Progressive pigmented purpuric dermatosis and platelet delta storage pool deficiency in a child

Abstract

To the Editor: A previously healthy 11-year-old female sought medical advice for asymptomatic pigmented skin lesions on her legs which had developed during the last two months. On physical examination, a dozen of irregular round orange-brown macules, 2 to 4 cm in diameter, with petechiae at the edge of the lesions were present on legs (Figure 1A). The patient reported nomucocutaneous bleeding, she has never had any surgery or tooth extraction, and denied any trauma and drug intake. Cutaneous biopsy specimen from one leg lesion showed perivascular extravasated red blood cells, an infiltrate of lymphocytes and macrophages, endothelial cell swelling, and slight hemosiderin deposits around capillaries, in upper dermis. Therefore, diagnosis of progressive PPD disease was highly suspected. No treatment was given, and one year later, lesions were still present. However, the purpuric dermatosis of unknown cause prompted us to study hemostasis, including platelet function tests. Platelet count, prothrombin time, activated partial thromboplastin time, and von Willebrand factor activity were normal. Light transmission aggregometry disclosed a lack of the second wave of aggregation in response to ADP and to epinephrine and reversible aggregation to arachidonate, to collagen and to thrombin receptor activating peptide (TRAP). Response to ristocetinwas normal. Adenosine triphosphate release after collagen and TRAP-induced platelet activation measured by chemiluminescence in whole blood was decreased. Examination of platelets by transmission electron microscopy revealed a reduced number of dense granules 1.8 ± 2.5 per platelet (reference values: 4.14–7.74 dense granules/platelet), while 43%of themwere empty, confirming delta storage pool disease (δ-SPD) diagnosis (Figure 1B and C). RUNX1 mutation by Sanger sequencing was not detected. Laboratory investigations confirmed δ-SPD diagnosis to her father with a history of gingivorrhagia and epistaxis never explored. Delta SPD is a platelet function disorder caused by a qualitative or quantitative deficiency of platelets’ dense granules. Normal human platelets contain three to eight dense granules containing small molecules at high concentration: serotonin, ADP, ATP, Ca+2, pyrophosphate and polyphosphate, Mg+2 and K+.1,2 Delta SPD can be an isolated finding or a part of syndromic disorders, such as Hermansky– Puldak syndrome, Chediak–Higashi syndrome, Wiskott–Aldrich syndrome, thrombocytopenia-absent radius syndrome, and Paris Trousseau syndrome, or as an acquired disorder. Granule deficiency may be severe or partial, isolated or in combination with α-granule