Patients Underwent Plasma Exchange Research Articles

Chemotherapy plus therapeutic plasmapheresis with 4% human albumin solution in multiple myeloma patients with acute kidney injury: a prospective, open-label, proof-of-concept study

As no unified treatment protocol or evidence yet exists for plasmapheresis without plasma, this study explored the outcomes of using 4% human albumin (ALB) solution as a replacement solution in patients undergoing plasma exchange for multiple myeloma (MM) patients with acute kidney injury (AKI). This study was prospectively registered (ChiCTR2000030640 and NCT05251896). Bortezomib-based chemotherapy plus therapeutic plasmapheresis (TPP) with 4% human ALB solution was assessed for three years in patients with MM aged >18 years, with AKI according to the Kidney Disease Improving Global Outcomes criteria, and without previous renal impairment from other causes. The primary endpoints were changes in renal function over 18 weeks and survival outcomes at 36 months. The secondary endpoints were the incidence of adverse reactions and symptom improvement. Among the 119 patients included in the analysis, 108 experienced renal reactions. The M protein (absolute changes: median −12.12%, interquartile ranges (IQRs) −18.62 to −5.626) and creatine (median −46.91 μmol/L, IQR −64.70 to −29.12) levels decreased, whereas the estimated glomerular filtration rate (eGFR) increased (median 20.66 mL/(min·1.73 m2), IQR 16.03–25.29). Regarding patient survival, 68.1% and 35.3% of patients survived for >12 and >36 months, respectively. The three symptoms with the greatest relief were urine foam, poor appetite, and blurred vision. All 11 patients (7.6%) who experienced mild adverse reactions achieved remission. In conclusion, in MM patients with AKI, plasma-free plasmapheresis with 4% human ALB solution and bortezomib-based chemotherapy effectively alleviated light chain damage to kidney function while improving patient quality of life.

PB0563 Evaluation of the Rapid and Easy-to-Use Point-of-Care qLabs FIB® System to Quantify Functional Fibrinogen Levels in Patients Undergoing Plasma Exchange Therapy

PB0563 Evaluation of the Rapid and Easy-to-Use Point-of-Care qLabs FIB® System to Quantify Functional Fibrinogen Levels in Patients Undergoing Plasma Exchange Therapy

Healthcare utilization and outcomes of living donor liver transplantation for patients with APASL-defined acute-on-chronic liver failure.

Liver transplantation (LT) is associated with excellent survival in patients with acute-on-chronic liver failure (ACLF). There is a lack of data assessing the healthcare utilization and outcomes of patients with APASL-defined ACLF undergoing living donor liver transplantation (LDLT). Our aim was to assess pre-LT healthcare utilization and post-LT outcomes in such patients. Patients with ACLF who underwent LDLT at our center between 1st April 2019 and 1st October 2021 were included. Seventy-three ACLF patients willing to undergo LDLT were listed; eighteen patients died within 30days. Fifty-five patients underwent LDLT (age:38.05 ± 14.76years; alcohol:52.7%; males:81.8%). Most were in grade II ACLF (87.3%) at the time of LDLT (APASL ACLF Research Consortium [AARC] score: 9.05 ± 1; MELD NA: 28.15 ± 4.13). Survival rate was 72.73%; mean follow-up period of 925.21days; 58.2% (32/55) developed complications during the first year post-LT; 45% (25/55) and 12.7% (7/55) developed infections within and after 3months. Pre-LT, each patient required a median of 2 (1-4) admissions for 17 (4-45) days. Fifty-six percent (31/55) of patients underwent plasma exchange pre-LDLT. A median amount of Rs. 8,25,090 (INR 26,000-43,58,154) was spent to stabilize the patient (who were sicker and waited longer to undergo LDLT); though post-LT survival benefit was not observed. LDLT was associated with 73% survival and, thus, is a viable option in those with APASL-defined ACLF. There was a pre-LT high healthcare resource utilization of plasma exchange, with the intention of optimization, while survival benefit has not been demonstrated.

Two ischemic stroke events within 48 h: a case report of an unusual presentation of thrombotic thrombocytopenic purpura

BackgroundThrombotic thrombocytopenic purpura (TTP) considers a rare cause of ischemic stroke (IS). We reported a case of a newly diagnosed patient with acquired immune-mediated TTP (iTTP), in whom two IS events developed during 48 h.Case presentationA 59-year-old diabetic male was presented to the hospital 24 h after symptoms onset, including left hemiparesis, dysarthria, and decreased consciousness. A brain CT scan was performed with the suspicion of acute IS, indicating infarct lesions in the right middle cerebral artery (MCA) territory. The patient was not eligible for thrombolytic therapy due to admission delay. Over the next 24 h, the patient’s neurological condition deteriorated, and the second brain CT scan showed new ischemic lesions in the left MCA territory. Initial laboratory evaluation indicated thrombocytopenia without evidence of anemia. However, in the following days, thrombocytopenia progressed, and microangiopathic hemolytic anemia (MAHA) developed. The ADAMTS-13 (a disintegrin and metalloproteinase with a thrombospondin type 1 motif, member 13) activity and inhibitors assay confirmed the diagnosis of iTTP. The patient underwent plasma exchange activity and inhibitors assay confirmed the diagnosis of iTTP. The patient underwent and pulse IV methylprednisolone. Rituximab was also added due to the refractory course of the disease. After a prolonged hospital course, he had considerable neurologic recovery and was discharged.ConclusionsClinicians should consider two points. First, TTP should be considered in any patient presenting with IS and having thrombocytopenia or anemia without other symptoms of TTP. Second, worsening the patient's condition during hospitalization may indicate a new stroke and should be investigated immediately.

