) can cause afibrinogenemia, hypofibrinogenemia, dysfibrinogenemia, or hypodysfibrinogenemia. (See "Disorders of fibrinogen", section on 'Fibrinogen synthesis and circulating levels'.)

These conditions can be associated with bleeding that requires treatment with fibrinogen. Fibrinogen may also be used prophylactically if bleeding risk is high, such as during pregnancy. Fibrinogen concentrates are first-line therapy, but Cryoprecipitate may be used when fibrinogen concentrates are unavailable. Details are discussed separately. (See "Disorders of fibrinogen", section on 'Management'.)

Liver disease — Liver disease has complex effects on the coagulation system, with both thrombotic and hemorrhagic consequences. For patients with liver disease and bleeding or need for a surgical procedure who have very low fibrinogen levels, administration of a source of fibrinogen may be appropriate. However, fibrinogen is not used to treat isolated laboratory abnormalities.

Guidelines from the British Society of Haematology and other American and European liver societies do not recommend prophylactic transfusion of Cryoprecipitate in patients with liver disease undergoing low bleeding risk procedures such as paracentesis [20,24,25]. This subject, including a comprehensive approach to the management of bleeding in individuals with liver disease, is discussed in detail separately. (See "Hemostatic abnormalities in patients with liver disease", section on 'Bleeding'.)

DIC — Disseminated intravascular coagulation (DIC) is a systemic process in which coagulation and fibrinolysis become abnormally (and often massively) activated, typically due to an underlying disorder such as infection, malignancy, or complication of pregnancy. DIC has both thrombotic and hemorrhagic complications. (See "Evaluation and management of disseminated intravascular coagulation (DIC) in adults", section on 'Acute DIC'.)

Administration of a source of fibrinogen may be helpful in patients with serious bleeding (or serious concern about bleeding) who have a fibrinogen level <100 mg/dL.

A comprehensive approach to the management of bleeding in individuals with DIC, including the treatment of the underlying cause, supportive interventions, and indications for coagulation factor replacement, is presented in detail separately. (See "Evaluation and management of disseminated intravascular coagulation (DIC) in adults", section on 'Treatment'.)

Uremic bleeding — Patients with uremia are thought to have an increased risk of bleeding primarily due to platelet dysfunction rather than coagulation abnormalities. In the past, Cryoprecipitate was used to treat bleeding if it was life threatening and other first-line therapies such as desmopressin (DDAVP) and transfusions were ineffective [26]. Cryoprecipitate is still included in some transfusion protocols, but use has decreased over time. (See "Uremic platelet dysfunction", section on 'Treatment of bleeding'.)

INAPPROPRIATE AND OBSOLETE USES

Ineffective

●Cryoprecipitate and fibrinogen concentrate cannot treat bleeding due to deficiencies of factors that are absent from these products, including factors XI, IX, VII, V, and thrombin (factor IIa).

●These therapies have no role in treating bleeding due to thrombocytopenia, platelet dysfunction, or anticoagulation. Treatment of these disorders is discussed separately. (See "Management of warfarin-associated bleeding or supratherapeutic INR" and "Management of bleeding in patients receiving direct oral anticoagulants" and "Diagnostic approach to thrombocytopenia in adults", section on 'Bleeding or other symptoms'.)

●At one time, Cryoprecipitate was used as a source of fibronectin to treat sepsis, but use for this indication was discontinued based on lack of efficacy [27].

Disorders for which better alternatives are available — Cryoprecipitate is generally not used to treat disorders for which specific clotting factor concentrates are available:

●Congenital hypofibrinogenemia – Fibrinogen concentrate

●Hemophilia A (factor VIII deficiency) – Factor VIII concentrate

●Factor XIII deficiency – Factor XIII concentrate

●von Willebrand disease (VWD) – von Willebrand factor (VWF) concentrate

In patients with these conditions, Cryoprecipitate may be used in unusual circumstances such as treatment of bleeding when a recombinant or plasma-derived factor concentrate is not available. (See "Treatment of bleeding and perioperative management in hemophilia A and B", section on 'Acute therapy for bleeding' and "Rare inherited coagulation disorders", section on 'Factor XIII deficiency (F13D)' and "von Willebrand disease (VWD): Treatment of major bleeding and major surgery".)

DOSING AND ADMINISTRATION

Target fibrinogen (for either product) — When treatment of hypofibrinogenemia is indicated, the target fibrinogen level is generally at least 100 mg/dL. At least 150 mg/dL is optimal, and higher targets are appropriate in some settings such as postpartum hemorrhage.

