Publications by authors named "Daniela Belotti"

15 Publications

  • Page 1 of 1

Sleeping Beauty-engineered CAR T cells achieve antileukemic activity without severe toxicities.

J Clin Invest 2020 11;130(11):6021-6033

Tettamanti Research Center, Department of Pediatrics, University of Milano-Bicocca/Fondazione MBBM, Monza, Italy.

BACKGROUNDChimeric antigen receptor (CAR) T cell immunotherapy has resulted in complete remission (CR) and durable response in highly refractory patients. However, logistical complexity and high costs of manufacturing autologous viral products limit CAR T cell availability.METHODSWe report the early results of a phase I/II trial in B cell acute lymphoblastic leukemia (B-ALL) patients relapsed after allogeneic hematopoietic stem cell transplantation (HSCT) using donor-derived CD19 CAR T cells generated with the Sleeping Beauty (SB) transposon and differentiated into cytokine-induced killer (CIK) cells.RESULTSThe cellular product was produced successfully for all patients from the donor peripheral blood (PB) and consisted mostly of CD3+ lymphocytes with 43% CAR expression. Four pediatric and 9 adult patients were infused with a single dose of CAR T cells. Toxicities reported were 2 grade I and 1 grade II cytokine-release syndrome (CRS) cases at the highest dose in the absence of graft-versus-host disease (GVHD), neurotoxicity, or dose-limiting toxicities. Six out of 7 patients receiving the highest doses achieved CR and CR with incomplete blood count recovery (CRi) at day 28. Five out of 6 patients in CR were also minimal residual disease negative (MRD-). Robust expansion was achieved in the majority of the patients. CAR T cells were measurable by transgene copy PCR up to 10 months. Integration site analysis showed a positive safety profile and highly polyclonal repertoire in vitro and at early time points after infusion.CONCLUSIONSB-engineered CAR T cells expand and persist in pediatric and adult B-ALL patients relapsed after HSCT. Antileukemic activity was achieved without severe toxicities.TRIAL REGISTRATIONClinicalTrials.gov NCT03389035.FUNDINGThis study was supported by grants from the Fondazione AIRC per la Ricerca sul Cancro (AIRC); Cancer Research UK (CRUK); the Fundación Científica de la Asociación Española Contra el Cáncer (FC AECC); Ministero Della Salute; Fondazione Regionale per la Ricerca Biomedica (FRRB).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1172/JCI138473DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC7598053PMC
November 2020

Linking cell function with perfusion: insights from the transcatheter delivery of bone marrow-derived CD133 cells in ischemic refractory cardiomyopathy trial (RECARDIO).

Stem Cell Res Ther 2018 09 14;9(1):235. Epub 2018 Sep 14.

Vascular Biology and Regenerative Medicine Unit, Centro Cardiologico Monzino-IRCCS, Via Carlo Parea 4, 20138, Milan, Italy.

Background: Cell therapy with bone marrow (BM)-derived progenitors has emerged as a promising therapeutic for refractory angina (RA) patients. In the present study, we evaluated the safety and preliminary efficacy of transcatheter delivery of autologous BM-derived advanced therapy medicinal product CD133 cells (ATMP-CD133) in RA patients, correlating perfusion outcome with cell function.

Methods: In the phase I "Endocavitary Injection of Bone Marrow Derived CD133 Cells in Ischemic Refractory Cardiomyopathy" (RECARDIO) trial, a total of 10 patients with left ventricular (LV) dysfunction (ejection fraction ≤ 45%) and evidence of reversible ischemia, as assessed by single-photon emission computed tomography (SPECT), underwent BM aspiration and fluoroscopy-based percutaneous endomyocardial delivery of ATMP-CD133. Patients were evaluated at 6 and 12 months for safety and preliminary efficacy endpoints. ATMP-CD133 samples were used for in vitro correlations.

