Whole blood

Whole blood (WB) is donated blood that is not subsequently fractionated into components[i]. It is used in treatment of massive hemorrhage, as well as in the setting of autologous donation and acute normovolemic hemodilution. One “unit” contains approximately 500 ml (goal collection weight 485-585 grams), and will increase hemoglobin value by approximately 1 to 2 g/dL[ii].

This article will focus mostly on WB use in the setting of massive hemorrhage.

WB is collected in either CPD or CPD-1 anticoagulants, and is FDA-approved for the treatment of massive hemorrhage if appropriately collected, stored, and tested for transfusion transmitted diseases (TTD) by a licensed blood donation center[iii], [xi]. When refrigerated at 1-6 degrees Celsius, it has a shelf life of 21 days in CPD or 35 days in CPD-1. If not refrigerated within 8 hours after collection, it can be used for up to 24 hours. However, after approximately 2 weeks of storage, the hemostatic function of WB may vary or begin to degrade. This is most pronounced in platelet function, and supplementation with fresher units of WB or with other components may be necessary.

The current body of literature that exists suggests that WB may be as effective, if not more effective, than component therapy in resuscitation of massive hemorrhage, however more research is required to recommend routine use of WB transfusion. [iv], [x], [xi]. With that being said, there are certain advantages of WB transfusion over component therapy in this clinical setting. First, WB causes less of a dilutional effect. A 1:1:1 mixture of packed red blood cells, fresh frozen plasma, and platelets yields an in vitro mixture of a hematocrit of 29%, coagulation factor concentration of 62% of WB, and platelet count of 90,000/mcL. [x], [xi]On the other hand, WB is composed of a hematocrit of 38-50%, platelet count of 150-400k, 100% plasma coagulation factors, and 1000mg of fibrinogen. Second, all elements of a massive transfusion are present in one bag. Third, WB only requires refrigeration. Finally, in the combat setting, WB may be more readily available in the form of a walking blood bank.

History

WB transfusion is not new, and has been documented to have been used in select Allied hospitals in World War I. Its use continued through the Vietnam War, however, the use of component therapy eventually prevailed for sustainability of transfusion medicine, as one unit of WB could be separated into several components to maximize that unit’s potential for potentially multiple patients.[v] More recently in the 21^st century, WB has seen a resurgence in utilization by the US military in the conflicts in Iraq and Afghanistan, and as of 2021, the use of WB in trauma has become common practice in over 70 civilian centers across the United States[vi].

Indications and dosing

WB has FDA approval for large volume hemorrhage such as that seen with major trauma, requiring massive transfusion and rapid correction of anemia, coagulopathy, acidosis, and hypothermia.[vii]

The most common use of whole blood in the United States is currently autologous donation for elective surgery.^vii

In low-income countries, over 40% of donated blood is transfused as whole blood.[viii]

For an adult, 1 unit (~500ml) will increase the hemoglobin concentration by approximately 1-2 g/dL.

The United States Joint Trauma System recommends low-titer O whole blood as the first line resuscitative fluid for damage control resuscitation over component therapy in adults.[ix]

Although not FDA approved for pediatric use, WB has been transfused safely to this population.[x] Although initial evidence is promising, more research is required to determine the safety and efficacy of WB versus component therapy. Currently, the United States Joint Trauma System recommends a “unit dose” to be 10-15 ml/kg of WB for children <40kg requiring a massive transfusion in the setting of trauma, with no known contraindication outside of those considered for adults.^xii

WB transfusion is not FDA approved for pregnant females, however, is likely safe when appropriately administered.^x

Contraindications

Whole blood transfusions are not indicated when component specific therapy is indicated and available (e.g., pRBC used to treat anemia alone; FFP to treat elevated INR alone).^vii The use of whole blood when only monocomponent therapy is indicated and available could lead to complications such as volume overload.

Patient refusal is of course a contraindication.

