Acute pancreatitis due to severe hypertriglyceridemia in the COVID-19 era: The role of therapeutic plasma exchange.

The psychosocial consequences of the COVID-19 pandemic caused multifaceted challenges in clinical and therapeutic practices. This was the case at the Therapeutic Apheresis Unit of the Padua University Hospital too. Several published reports describe the increase in alcohol and food addiction diseases. In this context, during the last months, the Padua Therapeutic Apheresis Unit treated many more patients with acute pancreatitis due to severe hypertriglyceridemia with therapeutic plasma exchange than in the previous ten years. Furthermore, retrospective cohort studies have been recently published describing the onset of acute pancreatitis during the COVID-19 infection even if, to date, there is still insufficient evidence to estabilish a direct causality. Anyway, the COVID-19 pandemic translated into changes of the overall disease prevalence scenario and therefore the Padua Therapeutic Apheresis Unit will need to reorganise its Therapeutic Apheresis activity.

To Transplant or Not to Transplant During the SARS-CoV-2 Pandemic? That Is the Question.

The novel coronavirus disease 2019 has grown to be a global public health emergency. The rapid spread of the infection has raised many questions in the oncohematological scientific community regarding the appropriateness of high-dose chemotherapy with autologous stem cell transplantation (ASCT). We here report two cases of patients who received ASCT at our Institute during the epidemic in Italy, affected with Hodgkin lymphoma and germ cell tumor, respectively. The two patients underwent a nasopharyngeal swab for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) on hospital admittance and during the period of bone marrow aplasia. They were attended to exclusively by dedicated health care staff who followed specifically implemented protocols for bedside nursing and care. They completed the procedure without unexpected side effect. Our experience demonstrates how ASCT can be performed safely if procedures are reorganized ad hoc to reduce the risk of SARS-CoV-2 infection.

Therapeutic apheresis during pregnancy: A single center experience.

INTRODUCTION: Therapeutic apheresis (TA) represents a treatment option for pre-existing conditions or diseases occurring during gestation. Although pregnancy is not a contraindication per se, due to the lack of evidence-based guidelines and presumed risk of maternal/fetal adverse events there is a general resistance to its application. MATERIAL AND METHODS: Between January 2005 and August 2017, at the Apheresis Unit of the University Hospital of Padua 936 TA procedures were performed during 57 pregnancies in 48 patients: 813 Plasma Exchange sessions, 119 Immunoadsorptions, 4 Red Blood Cell exchanges. The treated disease were as follows: antiphospholipid syndrome (18 patients), autoimmune congenital heart block (18), myasthenia gravis (3), Rh alloimmunization (2), systemic sclerosis (1), suspected autoimmune encephalitis (1), severe hypertriglyceridaemia (1), post partum hemolytic-uremic syndrome (1), sickle cell disease (1), lupus nephritis (1) and thrombotic thrombocytopenic purpura (1). RESULTS: In the time period considered the apheresis sessions applied to pregnant women were 7.1% of the total (n = 13.251). The median age at the first treatment was 33 years. The median week of gestation (WG) at the beginning of treatments was 21. Twenty (2.1%) sessions were complicated by adverse events, none requiring or prolonging hospitalization. There were 50 live births, 5 spontaneous abortions and 2 voluntary terminations of pregnancy. Median WG at delivery was 35 and caesarean section was performed in 46 cases. CONCLUSIONS: Our data showed that TA in pregnancy is well tolerated. Close collaboration between clinician, obstetrician and TA specialist is crucial to ensure a good outcome of high-risk pregnancies.

The Italian Register of therapeutic apheresis: How it has grown, how it has changed.

In Italy therapeutic apheresis procedures were carried out for the first time in the '70s. in the '80s the Italian Society of Hemapheresis was founded, formerly named SIDE, now SIdEM (Italian Society of Hemapheresis and Cellular Manipulation). From the beginning, the collection and the analysis of activity data have been seen as a way to improve the knowledge on mechanisms of action, to identify the correct rationale in order to intervene in the most appropriate clinical indications. Over the years the data collection has been refreshed and today we can rely on information representing the evolution of TA in Italy, from an organizational/technological viewpoint and according to clinical indications. Over the years the aspects that have mainly changed are the technologies, the organizational and managerial aspects and, above all, the clinical indications. The primary indication for therapeutic apheresis is still today the thrombotic thrombocytopenic purpura, but corrently, whenever a disease recognizes an autoimmune pathogenesis, the use of apheresis may be a valid therapeutic tool in the event of failure or partial efficacy of conventional drug therapy. The continuous monitoring of apheresis activity through Registries is a useful tool to follow the evolution of the apheresis practice.

