Variability in the Fibrinogen and Von Willebrand Factor Content of Cryoprecipitate Implications for Reducing Donor Exposure MAUREANE HOFFMAN, M.D., PH.D. AND PAUL JENNER, M.D.
THE ADVENT OF acquired immune deficiency syndrome (AIDS) has increased the general awareness of the potential complications of transfusion and resulted in changes in the practice of component therapy. Efforts are being made to reduce donor exposure by re-evaluating the need for transfusion and administering the minimum Received July 11, 1989; received revised manuscript and accepted for publication August 18, 1989. Presented at the 1988 annual meeting of the American Association of Blood Banks, Kansas City, Missouri. Address reprint requests to Dr. Hoffman: Blood Bank, CB No. 7600, North Carolina Memorial Hospital, The University of North Carolina, Chapel Hill, North Carolina 27514.
Department of Pathology and The Center for Thrombosis and Hemostasis, The University of North Carolina, Chapel Hill; and American Red Cross Blood Services, Carolinas Region, Charlotte, North Carolina
effective dose of blood products. Cryoprecipitate originally was produced as a concentrated source of factor VIII for the treatment of patients with hemophilia A. The availability of commercial Factor VIII concentrates revolutionized the treatment of hemophilia and reduced the use of cryoprecipitate as a source of Factor VIII. The development of recombinant Factor VIII preparations should remove the risk of infectious complications of Factor VIII therapy12 and may eliminate the use of cryoprecipitate for Factor VIII replacement. Cryoprecipitate is a clinically useful source of fibrinogen8 and von Willebrand's factor (vWF).4 The clinicians in this hospital use cryoprecipitate more frequently to provide fibrinogen and vWF than to provide Factor VIII (Hoffman, unpublished data). Minimum acceptable levels of Factor VIII in cryoprecipitate are prescribed by regulatory and accrediting agencies, and representative units are routinely assayed to assure that these standards are met. However, information on the fibrinogen and vWF content of cryoprecipitate produced by a specific supplier is rarely available. As pointed out previously,3'5,10 fibrinogen content can vary greatly with the method of cryoprecipitate preparation. Therefore, literature estimates of fibrinogen content are not necessarily accurate estimates of the composition of the product available from a given supplier. Because of this lack of information, physicians transfuse a cryoprecipitate dose that is more than enough to give the desired clinical response based on previous experience. Parameters such as cessation of hemorrhage, bleeding time, or clotting time often are monitored. This approach encourages administration of doses higher than the minimum that would be effective for a given indication. If accurate information on the composition of cryoprecipitate were available, a minimum effective dose could be
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Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
Advances in the preparation of commercial Factor VIII concentrates have decreased the clinical use of cryoprecipitate to replace Factor VIII coagulant activity. Cryoprecipitate is now frequently transfused as a source of fibrinogen or von Willebrand factor (vWF). The minimum acceptable content of Factor VIII is prescribed, but no attempt is made to optimize, standardize, or assess the content of fibrinogen or vWF in cryo. If reasonably accurate information on the composition of cryoprecipitate were available, the physician could calculate an appropriate dose of cryo, thus avoiding unnecessary donor exposures and waste of product. This study was designed to measure the functionally active vWF and fibrinogen in cryoprecipitate prepared by three techniques in an attempt to optimize the yield of these hemostatically important components, and to obtain accurate information on the composition of the product. Cryoprecipitate was made from 82 units of fresh frozen plasma (FFP) as follows: (1) most of the supernatant plasma was expressed from "dry" cryo; (2) about 15 mL of plasma was left in each "regular" unit; and (3) "overnight" units were made from FFP thawed overnight in a refrigerator rather than in a 4 °C water bath as for the dry and regular units. Dry, regular, and overnight units had volumes of 8.8 ± 1.5,16.6 ± 3.9, and 15.1 ± 2.4 mL/bag, respectively. Dry cryoprecipitate units had significantly less fibrinogen and vWF than regular or overnight units. The vWF multimer pattern for all three types of cryoprecipitate was indistinguishable from that of normal pooled plasma. Thus, the amount of plasma expressed during preparation has a significant impact on the vWF and fibrinogen content of the resulting product. The amounts of these clinically important proteins should be assayed as a step toward rational determination of optimal cryoprecipitate doses in specific clinical settings. (Key words: Coagulation proteins; Transfusion; Blood products) Am J Clin Pathol 1990;93:694-697
BRIEF SCIENTIFIC REPORTS
Vol. 93 • No. 5
calculated. This strategy would reduce the number of different blood donors to which a patient would be exposed and thus reduce the risk of transfusion-associated disease transmission. The present study was undertaken to measure the fibrinogen and vWF content of cryoprecipitate prepared by the Regional Red Cross affiliate, and to determine whether the recovery could be increased by increasing the volume of the cryoprecipitate units or prolonging the thawing time.
