Prolonged holding time and sampling protocol affects viscoelastic coagulation parameters as measured by the VCM-Vet™ using fresh equine native whole blood

Sandra Díaz Yucupicio Department of Veterinary Clinical Medicine, University of Illinois at Urbana Champaign, Urbana, IL

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Rebecca C. Bishop Department of Veterinary Clinical Medicine, University of Illinois at Urbana Champaign, Urbana, IL

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Meghan E. Fick Department of Veterinary Clinical Medicine, University of Illinois at Urbana Champaign, Urbana, IL

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Scott M. Austin Department of Veterinary Clinical Medicine, University of Illinois at Urbana Champaign, Urbana, IL

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Anne M. Barger Department of Veterinary Clinical Medicine, University of Illinois at Urbana Champaign, Urbana, IL

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Bailey Stolsworth Department of Veterinary Clinical Medicine, University of Illinois at Urbana Champaign, Urbana, IL

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Pamela A. Wilkins Department of Veterinary Clinical Medicine, University of Illinois at Urbana Champaign, Urbana, IL

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Abstract

OBJECTIVES

Determine the effect of sample holding time and single sample reuse on viscoelastic coagulation parameters when using fresh equine native whole blood.

ANIMALS

8 healthy adult horses from a university teaching herd.

PROCEDURES

Blood collected by direct jugular venipuncture (18 ga needle, 3 mL syringe) was held at 37 °C for 2, 4, 6, or 8 minutes according to 1 of 2 protocols. Syringes were gently inverted twice, a small amount of blood was expressed, testing cartridges were filled, and placed within the VCM-Vet™ device (Entegrion Inc). Protocol A: samples were processed from a single syringe. Protocol B: 4 syringes were drawn through a single needle. VCM-Vet™ measures assessed included clot time (CT), clot formation time (CFT), alpha angle (AA), amplitude at 10/20 minutes (A10/A20), maximal clot firmness (MCF), and lysis index at 30/45 minutes (LI30/LI45). Differences over time were examined using the Friedman test and post hoc Wilcoxon Rank Sum Test with Bonferroni correction, P ≤ .05.

RESULTS

Following Protocol A, there was a significant effect of holding time for CT (P = .02), CFT (P = .04), and AA (P = .05). CT and AA decreased over time, while CFT increased. Samples handled by Protocol B showed no significant difference over time for any of the VCM-Vet™ parameters.

CLINICAL RELEVANCE

Sample holding time and handling protocol impact VCM-Vet™ testing results of fresh equine native whole blood. Viscoelastic coagulation samples tested using the VCM-Vet™ may be held unagitated for up to 8 minutes after collection while warm, but should not be reused.

Abstract

OBJECTIVES

Determine the effect of sample holding time and single sample reuse on viscoelastic coagulation parameters when using fresh equine native whole blood.

ANIMALS

8 healthy adult horses from a university teaching herd.

PROCEDURES

Blood collected by direct jugular venipuncture (18 ga needle, 3 mL syringe) was held at 37 °C for 2, 4, 6, or 8 minutes according to 1 of 2 protocols. Syringes were gently inverted twice, a small amount of blood was expressed, testing cartridges were filled, and placed within the VCM-Vet™ device (Entegrion Inc). Protocol A: samples were processed from a single syringe. Protocol B: 4 syringes were drawn through a single needle. VCM-Vet™ measures assessed included clot time (CT), clot formation time (CFT), alpha angle (AA), amplitude at 10/20 minutes (A10/A20), maximal clot firmness (MCF), and lysis index at 30/45 minutes (LI30/LI45). Differences over time were examined using the Friedman test and post hoc Wilcoxon Rank Sum Test with Bonferroni correction, P ≤ .05.

RESULTS

Following Protocol A, there was a significant effect of holding time for CT (P = .02), CFT (P = .04), and AA (P = .05). CT and AA decreased over time, while CFT increased. Samples handled by Protocol B showed no significant difference over time for any of the VCM-Vet™ parameters.

CLINICAL RELEVANCE

Sample holding time and handling protocol impact VCM-Vet™ testing results of fresh equine native whole blood. Viscoelastic coagulation samples tested using the VCM-Vet™ may be held unagitated for up to 8 minutes after collection while warm, but should not be reused.

