Hemorrhagic shock is a common clinical scenario encountered in people, dogs, and cats.1–4 It is defined as a clinical state where tissue oxygen and nutrient delivery do not meet tissue demand and results in systemic oxygen delivery impairment. Hemorrhagic shock leads to decreases in effective circulating volume and cardiac output (CO), and decompensated hemorrhagic shock may result in decreased mean arterial pressure (MAP), acidosis, and coagulopathy.5,6 In people, it is well documented that hemostatic disorders worsen when resuscitation efforts include large amounts of “clear fluids,” such as isotonic crystalloids or synthetic colloids for intravascular fluid replacement.7 Therefore, employing a strategy that utilizes whole blood or blood component therapy for resuscitation has been proven to decrease mortality and reduce complications linked with excessive use of crystalloids, such as acute lung injury and cerebral edema.4,8–12
Trauma-induced coagulopathy (TIC), also known as acute traumatic coagulopathy, is a poorly understood hemostatic disorder characterized by a combination of hemorrhage, tissue injury, and hypothermia.10,13 While there is no standard definition for TIC, it has been described as an abnormal hemostatic response to trauma, with both bleeding and thrombotic phenotypes.13 Severe tissue injury, even in the absence of shock, can be followed by an early hypercoagulable state, representing a maladaptive response to normal clot formation in certain studies7,13 of hemorrhaging people. Coagulopathies have also been documented in hemorrhaging patients in the absence of trauma,14–16 highlighting the complex nature of this phenomenon and the difficulty in knowing which therapies may be needed to improve survival based on various bleeding phenotypes that can be seen.
Due to ethical concerns, recent experimental models associating hemorrhagic shock and tissue injury are rare, especially in animal species such as dogs.11,17,18 However, changes in traditional hemostasis testing, such as platelet count, prothrombin time (PT), activated partial thromboplastin time (aPTT), and more global hemostatic testing, such as viscoelastic testing, have been described in naturally occurring traumatic hemorrhagic shock, nontraumatic hemorrhage shock, such as spontaneous hemoabdomen in dogs, and hemorrhagic shock models.12,14–16,19–21
Traditional coagulation tests, such as PT and aPTT, do not allow for real-time evaluation of clot formation and breakdown and may not be useful to diagnose hypercoagulability.22 In clinical practice, whole-blood viscoelastic coagulation devices measure clot formation kinetics ex vivo.23–25 Specifically, viscoelastic coagulation devices, such as thromboelastography (TEG), rotational thromboelastometry (ROTEM), or viscoelastic coagulation monitor (VCM-Vet), can provide more information on initial clot formation, clot strength, and clot stability.23,24 All devices aforementioned have been tested in dogs.15,26,27
The impact of hemorrhagic shock on coagulation as assessed using VCM-Vet, a point-of-care, fully automated device, has not yet been studied. This cartridge-based device requires only a small amount of whole blood (approx 400 µL), which has advantages compared to other viscoelastic devices.27 Although the use of TEG or ROTEM are somewhat limited to referral practices, VCM-Vet is available in large emergency practices. The point-of-care nature of the device, as well as the small amount of blood needed, makes it particularly attractive for emergency situations.
The goal of our study was to assess changes in viscoelastic testing using the VCM-Vet device and traditional hemostatic tests in a nonterminal model of pressure-targeted hemorrhagic shock followed by retransfusion of shed blood in dogs. We hypothesized that there will be changes consistent with hemostatic disorders in both viscoelastic tests and traditional hemostatic testing results over time.
Methods
Eight purpose-bred, spayed female Beagles were used in this study. Each dog was determined to be healthy based on a physical examination, CBC, and biochemistry panel. All procedures were approved by the IACUC (#2237) at Colorado State University. This study was performed from September through December of 2021.
Anesthesia and instrumentation
Dogs were premedicated with hydromorphone (0.1 mg/kg, IM) and an IV catheter was placed in a cephalic vein. Following preoxygenation, general anesthesia was induced with propofol (5 to 10 mg/kg, IV) to effect. A cuffed endotracheal tube was placed and connected to an anesthetic circle system, and general anesthesia was maintained with isoflurane vaporized in 100% fraction of inspired oxygen. Dogs were spontaneously breathing throughout the study.
Dogs were instrumented with ECG, pulse oximetry, invasive blood pressure monitoring after cannulization of the dorsal metatarsal artery, esophageal temperature probe, and end-tidal CO2 via side-stream sampling for the duration of general anesthesia. Normothermia was maintained using a forced-air warming device and heated water blankets.
After induction and placement of anesthetic monitoring, a 20-gauge over-the-needle catheter was placed in a dorsal metatarsal artery, and a 16-gauge over-the-needle catheter was placed in a jugular vein. A 7.5F Swan-Ganz catheter (Biosensors International Inc) was placed using a flow-directed technique via the jugular vein, and the location in the pulmonary artery was confirmed via pressure waveform analysis. All catheters were placed using aseptic technique.
