LETTERS TO THE EDITOR
cardiovascular surgery, hepatic failure, liver transplant, or other acquired bleeding conditions, so that any opinion about relative efficacies is necessarily subjective. We encourage the authors to undertake such a study and look forward to their results. Particularly needed are data to support the suggestion that CRYO has a greater hemostatic efficacy than fibrinogen concentrates in the bleeding patient, mostly in liver transplant and coagulopathy of liver failure, perhaps due to fibrin stabilization by Factor (F)XIII. To our knowledge, FXIII is only mildly enriched in CRYO compared with FFP. Many studies demonstrate that fibrinogen concentrates increase the quality of the clot strength.4 A pilot study of liver transplant patients has demonstrated that fibrinogen concentrates have the potential to reduce the exposure to allogeneic blood products in this setting.5 The authors state that CRYO does not have supporters even among blood bankers and that fibrinogen concentrates have many campaigners. Clinically in the United States we use CRYO routinely as a source of fibrinogen replacement, and as we had stated in our review, we believe that CRYO will continue to have a place in inventory management for some smaller community hospitals. When advocating for either of the two products, we encourage the readers and the author of the letter to consider the current treatment of patients with hemophilia. In most countries where CRYO is still available, it is not used as a treatment for hemophilia due to the lack of antivirus processing. Furthermore, the World Federation of Hemophilia strongly recommends the use of inactivated plasma-derived concentrates in preference to CRYO. In fact, it has been suggested that the use of CRYO in acquired bleeding and surgical settings represents a paradigm of double standard. Of note is that several trials are under way to determine the utility of fibrinogen to reduce bleeding and the need for allogeneic blood products in major surgery, of which the authors are active participants.
CONFLICT OF INTEREST JHL serves on Steering Committees for CSL Behring and Grifols related to factor concentrate use in surgery; LTG has no disclosures.
Jerrold H. Levy, MD1 e-mail: [email protected] Lawrence T. Goodnough, MD2 e-mail: [email protected] 1 Department of Anesthesiology Duke University School of Medicine Durham, NC 2 Departments of Pathology and Medicine Stanford University School of Medicine Stanford Medical Center Palo Alto, CA 1444
TRANSFUSION Volume 54, May 2014
REFERENCES 1. Gröner A. Reply. Pereira A. Cryoprecipitate versus commercial fibrinogen concentrate in patients who occasionally require a therapeutic supply of fibrinogen: risk comparison in the case of an emerging transfusion-transmitted infection. Haematologica 2007;92:846-9. Haematologica 2008;93: e24-6; author reply e27. 2. Bevan DH. Cryoprecipitate: no longer the best therapeutic choice in congenital fibrinogen disorders? Thromb Res 2009;124(Suppl 2):S12-6. 3. Solomon C, Pichlmaier U, Schoechl H, et al. Recovery of fibrinogen after administration of fibrinogen concentrate to patients with severe bleeding after cardiopulmonary bypass surgery. Br J Anaesth 2010;104:555-62. 4. Dempfle CE, Kalsch T, Elmas E, et al. Impact of fibrinogen concentration in severely ill patients on mechanical properties of whole blood clots. Blood Coagul Fibrinolysis 2008;19: 765-70. 5. Noval-Padillo JA, Leon-Justel A, Mellado-Miras P, et al. Introduction of fibrinogen in the treatment of hemostatic disorders during orthotopic liver transplantation: implications in the use of allogenic blood. Transplant Proc 2010;42: 2973-4.