Hemostasis is a complex physiologic process that culminates in the production of a fibrin clot to prevent hemorrhage and thrombosis.14 Hemostatic changes are commonly observed in horses with sepsis, gastrointestinal disorders, or trauma.49 In these disorders, blood vessels, platelets, clotting, or fibrinolysis can be altered, resulting in pathological states of hypocoagulability or hypercoagulability.2,46,10 The complex interactions between blood cells, platelets, endothelial cells, and soluble plasma factors described in the cell-based model of coagulation highlight the potential limitations of standard plasma-based coagulation tests, such as prothrombin time (PT), partial thromboplastin time (PTT), fibrin(ogen) degradation products (FDP), or fibrinogen, which only provide information of specific components.13

Viscoelastic testing produces a global assessment of clot formation and dissolution in real-time and is a closer representation of in vivo hemostasis, reflecting the complex processes of coagulation.3,4,11 Viscoelastic testing has developed rapidly over the last 2 decades in the veterinary field.4,10,1214 This type of testing measures clot strength continuously through clot initiation, amplification, propagation, and lysis phases.3,15,16 Viscoelastic testing facilitates the identification of hypocoagulable and hypercoagulable states, thereby improving both the monitoring and management of patients with hemostatic disorders or comorbidities.3,10 Various viscoelastic tests have been validated in dogs, horses, and cats.4,10,12,13

The VCM-Vet™ (Entegrion Inc) is a point-of-care viscoelastic testing device that was developed for use in the field by the United States Armed Forces and adapted for veterinary use.1719 The VCM-Vet™ is a self-contained cartridge-based, reagent-free device that uses native whole blood, which limits artifactual changes due to operator, laboratory method, and sample handling errors compared with traditional viscoelastic modalities (ie, TEG [thromboelastography], ROTEM [rotational thromboelastography]). Changes in coagulation are graphically represented, suitable for visual interpretation, and are also provided as numerical and calculated parameters for analysis. The following values are provided: clotting time (CT), clot formation time (CFT), alpha angle (AA), amplitude at 10 and 20 minutes (A10/A20), maximum clot formation (MCF), and lysis index at 30 and 45 minutes (LI30/LI45).

It has previously been demonstrated that viscoelastic testing is affected by, among other handling variables, holding time.14,20,21 Multiple studies have mentioned that venipuncture is associated with contact activation due to blood exposure to needles, syringes, and vacutainer tubes used in blood collection.20,22 Other studies suggest that contact activation during sample holding time impacts the results by shortening CT and CFT.20,23 It has been demonstrated that equine whole blood may undergo more profound ex vivo activation of the contact pathway during sample holding compared with human and dog samples.20 There are no similar studies assessing these effects using fresh equine native whole blood, in any viscoelastic coagulation testing system.

The objective of this study was to determine the effect of increasing the holding time of fresh equine native whole blood on viscoelastic coagulation as measured by the VCM-Vet™ and the effect of repeated use of the same sample over time. We hypothesized that sample holding time and sample reuse would affect VCM-Vet™ viscoelastic coagulation parameters when using fresh equine native whole blood.

Materials and Methods

Horses

Eight adult mixed-breed mares from the teaching herd maintained by the veterinary teaching hospital were used for this study. Before enrollment in the study, the mares were determined to be healthy based on normal physical examination, normal complete blood count, and fibrinogen concentration. Additional enrollment criteria included a lack of clinical illness or medication administration in the 2 weeks before the study.

Sampling

Selection of venipuncture of either the left or right jugular vein was randomized. All sample collection and processing for viscoelastic coagulation testing was performed by a single operator (Sandra Díaz Yucupicio). Blood for viscoelastic testing was collected by atraumatic venipuncture of the assigned jugular vein using an 18 ga 1.5-inch needle attached to a 3 mL syringe.19 Immediately after viscoelastic testing was initiated, blood was collected from the contralateral jugular vein for routine hematology (PCV/TS [total solids]) and traditional coagulation profile testing (PT [prothrombin time] and PTT [partial thromboplastin time]) to confirm values were within our laboratory’s normal limits.

Viscoelastic coagulation testing

Four VCM-Vet™ devices (Entegrion Inc) were used to perform viscoelastic coagulation testing at different holding times (2, 4, 6, and 8 minutes after blood collection); the order of devices used was randomized for each individual horse. VCM-Vet™ cartridges were pre-heated and kept on the warming plate at 37 °C (Entegrion Inc), and samples were held on the warming plate until testing according to manufacturer recommendation. For each test, the sample was gently inverted twice to ensure mixing, a small amount of blood was expressed and discarded, and 0.3–0.5 mL of whole blood was placed into the depot well of the test cartridge. The depot well was then unattached from the cartridge just before the cartridge was inserted into the device. Values measured included: CT, CFT, AA, MCF, amplitude at 10 minutes (A10), amplitude at 20 minutes (A20) after clot formation, clot lysis at 30 minutes (LI30), and clot lysis at 45 minutes (LI45).

