Cryoprecipitate and Fibrinogen

Cryoprecipitate is the cold insoluble fraction of fresh frozen plasma, prepared by controlled thawing and centrifugation, and is rich in fibrinogen, factor VIII, von Willebrand factor, factor XIII and fibronectin. Fibrinogen concentrate is a purified plasma derived product with a defined fibrinogen content. Both treat bleeding caused by low fibrinogen, which develops early in obstetric haemorrhage and trauma and is poorly corrected by plasma.

Composition. A single donor unit has about 10 to 20 mL volume and at least about 150 mg of fibrinogen, with factor VIII, von Willebrand factor and factor XIII. An adult dose is a pool of units from several donors, usually 5 units in a pool.

Storage and handling. Frozen at minus 25 degrees Celsius or colder, with shelf life up to 12 months. Thawed in a validated water bath or device at about 30 to 37 degrees Celsius, and used promptly, usually within 4 to 6 hours at room temperature as the hospital sets. Do not refrigerate thawed cryoprecipitate. Fibrinogen concentrate is a stable powder, stored as the manufacturer states and reconstituted before use.

ABO and RhD. ABO compatible cryoprecipitate is preferred, and matching matters most in neonates and small children. RhD does not need to match.

Special groups. Neonates and children, pregnancy and postpartum haemorrhage, cardiac surgery, liver disease and congenital fibrinogen deficiency. In East Africa, cryoprecipitate preparation is limited to larger centres, and fibrinogen concentrate is often unavailable or costly.

Indications.

• Bleeding with fibrinogen under 1.5 g/L (under 2 g/L in postpartum haemorrhage), in trauma, obstetric haemorrhage, cardiac surgery, liver disease, disseminated intravascular coagulation and after thrombolysis.

• Congenital hypofibrinogenaemia and afibrinogenaemia, for bleeding or surgery, when concentrate is unavailable.

• Factor XIII deficiency and von Willebrand disease when specific concentrates are unavailable.

Non-indications. Low fibrinogen without bleeding or a planned high risk procedure, haemophilia A (use factor VIII concentrate), and volume expansion.

Choice between products. Fibrinogen concentrate gives a defined dose, is quick to give and has low volume and low reaction risk. Cryoprecipitate also supplies factor VIII, von Willebrand factor and factor XIII, is available in many systems and gives a similar fibrinogen rise at a larger volume.

Cautions. Thrombosis risk with high fibrinogen levels, particularly with fibrinogen concentrate and in patients with thrombotic disease, and allergic reactions.

Dose of cryoprecipitate.

• Adults: two pools (about 10 single donor units), with an expected rise in fibrinogen of roughly 1 g/L in an adult without ongoing loss, then repeat as results direct.

• Children: 5 to 10 mL/kg (about 1 single donor unit for each 5 to 10 kg), with the response checked.

• Dose is set by current fibrinogen, target and weight, and by bleeding.

Dose of fibrinogen concentrate.

• Acquired deficiency with bleeding: a usual first dose is 25 to 50 mg/kg, or dose calculated from target and current level.

• Calculation: dose in mg/kg equals (target fibrinogen minus measured fibrinogen, in g/L) divided by 0.017, using the product's incremental response. Verify with the product specification.

• In obstetric haemorrhage, an empirical dose of 2 to 4 g may be given while results are awaited, as hospital practice allows.

• Congenital afibrinogenaemia: dose to keep fibrinogen at least about 1 g/L for prophylaxis and 1.5 g/L or more for surgery, as the haematologist directs.

Targets. Fibrinogen over 1.5 g/L in bleeding, and over 2 g/L in postpartum haemorrhage. Use Clauss fibrinogen, or viscoelastic results where available, for rapid direction in massive haemorrhage.

Compatibility and testing. ABO compatible preferred, no crossmatch. Send a sample for fibrinogen before replacement, but do not delay treatment in life-threatening bleeding.

Rate and time limit. Cryoprecipitate pools over about 30 minutes or as fast as tolerated, in bleeding rapidly. Fibrinogen concentrate over about 5 to 10 minutes or at the rate stated by the product. Use within the time limit after thawing or reconstitution.

Equipment and fluids. Blood giving set with filter for cryoprecipitate, and the supplied set for fibrinogen concentrate. Only 0.9% sodium chloride in the same line, and no other drugs.

Monitoring. Fibrinogen 10 to 60 minutes after the dose, together with bleeding, prothrombin time, platelets and, where available, viscoelastic results.

Special groups.

• Pregnancy: early replacement in postpartum haemorrhage, with fibrinogen over 2 g/L and early recognition of falling levels.

• Neonates: small volume with attention to overload.

• Liver disease: replace for bleeding only, and avoid volume overload.

Expected effects. Rise in fibrinogen, firmer clot and reduced bleeding.

Serious reactions. Allergic reactions and anaphylaxis, transfusion related acute lung injury, transfusion associated circulatory overload, thrombosis (particularly with fibrinogen concentrate and high levels), bacterial contamination (rare) and haemolysis from ABO incompatible plasma in small recipients.

Immediate interruption criteria. Dyspnoea, hypoxia, hypotension, urticaria with systemic signs, fever with rigors or unexpected deterioration. Stop the transfusion, assess the patient, keep intravenous access, recheck identity of patient and unit, and inform the blood bank. Do not restart without authorised clinical evaluation.

Follow up. Repeat fibrinogen after each dose until bleeding stops and the level is stable. Consider thromboprophylaxis once bleeding is controlled and fibrinogen is high.

Referral and escalation. Haematology for congenital deficiencies, refractory hypofibrinogenaemia and thrombotic events. Obstetric and anaesthetic teams in postpartum haemorrhage, and the blood bank for supply when large numbers of pools are needed.