Potential Usefulness of D-Dimers Assay in Treated Patients with FVIII Deficiency to Detect a Prothrombotic State

Introduction

The D-dimer (DD) assay represents a major biological test for the diagnosis and monitoring of thrombotic conditions. DD testing is usually not performed as part of the routine laboratory management of patients with hemophilia (PWH). There is an increasing concern about the risk of thrombotic complications in PWH, whether related to age, the presence of cardiovascular risk factors, invasive thrombogenic procedures, over-correction of FVIII or FIX, or the administration of new therapeutic agents in particular rebalancing agents such as TFPI-inhibiting molecules or Fitusiran. Arterial and venous thrombotic events have indeed recently been reported in PWH treated with these agents. It is therefore important to have simple, easily accessible biological tests available to detect and monitor the development of any prothrombotic condition in PWH with these agents and at increased risk of thrombosis. Baseline DD concentrations in PWH have not been extensively studied yet.

Patients and methods

We prospectively measured over a 18 months period the DD level in all consecutive PWH with hemophilia A (PWHA) in routine clinics outside bleeding episode, invasive procedure or acute medical or surgical problems. A total of 65 adult PWHA (17-76 yr) with severe (58) to moderate (n=7) disease without inhibitor on replacement therapy with FVIII were included. CRP, fibrinogen, FVIII and VWF levels were also measured at time of DD assay.

Results

Thirty-three patients had not measurable DD (< 250 ng/ml), 15 had levels below 500 ng/ml, 10 had levels between 500-1000 ng/ml and 7 > 1000 ng/ml. Age>70 (3), smoking (7), arterial vascular disease (2), liver cancer (2) could explain DD > 500 ng/ml in 15/17 patients.

Conclusions

Most PWHA on replacement therapy with FVIII had low or unmeasurable DD levels. The reasons for high DD level in PWHA do not differ from the general population. In most PWAH, the DD assay could be a useful tool to detect prothrombotic state, potentially related to hemophilia therapies.