Clinical Significance of Hemostatic Parameters in the Patients with Transplantation-Related Complications during Hematopoietic Stem Cell Transplantation.

Introduction Hepatic veno-occlusive disease (VOD) and thrombotic microangiopathy (TMA) are important and serious thrombotic complications after hematopoietic stem cell transplantation (HSCT), but the early diagnosis remains difficult since their clinical manifestations are similar to those of other transplantation-related complications. Our aim in this study is to illustrate the early alteration of hemostatic parameters in recipients of hematopoietic stem cell transplantation and then determine its value in transplantation-related thrombotic complications and other post-HSCT clinical settings, such as acute graft-versus-host disease (aGVHD) and infection.

Methods Plasma from 95 patients undergoing HSCT was collected prior to conditioning therapy and then weekly until five weeks after HSCT. Hemostatic parameters were evaluated prospectively in our institution. 1. Plasminogen activator inhibitor-1(PAI-1), tissue-plasminogen activator(t-PA), protein C(PC), von Willebrand factor(vWF)and thrombomodulin(TM)were investigated by enzymimmunoassay. Other hemostatic parameters such as activated partial thromboplastin time(APTT), prothrombin time(PT), fibrinogen (Fg), antithrombin III(AT III) and D-dimer(D-Di) were measured with hemagglutinin equipment in the same time. 2. According to the different settings after transplantation, three groups of transplant associated complications were classified as thrombus group (VOD n=5, TMA n=1), aGVHD group (n=29) and infection group (n=19). Systemic analyses were carried out for the hemostatic parameters and transplantation-related thrombotic complications or other clinical settings.

Results Significant increase was observed in the levels of fibrinogen, t-PA and PAI-1 after transplant, while Protein C and ATIII decreased significantly(P<0.05). No significant change existed in PT, vWF and APTT levelsfollowing HSCT(P>0.05). All the patients with three different complications presented with significantly increased PAI-1 and lower level of Protein C compared with those who had no complication (P<0.05), other parameters didn’t change apparently in the same time(P>0.05). However, 6 patients with thrombotic complications (VOD5, TMA1) extremely showed elevated PAI-1 levels after the clinical onset of thrombotic complications by comparison with highest post-HSCT values in the aGVHD patients or infection patients (P<0.05). Significant decreased level of Protein C was simultaneously found in the 29 patients with aGVHD compared with the 19 patients with infection(P<0.01)and the 6 patients with thrombotic complications(P<0.05).

Conclusion All the results demonstrated early hemostatic imbalance is one important manifestation during HSCT, reflecting prothrombotic states and endothelial damage, which may be caused by the conditioning regimen and/or transplantation-related complications. There is apparent correlation between the alteration of hemostasis related parameters and various transplantation-associated complications. The extreme elevation of PAI-1 can be considered as important value to distinguish the development of thrombotic complications from other transplantation-related complications, while Protein C diminution promotes the early diagnosis of aGVHD from thrombosis and infection.