A 56-year-old female with high grade cervical dysplasia underwent a therapeutic LEEP procedure. Immediately after the procedure hemostasis was achieved, however over the next few days she had repeated re-bleeding at the cervix.  CBC and screening coagulation assay findings were normal.  A peripheral blood smear demonstrated agranular/hypogranular platelets and a lumi-aggregation study demonstrated functional impairment in response to agonists in the arachidonic acid/thromboxane pathway.

Grey platelet syndrome is a rare cause of mild to moderate bleeding tendencies often diagnosed in childhood, but occasionally diagnosed later in life. It is caused by an absence of protein-containing alpha granules in both megakaryocytes and platelets resulting in large, agranular, colorless, poorly functioning platelets [1].  Dense granules (visible by electron microscopy but not light microscopy) are not affected in typical grey platelet syndrome.  Platelet aggregation responses in grey platelet syndrome are variable, with thrombin and/or collagen-induced platelet aggregation being most commonly reported to be abnormal [1].  Grey platelet syndrome is typically caused by NBEAL2 mutation [2-4]. 

Artifactually colorless platelets are rarely seen in “pseudo- gray platelet syndrome” when blood collected in EDTA containing tubes [5]. In pseudo grey-platelet syndrome, some patient’s blood samples undergo in-vitro degranulation of all platelets in response to the EDTA, which is seen peripheral blood smear. It is expected that in such a case the functional platelet aggregation assay, where blood is collected in a citrate tube, will be normal. 

Learning points from the case:

1. Agranular platelet morphology on peripheral blood smear

2. Platelet aggregation defects are seen in grey platelet syndrome

References:

1. Nurden, A. T., & Nurden, P. (2007). The gray platelet syndrome: clinical spectrum of the disease. Blood Reviews, 21(1), 21-36.

2. Gunay-Aygun M et al. (2011). NBEAL2 is mutated in gray platelet syndrome and is required for biogenesis of platelet α-granules. Nat Genet. 43(8):732-4.

3. Albers CA et al. (2011). Exome sequencing identifies NBEAL2 as the causative gene for gray platelet syndrome. Nat Genet. 43(8):735-7.

4. Kahr WH et al. (2011). Mutations in NBEAL2, encoding a BEACH protein, cause gray platelet syndrome. Nat Genet. 43(8):738-40.

5. Cockbill SR et al. (1988) Pseudo grey platelet syndrome, grey platelets due to degranulation in blood collected into EDTA. Eur J Haematol. 41:326–333.

6. Kahr WH et al. (2013). Abnormal megakaryocyte development and platelet function in Nbeal2(-/-) mice. Blood. 122(19):3349-58.