Platelet characteristics of patients with the ITGA2B R995W mutation
Patient . | Sex . | Age, y . | ITGA2B mutation . | Platelet count, × 109/L* . | Platelet size, μm† . | Surface expression relative to control platelets, %‡ . | αIIb/β1 tubulin ratio to controls§ . | Duke bleeding time, minutes‖ . | Platelet aggregation¶ . | Bleeding tendency . | Initial diagnosis . | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
αIIb . | β3 . | αIIbβ3 . | GPIbα . | GPIX . | ADP, % . | Collagen (2.0 μg/mL), % . | Ristocetin (1.3 mg/mL), % . | ||||||||||
Family 1 | |||||||||||||||||
Patient 1 | Male | 55 | R995W | 65 | 3.9 ± 0.9 | 53.8 | 67.0 | — | 143.1 | 143.8 | 0.82 | 4.5 | 11 (3μM) | 28 | 77 | − | Unknown thrombocytopenia |
Family 2 | |||||||||||||||||
Father | Male | 46 | R995W | 79 | 3.3 ± 0.9 | 51.3 | 51.4 | 56.5 | 106.7 | 109.8 | — | — | — | — | — | − | — |
Patient 2 | Male | 4 | R995W | 82 | 3.6 ± 1.0 | 54.0 | 58.6 | 61.8 | 138.3 | 134.7 | 0.75 | 5 | — | — | — | Epistaxis | Congenital thrombocytopenia |
Sister | Female | 9 | R995W | 85 | 3.4 ± 1.0 | 55.6 | 60.6 | 68.4 | 120.0 | 133.1 | 0.71 | 3.5 | — | — | — | − | — |
Family 3 | |||||||||||||||||
Mother | Female | 56 | R995W | 80 | 2.8 ± 0.8 | 58.4 | 63.4 | 65.8 | 116.5 | — | 0.73 | — | − | — | |||
Patient 3 | Female | 27 | R995W | 74 | 3.5 ± 1.0 | 64.4 | 69.7 | 63.8 | 124.8 | — | — | — | 43 (10μM) | 44 | 72 | − | cITP |
Sister | Female | 24 | R995W | 100 | 3.6 ± 1.0 | 59.3 | 70.2 | 70.8 | 110.9 | — | 0.63 | — | — | — | — | − | — |
Family 4 | |||||||||||||||||
Maternal grandfather | Male | 58 | R995W | 66 | 3.4 ± 0.9 | — | — | — | — | — | 0.63 | — | 20 (3μM) | 9 | — | Hemorrhage in exodontia | — |
Mother | Female | 30 | R995W | 66 | 2.8 ± 0.8 | 56.3 | 62.5 | 57.5 | 127.2 | 112.1 | 0.63 | 2.5 | — | — | Purpura, hemorrhage in exodontia | cITP | |
Patient 4 | Female | 4M | R995W | 82 | 3.2 ± 1.0 | 63.3 | 62.9 | 62.3 | 147.7 | 140.5 | 0.63 | — | 23 (3μM) | 11 | — | − | NAITP |
Brother | Male | 5 | R995W | 122 | 3.1 ± 0.8 | — | — | — | — | — | — | — | — | — | — | − | — |
Mean ± SD | 81.9 ± 16.8# | 3.3 ± 0.3# | 57.4 ± 4.4** | 62.9 ± 5.8** | 63.3 ± 5.0** | 126.1 ± 14.3** | 129.0 ± 14.5** | 0.7 ± 0.07# |
Patient . | Sex . | Age, y . | ITGA2B mutation . | Platelet count, × 109/L* . | Platelet size, μm† . | Surface expression relative to control platelets, %‡ . | αIIb/β1 tubulin ratio to controls§ . | Duke bleeding time, minutes‖ . | Platelet aggregation¶ . | Bleeding tendency . | Initial diagnosis . | ||||||
---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|---|
αIIb . | β3 . | αIIbβ3 . | GPIbα . | GPIX . | ADP, % . | Collagen (2.0 μg/mL), % . | Ristocetin (1.3 mg/mL), % . | ||||||||||
