• Open Access

Hypercoagulability and ACTH-Dependent Hyperadrenocorticism in Dogs


  • This study was presented in part at the 2012 American College of Veterinary Internal Medicine Forum, New Orleans, LA

Corresponding author: S.L. Blois, DVM, DVSc, DACVIM. Department of Clinical Studies, Ontario Veterinary College, University of Guelph, Guelph, ON, N1H 2B2; e-mail: sblois@uoguelph.ca.



Dogs with hyperadrenocorticism are at risk of thromboembolic disease, which might be caused by an underlying hypercoagulable state.


To assess hemostatic function in dogs with ACTH-dependent hyperadrenocorticism (ADHAC) before and after treatment.


Nineteen dogs with ADHAC and 40 normal dogs.


Prospective, observational study. Dogs with ADHAC were recruited from the referral hospital patient population; normal dogs were recruited from staff and students at the study's institution. Hemostasis was assessed before and at 3 and 6 months after treatment with trilostane (T0, T3, T6) by kaolin-activated thrombelastography with platelet mapping (TEG-PM), prothrombin time, activated partial thromboplastin time, fibrinogen concentration, and antithrombin activity (AT).


Dogs with ADHAC had statistically significantly increased α-angle (P < .01) and maximum amplitude (MA)thrombin (P < .01) on TEG-PM, and significantly decreased κ (P < .005) at T0, T3, and T6. Platelet count (P < .001) and fibrinogen concentration (P < .001), but not AT activity, were increased in dogs with ADHAC at T0, T3, and T6.

Conclusions and Clinical Importance

Dogs with ADHAC have thrombelastographic evidence of hypercoagulability and remained hypercoagulable during treatment. AT deficiency does not appear to be involved in the pathogenesis of hypercoagulability in this population.


arachidonic acid


ACTH-dependent hyperadrenocorticism


adenosine diphosphate


activated partial thromboplastin time




clot lysis at 30 minutes


global clot strength


low-dose dexamethasone suppression test


maximum amplitude


prothrombin time

R value

reaction value


systolic blood pressure


thrombelastography platelet mapping




urinary protein-to-creatinine ratio

ACTH-dependent hyperadrenocorticism (ADHAC) is characterized by chronic hypercortisolemia secondary to an ACTH-secreting pituitary tumor.[1] Hyperadrenocorticism in dogs has been associated with thromboembolic disease, and thrombi occur in pulmonary veins, splenic veins, aorta, and iliac arteries of dogs with hyperadrenocorticism.[2-6] The exact incidence and risk of thromboembolic disease in dogs with hyperadrenocorticism have not been defined and the pathogenesis of thromboembolic disease is incompletely understood. These patients might be hypercoagulable.[7] Thrombelastography (TEG) is a point-of-care test that has been validated in dogs[7] and has the advantage of being able to detect dogs who are hypercoagulable.[8-16] However, thrombin generated by standard TEG assays might obscure the contribution of individual and potentially weaker platelet agonists to thrombus formation. A modification in TEG, platelet mapping (TEG-PM), has been developed to separately analyze the contributions of thrombin, fibrin, and platelets to clot formation. The contribution of the platelet agonists adenosine diphosphate (ADP) and arachidonic acid (AA) to platelet activation can be individually assessed with results reported as maximum amplitude (MA)ADP and MAAA. Fibrin clot strength in the absence of platelet activation is assessed as a baseline (MAfibrin). A standard kaolin-activated TEG assay assesses the maximum clot strength for that patient (MAthrombin).[17] In healthy dogs receiving clopidogrel treatment, MAADP correlated with ADP-induced platelet aggregation measured by impedance aggregometry.[18]

The objective of this prospective longitudinal study was to assess dogs with ADHAC for evidence of hypercoagulability before and after treatment with trilostane, using TEG-PM as well as conventional hemostatic tests including prothrombin time (PT), activated partial thromboplastin time (aPTT), and fibrinogen concentration. In addition, urinary protein-to-creatinine ratio (UPCR), plasma antithrombin (AT) activity, and systolic blood pressure (SBP) were evaluated to examine the possible relationship between urinary protein loss and hypertension with coagulation status.

