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]

Question 2

PRIMARY HEMOSTASIS

Factors that cause thrombocytopenia:

Answer 2

• Splenomegaly
• Reduced synthesis of thrombopoietin by the diseased liver
• Consumption coagulopathy

Question 3

PRIMARY HEMOSTASIS

vWF antigen levels are strongly __________ in patients with liver disease.

Answer 3

Elevated

Question 4

SECONDARY HEMOSTASIS

FVIII levels are increased, which may be related to:

Answer 4

• Evated level of its carrier protein vWF
• Decreased clearance of factor VIII from the circulation by the liver low-density lipoprotein-related receptor

Question 5

Fibrinogen levels are frequently in the __________ range in patients with chronic liver disease but may be ____________ in patients with decompensated cirrhosis or acute liver failure.

Answer 5

Normal: CLD

Decreased: Decompensated cirrhosis or acute liver failure

Question 6

TRUE OR FALSE

The PT and aPTT are sensitive to levels of procoagulant proteins in plasma and to the natural anticoagulants, protein C, protein S, and antithrombin

Answer 6

FALSE

The PT and aPTT are sensitive to levels of procoagulant proteins in plasma but not to the natural anticoagulants, protein C, protein S, and antithrombin

The use of a more sophisticated test of coagulation, such as total thrombin generation test, illustrates the limitation of PT and aPTT.

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.

Question 7

Lab test that is 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

Except for_________________________, all proteins involved in fibrinolysis, both pro- and antifibrinolytic, are synthesized by the liver.

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.

Question 9

TRUE OR FALSE

Because both procoagulant and anticoagulant proteins decline in patients with chronic liver diseases, it has been postulated that the hemostatic system is rebalanced

Answer 9

TRUE

Because both procoagulant and anticoagulant proteins decline in patients with chronic liver diseases, it has been postulated that the hemostatic system is rebalanced

• This model also explains why most patients with liver disease usually do not exhibit severe bleeding manifestations—neither during minor invasive procedures, such as biopsies and paracentesis, nor during major surgeries, including liver transplantation.
• Furthermore, patients with liver disease may even have increased risk of venous thromboembolism (VTE), not only liver-specific thrombosis but also deep venous thrombosis (DVT).

Question 10

Changes That Impair Hemostasis (Bleeding)

Answer 10

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 11

Changes That Promote Hemostasis (Thrombosis)

Answer 11

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 12

TRUE OR FALSE

The imbalance in acute liver failure may lead to a prothrombotic state

Answer 12

TRUE

The imbalance in acute liver failure may lead to a prothrombotic state

A severe decrease of coagulation factors is observed, with strongly increased INR.

However:
* Near-normal platelet counts
* Highly elevated levels of vWF and strongly decreased levels of ADAMTS13
* Increased level of PAI-1 and reduced levels of plasminogen

Question 13

Stage in liver transplantation characterized The most severe hemostatic changes during liver transplantation occur:

Answer 13

Immediately after reperfusion of the donor liver

The levels of procoagulant factors rise more rapidly than the levels of anticoagulant factors, which results in a temporary hypercoagulable state.

Question 14

The most severe bleeding manifestation in patients with liver disease is

Answer 14

Bleeding from ruptured esophageal varices

The risk for procedural bleeding is low, and when bleeding occurs, it may be unrelated to hemostasis

Question 15

TRUE OR FALSE

Treatment with fresh-frozen plasma (FFP) or coagulation factor concentrates is indicated in controlling variceal bleeding.

Answer 15

FALSE

Treatment with fresh-frozen plasma (FFP) or coagulation factor concentrates is not indicated in controlling variceal bleeding.

Infusion of plasma may even lead to more bleeding as a result of an increase of portal pressure.

Question 16

TRUE OR FALSE

Current guidelines, 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.

Answer 16

TRUE

Current guidelines, 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.

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

Question 17

Recent guidelines advocate the use of fibrinogen concentrate or cryoprecipitate to achieve fibrinogen levels above _____ in patients with cirrhosis who bleed or undergo high-risk procedures.

Answer 17

120 mg/dL

Question 18

Study that used a short course of eltrombopag was used to elevate the platelet count before invasive procedures among n patients with hepatitis C

Answer 18

Eltrombopag Evaluated for its Ability to Overcome Thrombocytopenia and Enable Procedures (ELEVATE) study

Use of eltrombopag was associated with a higher rate of thrombosis, but no difference in bleeding was observed in this study, which may be related to the highly elevated vWF levels and platelet counts greater than 200,000/μL in patients with liver disease

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).

The use of DOACs is not yet recommended in patients with liver disease, but recently, some case series have been published in patients with splanchnic vein thrombosis.