Table 3.
Inherited defects of platelet granules.
| Granule | Disease (OMIM code) | Inh. | Genes | Clinical & Laboratory Phenotype in Most Reported Cases | Ref. |
|---|---|---|---|---|---|
| α and δ | Idiopathic granule deficiency | AR/AD | Nc | Platelet count normal or slightly decreased. Normal platelet morphology δ and α -granule defect by electron microscopy. Reduced LTA and/or absence of second aggregation wave with weak/low dose agonists (ADP, epinephrine, collagen). Defect of granular protein release by flow cytometry. Absent or very moderate hemorrhagic symptoms, associated with situations of high hemorrhagic risk. |
[50,99] |
| α | Grey Platelet Syndrome (GPS) (139090) | AR AD |
NBEAL2
GFI1B |
See Table 1. | |
| Quebec Syndrome (QS) (601709) | AD | PLAU | Moderate thrombocytopenia and normal morphology. LTA absent or reduced with epinephrine and normal with other agonists. Defect of procoagulant platelet activity and increased fibrinolytic activity α-granule protein defect by flow cytometry. (P-selectin, factor V). Mucocutaneous, visceral and/or post-surgery bleeding. Response to anti-fibrinolytics but lack of response to platelet transfusions. |
[100,101] | |
| δ | Hermansky-Pudlak Syndrome (HPS) (203300, 608233, 614072, 614073, 614074, 614075, 614076, 614077, 614171, 617050, 619172) | AR |
HPS1,
HPS2-[ AP3B1], HPS3, HPS4, HPS5, HPS6, HPS7-[ DTNBP1] HPS8-[ BLOC1S3] HPS9-[ BLOC1S] HPS10-[ AP3D1], HPS11 [BLOC1S5] |
Normal platelet count and morphology. Selective δ-granule defect by electron microscopy. Reduced LTA and/or absence of second wave with weak/low dose agonists (ADP, epinephrine, collagen). Radio-labelled serotonin uptake, mepacrine uptake, and CD63 release defects by flow cytometry. Oculocutaneous albinism; accumulation of lipofuscin-like ceroid material in cells of the phagocytic mononuclear system; neutropenia, immunodeficiency, pulmonary fibrosis, granulomatous colitis depending on the subtype. Genotype–phenotype relationship. Mild to moderate bleeding tendency. |
[50,99,102,103,104,105] |
| Chediak-Higashi Syndrome (CHS) (214500) | AR | LYST | Normal platelet count and morphology. δ-granule defect by electron microscopy. Reduced LTA and/or absence of second aggregation wave with weak/low dose agonists (ADP, epinephrine, collagen). Impaired uptake of radioactively labeled serotonin or mepacrine, and defect in CD63 release by flow cytometry. Oculocutaneous albinism; Immunodeficiency with predisposition to recurrent infections. In 85% of cases evolution to hemophagocytic lymphohistiocytosis with an accelerated phase. A juvenile milder form can be caused by missense variants maintaining Lyst expression/function. Genotype-Phenotype relationship. Mild to moderate bleeding tendency. |
[50,99,102,106] | |
| Griscelli Syndromes (214450, 607624, 609227) | AR |
RAB27
MYO5A MLPH |
Normal platelet count and morphology. δ-granule defect as in HPS and CHS. Variable neutropenia. Albinism, silver hair, neurological defects, lymphohistiocytosis, decreased cytotoxic function of NK cells and T-lymphocytes, according to subtype. |
[50,99,107] | |
| Delta-storage pool disease | AD/AR | - | Normal platelet numbers. Reduced second phase of aggregation with weak/low dose agonists (ADP, epinephrine, collagen). Absence of δ-granules in electron microscopy. Absent or mild bleeding tendency. |
[50,99] |
Inh: inheritance; AD: autosomal dominant; AR: autosomal recessive; LTA: light transmission aggregometry.