The handling of samples during holding time was different for protocol A and protocol B (Figure 1). Sampling was performed for protocol A and horses were allowed a minimum of a 2-week rest period before sampling for protocol B. For protocol A, samples were processed from a single 3 mL syringe. At 2, 4, 6, and 8 minutes after venipuncture, the syringe was gently inverted, the sample was placed in the VCM-VetTM cartridge as described above, and the syringe was returned to the warming plate. For protocol B, a separate syringe was used for each holding time and discarded after use. Four 3 mL samples were drawn through a single needle (18 ga 1.5-inch) via initial jugular venipuncture. The 4 blood samples were rested on the warming plate and kept at 37 °C while not in use. At 2, 4, 6, and 8 minutes after venipuncture, a single syringe was used as described and then discarded.

Figure 1
Figure 1

Schematic illustrating the 2 sampling protocols that were compared during this study. For protocol A, samples were processed from a single syringe and held on a warming plate between processing. For protocol B, 4 samples were collected through a single venipuncture, and each syringe was used once. Figure created with BioRender.com.

Citation: American Journal of Veterinary Research 84, 6; 10.2460/ajvr.23.02.0039

Statistical analysis

All data were evaluated using commercial statistical software, R version 4.1.2 (R Studio; R Core Team),24 and P ≤ .05 was considered significant for all analyses. Shapiro-Wilk test, QQ plots, and histograms were used to evaluate the normality of the data. Plots were generated using the R package ggpubr version 0.6.0.25 Because data were not normally distributed, median and interquartile ranges were reported for the descriptive statistics. Differences in sample holding time were assessed by the Friedman test. Where a significant effect of time was demonstrated, Wilcoxon Rank Sum Test with Bonferroni adjustment was performed.

Results

A total of 8 mares were included in both protocols in this study. Breeds included were Thoroughbred (2), Warmblood (1), Quarter Horse (3), Arabian (1), and Standardbred (1). Ages ranged from 10 to 27 years (mean 15 years) and weights were from 447 kg to 700 kg (mean 563 kg). PCV, TS, fibrinogen, PT, and PTT were within normal limits in all the mares for both protocols (Table 1). For 1 sample from protocol A, PT and PTT could not be analyzed due to plasma coagulation within the tube. VCM-Vet™ parameters at 2 minutes were generally within the normal reference range for all horses at all times with noted exceptions, and are summarized (Table 2). Protocol A: A10, 1 horse below reference range; A20, 5 horses below reference range; MCF, 3 horses below reference range. Protocol B: A20, 1 horse above and 3 horses below reference range; MCF, 1 horse each above and below reference range.

Table 1

Values of PCV, TS, WBC, platelet concentration, and traditional coagulation parameters (fibrinogen concentration, PT, PTT) for protocol A and protocol B with reference ranges, presented as median (quartile 1, quartile 3).

Test Reference range Protocol A Protocol B
PCV (%) 32–42 36 (33, 38) 35 (34, 37)
TS (g/dL) 5.5–7.3 6.5 (6.2, 6.9) 6.7 (6.4, 6.8)
Fibrinogen (mg/dL) 125–262 123 (109, 146) 123.5 (109, 146)
PT (s) 8–15 12.3 (12.2, 12.6) 12.3 (11.9, 12.6)
PTT (s) 33–47 41.9 (40.2, 42.3) 40.4 (39.6, 41.8)
Platelets (X10∧3/uL) 100–600 169.5 (155, 196.5)
WBC (X10∧3/uL) 5.50–12.00 7.3 (6.35,8.21)
Neutrophils (X10∧3/uL) 3.00–7.00 4.35 (3.99, 5.67)
Lymphocytes (X10∧3/uL) 1.50–5.00 2.24 (2.13,3.04)

PT = Prothrombin time. PTT = Partial thromboplastin time. TS = Total solids.

Table 2

Values of VCM-Vet parameters for each time point under protocol A and protocol B, presented as median (quartile 1, quartile 3).

