When is Fresh Frozen Plasma (FFP) indicated in a patient with decompensated chronic liver disease and an elevated International Normalized Ratio (INR)?

Fresh Frozen Plasma is Not Indicated for Patients with Decompensated Chronic Liver Disease and Elevated INR

Fresh frozen plasma (FFP) is not recommended for patients with decompensated chronic liver disease and an elevated INR of 3.2, as it does not effectively reduce bleeding risk and may cause harm through volume overload and other complications. 1

Understanding INR in Liver Disease

• INR in liver disease reflects decreased synthesis of coagulation factors but does not accurately predict bleeding risk due to the concurrent reduction in anticoagulant proteins, creating a rebalanced hemostatic system 1
• The INR scale was specifically designed for monitoring vitamin K antagonist therapy and is not validated for assessing bleeding risk in cirrhosis 1
• Global tests of hemostasis, such as thrombin generation or viscoelastic tests, better capture the actual hemostatic status of patients with cirrhosis, though they have not been fully clinically validated 1

Evidence Against FFP Use in Liver Disease

• FFP transfusion in patients with cirrhosis and prolonged INR frequently does not lead to full normalization of the prothrombin time 1
• Ex vivo studies show FFP only minimally improves thrombin generating capacity in patients with cirrhosis, likely because it delivers both pro- and anticoagulant proteins 1
• In patients with compensated and decompensated cirrhosis, FFP administration only slightly improved global thrombin generating capacity in a few patients and actually worsened it in approximately one-third of cases 2
• A Cochrane review found no studies demonstrating the efficacy of prophylactic FFP in preventing bleeding in patients with cirrhosis undergoing invasive procedures 1

Risks of FFP Administration

• FFP increases blood volume and portal pressure, potentially exacerbating portal hypertension and increasing bleeding risk 1
• Transfusion-related acute lung injury is the leading cause of transfusion-related mortality and can be associated with FFP transfusion 1
• Transfusion-associated circulatory overload occurs in up to 8% of transfusions with a mortality rate of 5-15% 1
• Allergic or anaphylactic reactions to FFP occur at rates of 1:591 to 1:2,184 plasma units transfused 1
• Other risks include transmission of infections, febrile non-hemolytic transfusion reactions, red blood cell allo-immunization, and hemolytic transfusion reactions 1

Alternative Approaches

• For patients requiring invasive procedures, viscoelastic testing (TEG/ROTEM) can guide transfusion strategy and has been shown to significantly reduce blood product use (17% vs 100%) without increasing bleeding complications 1
• When correction is needed, low-volume cryoprecipitate may be preferred over high-volume FFP 1
• Prothrombin complex concentrates (PCCs) may be more effective at correcting INR but are not routinely recommended due to potential thrombotic risks 1, 3

Special Considerations

• Bleeding risk in cirrhosis is better predicted by technical factors or complications such as sepsis or kidney injury rather than by coagulation test abnormalities 1
• Patients with acute-on-chronic liver failure (ACLF) may have a more pronounced coagulopathy but still show the same pattern of minimal response to FFP 2
• Large volumes of FFP (≥6 units) may be required to cause significant INR improvement, which increases the risk of volume overload 4

Clinical Guidance

• The AASLD explicitly states that INR should not be used to gauge bleeding risk among patients with cirrhosis/ACLF 1
• The EASL strongly recommends against correction of prolonged INR with FFP to decrease procedure-related bleeding in patients with cirrhosis 1
• For patients requiring invasive procedures, less stringent preprocedural coagulation parameters (INR ≤2.0, platelets ≥25 x109/L) have been associated with fewer hemorrhagic complications and decreased preprocedural FFP/platelet administration compared to historical cut-off points 1