Journal of Clinical Apheresis 7:218 (1992)
Questions and Answers QUESTION In a recent article by Bick and Tse, “Hemostasis abnormalities associated with prosthetic devices and organ transplantation” (Lab Med 1992; 23:462-468) the authors discuss coagulation abnormalities following plasma exchange secondary to the removal of clotting factors. In addition, they state that thrombotic complications can be avoided by use of heparin in the replacement fluids or by the infusion of fresh frozen plasma as a source of AT-111. How serious are the coagulation anomalies caused by plasma exchange? REPLY We addressed this question to Duke 0. Kasprisin, M.D., Chairman of the Clinical Applications Committee of the American Society for Apheresis and Bruce C. McLeod, M.D., President of the American Society for Apheresis. Their reply is as follows: Plasma exchange is frequently used to remove plasma which contains pathologic substances. When plasma is withdrawn and replaced by saline and/or albumin, an inevitable consequence is a dilutional decrease in clotting factors, antibodies and other normal plasma constituents. Dilutional changes are less evident when cytoreduction procedures are performed by apheresis, i.e., plateletpheresis and leukophoresis. Whether the removal of these normal plasma constituents becomes clinically significant depends on the degree of depletion and the speed with which adequate factor levels can be restored. In the vast majority of patients undergoing plasma exchange the removal of clotting factors is not great enough to cause bleeding problems and most abnormal coagulation studies return to normal within 24 hours. Bleeding problems were noted in only 2.9% of procedures in one study of adult patients [ 11. Pediatric patients undergoing plasma exchange have also been evaluated. Children receiving plasma exchange developed abnormal partial thromboplastin times, prothrombin times and decreased individual clotting factors, HMW kininogen, prekallikrein, antithrombin I11 and plasminogen [2] but these values returned to normal
0 1992 Wiley-Liss, Inc.
within 24 hours and no bleeding problems were observed. This study also found no problems with thrombosis other than occlusion of vascular shunts. Clotting in access lines is not unique to plasma exchange and need not signify a systemic thrombotic problem. Since thrombotic problems are rare the routine addition of fresh frozen plasma to the replacement fluids does not seem warranted. In addition to the risks of transfusion transmitted viral illness there is evidence collected by Huestis [3] that serious problems are more common when fresh frozen plasma is used as a replacement fluid. In his worldwide survey of mortality during plasma exchange, he found that plasma was used in 76% of the cases that resulted in death. Of the 28 cardiac and respiratory deaths reported, plasma had been used in 26 (93%). Since plasma is not commonly used as a replacement during plasma exchange, these figures are even more worrisome. Therefore, the use of plasma as a replacement should be limited to those disorders where plasma has been shown to be of benefit, e.g., thrombotic thrombocytopenic purpura. Considering the large number of seriously ill patients who have been treated by plasma exchange without major complications, it appears that plasma exchange is a relatively safe procedure. REFERENCES Keller AJ, Chirnside A , Urbaniak SJ: Coagulation abnormalities produced by plasma exchange on the cell separator with special reference to fibrinogen and platelet levels. Br J Haematol 42:579, 1979. Rao AK, Schneider B, Beckett C , et al: The hemostatic system in children undergoing intensive plasma exchange. J Pediatr 100:62, 1982. Huestis DW: Complications of therapeutic apheresis. In Valbonesi M, Pineda AA, Biggs JC (eds) “Therapeutic Hemapheresis.” Milano, Italy: Wichtig Editore, 1986, p 179.
Please submit questions for this column directly to Harvey Klein, M.D., Chief, Department of Transfusion Medicine, Clinical Center, Bldg. 10, Room IC711, National Institutes of Health, Bethesda, MD 20892. Dr. Klein will distribute questions to the Clinical Applications Committee.
Questions and Answers QUESTION In a recent article by Bick and Tse, “Hemostasis abnormalities associated with prosthetic devices and organ transplantation” (Lab Med 1992; 23:462-468) the authors discuss coagulation abnormalities following plasma exchange secondary to the removal of clotting factors. In addition, they state that thrombotic complications can be avoided by use of heparin in the replacement fluids or by the infusion of fresh frozen plasma as a source of AT-111. How serious are the coagulation anomalies caused by plasma exchange? REPLY We addressed this question to Duke 0. Kasprisin, M.D., Chairman of the Clinical Applications Committee of the American Society for Apheresis and Bruce C. McLeod, M.D., President of the American Society for Apheresis. Their reply is as follows: Plasma exchange is frequently used to remove plasma which contains pathologic substances. When plasma is withdrawn and replaced by saline and/or albumin, an inevitable consequence is a dilutional decrease in clotting factors, antibodies and other normal plasma constituents. Dilutional changes are less evident when cytoreduction procedures are performed by apheresis, i.e., plateletpheresis and leukophoresis. Whether the removal of these normal plasma constituents becomes clinically significant depends on the degree of depletion and the speed with which adequate factor levels can be restored. In the vast majority of patients undergoing plasma exchange the removal of clotting factors is not great enough to cause bleeding problems and most abnormal coagulation studies return to normal within 24 hours. Bleeding problems were noted in only 2.9% of procedures in one study of adult patients [ 11. Pediatric patients undergoing plasma exchange have also been evaluated. Children receiving plasma exchange developed abnormal partial thromboplastin times, prothrombin times and decreased individual clotting factors, HMW kininogen, prekallikrein, antithrombin I11 and plasminogen [2] but these values returned to normal
0 1992 Wiley-Liss, Inc.
within 24 hours and no bleeding problems were observed. This study also found no problems with thrombosis other than occlusion of vascular shunts. Clotting in access lines is not unique to plasma exchange and need not signify a systemic thrombotic problem. Since thrombotic problems are rare the routine addition of fresh frozen plasma to the replacement fluids does not seem warranted. In addition to the risks of transfusion transmitted viral illness there is evidence collected by Huestis [3] that serious problems are more common when fresh frozen plasma is used as a replacement fluid. In his worldwide survey of mortality during plasma exchange, he found that plasma was used in 76% of the cases that resulted in death. Of the 28 cardiac and respiratory deaths reported, plasma had been used in 26 (93%). Since plasma is not commonly used as a replacement during plasma exchange, these figures are even more worrisome. Therefore, the use of plasma as a replacement should be limited to those disorders where plasma has been shown to be of benefit, e.g., thrombotic thrombocytopenic purpura. Considering the large number of seriously ill patients who have been treated by plasma exchange without major complications, it appears that plasma exchange is a relatively safe procedure. REFERENCES Keller AJ, Chirnside A , Urbaniak SJ: Coagulation abnormalities produced by plasma exchange on the cell separator with special reference to fibrinogen and platelet levels. Br J Haematol 42:579, 1979. Rao AK, Schneider B, Beckett C , et al: The hemostatic system in children undergoing intensive plasma exchange. J Pediatr 100:62, 1982. Huestis DW: Complications of therapeutic apheresis. In Valbonesi M, Pineda AA, Biggs JC (eds) “Therapeutic Hemapheresis.” Milano, Italy: Wichtig Editore, 1986, p 179.
Please submit questions for this column directly to Harvey Klein, M.D., Chief, Department of Transfusion Medicine, Clinical Center, Bldg. 10, Room IC711, National Institutes of Health, Bethesda, MD 20892. Dr. Klein will distribute questions to the Clinical Applications Committee.