MO318END-STAGE RENAL DISEASE RELATED FACTORS IN ANCA-ASSOCIATED VASCULITIS

Abstract Background and Aims Management of ANCA-Associated Vasculitis (AAV) is in constant update. The aim of the study is to describe our experience as a territorial reference center with this systemic disease and to analyze which factors have a significant influence on the development of end-stage renal disease (ESRD). Method Retrospective observational study. All the patients who developed AAV in our center between 2010 and 2019 were included. Demographic variables (age, sex), renal function, other vasculitis related symptoms, induction and maintenance therapy, response degree and follow-up were collected. Categorical variables are expressed as percentages and compared using Chi2 test. Quantitative variables are expressed as mean ± standard deviation and compared using Mann-Whitney U test. Cox regression was performed to determine independent predictors of ESRD. Kaplan-Meier was used to estimate ESRD-free survival. Statistical significance for a value of p< 0,05. Statistical analysis was performed with SPSS 25.0. Results 45 patients were analyzed, with an average age of 70 ± 11 years. 62.2% were men. Mean time of follow-up 36 ± 31.6 months. 37.8% presented c-ANCA autoantibodies and 57.8% p-ANCA. Mean baseline serum creatinine level was 5.51 ± 3.65 mg/dl and proteinuria 2.82 ± 2.48 g/24h. 77.8% received cyclophosphamide as induction immunosuppressive treatment whereas 13.3% rituximab. 50% received azathioprine, 36.1% mycophenolate and 13.9% rituximab as maintenance treatment. 37.8% patients underwent plasma exchange therapy and 44.4% hemodialysis. Complete remission was achieved by 13.3% of patients, while 57.8% partial remission. 28.9% had absence of remission. 28.9% achieved ESRD. ESRD was associated with undergoing hemodialysis (69.2% vs 30.8% p=0.033), to the type of response (complete 7.7% vs partial 23.1% vs no response 69.2%), baseline creatinine level (8.36 ± 5.44 vs 4.35 ± 1.64 mg/dl p=0.011), creatinine 6 months after induction treatment (4.3 ± 2.05 vs 2.04 ± 0.77 mg/dl p=0.001) and at the end of follow-up (6.33 ± 2.47 mg/dl vs 2.2 ± 1.29 mg/dl p=0.001) and also to baseline proteinuria (4.21 ± 3.12 vs 2.25 ± 1.96 p=0.003), proteinuria 6 months after induction treatment (1.4 ± 1.46 vs 0.58 ± 0.73 g/24h p=0.014) and at the end of follow-up (2.48 ± 1.9 vs 1.12 ± 1.64 p=0.001). Logistic regression only showed end of follow up serum creatinine level as an independent risk factor of ESRD (OR3.74 IC 95% 1.01-13.75 p=0.047). ESRD-free survival chance after 5 of follow-up was 67%. Conclusion Only serum creatinine level at the end of follow-up could be found as an associated factor with ESRD. Greater number of patients would be needed in order to obtain other factors leading to ESRD in patients with AAV.

Laparotomy Exploration In Pediatric With Severe Thrombocytopenia: A Report

Introduction: Perioperative bleeding in patients was a serious problem in the exploration of laparotomy, especially in severe thrombocytopenia patients. In addition, spontaneous bleeding often occurs in patients who have a platelet count of less than 10 to 20.109 cells. L-1 blood. When surgery must be performed on a patient with platelet counts < 50.109 cells L-1, platelet concentrate was urgently needed to be transfused during induction of anesthesia. Benefits and risks of transfusion before surgery had to be done on a per-patient basis. The available data was very limited in informing perioperative management of patients with thrombocytopenia. However, there have been previous reports of surgery cases in 66-year-old patients with a history of immune thrombocytopenia (ITP) and diagnosed with acute appendicitis related to disseminated intravascular coagulation (DIC), showing excellent postoperative hemostasis. Another one, a seven-year-old boy who has a severe refractory case of ITP with very low platelet counts was referred to urgent splenectomy performed without increase platelet counts before, and then the patient underwent plasma exchange (PE) after surgery. Those reports aimed to present 2 cases of laparotomy exploration in pediatric patients with severe thrombocytopenia. Case Report: The first laparotomy exploration was conducted on an 11-year-old boy who suffered acute perforated appendicitis. The patient obtained general anesthesia with intubation. The second laparotomy exploration was conducted on a 1-month-old baby boy with a weight of 3400 grams who suffered bowel low-level obstruction suspect Hirschsprung disease. The patient also obtained general anesthesia with intubation. Discussion The general anesthesia with oral intubation was successfully afforded to both patients for the laparotomy exploration with the preoperative condition under severe thrombocytopenia with receiving platelet transfusion therapy before surgery. Complications of spontaneous bleeding at the time of intubation were not found, no bleeding-difficult-intubation during surgery, and no symptoms of spontaneous bleeding were found. Postoperatively, platelet levels gradually improved. Conclusion: Exploration of laparotomy in patients with severe thrombocytopenia can be carried out with the support of platelet transfusion and providing general anesthesia with oral intubation to patients.

