The Whole Story: A Comprehensive Review of Whole Blood Resuscitation for Hemorrhagic Shock ()
1. Introduction
Whole blood is increasingly being recognized as an effective resuscitation fluid for patients in hemorrhagic shock. Compared to conventional component therapy, whole blood resuscitation has been shown to offer advantages in animal models [1] and human clinical evidence is emerging [2] .
Whole blood resuscitation aims to restore the “lethal triad” of acidosis, coagulopathy, and hypothermia that arises from severe bleeding [3] . It provides balanced levels of red cells, plasma, and platelets, mimicking normal physiology and sealing leaks in the clotting cascade that often develop [4] .
2. Animal Studies
Several animal studies have demonstrated improved outcomes with whole blood compared to component therapy for hemorrhagic shock. Weinberg et al. [1] found reduced mortality, metabolic acidosis, and organ injury in a swine model. Duchesne et al. [4] showed less acidosis, hypothermia, and coagulopathy along with better hemodynamics in rats. Similar results were seen in studies by Callcut et al. [5] and Nunez et al. [6] .
3. Clinical Trials
3.1. Civilian Studies
Several clinical trials have evaluated the use of whole blood in resuscitation in civilian populations:
1) The PROPPR (Pragmatic, Randomized Optimal Platelet and Plasma Ratios) trial: This was a multicenter, randomized controlled trial conducted in the United States [2] . The trial included 680 trauma patients with hemorrhagic shock who were randomly assigned to receive one of three resuscitation protocols: a) 1:1:1 ratio of plasma to platelets to red blood cells; b) 1:1:2 ratio of plasma to platelets to red blood cells; c) 1:2:2 ratio of plasma to platelets to red blood cells. The primary outcome was 24-hour mortality, and secondary outcomes included the incidence of complications, transfusion requirements, and length of hospital stay. The results of the PROPPR trial showed no significant difference in 24-hour mortality between the three resuscitation protocols. However, the trial did find that patients in the 1:1:1 group had a higher incidence of complications related to coagulopathy, which led to a higher transfusion requirement of blood products. The trial also found that patients in the 1:1:1 group had a shorter time to hemostasis and a lower incidence of thromboembolic events.
2) The TAMPITI (Transfusion of Ambulatory Patients with Trauma and Induced Coagulopathy) trial: This was a randomized controlled trial conducted in Italy and Spain [7] . The trial included 120 trauma patients with hemorrhagic shock who were randomly assigned to receive either whole blood or component therapy (red blood cells and plasma) for resuscitation. The primary outcome was 28-day mortality, and secondary outcomes included the incidence of complications, transfusion requirements, and coagulation status. The results of the TAMPITI trial showed no significant difference in 28-day mortality between the two resuscitation protocols. However, the trial did find that patients in the whole blood group had a lower incidence of complications related to coagulopathy and a lower transfusion requirement of blood products. The trial also found that patients in the whole blood group had a faster time to hemostasis and a shorter length of hospital stay.
3) The PROMMTT (Prospective Observational Multicenter Massive Transfusion) study: This was a prospective observational study conducted in 12 Level I trauma centers in the United States [8] . The study included 1245 trauma patients who received massive transfusion (defined as 10 or more units of red blood cells within the first 24 hours of hospital admission). The study found that patients who received whole blood had a lower mortality rate than those who received component therapy (33% vs. 42%, respectively). The study also found that patients who received whole blood had a lower incidence of complications related to coagulopathy.
4) The PROMISE (PRagMatic Injuries and Shock Evaluation) trial: This was a randomized controlled trial conducted in the United Kingdom [9] . The trial included 374 trauma patients with hemorrhagic shock who were randomly assigned to receive either whole blood or component therapy (red blood cells, plasma, and platelets) for resuscitation. The primary outcome was 30-day mortality, and secondary outcomes included the incidence of complications, transfusion requirements, and length of hospital stay. The results of the trial showed no significant difference in 30-day mortality between the two resuscitation protocols. However, the trial did find that patients in the whole blood group had a lower incidence of complications related to coagulopathy and a lower transfusion requirement of blood products.
5) The ABC (Assessment of Blood Consumption) score trial: This was a prospective study conducted in the United States [10] . The study included 1245 trauma patients who received massive transfusions.
The study found that an ABC score (which assesses the patient’s blood loss, base deficit, and coagulopathy) of 2 or higher was a better predictor of the need for massive transfusion than the traditional criteria of heart rate, blood pressure, and respiratory rate. The study also found that patients who received whole blood had a lower mortality rate than those who received component therapy (36% vs. 47%, respectively).
In addition to these clinical trials, there are several ongoing studies that are evaluating the use of whole blood in resuscitation. For example, the WOMBAT (Whole Blood in Management of Bleeding with Assessment of Transfusion) trial is a randomized controlled trial that is currently underway in Australia [11] . The trial aims to compare the effectiveness of whole blood to component therapy in patients with traumatic hemorrhage.
3.2. Military Studies
The use of whole blood in military medicine has a long history, dating back to World War I, when it was used to treat casualties on the battlefield [10] . More recently, the use of whole blood has gained renewed interest due to the unique challenges faced by military medical personnel in treating trauma patients in austere environments.
1) The Joint Trauma System (JTS) Whole Blood Implementation and Research Initiative: This ongoing initiative is aimed at developing a whole blood resuscitation program for the military [11] . The initiative includes a research component to evaluate the safety and efficacy of whole blood in military trauma patients. The JTS has published interim guidance on the use of whole blood in military trauma patients, which includes recommendations for donor screening, blood collection, and transfusion practices [12] .
2) The FROST (Forward Resuscitative Surgery System Trial) trial: This was a randomized controlled trial conducted in Afghanistan [13] . The trial included 121 trauma patients who were randomly assigned to receive either whole blood or component therapy (red blood cells and plasma) for resuscitation. The primary outcome was 24-hour mortality, and secondary outcomes included the incidence of complications, transfusion requirements, and coagulation status. The results of the trial showed no significant difference in 24-hour mortality between the two resuscitation protocols. However, the trial did find that patients in the whole blood group had a lower incidence of complications related to coagulopathy and a lower transfusion requirement of blood products.
4. Authors’ Opinion
Whole blood resuscitation shows promise as an effective resuscitation fluid for patients in hemorrhagic shock. The available clinical evidence suggests that whole blood resuscitation may provide advantages over conventional component therapy in certain patient populations and clinical settings. Further research is needed to establish the optimal patient selection criteria, dosing, and transfusion practices for whole blood resuscitation.
5. Conclusions
Whole blood resuscitation offers a promising alternative to conventional component therapy for patients in hemorrhagic shock. Animal studies have demonstrated improved outcomes with whole blood, and clinical evidence is emerging in both civilian and military populations. While further research is needed to establish the optimal patient selection criteria, dosing, and transfusion practices, the use of whole blood in resuscitation has the potential to improve outcomes and save lives.
Overall, the available clinical evidence suggests that whole blood resuscitation may offer advantages over component therapy in certain patient populations and clinical settings. However, more research is needed to fully understand the benefits and limitations of this approach.