Protocol A Protocol B
VCM vet parameter REF 2 min 4 min 6 min 8 min 2 min 4 min 6 min 8 min
CT (s) 536–1270 929 (884, 943) 918 (720, 1035) 807.5 (763, 890) 737.5 (666,779) 855.5 (764, 960) 840.5 (675, 1015) 710.5 (649, 978) 576 (489, 725)
CFT (s) 123–574 488 (338, 553) 420 (333, 520) 554 (362, 1082) 604.5 (514, 737) 388.5 (346, 487) 362.5 (262, 457) 370.5 (264, 469) 350 (261, 454)
AA (deg) 12–51 30.5 (26, 34) 29.5 (27, 34) 25.5 (23, 31) 26.5 (22, 29) 31.5 (29, 32) 31.5 (26, 37) 33.5 (26, 40) 32.5 (22, 39)
A10 (VCM units) 9–27 11.5 (11, 16) 13.5 (11, 16) 11 (8, 15) 10 (9, 11) 14 (11, 19) 15.5 (13, 21) 14.5 (13, 20) 16.5 (9, 21)
A20 (VCM units) 18–36 16 (14, 21) 18 (15, 21) 15 (11, 19) 14 (12, 14) 17 (15, 27) 24.5 (19, 27) 20.5 (17, 24) 21 (12, 24)
MCF (VCM units) 17–39 16.5 (14, 22) 19 (16, 22) 16 (12, 19) 15 (13, 16) 24 (17, 29) 25 (20, 32) 20.5 (18, 28) 23 (13, 25)
LI30 (%) 97–100 100 (99, 100) 100 (99, 100) 100 (99, 100) 100 (98, 100) 100 (99, 100) 99.5 (99, 100) 100 (98, 100) 100 (99, 100)
LI45 (%) 82–100 93.5 (90, 97) 93 (91, 95) 97 (90, 98) 96 (93, 98) 95 (92, 98) 93.5 (92, 94) 96 (94, 98) 95 (93, 97)

AA = Alpha angle. CT = Clotting time. CFT = Clot formation time. MCF = Maximum clot formation. REF = Institution-specific reference ranges.11

Under protocol A, there was a significant effect of holding time for CT (P = .02), CFT (P = .04), and AA (P = .05) (Figure 2). CT decreased over time, with significant differences between measurements at 4 and 6 minutes (P = .04) and 4 and 8 minutes (P = .04).

Figure 2
Figure 2

Box plots illustrating values of selected VCM-Vet parameters measured under protocol A. There was significant difference over holding time on (A) clot time (CT; P = .02), (B) clot formation time (CFT; P = .04), and (C) Alpha angle (AA; P = .04). Brackets reflect adjusted P-values for post hoc comparisons between timepoints; a significant effect was seen for CFT at 6 and 8 minute holding times compared with 4 minutes.

Citation: American Journal of Veterinary Research 84, 6; 10.2460/ajvr.23.02.0039

AA decreased over time and CFT increased; however, there was no statistically significant difference in between-timepoint comparisons. Samples handled by protocol B showed no significant difference over time for any of the VCM-Vet parameters.

Discussion

In the present study, we determined that changes in viscoelastic coagulation test parameters as measured by VCM-VetTM occurred with prolonged holding times and sample agitation. The most significant effect during holding time was observed for CT, suggesting that contact activation occurs within the syringe before test initiation. Analysis of the sample within 2–4 minutes of collection is recommended. However, despite statistically significant differences over time for protocol A, there was no significant difference in coagulation parameters when samples were held without agitation in protocol B. All measured values that were within the reference interval at baseline remained within the large reference range of the horse and, therefore, sample holding up to 8 minutes is unlikely to result in artifactual changes that impact the clinical interpretation of results. However, with sequential patient monitoring, the impact of sample holding time variability may affect clinical interpretation, which would most likely interfere with patient monitoring over time.

The VCM-Vet™ operator’s manual recommends running the samples within 4 minutes of collection. Determination of the effect of holding time on test parameters is important because once coagulation is initiated, clot formation begins, and hastens coagulation concerning testing.26 Holding time could affect results, interpretation, and clinical decision-making related to patients.21,2729 Ex vivo contact activation was observed in equine whole blood during sample holding time before thromboelastometry using ROTEM (Werfen), suggesting that factor XII and factor XI were activated ex vivo because of exposure of the blood to artificial surfaces.20 Ex vivo contact activation may also be affected by the material and surfaces where the blood is held or collected.20,22

