Why is a balanced blood transfusion initiated after administration of 4 units of packed red blood cells (PRBCs)?

From the Guidelines

Balanced blood transfusion protocols typically begin after 4 units of packed red blood cells (PRBCs) because this threshold represents the point where coagulopathy and dilutional effects become clinically significant, as supported by the European guideline on management of major bleeding and coagulopathy following trauma: sixth edition 1. When a patient receives large volumes of PRBCs alone, they develop deficiencies in platelets and clotting factors since these components are not present in meaningful amounts in PRBC units.

• The administration of platelets as part of a fixed-ratio blood product strategy in massive bleeding is associated with significantly decreased 24 h and 30-day mortality, as well as improved haemostasis 1.
• Receiving higher ratios of platelets and plasma relative to pRBC hastens haemostasis in subjects who have yet to achieve haemostasis within 3 h after hospital admission 1. After approximately 4 units of PRBCs (about 40% of total blood volume in an average adult), patients begin to show measurable coagulation abnormalities that increase bleeding risk.
• A recent literature review suggested that MT protocols in adult trauma patients should utilise ratios between 1:1:1 and 1:1:2 1. At this point, implementing a balanced transfusion approach with a 1:1:1 ratio of PRBCs, plasma, and platelets helps prevent trauma-induced coagulopathy.
• The pre-emptive administration of platelets as part of a fixed-ratio blood product strategy in massive bleeding is controversial, but further analysis of the PROPPR trial data suggests that transfusion of platelets in bleeding patients is associated with significantly decreased mortality and improved haemostasis 1. This balanced approach mimics whole blood composition and addresses all aspects of the coagulation system simultaneously.
• For initial coagulation support, while awaiting viscoelastic or laboratory tests, the administration of 2 g fibrinogen based on clinical criteria at admission has been proposed, to mimic the 1:1 ratio corresponding to the first 4 units of pRBC and potentially correct hypofibrinogenemia 1. For massive transfusion protocols, this typically means giving 1 unit of plasma and 1 unit of platelets for every PRBC unit once the 4-unit threshold is crossed.
• A randomised comparison of fibrinogen concentrate and cryoprecipitate in hypofibrinogenaemic trauma patients found that both treatments effectively increased plasma fibrinogen, with greater elevation in fibrin-based clot amplitude after the first administration with fibrinogen concentrate 1. This strategy has been shown to improve outcomes in patients with severe hemorrhage by maintaining hemostatic function while addressing oxygen-carrying capacity needs.

From the Research

Blood Transfusion Ratios

The practice of starting balanced blood transfusion after 4 units of packed red blood cells is based on several studies that have investigated the optimal ratio of fresh frozen plasma (FFP) to packed red blood cells (RBC) in massively transfused trauma patients.

• A study published in 2008 2 found that a 1:1 FFP:RBC ratio within the first 6 hours reduced life-threatening coagulopathy, but did not translate into a survival benefit.
• Another study published in 2011 3 found that a high FFP:RBC ratio decreased mortality in all massively transfused trauma patients, regardless of admission international normalized ratio (INR).
• A 2018 meta-analysis 4 found that a balanced transfusion ratio of plasma to packed red blood cells improved outcomes in both trauma and surgical patients.

Optimal Transfusion Ratio

The optimal transfusion ratio is still a topic of debate, but several studies suggest that a ratio of 1:1 to 1:1.5 FFP:RBC may be beneficial in reducing mortality and coagulopathy.

• A study published in 2020 5 found that reconstitution of blood with FFP at different ratios resulted in haematocrit or fibrinogen levels that were borderline with regard to recommended substitution triggers.
• The 2018 meta-analysis 4 found that a ratio of 1:1.5 provided the largest 24-h and 30-day survival benefit.

Clinical Decision Making

The decision to start balanced blood transfusion after 4 units of packed red blood cells should be based on individual patient needs and clinical judgment.

• A guide to clinical decision making published in 2019 6 emphasizes the importance of careful adaptation of blood product indications to the patient's current clinical situation and pre-existing diseases.