Coagulation measurements
Blood for the VCM-Vet (Entegrion Inc) and coagulation assays was collected using a 3-syringe technique from the jugular venous catheter.28 Immediately after blood collection, blood was transferred into 1 1.8-mL 3.2% sodium citrate tube and 1 2-mL EDTA tube. Both tubes were gently inverted 5 to 7 times prior to analysis. The citrate tube was used for traditional hemostatic testing (Stago STA Compact Max) and the EDTA for the complete blood cell count (Advia 2120i; Siemans). Automated platelet count was confirmed via manual blood smear review.
Viscoelastic coagulation monitor testing was performed according to manufacturer recommendation.29 In brief, immediately after whole-blood collection, the device needle was removed and approximately 400 μL of blood, without the addition of anticoagulants, was used to fill the VCM-Vet cassette. After filling, the cassette was inserted into the VCM-Vet, which automatically initiated the test. Due to the timing of samples, 2 different VCM-Vet devices were used.
Experimental design
Once each dog was anesthetized and instrumented, the MAP was stabilized at 70 to 80 mm Hg for 10 minutes before measurements (CO, MAP, heart rate, VCM-Vet parameters, traditional hemostatic variables, Hct, platelet count, and WBC count) were obtained (T1). If necessary, dobutamine (0.5 to 3 μg/kg/min, IV), dopamine (5 to 20 μg/kg/min, IV), phenylephrine (0.5 to 2 μg/kg/min, IV), and/or an IV bolus of crystalloids (3 to 20 mL/kg) were used to stabilize blood pressure within the desired range. Two dogs received an intervention, dopamine (n = 1) or dobutamine (n = 1), to achieve target blood pressure. These were discontinued at least 15 minutes prior to data collection.
A low CO state was induced by removing the dog's blood via syringe attached to the preplaced jugular venous catheter over 20 minutes, targeting a MAP of 40 mm Hg or until 60% of the dog's total blood volume (blood volume = 90 mL/kg)30 was removed, whichever occurred first. Blood was transferred to and stored in blood collection bags containing citrate phosphate dextrose adenine (CPDA-1) at room temperature on a blood rocker. After 10 minutes, T2 measurements were collected. Half of the withdrawn blood was then transfused back into the patient over 20 minutes using 60-mL syringes and a Hemonate filter (Utah Medical Products), and, after a 10-minute equilibration period, the remaining 50% of the shed blood was transfused over 20 more minutes; after 10 minutes, the final T3 measurements were obtained. After completion of the study, dogs were deinstrumented and allowed to recover from anesthesia. All dogs survived without complication.
Data recorded included dogs’ demographic information, CO, MAP, and heart rate. Viscoelastic coagulation monitor variables reported included clot time (CT), clot formation time (CFT), α-angle, maximum clot formation (MCF), amplitude at 10 minutes (A10), amplitude at 20 minutes (A20), clot lysis index at 30 minutes (LI30), and clot lysis index at 45 minutes (LI45). Traditional hemostatic variables reported included platelet count, PT, aPTT, fibrinogen, antithrombin (AT), and D-dimers (Stago STA Compact Max). Hematocrit and WBCs were also recorded (Advia 2120i; Siemans). All variables were recorded at all 3 time points (T1, T2, and T3).
To assess individual dogs’ viscoelastic tracing and determine their hemostatic profile, we defined the following VCM-Vet parameters as hypocoagulable: increased CT, increased CFT, decreased α-angle, decreased A10, decreased A20, or decreased MCF compared to the established normal dog reference range.26 The following VCM-Vet parameters were considered hypercoagulable: decreased CT, decreased CFT, increased α-angle, increased A10, increased A20, or increased MCF compared to the established reference ranges. Individual tracings were considered hypocoagulable if at least 2 VCM-Vet parameters were hypocoagulable and hypercoagulable if at least 2 VCM-Vet parameters were hypercoagulable. Inconclusive tracings were defined as having a VCM-Vet parameter in both the hypocoagulable and hypercoagulable categories. Hyperfibrinolysis was defined as having a decreased LI30 or LI45 compared to the established canine reference range. Hypofibrinolysis was considered impossible as the established reference interval for dogs includes 100%. The VCM-Vet tracings were considered normal if they were not hypercoagulable, hypocoagulable, or hyperfibrinolytic.
Statistical methods
Descriptive statistics were used to describe patient demographics. Because of the small sample size, data are reported as median (minimum-maximum), and nonparametric tests were used. Complete blood count, VCM-Vet parameters, and PT, aPTT, fibrinogen, AT, and D-dimer values between each time point were tested with a Friedman test for repeated measures with post hoc multiple comparisons between time points. All statistical analyses were performed with commercially available software (MedCalc Software Ltd, version 20.026). Statistical significance was set at P < .05.