Italian Registry of Therapeutic Apheresis.

Since the 80s the Italian Society of Apheresis and Cell Manipulation (SIdEM) started to monitor the adverse events of therapeutic apheresis (TA) procedures. In subsequent years other variables were added and a national TA registry was created, with a fluctuating adhesion over the years. From 2010 to 2013 the Registry was shared with the Italian Society of Nephrology (SIN): the collection method required data of each patient and a lack of adhesion was observed, mainly because of a heavy workload needed to fill out all the fields. SIdEM was then forced to simplify the form by collecting aggregated data. At the same time, the Italian Privacy Authority (IPA) gave a negative opinion on the use of the SIdEM-SIN registry because it did not prevent the possibility to identify the patients and raised the question whether a national registry could be managed by a scientific society or if it should be under the control of the Regulatory Authority (CNS - National Blood Centre). Since 2015 SIdEM has continued to collect aggregated data, with a simple form sent to each Italian TA unit. Today the main limitation of our Registry is the absence of informatic and financial support and the main limit of all TA Registries is represented by the voluntary adhesion, which can be limited by lack of time and interest or reluctance to show and share own data. In the last year SIdEM has started to work with the CNS in order to implement and integrate the Registry into the Information System of the Transfusion Units (SISTRA), a system that monitors the activities of the whole Italian blood system.The hypothesis of a Global Registry is fascinating. In order to have the greatest adhesion it should be easy and fast to fill in and, possibly, based on aggregated data.

Personalized treatment with immunoadsorption and intravenous immunoglobulin in a case of severe Rh alloimmunization during pregnancy unresponsive to plasma - exchange.

INTRODUCTION: Despite prophylaxis, a small proportion of RhD-negative women may develop anti-D antibodies after a sensitizing event occurring during pregnancy or delivery of a D-positive baby. Intrauterine transfusion (IUT) is the treatment of choice in case of fetal anemia, but it cannot be performed early during pregnancy. Combined treatment with therapeutic plasma-exchange (TPE) and intravenous immunoglobulin (IVIG) can avoid or delay IUT. Immunoadsorption (IA) could represent a more effective treatment in selected cases. CASE REPORT: We report a D-negative female with a history of induced abortion and hydrops fetalis, referred at 8 weeks of gestation with a high anti-D titer. Despite implementing a TPE-IVIG protocol, the patient experienced a spontaneous abortion. At the beginning of her fourth pregnancy, only after a partially effective intensive TPE course, cycles of IA-IVIG were performed. Despite a suboptimal response on the anti-D titer, Doppler ultrasonographic measurements of the fetal middle cerebral artery peak systolic velocity first showed evidence of anemia at 30 weeks of gestation and a IUT was required. After the IUT, anemia persisted with a subsequent dramatic rise in titer, requiring an emergent cesarean section. The infant subsequently underwent successful treatment with IVIG, phototherapy and exchange transfusion and was discharged 7 weeks later without neurological deficits. DISCUSSION: The treatment of high titer anti-D antibodies during pregnancy may require a multidisciplinary approach with utilization of different apheresis strategies in order to have a successful pregnancy outcome.

Treosulfan-Based Conditioning Regimen in Sibling and Alternative Donor Hematopoietic Stem Cell Transplantation for Children with Sickle Cell Disease.

