LETTERS
Letter: The whole is greater than the sum of its parts: Hemostatic profiles of whole-blood variants To the Editor:
W
e read with great interest the recent study on hemostatic profiles of wholeblood (WB) variants by Kornblith et al.1 in this journal, where they aimed to study several laboratory parameters of donated WB and reconstituted whole blood (RWB) under several mixed ratios and conditions. Interestingly, standard coagulation tests (SCTs) such as prothrombin time and partial thromboplastin time were substantially prolonged for both room temperature WB and cooled WB. The activity of coagulation factors were approximately 30% lower than previously reported in healthy volunteers.2 This finding is hard to explain. Usually, 450 mL of donated blood is collected in a package prefilled with 63 mL of citrate phosphate dextrose anticoagulant to conserve the WB, but this results in an approximate 12% dilution of the coagulation factors.3 Therefore, measurement of coagulation activity in donated WB should result in normal SCT result and ROTEM parameters. Weiss et al.2 used a stepwise method to dilute WB and found that EXTEM clotting time (CT) exceeded the normal upper limit of 80 seconds after a 60% dilution of the coagulation factors. In contrast, EXTEM CT in the current study was 220 seconds, with an extremely high SD value of 216.3 seconds. Importantly, RWB from red blood cells, fresh frozen plasma (FFP), and platelet concentrates mixed at a ratio of 1:1:1 also failed to normalize SCT results and concentration of coagulation factors. Moreover, EXTEM and INTEM CT were 1.5 times higher than the normal upper limit.4 Interestingly, fibrinogen concentration was higher in RWB than in donated WB. One explanation could be that donated and reconstituted WB variants were already anticoagulated with various forms of citrated additives in the initial collection bags, thereby inactivating all available calcium needed for coagulation. According to the authors, the samples for SCTs and ROTEM analyses were drawn from this already citrated WB bag into tubes containing 3.2% (0.109 mol/L) sodium citrate (usually in a 1:9 ratio of citrate to blood sample). First, this unnecessarily further dilutes the sample (usually by approximately 10%).
TO THE
EDITOR
Second and more importantly, a much higher dose for recalcification (e.g., star-TEM reagent) is needed for appropriate ROTEM analysis and an intact coagulation cascade. However, according to the authors, this was unfortunately not accounted for by the automated pipette program of the ROTEM device used. This presumably resulted in major flaws in all of the ROTEM results. It seems that a major systematic error in the preparation and/or measurement of samples occurred. Therefore, these results must be interpreted with extreme caution. Furthermore, according to the presented results, it might be impossible to normalize SCT results or ROTEM CT by transfusion of red blood cells, FFP, and platelet concentrates at a ratio of 1:1:1. If the presented results mirror the true coagulation capacity of the transfused blood products, an alternative approach to high ratio FFP administration (e.g., coagulation factor concentrates) is necessary to normalize both SCT results and ROTEM CT.5 C.J.S. has received speaker honoraria, travel support, and research funding from CSL Behring and research support from Tem International. M.P. has received research support from CSL Behring and Tem International. H.S. has received speaker honoraria and research support from CSL Behring and Tem International.
Christoph J. Schlimp, MD Ludwig Boltzmann Institute for Experimental and Clinical Traumatology AUVA Research Centre Vienna, Austria AUVA Trauma Hospital Klagenfurt, Austria
Martin Ponschab, MD Ludwig Boltzmann Institute for Experimental and Clinical Traumatology AUVA Research Centre Vienna, Austria AUVA Trauma Hospital Linz, Austria
Herbert Scho¨chl, MD Ludwig Boltzmann Institute for Experimental and Clinical Traumatology AUVA Research Centre Vienna, Austria AUVA Trauma Centre Salzburg, Austria
REFERENCES 1. Kornblith LZ, Howard BM, Cheung CK, et al. The whole is greater than the sum of its parts: hemostatic profiles of whole blood variants. J Trauma Acute Care Surg. 2014;77(6):818Y827 2. Weiss G, Lison S, Spannagl M, et al. Expressiveness of global coagulation parameters in dilutional coagulopathy. Br J Anaesth. 2010;105:429Y436.
