Hemostatic Disorder in

Hepatic Disease
Dr. Tjatur Winarsanto SpPD
RS Ciremai
Cirebon 2011

Coagulopathy is a medical term for a

defect in the body's mechanism for
blood clotting
There are several possible causes
that generally result in excessive
bleeding and a lack of clotting.

:Causes of coagulopathy
Inherited:

- Deficiency of coagulation factor

e.g Haemophilia (A/B), vonWillibrand

disease, etc
- Platelet disorder e.g Glanzmann
thromboasthenia, platelel granule
disorder,
etc
- Fibrinolytic disorder e.g plasminogen
activator
inhibitor-1 deficiency, etc

- Vascular e.g haemorrhagic

telangiectasia.
- Connective tissue disorder e.g
EhlersDanlos syndrome

Acquired:
- Drugs; anticoagulants e.g warfarin,
antiplatelet agents, myelosuppressents,
haematotoxin venoms e.g certain
species of snakes eg Bothrops,
rattlesnakes and other species of viper,

antithrombins, etc...
- Haematologic disorder e.g acute leukaemia,
myelodysplasia, monoclonal gammopathy,
etc

- Dissimination intravascular coagulopathy

(DIC);acute e.g sepsis, trauma, obstetric,
etc
chronic e.g malignancies, giant
haemangioma, etc
- Thrombocytopenia e.g autoimmune,
hypersplenism, hypoplasia, etc
- Acquired antibodies to coagulation factors
e.g antiphospholipid syndrome, etc

- Vitamin K deficiency e.g malabsorption,

prolonged antibiotics, prolonged
biliary
obstruction, etc
- Vascular e.g scurvy, Henoch-schnlein,
vasculitis, etc
- Renal failure.
- Liver disease.

Role of liver in coagulation:

Synthesis of coagulation factors I,

II, V, VII, IX & X
[Vitamin K dependent factors are II, VII, IX
and X ]

[ All coagulation factors are produced

in the liver except for von
Willebrand's factor which is produced
in endothelial cells.
Von Willebrand's factor is a major
source of factor VIII however the
spleen is also a source for factor VIII]

Inhibition of fibrinolysis / coagulation;

the liver is responsible for synthesizing
plasma anticoagulant proteins
e.g. protein C, protein S and
antithrombin
III.
Absorption of vitamin K

 Clearance

of activated coagulation
factors; fibrin and tissue plasminogen
activator (tPA) are removed from the
circulation
by
the
liver's
reticuloendothelial system

Accordingly
- The liver has a pivotal role in the
coagulation process so it is not
surprising that clotting abnormalities
are a prominent feature of acute and
chronic liver disease.
-

Liver disease can cause both

quantitative
and
qualitative
abnormalities in clotting factors.

The clinical presentation of hepatic

coagulopathy depends on the severity
and nature of the underlying disease
A coagulation defect is suggested by:
- Bleeding at any site;
spontaneous or traumatic.
- Acute viral / toxic hepatitis present
with coagulopathy in only fulminant
cases.

Factors that contribute to defective

hemostasis in patients with liver
disease
- Dysfibrinogenaemia.
- Thrombocytopenia (autoimmune, folate
deficiency, sequestrated in splenomegaly)
- Qualitative platelet defects
- Myelosuppression of thrombopoiesis
(eg, by alcohol, hepatitis virus infection)
- DIC

:Laboratory Findings

Prolonged Prothrombin time (PT)

Fibrinogen levels are usually

normal. Its synthesis is affected
only in severe disease.

Factor V is affected first in disease.

Factor VII is the earliest of all to decline

because of its short half-life (6 hours).

Factor VIII
may be normal or even
increased in liver disease except in the
presence of DIC.

 Platelet counts are normal unless

spleen is also enlarged or the person
recently drank alcohol
-

Platelet function may also be

affected
i.e adhesion and aggregation.
Hence,
prolongation of bleeding time.

 Liver function tests abnormal,

depending on the type of liver
disease
(in end-stage liver disease, liver
tests may
become "normalized" because so
much of
the liver is now non-functioning.)

:Treatment

Fresh frozen plasma infusion:

- to replace deficient coagulation factors.
- Administered=10-15 ml/kg, q12h; assess
coagulation values after each infusion.
- Plasma exchange may be considered if
repeated infusions of fresh frozen plasma are
required and there is evidence of volume
overload.

;in Vitamin K deficiency

- Vitamin K supplementation:
Administer 10 mg subcutaneously;
repeat parenterally in 24 hr.
- Prothrombin complex concentrate:
may be used but it does not contain
factor
V
and
may
result
in
thrombosis.

 Platelet

transfusion:
in thrombocytopenia but may be
ineffective in splenomegaly.

Cryoprecipitate

infusion:
administer if fibrinogen value <75
mg/dl; use dosage of 2 bags per 10
kg, q12h

Heparin administration:
may be considered if there is evidence of
DIC; role is not well defined but not
recommended for routine use

Antifibrinolytic agents:
are adminstered prior to certain
procedures like dental extraction
provided that DIC is ruled out as they
may enhance thrombosis.