Ileana Lopez-Plaza, M.D., Associate Medical Director, Centralized
Transfusion Service
INTRODUCTION
Cryoprecipitate is a human blood component obtained from fresh frozen
plasma (FFP) prepared from a unit of whole blood (WB). When FFP is thawed in the cold, a
cryoprecipitate forms which is rich in fibrinogen, factor VIII, von Willebrand factor,
factor XIII, and fibronectin.
COMPOSITION AND STORAGE
One unit of cryoprecipitate derived from a unit of whole blood contains
a volume of 10-20 mL, 80-100 units of factor VIII which consists of both the procoagulant
activity and the von Willebrand factor, 150-250 mg of fibrinogen, 50-100 units of factor
XIII, and 50-60 mg of fibronectin. It can be stored at -18° C for a maximum of one
year. When ordered, cryoprecipitate is thawed in a 37° C waterbath and issued in
individual bags or as a pooled product. Once thawed it must be kept at room temperature
and has an expiration time of 6 hours for unpooled cryoprecipitate, and 4 hours for the
pooled product.
THERAPEUTIC INDICATIONS
In the past, cryoprecipitate rich in factor VIII and von Willebrand
factor, was considered the treatment of choice for factor VIII replacement in Hemophilia A
and von Willebrand disease. The development of virally safe factor concentrates have
supplanted the role of cryoprecipitate as the therapy of choice for treating these
diseases. Currently, the primary indications for cryoprecipitate are for treating
fibrinogen deficiency or dysfunction or as a source of fibrinogen for topical use (fibrin
glue).
Fibrinogen Deficiency or Dysfunction: Cyroprecipitate is
the product of choice for the management of bleeding patients with fibrinogen levels of
<100 mg/dL or with a dysfibrogenemia. The recommended initial dose if 6-10 units. Each
unit will raise the fibrinogen level by approximately 5-10 mg/dL in an average adult. The
target hemostatic concentration of fibrinogen should be >100 mg/dL.
Fibrin Glue: Cryoprecipitate can be used as a source of
fibrinogen to make fibrin glue. Fibrin glue can be used as a topical adhesive or
hemostatic agent to decrease microvascular bleeding during surgical procedures. The use of
topical fibrinogen or fibrin glue has been described in detail in the Transfusion
Medicine Update, July 1992.
von Willebrands Disease: von Willebrands
Disease is a congenital bleeding disorder consisting of heterogeneous deficiencies or
abnormalities of the von Willebrand multimers. The therapy of choice in patients with mild
or moderate von Willebrands disease, with the exception of type IIb, is desmopressin
(DDAVP) 0.3m g/kg. DDAVP is a synthetic agent which causes the release of factor VIII and
von Willebrand factor from endothelial stores. For severe von Willebrands disease
the treatment of choice is a viral-inactivated factor VIII concentrate containing the high
molecular weight von Willebrand multimers (Humate PÒ , Armour). The second line of
therapy is cryoprecipitate in a recommended dose of 10-12 units as initial therapy. The
dose should be repeated every 12 hours, as needed.
Hemophilia A: Hemophilia A is an X-linked inherited
deficiency of the procoagulant activity portion of factor VIII. The first choice of
treatment for mild (>5% level) Hemophilia A is DDAVP. For moderate (1-5% level) and
severe (<1% level) Hemophilia the therapy of choice is factor VIII concentrates. These
are considered safer than cryoprecipitate product because they undergo a viral
inactivation treatment for transfusion transmitted viruses. When factor VIII concentrates
are not available cryoprecipitate can be used. Each unit of cryoprecipitate contains at
least 80 units of factor VIII.
Uremia: Uremic patients have multiple qualitative
platelet abnormalities that can manifest as a prolonged bleeding time and bleeding
diathesis. Hemodialysis is considered a first line treatment for this platelet defect,
however, it is not always effective. If hemodialysis fails to reverse the defect or if
this procedure cannot be performed, the treatment of choice is DDAVP. The effectiveness of
the DDAVP is believed to be due to the release of endogenous large von Willebrand factor
multimers into the circulation. However, its effectiveness is limited. Tachyphylaxis will
usually occur after repeated infusions of DDAVP. For those patients who do not respond to
DDAVP or who have a contraindication to the use of this agent, cryoprecipitate may be
beneficial. Cryoprecipitate contains large von Willebrand multimers which presumably
correct the bleeding diathesis. The cryoprecipitate is given as a dose of 10-12 units to
be repeated every 12 hours, as needed.
COMPLICATIONS
As a product derived from whole blood, the transfusion of
cryoprecipitate has the same risk of transmitting blood-borne pathogens such as HIV,
Hepatitits B, Hepatitis C, as the other blood components. Factor concentrates undergo
viral inactivation steps (heat, solvent/detergent) to inactivate the HIV, Hepatitis B, and
Hepatitis C viruses which make the factor concentrates a safer product to transfuse.
Cryoprecipitate also contains hemagglutinins (anti-A and/or anti-B). If large volumes of
ABO-incompatible cryoprecipitate are administered, intravascular hemolysis can occur.