Massive Transfusion

Massive transfusion is traditionally arbitrarily defined as replacement of >1 blood volume in 24 hours, or ≥10 units of whole blood (WB) or red blood cells (RBCs) in 24 hours as an approximation of the replacement of at least one blood volume. Other definitions may be more clinically useful, such as the “critical administration threshold,” defined as a requirement for ≥3 red blood cell units in one hour.

A Massive Transfusion Protocol (MTP) should be used in critically bleeding patients anticipated to require massive transfusion. Traditional labs generally won't return fast enough to guide the use of clotting factors, so this is protocoled (example below).

Specific Populations

Trauma

a significant proportion (25–40%) of severely injured trauma patients are already coagulopathic at the time of presentation to hospital. Exacerbated by hypothermia, acidemia, resuscitation with hypocoagulable fluids, hypoperfusion, and ongoing bleeding with further consumption of coagulation factors
PROPPR trial compared 1:1:1 transfusion (plt:plasma:RBC) to 1:1:2 (plt:plasma:RBC) in the resuscitation of trauma patients
- no statistically significant difference in 24-hour and 30-day mortality with the 1:1:1 versus the 1:1:2 component ratios
- possibly higher rates of anastomotic hemostasis and lower deaths from exsanguination in the 1:1:1 arm
- due to these findings, a 1:1:1 MTP was adopted in trauma as the standard of care
- In Canada, the units of platelets are derived from pooled apheresis rather than from whole blood donations, and are equivalent to ~5-6 whole blood units.

Cardiac surgery

The most common indication for MTP
Analyses show that a higher ratio of platelets and plasma to RBC is associated with better outcomes
Therefore, use 1:1:1 in these patients as well

Obstetric hemorrhage

Pregnancy and the postpartum period are hypercoagulable states with compensatory increased fibrinolysis.
Guidelines from the College Nationale Gynecologie et Obstetrics Francais (CNGOF) suggest maintaining the fibrinogen ≥200 mg/dL
Expert opinion from multiple groups reflects the data for trauma and suggest use of a 1:1:1 ratio for treating massive hemorrhage in obstetric patients.

Liver Disease

In patients with severe liver disease and active hemorrhage, attempts to normalize platelet number and plasma coagulation factor concentrations are probably helpful, with the caveats that increased blood volume will increase portal pressure, and increasing platelet counts in the face of splenomegaly is difficult.
In the absence of better day, consider a 1:1:1 MTP as well.

Goals of MTP

Recognize early blood loss
Maintain tissue perfusion and oxygenation by restoring blood volume and hemoglobin content
Stop bleeding with surgical or IR interventions
Use blood components to correct coagulopathies

Massive Transfusion Protocol (MTP)

When do you need massive transfusion?

Instability, bleeding, trajectory, and hemorrhagic shock?
The hemoglobin level takes hours to fall after bleeding. Consequently, checking the hemoglobin has little role in determining need for MTP. Hypotension is usually a late manifestation of hemorrhage. Worsening hypotension and vasopressor requirement should prompt consideration for MTP.

Avoid Crystalloids

Large volume crystalloid resuscitation is no longer recommended because it exacerbates coagulopathy and is associated with several deleterious side effects, including tissue edema, acidosis, reperfusion injury and multiorgan failure
ATLS recommends maximum 1 L crystalloids prior to switching to blood products

Activation

Labs (do not delay treatment while waiting)
1. Type and crossmatch
2. CBC, INR, PT, PTT, fibrinogen
3. Electrolytes, Ca/Phos/Mg, ionized calcium
4. VBG or ABG
Activate the MTP (site-specific)

Blood Typing

Uncrossmatched (O Rh negative or O Rh positive RBC) should be available immediately.
Group O Rh negative RBC should be reserved for women of child-bearing potential (younger than 45 to 50 years old).
Patients should be switched to crossmatched RBC as soon as it is available, which should be achievable within one hour for most patients (about 97 percent).
For a small number of patients who have a positive antibody screen, obtaining crossmatched RBC may take hours.

Procedural concerns

Access

Also try to get arterial access for live hemodynamic monitoring.

Intubation

Patients with exsanguinating hemorrhage will often need to be intubated (e.g., to facilitate endoscopic control of bleeding).
Intubating a patient who is extremely under-resuscitated may precipitate hemodynamic collapse.
It is often best to obtain access, give one round of massive transfusion (e.g., 6 units PRBCs, 6 units of platelets, and 6 units of FFP), and establish a reasonable blood pressure prior to intubation (“resuscitate before you intubate”).

Balanced Transfusion

1:1:1 pRBC:FFP:Platelets
Avoid crystalloid resuscitation
Consider additional fibrinogen (concentrated fibrinogen or cryoprecipitate)
- 10 units cryoprecipitate should increase the fibrinogen by ~75 mg/dL
- Consider a fibrinogen target >150-200 mg/dL

Post-MTP Targets

Parameters	Values to aim for
Temperature	>35 °C
Acid-base status	pH >7.2, base excess <–6, lactate <4 mmol/L
Ionised calcium (Ca)	>1.1 mmol/L
Haemoglobin (Hb)	This should not be used alone as transfusion trigger; and, should be interpreted in context with haemodynamic status, organ & tissue perfusion.
Platelet (Plt)	≥ 50 x 10^9 /L (>100 x 10^9 if head injury/ intracranial haemorrhage)
PT/APTT	≤ 1.5x of normal
Fibrinogen	≥ 1.0 g/L

Adjunct Care

TXA

Consider administration of TXA (limited evidence in MTP). Typical dosing is one gram IV given immediately, which may be followed by infusions of 1 gram over 8 hours repeatedly for 24 hours (the protocol used in the CRASH trials).

Reverse Existing Coagulopathies

Warfarin --> PCC, vitamin K
DOAC --> Andexxa, idarucizumab (dabigatran)
Platelet dysfunction --> DDAVP

Calcium

Hypocalcemia develops due to (1) pre-existing hypocalcemia and (2) blood products leading to calcium chelation by citrate.

When administering one round of MTP (containing 6 units PRBCs), it's probably reasonable to add either 1-2 gram of IV calcium chloride or 3-6 grams of IV calcium gluconate.