Myeloid malignancy presenting with a platelet storage pool disorder

Abstract

Platelet storage pool disorders (SPDs) are collectively characterized by either a congenital or an acquired defi ciency of alpha and/or dense platelet granules, resulting in a qualitative platelet function defect. Storage pool defi ciency in association with myeloid malignancies has been described [1,2], but rarely is the presenting manifestation of the disease. A 56-year-old female with a history of polymyalgia rheumatica, on corticosteroid therapy, was referred from her rheumatologist with a 2-year history of easy bruisability, prolonged bleeding with minor cuts, and recurrent bleeding from a gastric ulcer that was initially attributed to her steroid use. During her initial work-up she was found to have mild normocytic anemia (11 g/dL) and thrombocytopenia (115 000 / μ L). Her leukocyte count was 3800/ μ L with a normal diff erential. A peripheral smear revealed hypogranular platelets. Complete blood counts over the past 2 years had revealed normocytic anemia but a normal platelet and leukocyte count. Th rombocytopenia was fi rst noted 5 months prior to her presentation. Routine coagulation testing revealed a normal prothrombin time (PT) and a normal activated partial thromboplastin time (APTT). Qualitative platelet function tests revealed both epinephrine and adenosine diphosphate (ADP) closure times longer than 300 s. Platelet light transmission aggregation studies demonstrated absent aggregation in response to arachidonate (1.7 mM) and epinephrine (50 μ M) and normal aggregation in response to ADP (5 μ M), collagen (250 μ g/ mL) and ristocetin (0.75 mg/mL). Platelet electron microscopy revealed signifi cant platelet ultrastructural abnormalities (Figure 1), including a decrease in the number of dense bodies (mean dense body count/platelet was 0.5; normal range is 2) and alpha granules, abnormal platelet to platelet attachments, the presence of Golgi complexes and complex tubular networks. Platelet fl ow cytometry studies did not identify glycoprotein IIb, IIIa, Ib, IX, IV or Ia/IIa defi ciency. A bone marrow biopsy was performed. Th is revealed 60% cellularity, moderate megakaryocytic hyperplasia with occasional clusters and variable morphology, including small, monolobated forms, large, hyperlobated forms and hyperchromatic nuclei, grade 1 reticulin fi brosis, and no increase in blasts. JAK2V617F mutation analysis was negative and the karyotype revealed del20q in all metaphases. Th ese fi ndings were thought to be consistent with involvement by a chronic myeloid neoplasm that could not be further classifi ed. Repeat bone marrow biopsy 7 months after her initial diagnosis revealed marked hypercellularity (95%), an increase in the number of megakaryocytes with abnormal morphology and clustering, dysplastic granulocytes and grade 2 – 3 reticulin fi brosis, with no increase in myeloblasts. Collectively these fi ndings were thought to represent an acquired SPD that had developed in the setting of an underlying myelodysplastic/myeloproliferative neoplasm (MDS/MPN) overlap syndrome. Abnormalities of epinephrine, ADP or collagen-induced platelet aggregation have been shown in patients with myeloid malignancies [3 – 5]. Th e patients almost always