From the Guidelines
Familial chronic thrombocytopenia is primarily caused by genetic mutations that affect platelet production, function, or survival, with Wiskott-Aldrich syndrome being a notable cause, characterized by small platelet size and thrombocytopenia, as well as other clinical manifestations such as eczema, immune deficiency, and increased risk of autoimmune disorders and malignancies 1.
Causes of Familial Chronic Thrombocytopenia
The most common causes of familial chronic thrombocytopenia include:
- Inherited disorders such as Bernard-Soulier syndrome, MYH9-related disorders, and ANKRD26-related thrombocytopenia
- Mutations in transcription factors like RUNX1 and ETV6
- Wiskott-Aldrich syndrome, which is characterized by small platelet size and thrombocytopenia, as well as other clinical manifestations such as eczema, immune deficiency, and increased risk of autoimmune disorders and malignancies 1
- Other genetic causes, such as ACTN1-related thrombocytopenia and mutations in genes involved in platelet production and function, as listed in Table 1 of the study by the SSC of the ISTH 1
Diagnosis and Management
Diagnosis of familial chronic thrombocytopenia typically involves a combination of clinical evaluation, laboratory tests, and genetic analysis to identify the underlying genetic cause. Management focuses on preventing bleeding complications, rather than correcting the platelet count, and may include:
- Avoiding medications that impair platelet function, such as aspirin and NSAIDs
- Platelet transfusions before surgical procedures or during active bleeding episodes
- Monitoring for and managing other clinical manifestations, such as eczema and immune deficiency, in patients with Wiskott-Aldrich syndrome 1
From the Research
Causes of Familial Chronic Thrombocytopenia
Familial chronic thrombocytopenia can be caused by various genetic mutations that affect megakaryocyte differentiation and/or platelet formation and clearance. Some of the key factors that contribute to this condition include:
- Genetic mutations in genes implicated in megakaryocyte differentiation and/or platelet formation and clearance 2
- Mutations in genes such as MYH9, MPL, MECOM, RUNX1, ANKRD26, and ETV6, which can lead to different forms of inherited thrombocytopenia 3
- Mutations in novel genes such as MECOM, DIAPH1, TRPM7, SRC, FYB, and SLFN14, which have been identified using next-generation sequencing approaches 4
- Hypomorphic mutations of FLI1 and single nucleotide polymorphisms, such as that identified in ACTN1, which can also contribute to thrombocytopenia 4
Genetic Basis of Inherited Thrombocytopenias
The genetic basis of inherited thrombocytopenias is complex and heterogeneous, with over 30 genes implicated in the condition 4. Some of the key genes involved include:
- MYH9, which is associated with congenital macrothrombocytopenia and predisposes to kidney failure, hearing loss, and cataracts 3
- MPL and MECOM, which are associated with congenital thrombocytopenia evolving into bone marrow failure 3
- RUNX1, ANKRD26, and ETV6, which are associated with thrombocytopenias that predispose to hematological malignancies 3
Diagnosis and Classification of Inherited Thrombocytopenias
The diagnosis and classification of inherited thrombocytopenias can be challenging due to the high degree of heterogeneity in the condition 2. However, the use of next-generation sequencing and other diagnostic tools has improved our understanding of the genetic basis of the condition and enabled more accurate diagnosis and classification 4. Some of the key diagnostic criteria include: