cryoprecipitate

Cryoprecipitate is a blood product containing specialized insoluble blood proteins known as coagulation factors that regulate the clotting and clot-dissolving processes.

Cryoprecipitate is obtained from plasma, the fluid component of blood, and is used to treat patients with blood clotting (coagulation) disorders and to control hemorrhage during major surgery or during and after childbirth.

Plasma is a straw-colored fluid that carries the blood cells, gases, enzymes, and nutrients to all the body organs and carries back the waste products for elimination. 

Cryoprecipitate is obtained from fresh frozen plasma (FFP) by thawing it at 1 to 6 degrees Celsius and extracting the precipitate that forms, by centrifugation process. The precipitate is resuspended in plasma and can be refrozen at -18 degrees C and stored for up to a year. Cryoprecipitate contains coagulation factors XIII, VIII, von Willebrand factor, and fibrinogen, all of which play important roles in blood clot formation. Cryoprecipitate is administered to patients who are deficient in these factors and are bleeding or at a high risk of bleeding.

• Do not administer cryoprecipitate to replace isolated factor deficiencies of factors XIII, VIII, or von Willebrand factor if the appropriate factor concentrates are available.
• Cryoprecipitate is deficient in all coagulation factors other than fibrinogen, factor VIII, factor XIII, and von Willebrand factor. Do not use it to treat deficiencies of other factors, or as a single agent when replacement of multiple coagulation factors is required.
• All cryoprecipitate transfusions must be given using 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 medications or fluids other than normal saline should be simultaneously given through the same line as cryoprecipitate without prior consultation with the medical director of the blood bank.
• ABO compatibility is not required except in neonates and small children because each unit of cryo has a low volume, unless high volumes of cryo are required to be transfused.
• Plasma transfusions may be used in place of Factor XIII replacement if the patient is not at significant risk of volume overload, because it may reduce the number of donor exposures. Fresh frozen plasma can provide all the factors present in cryo in equal or greater amounts, however, a higher volume of plasma will be required to provide an equivalent volume of factors.
• Exercise caution with the rate of transfusion. Rapid or massive cryo transfusion may cause irregular heart rhythms (arrhythmias), heart failure, low body temperature (hypothermia), shortness of breath (dyspnea), low blood calcium levels (hypocalcemia), and/or high potassium levels (hyperkalemia).
• Monitor patients for signs of transfusion reaction, including vital signs, before, during, and after transfusion. If a transfusion reaction is suspected, stop the transfusion, assess and stabilize the patient, and notify the blood bank to initiate an investigation.
• Cryo transfusions carry the risk for non-septic infections including human immunodeficiency virus (HIV) hepatitis B and C viruses (HBV and HCV), human T-lymphotropic virus (HTLV), cytomegalovirus (CMV), West Nile virus (WNV), parvovirus B19, Lyme disease, babesiosis, malaria, Chagas disease, and variant Creutzfeldt-Jakob disease (vCJD).
• Consult with the blood bank medical director or a hematologist if you have questions regarding special transfusion requirements.

Common side effects of cryoprecipitate include:

• Hemolytic transfusion reactions that destroy red blood cells
• Feverish (febrile) non-hemolytic reactions
• Transfusion-associated circulatory overload (TACO)
• Transfusion-related acute lung injury (TRALI)
• Transfusion-transmitted infections and septic reactions
• Transfusion-associated graft-versus-host disease (TA-GVHD)
• Allergic reactions such as:
  • Hives (urticaria)
  • Itching (pruritus)
• Severe allergic reaction (anaphylaxis)
• Post-transfusion bruising (purpura)

Call your doctor immediately if you experience any of the following symptoms or serious side effects while using this drug:

• Serious heart symptoms include fast or pounding heartbeats, fluttering in your chest, shortness of breath, and sudden dizziness;
• Severe headache, confusion, slurred speech, severe weakness, vomiting, loss of coordination, feeling unsteady;
• Severe nervous system reaction with very stiff muscles, high fever, sweating, confusion, fast or uneven heartbeats, tremors, and feeling like you might pass out; or
• Serious eye symptoms include blurred vision, tunnel vision, eye pain or swelling, or seeing halos around lights.

This is not a complete list of all side effects or adverse reactions that may occur from the use of this drug. Call your doctor for medical advice about serious side effects or adverse reactions. You may also report side effects or health problems to the FDA at 1-800-FDA-1088.

Adult:

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 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 5 kg 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 10 kg 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 and 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:

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 5 kg 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 10 kg 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

Inform your doctor of all medications you are currently taking, who can advise you on any possible drug interactions. Never begin taking, suddenly discontinue, or change the dosage of any medication without your doctor’s recommendation.

• Cryoprecipitate has no known severe, serious, moderate, or mild interactions with other drugs.

The drug interactions listed above are not all of the possible interactions or adverse effects. For more information on drug interactions, visit the RxList Drug Interaction Checker.

It is important to always tell your doctor, pharmacist, or health care provider about all prescription and over-the-counter medications you use, as well as the dosage for each, and keep a list of the information. Check with your doctor or healthcare provider if you have any questions about the medication.

• Cryoprecipitate may be used in pregnant women to maintain adequate fibrinogen levels and to control bleeding in the event of hemorrhage before, during, and post-childbirth.
• Pregnant women normally have higher levels of fibrinogen to prevent excessive bleeding during labor, and cryoprecipitate transfusion may be indicated at higher levels, such as when it is below 200 mg/dL. Standard cryoprecipitate transfusion is performed typically when fibrinogen is below 100-150 mg/dL.
• There is no information available on cryoprecipitate infusion in nursing mothers.