130 Hemostatic Alterations in Liver Diseases and Liver Transplantation Flashcards
Liver parenchymal cells are the site of synthesis of most coagulation factors except
Factor VIII [FVIII]
Liver parenchymal cells are the site of synthesis of most coagulation factors (except factor VIII [FVIII]); the natural inhibitors of coagulation, including protein C, protein S, and antithrombin; and essential components of the fibrinolytic system, such as plasminogen, α 2 -antiplasmin, and thrombin activatable fibrinolysis inhibitor (TAFI).
The liver also regulates hemostasis and fibrinolysis by clearing activated coagulation factors and coagulation factor–inhibitor complexes from the circulation.
TRUE OR FALSE
More than 75% of patients with chronic liver disease, especially in moderate to severe cirrhosis (Child B and C), have reduced platelet counts (<150,000/ μL)
TRUE
More than 75% of patients with chronic liver disease, especially in moderate to severe cirrhosis (Child B and C), have reduced platelet counts (< 150,000/ μL)
13% have platelet counts between 50,000 and 75,000/μL
vWF antigen levels are strongly (elevated or reduced) in patients with liver disease.
Elevated
Causes of thrombocytopenia in liver disease
- Splenomegaly resulting in sequestration of platelets in the spleen
- Reduced synthesis of thrombopoietin by the diseased liver
- Consumption coagulopathy
FVIII is synthesized primarily in ______________ , whose function is preserved in liver disease.
Hepatic sinusoidal endothelial cells
TRUE OR FALSE
Fibrinogen levels are frequently in the normal range in patients with chronic liver disease but may be decreased in patients with decompensated cirrhosis or acute liver failure.
TRUE
Fibrinogen levels are frequently in the normal range in patients with chronic liver disease but may be decreased in patients with decompensated cirrhosis or acute liver failure.
Qualitative changes in fibrinogen : both defects in speed of clot formation and a thrombogenic clot structure once the clot has matured
A more sophisticated test of coagulation measuring the total amount of thrombin generated during coagulation
Total thrombin generation test
- These results suggest that thrombin generation in vivo can be normal in patients with liver failure and that a prolonged PT does not per se indicate a bleeding risk.
- These findings indicate that a concomitant decrease of pro- and anticoagulant factors results in a rebalanced hemostatic system.
Coagulation test still used in prognostic scores for patients with acute or chronic liver disease
International normalized ratio (INR)
The model of end-stage liver disease (MELD) score is used to prioritize patients for liver transplantation.
All proteins involved in fibrinolysis, both pro- and antifibrinolytic, are synthesized by the liver EXCEPT
Tissue plasminogen activator (t-PA) and plasminogen-activator inhibitor (PAI)-1
- Therefore, chronic liver disease leads to decreased plasma levels of plasminogen, α 2 -antiplasmin, TAFI, and factor XIII.
- Plasma levels of t-PA are elevated as a result of increased secretion from endothelial cells and/or reduced clearance by the diseased liver.
- Plasma levels of PAI-1 also are increased but not to the same extent as t-PA, which may lead to a shift in balance in the fibrinolytic system.
Changes That Impair
Hemostasis/ Contribute to Bleeding
Primary Hemostasis
* Thrombocytopenia
* Platelet function defects
* Enhanced production of nitric oxide and prostacyclin
Secondary Hemostasis
* Low levels of factors II, V, VII, IX, X, and XI
* Vitamin K deficiency
* Dysfibrinogenemia
Fibrinolysis
* Low levels of α2-antiplasmin, factor XIII, and TAFI
* Elevated t-PA levels
Changes That Promote
Hemostasis/ Contribute to Thrombosis
Primary Hemostasis
* Elevated levels of vWF
* Decreased levels of ADAMTS13
Secondary Hemostasis
* Elevated levels of factor VIII
* Decreased levels of protein C, protein S, antithrombin, α2-macroglobulin, and heparin
cofactor II
Fibrinolysis
* Low levels of plasminogen
* Increase in PAI-1 levels
TRUE OR FALSE
Spontaneous bleeding is not frequently encountered in patients with acute liver failure.
TRUE
Spontaneous bleeding is not frequently encountered in patients with acute liver failure.
- A severe decrease of coagulation factors is observed, with strongly increased INR.
- In contrast to chronic liver disease, patients with acute liver failure frequently have near-normal platelet counts.
The most severe hemostatic changes during liver transplantation occur when
Immediately after reperfusion of the donor liver
The most severe bleeding manifestation in patients with liver disease is
Bleeding from ruptured esophageal varices
TRUE OR FALSE
Abnormal coagulation tests in patients with liver disease are not necessarily associated with a bleeding risk.
TRUE
Abnormal coagulation tests in patients with liver disease are not necessarily associated with a bleeding risk.
The current guideline of the American Association for the Study of Liver Diseases (AASLD) and the “Choosing wisely” campaigns of the AASLD and the Canadian Association for the Study of Liver Disease do not recommend the routine use of FFP transfusion for prophylactic correction of an abnormal PT before interventions, such as liver biopsy, whereas other guidelines advise the use of FFP with a low grade of evidence.
