Page 355 - Essential Haematology
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Chapter 25 Bleeding disorders / 341
of the membrane glycoproteins IIb/IIIa which Acquired d isorders
together form the VWF and fi brinogen receptor
Antiplatelet d rugs
(see Fig. 24.5 ). It usually presents in the neonatal
period and, characteristically, platelets fail to aggre- Aspirin therapy is the most common cause of defec-
gate in vitro to any agonist except ristocetin. tive platelet function. It produces abnormal closure
times in the platelet function analysis - 100 (PFA -
100) test and, although purpura may not be obvious,
Bernard – Soulier s yndrome the defect may contribute to the associated gastroin-
testinal haemorrhage. The cause of the aspirin defect
In this disease the platelets are larger than normal
is inhibition of cyclo - oxygenase with impaired
and there is a defi ciency of GPIb. There is defective
thromboxane A 2 synthesis (see Fig. 27.8 ). Th ere is
binding to VWF, defective adherence to exposed
consequent impairment of the release reaction and
subendothelial connective tissues and platelets do
aggregation with arachidonic acid, collagen, adrena-
not aggregate with ristocetin. There is a variable
line and adenosine diphosphate (ADP) (Fig. 25.10 ).
degree of thrombocytopenia.
After a single dose the defect lasts 7 – 10 days (i.e.
the life of the platelet). Aspirin is contraindicated
in patients with gastrointestinal or genitourinary
Storage p ool d iseases
bleeding, retinal bleeding, peptic ulcer, haemophilia
In the rare grey platelet syndrome, the platelets are or uncontrollable hypertension.
larger than normal and there is a virtual absence of Dipyridamole inhibits platelet aggregation by
α granules with deficiency of their proteins. In the blocking reuptake of adenosine and is usually used
more common δ - storage pool disease there is a defi - as an adjunct to aspirin. Clopidogrel inhibits
ciency of dense granules. binding of ADP to its platelet receptor (see Fig.
Platelet - dependent haemostasis is abnormal in 27.8 ), shown by impaired aggregation with ADP
von Willebrand disease because of an inherited (Fig. 25.10 ) and is mainly used for prevention of
defect in VWF (see p. 352) . thrombotic events (e.g. after coronary stenting or
ADP Adrenaline Collagen Arachidonic
(2 µmol/l) (2 µmol/l) acid
100
Optical density (%) 50
75
25
0
0 2 4 6 8 10 12 14
Time (min)
Control Patient on aspirin therapy Patient on clopidogrel
Figure 25.10 Defective platelet aggregation in patients on aspirin or clopidogrel therapy. With aspirin there is no
secondary phase aggregation with adenosine diphosphate (ADP) and reduced responses to arachidonic acid,
adrenaline and collagen. With clopidogrel the defect is mainly in ADP induced aggregation.