In this study, there was a significant effect of holding time (P = .02) for CT under protocol A (Figure 2), with a decrease observed over time. Clot time represents the first step of clot formation and is the time from the beginning of the test until the time when the clot begins to form, specifically when the curve reaches an amplitude of 1% above the baseline. Even though in both protocols the parameters stayed within equine normal limits, the decrease of CT over time suggests that holding time could affect the test results, shifting interpretation towards hypercoagulable states.3,11 CT is affected by clotting factors VII, FX, and FXII, and it has been suggested that ex vivo activation of FXII causes contact activation.20 Similar to the findings of the current study, a previous study found that the shift toward hypercoagulability during sample holding is primarily attributable to the activation of the contact system.21 Studies have evaluated the effect of resting time in samples with tissue factor-activated assays and determined that samples rested for longer periods of time appeared hypercoagulable.28,30 This was supported by a significantly decreased CT in samples rested for longer periods of time.30

There was also a significant increase in CFT over time in protocol A. CFT represents the speed and strength of clot development; prolongation of CFT is associated with hypocoagulability, and shortened CFT is associated with hypercoagulability.3,4 When the same sample was reused in protocol A, CFT increased above baseline and was outside of the reference range at 6 and 8 minutes in most horses. We would suggest that the CFT changes observed in protocol A are related to contact activation after reuse and agitation of the syringe before sampling at each time.

While statistical analysis demonstrated that there was an effect on AA over time, there was no significant difference between specific time points identified in post hoc comparisons. Visual inspection of the data (Figure 2) suggests that AA became more variable with increasing holding and sample agitation. The magnitude of observed change is unlikely to be of clinical importance.

There was no significant difference in test parameters for protocol B. This finding suggests that while the reuse of a single sample (protocol A) affects some parameters, holding a sample without agitation (protocol B) does not significantly affect test measurements. The changes observed over time with protocol A are likely due to the consumption of coagulation factors and/or the initiation of coagulation within the syringe, increased by sample agitation during sample reuse, and discourage the use of the same syringe repeatedly over time. An example of sample reuse in a clinical setting would be loading an additional cartridge if there was an error or malfunction while beginning the test. Excessive agitation of a single sample before testing may produce the same effect as protocol A, although it was not directly assessed in this study.

Variations in sample collection and handling can influence the results of viscoelastic testing, ultimately leading to misinterpretation of results. During this study minimizing sources of variability and error was fundamental, with specific measures incorporated to decrease variability. Traumatic venipuncture and sampling techniques may affect the results of viscoelastic testing causing platelet activation and initiating premature blood clot formation and promoting a prothrombotic tendency.23,31 Sample collection and handling were performed by a single operator experienced with jugular venipuncture, and each venipuncture was performed with minimal trauma to the large and easily accessed equine jugular vein.23,30 Despite the atraumatic technique, blood collection by venipuncture is associated with contact activation due to blood exposure to endothelial tissue factor and the material of the collection supplies, so is likely that contact activation started during venipuncture in this study.20,21 It has been reported that material used for blood collection could initiate contact activation.20,22 Polypropylene and polycarbonate containers (syringes) reduce surface activation compared with glass, but contact activation is still present.22 During this study, samples were collected in a syringe, which could contribute to contact activation. All the samples in both protocols were collected in the same manner to reduce variability and minimize the effects of collection-induced contact activation.

Some studies suggest that discarding blood can minimize the effects of a suboptimal venipuncture.23 In both protocols, a small amount of blood from the hub of the syringe was discarded before loading the test cartridge to minimize any effect of red blood cell rouleau within the syringe. However, a true discard sample was not obtained in this study.

Studies also suggest that holding temperatures affect contact activation as measured by other viscoelastic testing devices.12,20,30,32 To our knowledge, the effect of holding temperature on VCM-VetTM results with equine whole blood has not been evaluated. Therefore, to decrease potential variability, blood samples and cartridges were kept on the warming plate at 37 °C, as per manufacturer recommendations.

The findings of the current study are limited to healthy adult mares. The study was restricted to 1 sex to increase the uniformity of the study population. Studies in humans suggest that sex could affect the results of the viscoelastic testing, with longer clot times or more hypercoagulable states in females.33,34 To our knowledge, there are no studies to date showing data supporting these findings in horses. Another limitation was the small number of horses; a larger sample size may be required to identify differences in additional VCM-Vet™ parameters. Further studies with larger populations of different sexes and ages are necessary to extrapolate the results with these variables to different populations. Because the objective of the study was to compare changes over time, rather than deviations from normal. Therefore, a normal coagulation profile was not a requirement for study inclusion; baseline viscoelastic test parameters were outside of the institutional reference range in some horses.

