Hemostatic Disorder in Hepatic DiseaseDr. Tjatur Winarsanto SpPDRS CiremaiCirebon 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 Ehlers- Danlos 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
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.
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