Results: Patients were treated safely with a mean number of 6.57 ± 3.45 ×  10 ATMP-CD133. At 6-month follow-up, myocardial perfusion at SPECT was significantly ameliorated in terms of changes in summed stress (from 18.2 ± 8.6 to 13.8 ± 7.8, p = 0.05) and difference scores (from 12.0 ± 5.3 to 6.1 ± 4.0, p = 0.02) and number of segments with inducible ischemia (from 7.3 ± 2.2 to 4.0 ± 2.7, p = 0.003). Similarly, Canadian Cardiovascular Society and New York Heart Association classes significantly improved at follow-up vs baseline (p ≤ 0.001 and p = 0.007, respectively). Changes in summed stress score changes positively correlated with ATMP-CD133 release of proangiogenic cytokines HGF and PDGF-bb (r = 0.80, p = 0.009 and r = 0.77, p = 0.01, respectively) and negatively with the proinflammatory cytokines RANTES (r = - 0.79, p = 0.01) and IL-6 (r = - 0.76, p = 0.02).

Conclusion: Results of the RECARDIO trial suggested safety and efficacy in terms of clinical and perfusion outcomes in patients with RA and LV dysfunction. The observed link between myocardial perfusion improvements and ATMP-CD133 secretome may represent a proof of concept for further mechanistic investigations.

Trial Registration: ClinicalTrials.gov, NCT02059681 . Registered 11 February 2014.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1186/s13287-018-0969-zDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC6137884PMC
September 2018

Phase II Study of Sequential Infusion of Donor Lymphocyte Infusion and Cytokine-Induced Killer Cells for Patients Relapsed after Allogeneic Hematopoietic Stem Cell Transplantation.

Biol Blood Marrow Transplant 2017 Dec 13;23(12):2070-2078. Epub 2017 Jul 13.

USC Hematology and Bone Marrow Transplant Unit ASST Papa Giovanni XXIII Bergamo, Bergamo, Italy; Università degli Studi di Milano, Milan Italy.

Seventy-four patients who relapsed after allogeneic stem cell transplantation were enrolled in a phase IIA study and treated with the sequential infusion of donor lymphocyte infusion (DLI) followed by cytokine-induced killer (CIK) cells. Seventy-three patients were available for the intention to treat analysis. At least 1 infusion of CIK cells was given to 59 patients, whereas 43 patients received the complete cell therapy planned (58%). Overall, 12 patients (16%) developed acute graft-versus-host disease (aGVHD) of grades I to II in 7 cases and grades III to IV in 5). In 8 of 12 cases, aGVHD developed during DLI treatment, leading to interruption of the cellular program in 3 patients, whereas in the remaining 5 cases aGVHD was controlled by steroids treatment, thus allowing the subsequent planned administration of CIK cells. Chronic GVHD (cGVHD) was observed in 11 patients (15%). A complete response was observed in 19 (26%), partial response in 3 (4%), stable disease in 8 (11%), early death in 2 (3%), and disease progression in 41 (56%). At 1 and 3 years, rates of progression-free survival were 31% and 29%, whereas rates of overall survival were 51% and 40%, respectively. By multivariate analysis, the type of relapse, the presence of cGVHD, and a short (<6 months) time from allogeneic hematopoietic stem cell transplantation to relapse were the significant predictors of survival. In conclusion, a low incidence of GVHD is observed after the sequential administration of DLI and CIK cells, and disease control can be achieved mostly after a cytogenetic or molecular relapse.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbmt.2017.07.005DOI Listing
December 2017

Full GMP-compliant validation of bone marrow-derived human CD133(+) cells as advanced therapy medicinal product for refractory ischemic cardiomyopathy.

Biomed Res Int 2015 1;2015:473159. Epub 2015 Oct 1.

Laboratory of Vascular Biology and Regenerative Medicine, Centro Cardiologico Monzino, IRCCS, Via Parea 4, 20138 Milan, Italy ; Department of Clinical Sciences and Community Health, Università degli Studi di Milano, Via Festa del Perdono 7, 20122 Milan, Italy.

According to the European Medicine Agency (EMA) regulatory frameworks, Advanced Therapy Medicinal Products (ATMP) represent a new category of drugs in which the active ingredient consists of cells, genes, or tissues. ATMP-CD133 has been widely investigated in controlled clinical trials for cardiovascular diseases, making CD133(+) cells one of the most well characterized cell-derived drugs in this field. To ensure high quality and safety standards for clinical use, the manufacturing process must be accomplished in certified facilities following standard operative procedures (SOPs). In the present work, we report the fully compliant GMP-grade production of ATMP-CD133 which aims to address the treatment of chronic refractory ischemic heart failure. Starting from bone marrow (BM), ATMP-CD133 manufacturing output yielded a median of 6.66 × 10(6) of CD133(+) cells (range 2.85 × 10(6)-30.84 × 10(6)), with a viability ranged between 96,03% and 99,97% (median 99,87%) and a median purity of CD133(+) cells of 90,60% (range 81,40%-96,20%). Based on these results we defined our final release criteria for ATMP-CD133: purity ≥ 70%, viability ≥ 80%, cellularity between 1 and 12 × 10(6) cells, sterile, and endotoxin-free. The abovementioned criteria are currently applied in our Phase I clinical trial (RECARDIO Trial).
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1155/2015/473159DOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC4606188PMC
August 2016