Results
Eight healthy, nonsplenectomized, female, spayed, purpose-bred Beagles were enrolled in this study. The median age was 5 years (2.5 to 5.5). The median body weight was 8.8 kg (6.6 to 11.5).
The median blood volume withdrawn was 41.9 mL/kg (19.1 to 46.1). The median MAP at T1, T2, and T3 was 71.5 mm Hg (68 to 89), 46.5 mm Hg (35 to 55), and 69 mm Hg (60 to 85), respectively. The median time between T2 and T3 measurements was 63 minutes (50 to 70).
The median CO at T1, T2, and T3 was 2.7 L/min (1.2 to 3.8), 2.0 L/min (1 to 2.6), and 2.5 L/min (1.8 to 5.3), respectively.
Due to blood sample clotting, CBC was not performed for 1 dog at T1 and another dog at T3. Median Hct, WBC count, and platelet count were significantly (P < .001, P = .02, and P = .002, respectively) lower over time, with significant differences (P < .05) between each individual time points found on pairwise comparison for WBC and platelet count (Table 1). Over time, samples had significantly higher coagulability (increased median α-angle, A10, and A20) and fibrinolysis (decreased median LI30 and LI45) and significantly longer aPTT; however, all values remained within reference limits (Tables 2 and 3).
Results for CBC-related variables of interest at baseline (T1) compared with hemorrhagic shock (T2) and after autotransfusion of shed blood (T3) over time for 8 heathy research Beagles enrolled in a hemorrhagic shock model conducted from September 2021 through December 2021.
| CBC variables | T1 | T2 | T3 | Normal value | P value |
|---|---|---|---|---|---|
| Hct (%) | 52 (45–67) | 45 (38–55) | 40 (36–55) | 35–57 | < .001 |
| WBC (X 103/μL) | 11.6 (5.9–15.7) | 5.0 (2.2–8.7) | 6.7 (4.1–11.5) | 5.0–14.1 | .002* |
| Plt count (X 103/μL) | 300 (182–385) | 259.5 (151–323) | 186 (110–248) | 211–494 | .002* |
| MPV (fL) | 10.6 (8.9–13.0) | 10.4 (9.7–12.1) | 11.4 (9.7–12.0) | 6.1–10.1 | .891 |
Values reported are median (range).
MPV = Mean platelet volume. Plt = Platelet.
*Significant (P < .05) differences between each individual time point.
Statistically significant P values are bolded.
Results for viscoelastic coagulation monitoring device (VCM-Vet) variables at T1 compared with T2 and T3 over time for 8 heathy research Beagles enrolled in a hemorrhagic shock model conducted from September 2021 through December 2021.
| VCM parameters | T1 | T2 | T3 | Normal values | P value |
|---|---|---|---|---|---|
| CT (min) | 3.75 (2.10–7.30) | 4.2 (2.20–6.00) | 2.05 (1.30–6.40) | 4.02–7.83 | > .99 |
| CFT (min) | 4.45 (2.40–10.3) | 3.05 (2.00–9.20) | 3.20 (1.30–9.40) | 1.73–4.43 | > .99 |
| α-Angle (°) | 46.5 (24.0–61.0) | 53.0 (28.0–62.0) | 54.5 (35.0–71.0) | 43–64 | < .001 |
| A10 (U) | 16.5 (10.0–26.0) | 20.5 (11.0–29.0) | 19.0 (10.0–32.0) | 16–30 | < .001 |
| A20 (U) | 24.0 (15.0–35.0) | 26.5 (16.0–36.0) | 25.5 (14.0–37.0) | 22–33 | < .001 |
| MCF (U) | 30.0 (20.0–44.0) | 33.0 (23.0–44.0) | 35.0 (19.0–66.0) | 29–44 | > .99 |
| LI30 (%) | 100 (66–100) | 100 (98–100) | 100 (39–100) | 99–100 | < .001 |
| LI45 (%) | 100 (73–100) | 100 (88–100) | 100 (45–100) | 99–100 | < .001 |
Values reported are median (range).
A10 = Amplitude at 10 minutes. A20 = Amplitude at 20 minutes. CFT = Clot formation time. CT = Clotting time. LI30 = Lysis index at 30 minutes. LI45 = Lysis index at 45 minutes. MCF = Maximal clot firmness. VCM = Viscoelastic coagulation monitor.
Statistically significant P values are bolded.
