Thrombocytopathies

Inherited platelet disorders typically present with lifelong mucocutaneous bleeding, including easy bruising, epistaxis, gingival bleeding, menorrhagia, and excessive haemorrhage following dental procedures or surgery; severe gastrointestinal or central nervous system bleeding may occur in rare cases. Severity ranges from mild laboratory phenotypes detected on routine investigation to life-threatening haemorrhage requiring transfusion support, and the severity of bleeding does not always correlate with platelet count or platelet function.

The clinical spectrum includes both non-syndromic forms, in which bleeding is the sole manifestation, and syndromic forms with extra-haematological features such as oculocutaneous albinism (Hermansky-Pudlak syndrome), eczema and immunodeficiency (), or nephropathy, cataracts, and sensorineural hearing loss (MYH9-related disease). Most forms become apparent in infancy or early childhood, whereas milder phenotypes may not come to medical attention until adolescence or adulthood, often after heavy menstrual bleeding or peri-procedural haemorrhage; syndromic forms typically declare themselves earlier through extra-haematological features.

The estimated prevalence is 1/10,000 to 1/1,000,000 across the inherited platelet disorder spectrum. Individual entities vary widely, with Glanzmann thrombasthenia and Bernard-Soulier syndrome each estimated at approximately 1/1,000,000 although higher rates have been reported in consanguineous populations.

More than 70 genes are included in diagnostic gene panels for inherited platelet disorders. The genetic forms broadly fall into membrane glycoprotein receptor defects, granule biogenesis and secretion defects (such as δ-granule deficiency), signalling and cytoskeletal defects, and inherited macrothrombocytopaenias. Frequently identified causes include Glanzmann thrombasthenia (ITGA2B, ITGB3; defective αIIbβ3 fibrinogen receptor), Hermansky-Pudlak syndrome (HPS1; δ-granule deficiency with oculocutaneous albinism), and MYH9-related disease (MYH9; macro with nephropathy, cataracts, and hearing loss).

The genetic conditions associated with inherited platelet disorders follow heterogeneous inheritance patterns. Autosomal recessive inheritance is frequently observed, particularly in consanguineous populations. In addition, conditions with autosomal dominant inheritance (e.g., MYH9-associated disorder, RUNX1-associated familial platelet disorder) and X-linked forms (e.g., ) are known.

• Where an inherited platelet disorder is suspected to have a genetic cause, molecular genetic testing can identify the underlying condition and confirm a clinical suspicion.
• The identified entity guides further clinical management and is a prerequisite for targeted medical care; therapeutic options are evaluated individually by the treating physicians.
• Identification of the underlying pathogenic germline variant enables predictive testing of at-risk family members and provides information relevant to family planning.

• Safdari SM, Jozdani S, Mottaghizadeh-Jazi M, Shayanmanesh M, Khanahmad A, Bakhtiyaridovvombaygi M, et al. Molecular diagnosis of inherited platelet disorders: a tale of two realities – advanced vs. resource-limited setting. Thromb J. 2025;23(1):119. PMID: .
• Sánchez-Fuentes A, Pérez-Botero J, Bastida JM, Rivera J. Diagnosis of inherited platelet disorders: clinical evaluation and functional and molecular assays. Biomolecules. 2025;15(6):846. PMID: .
• Downes K, Borry P, Ericson K, Gomez K, Greinacher A, Lambert M, et al. Clinical management, ethics and informed consent related to multi-gene panel-based high throughput sequencing testing for platelet disorders: communication from the SSC of the ISTH. J Thromb Haemost. 2020;18(10):2751-2758. PMID: .