Clinical characteristics of individuals with FPD/AML
| Pedigree/patient . | Bleeding history . | Thrombocytopenia . | Platelet function defect . | Age of onset of platelet abnormalities, y . | Malignancy . | Age at diagnosis of MDS/AML, y . | Mutation . |
|---|---|---|---|---|---|---|---|
| A I-2 | No | Yes | Unknown | 35 | AML evolved from MDS | 63 | SNA |
| A II-1 | No | Yes* | Unknown | 45 | None | NA | G336fsX563 (C terminal) |
| A II-2 | No | No | Unknown | NA | MDS-RAEB with normal karyotype | 37 | G336fsX563 |
| A II-3 | Easy bruising | Yes | Unknown | 40 | Nondiagnostic marrow aspirate showing mildly disorganized erythropoeisis and focal clusters of micromegakaryocytes with normal karyotype | NA | G336fsX563 |
| A II-4 | No | No | Unknown | NA | T-ALL | 12 | G336fsX563 |
| B I-1 | Easy bruising | Unknown | Unknown | NA | AML | 72 | SNA |
| B II-2 | Easy bruising | Yes | AA, ↓ response | Unknown | AML evolved from MDS | Unknown | SNA |
| ADP, 1° wave only | |||||||
| Collagen, ↓ response | |||||||
| Epinephrine, ↓ response | |||||||
| B II-5 | Easy bruising | No | AA, 1° wave only | Childhood | AML with monosomy 5 | 51 | A28fsX109 |
| ADP, 1° wave only | (N terminal) | ||||||
| Collagen, no response | |||||||
| Postsurgical bleeding | Epinephrine, ↓ response | ||||||
| B II-6 | No | Yes | Unknown | Unknown | Nondiagnostic marrow aspirate showing mild dyserythropoesis with normal karyotype | NA | SNA |
| B III-1 | Easy bruising; menorrhagia PPH | Yes | Collagen, ↓ response | 20 | None | NA | A28fsX109 |
| Epinephrine, ↓ response† | |||||||
| B III-4 | Easy bruising | Yes | Unknown | 20 | AML with normal karyotype | 28 | A28fsX109 |
| Epistaxis | |||||||
| B II-1, II-3, II-7, | Easy bruising | Yes | Unknown‡ | 60, 51, 31, 9, 7 | None | NA | SNA |
| IV-1, IV-2 | Epistaxis | ||||||
| C I-1 | No | Unknown | Unknown | NA | AML | 29 | SNA |
| C II-1 | Easy bruising; no postsurgical bleeding | Yes | Unknown | 10 | MDS-RARS with normal karyotype | 49 | D96H (N terminal) |
| C II-2 | No | Yes | Unknown | 7 | MDS-RA MLD with trisomy 8 | 45 | D96H |
| C III-2 | No | Yes* | Unknown | 18 | None | NA | D96H |
| C III-3 | No | Yes | Unknown | 15 | None | NA | D96H |
| D I-2 | Yes | Yes | ADP, 1° wave only | 29 | MDS-CMMoL with deletion of 11q23 | 48 | SNA |
| Collagen, ↓ response Epinephrine, no response | |||||||
| D I-3 | Yes | No | No | NA | AML | 64 | SNA |
| D II-1 | Yes | Yes | ADP, ↓ response | 21 | None | NA | K90fs (N terminal) |
| Collagen, ↓ response Epinephrine, no response | |||||||
| D II-3 | Unknown | Yes | Unknown | 12 | AML evolved from MDS (RAEB) with normal karyotype | 23 | SNA |
| E I-2 | Yes | Yes | Unknown | 10 | MDS | 52 | R292X (C terminal) |
| E II-2 | No | Unknown | Unknown | NA | AML (biphenotypic) | 8 | No mutation detected (post-HSCT samples) |
| Pedigree/patient . | Bleeding history . | Thrombocytopenia . | Platelet function defect . | Age of onset of platelet abnormalities, y . | Malignancy . | Age at diagnosis of MDS/AML, y . | Mutation . |
|---|---|---|---|---|---|---|---|
| A I-2 | No | Yes | Unknown | 35 | AML evolved from MDS | 63 | SNA |