3. Hess JR. Resuscitation of trauma-induced coagulopathy. Hematology Am Soc Hematol Educ Program. 2013;2013:664Y667. 4. Doran CM, Doran CA, Woolley T, et al. Targeted resuscitation improves coagulation and outcome. J Trauma Acute Care Surg. 2012;72:835Y843. 5. Scho¨chl H, Voelckel W, Grassetto A, et al. Practical application of point-of-care coagulation testing to guide treatment decisions in trauma. J Trauma Acute Care Surg. 2013; 74:1587Y1598.
Response: The whole is greater than the sum of its parts: Hemostatic profiles of whole-blood variants In Reply: e respectfully appreciate the AUVA’s interest in our work and their specific concerns over the prolonged standard coagulation measures and out-of-range ROTEM measurements in our study. We strongly disagree, however, that there are any compelling methodological issues and additionally disagree that it is difficult to explain these findings in the banked products compared with healthy volunteer blood. Unfortunately, the editorial claims seem to be based on incorrect assumptions regarding methodology and results, which we seek to remedy here. To clarify, our regional blood collection center colleagues collected the donated whole blood in a collection bag prefilled with 70 mL of anticoagulant, primarily citrate phosphate dextrose as per standard protocol. The clinical standard acceptable volume of whole blood for collection is 450 mL to 550 mL with added 70 mL of anticoagulant (which results in variable 13Y16% anticoagulant). The wholeblood units provided to us were either slightly overweight or underweight and therefore had a mean anticoagulant of 17%, only 1% greater than the clinical standard. Each whole-blood unit was split into four satellite bags without anticoagulant (designed specifically to avoid excess dilution and to standardize surface contact) and therefore retained their anticoagulant concentration after the split. For the reconstituted whole blood components, the red blood cells, platelets, and plasma (whole blood derived) all had an anticoagulant concentration of 15%. Therefore, the mean concentration of anticoagulant across all the products we analyzed was 15% to 17%, making it appropriate to compare coagulation measurements between these banked products.
W
J Trauma Acute Care Surg Volume 77, Number 6
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
1003
Letter: The whole is greater than the sum of its parts: Hemostatic profiles of whole-blood variants To the Editor:
W
e read with great interest the recent study on hemostatic profiles of wholeblood (WB) variants by Kornblith et al.1 in this journal, where they aimed to study several laboratory parameters of donated WB and reconstituted whole blood (RWB) under several mixed ratios and conditions. Interestingly, standard coagulation tests (SCTs) such as prothrombin time and partial thromboplastin time were substantially prolonged for both room temperature WB and cooled WB. The activity of coagulation factors were approximately 30% lower than previously reported in healthy volunteers.2 This finding is hard to explain. Usually, 450 mL of donated blood is collected in a package prefilled with 63 mL of citrate phosphate dextrose anticoagulant to conserve the WB, but this results in an approximate 12% dilution of the coagulation factors.3 Therefore, measurement of coagulation activity in donated WB should result in normal SCT result and ROTEM parameters. Weiss et al.2 used a stepwise method to dilute WB and found that EXTEM clotting time (CT) exceeded the normal upper limit of 80 seconds after a 60% dilution of the coagulation factors. In contrast, EXTEM CT in the current study was 220 seconds, with an extremely high SD value of 216.3 seconds. Importantly, RWB from red blood cells, fresh frozen plasma (FFP), and platelet concentrates mixed at a ratio of 1:1:1 also failed to normalize SCT results and concentration of coagulation factors. Moreover, EXTEM and INTEM CT were 1.5 times higher than the normal upper limit.4 Interestingly, fibrinogen concentration was higher in RWB than in donated WB. One explanation could be that donated and reconstituted WB variants were already anticoagulated with various forms of citrated additives in the initial collection bags, thereby inactivating all available calcium needed for coagulation. According to the authors, the samples for SCTs and ROTEM analyses were drawn from this already citrated WB bag into tubes containing 3.2% (0.109 mol/L) sodium citrate (usually in a 1:9 ratio of citrate to blood sample). First, this unnecessarily further dilutes the sample (usually by approximately 10%).