Routine neonatal coagulation testing increases use of fresh-frozen plasma We read with interest the findings of Christensen and colleagues1 that abnormal coagulation values do not appear to predict the risk of bleeding in the first week after preterm birth. We also note their tentative recommendation that observation (rather than treatment with freshfrozen plasma [FFP]) is indicated in the presence of an abnormal clotting test but no clinical evidence of bleeding. Much like the United States, UK FFP transfusion practice varies considerably.2 We would like to share the findings of a retrospective study of FFP transfusion practice (2003-2008) in two UK tertiary neonatal units which support the transfusion recommendations by Christensen and colleagues.1 Of note, we found an almost fivefold difference in the rate of FFP transfusion between our two regional, tertiary, and surgical neonatal units despite a comparable number of annual admissions. Routine admission coagulation screening of babies on admission was practiced in NICU1, whereas NICU2 had a policy of coagulation testing only when clinically indicated. A total of 4112 neonates were admitted to NICU1 and 3705 to NICU2 over the study period. All infants received routine parenteral vitamin K prophylaxis. A total of 164 (2.1%) admitted neonates received at least one FFP transfusion and 268 transfusions were given in total. There was a wide discordance in FFP transfusion rates between the
LETTERS TO THE EDITOR
units: 223 of 268 (83%) transfusion episodes occurred in NICU1 and 45 of 268 (17%) in NICU2. A total of 5.4% of NICU1 admissions received FFP compared to 1.2% of admissions to NICU2. In 72% of cases FFP was administered to correct isolated abnormal coagulation values without clinical evidence of bleeding. This was far more likely to occur in the unit with routine coagulation screening on admission (NICU1 172/223 (77%) vs. NICU2 21/45 (47%), p < 0.001). In 2009 a UK National Comparative Audit demonstrated that 62% of infants had received FFP in the absence of documented bleeding and 20% of doses given were likely to be subtherapeutic.3 We recorded the principal clinical reason for FFP use and pre- and posttransfusion laboratory measures of coagulation (prothrombin time [PT], activated partial thromboplastin time [APTT]), and fibrinogen using quoted preterm reference ranges of Andrew and colleagues.4 Paired pre- and posttransfusion coagulation studies were available for 193 of 268 (72%) of our transfusion episodes. If we consider only the cases where FFP was administered to correct isolated “abnormal” coagulation values, then FFP was only successful in bringing the baby into the normal range for APTT and PT (using reference ranges at time of original screening4) in 15 and 10% of cases, respectively. Christensen and coworkers devise a table in their article that defines abnormal coagulation values of preterm infants from blood drawn at birth. If we use their values for less than 28 and 28 to 34 weeks of gestation, we note that in a setting of isolated coagulopathy 68% (34/50) of infants less than 28 weeks of gestation and 59% (20/34) of infants 28 to 34 weeks of gestation are corrected to within the reference range (
cardiovascular surgery, hepatic failure, liver transplant, or other acquired bleeding conditions, so that any opinion about relative efficacies is necessarily subjective. We encourage the authors to undertake such a study and look forward to their results. Particularly needed are data to support the suggestion that CRYO has a greater hemostatic efficacy than fibrinogen concentrates in the bleeding patient, mostly in liver transplant and coagulopathy of liver failure, perhaps due to fibrin stabilization by Factor (F)XIII. To our knowledge, FXIII is only mildly enriched in CRYO compared with FFP. Many studies demonstrate that fibrinogen concentrates increase the quality of the clot strength.4 A pilot study of liver transplant patients has demonstrated that fibrinogen concentrates have the potential to reduce the exposure to allogeneic blood products in this setting.5 The authors state that CRYO does not have supporters even among blood bankers and that fibrinogen concentrates have many campaigners. Clinically in the United States we use CRYO routinely as a source of fibrinogen replacement, and as we had stated in our review, we believe that CRYO will continue to have a place in inventory management for some smaller community hospitals. When advocating for either of the two products, we encourage the readers and the author of the letter to consider the current treatment of patients with hemophilia. In most countries where CRYO is still available, it is not used as a treatment for hemophilia due to the lack of antivirus processing. Furthermore, the World Federation of Hemophilia strongly recommends the use of inactivated plasma-derived concentrates in preference to CRYO. In fact, it has been suggested that the use of CRYO in acquired bleeding and surgical settings represents a paradigm of double standard. Of note is that several trials are under way to determine the utility of fibrinogen to reduce bleeding and the need for allogeneic blood products in major surgery, of which the authors are active participants.
CONFLICT OF INTEREST JHL serves on Steering Committees for CSL Behring and Grifols related to factor concentrate use in surgery; LTG has no disclosures.
