Profilaxis con CCPa en pacientes con hemofilia A con inhibidores de alta respuesta Una estrategia alternativa al estándar de tratamiento / Prophylaxis with activated prothrombin complex concentrate in patients with hemophilia A with high response inhibitors An alternative approach to standard treatment

Introducción: la complicación más grave de los pacientes con hemofilia es el desarrollo de anticuerpos inhibidores; hasta un 30% de los pacientes con hemofilia A severa los desarrollan. Para erradicarlos, la inducción de tolerancia inmune es el tratamiento de elección; cuando persisten, los tratamientos profilácticos con agentes de puente como el concentrado de complejo de protrombina activado CCPa (FEIBA®) o rFVIIa (Novoseven®) ofrecen una alternativa terapéutica para reducir lossangrados y la artropatía hemofílica. Para evaluar la eficacia de profilaxis con CCPa se compararon los sangrados antes y después de recibir profilaxis (11-12 meses) en ocho pacientes hemofílicos con inhibidores de alta respuesta. Material y métodos: se realizó un estudio multicéntrico, se incluyeron niños y adultos con diagnóstico de hemofilia A, con título de inhibidores altos, de cuatro centros de atención en dos ciudades. Se excluyeron pacientes con hemofilia adquirida. Resultados: seis pacientes tenían hemofilia A severa y dos moderada; 7/8 pacientes tenían artropatía hemofílica. La media de edad fue 19 años (rango 7-38) y la del título de inhibidor 80 UB (rango 15-1178). La dosis de CCPa fluctuó entre 40 y 75 U/kg, dos a tres veces por semana. Las tasas anuales de sangrado global y de hemartrosis previas a profilaxis fueron (8/año y 3.1/año)y después de profilaxis durante un periodo de 11-12 meses fueron (1.08/año y 1/año); se encontró una reducción de 86 y 68% respectivamente. No hubo eventos de trombosis. El cumplimiento del esquema de tratamiento con CCPa fue mayor a 80%. Conclusiones: este es el primer reporte de casos en Colombia sobre el uso de CCPa en pacientes hemofílicos con inhibidores del factor VIII de alta respuesta. Persisten interrogantes sobre la duración o ajustes al esquema de tratamiento. (Acta Med Colomb 2015; 40:288-293).

The most serious complication of hemophilia patients is the development of inhibitory antibodies; up to 30% of patients with severe hemophilia A develop them. To eradicate these antibodies, induction of immune tolerance is the treatment of choice; when they persist, prophylactic treatment with bridge agents as activated prothrombin complex concentrate aPCC (FEIBA®) or rFVIIa (Novoseven®) offer a therapeutic alternative for reducing bleeding and hemophilic arthropathy. To evaluate the efficacy of prophylaxis with aPCC, bleeds were compared before and after receiving prophylaxis (11-12 months) in 8 hemophilia patients with high response inhibitors. Material and methods: a multicenter study was conducted in children and adults with a diagnosis of hemophilia A with high titer inhibitors in 4 attention centers in two cities. Patients with acquired haemophilia were excluded. Results: six patients had severe hemophilia A and 2 moderate; 7/8 patients had hemophilic arthropathy. The mean age was 19 years (range 7-38) and mean inhibitor titer was 80 UB (range 151178). aPCC dose ranged from 40-75 U / kg, 2-3 times a week. The overall annual rates of bleeding and hemarthrosis pre-prophylaxis were (8 / year and 3.1 / yr) and after prophylaxis during a period of 11- 12 months were (1.08 / year and 1 / year); a reduction of 86% and 68% respectively was found. There were no thrombotic events. Compliance scheme of aPCC treatment was higher than 80%. Conclusions: this is the first case report in Colombia on the use of aPCC in haemophilia patients with high responding inhibitors to factor VIII. Questions remain about the length or adjustments to the treatment schedule. (Acta Med Colomb 2015; 40:88-293).

Laparoscopic Cholecystectomy in a Hemophiliac Patient with Factor VIII Inhibitor

Hemophilia A is a severe bleeding disorder resulting from the lack of functional blood coagulation factor VIII. Accordingly, operations on patients with hemophilia A, except in a few cases, are performed with the administration of factor VIII. However, in those hemophilia A patients administered factor VIII inhibitor, factor VIII replacement therapy is ineffective. The treatment of hemophilic patients with factor VIII inhibitor is undertaken to utilize the hemostatic capacity of the activated forms of FVII, FIX and FX contained within prothrombin complex concentrates, which are purposely manufactured to contain Factor Eight Inhibitor Bypassing Activity (FEIBA) during surgery. Further, in the last few years, a new product, recombinant activated FVII (FVIIa, Novo-VII), which is thought to ensure hemostasis by binding, directly or in complex with tissue factor, to negatively charged phospholipids on the surface of activated platelets, has been licensed. Recently, we experienced a GB stone, with acute cholecystitis, in a fifty year old hemophilia A man treated with factor VIII inhibitor. Under medication with FEIBA and Novo-VII, a laparoscopic cholecystectomy was performed. Here, this case is reported, with a review of the literature.