Contributions
Abstract: PB1462
Type: Publication Only
Session title: Bleeding disorders (congenital and acquired)
Background
In mild hemophilia A (HA) (F8: C> 5%), Desmopressin (DDAVP) is the 1st therapeutic option. When DDAVP fails (40-50%) FVIII Concentrates (CF8) are of choice with the risk of development of “inhibitors” against F8. Previously, the incidence of inhibitors in non-severe (NS) HA was estimated between 3% and 13%. Recently, certain F8 genotypes eas associated with higher rates of inhibitors (even for some the incidence close to that of severe HA). On the other hand, there are limited data on the optimal therapeutic approach to eradicate inhibitors in these patients
Aims
To report the incidence of inhibitors -as well as their management- in a population of patients with mild HA, attended in a 3rd level center in the last year (2020/1 /1- 2020/31/12) in relation to surgical procedures
Methods
15 Surgical procedures performed on 10 patients with mild HA (F8: C> 5%), all on demand treatment, and the replacement treatments were recorded. The interventions were 5 tooth extractions (2 multiple), 3 major surgeries, 3 minor surgeries and 4 minor procedures. Only 2 patients had a genetic study. The age, type of surgery, number of previous days of exposure (ED) and duration of treatment are recorded (Table 1).The inhibitor is dislodged 15 days and 2 months after the end of treatment.
Results
Two patients (40% of those who received CF8) developed an inhibitor antiF8; In both cases, it was detected in the 2nd control: patient 4 presented it with maximum titer of 2.56 uBT (N <0.6) and patient 7 reached 12.8 uBT, both type 1 kinetics. Both patients lost response to DDAVP. In patient 4, a “watch and wait” strategy was chosen, with progressive clearance until negative titer at day (d) + 57, without bleeding symptons. For patient 7, an immunosuppression (IS) strategy was made (Prednisone 1 mg / Kg / day (5 weeks) and descent to suspension + AntiCD20 375 mg / m2 / weekly, 4 weeks) with progressive decrease in inhibitor titer (1st negative control to d + 51); suffered a retroperitoneal hematoma (treatment: Novoseven®, 7 d). At d+162 we certified the success of IS (Response to DDAVP, Inhibitor <0.4 uBT, F8: C 17%, Pharmacokinetic F8 (35 IU/Kg pdF8): recovery 2.25 and terminal half-life 8.75 h-WAPPS Hemo®)
Conclusion
The incidence of inhibitors in NS-HA increases progressively with the cumulative number of ED to CF8, apparently without reaching a plateau, unlike that observed in severe HA with estimated risk after 20, 50 and 100 SD at 3.5% (95% confidence interval (CI) 2.1–4.9), 6.7% (CI 4.5–8.9 ) and 13.3% (CI 9.6–17.0), respectively. The development of inhibitors in NS- HA is a relevant problem being important to establish strategies to reduce the risk: knowing the responsible mutation in order to estimate the risk, maximizing the use of DDAVP and antifibrinolytics,.. among other measures. Furthermore, it is imperative to know more about the treatment regimens aimed at the eradication of inhibitors in NS-HA. IS seems a valid option, as reported by Kempton in a cohort of 32 patients. The “wait and watch” strategy allows confirming the clearance of the inhibitor, but the confirmation of eradication is also influenced by clinical behavior, since, as we are reminded in the INSIGHT Study, many patients are not re-exposed to CF8 . Therefore, it is necessary to deepen the registration and modeling of simple and effective therapeutic strategies to manage this problem, in addition to the invaluable contribution of Emicizumab for the management of these patients, specially in cases in which suppression success is not achieved.
Keyword(s):
Abstract: PB1462
Type: Publication Only
Session title: Bleeding disorders (congenital and acquired)
Background
In mild hemophilia A (HA) (F8: C> 5%), Desmopressin (DDAVP) is the 1st therapeutic option. When DDAVP fails (40-50%) FVIII Concentrates (CF8) are of choice with the risk of development of “inhibitors” against F8. Previously, the incidence of inhibitors in non-severe (NS) HA was estimated between 3% and 13%. Recently, certain F8 genotypes eas associated with higher rates of inhibitors (even for some the incidence close to that of severe HA). On the other hand, there are limited data on the optimal therapeutic approach to eradicate inhibitors in these patients
Aims
To report the incidence of inhibitors -as well as their management- in a population of patients with mild HA, attended in a 3rd level center in the last year (2020/1 /1- 2020/31/12) in relation to surgical procedures
Methods
15 Surgical procedures performed on 10 patients with mild HA (F8: C> 5%), all on demand treatment, and the replacement treatments were recorded. The interventions were 5 tooth extractions (2 multiple), 3 major surgeries, 3 minor surgeries and 4 minor procedures. Only 2 patients had a genetic study. The age, type of surgery, number of previous days of exposure (ED) and duration of treatment are recorded (Table 1).The inhibitor is dislodged 15 days and 2 months after the end of treatment.
Results
Two patients (40% of those who received CF8) developed an inhibitor antiF8; In both cases, it was detected in the 2nd control: patient 4 presented it with maximum titer of 2.56 uBT (N <0.6) and patient 7 reached 12.8 uBT, both type 1 kinetics. Both patients lost response to DDAVP. In patient 4, a “watch and wait” strategy was chosen, with progressive clearance until negative titer at day (d) + 57, without bleeding symptons. For patient 7, an immunosuppression (IS) strategy was made (Prednisone 1 mg / Kg / day (5 weeks) and descent to suspension + AntiCD20 375 mg / m2 / weekly, 4 weeks) with progressive decrease in inhibitor titer (1st negative control to d + 51); suffered a retroperitoneal hematoma (treatment: Novoseven®, 7 d). At d+162 we certified the success of IS (Response to DDAVP, Inhibitor <0.4 uBT, F8: C 17%, Pharmacokinetic F8 (35 IU/Kg pdF8): recovery 2.25 and terminal half-life 8.75 h-WAPPS Hemo®)
Conclusion
The incidence of inhibitors in NS-HA increases progressively with the cumulative number of ED to CF8, apparently without reaching a plateau, unlike that observed in severe HA with estimated risk after 20, 50 and 100 SD at 3.5% (95% confidence interval (CI) 2.1–4.9), 6.7% (CI 4.5–8.9 ) and 13.3% (CI 9.6–17.0), respectively. The development of inhibitors in NS- HA is a relevant problem being important to establish strategies to reduce the risk: knowing the responsible mutation in order to estimate the risk, maximizing the use of DDAVP and antifibrinolytics,.. among other measures. Furthermore, it is imperative to know more about the treatment regimens aimed at the eradication of inhibitors in NS-HA. IS seems a valid option, as reported by Kempton in a cohort of 32 patients. The “wait and watch” strategy allows confirming the clearance of the inhibitor, but the confirmation of eradication is also influenced by clinical behavior, since, as we are reminded in the INSIGHT Study, many patients are not re-exposed to CF8 . Therefore, it is necessary to deepen the registration and modeling of simple and effective therapeutic strategies to manage this problem, in addition to the invaluable contribution of Emicizumab for the management of these patients, specially in cases in which suppression success is not achieved.
Keyword(s):