Cryoprecipitate (dosing and administration)

●ABO compatibility – It is recommended to use Cryoprecipitate that is ABO compatible with the recipient's red blood cells (RBCs), particularly in neonates, small children, solid organ transplant recipients, and hematopoietic stem cell transplant recipients, to avoid passive transfer of ABO antibodies that can cause hemolysis. RhD type need not be considered, since Cryoprecipitate does not contain significant RBCs [20].

●Calculate dose – Since Cryoprecipitate can be provided as single units or as "pools" containing multiple units, the clinician should calculate the appropriate dose based on single units and let the transfusion service provide those units in the most efficient packaging (multiple single units or [most often] pooled units).

For most adults, an appropriate dose of Cryoprecipitate is between 5 and 10 units (one to two 5-unit "pools") (table 2). A typical dose is provided in a volume of 50 to 200 mL. In the average patient, each unit raises the plasma fibrinogen concentration by at least 7 to 10 mg/dL, and 10 units will raise the fibrinogen level by approximately 70 to 100 mg/dL in a 70 kg recipient.

While most clinicians have a general sense of the appropriate dose, the Cryoprecipitate dose (in units) can be more quantitatively estimated or calculated as follows:

•Estimate percent fibrinogen increase per unit – In the average adult, each unit raises the plasma fibrinogen concentration by at least 7 to 10 mg/dL; thus, 10 units (or two 5-unit pools) will raise the fibrinogen by approximately 70 to 100 mg/dL.

•Calculate by plasma volume – Calculate the recipient's blood volume by multiplying their weight in kg by 70 mL/kg. As an example, the blood volume of a 60 kg female = 60 kg x 70 mL/kg = 4200 mL. Then calculate the recipient's plasma volume by multiplying their blood volume by [1 - their percent hematocrit]. In the same example, if the hematocrit is 35 percent, multiply 4200 mL x [1 - 0.35]; 4200 mL x 0.65 = 2730 mL. Then convert their plasma volume to dL by dividing by 100. In the same example, 2730 mL ÷ 100 = 27.3 dL. Then calculate the desired change in fibrinogen. In this example, if the recipient's fibrinogen is 50 mg/dL and the desired level is 150 mg/dL, the desired increase is 100 mg/dL. Then multiply the plasma volume by the desired change in fibrinogen. In this example, 27.3 dL x 100 mg/dL = 2730 mg fibrinogen. The Association for the Advancement of Blood & Biotherapies (AABB) Technical Manual recommends this calculation use an assumption that each unit of Cryoprecipitate contains 250 mg of fibrinogen, so 2730 mg ÷ 250 mg/unit = 10.9 units of Cryoprecipitate needed.

●Thaw from frozen – Cryoprecipitate must be thawed in the blood bank prior to issue and transfusion; thus, there is an approximately 30-minute delay after the product is ordered before it can be administered. Cryoprecipitate is generally only thawed for specific patients after the order is received. It must be transfused within six hours after thawing, or, if pooled, within four hours.

●Infusion rate and setup – Cryoprecipitate can be infused as rapidly as tolerated (generally 2 to 5 mL per minute in a patient without hypervolemia). In trauma cases or other emergency situations, the administration rate can be increased.

Cryoprecipitate should be infused through a standard blood transfusion filter.

●Compatible fluids – No other medications or fluids other than normal saline should be given simultaneously through the same line without prior consultation with the medical director of the blood bank.

●Monitoring and dosing interval

•Low fibrinogen – The target fibrinogen level is generally at least 100 mg/dL. At least 150 mg/dL is optimal, and higher levels are appropriate in some settings such as postpartum hemorrhage. (See 'Postpartum hemorrhage' above.)

The British Society of Haematology Guidelines recommend transfusion of Cryoprecipitate if a patient has a fibrinogen level below 100 mg/dL and significant risk factors for bleeding prior to a procedure, but the guideline notes that data are insufficient to recommend a transfusion threshold or optimal dose [20].

The half-life of fibrinogen is approximately 3 to 3.5 days (77 to 88 hours); dosing is generally based on monitoring of the fibrinogen level (once daily, more frequently if increased or unexpected bleeding occurs, less frequently as healing is completed) rather than a set dosing interval. If the trough level is too low, it is preferable to shorten the dosing interval (give more frequent infusions) rather than increase the amount of Cryoprecipitate per dose. (See "Disorders of fibrinogen", section on 'Management'.)

•Low factor XIII – If factor XIII concentrate is not available, a typical dose of Cryoprecipitate to treat bleeding in a person with factor XIII deficiency is approximately one unit (bag) per 10 kg of body weight (eg, one 5-unit pool in a 50 kg person). A factor concentrate for factor XIII can be used for individuals with factor XIII deficiency if available. (See "Plasma derivatives and recombinant DNA-produced coagulation factors", section on 'Factors XIII and X'.)

