Giustina De Silvestro

Aprotinin efficacy on intraoperative bleeding and transfusion requirements in orthotopic liver transplantation.

Background: Bleeding complications frequently occur during orthotopic liver transplantation (OLT), particularly in patients with liver cirrhosis. Enhanced fibrinolytic activity in plasma was seen to play a key role in the development of the hemostatic disorder and of hemorrhages. Aprotinin, a serine protease inhibitor, has been used in the prevention and/or treatment of hyperfibrinolytic states.

Hepatocyte transplantation in the treatment of acute liver failure: microencapsulated hepatocytes versus hepatocytes attached to an autologous biomatrix.

A liver transplant is considered today to be the only effective therapeutic solution for many otherwise intractable hepatic disorders. However, liver transplantation is beset by shortage of donors. Over the years, many liver support systems have been developed to supply the liver functions, mostly as a bridge to transplantation. Transplantation of isolated hepatocytes (HcTx) instead of whole liver has constituted one of the most appealing possibilities to treat several diseases. We compared two different models of HcTx in a surgical model of acute liver failure in pigs, using microencapsulated hepatocytes (MHcTx) and hepatocytes attached to a porcine biomatrix (PBMHcTx), both transplanted into peritoneum. The collected data were survival, laboratory findings, hemodynamic parameters, light microscopy, histology, MTT, and glycogen content. The group with PBMHcTx has a better outcome than the group with MHcTx (p < 0.05). Histology showed normal morphology of the hepatocytes, high glycogen content, 75% viability, positive MTT, and 95% adhesion of the hepatocytes to the biomatrix. Our biomatrix (PBM) provides cell-to-cell contact and interaction with extracellular matrix, which have been shown to play major roles in hepatocyte survival and physiologic regulation of gene expression, and guarantee a prompt engraftment and an adequate neovascularization. PBMHcTx is a useful method to treat acute liver failure and it indicates a possible liver-direct gene therapy in the treatment of inherited and acquired disorders.

Plasma exchange and immunoadsorption effectively remove antiphospholipid antibodies in pregnant patients with antiphospholipid syndrome.

Conventional therapy with aspirin and/or heparin is at times incapable of preventing complications in high risk pregnancies of patients with antiphospholipid syndrome (APS). In those cases, a so‐called second‐line treatment protocol is used in addition to conventional therapy strategies. This manuscript is a report on three APS pregnant patients who were successfully treated with plasma exchange (PE) (two cases) or with immunoadsorption (IA) (one case) as a second‐line treatment strategy. The efficacy of these procedures in removing anticardiolipin (aCL) and anti‐β2glycoprotein I (aβ2GPI) antibodies from blood was evaluated. Serum samples were collected before and after 87 apheretic treatment sessions. Serum IgG/M aCL and IgG/M aβ2GPI antibodies were determined using an “in‐house” enzyme‐linked immunosorbent assay and showed that all three patients had medium/high IgG aCL and aβ2GPI titers. All three women had a successful pregnancy. A significant decrease in IgG aCL (P = 0.0001) and aβ2GPI (P = 0.0001) antibody titers was observed after PE and IA sessions. There was moreover a significant, steady fall in serum IgG aCL pretreatment levels during the course of all three pregnancies (P = 0.0001, P = 0.0001, P = 0.001). The fall in IgG aβ2GPI was significant in two of the patients (P = 0.0001, P = 0.0001) both with high antibody titers, but not in one with medium antibody titers, who was treated with PE (P = 0.17). J. Clin. Apheresis 2012.

Frequency of a mutated CCR-5 allele (delta32) among Italian healthy donors and individuals at risk of parenteral HIV infection.