Results for traditional coagulation variables at T1 compared with T2 and T3 over time for 8 heathy research Beagles enrolled in a hemorrhagic shock model conducted from September 2021 through December 2021.
| Traditional coagulation variables | T1 | T2 | T3 | Normal value | P value |
|---|---|---|---|---|---|
| PT (s) | 8.1 (7.6–8.7) | 8.75 (8.5–9.8) | 8.95 (8.3–10.4) | 5.4–11.9 | .44 |
| aPTT (s) | 12.6 (10.8–13.4) | 13.1 (11.1–14.2) | 13.0 (11.2–13.9) | 8.9–18.7 | < .001 |
| Antithrombin (μg/mL) | 148 (109–186) | 108 (94–147) | 106 (92–135) | 65–145 | > .99 |
| D-dimer (mg/L FEU) | 0.16 (0.06–1.05) | 0.19 (0.07–3.05) | 0.33 (0.10–2.44) | 0–575 | > .99 |
| Fibrinogen (mg/dL) | 180 (165–301) | 127.5 (117–225) | 126.5 (91–202) | 150–490 | .91 |
Values reported are median (range).
aPTT = Activated partial thromboplastin time. FEU = Fibrinogen equivalent units. PT = Prothrombin time.
Statistically significant P values are bolded.
No significant changes were seen in the following VCM-Vet parameters over time: CT, CFT, MCF, and AT (P > .99 for all; Tables 2 and 3). No significant changes were seen over time in the following traditional coagulation tests: AT, D-dimer, fibrinogen, and PT (P > .99, P > .99, P > .99, P = .91, and P = .44, respectively; Tables 2 and 3).
At T1, 4 dogs (dogs #2, #3, #5, and #6) were hypocoagulable, no dogs were hypercoagulable, and 2 dogs (dogs #1 and #6) were hyperfibrinolytic. At T2, 1 dog (dog #2) was hypocoagulable, 1 dog (dog #8) was hypercoagulable, and 2 dogs (dogs #3 and #4) were hyperfibrinolytic. At T3, 1 dog (dog #3) was hypercoagulable, 1 dog (dog #5) was hypercoagulable, and 1 dog (dog #1) was hyperfibrinolytic (Supplementary Table S1).
After completion of the study, all dogs recovered from general anesthesia and survived without complication.
Discussion
Our hemorrhagic shock model showed significant increase in α-angle, A10, and A20 over time, consistent with hypercoagulability, although a significant prolongation in PTT consistent with hypocoagulability was also shown. It also showed significant shortening of LI30 and LI45 over time, consistent with hyperfibrinolysis, despite all values remaining within reference range, highlighting complex hemostasis disturbances in the model. No significant changes in PT, fibrinogen, AT, D-dimers, or fibrinogen degradation products were seen. These findings support our hypothesis of changes in the viscoelastic and traditional coagulation testing results, consistent with a coagulopathy, albeit complex.
Our study31 showed a significant decrease in platelet count to a median of 186 X 103/µL. This is below our institution's reference interval of 211 to 494 X 103/µL but should not be low enough to cause clinically significant bleeding. Our study contrasts with a canine hemorrhagic shock model by Lynch et al,15 which found a platelet count of 181 ± 47 X 103/µL without a statistical difference over time despite a prolonged period (60 minutes) of shock.15 However, the Beagles in the study by Lynch et al15 had a relatively low platelet count at baseline (approx 150 X 103/µL), whereas our study's dogs had a normal platelet count at baseline (approx 300 X 103/µL). The median platelet count in our study is relatively lower than the 225 to 286 X 103/µL previously described in naturally occurring trauma dogs21,32 but consistent with dogs presented with TIC after an acute trauma33 and relatively similar or higher compared to the 104 to 131 X 103/µL published in dogs with spontaneous hemoabdomen.16,34
Our study is the first to report VCM-Vet parameters in hemorrhagic shock in dogs, showing a combination of hypercoagulable and hyperfibrinolytic changes. Both hypocoagulable, hypercoagulable, and hyperfibrinolytic tracings have been described in naturally occurring trauma and shock models in dogs using different viscoelastic methods.14,16 Our study, showing no significant changes in CT and CFT, contrasts with previous literature. In a fixed-pressure experimental model designed to describe coagulopathies based on different resuscitation fluids in Greyhounds, the viscoelastic device ROTEM showed significantly prolonged EXTEM CT, INTEM CFT, and EXTEM CFT.14 Another fixed-pressure experimental model of hemorrhagic shock in 5 Beagles documented a significant prolongation of reaction time (equivalent to the parameter CT in VCM-Vet) over time.15 Those differences can be explained by breed differences in Greyhound tracings,35 lack of activators in VCM-Vet that could contribute to poor sensitivity of CT and CFT compared to TEG and ROTEM, or a longer period of hypotension (ie, 60 minutes) in the other experimental models.14,15 Our study documented a significant increase in α-angle over time, consistent with a hypercoaguable tracing. This is consistent with another study using ROTEM, which also documented a significant increase in α-angle over time, albeit in the context of volume resuscitation using crystalloids and colloids and did not measure any changes prior to volume resuscitation.19 The study by Lynch et al15 in Beagles did not document an increase in α-angle, but the baseline α-angle in their study was approximately 58°, compared to 47° in our study, which, combined with a lower number of dogs (n = 5) in that study, may explain their lack of statistical significance despite a relative increase in the α-angle over time in their study.
