A heterogeneous group of inherited or acquired platelet function disorders characterised by quantitative or qualitative abnormalities of platelet storage granules, resulting in impaired secretion and defective amplification of platelet activation. Storage pool deficiencies may involve δ-granules (dense granules), α-granules, or both, and may occur as isolated platelet disorders or as part of multisystem syndromes. The clinical phenotype ranges from mild mucocutaneous bleeding to significant perioperative or obstetric haemorrhage. The term therefore encompasses several biologically and genetically distinct disorders rather than a single disease entity.

Epidemiology
The overall prevalence of storage pool deficiencies is unknown because the disorders are heterogeneous, frequently underdiagnosed, and diagnostic testing is specialised and not standardised between laboratories. Isolated δ-storage pool deficiency (δ-SPD) is probably among the more frequently encountered inherited platelet secretion disorders in specialised haemostasis practice, but reliable population-based prevalence estimates are unavailable.

Syndromic forms are individually rare. Hermansky–Pudlak syndrome (HPS), for example, is rare globally but occurs with markedly increased frequency in certain founder populations. Gray platelet syndrome (GPS), a prototypical α-storage pool disorder, is extremely rare, with only a limited number of cases described.

Both sexes may be affected. Inheritance varies according to the specific disorder and may be autosomal recessive, autosomal dominant, X-linked, or, in some nonsyndromic forms, currently undefined.

Clinical description
Storage pool deficiencies typically cause a mucocutaneous bleeding phenotype of variable severity. Common manifestations include easy bruising, petechiae, epistaxis, gingival bleeding, heavy menstrual bleeding, postpartum haemorrhage, and excessive bleeding following dental procedures, surgery, trauma, or other haemostatic challenges. Spontaneous deep tissue, joint, and muscle bleeding is uncommon and should prompt consideration of a coagulation factor deficiency or another haemostatic disorder.

The severity of bleeding is highly variable, even among individuals with apparently similar laboratory abnormalities. Many patients have mild bleeding that becomes apparent only during surgery, childbirth, dental extraction, or significant trauma. Some patients, however, may experience clinically important or occasionally severe haemorrhage.

The clinical phenotype depends partly on the type of granule affected:

– δ-storage pool deficiency (δ-SPD) primarily affects dense granules containing ADP, ATP, serotonin, calcium and other small molecules required for platelet activation and secretion. It is generally associated with a mild-to-moderate bleeding phenotype but may produce significant perioperative or obstetric bleeding.
– α-storage pool deficiency (α-SPD) involves deficiency or abnormality of platelet α-granules and their protein contents. Gray platelet syndrome is the best-characterised inherited α-storage pool disorder and is typically associated with thrombocytopenia and large, pale or “gray” platelets.
– Combined αδ-storage pool deficiency affects both granule populations and may occur in several inherited syndromes, including some disorders associated with thrombocytopenia.
– Syndromic storage pool deficiencies may be accompanied by abnormalities outside the platelet lineage. Hermansky–Pudlak syndrome is associated with oculocutaneous albinism and, in some subtypes, pulmonary fibrosis, granulomatous colitis or immunodeficiency. Chediak–Higashi syndrome is associated with partial albinism, immunodeficiency and susceptibility to severe infections. Griscelli syndrome may combine pigmentary abnormalities, immune dysfunction and platelet abnormalities.

Some disorders that are traditionally discussed within the broader storage-pool spectrum have additional distinctive features. Quebec platelet disorder, for example, is an inherited α-granule disorder characterised by increased platelet urokinase-type plasminogen activator and proteolytic degradation of several α-granule proteins, with bleeding that may respond particularly well to antifibrinolytic therapy.

Acquired abnormalities of platelet granules can also occur, particularly in association with haematological malignancies, myelodysplastic or myeloproliferative disorders, and some autoimmune diseases. These should be distinguished from inherited SPD.

Etiology
Storage pool deficiencies result from abnormalities in the number, formation, trafficking, content, or secretion of platelet granules.

Platelet δ-granules (dense granules) contain ADP, ATP, serotonin, calcium and other small molecules that are released following platelet activation. Their secretion amplifies platelet activation and promotes recruitment and aggregation of additional platelets. Deficiency or abnormal content of these granules therefore produces a platelet secretion defect.
Platelet α-granules contain numerous proteins involved in platelet adhesion, coagulation, inflammation, and tissue repair, including von Willebrand factor, fibrinogen, factor V, platelet factor 4, P-selectin and growth factors. Deficiency or abnormality of α-granules therefore produces a different, although overlapping, platelet phenotype.