The aim of this study was to assess the frequency of a truncated allele of the CCR-5 gene (delta32) in Italy, and address its possible role in parenteral HIV transmission, as well as its influence in HIV-associated disease progression. In 371 unrelated seronegative healthy blood donors the delta32 allele frequency was 0.047; this figure was significantly different from those reported in northern America and northern Europe populations. However, delta32 allele frequency in healthy individuals did not differ significantly from that found in 54 seronegative drug users (0.065), 98 seronegative hemophiliacs (0.051), and 81 seropositive hemophiliacs (0.049). Although in seropositive hemophiliacs the wt/delta32 heterozygous genotype was associated with a trend to a slower decline in CD4+ cell counts, its presence did not seem to influence disease progression, as comparable delta32 allele frequency frequencies were found among progressing (0.042) and nonprogressing (0.111) patients. These data do not seem to support a protective role of the delta32 allele in preventing HIV infection through the parenteral route, or in influencing the natural history of the disease in this particular risk category, although the delta32 heterozygous state was associated with lower plasma viremia levels. On the other hand, the finding of non-syncytium-inducing HIV strains in the majority of delta32 heterozygous seropositive patients suggests that its presence could not be a major factor in driving a switch toward more cytopathic, T-tropic HIV strains through selective pressure in coreceptor usage.

The Italian Registry of Pediatric Therapeutic Apheresis: A report on activity during 2005

The results of the 2005 Survey of the Italian Society for Apheresis and Cell Manipulation (SIdEM) reporting on the pediatric procedures carried out in 18 Italian Apheresis Units are presented here. Utilizing a standardized questionnaire, the survey collected data on techniques, types of blood separators, clinical indications, and adverse events. A total of 1,693 apheresis procedures were carried out in 355 pediatric patients: 219 plasma‐exchange, 291 peripheral blood stem cell collections, 791 extracorporeal photochemotherapy (ECP), 265 LDL‐apheresis, 71 erythro‐exchange, 9 cytoreductive apheresis, 47 immunoadsorption sessions. Adverse events were registered in 94 procedures (5.6%), most of which of mild entity, e.g., insufficient flow rate (50.0%) and symptomatic hypocalcemia (24.4%). Our data indicate that all types of apheresis procedures can be safely carried out in children. ECP, utilized primarily for the treatment of graft versus host disease (GvHD) and rejection of solid organ transplantation, are burgeoning procedures in pediatric patients, whereas plasma exchange, which is a common treatment in adults, is infrequently utilized in pediatric medicine. J. Clin. Apheresis, 2009.

Case reports of the use of immunoadsorption or plasma exchange in high-risk pregnancies of women with antiphospholipid syndrome.

Conventional treatment of antiphospholipid syndrome (APS) pregnancies with aspirin and/or heparin is sometimes unable to counteract maternal and/or fetal complications. In this article we report the cases of two patients who were unresponsive to conventional treatment for APS during their first pregnancy, and who were treated in the following pregnancy with plasma exchange and immunoadsorption respectively, in addition to conventional therapy. Both patients had a history of thrombotic events, a previous pregnancy loss at the 11th week of gestation and the same antiphospholipid antibody profile (lupus anticoagulant activity and high titers of immunoglobulin G (IgG) anti‐β2 glycoprotein I and IgG anticardiolipin antibodies). Patient 1 was treated from the fourth week of her second pregnancy with weekly plasma exchange. Due to fetal growth restriction and oligohydramnios in the 26th week she delivered, by cesarean section, a healthy female infant weighing 730 g who survived. Patient 2 was treated from the seventh week of her second pregnancy with twice a week protein A immunoadsorption. The pregnancy proceeded normally until the 36th week, when, due to slight intrauterine growth restriction, she delivered a healthy baby girl weighing 2375 g by cesarean section. Anti‐β2 glycoprotein I antibody trends were similar during both types of treatment. On the basis of our findings obtained from only two cases it is impossible to define the best aphaeretic treatment of APS high risk pregnancies. Nevertheless, as a whole these data suggest better disease control using the immunoadsorption technique as compared to plasma exchange, despite their apparently similar anti‐β2 glycoprotein I antibody removal capabilities.