BACKGROUND AND OBJECTIVES: Lack of suitable donors and regimen related toxicity are major barriers for hematopoietic stem cell transplantation (HSCT) in patients with sickle cell disease (SCD). The aim of the study is the assessment of efficacy and toxicity of Treosulfan-based conditioning regimen for SCD also when alternative donors such as mismatched unrelated donor and haploidentical donor are employed. METHODS: We report our single-center experience: 11 patients with SCD received HSCT with a Treosulfan/Thiotepa/Fludarabine/Anti-thymoglobulin conditioning regimen between 2010 and 2015. The donor was a matched sibling donor (n= 7), a haploidentical parent (n= 2), a matched unrelated donor (n= 1) or a mismatched unrelated donor (n=1). The haploidentical and mismatched unrelated donor grafts were manipulated by removing TCRαß and CD19 positive cells. RESULTS: All patients survived the procedure and achieved stable engraftment. Stable mixed chimerism was observed in 5/11 patients. Grade III-IV regimen related toxicity was limited to mucositis and no grade III-IV graft-versus-host disease (GvHD) occurred. No SCD manifestation was observed post transplant and cerebral vasculopathy improved in 3/5 evaluable patients. Organ function evaluation showed no pulmonary, cardiac or renal toxicity but gonadal failure occurred in 1/4 evaluable patients. CONCLUSION: Our data suggest that Treosulfan is associated with low toxicity and may be employed also for unrelated and haploidentical donor HSCT.

Successful treatment of pyoderma gangrenosum with granulocyte and monocyte adsorption apheresis.

Pyoderma gangrenosum is a neutrophilic dermatosis clinically characterised by the presence of painful skin ulcerations with erythematous and undetermined borders and histologically by the presence of neutrophilic infiltrates in the dermis. Granulocyte and monocyte adsorption apheresis, also called granulocytapheresis, is a therapeutic strategy for extracorporeal immunomodulation that selectively removes activated granulocytes and monocytes/macrophages from the peripheral blood. Here, we report a case of a 73-year-old patient affected by a severe form of pyoderma gangrenosum presenting with multiple painful ulcers and pustules on his trunk and extremities. The disease was resistant to high doses of methylprednisolone and methotrexate and successfully treated by granulocyte and monocyte adsorption apheresis. To the best of our knowledge, this is the first report on the efficacy of granulocyte and monocyte adsorption apheresis in pyoderma gangrenosum in Europe.

Plasma exchange in pediatric anti-NMDAR encephalitis: A systematic review.

OBJECTIVE: To clarify the most frequent modalities of use of plasma exchange (PE) in pediatric anti-N-methyl-d-aspartate receptor (anti-NMDAR) encephalitis and to establish the most effective association with other immunotherapies. METHODS: Systematic literature review on PE in pediatric anti-NMDAR encephalitis (2007-2015). RESULTS: Seventy-one articles were included (mostly retrospective), reporting a total of 242 subjects (73.2%, 93/127 females; median age at onset 12years, range 1-18). Median time to immunotherapy was 21days (range 0-190). In most cases, PE was given with steroids and IVIG (69.5%, 89/128), or steroids only (18%, 23/128); in a minority, it was associated with IVIG only (7%, 9/128), or was the only first-line treatment (5.5%, 7/128). In 54.5% (65/119), PE was the third treatment after steroids and IVIG, in 31.1% (37/119) the second after steroids or IVIG; only in 14.3% (17/119) was it the first treatment. Second-line immunotherapies were administered in 71.9% (100/139). Higher rates of full/substantial recovery at follow-up were observed with immunotherapy given ⩽30days from onset (69.4%, 25/36) compared to later (59.2%, 16/27), and when PE was associated with steroids (66.7%, 70/105) rather than not (46.7%, 7/15). Significant adverse reactions to PE were reported in 6 patients. CONCLUSION: Our review disclosed a paucity of quality data on PE in pediatric anti-NMDAR encephalitis. PE use in this condition has been increasingly reported, most often with steroids and IVIG. Despite the limited number of patients, our data seem to confirm the trend towards a better outcome when PE was administered early, and when given with steroids.

Maternal autoantibody profiles at risk for autoimmune congenital heart block: a prospective study in high-risk patients.

