PB1180 - The ex vivo effects of varying factor VIII concentration on clot formation and structure in Haemophilia A patients

Tuesday, July 12, 2022

6:30 PM – 7:30 PM

Location: Exhibition

Presentation Format: In-Person

Presenting Author(s)

Chanel G. Morris, MSC

University of Pretoria
Johannesburg, Gauteng, South Africa

Co-Author(s)

JB

Janette Bester

Senior Lecturer
University of Pretoria
Tshwane, Gauteng, South Africa
JP

Johan Potgieter

Head of Department
University of Pretoria
Tshwane, Gauteng, South Africa

Background: Haemophilia A (HA) is an X-linked inherited bleeding disorder, caused by a deficiency of coagulation factor VIII (FVIII). Patients are not able to produce a stable fibrin clot in the propagation phase as they do not generate sufficient thrombin on platelets. The mainstay of treatment for HA in South Africa remains replacement therapy with standard half-life FVIII clotting factor concentrate (CFC).

Aims: The study aims to examine the kinetics of blood clot formation and clot architecture at varying concentrations of FVIII in adult patients with moderate to severe HA

Methods: Whole blood of 20 HA patients with native FVIII deficient levels, and with ex vivo addition of factor VIII CFC to 10-15 IU/dL and to 30-35 IU/dL were examined using scanning electron microscopy and thromboelastography® and compared to whole blood from 10 healthy volunteers. The 10-15 IU/dL factor VIII target level was chosen as equivalent for emicizumab 50 µg/mL concentration and the presumptive level at which all bleeds were prevented in patients on prophylaxis.

Results: Scanning electron microscopy revealed distinct differences between the comparative groups. Haemophilia patients have disorganised fibrin networks with loose fibers and crosslinking. The fibrin network improved with an increase in factor VIII concentration. Blood plasma spiked to a 10-15 IU/dL factor VIII concentration, showed improvements in fibrin concentration and organisation of the fibrin network. Blood plasma spiked to a 30-35 IU/dL FVIII concentration showed an organised, stable fibrin network, comparable with the control group. Thromboelastography® showed prolonged clot formation with decreased clot strength in HA patients. When spiked with FVIII concentrate, the overall clot profile improved. While the quality of the clot improved at 30-35 IU/dL FVIII concentration, the only parameters that normalised were the R-time and alpha angles.

Conclusion(s): FVIII concentrations of 10-15 IU/dL improved the quality of the clot, which was further enhanced by increases to 30-35 IU/dL.