Management of Urgent Bleeding in Patients with Hemophilia A: Focus on the Use of Emicizumab.

Management of patients with hemophilia A (HA) requires the knowledge and experience of specialized health care professionals. However, these patients may need to be attended in emergencies, outside the referral hospital, where health care professionals do not know about hemophilia and/or new innovative treatments. This study aimed to develop a simple and practical algorithm that could be used in emergency situations by nonspecialized treaters in HA and bleeding with or without factor VIII (FVIII) inhibitors under emicizumab prophylaxis. A group of experts agreed on a simple algorithm, easy to operate, adapted from previous international guidelines, and based on their clinical experience. The proposed algorithm starts with identifying the patient, confirming the diagnosis of HA, prophylaxis with emicizumab, and/or use of other treatments. After stabilizing the patient and stratifying the bleeding risk, the patient is managed according to the presence/absence of FVIII inhibitors. Patients without FVIII inhibitors should receive FVIII concentrate. Dose and follow-up depend on bleeding localization and severity. Patients with FVIII inhibitors should preferably receive recombinant activated factor VII as bypass agent. A basic coagulation assay, FVIII assessment, and FVIII inhibitors detection assays are necessary in an emergency. However, these tests should be interpreted with caution and appropriately chosen, as emicizumab may alter the results. The management of patients with HA is challenging in emergency situations, especially if they are treated with new agents. Nonspecialized in coagulopathies health care professionals have limited understanding of the disease, highlighting the need for an algorithm to assist them in making informed decisions.

Catepsina K como biomarcador de afectación ósea en la enfermedad de Gaucher tipo 1 / Cathepsin K as a biomarker of bone involvement in type 1 Gaucher disease

Fundamento y objetivo: La enfermedad de Gaucher es un trastorno hereditario, que se origina como consecuencia del déficit de la actividad β-glucocerebrosidasa ácida, responsable de la degradación de glucosilceramida hasta ceramida y glucosa. Aunque el trastorno de base es fundamentalmente hematológico, el hueso es la segunda estructura más frecuentemente afectada. La catepsina K (CATK) es una enzima implicada en el proceso de remodelado óseo, habiéndose propuesto que la determinación de sus concentraciones séricas podría aportar información complementaria a la de otros biomarcadores. Pacientes y métodos: Se realizó un estudio en 20 controles sanos y 20 pacientes con enfermedad de Gaucher tipo 1, de las comunidades autónomas de Andalucía y Extremadura. Se determinaron como biomarcadores de remodelado óseo la bone alkaline phosphatase (B-ALP, «fosfatasa alcalina ósea»), el amino-terminal propeptide of procollagen type 1 (P1NP, «propéptido aminoterminal del procolágeno 1»), la β-Cross Laps, carboxy-terminal telopeptide of collagen type 1 (CTx, «fracción β del colágeno tipo 1») y CATK por técnicas de electroquimioluminiscencia y enzimoinmunoanálisis. Resultados: Existe un incremento en los niveles de CATK y las ratios CATK/P1NP y CATK/B-ALP en los pacientes con Gaucher tipo 1 respecto a la media obtenida en el grupo control. Por otro lado, considerando la existencia o no de manifestaciones óseas en el grupo de pacientes, la CATK y la ratio CATK/P1NP muestran niveles medios superiores en aquellos pacientes con daño óseo respecto a los que no lo presentan. Conclusiones: Aunque los estudios radiológicos constituyen el gold-standard para el seguimiento de enfermedad ósea en pacientes con enfermedad de Gaucher tipo 1, debe considerarse la utilidad de la CATK como posible indicador de daño óseo en estos pacientes. Asimismo, este parámetro puede utilizarse en la monitorización del tratamiento de la enfermedad ósea (AU)

Background and objective: Gaucher disease is an inherited disorder caused by deficit of acid β-glucocerebrosidase, responsible for the degradation of glucosylceramide to ceramide and glucose. Although the disorder is primarily hematologic, bone is the second most commonly affected structure. Cathepsin K (CATK) is an enzyme involved in bone remodelling process. It has been proposed that determination of its serum concentrations may provide additional information to other biomarkers. Patients and methods: The study included 20 control subjects and 20 Gaucher type 1 patients from Andalusia and Extremadura regions. We analyzed the biomarkers of bone remodelling: the bone alkaline phosphatase (B-ALP), the N-terminal propeptide of type 1 procollagen (P1NP), the β carboxyterminal telopeptide of type 1 collagen (CTx) and the CATK through electrochemiluminescence and immunoassay techniques. Results: There is an increase in levels of CATK, CATK/P1NP and CATK/B-ALP ratios in type 1 Gaucher patients compared to the control group. Considering the existence of skeletal manifestations in the patient group, the CATK and CATK/P1NP ratio showed higher levels in patients with bone damage compared to those without it. Conclusions: Although imaging studies are the gold standard for monitoring bone disease in type 1 Gaucher patients, the utility of CATK should be considered as a possible indicator of bone damage in these patients. Furthermore, this parameter can be used in the monitoring of the treatment of bone pathology (AU)

[Cathepsin K as a biomarker of bone involvement in type 1 Gaucher disease]. / Catepsina K como biomarcador de afectación ósea en la enfermedad de Gaucher tipo 1.

BACKGROUND AND OBJECTIVE: Gaucher disease is an inherited disorder caused by deficit of acid ß-glucocerebrosidase, responsible for the degradation of glucosylceramide to ceramide and glucose. Although the disorder is primarily hematologic, bone is the second most commonly affected structure. Cathepsin K (CATK) is an enzyme involved in bone remodelling process. It has been proposed that determination of its serum concentrations may provide additional information to other biomarkers. PATIENTS AND METHODS: The study included 20 control subjects and 20 Gaucher type 1 patients from Andalusia and Extremadura regions. We analyzed the biomarkers of bone remodelling: the bone alkaline phosphatase (B-ALP), the N-terminal propeptide of type 1 procollagen (P1NP), the ß carboxyterminal telopeptide of type 1 collagen (CTx) and the CATK through electrochemiluminescence and immunoassay techniques. RESULTS: There is an increase in levels of CATK, CATK/P1NP and CATK/B-ALP ratios in type 1 Gaucher patients compared to the control group. Considering the existence of skeletal manifestations in the patient group, the CATK and CATK/P1NP ratio showed higher levels in patients with bone damage compared to those without it. CONCLUSIONS: Although imaging studies are the gold standard for monitoring bone disease in type 1 Gaucher patients, the utility of CATK should be considered as a possible indicator of bone damage in these patients. Furthermore, this parameter can be used in the monitoring of the treatment of bone pathology.