| Autor: |
Bernardo Á; Department of Hematology, Central University Hospital of Asturias (HUCA), 33011 Oviedo, Spain.; Platelet Research Lab, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain., Caro A; Department of Hematology, Central University Hospital of Asturias (HUCA), 33011 Oviedo, Spain.; Platelet Research Lab, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain., Martínez-Carballeira D; Department of Hematology, Central University Hospital of Asturias (HUCA), 33011 Oviedo, Spain.; Platelet Research Lab, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain., Corte JR; Department of Hematology, Central University Hospital of Asturias (HUCA), 33011 Oviedo, Spain., Vázquez S; Department of Hematology, Central University Hospital of Asturias (HUCA), 33011 Oviedo, Spain., Palomo-Antequera C; Department of Internal Medicine, Central University Hospital of Asturias (HUCA), 33011 Oviedo, Spain.; Bone Metabolism, Vascular Metabolism and Chronic Inflammatory Diseases Group, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain., Andreu A; Department of Pharmacology, University of Navarra, 31008 Pamplona, Spain., Fernández-Pardo Á; Hemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), 46026 Valencia, Spain., Oto J; Hemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), 46026 Valencia, Spain., Gutiérrez L; Platelet Research Lab, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain.; Department of Medicine, University of Oviedo, 33006 Oviedo, Spain., Soto I; Department of Hematology, Central University Hospital of Asturias (HUCA), 33011 Oviedo, Spain.; Platelet Research Lab, Instituto de Investigación Sanitaria del Principado de Asturias (ISPA), 33011 Oviedo, Spain., Medina P; Hemostasis, Thrombosis, Arteriosclerosis and Vascular Biology Research Group, Medical Research Institute Hospital La Fe (IIS La Fe), 46026 Valencia, Spain. |
| Abstrakt: |
Hemophilia A (HA) is a rare bleeding disorder caused by factor VIII (FVIII) deficiency due to various genetic mutations in the F8 gene. The disease severity inversely correlates with the plasma levels of functional FVIII. The treatment of HA patients is based on FVIII replacement therapy, either following a prophylactic or on-demand regime, depending on the severity of the disease at diagnosis and the patient's clinical manifestations. The hemorrhagic manifestations are widely variable amongst HA patients, who may require monitoring and treatment re-adjustment to minimize bleeding symptoms. Notably, laboratory monitoring of the FVIII activity is difficult due to a lack of sensitivity to various FVIII-related molecules, including non-factor replacement therapies. Hence, patient management is determined mainly based on clinical manifestations and patient-clinician history. Our goal was to validate the ST Genesia ® automated thrombin generation analyzer to quantify the relative hemostatic status in HA patients. We recruited a cohort of HA patients from the Principality of Asturias (Spain), following treatment and at a stable non-bleeding phase. The entire cohort (57 patients) had been comprehensively studied at diagnosis, including FVIII and VWF activity assays and F8 genetic screening, and then clinically monitored until the Thrombin Generation Test (TGT) was performed. All patients were recruited prior to treatment administration, at the maximum time-window following the previous dose. Interestingly, the severe/moderate patients had a similar TGT compared to the mild patients, reflecting the non-bleeding phase of our patient cohort, regardless of the initial diagnosis (i.e., the severity of the disease), treatment regime, and FVIII activity measured at the time of the TGT. Thus, TGT parameters, especially the peak height (Peak), may reflect the actual hemostatic status of a patient more accurately compared to FVIII activity assays, which may be compromised by non-factor replacement therapies. Furthermore, our data supports the utilization of combined TGT variables, together with the severity of patient symptoms, along with the F8 mutation type to augment the prognostic capacity of TGT. The results from this observational study suggest that TGT parameters measured with ST Genesia ® may represent a suitable tool to monitor the hemostatic status of patients requiring a closer follow-up and a tailored therapeutic adjustment, including other hemophilia subtypes or bleeding disorders. |
