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Coagulation Disorders Platelet Disorders
Congenital Disorders of Platelet Function
a report by
Gian Marco Podda, Mariateresa Pugliano and Marco Cattaneo
San Paolo Hospital, Department of Medicine, Surgery and Dentistry, University of Milan
When a blood vessel is injured, platelets adhere to the exposed cytoplasmic vacuoles and membrane complexes in the giant platelets.
subendothelium (platelet adhesion). The platelets are activated (platelet These abnormalities extend to megakaryocytes (MK). With an estimated
activation) and secrete their granule contents (platelet secretion). The prevalence of 1/1,000,000 cases,
1
BSS is a relatively severe bleeding
granule contents include platelet agonists (adenosine diphosphate [ADP] disorder. Typical bleeding manifestations of the disorder include epistaxis,
and serotonin) that, by interacting with specific platelet receptors, contribute gum bleeding and both post-surgical and post-traumatic bleeding. Most
to the recruitment of additional platelets to form aggregates (platelet heterozygotes have intermediate amounts of the GP complex and may
aggregation). Platelets also play a role in coagulation, providing the have some giant platelets without a bleeding diathesis.
2–5
necessary surface of procoagulant phospholipids (platelet procoagulant
activity). Congenital or acquired abnormalities of platelet numbers or In primary haemostasis initial platelet adherence and recruitment depends
functions are associated with a heightened risk of bleeding, proving that on GPIb-α binding to immobilised von Willebrand factor (VWF).
6
BBS
platelets play an important role in haemostasis. Patients with platelet platelets are characterised by a significantly reduced ability to adhere to the
disorders typically have mucocutaneous bleedings of variable severity and subendothelium. The disease phenotype is primarily due to the inability of
excessive haemorrhage after surgery or trauma. VWF to bind to GPIb-α. The absence of GPIb-α-related binding sites for
thrombin, P-selectin, thrombospondin-1 (TPS-1), factor XI, factor XII,
Classification of the Congenital Disorders of α-Mβ-2 and high-molecular-weight kininogen may play an additional role in
Platelet Function the impairment of haemostasis. BSS platelets do not agglutinate in vitro
Inherited disorders of platelet function are generally classified based on when exposed to the antibiotic ristocetin or to the snake venom protein
the type of abnormal function. Platelet functions are intimately related botrocetin. This defect is not corrected by the addition of normal plasma. In
and a clear distinction between the disorders of platelet adhesion, this instance the platelet responses to physiological agonists are normal,
aggregation, activation, secretion and procoagulant activity may be with the exception of low concentrations of thrombin. Diagnosis of BSS is
problematic. We propose a classification of the inherited disorders of based on the demonstration of a GPIb–IX–V deficiency by either flow-
platelet function based on the shared common characteristic cytometry or immunoblotting. BSS is associated with genetic defects in
abnormalities of platelet components: GPIb-α, GPIb-β and GPIX, preventing the constitution and trafficking of the
receptor through the both the Golgi apparatus and the endoplasmic
• platelet receptors for adhesive proteins; reticulum. Mutations within GPV do not lead to BSS. The molecular defects
• platelet receptors for soluble agonists; responsible for BBS include frame shifts, deletions and point mutations.
3–5,7
• platelet granules;
• signal transduction pathways; and Platelet-type or Pseudo-von Willebrand Disease
• procoagulant phospholipids. Platelet-type von Willebrand disease (VWD) or pseudo-VWD is an
autosomal-dominant disease associated with amino acid substitutions that
Those inherited disorders of platelet function that are less well characterised
will be placed in a separate category of miscellaneous disorders.
Gian Marco Podda is a Fellow in the Thrombosis and Haematology Laboratory at San Paolo
Hospital, University of Milan. Prior to this he was a Research Associate of Molecular and
Abnormalities of the Platelet Receptors for
Experimental Medicine at the Scripps Research Institute in La Jolla. He received awards for his
Adhesive Proteins
work from the Italian Society of Haemostasis and Thrombosis (SISET) and has submitted
numerous papers on the subject of coagulation disorders. Dr Podda received his medical
degree in 1997 from the University of Milan.
Abnormalities of the Glycoprotein Ib–V–IX Complex
Mariateresa Pugliano is a Research Fellow within the Haematology and Thrombosis Unit at the
San Paolo Hospital, University of Milan. Prior to this, she attended a specialisation course in
Bernard-Soulier Syndrome
Haaematology at the IRCCS Policlinico at the Mangiagalli and Regina Elena Foundation within
Bernard-Soulier syndrome (BSS) is associated with both quantitative and the Maggiore Hospital in Milan. Dr Pudliano received her medical degree in 2004 from the
qualitative defects of the platelet glycoprotein complex GPIb–IX–V. The
University of Milan.
complex is formed of four glycoproteins. GPIb consists of two subunits,
GPIb-α and GPIb-β. Characterised by an autosomal recessive inheritance
Marco Cattaneo is a Full Professor and Director of Internal Medicine in the Department of
Medicine, Surgery and Dentistry at the San Paolo Hospital, University of Milan. He is Past
(only one case has been characterised by autosomal dominant inheritance),
President of the Italian Society for the Study of Thrombosis and Haemostasis (SISET) and
BSS also exhibits prolonged bleeding times, variable degrees of
has authored more than 170 original articles published in peer-reviewed scientific journals.
thrombocytopenia, giant platelets, decreased platelet adhesion and
Dr Cattaneo recieved his medical degree in 1975 from the University of Milan.
abnormal prothrombin consumption. Electron microscopy shows
© TOUCH BRIEFINGS 2008 43
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