Platelet δ-Storage Pool Disease: An Update

Abstract

Platelet dense-granules are small organelles specific to the platelet lineage that contain small molecules (calcium, adenyl nucleotides, serotonin) and are essential for the activation of blood platelets prior to their aggregation in the event of a vascular injury. Delta-storage pool diseases (δ-SPDs) are platelet pathologies leading to hemorrhagic syndromes of variable severity and related to a qualitative (content) or quantitative (numerical) deficiency in dense-granules. These pathologies appear in a syndromic or non-syndromic form. The syndromic forms (Chediak–Higashi disease, Hermansky–Pudlak syndromes), whose causative genes are known, associate immune deficiencies and/or oculocutaneous albinism with a platelet function disorder (PFD). The non-syndromic forms correspond to an isolated PFD, but the genes responsible for the pathology are not yet known. The diagnosis of these pathologies is complex and poorly standardized. It is based on orientation tests performed by light transmission aggregometry or flow cytometry, which are supplemented by complementary tests based on the quantification of platelet dense-granules by electron microscopy using the whole platelet mount technique and the direct determination of granule contents (ADP/ATP and serotonin). The objective of this review is to present the state of our knowledge concerning platelet dense-granules and the tools available for the diagnosis of different forms of δ-SPD.

Thrombocytopathies: Not Just Aggregation Defects—The Clinical Relevance of Procoagulant Platelets

“…δ-SPD can be associated with disorders of others lysosome related organelles leading to syndromic forms, known as Hermansky-Pudlack, Chediak-Higashi, and Grisicelli syndromes, in which albinism and immune deficiency are associated with platelet function defects [ 80 ]. Patients with non-syndromic δ-SPD have a mild to moderate bleeding diathesis, mainly mucocutaneous; however life-threatening bleedings can occur after surgery or trauma [ 81 ]. Clinical presentation of δ-SPD is highly variable and so far there are no validated recommendations concerning the decisional algorithm to reach an accurate diagnosis [ 81 ], nor for δ-SPD management [ 82 ].…”

“…Patients with non-syndromic δ-SPD have a mild to moderate bleeding diathesis, mainly mucocutaneous; however life-threatening bleedings can occur after surgery or trauma [ 81 ]. Clinical presentation of δ-SPD is highly variable and so far there are no validated recommendations concerning the decisional algorithm to reach an accurate diagnosis [ 81 ], nor for δ-SPD management [ 82 ].…”

“…The lack of dense-granules (and thus of ADP/ATP and serotonin) will be reflected by an impaired aggregation response to different agonists in vitro. Typically, LTA curves performed with citrated platelet rich plasma (PRP) are characterized by the absence of a second wave in ADP induced platelet aggregation and a diminished response to collagen induced aggregation (at low concentrations) [ 79 , 81 ]. However, a study reported that δ-SPD patients (23% of the cohort studied) had normal aggregation response [ 84 ].…”

“…δ-SPD platelets will have reduced dense-granules and low uptake and release of mepacrine [ 79 , 88 , 89 ]. Platelet content of adenine nucleotides and serotonin can be evaluated by chemiluminescence aggregometry and radio-labelled or chemical methods, respectively (reviewed in [ 59 , 81 ]). δ-SPD platelets will be characterized by reduced adenine nucleotides and serotonin content, with an elevated ATP/ADP ratio [ 90 ].…”

Platelet Phenotyping and Function Testing in Thrombocytopenia

“…The flow cytometric analysis of platelet count, size, and immature platelets (RNA stained by thiazole orange or SYTO-13) serves as alternative technique, but skilled personnel is required to permit intra-laboratory standardization and validation [ 33 , 34 ]. The quantitation of platelet surface receptors in citrated whole blood or the assessment of mepacrine uptake in isolated platelets ex vivo at resting conditions by flow cytometry is recommended to support the diagnosis of receptor-linked thrombocytopenias (e.g., BSS) [ 3 ] or δ-SPD [ 35 ] (see Section 5.3 ).…”