Hypercoagulability in Dogs with Protein‐Losing Nephropathy as Assessed by Thromboelastography

Lennon, Elizabeth M.; Hanel, Rita M.; Walker, Julie M.; Vaden, Shelly L.

doi:10.1111/jvim.12067

Cited by 42 publications

(73 citation statements)

References 32 publications

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“…25,26,[33][34][35] Thromboelastography, a method closely related to ROTEM, has previously been reported to detect hypercoagulability in dogs with protein-losing nephropathies. 31,32 Elevated TGA has been shown in both human NS and type 2 diabetes with albuminuria. 24,28 TGA has further been correlated with thrombus formation in multiple animal thrombosis models.…”

Section: Discussionmentioning

confidence: 99%

“…Similarly to TGA, ROTEM has been shown to correlate with hypercoagulability and thrombotic risk. [31][32][33][34][35][36] Correspondingly, PAN-nephrotic rats also exhibited differential proteinuria-dependent hypercoagulopathy derangements in ROTEM parameters (Figure 2A). Clot formation time (CFT) ( Figure 2B) was significantly decreased, whereas a-angle ( Figure 2C), amplitude at 10 (A10) ( Figure 2D) and 20 min (A20) ( Figure 2E), maximum clot firmness (MCF) ( Figure 2F), and residual clot firmness after urokinase-induced fibrinolysis at 60 min (lysis index at 60 min; LI60) ( Figure 2G) were all significantly increased in the rats exhibiting the highest levels of proteinuria (third and fourth quartiles; P,0.05 for each parameter).…”

Section: Pan-nephrotic Rats Exhibit Differential Derangements In Wholmentioning

confidence: 99%

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Disease Severity Correlates with Thrombotic Capacity in Experimental Nephrotic Syndrome

Kerlin

Waller

Sharma

et al. 2015

Journal of the American Society of Nephrology

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Thrombotic disease, a major life-threatening complication of nephrotic syndrome, has been associated with proteinuria and hypoalbuminemia severity. However, it is not fully understood how disease severity correlates with severity of the acquired hypercoagulopathy of nephrotic syndrome. Without this knowledge, the utility of proteinuria and/or hypoalbuminemia as biomarkers of thrombotic risk remains limited. Here, we show that two well established ex vivo hypercoagulopathy assays, thrombin generation and rotational thromboelastometry, are highly correlated with proteinuria and hypoalbuminemia in the puromycin aminonucleoside and adriamycin rat models of nephrotic syndrome. Notably, in the puromycin aminonucleoside model, hyperfibrinogenemia and antithrombin deficiency were also correlated with proteinuria severity, consistent with reports in human nephrotic syndrome. Importantly, although coagulation was not spontaneously activated in vivo with increasing proteinuria, vascular injury induced a more robust thrombotic response in nephrotic animals. In conclusion, hypercoagulopathy is highly correlated with nephrotic disease severity, but overt thrombosis may require an initiating insult, such as vascular injury. Our results suggest that proteinuria and/or hypoalbuminemia could be developed as clinically meaningful surrogate biomarkers of hypercoagulopathy to identify patients with nephrotic syndrome at highest risk for thrombotic disease and potentially target them for anticoagulant pharmacoprophylaxis.

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Section: Discussionmentioning

confidence: 99%

Section: Pan-nephrotic Rats Exhibit Differential Derangements In Wholmentioning

confidence: 99%

Disease Severity Correlates with Thrombotic Capacity in Experimental Nephrotic Syndrome

Kerlin

Waller

Sharma

et al. 2015

Journal of the American Society of Nephrology

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“…High molecular weight clotting factors such as factor V and VIII are also increased in humans with PLN, likely due to increased synthesis disproportionate to urinary loss . Hypovolemia leading to vascular stasis may also be a predisposing factor to thromboembolism in some PLN patients . In most dogs with PLN, the UPC ratio, serum albumin concentration, and plasma antithrombin activity are not predictive of thromboembolic complications and do not predict TEG‐based hypercoagulability .…”