Materials and Methods

Animals and Study Design

This study was performed at the University of Guelph between November 2009 and October 2011, in accordance with the standards of the Canadian Council on Animal Care and the Ontario Animals for Research Act. Informed consent was obtained from all dog owners and the study was approved by the University of Guelph Animal Care Committee.

Forty healthy control dogs, between the ages of 1 and 11 years, were recruited to determine reference intervals and used as a control group. The dogs were deemed healthy on the basis of physical examination, complete blood count (CBC), serum biochemical profile, and urinalysis. The dogs had not received any medications, excluding heartworm and flea prophylaxis, in the preceding 6 weeks.

Nineteen client-owned dogs with ADHAC that had not received previous treatment for hypercortisolism were included in the study. Exclusion criteria included a previous diagnosis of chronic kidney disease, diabetes mellitus, malignant neoplasia, hepatic insufficiency or congestive heart failure, and treatment with nonsteroidal anti-inflammatory agents or anticoagulant medications in the previous 6 weeks. Hyperadrenocorticism was suspected on the basis of consistent clinical signs, history, and physical examination features, as well as if patients displayed at least 3 of the following 5 clinicopathological findings: elevated alkaline phosphatase, elevated alanine aminotransferase, elevated cholesterol, urine specific gravity <1.020, and positive urine bacterial culture. Hyperadrenocorticism was diagnosed if at least 1 of the after 2 screening tests was positive: a supportive low-dose dexamethasone suppression test (LDDST, 8-hour cortisol ≥1.4 μg/dL [38 nmol/L])[19] and ACTH stimulation test (post-ACTH cortisol concentration >22 μg/dL [600 nmol/L]).[20-22] ADHAC was diagnosed if at least one of the following 2 tests was positive: a supportive LDDST result (4-hour sample <1.4 mg/dL [38 nmol/L]) or ≤50% of the baseline, or an 8-hour sample ≤50% of the baseline, but ≥1.4 mg/dL [38 nmol/L]),[1, 23] and ultrasound showing adrenal glands that were bilaterally normal or enlarged,[24] or in cases of asymmetrical enlargement, the smaller (contralateral) gland dorsoventral thickness was >0.5 cm.[25] All dogs had adrenal ultrasonography performed by a board-certified veterinary radiologist (SGN); adrenal glands were considered to be of normal size if the width was ≤0.75 cm.[24] Blood sample collection for evaluation of hemostasis was performed the day before trilostane1 administration was started (T0). The initial trilostane dose was 2–5 mg/kg PO q24h; response to treatment was assessed after 10–14 days and at 1 month, 3 months (T3), and 6 months (T6). At each recheck, a physical examination and ACTH stimulation test (2.2 units/kg ACTH gel2 IM, pre-ACTH and 2 hours post-ACTH samples) were performed. At T0, T3, and T6, CBC, serum biochemistry profile, PT, aPTT, fibrinogen concentration, TEG-PM, SBP, AT activity, and UPCR were also obtained. ADHAC was considered adequately controlled if clinical signs of hypercortisolism had resolved and post-ACTH cortisol concentration was within the target interval of 1.4 and 5.4 μg/dL (40–200 nmol/L).

Sampling Procedures

Jugular venipuncture was performed with a 20-gauge needle and 12-mL dry syringe. If the 1st venipuncture did not result in adequate blood flow, the needle was withdrawn and the opposite jugular vein was used. Immediately after venipuncture, the needle was removed from the syringe and blood was transferred into two 1.8 mL sodium citrate (3.2% citrate [1 volume 0.109 M citrate to 9 volumes blood] blood collection tubes3 ) and one 4 mL heparin (17 IU heparin/mL blood collection tube3) blood collection tube without vacuum assistance. The SBP was calculated as the mean of 3 readings obtained by the Doppler4 method as per the American College of Veterinary Internal Medicine consensus statement[26]; hypertension was defined as mean SBP ≥160 mmHg.[26] Urine was collected by free catch[27] or cystocentesis.