Removal of Anti-Thymocyte Globulin by Plasma Exchange in ABO-Incompatible and Positive Crossmatch Kidney Transplant Recipients

BackgroundRecipients of ABO-incompatible (ABOI) and positive crossmatch (PXM) kidney transplants are at high risk for antibody-mediated acute rejection. Despite aggressive immunosuppression in high-risk patients, the incidence of acute rejection remains considerably higher than in other groups. No published studies have examined plasma concentrations of anti-thymocyte globulin (ATG) in patients undergoing plasma exchange. The objectives of this study were to compare plasma ATG concentrations before and after plasma exchange in ABOI and PXM kidney transplant patients to determine the amount removed. Materials and MethodsThis prospective pharmacokinetic evaluation enrolled 10 patients undergoing ABOI or PXM kidney transplant at an academic medical center. Blood and waste plasma samples from 5 patients were assayed for total and active ATG concentrations. Patient records were monitored for renal function and rejection rates in the first 6 months post-transplant. ResultsTotal ATG concentrations decreased a mean of 59.78 ± 13.91% after each plasma exchange session, and active ATG levels decreased a mean of 56.8 ± 17.08%. Mean daily concentrations reflect a lack of expected ATG accumulation. Only 1 of 4 patients had detectable ATG concentrations after 30 days. After 6 months, the incidence of acute rejection in this sample was 44% and graft survival was 89%. ConclusionsThis is the first study to show that plasma exchange removes a substantial amount of ATG in high-risk kidney transplant patients. Based on these results, we believe these high-risk patients have been traditionally underdosed.

THU0600 A CASE OF SYSTEMIC SCLEROSIS COMPLICATED BY RENAL CRISIS: POTENTIAL ETIOPATHOGENETIC ROLE OF CYTOMEGALOVIRUS AND TREATMENT

Background:Scleroderma renal crisis (SRC) is a rare complication of systemic sclerosis (SSc), which can be triggered by viruses, such as Cytomegalovirus (CMV). SRC presents as a new-onset accelerated-phase hypertension with/without rapidly progressive renal failure.Objectives:Here we describe the case of a patient developing SSc complicated by the appearance of SRC after a recent episode of acute Cytomegalovirus infection.Methods:A 66-year-old male was referred to our Scleroderma Unit in March 2019. He presented with widespread skin rash, exertional dyspnoea and peripheral oedemas. He reported a myocarditis due to CMV occurred in October 2018. Antibodies anti-CMV IgM were detected in his serum. The patient developed a progressive cutaneous involvement characterized by diffuse oedema, sclerosis and melanoderma. Subsequently, Raynaud’s phenomenon, puffy hands and pitting scars occurred. Laboratory tests showed positive ANA in a titer of 1:640 in a nucleolar staining pattern. Additionally, persistence of anti-CMV IgM was found. Skin biopsy showed scleroderma-like finding. Nailfold capillaroscopy revealed a SSc pattern. Chest high resolution computed tomography displayed basal interstitial thickening and subpleuric ground-glass opacities. Therefore, the patient was diagnosed with SSc. Three weeks later he developed severe hypertension and a rapid, progressive renal impairment. Serum creatinine increased (up to 4.15 mg/dl), glomerular filtration rate impaired (25 ml/min). Renal biopsy (picture A, B) revealed acute thrombotic microangiopathy. A diagnosis of thrombotic thrombocytopenic purpura was excluded. The patient was diagnosed with SRC and we started therapy with ACE-inhibitor and loop diuretic. Even if the dosage of ACE-inhibitor was increased up to the maximum tolerate dose, his renal function did not improve and the blood pressure control was inadequate. Consequently, the patient underwent plasma exchange (PEx) sessions. Two weeks later there was an improvement of renal function and blood pressure normalized. Six months later the disease was controlled: glomerular filtration rate was 41 ml/min and blood pressure was within the normal range. The patient was treated with ACE-inhibitor and underwent fortnightly apheretic sessions. Treatment for scleroderma vasculopathy is ongoing.Results:Viral infections may be responsible for SSc. A brief interval between an acute viral infection and the onset of SSc may suggest CMV as a possible trigger for the disease. Similarly, other infectious agents could be involved in the multistep and multifactorial mechanism of SSc. This case sheds light on the potential and intriguing role of CMV in SSc. Moreover, it leads us to hypothesize a CMV possible direct role in sclerodermal kidney damage. Use of ACE-inhibitor significantly reduced the mortality rate due to this complication. Exact therapeutic mechanism of PEx in the treatment of SSc is unclear.Conclusion:In our case the integrated ACE-inhibitor-PEx approach has showed effectiveness and safety in the management of SRC.