Section: Discussionmentioning

confidence: 99%

“…Hypovolemia leading to vascular stasis may also be a predisposing factor to thromboembolism in some PLN patients . In most dogs with PLN, the UPC ratio, serum albumin concentration, and plasma antithrombin activity are not predictive of thromboembolic complications and do not predict TEG‐based hypercoagulability . The lack of ability to identify one marker that predicts hypercoagulablity in dogs with PLN suggests the predisposition is multifactorial.…”

Section: Discussionmentioning

confidence: 99%

Concurrent renal amyloidosis and thymoma resulting in a fatal ventricular thrombus in a dog

Loewen

Cianciolo

Zhang

et al. 2018

Veterinary Internal Medicne

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Thymoma‐associated nephropathies have been reported in people but not in dogs. In this report, we describe a dog with thymoma and concurrent renal amyloidosis. A 7‐year‐old castrated male Weimaraner was presented for progressive anorexia, lethargy, and tachypnea. The dog was diagnosed with azotemia, marked proteinuria, and a thymoma that was surgically removed. Postoperatively, the dog developed a large left ventricular thrombus and was euthanized. Necropsy confirmed the presence of a left ventricular thrombus and histopathology revealed renal amyloidosis. We speculate that the renal amyloidosis occurred secondary to the thymoma, with amyloidosis in turn leading to nephrotic syndrome, hypercoagulability, and ventricular thrombosis. This case illustrates the potential for thymoma‐associated nephropathies to occur in dogs and that dogs suspected to have thymoma should have a urinalysis and urine protein creatinine ratio performed as part of the pre‐surgical database.

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“…Protein‐losing nephropathy (PLN) in dogs is associated with a hypercoagulable state and thromboembolic risk . The true prevalence of thromboembolic complications in PLN dogs is difficult to ascertain but has been reported to be more than 40% in previous studies .…”

Section: Introductionmentioning

confidence: 99%

Platelet aggregometry testing during aspirin or clopidogrel treatment and measurement of clopidogrel metabolite concentrations in dogs with protein‐losing nephropathy

Shropshire

Johnson

Olver

2020

Veterinary Internal Medicne

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Background Dogs with protein‐losing nephropathy (PLN) are treated with antiplatelet drugs for thromboprophylaxis but no standardized method exists to measure drug response. It is also unknown if clopidogrel metabolite concentrations [CM] differ between healthy and PLN dogs. Objectives Assess response to aspirin or clopidogrel in PLN dogs using platelet aggregometry (PA) and compare [CM] between healthy and PLN dogs. Animals Six healthy and 14 PLN dogs. Methods Platelet aggregometry using adenosine diphosphate (ADP), arachidonic acid (AA), and saline was performed in healthy dogs at baseline and 1‐week postclopidogrel administration to identify responders or nonresponders. A decrease of ≥60% for ADP or ≥30% for AA at 1 or 3 hours postpill was used to define a responder. At 1 and 3 hours postclopidogrel, [CM] and PA were measured in healthy and PLN dogs. Platelet aggregometry was performed in PLN dogs at baseline, 1, 6, and 12 weeks after clopidogrel or aspirin administration. Results In PLN dogs receiving clopidogrel, PA differed from baseline at all time points for ADP but not for AA at any time point. Most dogs responded at 1 or both time points except for 1 dog that showed no response. For PLN dogs receiving aspirin, no differences from baseline were observed at any time point for either ADP or AA. No differences in [CM] were found at either time point between healthy and PLN dogs. Conclusions and Clinical Importance Platelet aggregometry may represent an objective method to evaluate response to clopidogrel or aspirin treatment and PLN dogs appear to metabolize clopidogrel similarly to healthy dogs.

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Hypercoagulability in Dogs with Protein‐Losing Nephropathy as Assessed by Thromboelastography

Cited by 42 publications

References 32 publications

Disease Severity Correlates with Thrombotic Capacity in Experimental Nephrotic Syndrome

Disease Severity Correlates with Thrombotic Capacity in Experimental Nephrotic Syndrome

Concurrent renal amyloidosis and thymoma resulting in a fatal ventricular thrombus in a dog

Platelet aggregometry testing during aspirin or clopidogrel treatment and measurement of clopidogrel metabolite concentrations in dogs with protein‐losing nephropathy

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