The half-life of factor XIII is long, 150 to 300 hours (approximately six days to two weeks), and the level needed for hemostasis is low; repeat dosing is generally required once every three to six weeks depending on the patient. (See "Rare inherited coagulation disorders", section on 'Factor XIII deficiency (F13D)'.)

Cryoprecipitate adverse effects

●Infection – Cryoprecipitate carries an approximately equivalent infectious risk as a unit of RBCs (table 3). However, since many units of Cryoprecipitate are pooled and transfused simultaneously, the risk per dose must be multiplied by the number of units in the pool. Pathogen-reduced Cryoprecipitate has a significantly lower risk of viral, bacterial, or parasitic infection compared with standard Cryoprecipitate. (See "Blood donor screening: Laboratory testing".)

●Volume overload – Cryoprecipitate is less likely to cause transfusion-related volume overload (TACO) than plasma (per unit of coagulation factor delivered); however, the risk is still proportional to the volume and speed of transfusion. (See "Transfusion-associated circulatory overload (TACO)".)

●Transfusion reactions – Cryoprecipitate has a lower risk of causing a hemolytic transfusion reaction than plasma, and this risk can be mitigated further if ABO compatibility is assured. This is because the volume and hence the quantity of alloantibodies to RBC is smaller than in plasma. The risk of allergic transfusion reactions (urticaria, anaphylaxis) is likely to be the same as plasma, although this has not formally been studied. (See "Immunologic transfusion reactions".)

●Thromboembolic events – Cryoprecipitate transfusion increases levels of fibrinogen and has been associated with thromboembolic complications in observational studies and clinical trials [14,28].

Additional information about these risks and their frequencies, and a suggested approach to a suspected transfusion reaction in an individual receiving Cryoprecipitate, including notification of the transfusion service or blood bank, is discussed in more detail separately. (See "Approach to the patient with a suspected acute transfusion reaction".)

Fibrinogen concentrate (dosing and administration)

●Reconstitute – Fibrinogen concentrate is lyophilized (powder) and must be reconstituted (typical volume of sterile saline, 50 mL). (See 'Fibrinogen concentrate (preparation/constituents)' above.)

●Calculate dose – The target fibrinogen level is generally at least 100 mg/dL. At least 150 mg/dL is optimal, and higher levels are appropriate in some settings such as postpartum hemorrhage. (See 'Postpartum hemorrhage' above.)

The initial dose calculation for the dose in mg/kg body weight is based on the formula: Dose = [Target fibrinogen level - measured fibrinogen level] ÷ correction factor.

The fibrinogen level is expressed in mg/dL. The correction factor is in mg/dL or mg/kg. The correction factor is 1.7 for RiaSTAP and Haemocomplettan and 1.8 for FIBRYGA.

Thus, the dose in mg is calculated as follows:

•RiaSTAP and Haemocomplettan: Dose (in mg) = [weight (in kg) x desired increase (in mg/dL)] ÷ 1.7.

•FIBRYGA: Dose (in mg) = weight (in kg) x desired increase (in mg/dL) ÷ 1.8. For FIBRYGA in children, divide by 1.4 instead of 1.8.

Additional information on dosing for congenital afibrinogenemia/hypofibrinogenemia is presented separately. (See "Disorders of fibrinogen", section on 'Fibrinogen concentrate: Dosing and monitoring'.)

●Monitoring and dosing interval – The half-life of fibrinogen is approximately 3 to 3.5 days (77 to 88 hours); dosing is generally based on monitoring of the fibrinogen level (once daily, more frequently if increased or unexpected bleeding occurs, less frequently as healing is completed) rather than a set dosing interval. If the trough level is too low, it is preferable to shorten the dosing interval (give more frequent infusions) rather than increase the amount of Cryoprecipitate per dose. (See "Disorders of fibrinogen", section on 'Management'.)

Fibrinogen concentrate adverse effects

●Allergic reactions – Fibrinogen concentrates are derived from FFP or PF24. While much less common than Cryoprecipitate transfusion, there is a risk of allergic or hypersensitivity reactions.

●Thromboembolic events – Fibrinogen concentrates increase fibrinogen levels and have been associated with increased risk of thrombosis. In a randomized trial in patients with bleeding after cardiac surgery that compared fibrinogen concentrate with Cryoprecipitate, thromboembolic events occurred in 7 percent of patients in the fibrinogen concentrate group and 9.6 percent of patients in the Cryoprecipitate group [14].

