| Domain | Disease-specific finding | Evidence type and key quantitative data | Suggested ontology terms |
|---|---|---|---|
| Identity / identifiers | Bleeding disorder, platelet-type, 21 (BDPLT21) is a rare constitutional FLI1-related inherited platelet disorder; supported identifiers include MONDO:0054577 and OMIM 617443. | Human disease synthesis from primary human reports and recent review-level curation; 2025 study explicitly describes “FLI1-related platelet disorder BDPLT21” and 2020 review links heterozygous FLI1 mutations to “Bleeding disorder platelet-type 21” (pqac-00000001, pqac-00000000) | MONDO:0054577; inherited platelet function disorder; inherited thrombocytopenia |
| Gene / inheritance | Causal gene: FLI1. Most reported families show heterozygous dominant disease; rare recessive FLI1 disease has been reported/mentioned for related phenotypes. | Human family studies with variant-level evidence in multiple families; 2025 report notes dominant or recessive inheritance patterns in FLI1-related platelet disease (pqac-00000009, pqac-00000006) | FLI1; autosomal dominant inheritance; autosomal recessive inheritance |
| Core phenotype | Variable mucocutaneous and bleeding phenotype with mild-to-moderate thrombocytopenia and macrothrombocytopenia; reported manifestations include purpura, epistaxis, menorrhagia, postpartum hemorrhage, pulmonary hemorrhage, and cutaneous/mucosal bleeding. | Human clinical evidence from several families; one recent patient had platelet counts 83–147 ×10^9/L and MPV 13.3 fL; one case required RBC transfusion, showing severity can occasionally be substantial (pqac-00000007, pqac-00000011, pqac-00000009) | HP:0001873 Thrombocytopenia; HP:0001904 Increased mean platelet volume; HP:0000978 Bruising susceptibility; HP:0000421 Epistaxis; HP:0000132 Menorrhagia; HP:0012147 Postpartum hemorrhage |
| Platelet laboratory signature | Dense-granule secretion/storage-pool defect with impaired aggregation and secretion, often alongside enlarged/abnormal granules. | Primary human platelet studies: reduced aggregation to low-dose ADP, collagen, and TRAP; reduced ATP secretion; reduced mepacrine uptake/release; reduced CD63 after stimulation; nearly absent dense granules; 25–29% giant α-granules; 7–9% vacuoles; 0–3% autophagosome-like structures (pqac-00000004, pqac-00000010, pqac-00000000) | HP:0003542 Platelet dense granule deficiency; HP:0011875 Abnormal platelet aggregation; HP:0001878 Abnormal platelet morphology |
| Key pathogenic variants | Reported pathogenic/likely pathogenic FLI1 ETS-domain variants include p.R337Q, p.K345E, p.R340C, p.G307R; additional FLI1 alterations reported include p.R337W, p.Y343C, and a frameshift deletion. | Human genetics plus functional assays; recent structural/functional study found p.R340C and p.K345E disruptive (ΔΔG about 1.49 and 1.48 kcal/mol), while p.G307R impaired homodimerization (ΔΔG 3.59 kcal/mol) (pqac-00000005, pqac-00000010, pqac-00000007) | FLI1 missense variant; FLI1 frameshift variant; ETS DNA-binding domain |
| Molecular mechanism | FLI1 dysfunction impairs megakaryopoiesis and platelet activation through reduced nuclear localization and/or stability, reduced transcriptional activity, impaired cooperation with GATA1, and reduced TLN1/talin-1 expression, causing defective αIIbβ3 integrin activation and granule abnormalities. | Human platelets, CD34+ megakaryocytes, scRNA-seq, and reporter assays: 626 differentially expressed genes; platelet activation pathway most downregulated; talin-1 reduced by 88% in patient platelets; G307R and K345E showed ~60% decreased half-life; fibrinogen binding reduced in K345E and R340C carriers (pqac-00000000, pqac-00000001, pqac-00000005, pqac-00000003) | GO:0045654 regulation of megakaryocyte differentiation; GO:0030168 platelet activation; GO:0007596 blood coagulation; GO:0008360 regulation of cell shape; megakaryocyte; platelet |
| Diagnostics | Diagnosis requires combined clinical and specialized platelet evaluation plus molecular testing; useful disease-focused clues include MYH10 positivity, dense-granule deficiency on EM, and secretion/aggregation defects. | Human disease-specific and general inherited platelet disorder evidence: intracellular flow cytometry for MYH10 can distinguish affected individuals; LTA remains a gold-standard platelet function test; dense-granule studies, flow cytometry, CBC/smear, and ultrastructure are recommended; NGS/gene panels are important because routine tests alone are insufficient (pqac-00000020, pqac-00000021, pqac-00000022, pqac-00000023) | HP:0032180 Abnormal platelet dense granules; MYH10 biomarker; light transmission aggregometry; transmission electron microscopy; next-generation sequencing |
| Management | No BDPLT21-specific molecular therapy or trial-based standard exists; current care is supportive and extrapolated from inherited platelet disorder practice. | Review-based management evidence: avoid aspirin/NSAIDs; use local hemostatic measures and tranexamic acid; hormonal therapy may help menorrhagia; severe situations may require transfusion-oriented support; pregnancy/postpartum and surgery warrant planning. IT cohorts show surgical bleeding 19.7% vs 1.4–6% in controls and postpartum hemorrhage 6.8–14.2% vs 3–7% in controls (pqac-00000008) | tranexamic acid; platelet transfusion; hemostatic support; genetic counseling |
| Epidemiology / prognosis gaps | Population prevalence, incidence, penetrance, sex ratio, long-term survival, formal quality-of-life measures, and malignancy risk are not well defined for BDPLT21. Emerging non-hematologic findings may include cardiac anomalies in some families. | Explicit evidence gap from recent case series/reports: only small numbers of patients/families described; cardiac findings reported include valvular malformation, interventricular communication, and bicuspid aortic valve with ascending aorta dilation (pqac-00000009, pqac-00000011) | evidence gap; cardiac abnormality; variable expressivity |
| Models | Key models include Fli1 mouse models, patient-derived and isogenic human iPSC megakaryocytes, primary human CD34+ megakaryocytes, and transfected cell-line assays. No established natural veterinary disease model was identified in the gathered evidence. | Mouse limitation: Fli1−/− embryonic lethal at E11.5; Fli1+/− mice may be minimally affected. Human iPSC/megakaryocyte models recapitulate decreased megakaryocyte yield, reduced platelet release, impaired colony formation, shortened platelet half-life, reduced ploidy, and reduced proplatelet formation (pqac-00000013, pqac-00000012, pqac-00000014, pqac-00000017, pqac-00000015) | model organism; induced pluripotent stem cell-derived megakaryocyte; megakaryocyte differentiation assay; platelet model |


*Table: This compact table summarizes the highest-value disease facts for Bleeding disorder, platelet-type, 21, including identity, genetics, phenotype, mechanism, diagnostics, management, and evidence gaps. It is designed for rapid knowledge-base population using only evidence gathered in the conversation.*