The case for the use of whole blood in prehospital civilian medicine
You’re called to the home of a 38-year-old woman who has been fainting. When you arrive, her husband tells you that she’s been experiencing heavy vaginal bleeding for about two weeks. She recently underwent a caesarean-section delivery of her second child.
On exam, she appears pale and sweaty, with notable pallor of the lips and gums. Her eyes remain closed as she stumbles over her words and barely follows commands. Her initial set of vitals are as follows:
>>Blood pressure (BP): 71/55 mmHg
>>Heart rate (HR): 116 beats per minute
>>Respiratory rate (RR): 28 breaths per minute
>>Temperature: 36°C (96.8°F)
>>Point-of-care lactate: 4.7 mmol/L
Your patient complains of shortness of breath and appears to lose consciousness several times as you load her into your ambulance. You suspect that she’s suffering from hypovolemic shock secondary to blood loss. What would be your fluid of choice for resuscitation?
Increasing numbers of EMS agencies are developing the capability to administer blood products to patients in need. Although this relatively new therapy in EMS appears to decrease mortality, there’s more that can be done.
The U.S. military has been successfully transfusing whole blood at the point of injury (POI) for severely wounded patients on the battlefield. The Ranger Group O Low Titer (ROLO) whole blood program has allowed U.S. Army combat medics to replace the blood lost from combat wounds at the POI.
Whole blood is the natural, unseparated blood collected from a donor. It contains all the components of blood that you’d find in healthy blood (i.e., red cells, plasma, clotting factors and platelets)—because it is normal, healthy blood.
Since the late 1970s, prehospital trauma resuscitation has relied on administration of crystalloid solutions such as 0.9% sodium chloride or “normal” saline, lactated Ringer’s, and colloids like hydroxyethyl starch (HES).
The use of crystalloids in resuscitation stems from the Vietnam War and studies carried out in the 1970s and 1980s. Advanced Trauma Life Support (ATLS) built its curriculum around the recommendation to start resuscitation with a two-liter bolus of crystalloids.1 However, many of these protocols weren’t founded upon evidence-based medicine.
The last 17 years of war have brought tremendous advances in prehospital and trauma care to both the military and civilian sectors. Evidence now suggests that whole blood is a better option for trauma resuscitation and can increase survival of severely injured patients.2–4
In today’s EMS setting, it’s uncommon for ground EMS services to carry and use blood components. Most services that carry blood components are helicopter-based. There are a few published studies, with varying outcomes.5–9 A study of prehospital blood product transfusion in Afghanistan recently presented data that demonstrated a 20-fold survival benefit when blood is given within 34 minutes of injury,10 and recent data from the U.K. suggest prehospital blood may reduce transfusion requirements.9 Although combat data doesn’t always correlate with civilian medicine, this data may still present some benefit for EMS.
Trauma is the leading cause of death for patients under 46 years old, and uncontrolled hemorrhage remains the number one cause of preventable death in trauma.11 Even in urban areas, the role of blood transfusions is relevant. The time is now for EMS to embrace blood as the fluid of choice in trauma resuscitation.
RESURGENCE of Whole Blood
In 2011, an international group of physicians, blood bankers and researchers formed the Trauma Hemostasis and Oxygenation Research (THOR) Network and held the first Remote Damage Control Resuscitation (RCDR) Symposium in Norway.12
This group advocated for the use of whole blood with one of the co-founders, Geir Strandenes, developing a low titer group O whole blood (LTOWB) program for Norwegian Naval Special Operation Commando.13 This information was used by the U.S. Army’s 75th Ranger Regiment, in conjunction with the U.S. Army Institute of Surgical Research and Armed Services Blood Program (ASBP), to develop the first LTOWB program that screened donors before deployment for use at the POI.14
Using historical data from World War II, the program defined low titer as immunoglobulin M (IgM) anti-A and anti-B < 256. Volunteers were tested for transmitted transfusion diseases (TTDs) and titer tested prior to deployment. Although the ROLO program was initially designed to deliver fresh whole blood (FWB), the chaotic nature of combat makes drawing a unit of FWB difficult.
To decrease the amount of time it takes to administer a unit of FWB, the ASBP began shipping cold-stored LTOWB to Afghanistan in March 2016, with the first unit being administered in later the same month. The cold-stored LTOWB product is an FDA licensed product, with an IgM anti-A and anti-B titer of < 150.
There are three options for using LTOWB. The first option is to draw a unit of FWB from a prescreened low titer donor at the POI. This has been shown to be very effective, but it takes a trained responder 8–15 minutes to collect a single unit.
The second option involves collecting whole blood from low titer donors the day before a mission, keeping it stored at 33.8–42.8 degrees F, then carrying it on the mission in an approved container.
The third option is to ship the FDA-licensed cold-stored LTOWB to from ASBP Donation Centers to operational units and combat hospitals in combat theaters. The third option is the most feasible for civilian EMS providers.
Why Use Whole Blood?
There are three reasons why whole blood is ideal for prehospital use. First, whole blood is superior to crystalloids and colloids. There’s very little room to argue that crystalloid and colloid fluids are appropriate in resuscitation. The hazards of dilutional coagulopathy and acidosis are well documented.15-18
Second, whole blood administration is easier than the administration of components. The administration of whole blood is the simplest way to deliver the functionality of lost blood back to the patient.
