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Genetic disorder characterized by giant platelets,
mild-to-moderate thrombocytopenia, abnormal platelet function, and bleeding
disproportionate to the reduced number of platelets.
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Giant Platelet Syndrome; Familial Macrothrombocytopenia;
Deficiency of Platelet Glycoprotein Ib; Hemorrhagiparous Thrombocytic
Dystrophy.
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First described in 1948 by Jean Bernard and Jean-Pierre
Soulier, French hematologists.
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Probably less than 1:1,000,000 in the general
population.
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Autosomal recessive. Genetic research located
the GP-1BA gene on 17pter-p12 for the classic Bernard-Soulier syndrome (type
A) and the GP-1BB gene on 22q11.2 for type B.
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The mutation results in a deficiency of platelet
membrane glycoprotein (GP) Ib (GP-1BA), GP-Is (glycocalicin), GP-V, and
GP-IX. (Glycocalicin results from proteolytic cleavage of GP-1BA.) These
factors are responsible for the interaction between von Willebrand factor
and the platelet membrane and are essential for normal platelet adhesion in
the early phase of primary hemostasis. Furthermore, the giant platelets show
altered binding of factors V and XI and do not develop regular coagulation
activity upon contact with collagen.
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Bleeding tendency noted during childhood. Clinical
picture and morphologic features of the platelets on blood smear
examination, which shows increased size (giant platelets may have a diameter
up to 8 μm) with dense granulomeres, resulting in a pseudonucleated or
lymphocytoid aspect.
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Moderate-to-severe bleeding of purpuric type
(bruising, epistaxis, menorrhagia). Bleeding time is prolonged, but clot
retraction and platelet aggregation by adenosine diphosphate and collagen
are normal. Heterozygous family members may show approximately half the
normal levels of platelet GP Ib-IX-V expression; however, they suffer from
only mild bleeding diatheses, if at all. Affected patients have a history of
frequent episodes of epistaxis, gingival and cutaneous bleeding, and
hemorrhage associated with trauma. Platelet counts may range from very low
(<30,000/μL) to marginally low or normal (∼200,000/μL). In
individual patients it may fluctuate considerably over a period of years.
Skin bleeding time may range from only marginally prolonged (5-10 minutes)
to more than 20 minutes. The severity of symptoms may progressively worsen or
become alleviated throughout puberty and adult life. Splenectomy apparently
has been beneficial in moderating thrombocytopenia and the severity of
clinical symptoms.
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Check platelet count and bleeding
time. Bleeding tendency is variable (some patients remain asymptomatic until
later adulthood), but can be severe during surgery, trauma, or pregnancy.
Evaluate hematologic status (complete blood count, bleeding time, platelet
function tests, prothrombin time, partial thromboplastin time). Activated recombinant
factor VII (rFVIIa) and fresh plasma concentrate should be immediately available in
the event they are required.
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Avoid central neuraxial blocks. Direct
laryngoscopy and tracheal intubation must be atraumatic. General supportive
measures and specific treatment of bleeding episodes. Severe hemorrhagic
shock occurs spontaneously or secondary to surgery. High-dose recombinant factor VIIa
has been used to correct bleeding and was postulated to act on platelets in
the absence of tissue factor to activate factors IX and X and thus enhance
thrombin generation. Transfusion of platelet-rich plasma is another
technique that has been used successfully to stop severe hemorrhage.
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Consider use of desmopressin acetate
(DDAVP) and antifibrinolytics. Avoid drugs or products adversely affecting
platelet function, such as nonsteroidal antiinflammatory drugs and
hydroethyl starch. Halothane and sevoflurane (and dibucaine) may affect
platelet function. Antifibrinolytics may or may not be beneficial.
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Thrombopathic Thrombocytopenia: Although this disorder is similar ...