Acute bleeding events and hemostatic management before and after emicizumab initiation for the complete cohort (N = 62)
| . | Before emicizumab initiation . | After emicizumab initiation . |
|---|---|---|
| Bleeds | ||
| Patients with acute bleeding | 59 (95.2%) | 8† (12.9%) |
| Patients with severe acute bleeding∗ | 48 (77.4%) | 3 (4.8%) |
| Acute bleeding site‡ | ||
| Soft tissue | 48 (77.4%) | 3 (4.8%) |
| Hematuria | 8 (12.9%) | 2 (3.2%) |
| Gastrointestinal | 6 (9.7%) | 2 (3.2%) |
| Hemarthrosis | 5 (8.1%) | 3 (4.8%) |
| Retroperitoneal | 5 (8.1%) | 0 (0%) |
| Mucosal | 3 (4.8%) | 0 (0%) |
| Epistaxis | 2 (3.2%) | 0 (0%) |
| Central nervous system | 2 (3.2%) | 0 (0%) |
| Pulmonary | 1 (1.6%) | 0 (0%) |
| Retinal | 1 (1.6%) | 0 (0%) |
| None | 3§ (4.8%) | 54 (87.1%) |
| Bleeding trigger | ||
| Spontaneous | 38 (61.3%) | 4 (6.5%) |
| Procedural | 11 (17.7%) | 2 (3.2%) |
| Traumatic | 7 (11.3%) | 3 (4.8%) |
| Unknown | 3 (4.8%) | 1 (1.6%) |
| Rescue hemostatic agents used‡ | ||
| rFVIIa | 26 (41.9%) | 8 (12.9%) |
| Recombinant porcine FVIII | 21 (33.9%) | 1 (1.6%) |
| aPCC | 20 (32.3%) | 0 (0%) |
| FVIII replacement factor | 8 (12.9%) | 1 (1.6%) |
| Antifibrinolytic | 7 (11.3%) | 1 (1.6%) |
| Plasma | 4 (6.5%) | 0 (0%) |
| DDAVP | 2 (3.2%) | 0 (0%) |
| Cryoprecipitate | 2 (3.2%) | 0 (0%) |
| PCC | 1 (1.6%) | 0 (0%) |
| Platelet transfusion | 1 (1.6%) | 0 (0%) |
| None | 13 (21.0%) | 54 (87.1%) |
| RBC transfusions administered | ||
| No | 26 (41.9%) | 59 (95.2%) |
| Yes | 36 (58.1%) | 3 (4.8%) |
| pRBC units, median (range) | 5 (1-30) | 3 (1-7) |
| Procedures required for hemostasis | ||
| Yes|| | 19 (30.6%) | 3 (4.8%) |
| No | 43 (69.4%) | 59 (95.2%) |
| Hospitalization (d), median (range) | 11 (0-60) | 3 (0-30) |
| Control of initial bleeding | ||
| Complete resolution or NA | 23 (37.1%) | 62¶ (100.0%) |
| Partial resolution | 22 (35.5%) | 0 (0%) |
| No control | 17 (27.4%) | 0 (0%) |
| Mean breakthrough bleed rate per patient-week, (95% CI)# | — | 0.02 (0.00-0.03) |
| Mean 12-wk breakthrough bleed rate per patient# | — | 0.18 (0.03-0.34) |
| . | Before emicizumab initiation . | After emicizumab initiation . |
|---|---|---|
| Bleeds | ||
| Patients with acute bleeding | 59 (95.2%) | 8† (12.9%) |
| Patients with severe acute bleeding∗ | 48 (77.4%) | 3 (4.8%) |
| Acute bleeding site‡ | ||
| Soft tissue | 48 (77.4%) | 3 (4.8%) |
| Hematuria | 8 (12.9%) | 2 (3.2%) |
| Gastrointestinal | 6 (9.7%) | 2 (3.2%) |
| Hemarthrosis | 5 (8.1%) | 3 (4.8%) |
| Retroperitoneal | 5 (8.1%) | 0 (0%) |
| Mucosal | 3 (4.8%) | 0 (0%) |
| Epistaxis | 2 (3.2%) | 0 (0%) |
| Central nervous system | 2 (3.2%) | 0 (0%) |
| Pulmonary | 1 (1.6%) | 0 (0%) |
| Retinal | 1 (1.6%) | 0 (0%) |
| None | 3§ (4.8%) | 54 (87.1%) |
| Bleeding trigger | ||
| Spontaneous | 38 (61.3%) | 4 (6.5%) |
| Procedural | 11 (17.7%) | 2 (3.2%) |
| Traumatic | 7 (11.3%) | 3 (4.8%) |
| Unknown | 3 (4.8%) | 1 (1.6%) |
| Rescue hemostatic agents used‡ | ||
| rFVIIa | 26 (41.9%) | 8 (12.9%) |
| Recombinant porcine FVIII | 21 (33.9%) | 1 (1.6%) |
| aPCC | 20 (32.3%) | 0 (0%) |
| FVIII replacement factor | 8 (12.9%) | 1 (1.6%) |
| Antifibrinolytic | 7 (11.3%) | 1 (1.6%) |
| Plasma | 4 (6.5%) | 0 (0%) |
| DDAVP | 2 (3.2%) | 0 (0%) |
| Cryoprecipitate | 2 (3.2%) | 0 (0%) |
| PCC | 1 (1.6%) | 0 (0%) |
| Platelet transfusion | 1 (1.6%) | 0 (0%) |
| None | 13 (21.0%) | 54 (87.1%) |
| RBC transfusions administered | ||
| No | 26 (41.9%) | 59 (95.2%) |
| Yes | 36 (58.1%) | 3 (4.8%) |
| pRBC units, median (range) | 5 (1-30) | 3 (1-7) |
| Procedures required for hemostasis | ||
| Yes|| | 19 (30.6%) | 3 (4.8%) |
| No | 43 (69.4%) | 59 (95.2%) |
| Hospitalization (d), median (range) | 11 (0-60) | 3 (0-30) |
| Control of initial bleeding | ||
| Complete resolution or NA | 23 (37.1%) | 62¶ (100.0%) |
| Partial resolution | 22 (35.5%) | 0 (0%) |
| No control | 17 (27.4%) | 0 (0%) |
| Mean breakthrough bleed rate per patient-week, (95% CI)# | — | 0.02 (0.00-0.03) |
| Mean 12-wk breakthrough bleed rate per patient# | — | 0.18 (0.03-0.34) |
CI, confidence interval; DDAVP, desmopressin; NA, not applicable.
Severe acute bleeding defined as a drop in hemoglobin of >2 g/dL, requiring >2 RBC transfusions, and/or organ-, limb-, or life-threatening.
Three of the 8 patients had breakthrough bleeding only during the emicizumab loading phase, including 1 who had a severe bleed that required pRBCs. Supplemental Table 1 further describes breakthrough bleeds during the emicizumab maintenance phase.
Percentages do not add up to 100% because respondents could select multiple answers for this variable.
All 3 patients had remote bleeding before the AHA diagnosis.
Procedures included arterial embolization, endoscopy, intubation, fasciotomy, drainage, cauterization, and cystoscopy.
All patients had resolution of initial bleeding after starting emicizumab. Four patients experienced new breakthrough bleeding during loading, and there were 6 bleeds in 5 patients during maintenance. All ultimately had resolution of bleeding while on emicizumab.
Calculations based on patients with at least 12 weeks of follow-up (n = 55).