Blood and Tissue Resources

New York State Council on Human Blood and Transfusion Services

Guidelines for the Administration of Cryoprecipitate

Guidelines (PDF file size: 41k)

I. Introduction

Cryoprecipitate, or "cryo", whose official US Food and Drug Administration (FDA) name is Cryoprecipitated Antihemophilic Factor, is the cold-insoluble portion of fresh frozen plasma (FFP) that precipitates when FFP is thawed at refrigerator temperatures (1-6C). Considered a blood component, it contains clotting factor proteins from a single donor resuspended in approximately 10 to 15 mL of plasma. Each unit contains a minimum of 80 IU of factor VIII and at least 150 mg of fibrinogen, in addition to significant amounts of von Willebrand factor and factor XIII. Stored frozen at = -18C until needed, cryoprecipitate must be stored at room temperature after thawing. It must be transfused within six hours of thawing and four hours of pooling, if pooling is performed. Cryoprecipitate is the only fibrinogen concentrate avail-able for intravenous use. Manufactured pathogen-inactivated fibrinogen concentrates may be used topically during surgery.

II. Indications For Cryoprecipitate

1. Hypofibrinogenemia or afibrinogenemia, in association with bleeding or prior to an invasive procedure
   Hypofibrinogenemia may be due to:
   1. lack of synthesis (e.g., liver disease);
   2. consumption (e.g., disseminated intravascular coagulation [DIC], abruptio placentae, amniotic fluid embolus, and treatment with asparaginase);
   3. dilution (e.g., massive transfusion or intensive plasma exchange); or
   4. inheritable deficiency
2. Any of the following conditions in association with bleeding or prior to surgery:
   1. von Willebrand disease for which other treatments, such as desmopressin (DDAVP) and von Willebrand factor-containing concentrates, are insufficient, contraindicated, unavailable, or have been ineffective (see Table 1);
   2. dysfibrinogenemias, both inheritable and acquired (e.g., due to liver disease);
   3. factor XIII deficiency;* and
   4. hemophilia A when other therapies, such as DDAVP and factor VIII concentrate, are inappropriate or unavailable in an emergency
      
      *Note: Cryoprecipitate is indicated for replacement in the case of factor XIII deficiency.¹ FFP may also be used, but infusion requires much larger volumes. Factor XIII concentrate is currently considered investigational in the US. Factor XIII deficiency is rare; however, there is no clear consensus on treatment, and consultation with a coagulation expert is recommended.
3. Uremia with bleeding, if the patient is unresponsive to other treatment modalities, including dialysis, DDAVP, and estrogen
4. Kasabach-Merritt syndrome (hemangioma-thrombocytopenia syndrome) with co-morbid DIC
5. Surgical and other invasive procedures, as a source of fibrinogen if mixed with thrombin at bleeding sites to form fibrin sealant

Table 1. Responsiveness to DDAVP in von Willebrand disease

* Risk of thrombocytopenia

Note: A trial dose should be given prior to administration of a full dose.

III. Cryoprecipitate Administration and Fibrin Sealant Application

1. Cryoprecipitate
   1. For fibrinogen replacement, two units of cryoprecipitate/10 kg of body weight generally raises fibrinogen concentration by 100 mg/dL, except in cases of DIC or continued bleeding with massive transfusion. Therapy should be based on clinical status, with a goal of achieving and maintaining a fibrinogen concentration of 100 mg/dL, as clinically indicated.^2,3
   2. Cryoprecipitate is usually pooled and transfused through a 170 - 250 micron filter.
2. Fibrin Sealant
   1. Patients should be informed that they will be receiving a blood product, albeit in a non-traditional form.
   2. Rare adverse antibody-mediated coagulation reactions to fibrin sealant have been reported.⁴ Bovine thrombin may be contaminated with bovine factor V, which may induce antibody formation. Those antibodies may form immune complexes with human factor V, and also with factors VIII, II, and/or XI, leading to a decrease in functioning coagulation factors. Bleeding has been reported, usually in association with factor V deficiency; anamnestic responses may occur. Antibodies induced by bovine thrombin have also been reported to cause thrombosis. Improvements in preparation of newer products have reduced bovine factor V contamination and the risk of bleeding.

References

1. Acharya SS, Coughlin A, Dimichele DM. North American Rare Bleeding Disorder Study Group. Rare bleeding disorder registry: deficiencies of factors II, V, VII, X, XIII, fibrinogen and dysfibrinogenemias. J Thromb Haemost 2004;2:248-56.
2. Becker J, Glackall D, Evans C, et al. Scientific Section Coordinating Committee. Guidelines for blood utilization review. Bethesda: American Association of Blood Banks, 2001.
3. Stainsby D, MacLennan S, Hamilton PJ. Management of massive blood loss: a template guideline. Br J Anaesth 2000;85:487-91.
4. Nichols WL. Adverse antibody-mediated reactions to topical bovine thrombin and fibrin glue. In: U.S.A. Department of the Army, Food and Drug Administration, and National Institutes of Health. Fibrin sealant: characteristics and clinical uses. Proceedings of the Uniformed Services University of the Health Sciences, 1994:5-10.

Pertinent Literature

• Alving BM. Beyond hemophilia and von Willebrand disease: treatment of patients with other inherited coagulation factor and inhibitor deficiencies. In: Alving BM, ed. Blood components and pharmacologic agents in the treatment of congenital and acquired bleeding disorders. Bethesda: American Association of Blood Banks, 2000:341-56.
• Pantanowitz L, Kruskall MS, Uhl L. Cryoprecipitate. Patterns of use. Am J Clin Pathol 2003; 119:874-81.
• Poon MC. Cryoprecipitate: uses and alternatives. Transfus Med Rev 1993;7:180-92.
• American Association of Blood Banks, America's Blood Centers, American Red Cross. Circular of Information for the Use of Human Blood and Blood Components. Bethesda, MD: American Association of Blood Banks, 2002.