Laboratory Methods

Prothrombin time, aPTT, and fibrinogen concentration5 testing were performed on citrated plasma. The citrated kaolin TEG and MAfibrin assays (TEG 5000 Thrombelastograph Hemostasis Analyzer6 ) were initiated after sample equilibration for 30 minutes at room temperature.[7] For the citrated kaolin TEG assay, 1.0 mL of citrated whole blood was added to a kaolin-coated vial,6 then 340 μL of this sample was added to a TEG cup containing 20 μL of 0.2 M calcium chloride.6Data collected from citrated kaolin TEG analysis included reaction (R) time, α-angle, kappa (κ), MA, and clot lysis at 30 minutes (CL30). To analyze MAfibrin, 10 μL of Activator F reagent6 was added to a TEG cup, followed by 340 μL of heparinized blood. After completion of these 2 assays (approximately 90 minutes after venipuncture), the MAADP and MAAA assays were initiated. To analyze MAADP, 10 μL of the Activator F reagent was added to a TEG cup, followed by 10 μL of the ADP reagent,6 then 340 μL of heparinized blood, for a final ADP concentration of 2 μM. A similar procedure was used to analyze MAAA, with the exception of adding 10 μL of the AA reagent,6 giving a final AA concentration of 1 mM. For all assays, TEG cups were prewarmed to 37°C. AT activity testing was performed by an automated chromogenic assay, utilizing bovine factor Xa and the chromogenic substrate S-2765.7 Chemistry strip analysis,8 specific gravity, sediment examination, and UPCR were performed on urine samples. Samples were excluded from UPCR measurement when there was hematuria, pyuria (>5 red or white blood cells per high power field), or bacteriuria, or if there was a positive urine bacterial culture.[27] UPCR ≥0.5 was considered to represent significant proteinuria.[28]

Statistical Analysis

Statistical analysis was performed by statistical software.9 To evaluate whether a standard normal distribution was present, a Shapiro–Wilk test and examination of the residuals were performed. A general linear mixed model including time and group as fixed effects, and dog as a random effect, was used to determine if the parameters of interest changed over time or between groups. Repeated measures made over time on the same animal were accounted for by fitting different autocorrelation structures. Posthoc tests were performed when the global testing indicated differences between groups or time points, and were adjusted by Tukey's method. Level of significance was set at P < .05. Correlations were calculated by Spearman's correlation coefficient. Data from all time points were included.


The age of the normal dogs was 4 years (median, range 1–11 years) and for the ADHAC group at T0, it was 11 years (range 5–14 years, P < .0001). Four of 19 dogs were confirmed to have hyperadrenocorticism by an ACTH stimulation test and 15/19 dogs by a LDDST. Two of 19 dogs had both an ACTH stimulation test and a LDDST performed. Seven of 19 dogs had LDDST results consistent with ADHAC. Eleven of 19 dogs had sonographically normal adrenal glands, 5/19 had bilaterally symmetrical adrenal enlargement, and 3/19 had asymmetrical adrenal enlargement with the smaller gland diameter >0.5 cm.[25]

Fifteen of 19 dogs with ADHAC were followed up for the duration of the study and underwent the final evaluation at T6. Reasons for withdrawal of the other 4 dogs from the study included development of permanent hypoadrenocorticism (1), development of concurrent diabetes mellitus (1), administration of meloxicam (1), and owner withdrawal (1). No dog was diagnosed with thromboembolic disease during the study period. At T3, all of the dogs' clinical signs had resolved and 13/16 had ACTH stimulation test results within the target interval. Two dogs required a dosage increase and 1 dog required a dosage decrease at T3. At T6, 11/15 dogs had ACTH stimulation test results within the target interval; 1 dog required a dosage increase and 3 dogs required a dosage decrease. The dose of trilostane was 2.9 ± 1.1 mg/kg/day (mean ± SD) at T0, 3.0 ± 1.2 mg/kg/day at T3, and 3.3 ± 1.4 mg/kg/day at T6; all dosing was performed once a day.

