USE OF TOPICAL FIBRINOGEN

Darrell J. Triulzi, M.D., Assistant Medical Director, Patient Transfusion Services

INTRODUCTION

There has been a growing interest in the use of operative sealants or adhesive agents to decrease intraoperative bleeding and to promote hemostasis.  For this purpose, a concentrated source of fibrinogen that can be readily converted to fibrin (“fibrin glue”) has been advocated by many surgeons.  Numerous reports attest to the efficacy of topical fibrinogen as a local hemostatic agent (Ann Thorac Surg 1990; 50:40-4).

fibrinogen preparation

At present, there are no commercially available sources of fibrinogen in the United States.  However, most blood banks can readily provide fibrinogen for topical use in the form of cryoprecipitate.  One unit of cryoprecipitate is derived from one unit of fresh frozen plasma and contains at least 150 mg. Of fibrinogen in a 15-25 ml volume.  Cryoprecipitate is prepared in a closed system to minimize bacterial contamination and is subject to the same rigid standards as all blood products including extensive screening for the blood borne pathogens.

mechanism of action

In the presence of calcium, fibrinogen is rapidly converted to fibrin by the action of thrombin to form a firm, non-friable clot.  Because of its adhesive properties, fibrin glue will tightly adhere to the surface of tissues thereby providing a hemostatic plug.  Cryoprecipitate also contains two other factors which promote hemostasis and wound healing, factor XIII and fibronectin.  The former is necessary for cross-linking fibrin monomers and strengthening the clot.  Fibrinopectin appears to facilitate fibroblastic growth into the fibrin seal.

administration

Topical fibrinogen in the form of cryoprecipitate is supplied in a sterile bag.  The contents must be aspirated with a syringe and mixed with reconstituted human or bovine thrombin.  Application can be carried out with a double-barreled syringe that allows for simultaneous mixing of the cryoprecipitate and thrombin.  The mixture is delivered through a soft-tip cannula or spray atomizer.  The clotting process is enhanced if the thrombin is reconstituted with calcium chloride.  Optimal doses of thrombin range from 500-1000 NIH units.  Amounts of thrombin in excess of this can lower the tensile strength of the fibrin seal whereas lower doses of thrombin will prolong the time for a clot to form.

Generally, a single bag of cryoprecipitate contains sufficient fibrinogen for topical use in a surgical procedure.

indications

Topical fibrinogen has been employed for local hemostasis in numerous surgical procedures and appears to be highly successful in reducing microvascular bleeding.  It also promotes adhesion between different tissues or to prosthetic devices.  By reducing surgical blood loss, topical fibrinogen may decrease the need for additional blood components and the number of donor exposures.  To date, specific guidelines for its use have not been formulated.

The most extensive reported use of topical fibrinogen is in cardiothoracic and vascular surgery.  It has been widely used to control foci of microvascular bleeding, to seal graft anastomoses, and prosthetic valves, and to reduce mediastinal drainage.  Topical fibrinogen has also been used for many general surgical neurosurgical, ENT, plastic, and orthopedic procedures.

RISKS

as topical fibrinogen is derived from cryoprecipitate, it has all the attendant risks of a homologous blood exposure.  The risk of bacterial contamination is very low as it is collected in a closed system under sterile conditions.  It is capable of transmitting blood borne pathogens, although with the current screening procedures, these risk are also quite low.  Each bag of cryoprecipitate represents one donor exposure.

availability

Topical fibrinogen in the form of cryoprecipitate is frozen as a single unit (one bag) and can be readily obtained from Central Blood Bank.  When a unit is requested, it is thawed and dispensed to the operating room.  ABO compatibility is not required as the product contains only small amounts of plasma.  A kit containing a double-barrel syringe adapter, soft-tipped cannula, and spray atomizer is available from Central Blood Bank.  Bovine thrombin and calcium chloride are obtained from the hospital’s pharmacy.

Copies of the Transfusion Medicine Update can be obtained by contacting Deborah Small at (412) 209-7320 or
by e-mail:  dsmall@itxm.org.