Our study did not find any significant change in MCF, which contrasts with the aforementioned study by Lynch et al.15 In that fixed-pressure hemorrhagic shock model measuring impact on TEG and PT/aPTT in Beagles, the MA, which is the TEG-equivalent to the VCM-Vet MCF parameter, was found to be decreased over time but still within reference ranges.15 In a prospective, multicenter observational study of 40 dogs experiencing acute trauma by Holowaychuk et al,36 a hypocoagulable state, defined by decreased α-angle and maximum amplitude (MA) was common, and a low MA was associated with nonsurvival when compared to surviving dogs. Those differences can be explained by timing of sampling as the median blood sample was collected 6.25 hours after the traumatic event compared to our study's median time in shock of 63 minutes.
Our study found a significant prolongation of PTT. Prolonged PTT without prolongation of PT was also noted in a canine experimental hemorrhagic shock model utilizing ROTEM by Diniz et al.19 Their study was focused on effects of resuscitation with different crystalloids immediately after removing blood to an Hct of 33%. Prolonged PTT was also noted in dogs evaluated within 12 hours of acute trauma and was the best predictor of nonsurvival in dogs.36 An elevated PTT without a change in PT in our study may indicate a loss of factor VIII, other intrinsic pathway factors (XII, XI, and IX), or a combination of these factors.37 PTT is also considered to be the most sensitive test of coagulation factor activity38 and is more sensitive than the PT to low fibrinogen, a common occurrence in actively bleeding dogs, illustrated by the hypofibrinogenemia at T2 and T3 in our study, although not statistically difference from baseline.37
Although our study found hemostatic changes in our hemorrhagic shock model, the clinical application to traumatic and nontraumatic hemorrhage in dogs is unknown. First, apart from platelet count and fibrinogen, all values were within the normal reference range for dogs. In the scenario where baseline values are available, changes in hemostatic values can help support a suspicion of coagulopathy. However, such baseline values are rare in clinical patients. Second, our model lacks tissue trauma that is crucial in the development of TIC and therefore may be more comparable to models of spontaneous hemorrhage, including spontaneous hemoabdomen. In dogs with spontaneous hemoabdomen, hemostatic changes before surgery are characterized by significant alterations in both coagulation and fibrinolysis.16,39 Studies show that these dogs often present with hypocoagulability and hyperfibrinolysis. Hypocoagulability is evidenced by prolonged PT and PTT, decreased MA, and low platelet counts. These abnormalities are often associated with protein C deficiency and the severity of shock as indicated by plasma lactate concentrations, values that our study did not evaluate.16,39 Hyperfibrinolysis is also common in dogs with spontaneous hemoperitoneum. This condition is identified through increased concentrations of D-dimers and elevated TEG lysis parameters, such as clot lysis at 30 minutes and clot lysis at 60 minutes when tissue plasminogen activator is added to the blood samples. Hyperfibrinolysis tends to resolve rapidly after surgical intervention to control hemorrhage.39 In 1 study, hyperfibrinolysis was found in 40% of the dogs at presentation, but significant decreases in fibrinolysis parameters were observed within 8 to 16 hours postoperatively, suggesting early resolution without the need for antifibrinolytic drugs.39 Our study showed similar hemostatic changes, including decreased platelet count, prolonged PTT, and hyperfibrinolysis, but did not show a decrease in MA.16,39
Lastly, it is possible that the device used in our study is not as sensitive as other viscoelastic devices used in previous studies. However, it has been shown that the VCM-Vet provides accurate information on whole-blood kinetics when compared to TEG.27 Advantages of the VCM-Vet to the practitioner include increased availability in emergency and critical care practices, patient-side availability, and lack of sample manipulation, along with species-specific parameters and a user-friendly interface. We utilized 2 VCM-Vet devices for our study. It has been suggested that each VCM-Vet device should have its own reference interval for dogs due to interdevice variability.26 A prior investigation showed moderate-to-good correlation between 2 VCM-Vet devices used, but some technical issues were reported, complicating the interpretation of results.26 In our study, we chose to use an established reference interval for data interpretation, a method commonly used in multicenter studies involving TEG40–43 or ROTEM41,42,44 in people. Recent literature has shown good correlation between different VCM-Vet devices.27