OBJECTIVE: This prospective study aimed to identify antibody profiles characterising mothers with fetuses developing congenital heart block (CHB) by comparing their antibody frequencies and levels with those in unaffected mothers. METHODS: Eighty-one consecutive pregnant patients positive to anti-Ro±anti-La antibodies, at high risk of developing fetal CHB were prospectively studied. The 16 patients with fetal CHB outcome were considered the study population and the 65 patients with normal pregnancy outcomes were considered the control cohort. Anti-Ro52, anti-Ro60, anti-p200 and anti-La antibodies were assayed using home-made ELISA assays. RESULTS: The prevalence of anti-p200 antibodies was significantly higher in the fetal CHB affected patients than in the controls (p=0.03). Combinations of anti-p200 with anti-Ro52 and anti-Ro60 antibodies were significantly more frequent in the women with fetuses developing CHB than in the controls (p=0.03 for all combinations). The women with fetal CHB had significantly higher mean anti-Ro52, anti-Ro60 and anti-p200 levels than the controls (p=0.003, p=0.0001 and p=0.04, respectively); mean anti-La/SSB level was not significantly different in the two cohorts (p=0.25). CONCLUSIONS: Since anti-p200, anti-Ro52 and anti-Ro60 antibodies, especially at high level, seem to identify patients at increased risk of developing fetal CHB, their detection could recognise anti-Ro/La positive women at risk for having an infant with this rare, potentially dangerous disorder.

Spontaneous splenic rupture following stem cell mobilization with G-CSF and plerixafor in AL amyloidosis.

BACKGROUND: AL amyloidosis is a rare plasma cell dyscrasia with multiorgan involvement. Good risk patients are candidate to high dose chemotherapy and autologous stem cell transplantation. However both transplantation and stem cell collection entail significant risk in such patients. Plerixafor is a novel mobilizing agent approved for use in "poor mobilizer" patients with lymphoma and multiple myeloma; experience in systemic amyloidosis patients is limited. CASE REPORT: We describe a case of spontaneous splenic rupture following administration of G-CSF and plerixafor in a patient with AL amyloidosis who previously underwent heart transplantation due to amyloid heart involvement. RESULTS AND CONCLUSION: This is the first report of spontaneous splenic rupture following stem cell mobilization with G-CSF and plerixafor in AL amyloidosis. The role of plerixafor has to be established. AL amyloidosis patients undergoing stem cell mobilization need careful monitoring of signs and symptoms of spontaneous splenic rupture.

Therapeutic apheresis in pregnancy: General considerations and current practice.

It is widely known that pregnancy does not represent a contraindication to therapeutic apheresis (TA) techniques. In fact, since the first experiences of TA in pregnancy for the prevention of hemolytic disease of the newborn, several diseases are at present treated with TA, mainly within 6 clinical categories: (a) TA is a priority and has no alternative equally effective treatment (e.g., thrombotic thrombocytopenic purpura); (b) TA is a priority but there are alternative therapies not contraindicated in pregnancy (e.g., myasthenia gravis); (c) TA is an effective tool of saving/avoiding drugs contraindicated in pregnancy (e.g., systemic lupus erythematosus); (d) TA is a treatment of specific conditions/complications of pregnancy with maternal and/or fetal risk (e.g., antiphospholipid syndrome); (e) TA is a treatment of specific conditions of pregnancy with exclusive fetal risk (e.g., hemolytic disease of the newborn); (f) TA is a treatment of disease which is strongly indicated and can exceptionally occur during pregnancy (e.g., Goodpasture's syndrome). When dealing with TA pregnant patients, some technical aspects due to the physiological changes of gestation have to be carefully considered, in particular the increase of the circulating blood volume. Moreover a multidisciplinary medical team, including an obstetrician, a clinical consultant, specialist in TA and in transfusion medicine, and a neonatologist stand as a basic requirement for the proper management of some clinical conditions that may be characterized by high maternal and fetal risk.

Plasma-exchange as a "rescue therapy" for dermato/polymyositis in acute phase. Experience in three young patients.

There are few data in the literature supporting the efficacy of plasma-exchange in dermato/polymyositis. The authors report three cases of patients with acute disease phase showing severe pharyngo-esophageal muscle weakness unresponsive to conventional therapy (corticosteroids and immunosuppressant agents) who were treated with plasma-exchange. As the patients were at high risk of "aspiration pneumonia", tracheostomy and PEG tubes were placed. The patients underwent a series of plasma-exchange for a mean of 15 weeks, during which time they progressively recovered muscle strength, their serum muscle enzyme values returned to normal levels, and MRI showed resolution of muscle edema. The tracheostomy and PEG tubes could be removed. Our findings suggest that plasma-exchange in association with immunosuppressant agents could play a relevant role in the management of dermato/polymyositis in acute phase.

