Emicizumab treatment and monitoring in a paediatric cohort: real‐world data

Abstract

Real-world data on emicizumab use and monitoring in paediatric severe haemophilia A (HA) patients are scarce. We therefore sought to evaluate safety, efficacy, and laboratory monitoring of emicizumab prophylaxis in a cohort of 40 children with severe HA, including 22 non-inhibitor patients and nine infants younger than one year. Bleeding, trauma, adverse events, and surgeries were documented during a median follow-up of 45 weeks. Emicizumab levels, activated partial thromboplastin time (aPTT) values, and thrombin generation were measured before and during therapy. Twenty patients experienced zero bleeds. All bleeding was trauma-related, and bleeding risk was positively correlated with the length of emicizumab prophylaxis. Sixteen surgical interventions were performed in 12 patients, with no thrombotic complications or thrombotic microangiopathy. Prolonged aPTT values normalised after emicizumab initiation, correlating with an increase in emicizumab plasma levels. Elevation in the thrombin generation was observed following emicizumab prophylaxis, with lower values recorded in younger infants. Emicizumab prophylaxis was safe and well tolerated. As all bleedings were trauma-related, laboratory monitoring could not predict bleeding risk. Our results do not support routine thrombin generation monitoring in children treated by emicizumab, yet further studies are warranted in the context of surgical procedures.

Emicizumab prophylaxis in haemophilia patients older than 50 years with cardiovascular risk factors: Real‐world data

“…This is in contrast to our previously reported paediatric cohorts, where the length of emicizumab prophylaxis was associated with increased bleeding risk, as most bleeding episodes among children were trauma related. 23,24 The issue of whether, when and for whom emicizumab treatment should be monitored is controversial. 25 However, as our patient population was underrepresented within previous trials, we believed that their longitudinal laboratory monitoring is of special value.…”

Emicizumab in tolerized patients with hemophilia A with inhibitors: A single‐institution pediatric cohort assessing inhibitor status

“…Due to the mechanism of action of nonfactor therapies such as emicizumab, individuals on these therapies require infusions of FVIII or a bypassing agent (BPA) for bleeding or surgical intervention 5–9 . Thus, the presence of an inhibitor and one’s response to FVIII remains the primary determinant of whether FVIII or BPAs are administered in these settings.…”

Management of a High-Risk Surgery with Emicizumab and Factor VIII in a Child with a Severe Hemophilia A and Inhibitor

“…In pediatrics, only minor procedures were described. [4][5][6][11][12][13] Our case is so, to our knowledge, the first description of a major orthopaedic surgery managed with FVIII concentrates in a child with severe hemophilia A with inhibitor while receiving a prophylaxis with emicizumab. The choice we made of using rFVIII-Fc for bleeding prevention during and after the surgery was foremost driven by the presence of a low titer inhibitor.…”

“…2,3 Nonetheless, there are "real life" matters that need to be explored in this new era of managing hemophilia patients, such as surgery management under emicizumab, especially in children. [4][5][6] Here, we report the first case, to our knowledge, of major orthopedic surgery managed with factor VIII infusions in a child with inhibitor receiving emicizumab.…”