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Global Coagulation Assays in Chronic Kidney Disease

B. Lui1, D. Barit1, M. Sashindranath2, C. Selan2, G. Donnan3, H. Nandurkar2, P. Ho1, H.Y. Lim2,1,3

1Northern Health, Epping, Australia, 2Australian Centre for Blood Diseases, Melbourne, Australia, 3University of Melbourne, Melbourne, Australia

Abstract Number: PB1042

Meeting: ISTH 2021 Congress

Theme: Vascular Biology » Blood Cells and Vessel Wall

Background: Chronic kidney disease (CKD) is associated with both increased risk of thrombotic and bleeding complications. Currently available coagulation assays are limited in their capacity to predict these outcomes.

Aims: To evaluate the use of global coagulation assays in patients with chronic kidney disease.

Methods: This is a prospective observational study in which patients with estimated glomerular filtration rate (eGFR) <30 mL/min/1.73m2 were recruited (n=84) and compared to healthy controls (n=153). Blood samples were collected for baseline bloods and global coagulation assays, which included whole blood thromboelastography and platelet-poor calibrated automated thrombogram (CAT), overall haemostatic potential (OHP), tissue factor pathway inhibitor (TFPI) and plasminogen activator inhibitor-1 (PAI-1).

Results: Compared to healthy controls (mean age 41.8 years, 67% female), CKD subjects (mean age 65.1 years, 38% female) had increased von Willebrand factor antigen (178 vs 102%, p<0.001), factor VIII levels (183 vs 108%, p<0.001) and prothrombotic thromboelastography parameters with increased maximum amplitude (69.9 vs 60.3mm, p<0.001). Fibrin generation parameters were increased (overall coagulation potential 44.5 vs 36.1, p<0.001) with impaired fibrinolytic potential (65.6 vs 81.3%, p<0.001) and peak thrombin was higher in CKD patients despite comparable endogenous thrombin potential. The differences remained with multivariate analysis modelling for age and sex. The global coagulation parameters did not correlate with urea level. D-Dimer (930 vs 430, p<0.001) was increased in the CKD group although it did not correlate with overall haemostatic potential parameters. Comparisons haemodialysis (n=45) and peritoneal dialysis (n=15) sub-populations demonstrated that peritoneal dialysis patients had higher thrombin with reduced overall fibrinolytic potential.

 Global coagulation assay parameters Normal controls (n=153) CKD eGFR<30 (n=82) P-value*
THROMBOELASTOGRAPHY: Maximum amplitude (mm), mean (SD) 60.3 (6.4) 70.1 (6.8) <0.001
CAT: Endogenous thrombin potential (ETP, nM.min), mean (SD) 1335 (258) 1286 (228) 0.52
CAT: Peak (nM), mean (SD) 219.7 (67.1) 231.2 (65.5) 0.038
CAT: Velocity index (nM/min), median (IQR) 64.3 (43.2, 93.5) 68.4 (56.3, 96.8) 0.005
OHP: Overall coagulation potential (%), mean (SD) 35.5 (9.7) 44.7 (10.7) <0.001
OHP: Overall haemostatic potential (%), median (IQR) 6.4 (4.8, 9.4) 16.4 (10.8, 21.6) <0.001
OHP: Overall fibrinolytic potential (%), median (IQR) 81.1 (77.4, 84.1) 64.1 (54.3, 71.7) <0.001
 TFPI (ng/mL), median (IQR) 14.5 (6.9, 27.4) 38.7 (21.4, 66.0) <0.001
PAI-1(ng/mL), median (IQR) 8.1 (2.8, 18.5) 7.4 (3.8, 19.5) 0.89

Global coagulation assay parameters in CKD patients compared to healthy controls

Conclusions: CKD appears to confer a prothrombotic state characterised by increased von Willebrand factor antigen, factor VIII levels, clot strength as well as both increased fibrin generation and hypofibrinolysis. The use of global coagulation assays to stratify thrombosis risk warrants further investigation.

To cite this abstract in AMA style:

Lui B, Barit D, Sashindranath M, Selan C, Donnan G, Nandurkar H, Ho P, Lim HY. Global Coagulation Assays in Chronic Kidney Disease [abstract]. Res Pract Thromb Haemost. 2021; 5 (Suppl 2). https://abstracts.isth.org/abstract/global-coagulation-assays-in-chronic-kidney-disease/. Accessed May 16, 2022.

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