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2192 Part XII: Hemostasis and Thrombosis Chapter 128: Hemostatic Alterations in Liver Disease and Liver Transplantation 2193

TABLE 128–1. Changes in the Hemostatic System in 50 to 80 percent of patients undergoing a liver transplantation, depend-
This improvement is also because of a better
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ing on the center.
Patients with Liver Disease That Contribute to Bleeding understanding of the coagulation profile during the various stages of
(Left) or Contribute to Thrombosis (Right) the surgical intervention. During the first stage of liver transplantation,
Changes That Impair Changes That Promote the removal of the diseased liver, no significant worsening of the preop-
Hemostasis Hemostasis erative hemostatic status occurs. After removal of the diseased liver, the
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PRIMARY HEMOSTASIS so-called anhepatic stage, significant hemostatic changes occur. Because
activated coagulation factors are not cleared from the circulation, DIC
Thrombocytopenia Elevated levels of VWF
can develop, with consumption of platelets and coagulation factors
Platelet function defects Decreased levels of ADAMTS13 and secondary hyperfibrinolysis. Moreover, hyperfibrinolysis may also
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Enhanced production of nitric occur as a result of defective clearance of t-PA. The most severe hemo-
oxide and prostacyclin static changes during liver transplantation occur immediately after
reperfusion of the donor liver. Platelets are trapped in the graft, giv-
SECONDARY HEMOSTASIS
ing rise to an aggravation of thrombocytopenia and causing damage to
Low levels of factors II, V, VII, Elevated levels of factor VIII the graft by induction of endothelial cell apoptosis. Release of tissue
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IX, X, and XI factor and t-PA from the reperfused graft causes DIC with primary or
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Vitamin K Deficiency Decreased levels of protein C, secondary fibrinolysis. Moreover, the graft also releases heparin-like
protein S, antithrombin, α -mac- substances that can inhibit coagulation. In addition, other factors such
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2
roglobulin, and heparin cofactor as hypothermia, metabolic acidosis, and hemodilution adversely affect
II hemostasis during this phase.
Dysfibrinogenemia During transplantation, the balance between VWF and ADAMTS13
changes because levels of VWF remain high, the functional properties
FIBRINOLYSIS
of VWF improve, and the levels of ADAMTS13 decline, which may par-
Low levels of α -antiplasmin, Low levels of plasminogen tially compensate for the hemostatic dysfunction. The platelet count
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2
factor XIII, and TAFI Increase in PAI-1 levels and hemostatic proteins are at their nadir after reperfusion and rise
Elevated t-PA levels gradually during the early postoperative period. However, the levels of
procoagulant factors rise more rapidly than the levels of anticoagulant
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ADAMTS13, a disintegrin-like and metalloprotease with thrombo- factors, which results in a temporary hypercoagulable state. A tran-
spondin domain 13; PAI-I, plasminogen activator inhibitor 1; TAFI, siently increased level of PAI-1 immediately after surgery can result in
thrombin-activatable fibrinolysis inhibitor; t-PA, tissue-type plas- a hypofibrinolytic state that may aggravate the hypercoagulable status.
minogen activator; VWF, von Willebrand factor.
CLINICAL PROBLEMS ENCOUNTERED
HEMOSTATIC ALTERATIONS IN IN PATIENTS WITH LIVER DISEASE
ACUTE LIVER FAILURE
BLEEDING IN PATIENTS WITH LIVER DISEASE
Patients presenting with acute liver failure, for instance in acetaminophen
intoxication, have profound changes in the hemostatic system. A severe Although sophisticated hemostatic tests have now shown that disorders
decrease of coagulation factors is observed, with strongly increased of primary hemostasis, a hypocoagulable status, and hyperfibrinolysis
INR. However, an intact thrombin generation has been observed in are generally not encountered or are only seen in a minority of patients
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acute liver failure patients and hardly any changes were observed using with chronic liver disease, bleeding still may occur in these patients. This
thromboelastography. 53,54 In contrast to chronic liver disease, patients is because individual patients still may have a compromised hemostatic
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with acute liver failure frequently have normal platelet counts. Highly function or because patients bleed for nonhemostatic reasons. The most
elevated levels of VWF are observed and strongly decreased levels of severe bleeding manifestation in patients with liver disease is bleeding from
ADAMTS13. This imbalance may lead to a prothrombotic state. In ruptured esophageal varices. This results from local vascular abnormalities
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patients with acute liver failure, there is an increased level of PAI-1, and and portal hypertension and not from deranged hemostasis. Occasionally,
reduced levels of plasminogen which is consistent with a hypofibrino- impaired hemostasis does cause easy bruising, purpura, epistaxis, gingival
lytic state. 53,56 A strong increase of procoagulant microparticles has been bleeding, menorrhagia and gastrointestinal bleeding. Also in acute liver
observed in acute liver failure. Spontaneous bleeding is not frequently failure bleeding has frequently been reported in the past, but more recent
57
encountered in patients with acute liver failure. 58 studies clearly indicate that spontaneous bleeding occurs rarely. 58
HEMOSTATIC ALTERATIONS DURING HEMOSTATIC MANAGEMENT OF PATIENTS
LIVER TRANSPLANTATION WITH LIVER DISEASE
Hemostatic Management of Bleeding Episodes
Liver transplantation performed in patients in acute or chronic liver Variceal bleeding in patients with liver disease should be imme-
failure has always been complicated by significant and sometimes diately managed by local interventions, such as endoscopy and
life-threatening bleeding problems requiring massive use of coagula- rubber band ligation or even shunt (transjugulair intrahepatic por-
tion factors and erythrocyte transfusion. Therefore blood products tosystemic shunt [TIPS]) placement. Fluid resuscitation should be
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59
were also transfused before and during transplantation to correct the given in case of hypotension and restricted blood transfusion in case
hemostatic dysfunction. Improved surgical techniques and anesthe- of severe drop of hemoglobin level. Because there is no evidence that
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siologic care have led to a remarkable reduction of blood loss during changes in hemostasis are associated with the risk of variceal bleed-
liver transplantation. Currently, no blood transfusion is given in up to ing, treatment with coagulation factor concentrates is not indicated.

Kaushansky_chapter 128_p2191-2198.indd 2193 9/18/15 10:38 AM