The genetic basis varies substantially between the different forms:

– Hermansky–Pudlak syndromes result from pathogenic variants affecting proteins involved in the biogenesis and trafficking of lysosome-related organelles. Multiple HPS genes have been identified, including HPS1, HPS3, HPS4, HPS5, HPS6, DTNBP1, BLOC1S3, BLOC1S5, BLOC1S6, AP3B1 and AP3D1.
– Chediak–Higashi syndrome is caused by pathogenic variants in LYST, resulting in abnormal lysosomal trafficking and giant intracellular granules.
– Gray platelet syndrome is most commonly associated with pathogenic variants in NBEAL2, which is required for normal α-granule formation and packaging.
– Quebec platelet disorder is associated with a distinctive duplication involving PLAUR, resulting in abnormal expression and storage of urokinase-type plasminogen activator.
– Other syndromic or combined α/δ disorders may involve genes such as WAS, FLI1, RUNX1, GATA1, and genes involved in lysosome-related organelle biogenesis and trafficking.
– In many patients with isolated/nonsyndromic δ-SPD, no causative genetic variant is identified, and the underlying molecular basis remains incompletely understood.

Storage pool abnormalities may also be acquired, particularly in association with haematological malignancy, myelodysplastic syndromes, myeloproliferative disorders, and autoimmune disease.

Management is individualised according to the specific storage pool disorder, bleeding phenotype, platelet count, previous haemostatic challenges, and the planned procedure.

Treatment options include:

– Antifibrinolytic agents, particularly tranexamic acid, for mucosal bleeding and dental, ENT, gynaecological, and other procedures involving tissues with high fibrinolytic activity.
– Desmopressin (DDAVP) may be considered in selected patients with some inherited platelet function disorders and can improve haemostasis in certain individuals, but the response is variable and a therapeutic trial before major procedures may be appropriate.
– Platelet transfusion may be used for significant bleeding or major surgery when other measures are insufficient, particularly in severe platelet function disorders. Routine prophylactic platelet transfusion is generally avoided in patients with mild phenotypes because of risks including alloimmunisation.
– Recombinant activated factor VII (rFVIIa) may be considered in selected patients with severe inherited platelet function disorders when platelet transfusion is ineffective, contraindicated, or undesirable. It should be reserved for specialist use because of thrombotic risk.
– Hormonal therapy and/or tranexamic acid may be used for heavy menstrual bleeding.
– Management of the underlying systemic disorder is essential in syndromic forms. For example, patients with Hermansky–Pudlak syndrome require monitoring for pulmonary and gastrointestinal complications, while Chediak–Higashi syndrome requires specialist management of immunodeficiency and risk of haemophagocytic/accelerated-phase disease.
– Patients with Gray platelet syndrome require management of thrombocytopenia and its associated complications in addition to treatment of the platelet dysfunction.
– In Quebec platelet disorder, antifibrinolytic therapy is particularly important because excessive fibrinolysis contributes substantially to the bleeding phenotype.

A written bleeding management plan is recommended, particularly for patients undergoing surgery, invasive dental procedures, or childbirth. Patients should inform healthcare professionals of the diagnosis before procedures, and management should ideally be coordinated with a haemostasis specialist.

Prognosis
Prognosis varies according to the specific storage pool disorder and whether it is isolated or syndromic. Patients with isolated δ-SPD often have a mild-to-moderate bleeding phenotype and generally have a good long-term prognosis, although significant perioperative or obstetric bleeding can occur.

Syndromic forms may have substantially greater morbidity because the prognosis is determined not only by the platelet disorder but also by associated systemic disease. Hermansky–Pudlak syndrome, for example, may be complicated by pulmonary fibrosis, granulomatous colitis or immunodeficiency depending on the subtype, while Chediak–Higashi syndrome can cause severe immunodeficiency and an accelerated phase with potentially life-threatening haemophagocytic disease.

Overall, bleeding can usually be managed effectively with appropriate recognition, avoidance of platelet-inhibiting medications where possible, antifibrinolytic therapy, and individualised perioperative planning. The major challenge is often accurate diagnosis, particularly in isolated δ-SPD, because routine platelet function testing may be normal and definitive testing requires specialised laboratory techniques.

Last update: September 2026