Initial symptoms of Bernard-Soulier syndrome (BSS) such as epistaxis, gingival bleeding, purpura and bruising, which range from mild to severe, often present in infancy and are common to many other bleeding disorders. Thus, laboratory testing is needed to diagnose BSS.1-3
Initial laboratory tests often reveal borderline prolonged to prolonged in vivo bleeding times, marginal to low platelet counts (<30–200x103 /µL) and large platelets present in the blood that reach approximately 3.5 µm. Absence of platelet aggregation in the presence of ristocetin during light transmission aggregometry (LTA) can be indicative of BSS. However, if addition of normal plasma corrects LTA results, further testing should be performed to exclude type 2B von Willebrand disease. Finally, flow cytometry analysis can confirm a diagnosis using antibodies directed against the four individual glycoprotein (GP) subunits of the GPIb-IX-V complex (GPIbα, GPIbβ, GPIX and GPV). A reduction in the GPIb-IX-V subunits indicates classical autosomal recessive BSS. Patients with dominant forms of BSS, such as the Bolzano mutation, can have only a mild reduction in GPIb-IX-V subunits.1-3
Algorithm for the laboratory diagnosis of BSS.
Initial laboratory screening
Initial laboratory screening in patients with BSS typically shows low platelet counts, a proportion of large platelets and marginal to prolonged bleeding times. All other routine coagulation test such as PT and aPTT are within the normal range.1-4
Light transmission aggregometry (LTA)
Platelets from patients with BSS aggregate normally in the presence of adenosine diphosphate (ADP), arachidonic acid, collagen and epinephrine during light transmission aggregometry. However, there is no aggregation curve in the presence of ristocetin. An uncorrected mixing test with normal plasma can exclude von Willebrand disease type 2B.1,2
Direct confirmation of a defective GPIb-IX-V protein complex can be achieved through flow cytometry. Analysis with antibodies against CD41 and CD61 should be normal. However analysis with antibodies against the GPIb-IX-V complex, CD42a (GPIX), CD42b (GPIbα), CD42c (GPIbβ), and CD42d (GPV), should be abnormal when gating for platelets in patients with BSS.1-4
1. Pham A, Wang J. Bernard-Soulier syndrome: an inherited platelet disorder. Arch Pathol Lab Med 2007;131:1834-6.
2. Lanza F. Bernard-Soulier syndrome (hemorrhagiparous thrombocytic dystrophy). Orphanet J Rare Dis 2006;1:46.
3. Alamelu J, Liesner R. Modern management of severe platelet function disorders. Br J Haematol 2010;149:813-23.
4. Diz-Kucukkaya R. Inherited platelet disorders including Glanzmann thrombasthenia and Bernard-Soulier syndrome. Hematology Am Soc Hematol Educ Program 2013;2013:268-75.