A 35-year-old man with cirrhosis presents with hematemesis and melena. Coagulation studies show: PT 18 s (prolonged), aPTT 42 s (prolonged), platelet count 65 × 10⁹/L, fibrinogen 120 mg/dL (low). Which of the following mechanisms is NOT responsible for the coagulopathy in this patient?

Explanation

## Coagulopathy in Cirrhosis: Multifactorial Mechanism ### Pathophysiology of Liver Disease Coagulopathy | Mechanism | Affected Factor(s) | Clinical Consequence | |-----------|-------------------|---------------------| | Impaired hepatic synthesis | II, VII, IX, X (Vit K-dependent) | Prolonged PT | | Reduced fibrinogen production | Fibrinogen (Factor I) | Low fibrinogen, prolonged PT/aPTT | | Impaired Factor V synthesis | Factor V | Prolonged PT/aPTT | | Splenic sequestration | Platelets | Thrombocytopenia | | Increased fibrinolysis | Plasminogen, plasmin | Consumption of fibrinogen, platelets | | Portal hypertension | Platelet pooling | Thrombocytopenia | **Key Point:** Cirrhosis causes a **balanced coagulopathy** — both procoagulants (Factors II, V, VII, X, fibrinogen) AND anticoagulants (Protein C, Protein S, antithrombin) are reduced. The net effect is variable bleeding risk, not always proportional to PT/aPTT. **High-Yield:** Factor V is **synthesized in the liver** and is NOT lost in ascitic fluid. Ascites contains albumin, immunoglobulins, and other plasma proteins, but not clotting factors in clinically significant amounts. Factor V deficiency in cirrhosis is due to impaired hepatic synthesis, not loss. **Clinical Pearl:** PT prolongation in cirrhosis reflects loss of short-half-life factors (VII, II, X, V). aPTT prolongation reflects loss of Factors II, V, IX, X, XI, XII. Fibrinogen is typically mildly reduced (120–200 mg/dL) unless there is DIC or advanced liver failure. **Warning:** Do NOT confuse loss of clotting factors in ascites with loss of albumin or immunoglobulins. Clotting factors are not selectively filtered into ascitic fluid; their deficiency in cirrhosis is purely synthetic. ### Why Factor V Loss in Ascites is NOT a Mechanism Factor V is a **large glycoprotein** (330 kDa) synthesized exclusively by hepatocytes and megakaryocytes. It is not filtered into ascitic fluid because: 1. It is too large to cross the peritoneal membrane 2. Ascites is an ultrafiltrate of plasma, not a protein-rich exudate in uncomplicated cirrhosis 3. Factor V levels correlate with hepatic synthetic function, not ascites volume **Mnemonic:** **LIVER** factors lost in cirrhosis: **L**ow Fibrinogen, **I**mpaired synthesis of Vit K factors, **V**itamin K-dependent factors (II, VII, IX, X), **E**rythrocytes (anemia from bleeding), **R**educed Factor V.