Dosing and uses of CRYO (cryoprecipitate)
Fibrinogen Replacement
1 unit of cryo per 5kg patient weight will increase fibrinogen by about 100 mg/dL.
Number of bags = 0.2 x weight (kg) to provide about 100mg/dL fibrinogen
Many institutions use a standard dose of 10 units and then repeat if needed.
In conditions with increased fibrinogen turnover, fibrinogen levels should be monitored to adjust dosing.
Factor XIII Replacement
1 unit of cryo per 5kg patient weight will provide 10 U/kg of factor XIII
Number of bags = 0.2 x weight (kg)
Factor XIII has a long half-life and can usually be dosed every 3-6 weeks. Dosing schedule can vary by patient. Consultation with a hematologist or transfusion medicine physician is recommended.
Factor VIII Replacement
Consultation with a hematologist or hemostasis expert is recommended. Dosing depends on patient factor VIII (8) level and requires routine monitoring of factor VIII (8) to determine appropriate dose.
Patients with inhibitors may not have adequate response requiring increased dosing or other measures.
In emergency situations, assume a desired increase of 100% for a loading dose. Dosing also depends on Plasma Volume (PV) which is a fraction of Total Blood Volume (TBV). TBV is typically estimated at 70 mL/kg, although it may vary based on age, sex, and body type.
TBV (mL) = 70 mL/kg x weight (kg)
PV (mL) = TBV x (1-Hct)
Number of bags = [Desired activity (%) – Current activity (%)] x PV / 80
Dosing should be repeated every 8-12 hours but will vary with each patient. Factor VIII activity (%) target depends on the indication.
Post surgery or major trauma replacement may be required for up to 10 days to maintain hemostasis.
von Willebrand Factor Replacement
Consultation with a hematologist or hemostasis expert is recommended. Dosing of 1 unit per 10kg patient weight will usually be enough to control bleeding.
Number of bags = 0.1 x weight (kg)
Repeat dosing may be required every 8-12 hours for up to 3 days followed by once daily dosing. Follow clinically to adjust dosing and with appropriate lab studies available at your institution.
Other Indications & Uses
Cryo is used most commonly for replacement of fibrinogen in patients that are bleeding or at increased risk of bleeding. Fibrinogen replacement may be indicated for hypofibrinogenemia or dysfibrinogenemia whether acquired or congenital. Many institutions transfuse cryo prior to administration of factor VIIa (7a) concentrate to ensure adequate fibrinogen for clot formation given the cost and short half-life of factor VIIa (7a) of about 4 hours.
Cryo may be used to treat bleeding due to Hemophilia A (factor VIII (8) deficiency) or von Willebrand disease when appropriate factor concentrates are not available and/or desmopressin (DDAVP) is contraindicated or ineffective. If the patient needs routine replacement of either of these factors for prophylaxis, every effort should be made to provide recombinant factor or factor specific concentrates.
Cryo may be used to treat or prevent bleeding due to Factor XIII (13) deficiency when factor XIII (13) concentrates are not available.
Cryo may be considered to treat uremic bleeding when other modalities have failed.
Commercially available, virus-inactivated fibrin sealants have replaced the use of cryo to make topical sealants for surgery.
Pediatric dosage forms and strengths
Fibrinogen Replacement
1 unit of cryo per 5 kg patient weight will increase fibrinogen by about 100 mg/dL.
Number of bags = 0.2 x weight (kg) to provide about 100 mg/dL fibrinogen
In conditions with increased fibrinogen turnover, fibrinogen levels should be monitored to adjust dosing.
Factor XIII Replacement
1 unit of cryo per 5kg patient weight will provide 10 U/kg of factor XIII
Number of bags =0.2 x weight (kg)
Factor XIII has a long half-life and can usually be dosed every 3-6 weeks. Dosing schedule can vary by patient. Consultation with a hematologist or transfusion medicine physician is recommended.
Factor VIII Replacement
Consultation with a hematologist or transfusion medicine physician is recommended. Dosing depends on patient factor VIII (8) level and requires routine monitoring of factor VIII (8) to determine appropriate dose. Dosing should be repeated every 8-12 hours but will vary with each patient. Post surgery or major trauma replacement may be required for up to 10 days to maintain hemostasis. Factor VIII activity (%) target depends on the indication. Patients with inhibitors may not have adequate response requiring increased dosing or other measures. In emergency situations, assume a desired increase of 100% for a loading dose. Dosing also depends on Plasma Volume (PV) which is a fraction of Total Blood Volume (TBV). TBV varies by age and is typically estimated as: Premature infant 90-105 mL/kg, Term newborn infant 80-90 mL/kg, and >3 months of age 70 mL/kg.
TBV (mL) = 70 mL/kg x weight (kg)
PV (mL) = TBV x (1-Hct)
Number of bags = [Desired activity (%) – Current activity (%)] x PV / 80
von Willebrand Factor Replacement
Consultation with a hematologist or hemostasis expert is recommended. Dosing of 1 unit per 10kg patient weight will usually be enough to control bleeding.