SUMMARY AND RECOMMENDATIONS

●Biology – Fibrinogen is cleaved to fibrin, the major structural component of the blood clot. Unlike enzymatic factors that only require a small concentration, circulating fibrinogen concentrations are much higher (200 to 400 mg/dL). (See 'Fibrinogen role in blood clotting' above.)

●Composition – Cryoprecipitate is manufactured using already frozen Fresh Frozen Plasma (FFP) or Plasma Frozen Within 24 Hours After Phlebotomy (PF24), thawing, and concentrating the proteins that precipitate. It contains fibrinogen (factor I), factor VIII, fibronectin, factor XIII, and von Willebrand factor (VWF). Pathogen-inactivated (PI) Cryoprecipitate is made from PI plasma. Fibrinogen concentrate is purified from pooled human plasma using several purification steps and heat treatment. RiaSTAP (Haemocomplettan in Israel) and FIBRYGA are purified using slightly different methods. (See 'Preparation and constituents' above and "Pathogen inactivation of blood products", section on 'Cryoprecipitate'.)

●Differences between Cryoprecipitate and fibrinogen concentrates – In a bleeding patient with low fibrinogen, either Cryoprecipitate or fibrinogen concentrate can provide a source of fibrinogen. Most institutions only carry one product. Differences between the products are summarized above (table 1). (See 'Differences between them' above.)

●Indications and contraindications – Common settings in which fibrinogen replacement is used include the following: the indications, choice between Cryoprecipitate and fibrinogen concentrate, and supporting evidence are discussed in the linked topics:

•Congenital fibrinogen disorders – (See "Disorders of fibrinogen", section on 'Management'.)

•Cardiac surgery – (See "Achieving hemostasis after cardiac surgery with cardiopulmonary bypass".)

•Postpartum hemorrhage – (See "Overview of postpartum hemorrhage", section on 'Early recognition, assessment, and intervention' and "Postpartum hemorrhage: Medical and minimally invasive management", section on 'Correct clotting factor deficiencies'.)

•Trauma and massive transfusion – (See "Initial management of moderate to severe hemorrhage in the adult trauma patient" and "Massive blood transfusion".)

•DIC, liver disease, kidney disease – (See "Hemostatic abnormalities in patients with liver disease", section on 'Bleeding' and "Evaluation and management of disseminated intravascular coagulation (DIC) in adults", section on 'Treatment' and "Uremic platelet dysfunction", section on 'Treatment of bleeding'.)

•Contraindications – Cryoprecipitate and fibrinogen concentrate have no role in treating bleeding due to thrombocytopenia, platelet dysfunction, or anticoagulation. Cryoprecipitate is generally not used for conditions for which a purified or recombinant factor concentrate is available. (See 'Inappropriate and obsolete uses' above.)

●Dosing

•Cryoprecipitate – Can be provided as single units or as "pools" containing five or more units. The clinician should check with the local hospital transfusion service or blood supplier to determine the exact composition of one "bag" of Cryoprecipitate (how many individual units are pooled to make up that "bag") to determine the correct dosage for a patient. In the average patient, each unit raises the plasma fibrinogen concentration by approximately 7 to 10 mg/dL; thus, 10 units will raise the fibrinogen by approximately 70 to 100 mg/dL in a 70 kg recipient (table 2). (See 'Dosing and administration' above.)

•Fibrinogen concentrate – The dosing is determined by subtracting the measured fibrinogen level from the target fibrinogen level and dividing it by the manufacturer’s correction factor. (See "Disorders of fibrinogen", section on 'Fibrinogen concentrate: Dosing and monitoring'.)

●Adverse effects – Cryoprecipitate carries risks of various types of transfusion reactions/complications, including transfusion-transmitted infection (table 3), volume overload, hemolytic transfusion reactions, thromboembolic events, and allergic reactions. The transfusion medicine service should be contacted to discuss possible evaluation and testing if a patient receiving Cryoprecipitate has a suspected transfusion reaction. Fibrinogen concentrate carries the risks of allergic reactions and thromboembolic events. (See 'Cryoprecipitate adverse effects' above and "Approach to the patient with a suspected acute transfusion reaction".)

●Other plasma components – Plasma products and other plasma-derived coagulation factor concentrates are discussed separately. (See "Clinical use of plasma components" and "Plasma derivatives and recombinant DNA-produced coagulation factors".)

ACKNOWLEDGMENT — The UpToDate editorial staff acknowledges extensive contributions of Arthur J Silvergleid, MD, to earlier versions of this and many other topic reviews.