130 Hemostatic Alterations in Liver Diseases and Liver Transplantation

Question 1

Liver parenchymal cells are the site of synthesis of most coagulation factors except

Answer 1

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.

Question 2

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)

Answer 2

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

Question 3

vWF antigen levels are strongly (elevated or reduced) in patients with liver disease.

Answer 3

Elevated

Question 3

Causes of thrombocytopenia in liver disease

Answer 3

• Splenomegaly resulting in sequestration of platelets in the spleen
• Reduced synthesis of thrombopoietin by the diseased liver
• Consumption coagulopathy

Question 4

FVIII is synthesized primarily in ______________ , whose function is preserved in liver disease.

Answer 4

Hepatic sinusoidal endothelial cells

Question 5

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.

Answer 5

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

Question 6

A more sophisticated test of coagulationmeasuring the total amount of thrombin generated during coagulation

Answer 6

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.

Question 7

Coagulation test still used in prognostic scores for patients with acute or chronic liver disease

Answer 7

International normalized ratio (INR)

The model of end-stage liver disease (MELD) score is used to prioritize patients for liver transplantation.

Question 8

All proteins involved in fibrinolysis, both pro- and antifibrinolytic, are synthesized by the liver EXCEPT

Answer 8

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.

Question 9

Changes That Impair
Hemostasis/ Contribute to Bleeding

Answer 9

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

Question 10

Changes That Promote
Hemostasis/ Contribute to Thrombosis

Answer 10

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

Question 11

TRUE OR FALSE

Spontaneous bleeding is not frequently encountered in patients with acute liver failure.

Answer 11

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.

Question 12

The most severe hemostatic changes during liver transplantation occur when

Answer 12

Immediately after reperfusion of the donor liver

Question 13

The most severe bleeding manifestation in patients with liver disease is

Answer 13

Bleeding from ruptured esophageal varices

Question 14

TRUE OR FALSE

Abnormal coagulation tests in patients with liver disease are not necessarily associated with a bleeding risk.

Answer 14

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.

Question 15

Recent guidelines advocate the use of fibrinogen concentrate or cryoprecipitate to achieve fibrinogen levels above

Answer 15

120 mg/dL

Vitamin K is generally recommended in patients with liver disease and prolonged INR; however, its clinical benefit has been questioned.

Question 16

TRUE OR FALSE

If platelet counts are below 50,000/μL, platelet transfusion is recommended before any intervention, as in other patients without underlying liver disease.

Answer 16

TRUE

If platelet counts are below 50,000/μL, platelet transfusion is recommended before any intervention, as in other patients without underlying liver disease.

In case of neurosurgical interventions, platelets should be transfused up to a level of 100,000/μL.

Question 17

Drug used y to improve primary hemostasis in patients with hepatitis C

Answer 17

Thrombopoietin analogues (eltrombopag, avatrombopag, and lusutrombopag)

In the Eltrombopag Evaluated for its Ability to Overcome Thrombocytopenia and Enable Procedures (ELEVATE) study, a short course of eltrombopag was used to elevate the platelet count before invasive procedures.

Question 18

It is thought to contribute significantly to impaired hemostasis during the anhepatic and reperfusion phases.

Answer 18

Hyperfibrinolysis

Question 19

TRUE OR FALSE

Liver disease should not be considered a contraindication for thromboprophylaxis with low-molecularweight heparin (LMWH).

Answer 19

TRUE

Liver disease should not be considered a contraindication for thromboprophylaxis with low-molecularweight heparin (LMWH).