Tuesday, December 26, 2023

Giving Blood in the Field: current TCCC recommendations

Due to occasional severe transfusion reactions, whole blood fell out of favor after WWII. Separating blood into components, such as plasma, red blood cells (RBCs), and platelets allowed for a longer shelf life, easier transport and storage logistics, and reduced risk of disease and transfusion reactions. Separate blood components are needed for many medical interventions. An exception, however, is trauma with massive blood transfusion needed. Recent evidence suggests that, for trauma patients in hypovolemic shock, whole blood produces better outcomes. 

TCCC recommendations have evolved through combat experience gained in Iraq and Afghanistan during the recent "Global War on Terror" (GWOT). Before the US invasion of Iraq, most forward resuscitation efforts for blood loss centered on providing non-blood products such as Hextend and PLASMA-LYTE. In 2003, TCCC recommended that blood be carried on casevac units if possible. In 2006, this recommendation was updated to specify low-titer type O blood. As ongoing studies demonstrated increased coagulopathy and reduced survival with non-blood product use, in 2014 TCCC moved blood products to the forefront of care for hemorrhagic shock. 2020 TCCC guidelines list whole blood as the "fluid of choice", with crystalloids, Hextend, and PLASMA-LYTE recommended only if blood products are unavailable.

Whole blood for trauma has a number of advantages. It contains clotting factors that are missing from individually packaged blood components, and has a reduced amount of artificial anti-clotting agents (which can lead to coagulopathy). Whole blood is faster and simpler to administer than individual blood products. This can be important during times of high demand on patient caregivers, reducing workload and opportunities for errors. In general, the sooner blood is given, the better the outcomes. A retrospective study of 502 US military combat casualties in Afghanistan between 2012 and 2015 showed that time to initial blood product transfusion was associated with a reduced 24-hour and 30-day mortality. 

Non-blood products such as crystalloids, Hextend, and PLASMA-LYTE come with several negative side-effects. They may contribute to the "Lethal triad"- a self-reinforcing cycle of acidosis, hypothermia, and coagulopathy which is hard to interrupt once it sets in. Expanding blood volume without adding RBCs does not increase oxygen-carrying capacity, leading to ongoing lactic acid production via anaerobic metabolism in oxygen-deprived tissues. Normal saline is acidic (pH 5.5) and infusing large volumes can cause acidosis. Lactated ringers is less acidic (pH 6.5), but is slightly hypotonic and some experts believe it may worsen swelling in TBI patients. Even isotonic crystalloids may seep into damaged tissues, rather than stay in the vascular compartment, due to osmotic differences. High-volume unwarmed fluids contribute to hypothermia, which develops easily and rapidly in trauma patients, due to reduced heat generation during anaerobic metabolism, reduced circulating blood volume, immobility, and physiologic responses to blood loss. Clot formation depends on a complex series of pH- and temperature-dependent chemical reactions. Acidosis and hypothermia both produce coagulopathy, which in turn further exacerbates acidosis and hypothermia. Once established, the lethal triad cycle is difficult to interrupt.

The current TCCC-preferred fluid for blood loss replacement in trauma victims is "LTOWB": cold-stored, low-titer O-negative whole blood. The "ABO" blood groups refer to the presence of A-type and B-type antigens on the surface of red blood cells. Most antibodies are only produced after an exposure to an antigen ("sensitization"). For instance, someone with a severe allergy to bees only experiences an allergic reaction after their second bee sting- the first sting merely introduces foreign material that the body that incites antibody production. But, in the case of antibodies that act against A-type and B-type antigens, this is not true. Each person is born with innate A and/or B antibodies, with no foreign blood exposure required. If a patient with type-A blood is given a transfusion of type-B blood, each of the patient's anti-B antibodies will adhere to several type-B antigens in the donor blood. This causes the donor RBCs to clump together ("agglutination"). These clumps block small blood vessels throughout the body. As the cells of clumps break down ("hemolysis"), they release hemoglobin, which can clog the kidneys and result in kidney failure. 

Image shows agglutination in a rapid blood-type test.

Those with blood type A innately have A antigens and anti-B antibodies. Those with blood type B have B antigens, and anti-A antibodies. Those with type O blood have no antigens, and both anti-A and anti-B antibodies. Therefore, type-O blood will not produce reactions in people with type A or B blood. 

