• Cryoprecipitate is a blood product derived from plasma and used for supplying clotting factors to a volume-sensitive patient.
• Transfusion of cryoprecipitate is mainly indicated for the treatment of congenital defects of:
  • Factor VIII (FVIII)
  • von Willebrand's factor (vWF)
  • Factor XIII (FXIII)
  • Fibrinogen
  • Fibronectin
• A cross-matching is not required, but ABO compatibility should be considered before transfusion.

• Normal coagulation is dependent on several components:
  • Fibrinogen is converted to fibrin by thrombin. Fibrin is a polymerized protein that is involved in clot formation.
  • FVIII and vWF mediate adhesion of circulating platelets to exposed subendothelium.
  • FXIII promotes clot stability by forming covalent bonds between fibrin monomers and by cross-linking alpha-2 antiplasmin, fibrinogen, fibronectin, collagen, and other proteins to enhance the mechanical strength of the fibrin clot and protect the clot from proteolytic degradation.
• Cryoprecipitate preparation
  • A unit of fresh frozen plasma (FFP) is thawed at 1–6°C.
  • Supernatant is the precipitated, cold-insoluble material that initially thaws.
  • It is resuspended in a small volume of plasma (10–15 mL).
• Freezing
  • The resuspended fraction is refrozen at -18°C.
  • The time should be minimized from attainin the supernatant and freezing.
• Storage
  • Up to 12 months
• Contents (about 15 mL per unit)
  • Fibrinogen: ~350 mg
  • FVIII: ~150 units; increased when the donor has higher baseline levels (e.g., postexercise)
  • vWF: ~150 units
    • ADAMTS13 (a vWF cleaving protease) is minimal in cryoprecipitate.
  • FXIII
• Thawing cryoprecipitate
  • Requires ~45–60 minutes
  • After thawing, cryoprecipitate should be administered within 4 hours.
• ABO compatibility
  • Not required, but should be considered before transfusion. The plasma used to reconstitute the cryoprecipitate may contain a small amount of RBCs. Incompatible ABO cells will likely be cleared without undue consequences and sensitization to Rh is unlikely; however, with larger volumes, it may become problematic.
• Duration of effect
  • Fibrinogen: 70–100 hours
  • FVIII: 12 hours
  • vWF: 10–24 hours
  • FXIII: 120–200 hours
• Special handling
  • Administer through a 180–260 µm standard blood tubing.
  • Consider mixing with 10–15 mL of normal saline to ensure complete removal of all material from each bag.

• Complications of cryoprecipitate administration:
  • Transfusion-related acute lung injury (TRALI) is caused by anti-HLA antibodies present in donor plasma. The risk appears to be lower with cryoprecipitate compared to FFP.
  • Possible worsening of disseminated intravascular coagulation and organ dysfunction by forming fibrin in microcirculations.
  • Viral transmission. The risks of viral transmission, particularly hepatitis C and human immunodeficiency virus, have been significantly reduced by the nucleic acid testing of donor blood.
  • Acute hemolytic transfusion reaction, nonhemolytic febrile and allergic reactions, or thrombosis have been reported; however, their occurrence is rare.
  • Venous and arterial thromboembolic complications should be cautioned because cryoprecipitate rapidly increases plasma fibrinogen, FVIII, FXIII, and vWF.
  • Hypocalcemia may result from massive transfusion due to citrate overload.
  • Platelet microparticles can play an active role in thrombosis, inflammation, and vascular reactivity.
• Human-derived fibrinogen is a potential alternative; however, adverse events include thrombotic complications and anaphylactic reactions.

• Cryoprecipitate rapidly increases plasma levels of fibrinogen, FVIII, FXIII, and vWF, which collectively exert hemostatic activity. Indications include the following (1):
  • Congenital fibrinogen deficiency, von Willebrand's disease, congenital FXIII deficiency for prevention (perioperative and peripartum), as well as treatment of bleeding. When possible, however, hereditary deficiencies of FVIII, FXIII, and vWF should be managed with virally inactivated human-derived products or recombinant products.
  • Massive transfusion with microvascular bleeding and fibrinogen <80–100 mg/dL. If fibrinogen measurement cannot be performed in a timely manner, clinical decision-making may warrant administration of cryoprecipitate (2).
  • Hemorrhage after cardiac surgery if fibrinogen level is below 150 mg/dL.
  • Hemorrhage secondary to thrombolytic therapy
  • Management of bleeding due to snake venom
  • Iatrogenic premature rupture of amniotic membranes
  • Amniotic fluid embolism
  • Uremia; prevention and treatment of bleeding
  • Fibronectin deficiency after major surgery, trauma, burns, and sepsis. Deficiency impairs the reticuloendothelial system from clearing particulate debris in the circulation resulting in the accumulation of fibrin microaggregates, collagenous debris, and immune complexes.
  • Topical use as in fibrin glue (virally inactivated human-derived fibrin sealant products are preferred)
• Cryoprecipitate has the benefit of causing less hemodilution and thrombocytopenia after infusion compared to FFP.

  	FFP	Cryoprecipitate	Fibrinogen
  Dose	8 U	2 U	4 g
  Volume (mL)	2,000	400	200
  Fibrinogen (mg/dL)	100	130	120
  Hct (%)	-11	-3	–1.5

• Large amounts of shed blood processed in the cell salvage system can deplete plasma fractions including fibrinogen.
• Fibrinogen measurements by the Clauss method may be falsely elevated after large amounts of hydroxyethylstarch infusion.
• Thromboelastography/metry can be used to guide fibrinogen replacement (3).

for fibrinogen replacement therapy, one unit of cryoprecipitate per 10 kg body weight increases plasma fibrinogen by ~50 mg/dL in the absence of continued consumption or massive bleeding. To increase it to 100 mg/dL, the required number of cryoprecipitate is 0.2 x weight (kg).

• Fibrinogen
• Fresh Frozen Plasma (Ffp)
• Transfusion-Related Lung Injury (TRALI)
• Blood Transfusion Infection

Kenichi A. Tanaka , MD, MSc

Satoru Ogawa , MD