The Serious Hazards of Transfusion (SHOT) study from the U.K. looked at the serious hazards of transfusion and found that approximately 78% of the incident reports resulted from human error, despite there being rules in place to improve practice.19
Third, the safety of whole blood transfusions is similar to component therapy, as TTD testing is completed for both. The U.S. military has successfully transfused over 10,000 units of whole blood across the world.20 The body of evidence will grow as more civilian agencies initiate their own whole blood programs.
Whole vs. Component
When blood components are made, whole blood is spun in a centrifuge to separate the red cells from plasma and platelets. The plasma can be further prepared into cryoprecipitate. The red cells are washed to remove remaining plasma proteins and an anticoagulant is added to the storage bag. Platelets are usually collected separately. This results in a series of blood products with a very low likelihood of causing transfusion reactions.
Once they’ve been prepared, red blood cells (RBCs) have a shelf life of 42 days. Plasma and cryoprecipitate can be kept frozen for a year, and once thawed will last for 24 hours. Platelets are normally kept at room temperature for only five days and must be constantly agitated, but they can also be stored frozen.22
When administered to a significantly injured patient, they’re usually transfused in a 1:1:1 ratio of RBC, FFP and platelets, depending on availability and local trauma center protocol.
Whole blood is collected from donors and stored in a refrigerator as-is. The collection bag has the same type of anticoagulant as the RBCs. The shelf life of whole blood is up to 35 days when collected using citrate phosphate dextrose adenine solution (CPDA-1) and must be used within 24 hours once brought to room temperature. Currently, most whole blood is collected using citrate phosphate dextrose (CPD) with a shelf life of 21 days.
It should be noted that the functionality of cold-stored whole blood decreases dramatically after 21 days. The process for preparing whole blood doesn’t require any special separation, washing or storage equipment, and the unit of blood contains all the individual components together.
Component therapy using a 1:1:1 ratio has several other disadvantages compared to whole blood. 23 (See Table 1, p. 52.) Component therapy has significantly lower function, with decreases in the percentage of useful red blood cells (hematocrit), platelets and coagulation factors. Once all the components have been combined, they have three times the volume of anticoagulant and additives as whole blood. 23, 24
Is it Safe?
All medical procedures have an inherent level of risk if done carelessly or incorrectly. If done properly, whole blood transfusions have a good risk-to-benefit ratio. The most concerning problem is transfusion reactions.
The most severe reactions come from the mismatch of antigens on the surface of red blood cells. Group O blood cells lack anti-A and anti-B antigens seen in all other blood types, which is why it’s considered the universal blood donor.
However, the plasma of group O whole blood has both anti-A and anti-B antibodies in quantities that vary by person. Fortunately, plasma transfusion reactions are both less common and less severe than blood cell transfusion reactions.25
The name “low titer” comes from the test to determine how many antibodies are in the plasma. The test measures IgM anti-A and anti-B antibodies. The military has had great success using titers < 256, but to be FDA-approved in the U.S., EMS agencies must use a titer of < 150.
About 40% of the U.S. population has group O blood, with another 40% having group A. The rest are spread between groups B and AB. By using LTOWB, we decrease the likelihood of human error, the possibility of severe blood cell related reactions and the potential for plasma-related reactions.13,14
A mismatch in the Rhesus (Rh) D antigen doesn’t cause an immediate hemolytic reaction after the first exposure and is nearly irrelevant in the emergency prehospital setting. According to the American Red Cross, 10-20% of the U.S. population does not have the Rh D antigen on the surface of their red blood cells, also known as Rh “negative.” After exposure to Rh “positive” blood, around 20-26% will develop a sensitivity within four weeks. However, only 3-4% will develop a strong immune response to future administration.25 Although it’s common practice to give women of childbearing age Rh-negative blood, if it isn’t available, Rh-positive whole blood should be transfused as it’s still preferred over colloid or crystalloid infusion.26
Incorporating Whole Blood
As previously stated, bolus of crystalloids and colloids can increase mortality and has no effective treatment in trauma. The current recommendation of 1:1:1 has three times the anticoagulants and additives.23 These additional additives can contribute to trauma-induced coagulopathy.
In late August 2017, Harris County Emergency Services District No. 48 (HCESD 48) Fire Department and Cypress Creek EMS (CCEMS) in Houston, Texas, began carrying cold-stored LTOWB for hemostatic resuscitation. Before this unconventional approach, both services had been carrying RBCs and fresh plasma since mid-2016. There were over 100 units transfused, and currently work is underway to obtain patient outcome data for publication. Both services are use a response vehicle with a paramedic who delivers blood and oversees its storage. The protocol’s inclusion criteria is 12 and older (should have two or more of the following):
>>Hemodynamically unstable (i.e., HR > 120; systolic B/P ≤ 90 mmHg);
>>Penetrating injury or blunt trauma with significant injury;
>>Positive focused assessment with sonography in trauma test (if available); and
>>Hemoglobin < 6.0 mmol/L (if available).
If criteria aren’t met, and providers feel the patient meets the threshold, HCESD 48 Fire Department peronnel are advised to contact the on-call medical director. CCEMS supervisors can give it at their descretion based on presenting factors.
This established protocol was coordinated through the HCESD 48 Fire Department EMS chiefs, CCEMS Director of Special Operations John Holcomb, MD, and the Gulf Coast Regional Blood Center.
Due to the shorter shelf life of LTOWB, there’s a higher potential for waste. In the future, it may be possible to make component therapy from the unused LTOWB units. This new protocol has the potential to influence many EMS systems and the transfusion of whole blood in the prehospital setting has the potential to save many lives.
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