Page 368 - Essential Haematology

354 / Chapter 26 Coagulation disorders

concentrates and recombinant preparation of factors antagonists. Warfarin is associated with a decrease
VII and XIII are available. in the functional activity of factors II, VII, IX and
X and proteins C and S, but immunological
methods show normal levels of these factors. Th e
Acquired c oagulation d isorders
non - functional proteins are called PIVKA (proteins

The acquired coagulation disorders (Table 26.4 ) are formed in vitamin K absence). Conversion of
more common than the inherited disorders. Unlike PIVKA factors to their biologically active forms is
the inherited disorders, multiple clotting factor a post - translational event involving carboxylation of
deficiencies are usual. glutamic acid residues in the N - terminal region

where these factors show strong sequence homology
(Fig. 26.8 ). Gamma - carboxylated glutamic acid
Vitamin K d efi ciency
binds calcium ions, inducing a reversible shape
Fat - soluble vitamin K is obtained from green veg- change in the N - termini of vitamin K dependent
etables and bacterial synthesis in the gut. Defi ciency proteins. This exposes hydrophobic residues which

may present in the newborn (haemorrhagic disease bind to phospholipid. In the process of carboxyla-
of the newborn) or in later life. tion, vitamin K is converted to vitamin K epoxide

Deficiency of vitamin K is caused by an inade- which is cycled back to the reduced form by a
quate diet, malabsorption or inhibition of vitamin reductase (VKORC - 1). Warfarin interferes with the
K by drugs such as warfarin which act as vitamin K action of vitamin K epoxide reductase leading to a

functional vitamin K deficiency.
Table 26.4 The acquired coagulation

disorders. Haemorrhagic d isease of the n ewborn
Defi ciency of vitamin K - dependent factors Vitamin K - dependent factors are low at birth and
Haemorrhagic disease of the newborn fall further in breast - fed infants in the fi rst few
Biliary obstruction days of life. Liver cell immaturity, lack of gut bacte-
Malabsorption of vitamin K (e.g. tropical sprue, rial synthesis of the vitamin and low quantities in
gluten - induced enteropathy) breast milk may all contribute to a defi ciency which
Vitamin K - antagonist therapy (e.g. coumarins, causes haemorrhage, usually on the second to fourth
indandiones) day of life, but occasionally during the fi rst 2
Liver disease – complex dysregulation with months.
synthetic failure of pro - and anticoagulant
factors
Diagnosis
Disseminated intravascular coagulation –
The PT and APTT are both abnormal. Th e platelet

consumption of all clotting factors and platelets
count and fibrinogen are normal with absent fi brin

Inhibition of coagulation degradation products.
Specifi c inhibitors (e.g. antibodies against factor
VIII) Treatment
Non - specifi c inhibitors (e.g. antibodies found in 1 Prophylaxis. For many years vitamin K has been

systemic lupus erythematosus, rheumatoid given to all newborn babies as a single intramus-
arthritis which paradoxically cause thrombosis)
cular injection of 1 mg. This remains the most

Miscellaneous appropriate and safest treatment. Following
Diseases with M - protein production that interfere epidemiological evidence suggesting a possible
with haemostasis link between intramuscular vitamin K and an
L - Asparaginase increased risk of childhood tumours (which has
Therapy with heparin, defi brinating agents or not been substantiated), some centres recom-
thrombolytics
mended an oral regimen but this has never been
Massive transfusion syndrome
subjected to randomized controlled trial.