Treatment of Acute Graft-versus-Host Disease in Childhood with Extracorporeal Photochemotherapy/Photopheresis: The Padova Experience.

Acute graft-versus-host disease (aGVHD) is the major cause of morbidity and mortality after allogeneic hematopoietic stem cell transplantation. Systemic steroid treatment represents the first-line therapy for aGVHD and is associated with a response rate of 30% to 60%. Steroid-resistant patients have a poor prognosis with high transplantation-related mortality (TRM). Several second-line therapies have been proposed for the management of unresponsive aGVHD, without proven beneficial effects on patients' outcome or overall long-term survival. For these reasons, extracorporeal photochemotherapy/photopheresis (ECP), a cell-based approach to control GVHD that spares generalized immunosuppression, seems to be promising. In this study, we report the outcome of 72 consecutive pediatric patients treated with ECP between 1997 and 2013 for aGVHD. Among them, 21 patients had steroid-resistant aGVHD, 42 had steroid-dependent aGVHD, and 9 did not receive steroid as first-line therapy because of clinical contraindications. A complete response was obtained in 72% of patients, a partial response was observed in 11%, and there was no response in 17% of patients. At day +180, TRM was 4% in the whole cohort; TRM was 3% and 20% among responders and nonresponders to ECP, respectively (P < .0001). The 5-year overall survival was 71%, showing a difference between responders and nonresponders of 78% and 30%, respectively (P = .0004). The 5-year time to progression of primary disease was 81%, without any significant difference between the 2 groups. Moreover, the 5-year progression-free survival of primary disease was 72%, with a significant difference (P = .0007) between responders (79%) and nonresponders (30%) to ECP. In conclusion, this study demonstrates that ECP is highly effective in aGVHD without a negative impact on primary disease.

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

BACKGROUND: 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. STUDY DESIGN AND METHODS: We evaluated the efficacy of plasma exchange (PE) in removing 52- and 60-kDa anti-Ro/SSA and anti-La/SSB antibodies in pregnant women with CHB treated with a combined therapy including PE, intravenous immunoglobulins, and steroids. Antibody levels were monitored in 10 consecutive pregnant women diagnosed with CHB and prospectively followed between 2009 and 2013. Assaying was performed using a homemade enzyme-linked immunosorbent assay test on blood samples collected immediately before and after PE sessions. RESULTS: A significant decrease in mean post-PE antibody levels was noted in all the cases examined. An analysis of antibody level trends in the samples collected before PE sessions showed that there was a steady, significant decrease in 90% of the patients with 52-kDa anti-Ro/SSA, in 80% of those with 60-kDa anti-Ro/SSA antibodies, and in 100% of those with anti-La/SSB antibodies. CONCLUSION: This study demonstrates that PE is effective in removing antibodies linked to the pathogenesis of CHB. PE treatment was found to have a long-term efficacy in all the women positive for anti-La/SSB antibodies and in most of the women positive for 52- and 60-kDa anti-Ro/SSA antibodies. It is interesting that the significant, immediate, and long-term fall in antibody levels that was observed in these patients took place in all the women whose CHB was reversed. This finding could give PE an important role in the treatment of CHB.

Stress, burnout, and job satisfaction in 470 health professionals in 98 apheresis units in Italy: A SIdEM collaborative study.

