Coagulation and Circulating Heparin Profile in Patients with End‐Stage Renal Disease Undergoing Maintenance Hemodialysis

Abstract

IntroductionUnfractionated heparin is widely used as an anticoagulant for maintenance hemodialysis in end‐stage renal disease (ESRD) patients. Since these patients are administered with heparin repeatedly throughout treatment, it is hypothesized that detectable circulating levels of heparin may be present in their blood 48 hours post‐dialysis session. Changes in the profile of coagulation factors for the intrinsic and extrinsic pathway may also be associated with repeated heparization and can be measured using global clotting assays. The profiling of these parameters may provide the hemostatic status of patients in reference to circulating residual heparin in the pre‐dialysis blood samples.Materials/ MethodsThis study included 95 patients with ESRD undergoing maintenance hemodialysis, which was administered 3 times per week in 48‐hour intervals. Citrated blood samples were collected, centrifuged, and platelet‐poor plasma was retrieved. Plasma samples were analyzed utilizing clot‐based methods including activated partial thromboplastin time (aPTT), prothrombin time (PT), and thrombin time (TT). Employing a chromogenic assay, the circulating levels of heparin in each patient were measured. All of these samples were also analyzed for thrombin generation capacity using calibrated automated thrombogram (CAT, Diagnostica Stago. Paris, France).ResultsIn the clotting assays, prothrombin time was elevated (16.4 ± 20.3 sec.) in comparison to the normal control (11.1 ± 2.1 sec.). Activated partial thromboplastin time was also prolonged (43.09 ± 43.1 sec.) when compared to normal human plasma (32.3 ± 4.2 sec.). The thrombin time values were also higher (44.6 ± 83.1 sec.) in comparison to normal (11.2 ± 2 sec.). Circulating heparin levels, measured by anti‐Xa methods, were found to be 0.11 ± 0.21 U/ml and anti‐IIa levels being 0.25 ± 0.27 U/ml. The anti‐Xa/anti‐IIa ratio were determined to be 0.43. In the thrombin generation assay, the ESRD samples showed wide variation and a lowered thrombin generation value (107 ± 55.2 nM) in comparison to normal control (185 ± 16.5 nM).DiscussionThese results suggest patients undergoing maintenance hemodialysis exhibit a mild hypocoagulable state as determined by PT and aPTT methods. Although both methods demonstrated wide variation, this prolongation indicated defective intrinsic and extrinsic pathways. Moreover, the thrombin time elevation is suggestive of defective common pathway and the presence of circulating heparin. The circulating levels of heparin were lower in anti‐Xa compared to anti‐IIa, suggesting the presence of higher molecular weight components of heparin. This is likely due to impaired clearance of higher molecular weight heparin components caused by maintenance hemodialysis. The decreased thrombin generation observed in these patients may be partly due to the defects in the coagulation process and presence of heparin in the ESRD patients.Support or Funding InformationNAThis abstract is from the Experimental Biology 2019 Meeting. There is no full text article associated with this abstract published in The FASEB Journal.