Background: Emicizumab is a bispecific antibody that bridges factor IXa and factor X to restore hemostasis in patients with hemophilia A (HA). Its efficacy and safety have been proven in multicenter trials. However, real world data regarding its use in very young children are currently lacking. Ancillary test results for monitoring emicizumab's hemostatic effect and their clinical correlations are scarce.
Methods:Children with HA and inhibitors treated by emicizumab were prospectively followed at our center. Laboratory follow-up included rotational thromboelastometry (ROTEM) and thrombin generation (TG), prior to and during treatment.Results: Eleven children whose median age was 26 months were treated by emicizumab and followed for a median of 36 weeks. During follow-up, none experienced hemarthrosis or any other spontaneous bleeds. For 7/11 patients, emicizumab prophylaxis was sufficient to maintain hemostasis without additional supplemental therapy. Only 4/11 patients were occasionally treated with recombinant activated FVII for trauma. Two minor surgeries were safely performed without supplemental therapy while another procedure was complicated by major bleeding. TG parameters improved for all patients, correlating with their clinical status. Interestingly, the lowest TG values were obtained for patients experiencing bleeding episodes, while ROTEM parameters in all patients were close to the normal range.
Conclusions:This study confirms the safety and efficacy of emicizumab in reducing bleeds in young children with HA with inhibitors, including infants. However, surgeries warrant caution as emicizumab prophylaxis may not be sufficient for some procedures. TG may more accurately reflect the hemostasis state than ROTEM in pediatric patients treated with emicizumab.
K E Y W O R D Semicizumab, hemophilia A, inhibitors, ROTEM, thrombin generation
Leukocyte adhesion deficiency type 1 (LAD-1) is an autosomal recessive primary immunodeficiency, hallmarked by defective polymorphonuclear transmigration. It is caused by mutations in the gene encoding CD18, which interfere with the CD18/CD11 heterodimerization and expression on leukocyte cell surface. LAD-1 diagnosis rests primarily on the measurement of CD18 expression. However, CD18 measurement entails its pitfalls. Here we present a cohort of ten LAD patients and a review of the relevant literature illustrating the difficulties in sole reliance on CD18 measurement for initial diagnosis. These include normal range expression in some mutations, great variability between patients with the same mutation and subjective interpretation of results. We think there is a need for additional markers as part of the initial LAD diagnostic algorithm. We suggest CD11a expression, which was near absent in all patients in our cohort. The dual use of CD18 and CD11a can increase testing sensitivity and prevent delayed diagnosis of LAD-1.
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