Why is Fresh Frozen Plasma (FFP) administered after transfusing 3 units of Packed Red Blood Cells (PRBCs)?

Why FFP is Given After 3 Units of PRBCs

The traditional practice of giving FFP after 3 units of PRBCs is outdated and not supported by current evidence; modern massive transfusion protocols recommend early FFP administration at higher ratios (1:1 to 1:2 FFP:PRBC) from the start of resuscitation, not after an arbitrary number of PRBC units. 1

Evolution of Transfusion Practice

The historical approach was based on flawed assumptions about dilutional coagulopathy:

• Old paradigm: FFP was traditionally given when PT or APTT exceeded 1.5 times normal OR after 10 RBC units had been transfused, with many protocols stipulating 1 unit FFP for every 4 units PRBCs 1
• Current understanding: Trauma-induced coagulopathy occurs early and is not purely dilutional—it results from consumption of hemostasis factors at injury sites and systemic coagulation activation 1

Evidence-Based Rationale for Early High-Ratio FFP

Military and civilian data demonstrate that early high-ratio FFP transfusion (approaching 1:1 or at minimum 1:2) significantly reduces mortality compared to delayed or low-ratio strategies:

• Casualties receiving FFP:PRBC ratios of 1:4 or lower had three-fold higher mortality than those receiving 2:3 ratios 1
• FFP:PRBC ratios ≥1:1.5 are independently associated with 52% lower mortality risk after controlling for confounders 2
• The mortality benefit from high FFP:PRBC ratios applies to ALL massively transfused trauma patients, regardless of admission INR 3

Optimal FFP:PRBC Ratio

The evidence suggests ratios between 1:2 and 1:1 provide maximal benefit:

• Ratios of 1:2 to 3:4 show maximal hemostatic effect: 12% decrease in PT, 56% decrease in clotting time, and 38% increase in clot firmness 4
• Ratios ≥1:1 do not confer additional hemostatic advantage over 1:2 to 3:4 ratios 4
• Seven studies showed better outcomes with high FFP:RBC ratios, while only two did not 1

Current Guideline Recommendations

European trauma guidelines recommend early FFP treatment in massive bleeding, not delayed administration:

• Initial recommended dose is 10-15 ml/kg FFP 1
• FFP should be given early in thawed form for patients with massive bleeding (Grade 1B recommendation) 1
• Further FFP doses depend on coagulation monitoring and amount of other blood products administered 1

Critical Pitfalls to Avoid

Waiting for laboratory confirmation or arbitrary PRBC thresholds delays life-saving treatment:

• Do not wait for PT/APTT results before initiating high-ratio FFP in massive hemorrhage—coagulopathy is present early 1, 3
• Do not use outdated 1:4 ratios or wait until 10 units of PRBCs have been given 1
• Recognize that FFP benefits are confined to patients with actual or impending coagulopathy, not prophylactic use in non-bleeding patients 4

Important Safety Considerations

FFP carries significant risks that must be balanced against benefits:

• FFP is associated with transfusion-related acute lung injury (TRALI), circulatory overload, ABO incompatibility, and infectious disease transmission 1
• FFP and platelet concentrates are the most frequently implicated products in TRALI 1
• Early empirical FFP may increase delayed traumatic intracerebral hematoma frequency in severe head injury 1
• High FFP:PRBC ratios (≥1:1.5) are associated with almost twofold higher risk of acute respiratory distress syndrome 2

Alternative Strategies

Fibrinogen concentrate and cryoprecipitate are superior to FFP for correcting hypofibrinogenemia:

• FFP should be avoided for hypofibrinogenemia correction if fibrinogen concentrate or cryoprecipitate are available 1
• FFP contains only ~70% normal levels of clotting factors and shows wide variability in fibrinogen content 1
• The RETIC trial showed FFP was insufficient to correct hypofibrinogenemia compared to fibrinogen concentrate, with 52% of FFP patients requiring rescue CFC therapy versus only 4% in the CFC group 1