Page 369 - Essential Haematology

Chapter 26 Coagulation disorders / 355

Hepatic
metabolized Precursor forms of
factors II, VII, IX, X Glutamic
CYP2C9 protein C and acid
Warfarin protein S (PIVKA)
inhibits
Vitamin K
Vitamin K
reductase
VKORC-1 Vitamin K
epoxide
Completed forms of Gamma binds Platelet
factors II, VII, IX, X carboxylated to
protein C and glutamic phospho-
lipid
protein S acid (gla)

Figure 26.8 The action of vitamin K in γ - carboxylation of glutamic acid in coagulation factors which are then
2 +
able to bind Ca and attach to the platelet phospholipid. Warfarin inhibits vitamin K reductase. It is metabolized
in the liver and genetic variations in the reductase enzyme VKORC - 1 and in the cytochrome CYP2C9 largely
account for wide variations in warfarin sensitivity of individuals.

2 In bleeding infants: vitamin K 1 mg intramuscu- 1 Biliary obstruction results in impaired absorption

larly is given every 6 hours with, initially, pro- of vitamin K and therefore decreased synthesis of
thrombin complex concentrate if haemorrhage is factors II, VII, IX and X by liver parenchymal
severe. cells.
2 With severe hepatocellular disease, in addition to

Vitamin K d eficiency in c hildren or a dults a deficiency of these factors, there are often
reduced levels of factor V and fi brinogen and
Deficiency resulting from obstructive jaundice, increased amounts of plasminogen activator.

pancreatic or small bowel disease occasionally causes 3 Functional abnormality of fi brinogen (dysfi brin-
a bleeding diathesis in children or adults. ogenaemia) is found in many patients.
4 Decreased thrombopoietin production from the
Diagnosis liver contributes to thrombocytopenia.

Both PT and APTT are prolonged. There are low 5 Hypersplenism associated with portal hyperten-
plasma levels of factors II, VII, IX and X.
sion frequently results in thrombocytopenia.
Treatment 6 Disseminated intravascular coagulation (DIC;
1 Prophylaxis: vitamin K 5 mg/day orally. see below) may be related to release of thrombo-

2 Active bleeding or prior to liver biopsy: vitamin plastins from damaged liver cells and reduced

K 10 mg slowly intravenously. Some correction concentrations of antithrombin, protein C and

of PT is usual within 6 hours. The dose should α 2 - antiplasmin. In addition, there is impaired
be repeated on the next 2 days after which removal of activated clotting factors and increased
optimal correction is usual. fi brinolytic activity.

3 Rapid correction may be achieved by infusion of 7 The net haemostatic inbalance in liver

prothrombin complex concentrate. disease may be prothrombotic rather than
haemorrhagic.
Liver d isease
Disseminated i ntravascular c oagulation
Multiple haemostatic abnormalities contribute to a
bleeding tendency and may exacerbate haemor- Widespread inappropriate intravascular deposition
rhage from oesophageal varices. of fibrin with consumption of coagulation factors