Examination of hemostatic parameters to detect hypercoagulability in dogs with severe protein‐losing nephropathy

Abstract

Hemostatic abnormalities consistent with systemic hypercoagulability are common in dogs with RF and PLN, however, no prothrombotic factors unique to PLN were identified in our study. The thrombotic tendency of PLN may therefore involve parameters we did not directly assess such as platelet reactivity, fibrinolysis, perturbations in blood flow, and/or endothelial dysfunction. High protein C is a novel finding in PLN dogs of unknown clinical relevance.

Thromboelastometry used for evaluation of blood coagulability in dogs with kidney diseases

“…Shortening of CT was observed in group F, but only on the ex-TEM profile, whereas the initial phase of the intrinsic pathway slowed down, as indicated by the prolongation of aPTT and the in-TEM CT. Further studies on a larger population with quantitative assessment of specific clotting factors and coagulation inhibitors are needed to better clarify this result and to investigate its clinical significance and possible correlation with uremic bleeding. Our results also indicate an increase in the rapidity of clot development and amplification (i.e., shorter CFT and increased α angle) in group F, whereas this alteration was not observed in group P. This result contrasts with that reported by Donahue et al (2011) and is probably due to differences in inclusion criteria: while Donahue et al's study included only dogs with a UPC > 2, ours included especially dogs with moderate proteinuria (0.5 ≤ UPC < 2) that have shown moderate haemostatic changes. The following phase of clot stabilization, as represented by MCF and MCE, was the only haemostatic change that was significantly different in both groups F and P. With the use of fib-TEM activator, which inhibits platelets, the contribution of functional fibrinogen to altering this phase in nephropathic dogs has been confirmed because significant alterations were found not only on the ex-TEM but also on the fib-TEM profile.…”

“…This last result contrasts with the results of a previous study conducted with non activated TEG (Donahue et al 2011). A possible explanation for this difference is that we used strong contact activators that yield more repeatable results but also limit the procedure's sensitivity to subtle changes.…”

“…Furthermore, the viscoelastic technique is a whole blood assessment that considers the role of plasmatic haemostatic components as well as platelets and cellular surfaces, and better reflects the cell-based model of coagulation (Smith 2009). A recent study has identified hypercoagulability by means of non-activated TEG in 7 dogs affected by renal failure and in 11 dogs with severe proteinuria (Donahue et al 2011). Thromboelastometry on canine whole blood has also been recently validated (Smith et al 2010).…”

Disease Severity Correlates with Thrombotic Capacity in Experimental Nephrotic Syndrome

“…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.…”

“…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).…”