Treatment of graft versus host disease with mesenchymal stromal cells: a phase I study on 40 adult and pediatric patients.

Biol Blood Marrow Transplant 2014 Mar 7;20(3):375-81. Epub 2013 Dec 7.

HSCT Pediatric Unit and Laboratory of Cell Therapy "S. Verri", San Gerardo Hospital, Monza, Italy.

This phase I multicenter study was aimed at assessing the feasibility and safety of intravenous administration of third party bone marrow-derived mesenchymal stromal cells (MSC) expanded in platelet lysate in 40 patients (15 children and 25 adults), experiencing steroid-resistant grade II to IV graft-versus-host disease (GVHD). Patients received a median of 3 MSC infusions after having failed conventional immunosuppressive therapy. A median cell dose of 1.5 × 10(6)/kg per infusion was administered. No acute toxicity was reported. Overall, 86 adverse events and serious adverse events were reported in the study, most of which (72.1%) were of infectious nature. Overall response rate, measured at 28 days after the last MSC injection, was 67.5%, with 27.5% complete response. The latter was significantly more frequent in patients exhibiting grade II GVHD as compared with higher grades (61.5% versus 11.1%, P = .002) and was borderline significant in children as compared with adults (46.7 versus 16.0%, P = .065). Overall survival at 1 and 2 years from the first MSC administration was 50.0% and 38.6%, with a median survival time of 1.1 years. In conclusion, MSC can be safely administered on top of conventional immunosuppression for steroid resistant GVHD treatment. Eudract Number 2008-007869-23, NCT01764100.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbmt.2013.11.033DOI Listing
March 2014

Platelet-lysate-expanded mesenchymal stromal cells as a salvage therapy for severe resistant graft-versus-host disease in a pediatric population.

Biol Blood Marrow Transplant 2010 Sep 27;16(9):1293-301. Epub 2010 Mar 27.

Clinica Pediatrica, Università Milano Bicocca, Ospedale San Gerardo, Via Donizetti 106, Monza, MI, Italy.

Despite advances in graft-versus-host-disease (GVHD) treatment, it is estimated that overall survival (OS) at 2 years for hematopoietic cell transplantation (HCT) recipients who experience steroid-resistant GVHD is 10%. Among recent therapeutic approaches for GVHD treatment, mesenchymal stromal cells (MSCs) hold a key position. We describe a multicenter experience of 11 pediatric patients diagnosed with acute or chronic GVHD (aGVHD, cGVHD) treated for compassionate use with GMP-grade unrelated HLA-disparate donors' bone marrow-derived MSCs, expanded in platelet-lysate (PL)-containing medium. Eleven patients (aged 4-15 years) received intravenous (i.v.) MSCs for aGVHD or cGVHD, which was resistant to multiple lines of immunosuppression. The median dose was 1.2 x 10(6)/kg (range: 0.7-3.7 x 10(6)/kg). No acute side effects were observed, and no late side effects were reported at a median follow-up of 8 months (range: 4-18 months). Overall response was obtained in 71.4% of patients, with complete response in 23.8% of cases. None of our patients presented GVHD progression upon MSC administration, but 4 patients presented GVHD recurrence 2 to 5 months after infusion. Two patients developed chronic limited GVHD. This study underlines the safety of PL-expanded MSC use in children. MSC efficacy seems to be greater in aGVHD than in cGVHD, even after failure of multiple lines of immunosuppression.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1016/j.bbmt.2010.03.017DOI Listing
September 2010

GMP-based CD133(+) cells isolation maintains progenitor angiogenic properties and enhances standardization in cardiovascular cell therapy.

