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Frontiers in veterinary science2018; 5; 106; doi: 10.3389/fvets.2018.00106

Subcutaneous Administration of Low-Molecular-Weight Heparin to Horses Inhibits Ex Vivo Equine Herpesvirus Type 1-Induced Platelet Activation.

Abstract: 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 × 106 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 × 106 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.
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Publication Date: 2018-05-28 PubMed ID: 29892605PubMed Central: PMC5985713DOI: 10.3389/fvets.2018.00106Google Scholar: Lookup
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Summary

This research summary has been generated with artificial intelligence and may contain errors and omissions. Refer to the original study to confirm details provided. Submit correction.

The research investigates the effect of low-molecular-weight heparin (LMWH) on horses infected with the equine herpesvirus type 1 (EHV-1), finding that administering LMWH can help inhibit the virus-induced activation of platelets, potentially preventing the serious thrombotic consequences of the infection. Further evaluations of dosage regimens are needed.

Study Design and Goals

  • The study aimed to determine whether platelets taken from horses treated with unfractionated heparin (UFH) or low-molecular-weight heparin (LMWH) become resistant to the activation induced by EHV-1.
  • Nine healthy adult horses were injected subcutaneously with either UFH, LMWH, or saline at regular intervals.
  • Heparin is an anticoagulant previously shown to inhibit EHV-1-induced platelet activation.

Testing and Measurements

  • Blood samples were collected before treatment and 36, 40, and 60 hours after treatment.
  • Two strains of EHV-1 were added to the equine platelet-rich plasma (PRP), and platelet activation was measured through the presence of P selectin in the platelet membrane.
  • The researchers also monitored drug concentrations through a Factor Xa inhibition assay (anti-Xa).

Results Summary

  • The study found that LMWH, but not UFH, was able to inhibit platelet activation caused by low concentrations of the EHV-1 strains at the 40-hour mark. At this time, higher than normal anti-Xa activities were also registered in the LMWH group but not UFH.
  • By 60 hours, the platelet inhibitory effect was no longer detected, and anti-Xa activity had also decreased in the LMWH group.
  • Neither type of heparin was able to inhibit platelet activation induced by high concentrations of one of the strains, RacL11.

Conclusion and Implications

  • The results demonstrate a significant variability between horses in terms of EHV-1-induced platelet activation both at baseline and post-treatment.
  • Minor reactions were noted at the injection site in horses given either type of heparin.
  • These findings suggest that LMWH might help prevent the thrombotic effects of EHV-1 infection and calls for more research to fine-tune the dosage regimen.

Cite This Article

APA
Stokol T, Serpa PBS, Brooks MB, Divers T, Ness S. (2018). Subcutaneous Administration of Low-Molecular-Weight Heparin to Horses Inhibits Ex Vivo Equine Herpesvirus Type 1-Induced Platelet Activation. Front Vet Sci, 5, 106. https://doi.org/10.3389/fvets.2018.00106

Publication

Frontiers in veterinary science
ISSN: 2297-1769
NlmUniqueID: 101666658
Country: Switzerland
Language: English
Volume: 5
Pages: 106

Researcher Affiliations

Stokol, Tracy
  • Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States.
Serpa, Priscila B S
  • Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States.
Brooks, Marjory B
  • Department of Population Medicine and Diagnostic Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States.
Divers, Thomas
  • Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States.
Ness, Sally
  • Department of Clinical Sciences, College of Veterinary Medicine, Cornell University, Ithaca, NY, United States.

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Citations

This article has been cited 3 times.
  1. Theuerkauf K, Obach-Schröck C, Staszyk C, Moritz A, Roscher KA. Activated platelets and platelet-leukocyte aggregates in the equine systemic inflammatory response syndrome. J Vet Diagn Invest 2022 May;34(3):448-457.
    doi: 10.1177/10406387221077969pubmed: 35168432google scholar: lookup
  2. Huang L, Chen G, Hu B, Liang S, Chu W, Chen L. Preventive application of low molecular weight heparin ameliorates peripherally inserted central catheter-related venous thrombosis. Int J Clin Exp Pathol 2020;13(3):403-410.
    pubmed: 32269677
  3. Serpa PBS, Brooks MB, Divers T, Ness S, Birschmann I, Papich MG, Stokol T. Pharmacokinetics and Pharmacodynamics of an Oral Formulation of Apixaban in Horses After Oral and Intravenous Administration. Front Vet Sci 2018;5:304.
    doi: 10.3389/fvets.2018.00304pubmed: 30564584google scholar: lookup
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