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THE ADVENT OF acquired immune deficiency syndrome (AIDS) has increased the general awareness of the potential complications of transfusion and resulted in changes in the practice of component therapy. Efforts are being made to reduce donor exposure by re-evaluating the need for transfusion and administering the minimum Received July 11, 1989; received revised manuscript and accepted for publication August 18, 1989. Presented at the 1988 annual meeting of the American Association of Blood Banks, Kansas City, Missouri. Address reprint requests to Dr. Hoffman: Blood Bank, CB No. 7600, North Carolina Memorial Hospital, The University of North Carolina, Chapel Hill, North Carolina 27514.
Department of Pathology and The Center for Thrombosis and Hemostasis, The University of North Carolina, Chapel Hill; and American Red Cross Blood Services, Carolinas Region, Charlotte, North Carolina
effective dose of blood products. Cryoprecipitate originally was produced as a concentrated source of factor VIII for the treatment of patients with hemophilia A. The availability of commercial Factor VIII concentrates revolutionized the treatment of hemophilia and reduced the use of cryoprecipitate as a source of Factor VIII. The development of recombinant Factor VIII preparations should remove the risk of infectious complications of Factor VIII therapy12 and may eliminate the use of cryoprecipitate for Factor VIII replacement. Cryoprecipitate is a clinically useful source of fibrinogen8 and von Willebrand's factor (vWF).4 The clinicians in this hospital use cryoprecipitate more frequently to provide fibrinogen and vWF than to provide Factor VIII (Hoffman, unpublished data). Minimum acceptable levels of Factor VIII in cryoprecipitate are prescribed by regulatory and accrediting agencies, and representative units are routinely assayed to assure that these standards are met. However, information on the fibrinogen and vWF content of cryoprecipitate produced by a specific supplier is rarely available. As pointed out previously,3'5,10 fibrinogen content can vary greatly with the method of cryoprecipitate preparation. Therefore, literature estimates of fibrinogen content are not necessarily accurate estimates of the composition of the product available from a given supplier. Because of this lack of information, physicians transfuse a cryoprecipitate dose that is more than enough to give the desired clinical response based on previous experience. Parameters such as cessation of hemorrhage, bleeding time, or clotting time often are monitored. This approach encourages administration of doses higher than the minimum that would be effective for a given indication. If accurate information on the composition of cryoprecipitate were available, a minimum effective dose could be
694
Downloaded from http://ajcp.oxfordjournals.org/ by guest on June 6, 2016
Advances in the preparation of commercial Factor VIII concentrates have decreased the clinical use of cryoprecipitate to replace Factor VIII coagulant activity. Cryoprecipitate is now frequently transfused as a source of fibrinogen or von Willebrand factor (vWF). The minimum acceptable content of Factor VIII is prescribed, but no attempt is made to optimize, standardize, or assess the content of fibrinogen or vWF in cryo. If reasonably accurate information on the composition of cryoprecipitate were available, the physician could calculate an appropriate dose of cryo, thus avoiding unnecessary donor exposures and waste of product. This study was designed to measure the functionally active vWF and fibrinogen in cryoprecipitate prepared by three techniques in an attempt to optimize the yield of these hemostatically important components, and to obtain accurate information on the composition of the product. Cryoprecipitate was made from 82 units of fresh frozen plasma (FFP) as follows: (1) most of the supernatant plasma was expressed from "dry" cryo; (2) about 15 mL of plasma was left in each "regular" unit; and (3) "overnight" units were made from FFP thawed overnight in a refrigerator rather than in a 4 °C water bath as for the dry and regular units. Dry, regular, and overnight units had volumes of 8.8 ± 1.5,16.6 ± 3.9, and 15.1 ± 2.4 mL/bag, respectively. Dry cryoprecipitate units had significantly less fibrinogen and vWF than regular or overnight units. The vWF multimer pattern for all three types of cryoprecipitate was indistinguishable from that of normal pooled plasma. Thus, the amount of plasma expressed during preparation has a significant impact on the vWF and fibrinogen content of the resulting product. The amounts of these clinically important proteins should be assayed as a step toward rational determination of optimal cryoprecipitate doses in specific clinical settings. (Key words: Coagulation proteins; Transfusion; Blood products) Am J Clin Pathol 1990;93:694-697
BRIEF SCIENTIFIC REPORTS
Vol. 93 • No. 5
calculated. This strategy would reduce the number of different blood donors to which a patient would be exposed and thus reduce the risk of transfusion-associated disease transmission. The present study was undertaken to measure the fibrinogen and vWF content of cryoprecipitate prepared by the Regional Red Cross affiliate, and to determine whether the recovery could be increased by increasing the volume of the cryoprecipitate units or prolonging the thawing time.
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