PMID- 29892605 OWN - NLM STAT- PubMed-not-MEDLINE LR - 20231105 IS - 2297-1769 (Print) IS - 2297-1769 (Electronic) IS - 2297-1769 (Linking) VI - 5 DP - 2018 TI - Subcutaneous Administration of Low-Molecular-Weight Heparin to Horses Inhibits Ex Vivo Equine Herpesvirus Type 1-Induced Platelet Activation. PG - 106 LID - 10.3389/fvets.2018.00106 [doi] LID - 106 AB - Equine herpesvirus type 1 (EHV-1) is a major cause of infectious respiratory disease, abortion and neurologic disease. Thrombosis in placental and spinal vessels and subsequent ischemic injury in EHV-1-infected horses manifests clinically as abortion and myeloencephalopathy. We have previously shown that addition of heparin anticoagulants to equine platelet-rich plasma (PRP) can abolish ex vivo EHV-1-induced platelet activation. The goal of this study was to test whether platelets isolated from horses treated with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) were resistant to ex vivo EHV-1-induced activation. In a masked, block-randomized placebo-controlled cross-over trial, 9 healthy adult horses received 4 subcutaneous injections at q. 12 h intervals of one of the following treatments: UFH (100 U/kg loading dose, 3 maintenance doses of 80 U/kg), 2 doses of LMWH (enoxaparin) 80 U/kg 24 h apart with saline at the intervening 12 h intervals, or 4 doses of saline. Blood samples were collected before treatment and after 36 h, 40 h (4 h after the last injection) and 60 h (24 h after the last injection). Two strains of EHV-1, Ab4 and RacL11, were added to PRP ex vivo and platelet membrane expression of P selectin was measured as a marker of platelet activation. Drug concentrations were monitored in a Factor Xa inhibition (anti-Xa) bioassay. We found that LMWH, but not UFH, inhibited platelet activation induced by low concentrations (1 x 10(6) plaque forming units/mL) of both EHV-1 strains at 40 h. At this time point, all horses had anti-Xa activities above 0.1 U/ml (range 0.15-0.48 U/ml) with LMWH, but not UFH. By 60 h, a platelet inhibitory effect was no longer detected and anti-Xa activity had decreased (range 0.03 to 0.07 U/ml) in LMWH-treated horses. Neither heparin inhibited platelet activation induced by high concentrations (5 x 10(6) plaque forming units/mL) of the RacL11 strain. We found substantial between horse variability in EHV-1-induced platelet activation at baseline and after treatment. Minor injection site reactions developed in horses given either heparin. These results suggest that LMWH therapy may prevent thrombotic sequelae of EHV-1, however further evaluation of dosage regimens is required. FAU - Stokol, Tracy AU - Stokol T AD - Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States. FAU - Serpa, Priscila B S AU - Serpa PBS AD - Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States. FAU - Brooks, Marjory B AU - Brooks MB AD - Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States. FAU - Divers, Thomas AU - Divers T AD - Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States. FAU - Ness, Sally AU - Ness S AD - Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States. LA - eng PT - Journal Article DEP - 20180528 PL - Switzerland TA - Front Vet Sci JT - Frontiers in veterinary science JID - 101666658 PMC - PMC5985713 OTO - NOTNLM OT - EHV-1 OT - P selectin OT - heparin OT - thrombin generation OT - unfractionated heparin EDAT- 2018/06/13 06:00 MHDA- 2018/06/13 06:01 PMCR- 2018/01/01 CRDT- 2018/06/13 06:00 PHST- 2017/12/25 00:00 [received] PHST- 2018/04/30 00:00 [accepted] PHST- 2018/06/13 06:00 [entrez] PHST- 2018/06/13 06:00 [pubmed] PHST- 2018/06/13 06:01 [medline] PHST- 2018/01/01 00:00 [pmc-release] AID - 345291 [pii] AID - 10.3389/fvets.2018.00106 [doi] PST - epublish SO - Front Vet Sci. 2018 May 28;5:106. doi: 10.3389/fvets.2018.00106. eCollection 2018.