Ibrutinib for Pure Red Cell Aplasia after Allogeneic Hematopoietic Stem Cell Transplant with Major ABO Incompatibility

<h3>Introduction</h3> Since Human leukocyte antigen (HLA) and ABO blood group system are inherited independently and with up to 50% of allogeneic hematopoietic cell transplantations (HCT) are performed with donor-recipient ABO incompatibility, recipients are at increased risk for acute and delayed hemolytic reaction and delayed RBC precursors engraftment; i.e. pure RBC aplasia (PRCA). PRCA is a sever consequence of major and bi-directional ABO mismatch after alloHCT, leading to frequent transfusions, iron overload and secondary complications. Risk factors for PRCA after Major ABO incompatibility include; stem cell source, conditioning intensity, and titer of iso-agglutinins. Treatment is mostly supportive with transfusions and growth factors as well as withdrawing immunosuppressive therapy (IS). Targeting recipient immune system with high-dose steroids, DLI, and rituximab have been reported with variable results. Here we report a case series of a novel method of targeting recipient iso-agglutinins-producing B cells by Ibrutinib. <h3>Methods</h3> We report 3 cases of PRCA refractory to conventional therapy who responded to ibrutinib, a BTK inhibitor targeting recipient B cells to allow engraftment of donor RBCs. Patient, transplant and disease characteristic including prior therapies, time to transfusion independence, and switch of blood group (BG) are summarized in Table 1. First patient's day 30 post-transplant bone marrow biopsy (BMBx) showed complete remission (CR) with full donor chimera, but BG remained O. He developed severe anemia requiring transfusions and Day 100 BMBx showed CR with markedly decreased number of erythroid progenitors. He did not respond to IS withdrawal, prednisone, rituximab or bortezomib. But BMBx 4 weeks after starting ibrutinib showed trilineage hematopoiesis. Second patient remained RBC transfusion dependent post-HCT with Day 100 biopsy showing PRCA and full donor chimera. BG remained O. He developed severe GVHD of skin and eyes after DLI and His PRCA was refractory to multiple lines of therapies but responded to ibrutinib. Third patient underwent HCT for refractory AML with MDS; Anti-A isoagglutinin level pre-HCT was high and patient underwent plasma exchange. Day 30 BMBx showed CR and full donor chimera. Day +73 BMBx showed CR with near absent erythropoiesis. PRCA was refractory to rituximab and responded to ibrutinib. <h3>Conclusion</h3> All three patients with PRCA refractory to multiple lines of therapy responded to ibrutinib with median time to transfusion independence of 4 weeks and median time to BG switch of 6 weeks. All patients tolerated therapy well. Our experience at City of Hope shows that ibrutinib could offer a safe and efficacious treatment option for cases of refractory PRCA. Prospective studies are needed to assess if early therapy with ibrutinib could reduce the morbidity resulting from frequent transfusions, and GVHD complications.

Transplantation-Associated Microangiopathy (TAM) in Recipients of HLA-Haploidentical Hematopoietic Stem Cell Transplants Using Ptcy, CNI and MMF for GvHD Prophylaxis

Transplant-associated microangiopathy (TAM) is a life-threatening complication after allogeneic transplantation, related to endothelial toxicity caused by chemoradiotherapy, infections, immunosuppressive drugs and GvHD. Clinical manifestations include severe thrombocytopenia, microangiopathic hemolysis and organ dysfunction (e.g. renal, neurological) in the absence of disseminated intravascular coagulation. The reported incidence of TAM after allogeneic hematopoietic stem cell transplantation (HSCT) varies between 0,5 to 70%. Data for TAM occurrence and outcome in the context of HLA-haploidentical transplantation (haplo-HSCT) are rare. Here, we report our experience on TAM incidence, disease manifestation, treatment and outcome in T-cell-replete haplo-HSCT using PTCY as GvHD prophylaxis. We retrospectively analyzed the treatment course of 148 adult patients undergoing haplo-HSCT with regard to the incidence of TAM at our center from January 2012 to April 2019. The diagnosis of TAM required the fulfillment of the criteria as defined by Ruutu et al., Haematologica 2007. Median age of the entire cohort was 54 years (23-74). The majority of patients was transplanted for myeloid disease (60%). Postgrafting immunosuppression consisted of PTCY, CNI and MMF in all patients. Median follow-up time upon survivors was 3 years (4 months - 7 years). Twenty of 148 patients developed TAM, with a cumulative incidence of 10% at day 100. Median interval from haplo-HSCT to TAM onset was 63 days (23-295 days), with seven patients showing TAM after day +100. Median platelet count at diagnosis was 20 x 109/L (range: 6-116), predominantly de novo or worsening thrombocytopenia. Median LDH level was 437 IU/L (305-1445 IU/L). Serum haptoglobin levels were decreased in 85% of the TAM patients. 12/20 patients had active infection at the time of TAM diagnosis, most commonly viral (10/12). All but three patients presented with concurrent active acute GvHD requiring systemic steroid treatment in 16 patients Renal function abnormalities were diagnosed in 55% of the patients affected by TAM, with 4 patients requiring hemodialysis. Nine patients developed grade III hypertension and three patients showed neurologic dysfunction. Upon diagnosis of TAM, CNI dose was reduced (7 patients) or temporarily discontinued (7 patients). No switch to another CNI was performed. FFPs were transfused in nine patients, three patients underwent plasma exchange therapy without any effect. In four patients rituximab was applied. With a CI of 18% vs 2% (p0.002) using a PBSC graft was a risk factor for TAM development when compared to BM. Neither origin of disease (myeloid/lymphoid) nor sex of patient/donor or conditioning intensity (RIC/MAC) influenced the incidence significantly. Estimated one-year and three-year overall survival did not differ between the TAM and the non-TAM cohort (61% vs 61% and 46% vs 47%, p=0.9). Only one patient died because of TAM. With an incidence of 10% at day +100 at our center TAM is a serious but not rare complication after haplo-HSCT using PTCY, CNI and MMF for GvHD prophylaxis. However, in our cohort disease course was moderate with low TAM-associated mortality. The use of a PBSC graft was the only factor influencing TAM incidence. Disclosures Hiddemann: F. Hoffmann-La Roche: Research Funding.