The dogs with ADHAC had a significantly shorter PT compared with the normal dogs at all time points (T0/T3/T6: P < .001; Table 1). The PT did not change significantly over time in the dogs with ADHAC (Table 1). At all time points, the dogs with ADHAC had significantly higher fibrinogen concentration than the normal dogs (T0/T3/T6: P < .001; Table 1). Fibrinogen concentration decreased significantly during treatment of ADHAC (T0–T3: P = .023, T0–T6: P = .037). The dogs with ADHAC had significantly higher platelet counts at all time points compared with the normal dogs (T0/T3/T6: P < .001); platelet numbers did not change significantly over time (Table 1).

Table 1. Selected values for control dogs and ADHAC dogs before treatment (T0) and after 3 and 6 months of trilostane treatment (T3, T6)
  1. ADHAC, ACTH-dependent hyperadrenocorticism; PT, prothrombin time; aPTT, activated partial thromboplastin time; R, reaction value; MA, maximum amplitude; CL30, clot lysis at 30 minutes; UPCR, urine protein-to-creatinine ratio; AT, antithrombin; SBP, systolic blood pressure.

  2. Median (range).

  3. a

    Indicates a significant difference to the control group (P < .05).

  4. b

    Indicates ADHAC groups at T3 or T6 with a significant difference to T0 (< .05).

Platelet count (×109/L)243 (122–487)464 (161–663)a470 (90–708)a401 (234–881)a
PT (seconds)7.6 (6.0–9.4)6.6 (5.8–7.2)a7.0 (5.6–7.7)a6.7 (5.6–7.6)a
aPTT (seconds)13.7 (9.4–43.7)14.0 (10.1–35.1)15.8 (11.5–40.3)16.5 (11.7–47.6)
Fibrinogen (g/L)1.9 (1.3–4.4)3.9 (2.1–7.0)a3.4 (2.0–4.9)a,b2.9 (1.9–5.0)a,b
R (minutes)2.9 (1.7–6.9)3.2 (1.2–8.2)3.2 (2.0–4.6)3.2 (1.9–4.2)
Kappa (minutes)1.9 (0.9–3.2)1.3 (0.8–2.0)1.3 (0.9–1.8)a1.2 (0.8–4.2)a
α-angle (°)64.7 (50–76.5)71.2 (57.0–78.2)a72.6 (65.0–76.6)a72.9 (48.0–78.4)a
MAthrombin (mm)54.4 (42.6–71.5)67.1 (50.4–73.3)a61.0 (44.8–70.7)a,b63.0 (44.7–70.8)a,b
CL30 (%)98.5 (88.4–100)100 (92.9–100)98.9 (86.2–100)98.6 (85.4–100)
MAfibrin (mm)5.5 (2.3–68.7)61.4 (2.7–83.0)a62.5 (2.5–75.6)b43.6 (3.6–67.5)b
MAADP (mm)43.1 (3.2–66.2)58.1 (7.5–79.1)61.7 (5.2–79.6)b60.7 (7.3–80.2)
MAAA (mm)51.2 (7.4–66.9)62.8 (25.1–84.9)b57.0 (29.8–70.1)56.3 (24.1–70.2)
UPCR1.3 (0.2–7.1)0.6 (0.0–4.7)b0.25 (0.1–3.9)b
AT activity (%)93 (81–114)102 (82–114)97 (90–111)
SBP (mmHg)160 (110–227)140 (100–180)150 (85–180)