Overall, the findings of this study support that clotting occurs more rapidly, with decreased measured clot strength, when samples are held and reused, suggesting that ex vivo contact activation of coagulation occurred within the syringe withholding time. These changes could distort the results during coagulation assessment, potentially confounding recognition and treatment of hypocoagulable or hypercoagulable-related disease states. Multiple factors can influence contact activation, and awareness of sources of variability is important to avoid over-interpretation of artifactual changes that are not reflective of in vivo coagulation. Further investigation to establish protocols for sampling and handling for VCM-Vet™ may be necessary to ensure the accuracy and reliability of testing results. Standardization of holding time is essential to decrease artifactual changes in viscoelastic coagulation as measured by VCMVet™; sample analysis within 2–4 minutes of the collection is recommended when using equine whole blood and repeated testing from a single sample syringe should not be performed.

Acknowledgments

Financial support for this study was from the University of Illinois Companion Animal Grant. Funding sources did not have any involvement in the study design, data analysis, interpretation, or writing and publication of the manuscript.

The authors declare that there were no conflicts of interest.

The authors thank Entegrion Inc for providing VCM-Vet™ devices and cartridges used in the study.

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    Roeloffzen WW, Kluin-Nelemans HC, Mulder AB, et al. In normal controls, both age and gender affect coagulability as measured by thrombelastography. Anesth Analg. 2010;110:987994. doi:10.1213/ANE.0b013e3181d31e91

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  • Figure 1

    Schematic illustrating the 2 sampling protocols that were compared during this study. For protocol A, samples were processed from a single syringe and held on a warming plate between processing. For protocol B, 4 samples were collected through a single venipuncture, and each syringe was used once. Figure created with BioRender.com.

  • Figure 2

    Box plots illustrating values of selected VCM-Vet parameters measured under protocol A. There was significant difference over holding time on (A) clot time (CT; P = .02), (B) clot formation time (CFT; P = .04), and (C) Alpha angle (AA; P = .04). Brackets reflect adjusted P-values for post hoc comparisons between timepoints; a significant effect was seen for CFT at 6 and 8 minute holding times compared with 4 minutes.

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    Zambruni A, Thalheimer U, Leandro G, et al. Thromboelastography with citrated blood: comparability with native blood, stability of citrate storage and effect of repeated sampling. Blood Coagul Fibrinolysis. 2004;15:103107. doi:10.1097/00001721-200401000-00017

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    • Export Citation
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    deLaforcade A, Goggs R, Wiinberg B. Systematic evaluation of evidence on veterinary viscoelastic testing part 3: assay activation and test protocol. J Vet Emerg Crit Care (San Antonio). 2014;24:3746. doi:10.1111/vec.12147

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    • Export Citation
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    Flatland B, Koenigshof AM, Rozanski EA, et al. Systematic evaluation of evidence on veterinary viscoelastic testing part 2: sample acquisition and handling. J Vet Emerg Crit Care (San Antonio). 2014;24:3036. doi:10.1111/vec.12142

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    • Export Citation
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    Wang WH, Lynch AM, Balko JA, et al. Point-of-care viscoelastic coagulation assessment in healthy dogs during the perianesthetic period. BMC Vet Res. 2022;18:346. doi:10.1186/s12917-022-03442-x

    • PubMed
    • Search Google Scholar
    • Export Citation
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    Hyldahl Laursen S, Andersen PH, Kjelgaard-Hansen M, et al. Comparison of components of biological variation between 3 equine thromboelastography assays. Vet Clin Pathol. 2013;42:443450. doi:10.1111/vcp.12079

    • PubMed
    • Search Google Scholar
    • Export Citation
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    Smith A, Duchesne J, Marturano M, et al. Does gender matter: a multi-institutional analysis of viscoelastic profiles for 1565 trauma patients with severe hemorrhage. Am Surg. 2022;88:512518. doi:10.1177/00031348211033542

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    • Export Citation
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    Roeloffzen WW, Kluin-Nelemans HC, Mulder AB, et al. In normal controls, both age and gender affect coagulability as measured by thrombelastography. Anesth Analg. 2010;110:987994. doi:10.1213/ANE.0b013e3181d31e91

    • PubMed
    • Search Google Scholar
    • Export Citation

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