3176 Sickle Cell Intrahepatic Cholestasis Following Choledocholithiasis: A Case Report

INTRODUCTION: Sickle Cell Intrahepatic Cholestasis (SCIC) is an acute manifestation of Sickle Cell Disease (SCD) characterized by occlusive sickling in the liver, causing biliary obstruction. We present a case of a patient in vaso-occlusive crisis with SCIC following choledocholithiasis. CASE DESCRIPTION/METHODS: A 23-year-old male presented with severe abdominal pain after having a complicated stay for choledocholithiasis one week prior. Total bilirubin level was 42.2 mg/dL, and transaminases were elevated. Abdominal ultrasound did not demonstrate repeat biliary duct blockage. Magnetic Resonance Cholangiopancreatography revealed intrahepatic biliary duct dilation and scattered wedge-shaped enhancements peripherally. The patient underwent plasma exchange transfusion. Afterwards, patient rapidly recovered with reduction in bilirubin level and resolution of pain and jaundice. He was discharged without complication. DISCUSSION: SCIC is a rare and potentially fatal sequela of vaso-occlusive crisis in SCD. Our patient may have been predisposed to developing SCIC due to a prior complicated admission for choledocholithiasis which may have damaged the biliary system to induce SCIC. Plasma exchange transfusion results in rapid recovery and should be initiated quickly in these patients.

Clinical diagnosis and treatment of pediatric anti-N-methyl-D-aspartate receptor encephalitis: A single center retrospective study.

The aim of the present retrospective study was to investigate the diagnosis, treatment and prognosis of pediatric anti-N-methyl-D-aspartate receptor (anti-NMDAR) encephalitis. A total of 23 pediatric patients with anti-NMDAR encephalitis were included in the present study. The clinical data, laboratory test results, imaging examination, treatment outcomes, and follow-up records were reviewed and analyzed. A total of 8 patients exhibited prodromal symptoms, including fever, cough, and vomiting. Clinical symptoms included epilepsy, convulsions, ataxia, coma, dyskinesia, personal behavior change and hallucinations. A total of 20 cases had the initial neurologic symptoms of dyskinesia or seizure, whereas 3 cases exhibited psychiatric symptoms of personal behavior change and hallucinations. Furthermore, pediatric patients >6 years old had more psychiatric symptoms than those ≤6 years. A total of 20 cases exhibited abnormal electroencephalography records, with 1 case of extreme δ brush. A total of 10 cases exhibited abnormal brain magnetic resonance imaging detection. Furthermore, the CSF protein contents for pediatric patients ≤6 years old was significantly higher than those >6 years. For treatment, 18 pediatric patients received the first-line treatment of methylprednisone and intravenous injection of immunoglobulin, and 6 cases were subjected to the second-line treatment of rituximab. A total of 2 patients underwent plasma exchange and/or cyclophosphamide treatment. In follow-up, 12 cases reported no convulsion, whereas 11 cases had moderate or severe neurological and psychiatric sequelae. The recovery rate for pediatric patients ≤6 years old was significantly higher than those >6 years. Anti-NMDAR encephalitis is commonly seen in pediatric patients, mainly with initial neurological symptoms. These patients could respond to immunotherapy, and younger pediatric patients typically have a better prognosis.

Cold agglutinin disease complicating management of aortic dissection

BackgroundCold agglutinin disease is characterized by acrocyanosis, hemolytic anemia, and occasionally, frank hemoglobinuria. Although cold agglutinins are commonly detected, they are rarely clinically significant due to subphysiologic temperatures at which agglutination occurs. Cardiovascular surgical procedures requiring hypothermia present a unique challenge for these patients, requiring modification of the conduct of cardiopulmonary bypass and cardioplegia. Case ReportHerein we report a case of a patient with a prior history of symptomatic cold agglutinin disease and type A aortic dissection, presenting with dilation of his known diseased ascending aorta, requiring semi-urgent repair. The patient underwent plasma exchange on two successive days preceding surgery to reduce the cold agglutinin titre. A modified Bentall procedure and replacement of ascending aorta and hemiarch under deep hypothermic circulatory arrest was performed without complication. ConclusionsThis case demonstrates the efficacy of employing plasma exchange in preparation for cardiac surgery with deep hypothermic circulatory arrest in a patient with clinically significant cold agglutinin disease. Plasma exchange alone may be sufficient in preparing patients with cold agglutinin disease for procedures requiring significant hypothermia when the delayed onset of action of alternative therapies is not acceptable. Choice of replacement fluid is critical in ensuring maintenance of coagulation proteins perioperatively and minimizing complement activation.