TO THE
EDITOR
Second and more importantly, a much higher dose for recalcification (e.g., star-TEM reagent) is needed for appropriate ROTEM analysis and an intact coagulation cascade. However, according to the authors, this was unfortunately not accounted for by the automated pipette program of the ROTEM device used. This presumably resulted in major flaws in all of the ROTEM results. It seems that a major systematic error in the preparation and/or measurement of samples occurred. Therefore, these results must be interpreted with extreme caution. Furthermore, according to the presented results, it might be impossible to normalize SCT results or ROTEM CT by transfusion of red blood cells, FFP, and platelet concentrates at a ratio of 1:1:1. If the presented results mirror the true coagulation capacity of the transfused blood products, an alternative approach to high ratio FFP administration (e.g., coagulation factor concentrates) is necessary to normalize both SCT results and ROTEM CT.5 C.J.S. has received speaker honoraria, travel support, and research funding from CSL Behring and research support from Tem International. M.P. has received research support from CSL Behring and Tem International. H.S. has received speaker honoraria and research support from CSL Behring and Tem International.
Christoph J. Schlimp, MD Ludwig Boltzmann Institute for Experimental and Clinical Traumatology AUVA Research Centre Vienna, Austria AUVA Trauma Hospital Klagenfurt, Austria
Martin Ponschab, MD Ludwig Boltzmann Institute for Experimental and Clinical Traumatology AUVA Research Centre Vienna, Austria AUVA Trauma Hospital Linz, Austria
Herbert Scho¨chl, MD Ludwig Boltzmann Institute for Experimental and Clinical Traumatology AUVA Research Centre Vienna, Austria AUVA Trauma Centre Salzburg, Austria
REFERENCES 1. Kornblith LZ, Howard BM, Cheung CK, et al. The whole is greater than the sum of its parts: hemostatic profiles of whole blood variants. J Trauma Acute Care Surg. 2014;77(6):818Y827 2. Weiss G, Lison S, Spannagl M, et al. Expressiveness of global coagulation parameters in dilutional coagulopathy. Br J Anaesth. 2010;105:429Y436.
3. Hess JR. Resuscitation of trauma-induced coagulopathy. Hematology Am Soc Hematol Educ Program. 2013;2013:664Y667. 4. Doran CM, Doran CA, Woolley T, et al. Targeted resuscitation improves coagulation and outcome. J Trauma Acute Care Surg. 2012;72:835Y843. 5. Scho¨chl H, Voelckel W, Grassetto A, et al. Practical application of point-of-care coagulation testing to guide treatment decisions in trauma. J Trauma Acute Care Surg. 2013; 74:1587Y1598.
Response: The whole is greater than the sum of its parts: Hemostatic profiles of whole-blood variants In Reply: e respectfully appreciate the AUVA’s interest in our work and their specific concerns over the prolonged standard coagulation measures and out-of-range ROTEM measurements in our study. We strongly disagree, however, that there are any compelling methodological issues and additionally disagree that it is difficult to explain these findings in the banked products compared with healthy volunteer blood. Unfortunately, the editorial claims seem to be based on incorrect assumptions regarding methodology and results, which we seek to remedy here. To clarify, our regional blood collection center colleagues collected the donated whole blood in a collection bag prefilled with 70 mL of anticoagulant, primarily citrate phosphate dextrose as per standard protocol. The clinical standard acceptable volume of whole blood for collection is 450 mL to 550 mL with added 70 mL of anticoagulant (which results in variable 13Y16% anticoagulant). The wholeblood units provided to us were either slightly overweight or underweight and therefore had a mean anticoagulant of 17%, only 1% greater than the clinical standard. Each whole-blood unit was split into four satellite bags without anticoagulant (designed specifically to avoid excess dilution and to standardize surface contact) and therefore retained their anticoagulant concentration after the split. For the reconstituted whole blood components, the red blood cells, platelets, and plasma (whole blood derived) all had an anticoagulant concentration of 15%. Therefore, the mean concentration of anticoagulant across all the products we analyzed was 15% to 17%, making it appropriate to compare coagulation measurements between these banked products.
W
J Trauma Acute Care Surg Volume 77, Number 6
Copyright © 2014 Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited.
1003