J Cell Mol Med 2010 Jun 20;14(6B):1619-34. Epub 2009 Jul 20.

Laboratorio Interdipartimentale di Terapia Cellulare Stefano Verri, Azienda Ospedaliera San Gerardo, Monza, Milan, Italy.

The aim of the present study was to develop and validate a good manufacturing practice (GMP) compliant procedure for the preparation of bone marrow (BM) derived CD133(+) cells for cardiovascular repair. Starting from available laboratory protocols to purify CD133(+) cells from human cord blood, we implemented these procedures in a GMP facility and applied quality control conditions defining purity, microbiological safety and vitality of CD133(+) cells. Validation of CD133(+) cells isolation and release process were performed according to a two-step experimental program comprising release quality checking (step 1) as well as 'proofs of principle' of their phenotypic integrity and biological function (step 2). This testing program was accomplished using in vitro culture assays and in vivo testing in an immunosuppressed mouse model of hindlimb ischemia. These criteria and procedures were successfully applied to GMP production of CD133(+) cells from the BM for an ongoing clinical trial of autologous stem cells administration into patients with ischemic cardiomyopathy. Our results show that GMP implementation of currently available protocols for CD133(+) cells selection is feasible and reproducible, and enables the production of cells having a full biological potential according to the most recent quality requirements by European Regulatory Agencies.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1111/j.1582-4934.2009.00854.xDOI Listing
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3829025PMC
June 2010

The washouts of discarded bone marrow collection bags and filters are a very abundant source of hMSCs.

Cytotherapy 2009 ;11(4):403-13

Laboratory of Cell Therapy G. Lanzani, USC Hematology, Ospedali Riuniti di Bergamo, Bergamo, Italy.

Background Aims: Human multipotent mesenchymal stromal cells (hMSC) are considered good candidates for a growing spectrum of cell therapies. We have validated a protocol that makes use of the washouts of discarded collection sets, left over at the end of the filtration of bone marrow (BM) explants performed for hematopoietic stem cell (HSC) transplantation.

Methods: The method consists of direct plating of cells without density-gradient isolation followed by two detachment steps and expansion in 5% human platelet lysate (hPL).

Results: In a median of 26 days, 14 bags for adult patients and nine bags for pediatric patients for a standard dose of 1x10(6) hMSC/kg body weight could be prepared from the expansion of a fraction of the cells recovered from seven independent washouts. Moreover, 151 vials could be frozen from the remaining cells. The theoretical full expansion of all the frozen vials (validated by the expansion of two independent vials) could have allowed the production of 173 bags for adults and 348 bags for pediatric patients.

Conclusions: The washouts of discarded bags and filters left over at the end of routine BM explants filtration are a very abundant source of hMSC precursors that can be easily utilized for clinical applications.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1080/14653240902960437DOI Listing
September 2009

Rituximab as pre-emptive treatment in patients with thrombotic thrombocytopenic purpura and evidence of anti-ADAMTS13 autoantibodies.

Thromb Haemost 2009 Feb;101(2):233-8

Mario Negri Institute for Pharmacological Research, Clinical Research Center for Rare Diseases Aldo e Cele Daccò, 24020 Ranica, Bergamo, Italy.

Thrombotic thrombocytopenic purpura (TTP) is a rare and severe disease characterized by thrombocytopenia, microangiopathic haemolytic anemia, neurological and renal involvement associated with deficiency of the von Willebrand factor-cleaving protease, ADAMTS13. Persistence of high titers of anti-ADAMTS13 autoantibodies predisposes to relapsing TTP. Since relapses are associated with high morbidity and mortality rates, the optimal therapeutic option should be a pre-emptive treatment able to deplete anti-ADAMTS13 autoantibodies and avoid relapses. Five patients who presented with persistence of undetectable ADAMTS13 activity and high titers of autoantibodies, were treated with rituximab as pre-emptive therapy during remission. Four of them were affected by relapsing TTP and one was treated after the first episode. ADAMTS13 activity ranging from 15% to 75% with disappearance of inhibitors was achieved after three months in all patients, and persisted >20% without inhibitors at six months. In three patients disease-free status is still ongoing after 29, 24 and six months, respectively. Relapses were documented in two patients during follow-up: in one patient remission lasted 51 months; while in the other patient relapse occurred after 13 months. Results demonstrated that rituximab used as pre-emptive treatment may be effective in maintaining a sustained remission in patients with anti-ADAMTS13 antibodies in whom other treatments failed to limit the production of inhibitors, and suggests that re-treatment with rituximab should be considered when ADAMTS13 activity decreases and inhibitors reappear into the circulation, to avoid a new relapse.
View Article and Find Full Text PDF

Download full-text PDF

Source
February 2009

CD34+ stem cell recovery after positive selection of "overloaded" immunomagnetic columns.

