2. PHYSIOLOGICAL ROLE OF THE LIVER IN HEMOSTASIS

The liver is central to all three components of hemostasis:

A. Coagulation Factors (Pro-coagulant)

Synthesized by hepatocytes:

• Fibrinogen (Factor I)
• Factors II (Prothrombin), V, VII, IX, X, XI
• Factor XIII
• Vitamin K–dependent factors: II, VII, IX, X

B. Natural Anticoagulants

Also synthesized by the liver:

• Protein C
• Protein S
• Antithrombin III

C. Fibrinolytic System

• Plasminogen
• α2-antiplasmin
• Clearance of tPA

D. Platelet Regulation

• Thrombopoietin (TPO) synthesis
• Clearance of activated clotting factors

👉 Thus, liver failure affects clot formation, inhibition, and clot breakdown simultaneously.

3. PATHOPHYSIOLOGY OF COAGULOPATHY IN LIVER DISEASE

A. Reduced Synthesis of Coagulation Factors

• ↓ Factors II, V, VII, IX, X, XI
• Factor VII has the shortest half-life → PT prolongs early

B. Reduced Natural Anticoagulants

• ↓ Protein C, Protein S, Antithrombin III
• Creates pro-thrombotic tendency

C. Thrombocytopenia (Multifactorial)

1. Splenic sequestration (portal hypertension)
2. ↓ Thrombopoietin synthesis
3. Bone marrow suppression (alcohol, sepsis)
4. Immune-mediated platelet destruction

D. Platelet Dysfunction

• Impaired adhesion and aggregation
• Altered von Willebrand factor (vWF) interaction

E. Fibrinolytic Abnormalities

• ↓ Clearance of tPA → hyperfibrinolysis
• ↓ Plasminogen
• Net effect varies with disease stage

F. Endothelial Dysfunction

• ↑ vWF
• ↓ ADAMTS13
• Promotes platelet adhesion despite thrombocytopenia

4. REBALANCED HEMOSTASIS – THE MODERN CONCEPT 

In chronic liver disease:

👉 Net result:
A new balance that is:

• Unstable
• Easily tipped by infection, AKI, procedures, GI bleed

Here PT/INR reflects only pro-coagulant deficiency, NOT bleeding risk

5. LABORATORY ABNORMALITIES IN LIVER COAGULOPATHY

A. Conventional Tests (Limited Value)

—> INR was designed for warfarin monitoring — NOT cirrhosis

B. Global Coagulation Tests (Preferred in ICU)

Thromboelastography (TEG) / ROTEM

Assesses:

• Clot initiation
• Clot strength
• Fibrinolysis

Advantages:

• Bedside
• Dynamic
• Guides targeted transfusion

6. BLEEDING MANIFESTATIONS

A. Common Bleeding Sites

• Variceal bleeding (portal hypertension – NOT coagulopathy)
• Mucosal bleeding
• Procedure-related bleeding
• Intracranial hemorrhage (rare)

B. Important Concept

– Most GI bleeding in cirrhosis is portal hypertensive, not due to INR elevation

7. THROMBOTIC MANIFESTATIONS (UNDER-RECOGNIZED)

Despite abnormal INR, cirrhotic patients are prone to:

• Portal vein thrombosis
• Deep vein thrombosis
• Pulmonary embolism
• Hepatic artery thrombosis (post-transplant)

👉 Elevated INR does NOT protect against thrombosis

8. COAGULOPATHY IN ACUTE LIVER FAILURE (ALF)

ALF resembles consumptive coagulopathy + hyperfibrinolysis

9. MANAGEMENT PRINCIPLES (CRITICAL CARE FOCUS)

A. Do NOT Correct Numbers Prophylactically

• No routine FFP for elevated INR
• No platelet transfusion unless bleeding/procedure planned

B. Indications for Correction

C. Blood Product Use (Targeted)

>—TEG-guided transfusion reduces unnecessary blood use

D. Vitamin K

• Useful only in cholestasis, malnutrition
• Ineffective in synthetic failure

E. Anticoagulation in Cirrhosis

• Safe if indicated (DVT, PVT)
• Requires careful monitoring
• INR unreliable → use clinical judgment

10. COAGULOPATHY VS DIC