Limitations of this study include a small sample size of all female dogs. A study in people on the association between gender and TEG variables found significant differences in coagulation profiles between males and females.45 Females generally exhibited a hypercoagulable state compared to males. This was evidenced by shorter coagulation (K) times, steeper α-angles, higher maximal amplitudes, and larger strength (G) parameters.45 These findings indicate that women have faster fibrin deposition kinetics, greater overall clot strength, and increased platelet contribution to clot formation than men. This gender-related hypercoagulability was observed even after adjusting for age and race, suggesting that inherent physiological differences contribute to these variations in coagulation status. The impact of sex on canine hemostasis is unknown, although it is possible that our study findings would be similar in male dogs. Our study induced hemorrhagic shock with a relatively short duration of hypoperfusion prior to resuscitation measures. Indeed, equilibration time in our model was 10 minutes compared to 60 minutes in a study by Lynch et al15 and 120 minutes in a study by Diniz et al.19 While statistically significant changes were seen with a 10-minute equilibration time, it is possible that more changes could have been seen with a longer time. Blood was collected in CPDA-1 collection bags that will chelate calcium, an important component in the coagulation cascade.37 We believe the impact of CPDA-1 in this study to be minimal as we documented a hypercoagulable state rather than the hypocoagulable that would be expected in cases of hypocalcemia. Blood loss in this model was performed under controlled conditions while receiving 100% inhaled fraction of inspired oxygen, which is not representative of the clinical presentation of hemorrhagic shock but consistent with previous studies.12,14,15,19 Two dogs required either dopamine or dobutamine administration during induction of hemorrhagic shock, but we do not anticipate any effect on coagulation testing. Lastly, and as previously mentioned, there was no trauma component to this model. Without the systemic effects of tissue damage in potentiating coagulopathy, this model may not be applicable to every clinical case.10,17
In this canine fixed-pressure hemorrhagic shock model, we demonstrated a coagulopathy consistent with hypercoagulability and an increased PTT as well as hyperfibrinolysis. Further studies in clinical patients, or a repetition of this model with a longer time period of shock, are warranted to better understand the complex disturbances of naturally occurring hemorrhagic shock.
Supplementary Materials
Supplementary materials are posted online at the journal website: avmajournals.avma.org.
Acknowledgments
None reported.
Disclosures
Dr. Guillaumin has received speaking fees within the past 5 years from Entegrion as well as research support by means of cartridge donation for other projects.
No AI-assisted technologies were used in the generation of this manuscript.
Funding
Funded by a College Research Council Grant, Colorado State University.
ORCID
T. N. Baird https://orcid.org/0000-0001-6026-8541
K. M. Zersen https://orcid.org/0000-0003-0327-8537
J. Guillaumin https://orcid.org/0000-0001-8622-4387
References
- 1.↑
Cothren CC, Moore EE, Hedegaard HB, Meng K. Epidemiology of urban trauma deaths: a comprehensive reassessment 10 years later. World J Surg. 2007;31(7):1507–1511. doi:10.1007/s00268-007-9087-2
- 2.
Jutkowitz LA, Rozanski EA, Moreau JA, Rush JE. Massive transfusion in dogs: 15 cases (1997–2001). J Am Vet Med Assoc. 2002;220(11):1664–1669. doi:10.2460/javma.2002.220.1664
- 3.
Simpson SA, Syring R, Otto CM. Severe blunt trauma in dogs: 235 cases (1997–2003). J Vet Emerg Crit Care. 2009;19(6):588–602. doi:10.1111/j.1476-4431.2009.00468.x
- 4.↑
Tucker C, Winner A, Reeves R, et al. Resuscitation patterns and massive transfusion for the critical bleeding dog—a multicentric retrospective study of 69 cases (2007–2013). Front Vet Sci. 2022;8:788226. doi:10.3389/fvets.2021.788226
- 5.↑
Taghavi S, Nassar AK, Askari R. Hypovolemic shock. In: StatPearls. StatPearls Publishing; 2024. Accessed April 20, 2024. http://www.ncbi.nlm.nih.gov/books/NBK513297/
- 6.↑
Kuo K, Palmer L. Pathophysiology of hemorrhagic shock. J Vet Emerg Crit Care. 2022;32(suppl 1):22–31. doi:10.1111/vec.13126
- 7.↑
Bolliger D, Görlinger K, Tanaka KA. Pathophysiology and treatment of coagulopathy in massive hemorrhage and hemodilution. Anesthesiology. 2010;113(5):1205–1219. doi:10.1097/ALN.0b013e3181f22b5a
- 8.↑
Smart L, Hughes D. The effects of resuscitative fluid therapy on the endothelial surface layer. Front Vet Sci. 2021;8:661660. doi:10.3389/fvets.2021.661660
- 9.