Family 1 | |||||||||||||||||
Patient 1 | Male | 55 | R995W | 65 | 3.9 ± 0.9 | 53.8 | 67.0 | — | 143.1 | 143.8 | 0.82 | 4.5 | 11 (3μM) | 28 | 77 | − | Unknown thrombocytopenia |
Family 2 | |||||||||||||||||
Father | Male | 46 | R995W | 79 | 3.3 ± 0.9 | 51.3 | 51.4 | 56.5 | 106.7 | 109.8 | — | — | — | — | — | − | — |
Patient 2 | Male | 4 | R995W | 82 | 3.6 ± 1.0 | 54.0 | 58.6 | 61.8 | 138.3 | 134.7 | 0.75 | 5 | — | — | — | Epistaxis | Congenital thrombocytopenia |
Sister | Female | 9 | R995W | 85 | 3.4 ± 1.0 | 55.6 | 60.6 | 68.4 | 120.0 | 133.1 | 0.71 | 3.5 | — | — | — | − | — |
Family 3 | |||||||||||||||||
Mother | Female | 56 | R995W | 80 | 2.8 ± 0.8 | 58.4 | 63.4 | 65.8 | 116.5 | — | 0.73 | — | − | — | |||
Patient 3 | Female | 27 | R995W | 74 | 3.5 ± 1.0 | 64.4 | 69.7 | 63.8 | 124.8 | — | — | — | 43 (10μM) | 44 | 72 | − | cITP |
Sister | Female | 24 | R995W | 100 | 3.6 ± 1.0 | 59.3 | 70.2 | 70.8 | 110.9 | — | 0.63 | — | — | — | — | − | — |
Family 4 | |||||||||||||||||
Maternal grandfather | Male | 58 | R995W | 66 | 3.4 ± 0.9 | — | — | — | — | — | 0.63 | — | 20 (3μM) | 9 | — | Hemorrhage in exodontia | — |
Mother | Female | 30 | R995W | 66 | 2.8 ± 0.8 | 56.3 | 62.5 | 57.5 | 127.2 | 112.1 | 0.63 | 2.5 | — | — | Purpura, hemorrhage in exodontia | cITP | |
Patient 4 | Female | 4M | R995W | 82 | 3.2 ± 1.0 | 63.3 | 62.9 | 62.3 | 147.7 | 140.5 | 0.63 | — | 23 (3μM) | 11 | — | − | NAITP |
Brother | Male | 5 | R995W | 122 | 3.1 ± 0.8 | — | — | — | — | — | — | — | — | — | — | − | — |
Mean ± SD | 81.9 ± 16.8# | 3.3 ± 0.3# | 57.4 ± 4.4** | 62.9 ± 5.8** | 63.3 ± 5.0** | 126.1 ± 14.3** | 129.0 ± 14.5** | 0.7 ± 0.07# |
— indicates not applicable; ADP, adenosine diphosphate; cITP, chronic immune thrombocytopenia; and NAITP, neonatal alloimmune thrombocytopenic purpura.
Controls, 273.5 ± 60.4 ( × 109/L) (n = 1014).
Determined by microscopic observation of 200 platelets on a stained peripheral blood smear. Controls, 2.5 ± 0.3 μm (n = 31).
Platelets were reacted with fluorescein isothiocyanate-labeled monoclonal antibodies against αIIb (5B12; Dako Denmark), β3 (SZ21), αIIbβ3 (P2), GPIbα (SZ2; Beckman-Coulter), or GPIX (ALMA16; BD Biosciences) and analyzed in an Epics XL flow cytometer (Beckman-Coulter). Values are expressed as percentage of mean fluorescence intensities of control platelets.
Platelet αIIb/β1-tubulin ratio was determined by densitometric analysis of immunoblots using ImageQuant software Version 5.0 (Molecular Dynamics).
Normal range, 2 to 5 minutes.
Platelet aggregation was performed in platelet-rich plasma. Results are given as percentage maximum aggregation.
P < .001,
P < .0001 vs controls (2-tailed t test).