ACCEPTABLE UNIVERSAL BLOOD PRODUCTS FOR RESUSCITATION?

Transcription

1 ACCEPTABLE UNIVERSAL BLOOD PRODUCTS FOR RESUSCITATION? Paul M. Ness, M.D. Professor Pathology, Medicine, and Oncology The Johns Hopkins Medical Ins tu ons Bal more, Maryland, USA

2 BLOOD BANK BUREAUCRATS

3 TRANSFUSION MEDICINE CHALLENGES REGULATORY Food and Drug Administra on State of Maryland City of Bal more AABB CAP Joint Commission OPERATIONAL Cost containment Cost center status Blood shortages Blood wastage Split inventories Labor shortages Computer shortcomings

4 INDICATIONS FOR TRANSFUSION Restora on of blood volume Restora on of oxygen carrying capacity Replacement of cellular elements or plasma proteins Exchange transfusion

5 PREFERENTIAL USE OF COMPONENTS Avoids circulatory overload Limits harmful metabolic materials Concentrates required material for effec ve levels Minimizes risk of disease transmission Maximizes use of donated blood

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8 BLOOD PRESERVATIVES PRESERVATIVE STORAGE PERIOD Acid citrate dextrose Citrate phosphate dextrose CPDA- 1 Addi ves (AS- 1,etc) 21 days 21 days 35 days 42 days

9 RED CELL PRESERVATION 2,3- DPG levels measure oxygen carrying characteris cs; 2,3- DPG levels fall during storage but are corrected rapidly in vivo. Acceptable survival is 75% at 24 hours; correlates with level of cellular ATP. RBC metabolites increase during storage; potassium accumula on can be a problem for neonates.

10 LEUKODEPLETED COMPONENTS Reduce transfusion reac ons Reduce alloimmuniza on Reduce risk of viral transmission (CMV) Reduce immunomodula on (??)

11 Platelet Components Produced -- from whole blood platelet-rich plasma (PRP) buffy coat (in Europe and Canada) -- Platelet apheresis

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18 ABO Cri cal role in transfusion High an gen density on red cells Reciprocal arrangement whereby pa ents who are group A have naturally occurring an - B in their serum. ABO an bodies are high ter IgM an bodies which produce intravascular hemolysis Group O is universal donor and typically used for trauma Group AB plasma is typically used in trauma but with major supply issues

19 Immunogenicity Rh Clinical Importance High frequency of incompa bility 85% posi ve, 15% nega ve Rh posi ve blood typically used for trauma due to inadequate Rh nega ve supplies and acceptance that acute survival is higher priority than future Rh incompa ble pregnancies

20 Breaking the Bloody Vicious Cycle Coagulopathy Hemorrhage Hemodilu on and Hypothermia Resuscita on Control hemorrhage Use best possible resuscita on products Prevent hypothermia Prevent hemodilu on Treat coagulopathy

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22 FFP:RBC unit ra o - effect on mortality Data from the 10 th CSH, Baghdad 70 65% % Mortality N = 69 ISS = 16 34% N = 116 ISS = 17 17% N = 319 ISS = FFP:RBC unit ra o

23 Massive Transfusion Protocol (Procedure) Sample for type and screen to blood bank Blood products in containers (coolers) 1:1:1 ra o of RBCs:FFP:Platelets (6 u RBCs, 6u FFP, 1 apheresis unit platelets) Complete use of 1 cooler before next cooler Upon issuing a cooler, BB prepares next cooler 1 cooler every min un l protocol D/C d

24 Koch et al: storage impairs outcome Retrospec ve review of cardiac surgery pts 8802 units stored median 11 days given to 2872 pts 10,782 units stored median 19 days given to 3130 pts MORTALITY VENT > 72 H COMPOSITE RBC: mean 11d 1.7% 5.6% 22.4% RBC: mean 20d 2.8% 9.7% 25.9% P-value <

25 Biochemical/Func onal changes with RBC storage There are clearly changes that occur with RBC storage. é Inflammatory mediators é RBC adhesion é Immunomodulation é Hemolysis ê RBC deformability ê NO ê 2,3-DPG ê ATP.however, do they lead to significantly different outcomes in transfusion recipients?

