What are the guidelines for Fresh Frozen Plasma (FFP) transfusion in a patient with coagulopathy or bleeding disorder?

Fresh Frozen Plasma (FFP) Transfusion Guidelines

For patients with massive bleeding, administer FFP early at a dose of 10-15 ml/kg (approximately 3-4 units for a 70 kg adult), using high-ratio transfusion strategies of at least 1:2 FFP:RBC, ideally approaching 1:1 in trauma patients. 1, 2

Indications for FFP Transfusion

Definitive Indications

• Massive bleeding (>10 units RBC in 24 hours or >6 units in 6 hours) with documented or presumed coagulopathy 1, 2
• Significant bleeding with coagulopathy when PT or APTT >1.5 times normal control 1
• Active bleeding with INR >1.5-2.0 2, 3
• Warfarin reversal with active bleeding when prothrombin complex concentrate (PCC) is unavailable 1, 3

Contraindications - Do NOT Use FFP For:

• Prophylactic correction of mild coagulation abnormalities in non-bleeding patients before low-risk procedures 2, 4
• Volume replacement or hypovolemia - use crystalloids or colloids instead 2, 3
• Isolated hypofibrinogenemia - use cryoprecipitate or fibrinogen concentrate instead 1, 2, 5
• Cirrhotic patients without active bleeding - FFP can increase portal pressure 2

Dosing Strategy

Standard Dosing

• Initial dose: 10-15 ml/kg (approximately 700-1050 ml for a 70 kg patient = 3-4 units) 1, 2
• Each unit contains 250-300 ml volume 2, 5
• For warfarin reversal specifically: Lower doses of 5-8 ml/kg are usually sufficient 2, 3

Critical Dosing Threshold

• Doses below 10 ml/kg are unlikely to achieve the 30% factor concentration threshold needed for hemostasis 2
• Four units of FFP contain only approximately 2 g of fibrinogen, making it inefficient for isolated fibrinogen replacement 2, 5

Massive Transfusion Protocols

• Trauma patients: Use high-ratio transfusion strategies of at least 1:2 FFP:RBC, ideally approaching 1:1 1
• The PROPPR trial demonstrated that 1:1:1 ratios (FFP:platelets:RBC) improved hemostasis and reduced exsanguination deaths compared to 1:1:2 ratios 1
• Obstetric hemorrhage: Withhold FFP until 4 units of RBC have been transfused unless early coagulopathy is diagnosed, then maintain 1:1 ratio 2

Laboratory Guidance

When to Guide FFP with Lab Values

• If using FFP-based coagulation resuscitation strategy: Guide further FFP use by PT and/or APTT >1.5 times normal and/or viscoelastic evidence of coagulation factor deficiency 1
• Recheck coagulation parameters after transfusion to determine need for additional doses 2

Important Caveat

• In massive bleeding, do NOT wait for laboratory confirmation - administer FFP early based on clinical assessment 2, 3
• Coagulopathy in trauma often precedes laboratory abnormalities 1

Administration Practicalities

Thawing and Storage

• FFP can be thawed using: dry oven (10 min), microwave (2-3 min), or water bath (20-30 min) 2, 6
• Once thawed, FFP must be used within 30 minutes if removed from refrigeration 2, 3
• Thawed FFP stored at 4°C can be used for up to 24 hours (some evidence supports up to 5 days, though Factor VIII activity declines significantly) 2, 7, 6

Infusion Rate

• Infuse as rapidly as clinically tolerated in acute bleeding situations - the goal is rapid correction of coagulopathy, not adherence to a specific infusion rate 2
• Alert blood bank immediately to facilitate timely preparation 2

Blood Group Compatibility

• FFP must be ABO-compatible with the recipient 2, 3
• If blood type unknown, use type AB FFP 2, 3
• Type A plasma can be used for unknown blood types in trauma settings with acceptable safety profile 1

Alternatives to FFP - When to Choose Something Else

For Hypofibrinogenemia

• Use cryoprecipitate or fibrinogen concentrate instead of FFP when fibrinogen <1.0-1.5 g/L 1, 2, 5
• Cryoprecipitate delivers concentrated fibrinogen with minimal volume 5
• FFP is inefficient for fibrinogen replacement - four units contain only ~2 g fibrinogen 2, 5

For Warfarin Reversal

• Prothrombin complex concentrate (PCC) should be preferred over FFP for urgent warfarin reversal 1, 3
• Use FFP only when PCC is unavailable 1

Evidence from Recent Trials

• The RETIC trial (2023) showed FFP was insufficient to correct hypofibrinogenemia compared to fibrinogen concentrate 1
• 52% of patients in the FFP group required crossover rescue therapy with coagulation factor concentrates vs. only 4% in the fibrinogen concentrate group 1

Serious Risks and Monitoring

Major Complications

• Transfusion-related acute lung injury (TRALI) - the most serious complication; FFP and platelets are most frequently implicated 1, 2, 4
• Transfusion-associated circulatory overload (TACO) - especially with large volumes 2, 5, 4
• ABO incompatibility if not properly matched 1, 2
• Infectious disease transmission (including prion diseases) 1
• Allergic reactions 1, 5

Metabolic Complications

• Citrate toxicity with massive transfusion leading to hypocalcemia - citrate metabolism is impaired by hypoperfusion, hypothermia, and hepatic insufficiency 1
• Maintain ionized calcium >0.9 mmol/L during massive transfusion 1

Common Pitfalls to Avoid

Ineffective Use

• FFP transfusion for mild coagulation abnormalities (PT 13.1-17 seconds, INR 1.1-1.85) results in normalization in only 0.8% of patients 8
• Median decrease in INR is only 0.07 with FFP transfusion in mildly abnormal coagulation 8

Survivorship Bias

• Early observational studies suggesting benefit of high FFP:RBC ratios may have been confounded by survivorship bias - patients who died before thawed plasma arrived were sicker 1
• However, RCTs (PROPPR trial) confirmed benefit of high ratios despite this concern 1

Delayed Administration

• Minimizing delays in FFP administration is crucial - earlier time to hemostasis is independently associated with decreased 30-day mortality, acute kidney injury, ARDS, multiorgan failure, and sepsis 1