Transplant-Associated Thrombotic Microangiopathy: Prevalence, Prognostic Factors and Treatment Outcomes in Unrelated Allogeneic Transplant for Hematologic Diseases

Introduction: Transplant-associated thrombotic microangiopathy (TA-TMA) represents a devastating and life-threatening complication occurring more frequently in allogeneic compared to autologous hematopoietic cell transplantation (HCT). Although it has been a well-recognized syndrome for decades, our understanding in terms of epidemiology and more importantly, treatment options remains unclear. Therefore, we aimed to retrospectively investigate the incidence of TA-TMA in patients undergone HCT from unrelated donors and identify prognostic factors and treatment outcomes.Methods: We enrolled consecutive patients who underwent HCT from unrelated donors from 2003 to 2015. TA-TMA diagnosis was based on EBMT (European Bone Marrow Transplantation) criteria: increased (>4%) schistocytes in peripheral blood, thrombocytopenia, increased lactade dehydrogenase, decreased Hb. Anti-thymocyte globulin (ATG, rabbit) was used as standardised part of the conditioning in almost all patients (total dose of 5-7.5mg/kg). Prophylaxis for graft-versus-host disease (GVHD) consisted of cyclosporine or tacrolimus plus methotrexate in myeloablative and mycophenolate mofetil plus cyclosporine in reduced intensity conditioning transplants. Upon identification of TA-TMA, all possible causative factors were fully investigated. The mainstay of treatment strategy was withdrawal of calcineurin inhibitors, plasma infusion and plasma exchange combined with corticosteroid administration and in refractory cases, humanized anti-CD20 monoclonal antibody (Rituximab).Results: In total, we studied 179 patients, 74 male:105 female, aged 37±14 years, who underwent HCT from matched HLA A/B/C/DRB1 (8/8, n=88) and allele or antigen mismatched (n=91) grafts. Grafts derived from peripheral blood (157), bone marrow (18) and umbilical stem cells (4). Conditioning regimens were myeloablative (139), reduced intensity (28) and toxicity (12). Median follow-up was 11.5 (0.1-147.4) months.TA-TMA was diagnosed in 29 (16.2%) patients, 12 male:17 female, aged 34±12 years, 78 (9-721) days post-HCT for acute leukemia (21), Hodgkin (3) and non-Hodgkin (1), lymphoma, MDS (2), aplastic anemia (1) and MPN (1). Conditioning regimens were myeloablative in 24 (12 based on total body irradiation/TBI) and reduced intensity in 5 patients. Among patients with TA-TMA, 10 (34%) presented severe (grade III-IV) acute GVHD, 15 (52%) extensive chronic GVHD, 12 (41%) bacterial, 2 (7%) fungal and 21 (71%) viral (Cytomegalovirus and/or Epstein-Barr viremia) infectious episodes.In univariate analysis, age, gender, diagnosis, disease phase, previous lines of treatment, conditioning (intensity and TBI-based), ABO and HLA incompatibility, infections, acute and chronic GVHD were studied. The presence of TA-TMA was associated with severe acute and extensive chronic GVHD (p=0.001 and p=0.035 respectively) and TBI-based conditioning (p=0.043). In multivariate analysis, severe acute GVHD was the only independent factor associated with TA-TMA (β=3.4, p=0.038).Regarding treatment outcomes, 8 (28%) patients responded to cyclosporine cessation and plasma infusions. The rest 21 out of 29 patients underwent plasma exchange sessions; 14 (48%) of them responded to plasma exchange treatment. One patient that did not respond to plasma exchange received additional Rituximab treatment and the syndrome resolved. The other 6 (20.6%) patients were refractory and eventually succumbed. Treatment-related mortality was 33.3% (9/29) in TA-TMA patients and was directly associated with refractory microangiopathic syndrome in 6/29.Conclusion: Our results suggest that TA-TMA is not rare in unrelated transplant recipients and can be managed in a portion of patients that respond to cyclosporine cessation and plasma exchange. GVHD was the only independent predictor for the development of TA-TMA and therefore, successful prevention and treatment strategies for GVHD need to be timely employed to prevent complications. More importantly, transplanted patients with refractory microangiopathic syndrome showed increased TRM indicating that conventional treatment is inadequate. Recent data of increased complement activation in TA-TMA pave the way for targeted treatment with complement inhibitors in these patients. DisclosuresNo relevant conflicts of interest to declare.

Médecine transfusionnelle : au-delà de l’apport de facteurs déficitaires

Blood transfusion frequently consists in bringing blood components in patients presenting with global deficiency of cells or of certain factors allowing, i.e. hemostasis or oxygenation; transfusion is thus performed on a short period, or on a period that corresponds to the recovery of the bone marrow (that is deficient either quantitatively or qualitatively). In some other circumstances, patients must receive transfusions as the one treatment of their pathology; this can be for life, when the deficiency has a genetic origin, or episodically in the case of autoimmune disorders. Once hemotherapy is initiated, one must appreciate the balance between the benefits and the risks or overload, and adjust with subtractions and exchanges (of blood components). This paper presents examples of two cases: hemotherapy in sickle cell patients, and patients undergoing plasma exchange programs.