Safety considerations and adverse effects

The most important safety consideration when utilizing WB transfusion is prevention of an acute hemolytic reaction. The red blood cells from a unit of O-negative WB will be compatible to all recipients, however unlike with packed red blood cells (pRBC), group O WB may also contain anti-A and anti-B antibodies, which may trigger an acute hemolytic reaction of the recipient’s own blood cells if the recipient is a blood group other than group O. Therefore, stored units of WB are tested for titers, or “concentrations,” of anti-A and anti-B antibodies. Those units of group O WB with a low titer are then considered “low-titer O whole blood”, or LTOWB. Although institutional practices differ with what is considered a “low titer”[xi], the United States military considers anti-A and anti-B titers of less than 1:256 of group-O whole blood low-titer[xii].

Another way of mitigating an acute hemolytic reaction is to transfuse group-specific whole blood (group i.e., A to A, B to B, etc.), however in the setting of trauma requiring a massive transfusion, blood groups of the trauma patient are unlikely to be known, at least initially, and it may be safer to transfuse LTOWB.

As with any other blood product, other adverse effects include delayed hemolytic reactions, hyperkalemia, citrate toxicity, transfusion associated cardiac overload, transfusion associated acute lung injury, febrile nonhemolytic reaction, anaphylactic reaction, infection, and graft-versus-host disease.

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[i] Hillyer, Christopher D. (2007). Blood Banking and Transfusion Medicine: Basic Principles & Practice. Elsevier Health Sciences. p. 190. ISBN 978-0443069819. Archived from the original on 2017-01-12.

[ii] Plumer, Ada Lawrence (2007). Plumer's Principles and Practice of Intravenous Therapy. Lippincott Williams & Wilkins. p. 422. ISBN 9780781759441. Archived from the original on 2017-01-12.

[iii] Pidcoke HF, McFaul SJ, Ramasubramanian AK, et al. Primary hemostatic capacity of whole blood: a comprehensive analysis of pathogen reduction and refrigeration effects over time. Transfusion. 2013 Jan;53 Suppl 1:137S-149S.

[iv] Avery P, Morton S, Tucker H, et al Whole blood transfusion versus component therapy in adult trauma patients with acute major haemorrhage Emergency Medicine Journal 2020;37:370-378.

[v] McCoy, Christopher Cameron^∗; Brenner, Megan^†; Duchesne, Juan^‡; Roberts, Derek^§; Ferrada, Paula^||; Horer, Tal^¶; Kauvar, David^∗∗; Khan, Mansoor^††; Kirkpatrick, Andrew^‡‡,§§; Ordonez, Carlos^||||,¶¶; Perreira, Bruno^∗∗∗; Priouzram, Artai^†††; Cotton, Bryan A.^∗. Back to the Future: Whole Blood Resuscitation of the Severely Injured Trauma Patient. SHOCK 56(1S):p 9-15, December 2021. | DOI: 10.1097/SHK.0000000000001685

[vi] Seheult J, Dunbar N. Transfusion of blood components containing ABO-incompatible plasma does not lead to higher mortality in civilian trauma patients. Transfusion. 2020;60(11):2517–2528. doi: 10.1111/trf.16008.

[vii]Whole Blood (Blood Component). Medscape.  https://reference.medscape.com/drug/whole-blood-999509#4

[viii] "Blood safety and availability". www.who.int. Retrieved 2019-06-22.

[ix] Cap, A, Gurney J, Strandenes G, et al. Damage Control Resuscitation (CPG ID: 18). Joint Trauma System Clinical Practice Guideline. 12 Jul 2019.

[x] Hanna M, Knittel J, Gillihan J. The Use of Whole Blood Transfusion in Trauma. Curr Anesthesiol Rep. 2022;12(2):234-239. doi: 10.1007/s40140-021-00514-w. Epub 2022 Jan 17. PMID: 35069017; PMCID: PMC8761832.

[xi] McCoy CC, Brenner M, Duchesne J, Roberts D, Ferrada P, Horer T, Kauvar D, Khan M, Kirkpatrick A, Ordonez C, Perreira B, Priouzram A, Cotton BA. Back to the Future: Whole Blood Resuscitation of the Severely Injured Trauma Patient. Shock. 2021 Dec 1;56(1S):9-15. doi: 10.1097/SHK.0000000000001685. PMID: 33122511; PMCID: PMC8601673

[xii] Cap AP, Beckett A, Benov A, et al. Whole Blood Transfusion (CPG ID: 21). Joint Trauma System Clinical Practice Guideline. 15 May 2018.