Platelet-type bleeding disorder 20

Any inherited bleeding disorder, platelet-type in which the cause of the disease is a mutation in the SLFN14 gene, characterized by moderate thrombocytopenia, enlarged platelets in some individuals, and a mucocutaneous bleeding diathesis including bruising, epistaxis, gum bleeding, menorrhagia, and postpartum hemorrhage. Human platelet studies consistently show reduced aggregation in response to ADP, collagen, and PAR-1, accompanied by decreased ATP secretion and markedly reduced dense-granule numbers, indicating a secretion defect. SLFN14 missense variants impair protein stability and disrupt ribosomal RNA-regulatory pathways in megakaryocytes, leading to defective proplatelet formation, impaired megakaryocyte maturation, and reduced platelet output.