| A II-1 | No | Yes* | Unknown | 45 | None | NA | G336fsX563 (C terminal) |
| A II-2 | No | No | Unknown | NA | MDS-RAEB with normal karyotype | 37 | G336fsX563 |
| A II-3 | Easy bruising | Yes | Unknown | 40 | Nondiagnostic marrow aspirate showing mildly disorganized erythropoeisis and focal clusters of micromegakaryocytes with normal karyotype | NA | G336fsX563 |
| A II-4 | No | No | Unknown | NA | T-ALL | 12 | G336fsX563 |
| B I-1 | Easy bruising | Unknown | Unknown | NA | AML | 72 | SNA |
| B II-2 | Easy bruising | Yes | AA, ↓ response | Unknown | AML evolved from MDS | Unknown | SNA |
| ADP, 1° wave only | |||||||
| Collagen, ↓ response | |||||||
| Epinephrine, ↓ response | |||||||
| B II-5 | Easy bruising | No | AA, 1° wave only | Childhood | AML with monosomy 5 | 51 | A28fsX109 |
| ADP, 1° wave only | (N terminal) | ||||||
| Collagen, no response | |||||||
| Postsurgical bleeding | Epinephrine, ↓ response | ||||||
| B II-6 | No | Yes | Unknown | Unknown | Nondiagnostic marrow aspirate showing mild dyserythropoesis with normal karyotype | NA | SNA |
| B III-1 | Easy bruising; menorrhagia PPH | Yes | Collagen, ↓ response | 20 | None | NA | A28fsX109 |
| Epinephrine, ↓ response† | |||||||
| B III-4 | Easy bruising | Yes | Unknown | 20 | AML with normal karyotype | 28 | A28fsX109 |
| Epistaxis | |||||||
| B II-1, II-3, II-7, | Easy bruising | Yes | Unknown‡ | 60, 51, 31, 9, 7 | None | NA | SNA |
| IV-1, IV-2 | Epistaxis | ||||||
| C I-1 | No | Unknown | Unknown | NA | AML | 29 | SNA |
| C II-1 | Easy bruising; no postsurgical bleeding | Yes | Unknown | 10 | MDS-RARS with normal karyotype | 49 | D96H (N terminal) |
| C II-2 | No | Yes | Unknown | 7 | MDS-RA MLD with trisomy 8 | 45 | D96H |
| C III-2 | No | Yes* | Unknown | 18 | None | NA | D96H |
| C III-3 | No | Yes | Unknown | 15 | None | NA | D96H |
| D I-2 | Yes | Yes | ADP, 1° wave only | 29 | MDS-CMMoL with deletion of 11q23 | 48 | SNA |
| Collagen, ↓ response Epinephrine, no response | |||||||
| D I-3 | Yes | No | No | NA | AML | 64 | SNA |
| D II-1 | Yes | Yes | ADP, ↓ response | 21 | None | NA | K90fs (N terminal) |
| Collagen, ↓ response Epinephrine, no response | |||||||
| D II-3 | Unknown | Yes | Unknown | 12 | AML evolved from MDS (RAEB) with normal karyotype | 23 | SNA |
| E I-2 | Yes | Yes | Unknown | 10 | MDS | 52 | R292X (C terminal) |
| E II-2 | No | Unknown | Unknown | NA | AML (biphenotypic) | 8 | No mutation detected (post-HSCT samples) |
MDS indicates myelodysplasia; AML, acute myeloid leukemia; NA, not applicable; SNA, sample not available; RAEB, refractory anemia with excess blasts; RARS, refractory anemia with ringed sideroblasts; RA MLD, refractory anemia with multilineage dysplasia; CMMoL, chronic myelomonocytic leukemia; HSCT, hematopoietic stem cell transplantation; PPH, postpartum hemorrhage; AA, arachidonic acid; and ADP, adenosine diphosphate.
Borderline thrombocytopenia (140-150 × 109/L).
Also demonstrated defective dense granule function measured by flow cytometry.
IV-1 and IV-2 demonstrated closure times on PFA-100 to collagen/epinephrine of more than 300 seconds (normal, 84-176 seconds) and collagen/ADP of 136 to 142 seconds (normal, 63-111 seconds).