Endothelial cell-derived microparticles in allogeneic hematopoietic stem cell recipients.

Background: Alterations of microparticles derived from different cell types are described in a number of diseases associated with inflammation and hemostatic disorders.

Methods: In this prospective study, we firstly analyzed endothelial cell derived microparticles (EMP) in 19 hematopoietic stem cell recipients. Cultured human umbilical vein endothelial cells (HUVEC) stimulated with tumor necrosis factor-alpha (TNF-alpha) served as positive controls.

Evaluation of C-reactive protein, interleukin-6, and procalcitonin levels in allogeneic hematopoietic stem cell recipients.

Background: Prompt detection of transplant-related complications (TRC) as infections, acute graft-versus-host disease (aGVHD), microangiopathic hemolytic anemia, or veno-occlusive disease following allogeneic hematopoietic stem cell transplantation (HSCT) is essential.

Patients And Methods: We conducted a prospective trial on clinical significance of C-reactive protein (CRP), interleukin-6 (IL-6) and procalcitonin (PCT) serum levels in TRC. A total of 350 stem cell recipients were admitted.

Diagnosis of hepatic veno-occlusive disease by plasminogen activator inhibitor-1 plasma antigen levels: a prospective analysis in 350 allogeneic hematopoietic stem cell recipients.

Background: Veno-occlusive disease (VOD) is one of the most serious complications following allogeneic hematopoietic stem cell transplantation (HSCT) and is associated with a high mortality. We conducted a large trial in order to investigate the value of plasminogen activator inhibitor-1 (PAI-1) plasma antigen levels in VOD patients as PAI-1 has been described as a possible diagnostic marker of VOD.

Methods: In all, 350 stem cell recipients were included in our study.

Kinetics of dendritic cell chimerism and T cell chimerism in allogeneic hematopoietic stem cell recipients.

Dendritic cells (DC) as potent antigen-presenting cells (APC) and T cells as effector cells play an essential role in the pathophysiology of both graft-versus-host (GvH) and graft-versus-leukemia (GvL) reactions after transplantation. Therefore, we determined the kinetics of DC and T-cell chimerism establishment after allogeneic hematopoietic cell transplantation (AHCT) in a group of 144 patients, using fluorescence-activated cell sorting (FACS) or magnetic cell sorting (MACS) followed by FISH or STR-PCR analysis for chimerism evaluation. In all, three cell lines investigated (CD3(+) T cells, CD11c(+) DC1 and CD123(+) DC2), we found a rapid and consistent establishment of complete donor chimerism (CDC) in over 70% of all patients during the first 6 weeks after AHCT.

Peripheral dendritic cell chimerism in allogeneic hematopoietic stem cell recipients.

Background: Relapse and graft-versus-host disease (GVHD) represent major causes of morbidity and mortality following allogeneic hematopoietic stem cell transplantation (HSCT). Although leukocyte and T-cell chimerism analyses are performed routinely suggesting a predictive value on the patients outcome, little is known about chimerism of dendritic cells (DC) representing strong initiators of immune responses.

Methods: In this prospective study, peripheral DC1 (CD11c+) and DC2 (CD123+) chimerism was determined in hematopoetic stem cell recipients.

Recombinant activated factor VII in treatment of bleeding complications following hematopoietic stem cell transplantation.

Background: Bleeding is a common complication following hematopoietic stem cell transplantation (HSCT) and standard hemostatic treatment is often ineffective. We conducted a multicentre, randomized trial of the efficacy and safety of activated recombinant factor VII (rFVIIa, NovoSeven) in the treatment of bleeding following HSCT.

Methods: 100 patients with moderate or severe bleeding (52 gastrointestinal; 26 hemorrhagic cystitis; seven pulmonary; one cerebral; 14 other) were included from days +2 to +180 post-transplant (97 allogeneic; three autologous) to receive seven doses of rFVIIa (40, 80 or 160 microg kg(-1)) or placebo every 6 h.

Protein C and procollagen III peptide levels in patients with hepatic dysfunction after allogeneic hematopoietic stem cell transplantation.

Veno-occlusive disease (VOD) is one of the most serious complications following hematopoietic stem cell transplantation (HSCT) and is associated with a high mortality. We conducted a large trial on the clinical significance of protein C (PC) and procollagen III peptide (PNPIII) levels, which have been described as possible diagnostic markers of VOD. In total, 350 patients undergoing allogeneic HSCT were included.

Transforming growth factor beta-1 released from platelets contributes to hypercoagulability in veno-occlusive disease following hematopoetic stem cell transplantation.

Background: Hepatic veno-occlusive disease (VOD) is one of the most disastrous complications after allogeneic hematopoetic stem cell transplantation (HSCT). Thrombocytopenia with refractoriness to platelet transfusions suggests an increased platelet consumption in these patients. Interactions between platelets and endothelial cells might contribute to the hypercoagulable state at the sinusoidal endothelium as a central mechanism in the pathogenesis of VOD.

Impact of thrombophilic gene mutations and graft-versus-host disease on thromboembolic complications after allogeneic hematopoietic stem-cell transplantation.

Background: Hemostatic events in patients undergoing allogeneic hematopoietic stem-cell transplantation (HSCT) increase the morbidity and mortality in this cohort. Little is known about the impact of graft-versus-host disease (GvHD) or of thrombophilic gene mutations/polymorphisms on these complications.

Study Design: Eighty-nine allogeneic stem-cell recipients and their donors were evaluated prospectively for the presence of the factor V G1691A mutation, the prothrombin G20210A mutation, the 5,10-methylenetetrahydrofolate-reductase (MTHFR) C677T mutation, the glycoprotein IIIa PI(a1/a2) polymorphism, the fibrinogen-beta-chain 455G/A polymorphism, the plasminogen activator inhibitor-1 -675 4G/5G polymorphism, and the angiotensin-converting enzyme intron 16 I/D polymorphism.

