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Abstract: PO2376

Circulating Heparin and Its Relevance to Thrombin Generation Profile in ESRD Patients Undergoing Maintenance Hemodialysis

Session Information

Category: Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

  • 1800 Pharmacology (PharmacoKinetics, -Dynamics, -Genomics)

Authors

  • Siddiqui, Fakiha, Loyola University Medical Center, Maywood, Illinois, United States
  • Bontekoe, Emily, Loyola University Medical Center, Maywood, Illinois, United States
  • Hoppensteadt, Debra, Loyola University Medical Center, Maywood, Illinois, United States
  • Jeske, Walter, Loyola University Medical Center, Maywood, Illinois, United States
  • Bansal, Vinod K., Loyola University Medical Center, Maywood, Illinois, United States
  • Fareed, Jawed, Loyola University Medical Center, Maywood, Illinois, United States
Background

End stage renal disease (ESRD) is a complex pathophysiologic syndrome which results in vascular disorders and hemostatic disturbance. Despite the use of heparin during maintenance hemodialysis some of these patients exhibit hypercoagulable state. The purpose of this study was to characterize the thrombin generation (TG) profile in ESRD patients in relation to circulating heparin levels.

Methods

Citrated blood samples from 95 patients with ESRD undergoing maintenance hemodialysis were collected. NHP was prepared for referencing purposes. Individual samples were supplemented with heparinase. TG was assessed using a kinetic fluorogenic substrate method. TG parameters such as peak thrombin, lag time and area under the curve (AUC) were compiled. Circulating heparin levels were determined using activated partial thromboplastin time (aPTT) and chromogenic anti-Xa and IIa assays. The ESRD cohort was stratified into heparinized and heparin naïve groups.

Results

ESRD group showed decrease in peak thrombin (107.1 vs 168.3 nM) and AUC (589.8 vs 815.7 nM*min) with increase in lag time (2.9 vs 2.2 min) compared to NHP. Heparinase supplementation increase the lag time (3.4 min, p value <0.0001), while decrease the peak thrombin (100.0 nM, p value 0.0245) and AUC (503.4 nM*min, p value <0.0001). Such parameters as aPTT (43.2 vs 31.1 sec), anti Xa (0.21 vs 0.14 U/mL) and anti-IIa (0.27 vs 0.15 U/mL) decreased with heparinase treatment. Heparin naïve group showed decreased peak thrombin and AUC values whereas the lag time was increased. Simultaneously aPTT, anti-Xa and anti-IIa levels were decreased in this group. Heparinized patients did not show any difference in peak thrombin, decrease in AUC values and an increase in lag time. However, the aPTT, anti-Xa and anti-IIa were decreased in this group.

Conclusion

These studies showed that heparinase treatment of plasma samples from ESRD patients resulted in the decrease in the aPTT, anti-Xa and IIa levels suggesting the digestion of heparin. However, contrary to these results, TG parameters such as peak thrombin and AUC were decreased whereas lag time was increased suggesting that the depolymerized heparin fragments possessed thrombin generation inhibitory properties.