Increased Red Cell Phosphatidylserine Exposure Correlates with Enhanced Thrombin Generation In Sickle Trait Patients with End Stage Renal Disease

Phosphatidylserine (PS) exposure by red blood cells (RBCs) is increased in sickle cell disease, where it is thought to contribute to anemia, inflammation and activation of coagulation. RBCs from subjects with sickle cell trait (SCT) may also express more PS compared to controls. We recently reported a high prevalence of SCT in African Americans with end-stage renal disease (ESRD) - a state marked by anemia, profound inflammation and coagulation activation. No study has yet examined RBC PS exposure, inflammation or coagulation activation in African Americans patients with SCT and ESRD.

To determine whether RBC PS exposure is elevated in ESRD patients with SCT receiving hemodialysis compared to patients with normal hemoglobin genotype, and whether markers of coagulation activation and inflammation are similarly elevated. The relationship between RBC PS exposure, thrombin generation and inflammation was also examined.

We performed a cross sectional study of 10 patients with documented SCT and 9 race-matched controls. Both groups were receiving in center hemodialysis. The percentage of RBCs demonstrating PS exposure was determined by annexin-V binding and flow cytometry detection. Plasma thrombin/anti-thrombin (TAT) complexes and C-reactive protein (CRP) levels were determined by ELISA. Mann-Whitney U tests were used to examine differences between these variables among the groups. Medians and interquartile ranges (IQR) are shown. Spearman's correlation coefficient was used to assess the relationship among the variables tested.

Consistent with previous reports in ESRD patients, we found markedly elevated RBC PS exposure among both groups; however, patients with SCT had significantly elevated PS exposure compared to those without SCT (6.65%, [IQR: 5.1, 8.8] vs. 3.0%, [IQR: 2.1,4.2], p = 0.002). Furthermore, patients with SCT had higher TAT levels compared to those without SCT (16.1 ng/L [IQR: 11.9, 28.4] vs. 5.5 ng/L [IQR: 3.8, 8.6], p<0.0001). We also noted increased plasma CRP levels in those patients with SCT compared to control (33.7 mg/L [IQR: 22.8, 62.8] vs. 11.2 mg/L [IQR: 2.2, 19.5], p = 0.016). In patients with SCT, there was a striking correlation between PS exposure and TAT levels (r = 0.897, p<0.0001), but no correlation was noted between PS exposure and levels of CRP (r=-0.17, p = 0.63).

These data suggest that patients with SCT trait in ESRD may be subject to an increased risk of thrombotic complications related to increased PS exposure on RBCs.

No relevant conflicts of interest to declare.