Hemostatic Alterations in Patients Undergoing Hematopoietic Stem Cell Transplantation.

Damage of endothelial cells (EC) is known to be involved in pathogenesis of microangiopathy, hepatic veno-occlusive disease, sepsis, capillary leak syndrome, and acute or chronic graft-versus-host disease (GvHD) as major causes of morbidity and mortality in patients after hematopoietic stem-cell transplantation (HSCT). We recently demonstrated in 39 patients undergoing allogeneic stem cell transplantation that numbers of circulating EC (CEC) increased significantly after conditioning regimens and that patients treated with reduced intensity conditioning (RIC) showed significantly lower cell numbers (Woywodt et al., Blood, 2004 May 1;103(9):3603-5).

Here we report on the measurement of plasma levels of von Willebrand factor (vWF), thrombomodulin (TM), PAI-I and TAFI in the course of HSCT.

Measurement of vWF, TM, PAI-I and TAFI was performed in the 39 patients (20 male, 19 female; n = 21: HLA-matched unrelated donor; n = 18: related donors). Blood samples were collected before starting conditioning regimen (day −7), the day before transplantation (day −1) and at day +7, +14 and +21 after transplantation. 28 patients received a conventional regimen with cyclophosphamide (120 mg/kg) and either total body irradiation with 12 Gy (n = 14) or busulfan (16 mg/kg, n = 14). 11 patients undergoing stem-cell transplantation were treated with reduced intensity conditioning with fludarabine (150 mg/m²) and busulfan (8 mg/kg body) or melphalan (120 mg/m²).

Median baseline vWF was elevated (262%, range 68–612, normal range: 50–150). Median baseline PAI-I (11.3 U/l; range 1.8–34.4; normal range: < 20) and median baseline TAFI (90%; range 46–126; normal range: 70–120) were within normal limits. TM level was lower than normal values (median 3.95 ng/ml; range 2.69–9.36; normal range: 6.6–10.6). Levels of vWF increased after conditioning regimen and remained elevated until day +21 (day −1: median 262; day+7: 268; day +14: 327; day +21: 374; p < 0.01). Median TM remained low at all time points (day −1: median 4.26; day +7: 3.86; day +14: 3.97; day +21: 4.52).

Levels of TAFI remained unchanged (day −1: median 82; day +7: median 91, day +14: median 88; day +21: median 89). There were also no differences in levels of PAI-I before or after conditioning regimen or after transplantation (day −1: median 11.4, day +7: median 10.8, day + 14: median 14, day + 21: median 11.8). There was no significant difference in vWF in patients undergoing reduced intensity conditioning compared to patients treated with conventional regimens.

Interestingly, there was no correlation between the endothelial markers as vWF and TM and numbers of CEC.

Our data indicate that significant alterations of the hemostatic system occur in patients undergoing HSCT. Further studies are warranted to define the clinical role of both, hemostatic alterations and CEC in the course of HSCT.