AIMS: In Italian and international background, there are no studies focusing on stress, burnout indicators, and job satisfaction in health professionals working in the apheresis units. This study aims to fill this void both for scientific and clinical reasons. METHODS: The participants were 470 health professionals (220 physicians, 250 nurses), mostly female (73.4%), with an average age of 48.09 (with the 5° percentile under 32 years and the 95° percentile over 60), working in the Apheresis Units in the North (228), in the Center (131) and in the Southern-islands of Italy (111). The health professionals' years on the job were principally between one and 10 years (40.2%) or from 11 to 20 years (33.2%). The prevalent activity was therapeutic apheresis (48.5%). The self-report questionnaires were proposed electronically by a protected online site. RESULTS: Important stress levels were identified in the health professionals. Physicians principally showed medium (47.5%) and high (35.8%) stress levels. Stress levels of nurses were mostly low (57.7%) or medium (25.7%). Female gender in nurses [t(268) = -3.29; P = 0.001] and in physician professions [t(217) = -3.01; P = 0.03] was a risk factor for stress. Both job categories were placed at a high risk level for burnout syndrome comparing with normative scales, especially the health professionals working in the center of Italy for the scales "Emotional exhaustion" [F(2) = 4.39; P = 0.013] and "Professional inefficacy" [F(2) = 4.38; P = 0.013]. CONCLUSIONS: Health professionals working in the apheresis unit show high stress levels and burnout risk. New preventive programs and specific clinical interventions should be constructed.

Granulo-monocyto apheresis is more effective in mild ulcerative colitis than in moderate to severe disease.

AIM: To evaluate whether the effectiveness of Granulo-monocyto apheresis (GMA), a technique that consists of the extracorporeal removal of granulocytes and monocytes from the peripheral blood, might vary according to the severity of ulcerative colitis (UC) in patients with mild to moderate-severe disease UC activity. METHODS: We retrospectively reviewed prospectively collected data of patients undergoing GMA at our inflammatory bowel disease centre who had at least a 6 mo of follow-up. The demographics, clinical and laboratory data were extracted from the patients' charts and electronic records. The severity of UC was scored according to the Modified Truelove Witts Severity Index (MTWSI). A clinical response was defined as a decrease from baseline of ≥ 2 points or a value of MTWSI ≤ 2 points. RESULTS: A total of 41 (24 males/17 females; mean age 47 years) patients were included in the study. After GMA cycle completion, 21/28 (75%) of mild UC patients showed a clinical response compared with 7/13 (54%) of patients with moderate to severe disease (P = 0.27). At 6-mo, 14/28 (50%) of the mild UC patients maintained a clinical response compared with 2/13 (15%) of the patients with moderate to severe disease (P = 0.04). After the GMA cycle completion and during the 6-mo follow up period, 13/16 (81%) and 9/16 (56%) of mild UC patients with intolerance, resistance and contraindications to immunosuppressants and/or biologics showed a clinical response compared with 2/6 (33%) and 0/6 (0%) of patients with moderate to severe disease activity with these characteristics (P = 0.05 and P = 0.04, respectively). CONCLUSION: Patients with mild UC benefit from GMA more than patients with moderate to severe disease in the short-term period. GMA should be considered a valid therapeutic option in cases of contraindications to immunosuppressants, corticosteroids and/or biologics.

ABO blood groups and the risk of venous thrombosis in patients with inherited thrombophilia.

BACKGROUND: Although having a non-O blood type is now regarded as a risk factor for venous thromboembolism, the strength of this association is poorly defined, as is its interaction with inherited thrombophilia. MATERIALS AND METHODS: The prevalence of non-O blood group and inherited thrombophilia (deficiencies of natural anticoagulants, factor V Leiden and prothrombin G20210A mutation) was assessed in a series of 712 consecutive patients with proximal deep vein thrombosis of the lower limbs who were referred to our Institution between 2004 and 2010, and in 712 age- and gender-matched healthy volunteers. Odds ratios (OR) of deep vein thrombosis and their 95% confidence intervals (CI) were computed for non-O group and thrombophilia, both separately and in combination. RESULTS: A non-O blood group was present in 492 cases and 358 controls (OR 2.21; 95% CI, 1.78 to 2.75). A thrombophilic abnormality was present in 237 cases and 105 controls (OR 2.82; 2.18 to 3.66). The combination of non-O group and thrombophilia was present in 152 cases and 51 controls (OR 7.06; 4.85 to 10.28). DISCUSSION: Having a non-O blood group is associated with an increased risk of proximal deep vein thrombosis of the lower limbs with or without pulmonary embolism. The addition of inherited thrombophilia increases the thrombotic risk conferred by non-O group alone by almost 3-fold.