Bleeding complications after hematopoietic stem cell transplantation.

Hemostatic disturbances are common in patients undergoing hematopoietic stem cell transplantation (HSCT), and have a significant impact on morbidity and mortality. Graft-versus-host disease (GvHD), in which the donor's T lymphocytes mount an immune response against the recipient's cells, is a life-threatening condition that correlates strongly with the incidence and severity of bleeding episodes, highlighting the complex interaction between the hemostatic and immunological systems. Patients with GvHD of the gut also exhibit a deficiency of factor XIII (FXIII), further increasing the hemorrhagic risk.

Hemostatic complications in bone marrow transplantation: a retrospective analysis of 447 patients.

Background: Hemostatic complications are not uncommon after bone marrow transplantation (BMT). However, little is known about the frequency, localization, determinants, and outcome of hemostatic events in autologous and allogeneic BMT.

Methods: Four hundred forty-seven patients (364 allogeneic, 83 autologous transplants) were evaluated retrospectively for the presence of hemostatic complications (bleeding, thrombosis, hepatic veno-occlusive disease [VOD], microangiopathic hemolytic anemia) from the start of conditioning therapy until June 2000.

Characterization and identification of steroid sulfate transporters of human placenta.

Human trophoblasts depend on the supply of external precursors, such as dehydroepiandrosterone-3-sulfate (DHEA-S) and 16 alpha-OH-DHEA-S, for synthesis of estrogens. The aim of the present study was to characterize the uptake of DHEA-S by isolated mononucleated trophoblasts (MT) and to identify the involved transporter polypeptides. The kinetic analysis of DHEA-(35)S uptake by MT revealed a saturable uptake mechanism (K(m) = 26 microM, V(max) = 428 pmol x mg protein(-1) x min(-1)), which was superimposed by a nonsaturable uptake mechanism (diffusion constant = 1.

Platelet function rather than plasmatic coagulation explains hypercoagulable state in cholestatic liver disease.

Background/aims: As compared to other chronic liver diseases, cholestatic disorders are associated with a better outcome of variceal bleeding and less blood loss at transplantation, suggesting the presence of a hypercoagulable state. We have assessed plasmatic coagulation and platelet function in patients with cholestatic and non-cholestatic liver disease.

Methods: Thirty-seven patients with chronic cholestatic liver disease (primary biliary cirrhosis (PBC)/primary sclerosing cholangitis (PSC)), 53 patients with chronic hepatitis C (HCV) or alcoholic cirrhosis (C2), and 62 healthy controls were studied.

Flow cytometric findings in platelets of patients following allogeneic hematopoietic stem cell transplantation.

Following allogeneic hematopoietic stem cell transplantation (HSCT) patients may have an increased bleeding tendency in spite of a normal platelet count. Moreover, an association between chronic graft-versus-host disease (cGVHD) and a thrombophilic state has been observed. Platelet receptors and granules from 27 patients following HSCT (13 without cGVHD, 14 with cGVHD) were evaluated by flow cytometric analysis and compared to 62 healthy controls.

The impact of antithymocyte globulin on short-term toxicity after allogeneic stem cell transplantation.

Antithymocyte globulin (ATG) is commonly used in allogeneic haematopoietic stem cell transplantation (HSCT). Little information is available, however, as to the optimal protocol for use and the side-effects occurring if ATG is administered in high daily doses (10-30 mg/kg). We report our experience with ATG Fresenius (ATG-F) in conditioning for allogeneic HSCT.

Platelet flow cytometric findings in patients undergoing conditioning therapy for allogeneic hematopoietic stem cell transplantation.

The conditioning regimen preceding hematopoietic stem cell transplantation (HSCT) causes a rapid decrease in the platelet count and signs of disseminated intravascular coagulation, possibly indicating platelet activation. As impacts during the conditioning regimen may predict later transplantation-associated complications, we investigated changes in platelet membrane glycoproteins (GP) and the liberation of microparticles. Platelet receptors and granules of 49 patients undergoing HSCT were evaluated by flow cytometric analysis before and after the different phases of the conditioning regimen [chemotherapy, total body irradiation (TBI), therapy with antithymocyte globulin (ATG)] and final transplantation.

Impact of thrombophilic gene mutations on thrombosis risk in patients with gastrointestinal carcinoma.

Background: Patients with malignancies have an increased risk for thromboembolic events due to the release of tissue factor by the tumor, damage to the vessel wall, and immobilization. Moreover, tumors may improve their growth and metastatic spread by utilizing the coagulation system. To date, no information is available on the additional role of prothrombotic mutations in these patients.

Factor XIII activity levels in patients with allogeneic haematopoietic stem cell transplantation and acute graft-versus-host disease of the gut.

Severe graft-versus-host disease (GvHD) of the gut clinically resembles Crohn's disease and ulcerative colitis. As low plasma levels of factor XIII (FXIII) have been described in chronic inflammatory bowel disease (CIBD) and as beneficial effects of FXIII concentrates in CIBD have been reported, we studied the FXIII plasma activity levels in patients undergoing allogeneic stem cell transplantation (SCT). In 20 of 22 patients with an uncomplicated course of SCT, FXIII stayed within the normal range (median 102 iu/dl, range 74-122), but was significantly reduced with the lowest FXIII levels on d 0 and 7 (d 0: median 83 iu/dl, range 55-165, d 7: median 83, range 70-101).