The Influence of Coagulation Factor Biosimilars in Shortening the Activated Partial Thromboplastin Time in Patients with Hemophilia a

Introduction: Classical hemophilia, also known as hemophilia A, is an X-linked, recessive hereditary hemorrhagic disorder resulting from a congenital deficit of factor VIII that manifests as protracted and excessive bleeding either spontaneously or secondary to trauma. It is the most common hereditary disorder of hemostasis and occurs in more than 400,000 males worldwide, many of whom remain undiagnosed in the developing world. The activated Partial Thromboplastin Time in these patients usually exhibit high and the Prothrombin Time remain within the normal range. Though the factor VIII is deficient in Hemophilia, the levels of factor VII also affected. There are several studies comparing different recombinant biosimilars of concentrated FVII and FVIII in hemophilia patients, but none of them have analyzed or compared their effect on PT, aPTT, and levels of FVII and FVIII. The aim of this study is to compare the effects of two biosimilars of recombinant FVII and FVIII in patients with hemophilia A on PT, aPTT, FVII, and FVIII values.

Methods: We have tested biosimilars of factor VIII and factor VII on 30 severe Hemophilia plasma samples. Plasma samples were prepared by centrifugation of 10 ml of blood sample at 3500 rpm for 10 minutes. The factor VIII biosimilars such as Kogenate FS, and NovoEight and factor VII biosimilars such as AryoSeven and NovoSeven were used for this study. The concentrations of aryoseven, novoseven, kogenate, and novoeight were added to each of the plasma samples at final concentrations of 1mcg/mL, 1mcg/mL, 1IU/mL, and 1IU/mL, respectively. In order to understand the ability of these biosimilars in shortening the aPTT, a mixing study was carried out on the plasma samples. Also, the values of PT and FVIII were also tested and compared with the original values i.e. before adding the biosimilars to the samples. All the samples were tested on a fully automated coagulation analyzer Cevron alpha.

Results: In comparison of all of the investigational drugs to the original values of PT, aPTT and FVIII, among-group comparison with post-hoc pairwise comparisons showed high statistically significant difference for aPTT, compared to the pre-treatment value (p<0.001). Significant reduction in aPTT was observed after adding Kogenate FS and NovoEight (Med 32.1 and 29.5 vs. 90.0, respectively) and AryoSeven and NovoSeven (Med 54.9 and 60.5 vs. 90.0, respectively). A significant increase in FVIII values was noted with addition of AryoSeven and NovoSeven (Med 6.5 and 3.9 vs. 1.0, respectively), and particularly with addition of Kogenate FS and NovoEight (Med 102.3 and 161.8 vs. 1.0, respectively). Negative correlation was observed between PT and FVII values after adding Kogenate FS (r=-0.103, p<0.001), aPTT and FVIII values after adding Kogenate FS (r=-0.898, p<0.001), aPTT and FVIII values after adding NovoEight (r=-0.865, p<0.001), as well as aPTT and FVIII values after adding AryoSeven (r=-0.647, p<0.001).

Conclusion: All the investigated drugs significantly shorten aPTT values and increase values of FVIII and FVII. In terms of efficacy, no difference exists between AryoSeven and NovoSeven, as well as between Kogenate FS and NovoEight only in altering PT.

No relevant conflicts of interest to declare.