Stem Cells Dev 2005 Dec;14(6):740-3

Servizio Trasfusionale, Unità di Aferesi e Criobiologia and Laboratorio di Manipolazione Cellulare e Terapia Genica S. Verri, Ospedale S. Gerardo, Monza, Italy.

Techniques for CD34+ cell enrichment of hematopoietic progenitor cells in grafts destined for transplantation of certain patients with the aim of lowering the amount of infused T lymphocytes and subsequently decreasing the risk of graft versus host disease (GVHD) have been well developed. Adaptations of these techniques should be useful for isolation of other phenotypically defined stem cells. However, a major limitation of techniques now available consists of the number of total nucleated cells or phenotypically defined stem cells that can be processed in a single procedure. Here, we show that recommended levels are much lower than the levels of cells that can be effectively processed by immunomagnetic sorting. Twenty-nine procedures were performed using the Clini- MACS (Miltenyi Biotec) device, which is recommended for processing <6x10(10 )total nucleated cells or <6x10(8) CD34+ cells. Procedures were divided in groups according to their total cellular or CD34+ cell content. We achieved a median CD34+ cell recovery of 68.60% with a median purity of 98.56%, regardless of the loading dose when samples possessing 2-10x10(10) total nucleated cells and 0.8-12.5x10(8) CD34+ cells were applied to a single column. The median levels of CD3+ cells and CD19+ cells in the final product were depleted by 5 logs and 3.8 logs, respectively; no differences were noted when the initial loading dose was increased. Moreover, we found no correlation between the total number nucleated or CD34+ cells loaded and the resultant CD34+ cell recovery. In conclusion, levels of both total nucleated cells and CD34+ can be processed in a single procedure with satisfactory and similar CD34+ cell recovery when these columns are loaded with up to two times as many cells as recommended.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1089/scd.2005.14.740DOI Listing
December 2005

Rituximab prevents recurrence of thrombotic thrombocytopenic purpura: a case report.

Blood 2005 Aug 12;106(3):925-8. Epub 2005 Apr 12.

Mario Negri Institute for Pharmacological Research, Via Gavazzeni, 11, 24125 Bergamo, Italy.

Thrombotic thrombocytopenic purpura (TTP) is a rare disorder of small vessels that is associated with deficiency of the von Willebrand factor-cleaving protease, ADAMTS13. The presence of anti-ADAMTS13 autoantibodies is considered a factor predisposing to relapses. Despite close monitoring and intensive plasma treatment, in these patients acute episodes are still associated with substantial morbidity and mortality rates, and the optimal therapeutic option should be prevention of relapses. This study was conducted in a patient with recurrent TTP due to high titers of ADAMTS13 inhibitors, who used to have 2 relapses of TTP a year. The study compared the standard treatment plasma exchange with rituximab. Results documented that plasma exchange had only a small transient effect on ADAMTS13 activity and inhibitors; on the contrary, prophylaxis with rituximab was associated with disappearance of anti-ADAMTS13 antibodies, a progressive recovery of protease activity, and it allowed the patient to maintain a disease-free state during a more than 2-year follow-up.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1182/blood-2004-12-4885DOI Listing
August 2005

Complement activation: the missing link between ADAMTS-13 deficiency and microvascular thrombosis of thrombotic microangiopathies.

Thromb Haemost 2005 Mar;93(3):443-52

Mario Negri Institute for Pharmacological Research, Center for Research on Organ Transplantation, Chiara Cucchi de Alessandri e Gilberto Crespi, Villa Camozzi-Ranica (BG), Italy.

