Physiologic Mechanisms Which Contribute to Hemolysis
Acquired Alterations of Red Blood Cell Membrane
Burr Cells (Echinocytes)
Spur Cells (Acanthocytes)
Stomatocytes: mouth-shaped area of central pallor
Target Cells (Bell-Shaped Codocytes, Mexican Hat Cells): due to decreased lecithin/cholesterol acyltransferase (LCAT) activity, resulting in increased cholesterol:phospholipid ratio -> absolute increase in surface area of the red blood cell membrane
Hypersplenism (see Splenomegaly, [[Splenomegaly]]): due to portal hypertension
Epidemiology: coagulopathy is common in hepatic failure
Physiology: abnormal synthesis of multiple clotting factors and platelet dysfunction
Factor VII has a relatively short half-life in the circulation: accounts for increased INR
Platelet Dysfunction (see Coagulopathy, [[Coagulopathy]]): due to platelet granule storage pool defect
Some patients manifest permanent platelet degranulation
Clinical
Bleeding in acute liver failure is often associated with procedures, such as a central line, nasogastric tube or liver biopsy
Treatment: increased INR alone is not an indication for correction of coagulopathy
FFP: first-line therapy to correct coagulopathy
However, in some patients, due to a consumptive coagulopathy combined with impaired synthetic function, even large amounts of FFP may fail to decrease the INR
FFP is a large volume infusion and volume-related complications may occur: pulmonary edema, cerebral edema
Recombinant Activated Factor VIIa: while expensive, may be used for bleeding unresponsive to FFP and other measures (especially in the setting of cerebral edema)
Produces a rapid (although temporary) correction of the INR in acute hepatic failure: however, controlled trials demonstrating long-term benefit are lacking
Commonly used prophylactically in acute liver failure with coagulopathy prior to the placement of an intracranial pressure monitor
Platelets: should be considered when the platelet count is less than 50k
Cryoprecipitate: should be considered if the plasma fibrinogen is less than 100 mg/dL
Anti-Fibrinolytic Agents (epsilon-aminocaproic acid, tranexamic acid): do not improve clotting ability and are not useful to stop active bleeding
Increased Risk of Venous Thromboembolism
Risk of Venous Thrombembolism is High in Hospitalized Patients with Liver Disease, Despite Abnormal Coagulation Parameters: risk of venous thromboembolism was 6.3% in this population [MEDLINE]
Physiology: likely due to sympathetic overactivity, elevated serum progesterone, and enhanced sensitivity to carbon dioxide (Int J Cardiol, 2012) [MEDLINE]
Contraindications: encephalopathy (may worsen) and cardiac dysfunction (increases right-sided heart return and may precipitate CHF and worsen hepatopulmonary syndrome)
Cirrhotic cardiomyopathy. J Am Coll Cardiol. 2010;56(7):539 [MEDLINE]
Coagulopathy does not protect against venous thromboembolism in hospitalized patients with chronic liver disease. Chest. 2010;137(5):1145 [MEDLINE]
A perspective on cirrhotic cardiomyopathy. Transplant Proc. 2011 Jun;43(5):1649-53 [MEDLINE]
Abnormal hyperventilation in patients with hepatic cirrhosis: role of enhanced chemosensitivity to carbon dioxide. Int J Cardiol. 2012 Jan 12;154(1):22-6. doi: 10.1016/j.ijcard.2010.08.066. Epub 2010 Sep 20 [MEDLINE]
Treatment
Recombinant activated factor VII for coagulopathy in fulminant hepatic failure. Liver Transplant 2003; 9:438-443
Efficacy and safety of recombinant factor VII for treatment of severe bleeding: a systematic review. Crit Care Med. 2005;33:883-890