Jerrold H. Levy, MD1 e-mail: [email protected] Lawrence T. Goodnough, MD2 e-mail: [email protected] 1 Department of Anesthesiology Duke University School of Medicine Durham, NC 2 Departments of Pathology and Medicine Stanford University School of Medicine Stanford Medical Center Palo Alto, CA 1444
TRANSFUSION Volume 54, May 2014
REFERENCES 1. Gröner A. Reply. Pereira A. Cryoprecipitate versus commercial fibrinogen concentrate in patients who occasionally require a therapeutic supply of fibrinogen: risk comparison in the case of an emerging transfusion-transmitted infection. Haematologica 2007;92:846-9. Haematologica 2008;93: e24-6; author reply e27. 2. Bevan DH. Cryoprecipitate: no longer the best therapeutic choice in congenital fibrinogen disorders? Thromb Res 2009;124(Suppl 2):S12-6. 3. Solomon C, Pichlmaier U, Schoechl H, et al. Recovery of fibrinogen after administration of fibrinogen concentrate to patients with severe bleeding after cardiopulmonary bypass surgery. Br J Anaesth 2010;104:555-62. 4. Dempfle CE, Kalsch T, Elmas E, et al. Impact of fibrinogen concentration in severely ill patients on mechanical properties of whole blood clots. Blood Coagul Fibrinolysis 2008;19: 765-70. 5. Noval-Padillo JA, Leon-Justel A, Mellado-Miras P, et al. Introduction of fibrinogen in the treatment of hemostatic disorders during orthotopic liver transplantation: implications in the use of allogenic blood. Transplant Proc 2010;42: 2973-4.
Routine neonatal coagulation testing increases use of fresh-frozen plasma We read with interest the findings of Christensen and colleagues1 that abnormal coagulation values do not appear to predict the risk of bleeding in the first week after preterm birth. We also note their tentative recommendation that observation (rather than treatment with freshfrozen plasma [FFP]) is indicated in the presence of an abnormal clotting test but no clinical evidence of bleeding. Much like the United States, UK FFP transfusion practice varies considerably.2 We would like to share the findings of a retrospective study of FFP transfusion practice (2003-2008) in two UK tertiary neonatal units which support the transfusion recommendations by Christensen and colleagues.1 Of note, we found an almost fivefold difference in the rate of FFP transfusion between our two regional, tertiary, and surgical neonatal units despite a comparable number of annual admissions. Routine admission coagulation screening of babies on admission was practiced in NICU1, whereas NICU2 had a policy of coagulation testing only when clinically indicated. A total of 4112 neonates were admitted to NICU1 and 3705 to NICU2 over the study period. All infants received routine parenteral vitamin K prophylaxis. A total of 164 (2.1%) admitted neonates received at least one FFP transfusion and 268 transfusions were given in total. There was a wide discordance in FFP transfusion rates between the
LETTERS TO THE EDITOR
units: 223 of 268 (83%) transfusion episodes occurred in NICU1 and 45 of 268 (17%) in NICU2. A total of 5.4% of NICU1 admissions received FFP compared to 1.2% of admissions to NICU2. In 72% of cases FFP was administered to correct isolated abnormal coagulation values without clinical evidence of bleeding. This was far more likely to occur in the unit with routine coagulation screening on admission (NICU1 172/223 (77%) vs. NICU2 21/45 (47%), p < 0.001). In 2009 a UK National Comparative Audit demonstrated that 62% of infants had received FFP in the absence of documented bleeding and 20% of doses given were likely to be subtherapeutic.3 We recorded the principal clinical reason for FFP use and pre- and posttransfusion laboratory measures of coagulation (prothrombin time [PT], activated partial thromboplastin time [APTT]), and fibrinogen using quoted preterm reference ranges of Andrew and colleagues.4 Paired pre- and posttransfusion coagulation studies were available for 193 of 268 (72%) of our transfusion episodes. If we consider only the cases where FFP was administered to correct isolated “abnormal” coagulation values, then FFP was only successful in bringing the baby into the normal range for APTT and PT (using reference ranges at time of original screening4) in 15 and 10% of cases, respectively. Christensen and coworkers devise a table in their article that defines abnormal coagulation values of preterm infants from blood drawn at birth. If we use their values for less than 28 and 28 to 34 weeks of gestation, we note that in a setting of isolated coagulopathy 68% (34/50) of infants less than 28 weeks of gestation and 59% (20/34) of infants 28 to 34 weeks of gestation are corrected to within the reference range (
