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Transfusion

Cryoprecipitate

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Cryoprecipitate refers to the proteins that precipitate out of solution when a unit of fresh frozen plasma is slowly thawed in the cold at 1 to 6o C and then refrozen within one hour. Each bag contains Factor VIII, fibrinogen, von Willebrand factor, and Factor XIII suspended in 10 to 15 mL of residual plasma. Bags are stored at -180C or colder. The risk of viral transmission from cryoprecipitate is the same as other plasma products.



Indications & Dose
Since several bags of cryoprecipitate are transfused at a time, they are usually pooled into a sterile plastic transfer pack and stored at 20-24oC until administration. Cryoprecipitate outdates 6 hours after being thawed or 4 hours after being pooled. ABO compatible cryoprecipitate is desirable if large volumes will be transfused. Rh compatibility is not important. Cryoprecipitate should be infused through a standard blood filter at a rate of 4 to 10 mL/minute. At this rate, a pool of 10 bags can be infused in approximately 30 minutes.

Cryoprecipitate is the currently recommended blood component for treatment of:
  • Congenital afibrinogenemia or hypofibrinogenemia if bleeding or undergoing surgery
  • Dysfibrinogenemia
  • Acquired hypofibrinogenemia (fibrinogen < 100 mg/dL)
  • Factor XIII deficiency if bleeding or undergoing invasive procedure
  • Qualitative platelet defects
  • Continuous venovenous hemofiltration (CVVH). BUN and creatinine may be normal
  • Localized vascular bleeding (fibrin glue)
  • vWD if emergency & factor VIII concentrate containing multimeric vWF is not available
  • Hemophilia A if emergency & factor concentrate is not available
  • Prophylactic treatment for acute DIC associated with head trauma
Cryoprecipitate should be transfused to patients with congenital fibrinogen deficiency only when they are bleeding or prior to an invasive or surgical procedure. The circulating half-life of fibrinogen is 3 to 5 days.

Consumptive coagulopathies, such as DIC, may produce acquired hypofibrinogenemia. Cryoprecipitate should be given when the fibrinogen level falls below 100 mg/dL, which is the minimal level needed for hemostasis. Each bag of cryoprecipitate contains 200 to 250 mg of fibrinogen and will increase the plasma fibrinogen level of a 70-kg adult by 6 to 8 mg/dL. Generally, 10 bags of cryoprecipitate are given if the fibrinogen level is between 50 &100 mg/dL and 20 bags are given if it is less than 50 mg/dL. A fibrinogen level measured at 30 to 60 minutes after completion of the transfusion should be used to determine the need for additional doses. The therapeutic goal is to keep the plasma fibrinogen level above 100 mg/dL.

Cryoprecipitate is often given prophylactically for head trauma because of the associated localized disseminated intravascular coagulation that can result in intracranial hemorrhage. In patients with either blunt or penetrating head trauma, 10 units of cryoprecipitate should be given empirically or when serial fibrinogen levels indicate a precipitous drop in fibrinogen level.

Cryoprecipitate is the treatment of choice for patients with documented factor XIII deficiency whom are actively bleeding or undergoing an invasive or surgical procedure. Factor XIII deficiency can usually be treated with 1 bag of cryoprecipitate for every 10 kg of body weight. Factor XIII assays should be used to evaluate the need for repeat administration in Factor XIII deficiency.

Cryoprecipitate is beneficial in correcting the thrombopathy associated with uremia. Ten bags of cryoprecipitate are usually required to reverse a qualitative platelet defect. The maximum therapeutic effect takes at least 4 hours after infusion to develop and lasts approximately 24 hours. Repeat administration of cryoprecipitate provides limited improvement. The use of cryoprecipitate to correct a qualitative platelet defect should be reserved for life-threatening hemorrhage or prior to an invasive procedure. Alternatively, desmopressin (DDAVP) or dialysis can be used to correct the uremic platelet defect.

Cryoprecipitate can also be used as a local hemostatic sealant and this application is commonly referred to as fibrin glue. It is best used when cautery and suture cannot control localized bleeding. Diffuse bleeding will not improve with fibrin glue. The three essential ingredients of fibrin sealant are the fibrinogen present in cryoprecipitate, bovine or human thrombin, and calcium chloride. A vial of lyophilized thrombin is reconstituted with calcium chloride and aspirated into one chamber of a double-barreled syringe. One or two units of cryoprecipitate are generally used as a fibrin sealant depending on the severity of the bleeding and the surface area to be covered. A single unit of cryoprecipitate is aspirated into the other barrel. Both solutions are delivered simultaneously through a blunt tipped cannula or spray atomizer on to the bleeding site. A clot forms in a matter of seconds to minutes, and lasts up to 2 weeks. Adverse effects include the formation of antibodies to bovine thrombin and factor V, which may cause bleeding. Another potential complication is anaphylaxis.

Cryoprecipitate should not be used to treat von Willebrand's disease except in life and limb-threatening emergencies when multimeric vWF-containing Factor VIII concentrate (Humate P, Alphanate, or Koate DVI) is not immediately available. A reasonable dose of cryoprecipitate is 1 bag for every 10 Kg of body weight. This dose should be repeated every 8 to 12 hours. The amount of von Willebrand factor contained within a given unit of cryoprecipitate is highly variable and dependent upon the donor's plasma level.

Cryoprecipitate should be used to treat Hemophilia A only when Factor VIII concentrate is not available. Cryoprecipitate should never be used for the treatment of hemophilia B since it lacks Factor IX.