Prognosis of acute-on-chronic liver failure patients treated with artificial liver support system.

To establish a new model for predicting survival in acute-on-chronic liver failure (ACLF) patients treated with an artificial liver support system. One hundred and eighty-one ACLF patients who were admitted to the hospital from January 1, 2012 to December 31, 2014 and were treated with an artificial liver support system were enrolled in this retrospective study, including a derivation cohort (n = 113) and a validation cohort (n = 68). Laboratory parameters at baseline were analyzed and correlated with clinical outcome. In addition to standard medical therapy, ACLF patients underwent plasma exchange (PE) or plasma bilirubin adsorption (PBA) combined with plasma exchange. For the derivation cohort, Kaplan-Meier methods were used to estimate survival curves, and Cox regression was used in survival analysis to generate a prognostic model. The performance of the new model was tested in the validation cohort using a receiver-operator curve. The mean overall survival for the derivation cohort was 441 d (95%CI: 379-504 d), and the 90- and 270-d survival probabilities were 70.3% and 58.3%, respectively. The mean survival times of patients treated with PBA plus PE and patients treated with PE were 531 d (95%CI: 455-605 d) and 343 d (95%CI: 254-432 d), respectively, which were significantly different (P = 0.012). When variables with bivariate significance were selected for inclusion into the multivariate Cox regression model, number of complications, age, scores of the model for end-stage liver disease (MELD) and type of artificial liver support system were defined as independent risk factors for survival in ACLF patients. This new prognostic model could accurately discriminate the outcome of patients with different scores in this cohort (P < 0.001). The model also had the ability to assign a predicted survival probability for individual patients. In the validation cohort, the new model remained better than the MELD. A novel model was constructed to predict prognosis and accurately discriminate survival in ACLF patients treated with an artificial liver support system.

Predicting the Temporal Course of Laboratory Abnormality Resolution in Patients with Thrombotic Microangiopathy

Background:Screening for deficiency of ADAMTS- 13, a von Willebrand factor-cleaving protease, is commonly performed when there exists a clinical suspicion for thrombotic thrombocytopenic purpura (TTP). The clinical utility of ADAMTS13 testing at presentation has been questioned, as initial treatment decisions are variably influenced by results. Furthermore, current literature remains inconclusive about the differences in response to plasma exchange therapy in patients with severe (<5%) and non-severe (>5%) ADAMTS13 deficiency.Methods:With IRB approval, we performed a single center, retrospective review of patients undergoing plasma exchange therapy at Duke University Medical Center for indication of thrombotic microangiopathy from 2007 through June 2013. We retrospectively identified patients with “severe” deficiency (ADAMTS13² 5%, n=22) and those without severe deficiency (ADAMTS13 >5% or “non-severe” n=22). Cases of TTP associated with bone marrow transplantation, and chemotherapeutic agents were excluded. We trended daily laboratory values for creatinine, platelets, and LDH through completion of TPE . Time to recovery of laboratory abnormalities to normal was noted. We compared the time to resolution of laboratory abnormalities between patients with ADAMTS13² 5% (“severe”) to those with level >5% (“non-severe”).Results:Demographic and clinical information for TTP patients with ADAMTS13<5% and >5% are shown in the Table below. All patients underwent plasma exchange therapy plus steroids after diagnosis with TTP. Patients in both groups were comparable with respect to age and gender, but there were more episodes of recurrent TTP (n=9) in the ADAMTS13 <5% group compared to >5% (n=4). Patients with severe ADAMTS13 deficiency required more TPE (n=19 ) than patients with non-severe ADAMTS13 deficiency (n=13). There were 5 deaths in the non-severe ADAMTS13 cohort as compared to no deaths in the severe ADAMTS13 deficiency.Recovery of platelet count, LDH and Cr level to within normal range are shown for each group within 7, 14 and 21 days of presentation. Recovery of platelet counts for both groups were comparable. No recovery of platelet counts was seen in 3 patients for each group. The majority of patientÕs with and without severe ADAMTS13 deficiency appeared to recover platelet count by day 14 (81% for severe v. 75% for non-severe ADAMTS13 deficiency). Recovery of LDH differed in the two groups. Patients with non-severe ADAMTS13 deficiency were more likely to show no recovery in LDH (38% v. 4% in severe deficiency) or delayed LDH recovery (62% normalized LDH by D21 in non-severe v 95% in severe deficiency). As previously reported, patients with non-severe ADAMTS13 deficiency were more likely to have renal disease and less likely to recover renal function. Few patients in the severe deficiency group presented with abnormal renal function, but in those who had renal dysfunction, the majority (71%) recovered renal function by day 14.Conclusions:Our studies show the temporal resolution of laboratory parameters in patients with severe and non-severe ADAMTS13 deficiency. We show that both groups have similar platelet recovery patterns in response to TPE. However, patients with non-severe ADAMTS13 deficiency have delayed normalization of LDH, higher rates of ESRD and higher mortality. Although additional prospective analysis will need to be performed, this data provides preliminary data showing differing disease pathophysiology of the two groups and that patients with non-severe ADAMTS13 may benefit from alternative/adjunctive therapies to reduce mortality. TableClinical FeaturesADAMTS13 <5%ADAMTS13>5%Total number2222Males (M)/Females (F)7(M)/15(F)9(M)/13(F)Age (mean)4950Recurrent episodes94Mean # TPE1913Deaths05Platelet Count RecoveryTotal number with abnormal plts2221No recovery33*Plts >150K by day ² 713 (59%)9 (45%)Plts>150K by day ² 1418 (82%)15 (75%)Plts >150K by day ² 2121 (86%)15 (75%)LDH normalizationTotal number with elevated LDH2221No recovery1 (5%)8 (38 %)Normal LDH by day ²715(68 %)6 (29%)Normal LDH by day ²1420 (91%)10 (48%)Normal LDH by day ²2121 (95%)13 (62%)Renal function recoveryTotal number with abnormal Cr values at presentation712No recovery+29*Normal Cr by day 73 (42.85%)0Normal Cr by day 145 (71.42%)1 (8.33%)Normal Cr by day 215 (71.42%)3 (16.66%) DisclosuresArepally:TEVA Pharma: Consultancy.

