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. 2019 Oct 26;8(11):1796.
doi: 10.3390/jcm8111796.

Is There Any Improvement of the Coagulation Imbalance in Sickle Cell Disease After Hematopoietic Stem Cell Transplantation?

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Free PMC article

Is There Any Improvement of the Coagulation Imbalance in Sickle Cell Disease After Hematopoietic Stem Cell Transplantation?

Laurence Rozen et al. J Clin Med. .
Free PMC article

Abstract

Several components of the clotting system are modified towards hypercoagulability in sickle cell disease (SCD). To date, hematopoietic stem cell transplantation (HSCT) is the only validated curative treatment of SCD. Here, we investigated the changes in the hemostatic potential of SCD children who've received a successful HSCT. Seventeen children with severe SCD were enrolled in the study. Thrombin generation (TG) was performed on citrated platelet-poor plasma, obtained before and 3, 6, 9, 12 and 15 months after HSCT. TG was triggered using 1 pM tissue factor and 4 µM phospholipids with or without thrombomodulin (TM). Before the HSCT, SCD children showed a higher endogenous thrombin potential (ETP), higher peak, higher velocity and shorter time-to-peak of TG than the normal controls (NC). ETP did not significantly change following the HSCT. However, the peak, velocity and time-to-peak of TG reversed to normal ranges from 3 months post-HSCT and remained so up to 15 months post-HSCT. The reduction of ETP after the addition of thrombomodulin (RETP) was dramatically reduced in SCD children before HSCT as compared with the NC. A partial reversal of RETP was observed from 3 months through 15 months post-HSCT. No statistical difference was observed for patient age or donor hemoglobinopathy status. In summary, successful HSCT improves the kinetics of TG but not the total thrombin capacity in SCD children.

Keywords: coagulation; hematopoietic stem cell transplantation; hemostatic potential; sickle cell disease; thrombin generation test.

Conflict of interest statement

The authors declare no conflict of interest.

Figures

Figure 1
Figure 1
Comparison of the TG parameters with TM (median and range) between normal controls (NC) and sickle cell disease (SCD) patients before HSCT. ETP TM+: endogenous thrombin potential following addition of thrombomodulin, RETP: reduction of ETP with the addition of thrombomodulin, HSCT: hematopoietic stem cell transplantation, TM+: with addition of thrombomodulin, TT: time to peak, NC: normal control, *** p < 0.001 as compared to the controls using the Mann–Whitney test.
Figure 2
Figure 2
Modification of TG parameters (median and range) before and after successful HSCT, with (TM+) the addition of thrombomodulin. The range p2.5–p97.5 of NC is colored in green. ETP TM+: endogenous thrombin potential following addition of thrombomodulin, RETP: reduction of ETP with the addition of thrombomodulin, HSCT: hematopoietic stem cell transplantation, TM+: with addition of thrombomodulin, NC: normal control, *: p < 0.05, ** p < 0.01.

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