Gara-Boivin Carolyn, de Castillo Jérôme R E, Dunn Marilyn E, Bédard Christian
Department of Pathology and Microbiology, Faculté de Médecine Vétérinaire, Université de Montréal, Saint-Hyacinthe, QC, Canada.
GREPAQ - Department of Veterinary Biomedicine, Faculté de Médecine Vétérinaire, Université de Montréal, Saint-Hyacinthe, QC, Canada.
Vet Clin Pathol. 2017 Jun;46(2):269-277. doi: 10.1111/vcp.12489. Epub 2017 Apr 21.
Dalteparin is used to prevent thrombotic complications in dogs. Measurement of anti-factor Xa (anti-FXa) activity is currently used for monitoring therapy, but remains a nonfunctional test. The calibrated automated thrombogram (CAT) could be a suitable approach for functional monitoring.
We hypothesized that the CAT will detect decreased endogenous thrombin potential (ETP) in healthy dogs receiving dalteparin.
Twenty-four healthy adult Beagles were randomly allocated to 4 equal groups. A single subcutaneous (SC) dose of 50 U/kg, 100 U/kg, or 150 U/kg of dalteparin was given. Platelet-poor plasma (PPP) was collected over a 24-hour period and evaluated by thrombin generation (TG) via CAT, anti-FXa activity, and APTT. Analysis was performed with a repeated-measures general linear mixed model, and the treated groups were compared to a placebo group.
Time, dose, and time-dose interaction significantly affected ETP (P < .0001 for all effects), peak (P < .0001 for all effects), rate index (P < .0006 for all effects), and anti-FXa activity (P < .0001 for all effects). No significant time trend was detected in the control group. Dogs receiving the 100 U/kg dalteparin SC injection showed the most homogeneous response of ETP inhibition among treated groups. The % inhibition of ETP from baseline increased nonlinearly as a function of anti-FXa activity (r = .8186).
The CAT assay can be employed to measure the effects of dalteparin at different doses in healthy dogs, showing sensitivity to time- and dose-dependent changes in ETP and other TG variables. Further investigation of the CAT as a tool for monitoring low molecular weight heparin therapy in dogs is warranted.
达肝素用于预防犬的血栓形成并发症。目前，抗Xa因子（抗FXa）活性测定用于监测治疗，但仍是一项无效检测。校准自动血栓图（CAT）可能是一种合适的功能监测方法。
我们假设CAT将检测到接受达肝素的健康犬内源性凝血酶潜力（ETP）降低。
24只健康成年比格犬随机分为4组，每组数量相等。皮下（SC）注射单一剂量50 U/kg、100 U/kg或150 U/kg的达肝素。在24小时内收集乏血小板血浆（PPP），并通过CAT进行凝血酶生成（TG）评估、抗FXa活性和活化部分凝血活酶时间（APTT）测定。采用重复测量一般线性混合模型进行分析，并将治疗组与安慰剂组进行比较。
时间、剂量和时间-剂量相互作用对ETP（所有效应P <.0001）、峰值（所有效应P <.0001）、速率指数（所有效应P <.0006）和抗FXa活性（所有效应P <.0001）有显著影响。对照组未检测到明显的时间趋势。接受100 U/kg达肝素SC注射的犬在治疗组中ETP抑制反应最为一致。ETP相对于基线的抑制百分比随抗FXa活性呈非线性增加（r =.8186）。
CAT检测可用于测量不同剂量达肝素对健康犬的影响，显示出对ETP和其他TG变量的时间和剂量依赖性变化的敏感性。有必要进一步研究将CAT作为监测犬低分子量肝素治疗的工具。