A second transfusion consideration is presence or absence of Rh factor. 85% of Americans are Rh-positive; they have Rh antigens, and therefore will not produce anti-Rh antibodies. Only Rh-negative individuals can produce anti-Rh antibodies, and they only do so after sensitization. Sensitization can occur via pregnancy with an Rh-positive fetus, or via an Rh-mismatched transfusion. In the case of pregnancy, Rh+ cells rarely cross the placenta; exposure may occur during childbirth, and may become an issue if a second pregnancy with an Rh+ fetus occurs. Similarly, a first transfusion with Rh-mismatched blood is not a problem, however a second transfusion or Rh+ pregnancy might cause a reaction.

Low-titer O blood refers to low levels of anti-A and anti-B antibodies in the type-O donor's blood. Titers below <256 are very unlikely to cause transfusion reactions in blood recipients. For massive transfusion purposes, low A/B antibody titers are more important than presence or absence of Rhesus factors (i.e. whether the blood is "O-positive" or O-negative". Because rhesus-negative patients don't develop sensitivity to Rh-positive products until several weeks after exposure, Rh+ blood can be given to Rh- acute trauma patients without significant risk of a transfusion reaction. So, while ABO-mismatched transfusion reactions can be severe, Rh-mismatch is less concerning in acute trauma situations. For acute trauma, low-titer O blood is best. For general medical transfusion applications, O-negative blood is most useful. Generally, people with type-O-negative blood are 'universal donors', and those with type AB-positive are 'universal recipients'. 

Because supplies of blood products may be limited in the field, TCCC guidelines offer simplified criteria for when to give blood, and targets for holding off on giving additional units of blood. Patients who do not have signs of shock- such as altered mental status or a weak or absent radial pulse- do not require IV fluid resuscitation. These patients may be given oral fluids if available. Risk of vomiting and aspiration during surgery is very low. Patient outcomes are improved by using oral rehydration to resolve pre-existing dehydration which may have occurred during combat operations. Placement of IVs in stable patients who can be orally re-hydrated unnecessarily wastes supplies and caregiver time, increases risk of infection, hypothermia, and other complications, and is discouraged. However, early placement of IV/IO should be done in unstable patients, or those who may later decompensate. Saline locks should be flushed every two hours.

TCCC Blood Products Order of Preference:

1) "LTOWB" Cold stored low-titer O negative whole blood. This product has had disease testing performed (HIV, HBV, HCV, West Nile, syphilis, HTLV, Chagas), anti-A/B antibody titer <256, and leukocyte reduction. Shelf life is 21-35 days.

2) "FWB" Pre-screened low-titer O fresh whole blood. 16ga IV should be used to collect from the donor; placement of an 18ga in the recipient is sufficient, safe, and encouraged. Shelf life 6-8 hours. 

3) Plasma, RBCs, and platelets in 1:1:1 ratio

4) Plasma and RBCs in a 1:1 ratio. Shelf life 1 yr for plasma, 42 days for RBCs.

5) Plasma or RBCs alone. Some countries (including France, Germany, and South Africa) use freeze-dried plasma (FDP) for austere ops; FDP contains fibrinogen and other hemostatic factors.

Care should be used to prevent hypothermia; warm chilled blood before administration and use a filter to remove small clots. Citrate preservative used in blood collection bags binds with the patient's calcium, therefore 1g calcium should be given after administration of the first unit of blood (either 30mL 10% calcium gluconate or 10 mL 10% calcium chloride daily). Give blood until mental status improves, radial becomes palpable, or BP rises above 100. 














Monitor for reactions:
1) Anaphylaxis: wheezing, stridor, shortness of breath, hypotension, hives. Give 0.3mg epi + 25mg benadryl and monitor airway. Optionally give 10-40mg methylprednisolone slow IVP. 
2) Acute hemolytic reactions: rupture of RBCs and leakage of contents, generally due to blood mismatch. Symptoms include fever, flank pain, and red/brown urine. All 3 are rarely observed together in field, Pain may alternately occur in an arm, chest, or back, DIC may occur. Nausea may preceed other symptoms. Give 25mg benadryl via slow IV push.
Treatment measures for both anaphylactic and hemolytic reactions: immediately stop the transfusion, give normal saline, stabilize the patient, and try another blood product.




The Use of Low Titer Group O Whole Blood in Emergency Medicine

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