Why Cirrhosis Prolongs INR
Cirrhosis prolongs INR due to decreased synthesis of procoagulant factors (I, II, V, VII, X), but this does not accurately reflect bleeding risk because anticoagulant factors (protein C, antithrombin) are also reduced, creating a rebalanced hemostatic system. 1, 2
Pathophysiology of Coagulation Changes in Cirrhosis
Decreased Synthesis of Coagulation Factors
- The liver is responsible for synthesizing most coagulation factors
- In cirrhosis, there is diminished production of procoagulant factors I (fibrinogen), II (prothrombin), V, VII, and X 1, 2
- These factors are directly measured by the prothrombin time (PT), which is used to calculate INR
Rebalanced Hemostasis
- While procoagulant factors decrease, there is a parallel reduction in liver-derived anticoagulant factors:
- Protein C
- Antithrombin III
- Protein S 1
- This creates a new hemostatic balance rather than a pure bleeding tendency 1
Compensatory Mechanisms
- Elevated endothelial-derived factor VIII (not measured by INR) 1, 2
- Increased von Willebrand factor (vWF) which compensates for thrombocytopenia 1
- These changes can actually create a relatively hypercoagulable state despite prolonged INR 1, 2
Problems with INR Interpretation in Cirrhosis
INR Limitations
- INR was designed specifically for monitoring warfarin therapy, not liver disease 1
- INR only measures procoagulant factors but not anticoagulant factors 1, 2
- Different thromboplastin reagents used in the test cause significant variation in INR values between hospitals 1
Clinical Implications
- Prolonged INR does not accurately predict bleeding risk in cirrhosis patients 1, 3
- A meta-analysis showed no significant association between pre-procedural INR and periprocedural bleeding events (pooled odds ratio 1.52; 95% CI 0.99,2.33; P = 0.06) 3
- Attempts to "correct" INR with fresh frozen plasma (FFP) often fail to normalize it and may worsen portal hypertension 1
Alternative Assessment Methods
Viscoelastic Tests
- Thromboelastography (TEG) and rotational thromboelastometry (ROTEM) provide more comprehensive assessment of coagulation 1
- These tests measure both pro- and anticoagulant factors
- A randomized controlled trial showed TEG-guided transfusion strategy led to significantly lower use of blood products compared to standard of care (based on INR and platelet count) without increasing bleeding complications 4
Clinical Significance
- Despite elevated INR, patients with cirrhosis may have normal hemostasis or even be hypercoagulable 1, 2
- INR values ≥1.6-1.7 may indicate the starting point of significant coagulation dysfunction with increasing mortality risk 5
- The European Association for the Study of the Liver (EASL) guidelines state that INR does not predict post-procedural bleeding in patients with cirrhosis undergoing invasive procedures 1
In conclusion, while cirrhosis does prolong INR through decreased synthesis of procoagulant factors, this laboratory finding must be interpreted with caution as it does not accurately reflect the overall hemostatic balance or bleeding risk in these patients.