Johansson PI, Stensballe J, Ostrowski SR. Current management of massive hemorrhage in trauma. Scand J Trauma Resusc Emerg Med. 2012;20:47. doi:10.1186/1757-7241-20-47
- 10.↑
Kleinveld DJB, Hamada SR, Sandroni C. Trauma-induced coagulopathy. Intensive Care Med. 2022;48(11):1642–1645. doi:10.1007/s00134-022-06834-7
- 11.↑
Dahlquist A, Elander Degerstedt L, von Oelreich E, et al. Blast polytrauma with hemodynamic shock, hypothermia, hypoventilation and systemic inflammatory response: description of a new porcine model. Eur J Trauma Emerg Surg. 2022;48(1):401–409. doi:10.1007/s00068-020-01476-0
- 12.↑
Edwards TH, Rizzo JA, Pusateri AE. Hemorrhagic shock and hemostatic resuscitation in canine trauma. Transfusion. 2021;61(suppl 1):S264–S274. doi:10.1111/trf.16516
- 13.↑
Duque P, Calvo A, Lockie C, Schöchl H. Pathophysiology of trauma-induced coagulopathy. Transfus Med Rev. 2021;35(4):80–86. doi:10.1016/j.tmrv.2021.07.004
- 14.↑
Boyd CJ, Claus MA, Raisis AL, Hosgood G, Sharp CR, Smart L. Hypocoagulability and platelet dysfunction are exacerbated by synthetic colloids in a canine hemorrhagic shock model. Front Vet Sci. 2018;5:279. doi:10.3389/fvets.2018.00279
- 15.↑
Lynch AM, deLaforcade AM, Meola D, et al. Assessment of hemostatic changes in a model of acute hemorrhage in dogs. J Vet Emerg Crit Care. 2016;26(3):333–343. doi:10.1111/vec.12457
- 16.↑
Fletcher DJ, Rozanski EA, Brainard BM, de Laforcade AM, Brooks MB. Assessment of the relationships among coagulopathy, hyperfibrinolysis, plasma lactate, and protein C in dogs with spontaneous hemoperitoneum. J Vet Emerg Crit Care (San Antonio). 2016;26(1):41–51. doi:10.1111/vec.12346
- 17.↑
Frith D, Cohen MJ, Brohi K. Animal models of trauma-induced coagulopathy. Thromb Res. 2012;129(5):551–556. doi:10.1016/j.thromres.2011.11.053
- 18.↑
Eschbach D, Steinfeldt T, Hildebrand F, et al. A porcine polytrauma model with two different degrees of hemorrhagic shock: outcome related to trauma within the first 48 h. Eur J Med Res. 2015;20(1):73. doi:10.1186/s40001-015-0162-0
- 19.↑
Diniz MS, Teixeira-Neto FJ, Gonçalves DS, et al. Effects of 6% tetrastarch or lactated Ringer's solution on blood coagulation in hemorrhaged dogs. J Vet Intern Med. 2018;32(6):1927. doi:10.1111/jvim.15327
- 20.
Talbot CT, Zersen KM, Hess AM, Hall KE. Shock index is positively correlated with acute blood loss and negatively correlated with cardiac output in a canine hemorrhagic shock model. J Am Vet Med Assoc. 2023;261(6):874–880. doi:10.2460/javma.22.11.0521
- 21.↑
Abelson AL, O'Toole TE, Johnston A, Respess M, de Laforcade AM. Hypoperfusion and acute traumatic coagulopathy in severely traumatized canine patients. J Vet Emerg Crit Care (San Antonio). 2013;23(4):395–401. doi:10.1111/vec.12073
- 22.↑
Bédard C, Lanevschi-Pietersma A, Dunn M. Evaluation of coagulation markers in the plasma of healthy cats and cats with asymptomatic hypertrophic cardiomyopathy. Vet Clin Pathol. 2007;36(2):167–172. doi:10.1111/j.1939-165X.2007.tb00203.x
- 23.↑
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(1):37–46. doi:10.1111/vec.12147
- 24.↑
Flatland B, Koenigshof AM, Rozanski EA, Goggs R, Wiinberg B. Systematic evaluation of evidence on veterinary viscoelastic testing part 2: sample acquisition and handling. J Vet Emerg Crit Care (San Antonio). 2014;24(1):30–36. doi:10.1111/vec.12142
- 25.↑
Burton AG, Jandrey KE. Use of thromboelastography in clinical practice. Vet Clin North Am Small Anim Pract. 2020;50(6):1397–1409. doi:10.1016/j.cvsm.2020.08.001
- 26.↑
Buriko Y, Drobatz K, Silverstein DC. Establishment of normal reference intervals in dogs using a viscoelastic point-of-care coagulation monitor and its comparison with thromboelastography. Vet Clin Pathol. 2020;49(4):567–573. doi:10.1111/vcp.12926
- 27.↑
Buriko Y, Chalifoux NV, Clarkin-Breslin R, Silverstein DC. Comparison of a viscoelastic point-of-care coagulation monitor with thromboelastography in sick dogs with hemostatic abnormalities. Vet Clin Pathol. 2023;52(2):217–227. doi:10.1111/vcp.13198
- 28.↑
Barr CA, Gianotti G, Graffeo CE, Drobatz KJ, Silverstein DC. Effect of blood collection by the push-pull technique from an indwelling catheter versus direct venipuncture on venous blood gas values before and after administration of alfaxalone or propofol in dogs. J Am Vet Med Assoc. 2017;251(10):1166–1174. doi:10.2460/javma.251.10.1166
- 30.↑
de Laforcade A, Silverstein D. Classification and initial management of shock states. In: Small Animal Critical Care Medicine. 3rd ed. Saunders Elsevier; 2023:36–39.