Compared with the normal dogs, the citrated kaolin TEG variables that were significantly different for ADHAC dogs at all time points included: shorter κ (T0: P = .0022, T3/T6: < .001), higher α-angle (T0: = .0069, T3: = .0033, T6: P = .0014), and higher MAthrombin (T0: < .001, T3: = .0053, T6: P = .0025; Table 1). MAthrombin was the only one of these parameters that significantly changed (decreased) during treatment of ADHAC (T0–T3: P = .020, T0–T6: P = .042; Table 1). Compared with the normal dogs, the TEG-PM variables that were significantly different for ADHAC dogs included: higher MAfibrin at all time points (T0/T3: P < .001, T6: P = .011), higher MAADP at T3 (= .029), and higher MAAA at T0 (= .019; Table 1). None of these parameters significantly changed during treatment of ADHAC (Table 1).

Proteinuria was noted in 9/12 ADHAC dogs at T0, 5/9 dogs at T3, and 4/13 dogs at T6; UPCR significantly decreased during treatment of ADHAC (T0–T3: P = .015, T0–T6: P = .031; Table 1). The UPCR data were not reported for 6 dogs at T0 and 1 dog at T3 because of the presence of a bacterial urinary tract infection, an active urine sediment, or both; 1 urine sample at T3 was misplaced in the laboratory; 5 dogs at T3 and 2 dogs at T6 did not have urine obtained by free catch or cystocentesis. Plasma AT activity levels were measured in 8/19 dogs with ADHAC at T0, in 8/16 dogs at T3, and in 5/15 dogs at T6 (Table 1); samples were not obtained or sufficient sample volume was not stored for the remainder of dogs. Plasma AT activity was within the laboratory reference interval with the exception of 1 dog at T3 (114%, RI 75–112%). Plasma AT activity did not change during treatment of ADHAC (Table 1). Blood pressure was measured in all dogs at all time points, and hypertension was documented in 10/19 ADHAC dogs at T0, 5/16 dogs at T3, and 6/15 dogs at T6; blood pressure did not change during treatment of ADHAC (Table 1).

A moderate positive correlation was identified between fibrinogen concentration and MAthrombin (rs = 0.59, P < .0001) in ADHAC dogs. There was a weak positive correlation between MAfibrin and fibrinogen in ADHAC dogs (rs = 0.38, P = .007) and in normal dogs (rs = 0.43, P = .006).


In this study, dogs with ADHAC had several TEG variables that were consistent with hypercoagulability, including increased MAthrombin, decreased κ, and increased α-angle. Dogs with ADHAC remained hypercoagulable during treatment.

These findings are consistent with previous studies of iatrogenic hyperadrenocorticism in dogs in which there were increases in MAthrombin, decreased κ, and increased α-angle[29] or increases in MAthrombin alone.[30] In contrast with this study, another recent study found that dogs with hyperadrenocorticism did not have significantly different TEG variables compared with dogs with nonadrenal illness.[31] However, many dogs in the nonadrenal illness population of that study were hypercoagulable compared with their institutional reference intervals.[31]

Hypercoagulability did not resolve with medical treatment of ADHAC in this study, in agreement with a recent study.[31] Persistence of hypercoagulability might explain why thromboembolic disease has been reported in dogs with controlled hyperadrenocorticism.[32] Similarly, resolution of hypercoagulability does not consistently occur in humans after treatment of hyperadrenocorticism.[33, 34] The mean duration of action of trilostane in dogs is 18 hours,[35] meaning that in dogs dosed once daily, there is potentially a period of hypercortisolemia for part of each day; this might be sufficient to ensure ongoing hypercoagulability despite adequate control of clinical signs of ADHAC. An alternative explanation could be that irreversible endothelial dysfunction occurs in these patients. In addition, 2 dogs at T3 and 1 dog at T6 had post-ACTH cortisol results higher than the target range for trilostane treatment. As a result, these dogs might have been more hypercoagulable than they would have been if the cortisol concentration had been within the desired range, potentially influencing the findings of this study.