26 Age of Blood Issues Mul ple biochemical/structural changes are know to occur in RBCs during storage However, the data are in disagreement as to whether storage me affects pa ent outcomes - - Most studies are retrospec ve which can overstate differences in outcomes No large, prospec ve RCT of this ques on un l RECESS, which has completed ac ve recruitment The results could have significant implica ons for the logis cs of the blood supply The results may also be important in trauma since some MTP protocols preferen ally use older blood

27 Platelet Transfusion Progress 2014 Platelets now widely available Platelets can be stored for 5days, perhaps longer in the future Platelet alloimmuniza on has been reduced by LR and can be managed by platelet matching Bacterial sepsis has been reduced Platelet triggers (and platelet dosage) are evidence based

28 PLATELET TRANSFUSION GUIDELINES Platelet count <10,000/ ul in presence of marrow failure with no bleeding Platelet count < 50,000/ul in pa ents who are bleeding or with invasive procedures Platelets with qualita ve platelet abnormali es for bleeding or prophylaxis Platelet dosage appropriate for body mass; one unit/10 kg ( 6 units for most adults)

29 GOBSAT James Isbister MD Sydney Australia

30 FROZEN PLASMA

31 Plasma Components Thawed plasma: Widely used as source of immediately available plasma Not an FDA- approved product; not in CFR, cannot be distributed in interstate commerce Described in Circular of Informa on and AABB Stds (~ 1996) Star ng material: FFP (whole blood or apheresis, if collected in a closed system) or PF24 Store at 1 6 o C for up to 4 days a er ini al 24- hr post- thaw period Re- label as thawed; license number on label must be removed Does not require FDA variance 32

32 Problems with Current Plasma Products ABO an bodies Variable content of coagula on factors Poten al advantages of pooling Requirement for thawing Infec ous risks Glass bo les ( and plas c bags) break

33 Trauma Transfusion Needs Platelets with enhanced early hemosta c effect More AB plasma (or learning to be comfortable with A plasma for trauma Improved plasma storage and thawing equipment in trauma units and OR Freeze- dried or concentrated plasma

34 Dilu on Is Inevitable When Giving Blood Components Whole blood 500 ml Hct 38% 50% Plts 150 K 400 K Plasma coagula on factors = 100% Components 1 U PRBC = 335 ml with Hct 55% 1 U Plts = 50 ml with 5.5 x Plts 1 U plasma = 275 ml with 80% coagula on ac vity Thus: 1 U PRBC + 1 U Plts + 1 U FFP = 660 ml with Hct 29%, Plts 88 K/µL, and coagula on ac vity 65%. FFP, fresh frozen plasma; Hct, hematocrit; PRBC, packed red blood cells.

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37 Whole Blood Leukodeple on Sparing Platelets

38 Low An - A Titer Whole Blood CURRENT PRACTICES 1:8 universal plasma 1:16 ABO incompa ble organ transplants < 1:100 military guidelines PROBLEMS TO ADDRESS IgG or IgM Standardiza on Interna onal differences Lack of automated screening systems

39 Low Titer An - A is Uncommon

40 Whole Blood for Trauma Issues to Resolve How long can whole blood be stored at 4 degrees and maintain acceptable coagula on/platelet func on? Can systems be developed to recover RBC as a concentrate from whole blood not used in trauma? Is Rh posi ve whole blood acceptable for all recipients? What is an acceptable an - A ter? Will prospec ve randomized trials support evolving evidence that cold platelets and refrigerated whole blood have proven clinical advantages?

41 Improved Plasma Products for Resuscita on Pools to produce reliable coagula on levels and reduce allergic reac ons Universal plasma or Group A/AB Lyophilized or other rapidly recons tuted plasma Plas c containers

42 Further Thoughts Although blood bankers are conserva ve and slow to change, technical developments and well documented pa ent needs will compel new products and coopera on In this era of evidence based medicine, well designed and completed clinical trials will be important as necessary steps to implement changes.