Plasma D-Dimer Concentrations During (Experimental) EHV-1 Infections in the Horse

Equid Herpesvirus-1 (EHV-1) infections in horses can lead to Equid Herpesvirus Myeloencephalopathy (EHM), a neuropathological disorder caused by vasculitis and thrombosis of the CNS vasculature, followed by endothelial cell (EC) infection with EHV-1.1 D-dimers (DD) are cross-linked fibrin breakdown products, and plasma or CSF concentrations are increased following brain stroke (TIA) in humans. We investigated whether DD concentrations are increased in horses with EHM.

Material and methods
Horses or ponies (n= 28) from 3 EHV-1 infection experiments. Rectal temperatures and quantitative viremia data were collected together with plasma DD concentrations on the day prior to infection and during days 1 – 10 (or 12). Descriptive statistics and linear regression were used to demonstrate an association between fever, viremia and DD concentrations.

Results
Most animals developed biphasic fevers; and many were found viremic. There were 1/8 animals with EHM in study I, 6/10 in study III and 0/10 in study II. DD increases were common in many horses corresponding with the days of secondary fevers (OR 4.9 (CI 2.3 – 10.1; p=0.0013)) and also with viremic days (OR: 6.3, CI 3.4 – 11.8; p=0.0013).

Conclusions
DD concentration increases were strongly associated with viremia and likely caused by a viremia-associated cytokinemia. It needs to be determined which cytokines are circulating and whether certain cytokines increase the likelihood for EC infection with EHV-1.