The increased MAAA in dogs with untreated ADHAC suggests that increased platelet response to AA might contribute to hypercoagulability in these patients. Although the mean MAAA values at T3 and T6 were also higher than those of the reference interval, these differences were not significant. Overall, there was a trend for higher MAADP values in dogs with ADHAC at all time points compared with normal dogs, although this only reached significance at T3. However, there was a large degree of variability among these results, which might have masked significant changes at T0 and T6. To investigate these findings further, studies should be performed to compare the results of TEG-PM with other platelet function tests in dogs with ADHAC. A previous study of dogs with hyperadrenocorticism showed hypercoagulable TEG results, but in contrast to this study, platelet hypofunction was documented with a platelet function analyzer.10 The role of platelets in the hypercoagulable state associated with hyperadrenocorticism at this time is uncertain. Further studies, including additional platelet function testing such as aggregometry, are warranted in this population.

Thrombocytosis was common in this population of dogs with ADHAC. The mechanism by which glucocorticoids cause thrombocytosis is not well elucidated. However, glucocorticoids have a permissive effect on erythropoiesis,[36] so it is possible that they have a similar effect on thrombopoiesis. A definitive link between thrombocytosis and increased risk of thrombosis has not been made in dogs. The incidence of thromboembolic disease was 7.9% in a group of dogs with thrombocytosis (platelet count > 600 × 109/L).[37] However, most of the dogs had 1 or more underlying systemic diseases, most commonly neoplasia, endocrine disorders (including hyperadrenocorticism), and inflammatory diseases. As these diseases might be associated with thromboembolic disease in themselves, it is not certain whether thrombocytosis or the underlying diseases themselves lead to these thrombotic events. The incidence of thromboembolic disease in association with thrombocytosis is similar in humans and is reported to be 4–6%.[38, 39]

Fibrin clot strength in the absence of thrombin-induced platelet activation (TEG-PM MAfibrin) was also increased in dogs with ADHAC compared to the normal dogs. Hyperfibrinogenemia was common in these dogs with ADHAC, and is a potential explanation of the elevated MAfibrin. Furthermore, a mild positive correlation between MAfibrin and fibrinogen concentration was identified. Hyperfibrinogenemia increases risk of thromboembolic disease in humans,[40] although its significance in dogs is not well defined.[8, 10, 13] In addition, a previous study found increased CL60 in dogs that were administered prednisone, suggestive of decreased fibrinolysis.[30] Decreased fibrinolysis was not noted when CL30 was measured in this study, but CL60 was not examined. Further investigations of the role of elevated fibrinogen concentration, fibrin clot strength, and incidence of delayed fibrinolysis in dogs with hyperadrenocorticism are warranted in patients suspected to be hypercoagulable, including dogs with immune-mediated hemolytic anemia, neoplasia, and protein-losing diseases.

In this study, there was variability noted in MAfibrin results in both normal and ADHAC dogs, which might limit the use of TEG-PM in dogs. As MAfibrin contributes to both MAAA and MAADP, when MAfibrin approaches MAthrombin, it is not possible to assess the response to AA and ADP with TEG-PM. This might limit the utility of TEG-PM in dogs in disease states characterized by hypercoagulability, in which high MAfibrin values might be seen. It remains unclear whether the large variability noted in the MAfibrin results is a typical finding in dogs. Larger studies of both normal and diseased dogs are recommended to further characterize TEG-PM variables, especially MAfibrin, and to determine if this is a suitable method of analyzing platelet function in dogs.

