Assessment of the coagulation profile in hemato-oncological patients receiving ATG-based conditioning treatment for allogeneic stem cell transplantation.

Antithymocyte globulin (ATG) is increasingly used in pre-allogeneic stem cell transplantation (allo-SCT) conditioning regimens to prevent graft rejection and graft-versus-host disease. However, ATG was also found to be associated with increased incidence of thrombosis during organ transplantation. In the present study, we tested the coagulation status of 21 patients with hematologic malignancies undergoing allo-SCT who received ATG-based (11 patients) or non-ATG-based (10) conditioning treatment. We assessed several thrombophilia markers as well as circulating total and endothelial microparticles (TMP/EMP) and soluble CD40 ligand (CD40L). No significant difference in the mean values of prothrombin time, partial thromboplastin time, fibrinogen, antithrombin, protein C, protein S, thrombin-antithrombin III complex, homocysteine levels, prevalence of genetic thrombophilia markers and levels of EMP, TMP or CD40L was observed between the ATG-treated and ATG-untreated patients, as well as before and after conditioning in each group separately. Platelet counts decreased significantly in ATG-treated patients; however, this decrease was not associated with clinical or laboratory evidence of disseminated intravascular coagulation. No patient developed thromboembolic event or veno-occlusive liver disease. Our results suggest that allo-SCT is not associated with increased hypercoagulability and addition of ATG to conditioning regimen has no significant procoagulant effect.

Single and combined prothrombotic factors in patients with idiopathic venous thromboembolism: prevalence and risk assessment.

The inherited thrombophilias--deficiencies of protein C, protein S, and antithrombin III--and the prothrombotic polymorphisms factor V G1691A and factor II G20210A predispose patients toward venous thromboembolism (VTE). The aim of this study was to determine the prevalence of single and combined prothrombotic factors in patients with idiopathic VTE and to estimate the associated risks. The study group consisted of 162 patients referred for work-up of thrombophilia after documented VTE. The controls were 336 consecutively admitted patients. In all subjects factor V G1691A, factor II G20210A, and methylenetetrahydrofolate reductase (MTHFR) C677T were analyzed by specific polymerase chain reactions and restriction enzymes. Activities of antithrombin III and protein C, free protein S antigen, and lupus anticoagulant were determined in a subset of 109 patients who were not receiving oral anticoagulants. The prevalences of heterozygotes and homozygotes for factor V G1691A and factor II G20210A among patients and controls were 40.1% versus 3.9% and 18.5% versus 5.4%, respectively (P=0.0001). The prevalence of homozygotes for MTHFR C677T in patients was 22.8% and in controls, 14.3% (P=0.025). Heterozygous and homozygous factor V G1691A, factor II G20210A, and homozygous MTHFR C677T were found to be independent risk factors for VTE, with odds ratios of 16.3, 3.6, and 2.1, respectively. Two or more polymorphisms were detected in 27 of 162 patients (16.7%) and in 3 of 336 controls (0.9%). Logistic regression analysis disclosed odds ratios of 58.6 (confidence interval [CI], 22.1 to 155.2) for joint occurrence of factor V and factor II polymorphisms, of 35.0 (CI, 14.5 to 84.7) for factor V and MTHFR polymorphisms, and of 7.7 (CI, 3.0 to 19.6) for factor II and MTHFR polymorphisms. Among 109 patients in whom a complete thrombophilic work-up was performed, 74% had at least 1 underlying defect. These data indicate that in most patients referred for evaluation of thrombophilia due to idiopathic VTE, 1 or more underlying genetic predispositions were discernible. The presence of >1 of the prothrombotic polymorphisms was associated with a substantial risk of VTE.