Long-term therapy with plasma exchange in systemic sclerosis: effects on laboratory markers reflecting disease activity

Plasma exchange (PEX) is a technique that has been applied to the treatment of many immunological disorders, including connective tissue diseases. The crucial role of some humoral factors in the pathogenesis of systemic sclerosis (SSc) could explain the good clinical results obtained in terms of slowing down the disease progression, but the efficacy of PEX in the treatment of SSc is not yet well defined, owing to the lack of controlled studies and validated parameters of disease activity. To demonstrate the long-term efficacy of PEX in the treatment of SSc we treated a group of 28 SSc patients affected with recent onset and/or rapidly progressive disease. Most of these had a diffuse form of SSc, with anti-Sc170 antibody as a disease marker. Before and after long-term PEX treatment we evaluated disease activity parameters including the serum levels of interleukin 2 soluble receptor (sIL-2R) and aminoterminal type III procollagen peptide (PIIINP), plus the percentage of DR+ T cells in the peripheral blood. We also assessed clinical parameters of total skin score and total visceral score. The same parameters were evaluated in 25 SSc patients who did not satisfy the admission criteria for PEX, treated long-term with drugs only. At baseline, serum PIIINP and sIL-2R levels and the percentage of DR+ T cells were significantly increased in PEX patients as compared to others. Following long-term PEX treatment, all the laboratory parameters significantly decreased and the clinical scores showed a slight but not significant improvement. Conversely, in the other group of SSc patients treated for the same period with drugs only, no significant change of laboratory parameters was detected and the clinical scores slightly worsened. Our data suggest that long-term PEX therapy seems to be effective in slowing down the clinical course of patients with severe and rapidly progressive SSc.

Toward an international consensus—Integrating lipoprotein apheresis and new lipid-lowering drugs

BACKGROUND Despite advances in pharmacotherapy of lipid disorders, many dyslipidemic patients do not attain sufficient lipid lowering to mitigate risk of atherosclerotic cardiovascular disease. Several classes of novel lipid-lowering agents are being evaluated to reduce atherosclerotic cardiovascular disease risk. Lipoprotein apheresis (LA) is effective in acutely lowering the plasma concentrations of atherogenic lipoproteins including low-density lipoprotein cholesterol and lipoprotein(a), and novel lipid-lowering drugs may dampen the lipid rebound effect of LA, with the possibility that LA frequency may be decreased, in some cases even be discontinued. SOURCES OF MATERIAL This document builds on current American Society for Apheresis guidelines and, for the first time, makes recommendations from summarized data of the emerging lipid-lowering drug classes (inhibitors of proprotein convertase subtilisin/kexin type 9 or microsomal triglyceride transfer protein, high-density lipoprotein mimetic), including the available evidence on combination therapy with LA with respect to the management of patients with dyslipidemia. ABSTRACT OF FINDINGS Recommendations for different indications are given based on the latest evidence. However, except for lomitapide in homozygous familial hypercholesterolemia and alirocumab/evolocumab in heterozygous familial hypercholesterolemia subjects, limited data are available on the effectiveness and safety of combination therapy. More studies on combining LA with novel lipid-lowering drugs are needed. CONCLUSION Novel lipid-lowering agents have potential to improve the performance of LA, but more evidence is needed. The Multidisciplinary International Group for Hemapheresis TherapY and Metabolic DIsturbances Contrast scientific society aims to establish an international registry of clinical experience on LA combination therapy to expand the evidence on this treatment in individuals at high cardiovascular disease risk.

ABO-incompatible heart transplantation: crossing the immunological barrier

Due to the shortage of organ donors, heart transplantation cannot be offered to many infants with end-stage heart failure; this issue leads to mortality rates of 30-50% in patients in the paediatric age group awaiting operation. ABO-incompatible heart transplantation has been performed safely with no particular or invasive preparatory procedures other than plasma exchange during cardiopulmonary bypass for removing preformed antibodies, with no reports of hyperacute rejection. We report our first clinical experience of heart transplantation on a 2-month-old-infant (blood group O), diagnosed with intracardiac tumour, in which the donor was a 19-day-old newborn of blood group A. Sharing the know-how about ABO-incompatible heart transplantation in newborns and infants awaiting transplantation will help in decreasing mortality among this group of patients.

Plasma exchange effectively removes 52- and 60-kDa anti-Ro/SSA and anti-La/SSB antibodies in pregnant women with congenital heart block.

Pregnant women positive for 52‐ and 60‐kDa anti‐Ro/SSA and anti‐La/SSB antibodies can suffer from congenital heart block (CHB), a passively acquired autoimmune disease.