In this study, PT was significantly shorter in dogs with ADHAC compared with healthy dogs at all time points. The clinical relevance of this finding is not known, as all PT results were still within the previously established institutional canine reference interval. However, the significantly shorter PT identified in the ADHAC dogs of this study might be another marker of hypercoagulability and warrants future study. Subnormal PT results are not commonly found in dogs with thromboembolic disease,[2, 5, 13, 41] or dogs with thromboelastographic evidence of hypercoagulability.[9, 14, 42]

Despite the high prevalence of proteinuria, decreased plasma AT activity was not documented in any of the dogs with ADHAC; thus, AT deficiency does not appear to be a reason for the observed hypercoagulability. Previously, significantly lower AT activity in dogs with hyperadrenocorticism was reported in comparison with healthy dogs.[43] In contrast, the mean AT activity in the dogs with hyperadrenocorticism was 100%. Dogs with AT activity <60–80% of normal are thought to be at increased risk of hypercoagulability; therefore, it is unlikely that the AT activity of dogs in this study contributed to the observed hypercoagulability.[44, 45] However, a limitation of this study is that AT and UPCR were not measured in all dogs at all time points.

Another limitation of this study is that the normal population used to generate TEG-PM reference intervals was not age-matched to the ADHAC population to act as a true control group. Human TEG tracings become more hypercoagulable with aging, and might be partly attributable to a decline in hematocrit with increasing age.[46, 47] To the author's knowledge, the effect of age on canine TEG results has not been evaluated and further investigation is warranted. However, in this study, the hematocrit was not significantly different in the ADHAC dogs compared with the healthy dogs.

Hypertension was frequently found in this population of dogs with ADHAC. In agreement with previous studies, blood pressure did not decrease significantly despite resolution of hypercortisolemia.[48, 49] Hypertension in dogs with PDH might cause endothelial dysfunction, via increased shear stress on small blood vessels and increased expression of procoagulant factors such as platelet-activating factor. This could lead to activation of the coagulation cascade and increased risk of thrombus formation. However, stress might have influenced the blood pressure readings in this study,[50] which were all taken in the hospital environment, and the blood pressure of the healthy dogs was not measured for comparison. Nonetheless, further investigation into the role of endothelial dysfunction in the pathogenesis of thromboembolic disease in patients with ADHAC is warranted.

The LDDST and ACTH stimulation test have a limited specificity of approximately 80%, presenting a further limitation to this study, especially in light of the majority of dogs having normally sized adrenal glands on ultrasound.[1] No dogs in this study had apparent nonadrenal illness to account for their clinical signs. In addition, the vast majority of dogs with normally sized adrenal glands on ultrasound had adrenal gland width measurements at the upper end of the reference range. There is a recognized overlap in the adrenal gland sizes of normal and ADHAC dogs.[1, 24],11 However, there is a potential for false-positive diagnoses of ADHAC in this study.

In conclusion, dogs with naturally occurring ADHAC have evidence of hypercoagulability with several citrated kaolin TEG and TEG-PM variables significantly different from those of normal dogs, indicating a more rapid rate of clot formation and increased clot strength. PT was significantly shorter in the dogs with untreated ADHAC and hyperfibrinogenemia was common. AT activity in the ADHAC dogs was not significantly decreased despite the majority of dogs having significant proteinuria. Approximately, half of the dogs with untreated ADHAC were hypertensive. The majority of the hemostatic abnormalities identified in this study persisted in the dogs treated for ADHAC despite normalization of cortisol concentration. Further prospective studies are needed to evaluate the risk of thromboembolic disease in dogs with ADHAC and hemostatic abnormalities.


The investigators acknowledge the Ontario Veterinary College Pet Trust Fund for funding this study. In addition, the investigators thank Vétoquinol Canada and Dechra Veterinary Products, UK for supplying the trilostane used in this study.

Funding: This study was supported by a grant from the Ontario Veterinary College Pet Trust Fund.

Conflict of Interest Declaration: One author (SLB) has received funding from Vétoquinol Canada for speaking fees and preparation of educational materials in the last 3 years.


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