What is the initial management for coagulopathy in cirrhotic patients undergoing emergency surgery with an elevated International Normalized Ratio (INR)?

Management of Elevated INR in Cirrhotic Patients Undergoing Emergency Surgery

Do not routinely correct elevated INR with fresh frozen plasma (FFP) in cirrhotic patients undergoing emergency surgery, as INR does not predict bleeding risk in cirrhosis and FFP transfusion is ineffective and potentially harmful. 1

Understanding INR in Cirrhosis vs. Actual Bleeding Risk

The elevated INR in cirrhotic patients reflects a fundamentally different pathophysiology than warfarin-induced coagulopathy:

• INR was designed exclusively for monitoring vitamin K antagonist therapy and is not validated for assessing bleeding risk in liver disease. 2, 3 The test only measures a limited number of procoagulant proteins (factors II, V, VII, X, and fibrinogen) while ignoring anticoagulant proteins and endothelial function. 1

• Cirrhotic patients maintain a "rebalanced hemostasis" where both procoagulant and anticoagulant factors are proportionally reduced. 3 This explains why INR correlates poorly with actual bleeding risk in these patients. 1

• Technical factors, disease complications (sepsis, renal failure), and procedure-specific issues are better predictors of post-procedural bleeding than coagulation test abnormalities. 1 Renal dysfunction is an independent predictor of bleeding in patients with liver disease, even when INR and platelet counts appear stable. 1, 3

Why FFP Should NOT Be Used

The 2022 EASL guidelines provide a strong recommendation against FFP correction of prolonged INR in cirrhotic patients undergoing invasive procedures (including emergency surgery). 1

The evidence against FFP use is compelling:

• FFP transfusion in cirrhotic patients with prolonged INR frequently fails to normalize prothrombin time because FFP contains both pro- and anticoagulant proteins in physiological proportions. 1

• Ex vivo studies demonstrate that FFP only minimally improves thrombin generation capacity in cirrhotic patients, and actually worsens it in one-third of cases. 1 This occurs in patients with compensated cirrhosis, decompensated cirrhosis, acute-on-chronic liver failure, infection, or shock. 1

• No randomized controlled trials have demonstrated efficacy of prophylactic FFP in preventing bleeding in cirrhotic patients undergoing invasive procedures. 1

Specific Harms of FFP in Cirrhosis

FFP carries potentially life-threatening risks that are particularly relevant in cirrhotic patients:

• Increased portal pressure: FFP increases blood volume and portal pressure, potentially increasing bleeding risk by exacerbating portal hypertension. 1

• Transfusion-related acute lung injury (TRALI): The leading cause of transfusion-related mortality, which can be associated with FFP transfusion. 1

• Transfusion-associated circulatory overload (TACO): Occurs in <1% to 8% of transfusions with a mortality rate of 5-15%. Plasma transfusion is a particular risk factor due to large volumes and increased infusion rates. 1

• Allergic/anaphylactic reactions: Occur in 1:591 to 1:2,184 plasma units transfused. 1

Alternative Approach: Thromboelastography-Guided Management

Consider using viscoelastic testing (TEG/ROTEM) rather than conventional coagulation tests to guide transfusion decisions in cirrhotic patients undergoing emergency surgery. 4, 5

The evidence supporting this approach:

• A randomized controlled trial of 60 cirrhotic patients with significant coagulopathy (INR >1.8 and/or platelets <50 × 10⁹/L) undergoing invasive procedures showed that TEG-guided transfusion resulted in 16.7% receiving blood products versus 100% in the standard care group (P < 0.0001), with only 1 bleeding event (in the standard care group). 4

• A subsequent RCT in 96 cirrhotic patients with nonvariceal GI bleeding showed TEG-guided strategy resulted in only 26.5% receiving all three blood components versus 87.2% in standard care (P < 0.001), with no difference in failure to control bleeding or mortality. 6

• TEG values (R time and MA) were normal in 61% and 75% of cirrhotic patients respectively, despite abnormal conventional tests in most patients. 7

What About Prothrombin Complex Concentrates (PCCs)?

Routine use of PCCs to decrease procedure-related bleeding in cirrhotic patients is discouraged. 1

Important distinction: While four-factor PCC plus intravenous vitamin K is the most effective reversal strategy for warfarin-induced coagulopathy requiring urgent correction 8, this recommendation applies to patients on vitamin K antagonists, NOT to the intrinsic coagulopathy of cirrhosis. 2 The Journal of Hepatology specifically recommends avoiding PCCs in cirrhotic patients as they may increase thrombotic risk. 2

Platelet Management

Do not routinely transfuse platelets when the count is above 50 × 10⁹/L or when bleeding can be treated by local hemostasis. 1

For emergency high-risk procedures where local hemostasis is not possible:

• Platelet count 20-50 × 10⁹/L: Platelet transfusion or thrombopoietin receptor agonists should not be routinely performed but may be considered case-by-case. 1

• Platelet count <20 × 10⁹/L: Platelet transfusion or thrombopoietin receptor agonists should be considered case-by-case. 1

• No studies have specifically evaluated whether platelet transfusion decreases procedure-related bleeding in cirrhotic patients. 1

Fibrinogen Correction

Routine correction of fibrinogen deficiency to decrease procedure-related bleeding is discouraged. 1 A retrospective cohort of cirrhotic patients with very low fibrinogen levels (<150 mg/dL) showed that prophylactic cryoprecipitate administration did not modify bleeding or mortality risk. 1

Practical Algorithm for Emergency Surgery

1. Do NOT reflexively transfuse FFP based on elevated INR alone. 1

2. If available, obtain viscoelastic testing (TEG/ROTEM) to assess actual hemostatic capacity:

   • Transfuse FFP only if reaction time (R) >40 minutes 4
   • Transfuse platelets only if maximum amplitude (MA) <30 mm 4

3. If viscoelastic testing unavailable, proceed to surgery without prophylactic transfusion in most cases, as bleeding risk is not predicted by INR. 1

4. Address modifiable bleeding risk factors:

   • Treat active infection/sepsis aggressively 1
   • Optimize renal function if possible 1, 3
   • Ensure meticulous surgical technique 1

5. Have blood products immediately available for active bleeding management intraoperatively, but do not transfuse prophylactically. 1

Critical Pitfalls to Avoid

• Do not assume elevated INR automatically predicts bleeding risk in cirrhosis - this is the most common and dangerous misconception. 1, 3

• Do not use vitamin K - it is ineffective for cirrhosis-associated coagulopathy (only 16.7% of cirrhotic patients achieved the effectiveness endpoint with IV vitamin K). 9 Vitamin K is only indicated if the patient is also on warfarin. 2

• Do not delay emergency surgery to "correct" INR - this wastes time and exposes patients to transfusion risks without benefit. 1

• Do not confuse warfarin reversal guidelines with cirrhosis management - PCC and vitamin K are appropriate for warfarin reversal 8 but not for intrinsic cirrhotic coagulopathy. 2