Background: Venous occlusive disease (VOD) of the liver has been reported to be associated with haematopoietic stem cells transplant. This condition has been associated with high mortality rate of up to 90% as multiorgane failure may occur [McDonald et al. 1993]. Several markers of thrombosis have been suggested to be involved in the VOD pathogenesis. However, this condition continues to have a poor prognosis and to be poorly understood. Recently an increment of plasminogen activator inibitor (PAI-1) has been identified as a possibile valid marker of VOD. Patients with solid tumours may also develop VOD. Interestingly, patients with Wilms Tumor (TW) develop VOD following chemotherapy treatment without any HSCT. Microparticles have been reported in several prothrombotic conditions [Piccin et al 2007], however studies on their association with PAI-1 are lacking. We report on VOD cases within a paediatric cohort of children affected by TW treated with chemotherapy. Aims: The aim of this study was to investigate new biological marker involved with VOD. Methods: Twelve consecutive patients (F=7; M=5) with a diagnosis of TW were treated with a combination of chemotherapy regimen based on vincristin, actinomicine-D and doxorubicine. Only five patients developed VOD after a median of 4 weeks from diagnosis (range 1-14 weeks). In all cases, poor platelets plasma was stored at -80C°. Three consecutive sampling at intervals of 3 weeks, were carried out during hospitalisation on each case. Standard coagulative parameters were studied (PT, PTT, Fibrinogen, D-Dimer). Microparticle studies were carried out using flow cytometry. PAI-1 antigen (PAI-1:Ag) was measured by ELISA (Tint-Elize PAI-1, Hyphen BioMed - Neuville-sur-Oise, France), while PAI-1 activity (PAI-1:act) was measured using chromogenic assay (TriniLIZE PAI- 1 Activity, Trinity Biotech - Jamestown, NY, USA). Results: The analysis of consecutive measurements over time revealed a statistically significant negative correlation for PT (-0.264; p<0.001) and for Fibrinogen (-0.023; p< 0.008). MP, PAI-1:Ag and PAI-1:act showed a positive trend over time, however statistical significance was not reached. A linear regression study showed an inverse relationship of PAI-1: Ag and MP coeff (Mp= -0.005, P= 0.521). Interestingly, a polynomial relationship between PAI-1:act and MP was seen [PAI-1:act = cost+ (MP/1000)-2 + (MP/1000)2; coeff MP-2:23.0; p=0.002; MP2 :11.9; p=0.006; Model , p=0.006] (Figures 1 and 2). Summary and Conclusions: In conclusion, this preliminary data shows that following chemotherapy for TW based on vincristin, actinomicine-D and doxorubicine, some coagulative changes are present and persist over time. Moreover, we demonstrated a polynomial relationship between PAI-1:act and MP in patients with WT after chemotherapy. Although our numbers are small, we believe that prospective studies on MP and PAI-1 may help to shed light on VOD pathophysiology.
WILMS TUMOUR AND VENO-OCCLUSIVE DISEASE. THE ROLE OF MICROPARTICLES AND PAI-1
CESARO, SIMONE
2014-01-01
Abstract
Background: Venous occlusive disease (VOD) of the liver has been reported to be associated with haematopoietic stem cells transplant. This condition has been associated with high mortality rate of up to 90% as multiorgane failure may occur [McDonald et al. 1993]. Several markers of thrombosis have been suggested to be involved in the VOD pathogenesis. However, this condition continues to have a poor prognosis and to be poorly understood. Recently an increment of plasminogen activator inibitor (PAI-1) has been identified as a possibile valid marker of VOD. Patients with solid tumours may also develop VOD. Interestingly, patients with Wilms Tumor (TW) develop VOD following chemotherapy treatment without any HSCT. Microparticles have been reported in several prothrombotic conditions [Piccin et al 2007], however studies on their association with PAI-1 are lacking. We report on VOD cases within a paediatric cohort of children affected by TW treated with chemotherapy. Aims: The aim of this study was to investigate new biological marker involved with VOD. Methods: Twelve consecutive patients (F=7; M=5) with a diagnosis of TW were treated with a combination of chemotherapy regimen based on vincristin, actinomicine-D and doxorubicine. Only five patients developed VOD after a median of 4 weeks from diagnosis (range 1-14 weeks). In all cases, poor platelets plasma was stored at -80C°. Three consecutive sampling at intervals of 3 weeks, were carried out during hospitalisation on each case. Standard coagulative parameters were studied (PT, PTT, Fibrinogen, D-Dimer). Microparticle studies were carried out using flow cytometry. PAI-1 antigen (PAI-1:Ag) was measured by ELISA (Tint-Elize PAI-1, Hyphen BioMed - Neuville-sur-Oise, France), while PAI-1 activity (PAI-1:act) was measured using chromogenic assay (TriniLIZE PAI- 1 Activity, Trinity Biotech - Jamestown, NY, USA). Results: The analysis of consecutive measurements over time revealed a statistically significant negative correlation for PT (-0.264; p<0.001) and for Fibrinogen (-0.023; p< 0.008). MP, PAI-1:Ag and PAI-1:act showed a positive trend over time, however statistical significance was not reached. A linear regression study showed an inverse relationship of PAI-1: Ag and MP coeff (Mp= -0.005, P= 0.521). Interestingly, a polynomial relationship between PAI-1:act and MP was seen [PAI-1:act = cost+ (MP/1000)-2 + (MP/1000)2; coeff MP-2:23.0; p=0.002; MP2 :11.9; p=0.006; Model , p=0.006] (Figures 1 and 2). Summary and Conclusions: In conclusion, this preliminary data shows that following chemotherapy for TW based on vincristin, actinomicine-D and doxorubicine, some coagulative changes are present and persist over time. Moreover, we demonstrated a polynomial relationship between PAI-1:act and MP in patients with WT after chemotherapy. Although our numbers are small, we believe that prospective studies on MP and PAI-1 may help to shed light on VOD pathophysiology.
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