Number of bags = 0.1 x weight (kg)
Repeat dosing may be required every 8-12 hours for up to 3 days followed by once daily dosing. Follow clinically to adjust dosing and with appropriate lab studies available at your institution.
CRYO (cryoprecipitate) adverse (side) effects
Frequency not defined
Hemolytic Transfusion Reactions
Febrile Non-Hemolytic Reactions
Allergic Reactions ranging from urticaria to anaphylaxis
Septic Reactions
Transfusion Related Acute Lung Injury (TRALI)
Circulatory Overload
Transfusion Associated Graft Versus Host Disease
Post-transfusion Purpura
Warnings
Contraindications
Cryo should not be given for replacement of isolated factor deficiencies of factor VIII, von Willebrand factor, or factor XIII if the appropriate factor concentrates are available.
Cryo is deficient in all clotting factors other than fibrinogen, factor VIII, von Willebrand factor, and factor XIII and should not be used to treat deficiencies of other factors, nor used as the sole component when replacement of multiple factors is required.
Cautions
If a transfusion reaction is suspected, the transfusion should be stopped, the patient assessed and stabilized, the blood bank notified, and a transfusion reaction investigation initiated.
Massive or rapid transfusion may lead to arrhythmias, hypothermia, hyperkalemia, hypocalcemia, dyspnea, and/or heart failure.
Because each unit of cryo has low volume, ABO compatibility is not required except in neonates and small children unless high volumes of cryo are to be transfused.
Factor XIII replacement may also be replaced with plasma transfusions if the patient is not at significant risk of volume overload because it may reduce the number of donor exposures.
All of the factors in cryo are provided in equal or greater amounts in FFP; however the concentration is lower requiring more volume to obtain equivalent increases.
All transfusions must be given via blood administration sets containing 170- to 260-micron filters or 20- to 40-micron microaggregate filters unless transfusion is given via a bedside leukocyte reduction filter. No other medications or fluids other than normal saline should be simultaneously given through the same line without prior consultation with the medical director of the blood bank.
Patient’s should be monitored for signs of a transfusion reaction including vitals pre, during, and post transfusion.
Non-septic infectious risks include transmission of HIV (~1:2 mill), HCV (~1:1.5 mill), HBV (1:300k), HTLV, WNV, CMV, parvovirus B19, Lyme disease, babesiosis, malaria, Chaga’s disease, vCJD.
Consult with blood bank medical director or hematologist if you have questions regarding special transfusion requirements.
Pregnancy and lactation
Pregnancy categories
A: Generally acceptable. Controlled studies in pregnant women show no evidence of fetal risk.
B: May be acceptable. Either animal studies show no risk but human studies not available or animal studies showed minor risks and human studies done and showed no risk.
C: Use with caution if benefits outweigh risks. Animal studies show risk and human studies not available or neither animal nor human studies done.
D: Use in LIFE-THREATENING emergencies when no safer drug available. Positive evidence of human fetal risk.
X: Do not use in pregnancy. Risks involved outweigh potential benefits. Safer alternatives exist.
NA: Information not available.
Pharmacology of CRYO (cryoprecipitate)
Each unit (~10-15mL) provides:
Fibrinogen 150-250 mg with a half-life of 100-150 hours
Factor VIII (8) 80-150 U with a half-life of 12 hours
Von Willebrand factor 100-150 U with a half-life of 24 hours
Factor XIII (13) 50-75 U with a half-life of 150-300 hours
Cryo also contains fibronectin; however there are no clear indications for fibronectin replacement.
Mechanism of action
Each unit provides the above factors listed in the pharmacology section to support adequate hemostasis to treat or prevent bleeding.
Administration
Administer by IV infusion via a controlled-infusion device only.
Also has been administered by intracoronary infusion, intra-arterial infusion, or intracatheter instillation.
IV Administration
For treatment of PE, administer by IV infusion via a constant infusion pump capable of delivering a total volume of 195 mL.
Reconstitution
Reconstitute vial containing 250,000 units of urokinase by adding 5 mL of sterile water for injection without preservatives to provide a concentration of 50,000 units/mL. Gently roll and tilt vial until lyophilized powder dissolves to produce a clear or slightly straw-colored solution. Avoid shaking to minimize formation of filaments. Presence of such filaments does not indicate any decrease in potency; such solutions may be filtered through ≤0.45-mcm cellulose membrane filter.
Dilution
Following reconstitution, dilute further with 0.9% sodium chloride or 5% dextrose injection to yield a final infusion volume of 195 mL.
Rate of Administration
PE: Infuse at 90 mL/hour over 10 minutes (loading dose), then 15 mL/hour for 12 hours (maintenance dosage). To ensure delivery of entire dose, flush IV tubing with a volume of compatible diluent equal to that of tubing volume at a rate of 15 mL/hour.
PE: Has also been administered as a 2-hour IV infusion. (See PE under Dosage.)
Coronary artery thrombosis and MI: Administer 50% or 100% of the dose over 5 minutes as a rapid IV injection and the remainder, if any, as a continuous infusion over 45–90 minutes.
