Treatment and Prevention of Bleeds in Haemophilia Patients with Inhibitors to Factor VIII/IX
Abstract
:1. Introduction
2. Treatment of Acute Bleeding
3. Monitoring Therapeutic Efficacy of Haemostatic Treatment
4. Bleeding Prevention
5. Unresolved Issues and Unmet Needs
6. Concluding Remarks
Author Contributions
Conflicts of Interest
References
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Bypassing Agent | Activated Prothrombin Complex Concentrate (aPCC) | Recombinant Activated Factor VII (rFVIIa) |
---|---|---|
Source | Pooled human plasma | Recombinant coagulation FVIIa produced in baby hamster kidney (BHK) cells by recombinant DNA technology (Eptacog alfa) |
Therapeutic indications | Treatment of spontaneous bleeding and cover of surgical interventions in: haemophilia A patients with inhibitors to FVIII patients with acquired inhibitors to FVIII prophylaxis in haemophilia A patients with HR inhibitors and frequent joint bleeding. | Treatment of bleeding episodes and cover of surgical interventions in:
|
Recommended regimen(s) | 50 to 100 U*/kg Dose interval: 6–12 h. A single dose of 100 U/kg and a daily dose of 200 U/kg should not be exceeded unless the severity of bleeding warrants and justifies the use of higher doses. For prevention of bleeding episodes during prophylaxis, 70 to 100 U/kg every other day with dose adjusted based on the patient’s clinical response. | Initial dose: 90 μg/kg Dose interval: 2–3 h until haemostasis is achieved. If continued therapy is needed, the dose interval can be increased successively to every 4, 6, 8 or 12 h for as long as treatment is judged as being indicated. For mild to moderate bleeding episodes (including home therapy) two dosing regimens can be recommended:
|
Storage requirements | Room temperature (up to 25 °C) for up to 2 years. | Room temperature (up to 25 °C) for up to 2 years. |
Volume | Diluent volume: 20 mL. | Diluent volume: 1.1 mL (1 mg); 2.1 mL (2 mg); 5.2 mL (5 mg). |
Time of administration | The rate of intravenous administration should ensure the comfort of the patient and should not exceed a maximum of 2 U/kg per minute. | Intravenous bolus injection over 2–5 min |
Half-life in plasma | Varying half-lives for the single components (FII, FIX, FX, FVIIa) | 2.3 h (range 1.7–2.7) |
Inhibitor anamnesis | Possible in about 20%–30% of patients, since FVIII coagulant antigen (FVIII C:Ag) is present in a concentration of up to 0.1 U/1 U of aPCC. Upon continued administration, inhibitors may decrease over time. | No |
Association with antifibrinolytic agents | Systemic antifibrinolytics should be administered at least 6 h apart. | Commonly used. |
Laboratory monitoring | Not standardised | Not standardised |
Thrombotic risk | Yes | Yes |
Bypassing Agent | rFVIIa | aPCC | ||
---|---|---|---|---|
Study | Konkle et al. 2007 [76] | Lessinger et al. 2011 [77] PRO-FEIBA | Antunes et al. 2014 [78] PROOF | |
Design | Double-blind, parallel group trial | Open-label, cross-over trial (intra-individual comparison) | Open-label, two arm, parallel trial (inter-individual comparison) | |
Patients, n | 22 | 26 | 36 | |
Treatment | 90 μg/kg/day vs. 270 μg/kg/day | 85 ± 15 U/kg three times per week vs. on-demand treatment | 85 ± 15 U/kg each other day (n = 17) vs. on-demand (n = 19) | |
Follow-up | 3 months (vs. 3 months pre-study and 3 months post-prophylaxis) | 6 months in each treatment regimen (3 months wash-out) | 12 months | |
Age, years (range) | 15.7 (5.1–56.5) | 28.7 (2.8–62.8) | 23.5 (7–56) | |
Bleeding rate (as inclusion criterion) | ≥12 in 3 months | ≥6 in 6 months | ≥12 in 12 months | |
90 μg/kg/day | 270 μg/kg/day | |||
Mean bleeding rate on demand | 5.6 * | 5.3 * | 13.1 ^ | 28.7 # |
Bleeding rate on prophylaxis | 3.0 * | 2.2 * | 5.0 ^ | 7.9 # |
Reduction (%) on prophylaxis | 45% | 59% | 62% | 72.5% |
Reduction (%) of target joint bleeds on prophylaxis | 43% | 61% | 72% | 75% |
Other findings | Benefits extended during the 3 months after prophylaxis | 62% good responders (bleeding rate reduction >50%, overall 84%). In 23% 0 bleeds | Lower development of new target joints on prophylaxis. 26% additional reduction of bleeding rate in the last 6 months vs. first 6 months |
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Rocino, A.; Franchini, M.; Coppola, A. Treatment and Prevention of Bleeds in Haemophilia Patients with Inhibitors to Factor VIII/IX. J. Clin. Med. 2017, 6, 46. https://doi.org/10.3390/jcm6040046
Rocino A, Franchini M, Coppola A. Treatment and Prevention of Bleeds in Haemophilia Patients with Inhibitors to Factor VIII/IX. Journal of Clinical Medicine. 2017; 6(4):46. https://doi.org/10.3390/jcm6040046
Chicago/Turabian StyleRocino, Angiola, Massimo Franchini, and Antonio Coppola. 2017. "Treatment and Prevention of Bleeds in Haemophilia Patients with Inhibitors to Factor VIII/IX" Journal of Clinical Medicine 6, no. 4: 46. https://doi.org/10.3390/jcm6040046