Doses and therapeutic target levels for each RBD on on-demand and prophylaxis
| Deficient factor . | Plasma half-life . | Recommended trough levels . | On-demand dosages4 . | Long-term prophylaxis dosages4 . | |
|---|---|---|---|---|---|
| Previously reported . | After EN-RBD results6 . | ||||
| Fibrinogen | 2-4 days | 0.5-1 g/L | 1 g/L | Cryoprecipitate (15-20 mL/kg) | Cryoprecipitate: 1 bag every 10 kg every 7-10 days |
| Virus-inactivated plasma FFP (15-30 mL/kg) | Fibrinogen concentrate: 20-30 mg/kg per week adjusted to maintain trough fibrinogen level* | ||||
| Fibrinogen concentrate (50-100 mg/kg) | |||||
| Prothrombin | 3-4 days | 20-30% | >10% | Virus-inactivated plasma FFP (15-25 mL/kg) | PCC: 20-40 U/kg once a week |
| PCC (20-40 U/kg) | |||||
| FV | 36 hours | 10-20% | 10% | Virus-inactivated plasma FFP (15-25 mL/kg) | Virus-inactivated plasma FFP: 20 mL/kg 2 times/week |
| Platelet transfusions could be considered, with particular attention on alloimmunization | |||||
| FV and FVIII | FV 36 hours | 10-15% | 40% | As for FV + | Usually no need of prophylaxis |
| FVIII 10-14 hours | DDAVP for mild FVIII deficiency and pd- or recombinant FVIII concentrates for moderate and severe FVIII deficiency | ||||
| FVII | 4-6 hours | 10-15% | >20% | pd-FVII concentrate (30-40 U/kg) | Virus-inactivated plasma FFP: 10-15 mL/kg 2 times/week pdFVII: 30-40 U/kg 3 times/week |
| rFVIIa (15-30 μg/kg every 4-6 hours) | rFVIIa: 20-40 μg/kg 2-3 times/week* | ||||
| FX19 | 40-60 hours | 10-20% | >40% | Virus-inactivated plasma FFP (10-20 mL/kg) | PCC: 20-40 units/kg 2 times/week |
| PCC (20-30 U/kg) | pd-FX/FIX concentrate: 20 U/kg weekly | ||||
| pd-FX/FIX concentrate (10-20 U/kg) | pd-FX: 25 IU weekly | ||||
| pd-FX (25 IU/kg) | |||||
| FXI | 50 hours | 15-20% | — | Virus-inactivated plasma –FFP (15-20 mL/kg) | Not indicated |
| pd-FXI concentrate (15-20 U/kg) | |||||
| FXIII | 9-12 days | 2-5% | 30% | Cryoprecipitate (2-3 bags) | † |
| Virus-inactivated plasma –FFP (3-5 mL/kg) | Cryoprecipitate: 1 bag every 10 kg every 3 weeks | ||||
| pd- FXIII concentrate (20-40 U/kg) | pd-FXIII concentrate: 20-40 U or | ||||
| rFXIII-A (35 U/kg) | rFXIII-A: 35 U/kg every 4 weeks (in pregnant women interval needs to be shorter: 2-3 weeks) | ||||
| Vitamin K dependent | Prothrombin, FVII, FIX, FX (see specific factors) | Vitamin K1 10 mg for minor bleeding | Oral vitamin K1 5-20 mg/d | ||
| For severe bleedings: 4-factor PCC 20-30 U/kg or virus-inactivated plasma15-25 mL/kg | In poor responders, consider parenteral vitamin K1 5-20 mg/week | ||||
| Deficient factor . | Plasma half-life . | Recommended trough levels . | On-demand dosages4 . | Long-term prophylaxis dosages4 . | |
|---|---|---|---|---|---|
| Previously reported . | After EN-RBD results6 . | ||||
| Fibrinogen | 2-4 days | 0.5-1 g/L | 1 g/L | Cryoprecipitate (15-20 mL/kg) | Cryoprecipitate: 1 bag every 10 kg every 7-10 days |
| Virus-inactivated plasma FFP (15-30 mL/kg) | Fibrinogen concentrate: 20-30 mg/kg per week adjusted to maintain trough fibrinogen level* | ||||
| Fibrinogen concentrate (50-100 mg/kg) | |||||
| Prothrombin | 3-4 days | 20-30% | >10% | Virus-inactivated plasma FFP (15-25 mL/kg) | PCC: 20-40 U/kg once a week |
| PCC (20-40 U/kg) | |||||
| FV | 36 hours | 10-20% | 10% | Virus-inactivated plasma FFP (15-25 mL/kg) | Virus-inactivated plasma FFP: 20 mL/kg 2 times/week |
| Platelet transfusions could be considered, with particular attention on alloimmunization | |||||
| FV and FVIII | FV 36 hours | 10-15% | 40% | As for FV + | Usually no need of prophylaxis |
| FVIII 10-14 hours | DDAVP for mild FVIII deficiency and pd- or recombinant FVIII concentrates for moderate and severe FVIII deficiency | ||||
| FVII | 4-6 hours | 10-15% | >20% | pd-FVII concentrate (30-40 U/kg) | Virus-inactivated plasma FFP: 10-15 mL/kg 2 times/week pdFVII: 30-40 U/kg 3 times/week |
| rFVIIa (15-30 μg/kg every 4-6 hours) | rFVIIa: 20-40 μg/kg 2-3 times/week* | ||||
| FX19 | 40-60 hours | 10-20% | >40% | Virus-inactivated plasma FFP (10-20 mL/kg) | PCC: 20-40 units/kg 2 times/week |
| PCC (20-30 U/kg) | pd-FX/FIX concentrate: 20 U/kg weekly | ||||
| pd-FX/FIX concentrate (10-20 U/kg) | pd-FX: 25 IU weekly | ||||
| pd-FX (25 IU/kg) | |||||
| FXI | 50 hours | 15-20% | — | Virus-inactivated plasma –FFP (15-20 mL/kg) | Not indicated |
| pd-FXI concentrate (15-20 U/kg) | |||||
| FXIII | 9-12 days | 2-5% | 30% | Cryoprecipitate (2-3 bags) | † |
| Virus-inactivated plasma –FFP (3-5 mL/kg) | Cryoprecipitate: 1 bag every 10 kg every 3 weeks | ||||
| pd- FXIII concentrate (20-40 U/kg) | pd-FXIII concentrate: 20-40 U or | ||||
| rFXIII-A (35 U/kg) | rFXIII-A: 35 U/kg every 4 weeks (in pregnant women interval needs to be shorter: 2-3 weeks) | ||||
| Vitamin K dependent | Prothrombin, FVII, FIX, FX (see specific factors) | Vitamin K1 10 mg for minor bleeding | Oral vitamin K1 5-20 mg/d | ||
| For severe bleedings: 4-factor PCC 20-30 U/kg or virus-inactivated plasma15-25 mL/kg | In poor responders, consider parenteral vitamin K1 5-20 mg/week | ||||
Data on primary prophylaxis are experience of single centers and are not based on specific clinical trials. Grade of evidence is 2B (strength of recommendations are made if clinicians believe that benefits and risks and burdens are finely balanced and quality of evidence is low: further research is very likely to have an important impact) except for FVII and FXI grade 2C (quality of evidence is moderate; further research is likely to have an important impact).
Prophylaxis needs to be personalized based on patient’s clinical and family history.
Prophylaxis is highly recommended in severe patients.