Elevated anti-human factor Xa activity in rabbit and rodent plasma: Implications for preclinical assessment of human factor X in animal models of hemostasis

Verhoef, Daniël; Tjalma, Annabelle V.R.; Cheung, Ka Lei; Reitsma, Pieter H.; Bos, Mettine H.A.

doi:10.1016/j.thromres.2020.11.023

Cited by 6 publications

(9 citation statements)

References 38 publications

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“…Consistent with previous reports [ 9 , 17 , 18 ], we observed that rat, mouse, and rabbit samples had smaller thrombin signals and lower TPT and clot times than human plasmas. TPH values obtained in sheep and goat plasma in our experiments and previously [ 9 , 15 ] were lower than in human plasma. Similar to others [ 18 ], we observed surprisingly low TG in guinea pigs.…”

Section: Discussionsupporting

confidence: 93%

“…Extrapolation of animal study results to humans is affected by interspecies differences in the scale and function of the blood circulatory system as well as physiology and biochemistry of the hemostasis system [ 7 , 8 , 9 , 10 ]. The practical usefulness of an animal model depends on the similarity of the recorded coagulation responses in animals to those in humans, and, therefore, justification is needed for choosing the most suitable species for a particular scientific study.…”

Section: Introductionmentioning

confidence: 99%

“…Moreover, there is a limited amount of studies that compare TG between various species [ 8 , 10 , 15 , 16 ]. When interspecies differences were evaluated [ 9 , 17 , 18 , 19 ], the authors suggested that while some animals might have TG similar to humans, others might not. This type of data can bring useful evidence forward for coagulation investigations that are species specific.…”

Section: Introductionmentioning

confidence: 99%

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Comparative Thrombin Generation in Animal Plasma: Sensitivity to Human Factor XIa and Tissue Factor

Liang,

Tarandovskiy,

Surov

et al. 2023

IJMS

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Preclinical evaluation of drugs in animals helps researchers to select potentially informative clinical laboratory markers for human trials. To assess the utility of animal thrombin generation (TG) assay, we studied the sensitivity of animal plasmas to triggers of TG, human Tissue Factor (TF), and Activated Factor XI (FXIa). Pooled human, mouse, rat, guinea pig, rabbit, bovine, sheep, and goat plasmas were used in this study. TF- or FXIa-triggered TG and clotting were measured via fluorescence and optical density, respectively. Thrombin peak height (TPH) and time (TPT), clot time (CT), and fibrin clot density (FCD) were all analyzed. The trigger low and high sensitivity borders (LSB and HSB) for each assay parameter were defined as TF and FXIa concentrations, providing 20 and 80% of the maximal parameter value, unless the baseline (no trigger) value exceeded 20% of the maximal, in which case, LSB was derived from 120% of baseline value. Normal human samples demonstrated lower TPH HSB than most of the animal samples for both TF and FXIa. Animal samples, except mice, demonstrated lower TPT LSB for FXIa versus humans. Most rodent and rabbit samples produced baseline TG in the absence of TG triggers that were consistent with the pre-activation of blood coagulation. FCD was not sensitive to both TF and FXIa in either of the plasmas. Animal plasmas have widely variable sensitivities to human TF and FXIa, which suggests that optimization of trigger concentration is required prior to test use, and this complicates the extrapolation of animal model results to humans.

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Section: Discussionsupporting

confidence: 93%

Section: Introductionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Comparative Thrombin Generation in Animal Plasma: Sensitivity to Human Factor XIa and Tissue Factor

Liang,

Tarandovskiy,

Surov

et al. 2023

IJMS

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“…Being a hemostatic agent, the influence of biomaterials on the blood coagulation system is important to the hemostatic effect and the biosafety of the materials. 28 Herein, the four parameters of coagulation, that is APTT, TT, PT and FIB, were determined in vitro to evaluate the ability of AMPCs to coagulate blood as well as their impact on the blood coagulation system of biont.…”

Section: In Vitro Blood Coagulation Testmentioning

confidence: 99%

Hemostatic effect and safety evaluation of the absorbable macroporous polysaccharides composite hemostatic material prepared by a green fabrication approach

Ren

Gong

et al. 2022

J Biomater Appl

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Carboxymethyl chitosan is widely used in the medical field such as wound healing and other medical fields. We previously fabricated the absorbable macroporous polysaccharides composite hemostatics (AMPCs) mainly composed of carboxymethyl chitosan which possess excellent hemostatic effect. To further elucidate the impact of CMCTs on the hemostatic effect and biosafety of AMPCs, carboxymethyl chitosan with different properties were used to prepare AMPCs. By comparing the physical and chemical properties, AMPCs performed high water absorption ability, especially Group 1 (swelling ratio reached 5792%), which facilitated the rapid formation of blood clots. It was confirmed by blood clotting index (BCI) and blood coagulation tests in vitro that Group 1 showed a slightly higher coagulation capacity than groups 2 and 3, which may be due to the positive charge on the surface of the cations in the salts attaches to the negative charge on the surface of the red blood cells, an electrostatic neutralization reaction occurs. The biosafety was a preliminary evaluation by implanted AMPCs into the back of Sprague-Dawley rats and the tissue was harvested after feeding for 28 days. The AMPCs exhibited good biosafety for whole blood and major organs during the degradation in vivo: during the degradation of AMPCs, excluding changes in some serum indicators, no tissue necrosis or inflammatory cell infiltration was observed in these organs, either by gross observation or histological analysis. These findings demonstrate that expecting to develop a highly functional and safe hemostatic agent based on Group 1 for rapid hemostasis applications in emergencies.

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“…Compared to large animals, the dilution of rabbit plasma can enhance the production of thrombin. 28 Although the anticoagulation effects of rabbit and human blood were not very similar, but more thrombin of rabbit blood can help us evaluate the effectiveness of heparin. Jane et al 29 have developed a suitable method to evaluate the clotting time of the same base material in rabbit whole blood.…”

Section: Anticoagulant Properties Of Heparinmentioning

confidence: 99%

A heparin-functionalized covered stent prepared by plasma technology

et al. 2021

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In this study, the surface of the covered stent was treated by plasma technology to introduce amino functional groups, and glutaraldehyde and heparin were successfully grafted to prepare a heparin-functionalized covered stent (HPLCS). The preparation parameters such as plasma treatment power, plasma treatment time, concentration of glutaraldehyde and heparin, and pH of heparin solution were studied in detail. The functionalized heparin covered stent can make the titer of heparin reach 1.23 ± 0.03 IU/cm2. In animal experiments, after implantation in pigs for 6 months, the titer of heparin can still reach 0.93 ± 0.05 IU/cm2. This work provides a good method for preparing heparin covered stent.

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Elevated anti-human factor Xa activity in rabbit and rodent plasma: Implications for preclinical assessment of human factor X in animal models of hemostasis

Cited by 6 publications

References 38 publications

Comparative Thrombin Generation in Animal Plasma: Sensitivity to Human Factor XIa and Tissue Factor

Comparative Thrombin Generation in Animal Plasma: Sensitivity to Human Factor XIa and Tissue Factor

Hemostatic effect and safety evaluation of the absorbable macroporous polysaccharides composite hemostatic material prepared by a green fabrication approach

A heparin-functionalized covered stent prepared by plasma technology

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