An In Vitro Study Simulating Prophylactic Anticoagulation in Haemophilia A and B

Patients with haemophilia A (HA) and haemophilia B (HB) are at increased bleeding risk. A recent guidance document suggests considering pharmacological thromboprophylaxis on a case-by-case basis in these patients undergoing surgery at high-risk of venous thromboembolism. This study aimed to assess the effect of prophylactic doses of three anticoagulants (enoxaparin, rivaroxaban and unfractionated heparin [UFH]) on in vitro models of HA and HB.

FVIII- and FIX-deficient plasma were spiked with FVIII and FIX concentrates to mimic severe, moderate and mild HA (FVIII concentrations < 1%, 1.2% and 17.0%, respectively) and HB (FIX concentrations < 1%, 3.9% and 22.9%, respectively). Each pool was spiked with enoxaparin (concentration range 0.3-0.4 IU/mL), rivaroxaban (50-100 ng/mL) and UFH (0.2-0.3 IU/mL). The following assays were performed: prothrombin time (PT), activated partial thromboplastin time (APTT) and thrombin generation (using the semi-automated fluorogenic calibrated automated thrombin generation assay [CAT]).

The PT was not significantly affected by the anticoagulants. A significant prolongation of the APTT was observed; UFH showed the greatest increase, followed by rivaroxaban and enoxaparin. All anticoagulants impacted on the CAT curves. UFH showed the greatest reduction of the endogenous thrombin potential; rivaroxaban showed the greatest increase of lag time and time to peak. Peak thrombin and velocity index were similarly reduced by rivaroxaban and UFH, whereas enoxaparin was associated with smaller changes in all parameters.

A significant effect of three prophylactic anticoagulants was observed in factor-deficient plasmas. This study provides further insight into this topic and supports the concept of an individualised approach to haemophilia patients. Trial Registration: The authors have confirmed clinical trial registration is not needed for this submission.