Yonsei Med J.  2018 Aug;59(6):754-759. 10.3349/ymj.2018.59.6.754.

Increased Thrombogenicity in Chronic Renal Failure in a Rat Model Induced by 5/6 Ablation/Infarction

• Song TJ
• Kwon I
• Piao H
• Lee JE
• Han KR
• Chang Y
• Oh HJ
• Choi HJ
• Lee KY
• Kim YJ
• Han KH
• Heo JH

• KMID: 2415534
• DOI: http://doi.org/10.3349/ymj.2018.59.6.754

Abstract

PURPOSE
Abnormalities in hemostasis and coagulation have been suggested in chronic renal failure (CRF). In this study, we compared processes of thrombus formation between rats with CRF and those with normal kidney function.
MATERIALS AND METHODS
CRF was induced by 5/6 ablation/infarction of the kidneys in Sprague-Dawley rats, and surviving rats after 4 weeks were used. Ferric chloride (FeCl3)-induced thrombosis in the carotid artery was induced to assess thrombus formation. Whole blood clot formation was evaluated using rotational thromboelastometry (ROTEM). Platelet aggregation was assessed with impedance platelet aggregometry.
RESULTS
FeCl3-induced thrombus formation was initiated faster in the CRF group than in the control group (13.2±1.1 sec vs. 17.8±1.0 sec, p=0.027). On histological examination, the maximal diameters of thrombi were larger in the CRF group than in the control group (394.2±201.1 µm vs. 114.0±145.1 µm, p=0.039). In extrinsic pathway ROTEM, the CRF group showed faster clot initiation (clotting time, 59.0±7.3 sec vs. 72.8±5.0 sec, p=0.032) and increased clot growth kinetics (α angle, 84.8±0.2° vs. 82.0±0.6°, p=0.008), compared to the control group. Maximal platelet aggregation rate was higher in the CRF group than in the control group (58.2±0.2% vs. 44.6±1.2%, p=0.006).
CONCLUSION
Our study demonstrated that thrombogenicity is increased in rats with CRF. An activated extrinsic coagulation pathway may play an important role in increasing thrombogenicity in CRF.

Keyword

Chronic renal failure; thrombosis; ferric chloride; thromboelastometry

MeSH Terms

Animals
Blood Platelets
Carotid Arteries
Electric Impedance
Hemostasis
Kidney
Kidney Failure, Chronic*
Kinetics
Models, Animal*
Platelet Aggregation
Rats*
Rats, Sprague-Dawley
Thrombelastography
Thrombosis

Figure

• 

  Fig. 1 Method of rotational thromboelastometry. The obtained parameters were time to clot initiation (CT), time to clot formation (CFT), α angle for clot growth kinetics (initial rate of fibrin polymerization), and maximum amplitude representing the viscoelastic strength of clot at 10 min (MA10) and 20 min (MA20). CT, the latency time from adding the start reagent to blood until the clot starts to form; CFT, duration measured from r time to the point where the amplitude of the tracing measures reached 20 mm; α angle, the angle of tangent between 2 and the curve while CFT is the time from CT until a clot firmness of 20 mm point has been reached.

• 

  Fig. 2 FeCl3-induced thrombus formation in the carotid artery. (A and B) Hematoxylin and eosin staining (×100). Thrombus is indicated with black arrow. CRF, chronic renal failure. (C and D) Gross findings. The maximal diameter of thrombus is larger in CRF than in control mice. Fe-Cl3-induced thrombus formation site is indicated with white arrow.

• 

  Fig. 3 Results of rotational thromboelastometry. (A) Extrinsic pathway screening thromboelastometry (EXTEM) for CRF rats. (B) EXTEM for control rats. (C) Intrinsic pathway screening thromboelastometry (INTEM) for CRF rats. (D) INTEM for control rats. In EXTEM, the CRF group (A) showed a shorter time to clotting initiation [clotting time (black arrow), 59.0±7.3 s vs. 72.8±5.0 s, p=0.032] and a higher velocity to clot growth (α angle, 84.8±0.2° vs. 82.0±0.6°, p=0.008) than the control group (B). The clot formation time, MA10, and MA20 were not different between the two groups. However, in INTEM, the clotting time, clot formation time, α angle, MA10, and MA20 were not different between the CRF (C) and control groups (D).

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