Endothelial injury is the central factor in the events leading to thrombotic microangiopathy (TMA); however, the mechanisms involved are not fully understood. Here we investigate the role of neutrophils (PMNs) and of complement activation in inducing microvascular damage and loss of thromboresistance in TMA associated with ADAMTS-13 deficiency. PMNs isolated during the acute phase of the disease released excessive amounts of reactive-oxygen species (ROS), N-derived oxidants and proteinases and induced damage and thromboresistance loss in human microvascular endothelial cell line (HMEC-1) ex vivo. Endothelial cytotoxicity and thromboresistance loss was also induced by TMA serum. Complement-derived products were responsible for the above effects: in fact, TMA serum caused C3 and Membrane Attack Complex (MAC) deposition on HMEC-1 and its cytotoxic effect was abolished by complement inhibition. TMA serum caused surface expression of P-selectin on HMEC-1 which may promote PMN adhesion and resulted in increased PMN cytotoxicity, indicating that complement may have a role in PMN activation. In addition, TMA serum stimulated control PMNs to release ROS and proteinases, and to cause endothelial cell cytotoxicity. All of the above effects were abrogated by complement inactivation. These data document for the first time that complement-initiated PMN activation and endothelial injury may have a crucial role in microvascular thrombosis of TMA associated with ADAMTS-13 deficiency.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1160/TH04-07-0450DOI Listing
March 2005

Platelet activation during plasma-reduced multicomponent PLT collection: a comparison between COBE Trima and Spectra LRS turbo cell separators.

Transfusion 2004 Jan;44(1):125-30

Clinical Pathology Department-Immunohematolgy Unit, University of Milanco-Biccoca-San Gerardo Hospital, Monza, Milan, Italy.

Background: The wide diffusion of multicomponent collection in donor apheresis has led to the yielding of different components, such as plasma-reduced platelet-pheresis at high PLT concentration. We investigated whether this collection modality could induce more PLT activation compared to standard plateletpheresis.

Study Design And Methods: Forty-one plateletpheresis collections (20 Trima and 21 Spectra LRS Turbo v.7.0, COBE) were evaluated. Donor, procedure, and product data were recorded. ADP, collagen, and U46619 (a thromboxane-A2 analog)-induced PLT aggregation was investigated in basal (donor) and final (plateletpheresis unit) samples. The expression of PLT activation marker P-selectin (CD62P) was studied using flow cytometry in basal and final samples. In all cases, P-selectin was investigated in final samples after stimulation with ADP to assess for a possible further release of the antigen. Four additional plateletpheresis procedures were performed in donors from Group A, using the traditional, nonplasma-reduced program.

Results: Plateletpheresis obtained by means of the Trima device showed a lower response to in-vitro induced PLT aggregation and a higher percentage of P-selectin-expressing PLT when compared to products obtained using the Spectra device. Moreover, P-selectin release after ADP stimulation was reduced in plateletpheresis units obtained using the Trima device. These differences disappeared when a nonplasma-reduced collection program was used. In-vivo evaluation did not detect any difference between plateletpheresis obtained by means of the two cell separators.

Conclusions: Plateletpheresis units obtained by means of multicomponent collection show a higher degree of PLT activation compared to traditional plateletpheresis procedures when high-concentration plasma-reduced products are collected. Randomized clinical studies are needed to assess the real impact of these findings in terms of in-vivo efficacy of plasma-reduced plateletpheresis units.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1046/j.0041-1132.2004.00613.xDOI Listing
January 2004

Congenital absence of the inferior vena cava and genetic coagulation abnormalities: a rare associated risk factor for recurrent idiopathic deep vein thrombosis.

Clin Appl Thromb Hemost 2003 Oct;9(4):347-8

Haematology Division San Gerardo Hospital, Università di Milano-Bicocca Monza, Italy.

Congenital absence of the inferior vena cava (AIVC) has been reported as a risk factor of deep vein thrombosis (DVT) in young people. DVT is caused by an interaction between congenital coagulation abnormalities and acquired risk factors. We observed an 18-year-old patient with AIVC who developed recurrent deep vein thrombosis at the left leg. Molecular studies showed an etherozigousity for FV Leiden gene (G1691A) and a homozigousity for methylenetetraidrofolate reductase gene (C677T) in absence of folate and vitamin B12 deficiency. After the second DVT episode, the patient has been treated with heparin and oral anticoagulant without discontinuation.
View Article and Find Full Text PDF

Download full-text PDF

Source
http://dx.doi.org/10.1177/107602960300900412DOI Listing
October 2003