- 31.↑
Li R. Platelet disorders. In: Small Animal Critical Care Medicine. 3rd ed. Saunders Elsevier; 2023:595–598.
- 32.↑
Gottlieb DL, Prittie J, Buriko Y, Lamb KE. Evaluation of acute traumatic coagulopathy in dogs and cats following blunt force trauma. J Vet Emerg Crit Care (San Antonio). 2017;27(1):35–43. doi:10.1111/vec.12525
- 33.↑
Herrero Y, Schefer RJ, Muri BM, Sigrist NE. Prevalence of acute traumatic coagulopathy in acutely traumatized dogs and association with clinical and laboratory parameters at presentation. Vet Comp Orthop Traumatol. 2021;34(3):214–222. doi:10.1055/s-0040-1721707
- 34.↑
Martin A, Kutter A, Sigrist N. Rotational thromboelastometry (ROTEM) parameters in dogs with haemoperitoneum and their associations with clinical and laboratory signs. Schweiz Arch Tierheilkd. 2020;162(3):153–161. doi:10.17236/sat00249
- 35.↑
Vilar P, Couto CG, Westendorf N, Iazbik C, Charske J, Marín L. Thromboelastographic tracings in retired racing Greyhounds and in non-Greyhound dogs. J Vet Intern Med. 2008;22(2):374–379. doi:10.1111/j.1939-1676.2008.0061.x
- 36.↑
Holowaychuk MK, Hanel RM, Darren Wood R, Rogers L, O'Keefe K, Monteith G. Prospective multicenter evaluation of coagulation abnormalities in dogs following severe acute trauma. J Vet Emerg Crit Care. 2014;24(1):93–104. doi:10.1111/vec.12141
- 37.↑
Coagulation assays. eClinpath. Accessed July 8, 2024. https://eclinpath.com/hemostasis/tests/screening-coagulation-assays/
- 38.↑
Ford RB, Mazzaferro EM. Laboratory diagnosis and test protocols. In: Kirk and Bistner's Handbook of Veterinary Procedures and Emergency Treatment. Saunders Elsevier; 2012:551–634.
- 39.↑
DeStefano IM, Rozanski EA, Koethe B, de Laforcade AM. Rapid resolution of hyperfibrinolysis in dogs with spontaneous hemoperitoneum following surgical control of hemorrhage. J Vet Emerg Crit Care. 2023;33(3):305–314. doi:10.1111/vec.13300
- 40.↑
Jiang X, Chai S, Huang Y, et al. Design for a multicentre prospective cohort for the assessment of platelet function in patients with hepatitis-b-virus-related acute-on-chronic liver failure. Clin Epidemiol. 2022;14:997–1011. doi:10.2147/CLEP.S376068
- 41.↑
Baksaas-Aasen K, Gall LS, Stensballe J, et al. Viscoelastic haemostatic assay augmented protocols for major trauma haemorrhage (ITACTIC): a randomized, controlled trial. Intensive Care Med. 2021;47(1):49–59. doi:10.1007/s00134-020-06266-1
- 42.↑
Rigal JC, Boissier E, Lakhal K, Riche VP, Durand-Zaleski I, Rozec B. Cost-effectiveness of point-of-care viscoelastic haemostatic assays in the management of bleeding during cardiac surgery: protocol for a prospective multicentre pragmatic study with stepped-wedge cluster randomised controlled design and 1-year follow-up (the IMOTEC study). BMJ Open. 2019;9(11):e029751. doi:10.1136/bmjopen-2019-029751
- 43.↑
Cuffolo G, Katz-Summercorn AC, Hossain MA. The role of rapid thromboelastography in trauma. Expert Rev Med Devices. 2014;11(5):435–438. doi:10.1586/17434440.2014.940313
- 44.↑
Buscher H, Zhang D, Nair P. A pilot, randomised controlled trial of a rotational thromboelastometry-based algorithm to treat bleeding episodes in extracorporeal life support: the TEM protocol in ECLS study (TEMPEST). Crit Care Resusc. 2017;19(suppl 1):29–36.
- 45.↑
Rodgers SC, Carter KT, Patki D, O'Brien RC, Kutcher ME. Thromboelastography-based evaluation of gender-associated hypercoagulability. Am Surg. 2022;88(11):2619–2625. doi:10.1177/00031348221087905