Insights From the Use in Clinical Practice of Eculizumab in Adult Patients With Atypical Hemolytic Uremic Syndrome Affecting the Native Kidneys: An Analysis of 19 Cases

Atypical hemolytic uremic syndrome (aHUS) is a devastating form of renal thrombotic microangiopathy. Despite plasma exchange, the standard treatment of aHUS for decades, the renal prognosis for patients with aHUS has remained poor. We assessed the off-trial use of eculizumab in adult patients with aHUS affecting the native kidneys. A retrospective study was conducted. aHUS was defined as the presence of 3 or more of the following: acute kidney injury (serum creatinine >1.4 mg/dL [120 μmol/L]), mechanical hemolytic anemia, thrombocytopenia, and the presence of thrombotic microangiopathy features in a kidney biopsy specimen. Patients who had received 4 or more weekly 900-mg infusions of eculizumab were included. 19 patients were identified through a query sent to all French nephrology centers. Evolution of kidney function, hemolysis, and thrombocytopenia after the initiation of eculizumab therapy. All patients had acute kidney injury (serum creatinine range, 2.2-17.0 mg/dL) and 12 required hemodialysis. Thirteen patients carried a mutation in 1 complement gene and 1 had anti-factor H antibodies. For first-line therapy, 16 patients underwent plasma exchange and 3 patients received eculizumab. Median time between aHUS onset and eculizumab therapy initiation was 6 (range, 1-60) days and median time to platelet count normalization after eculizumab therapy initiation was 6 (range, 2-42) days. At the 3-month follow-up, 4 patients still required dialysis, 8 had non-dialysis-dependent chronic kidney disease, and 7 had normalized kidney function. At last follow-up (range, 4-22 months), 3 patients remained dialysis dependent, 7 had non-dialysis-dependent chronic kidney disease (estimated glomerular filtration rate, 17-55 mL/min/1.73 m(2)), and 9 had normal kidney function. Risks of reaching end-stage renal disease within 3 months and 1 year of aHUS onset were reduced by half in eculizumab-treated patients compared with recent historical controls. Retrospective study and use of historical controls. Our data indicate that eculizumab improves kidney disease outcome in patients with aHUS.

Tacrolimus‐induced thrombotic microangiopathy in orthotopic liver transplant patients: case series of four patients

Thrombotic microangiopathy (TMA) is a potentially fatal complication in solid organ and bone marrow transplant patients, with reported incidence of 0.5-3% and mortality of about 75%. To emphasise the importance of early diagnosis and prompt commencement of therapy results in improved clinical outcomes. A retrospective study of all patients who underwent orthotopic liver transplantation (OLTX) at the Western Australian Liver Transplantation Service from May 1994 to December 2010 was conducted to identify patients who developed tacrolimus-induced TMA. We identified four patients with tacrolimus-induced TMA post-OLTX, derived from a cohort of 104 patients treated with tacrolimus in our institution. The mean age at diagnosis was 40 years, and the mean time of onset was 63 ± 7.5 weeks after OLTX. The indications for OLTX in the four patients were fulminant hepatic failure in three (Wilson disease, paracetamol overdose and post-partum thrombotic thrombocytopenic purpura) and hepatitis C virus-related cirrhosis. All patients had tacrolimus post-OLTX. At diagnosis, tacrolimus was discontinued in all patients, and three of the four patients underwent plasma exchange and all patients improved clinically. Mean duration of follow up was 15 ± 7.5 months. There was no mortality 6 months post-TMA. Early diagnosis with immediate discontinuation or conversion of calcineurin inhibitors and plasma exchange should be offered to OLTX patients with TMA as it results in good outcomes.

The Monitoring of Serum Fibrinogen in Patients with End Stage Renal Disease Undergoing Plasma Exchange for High Risk Kidney Transplantation

Background: Plasma exchange is being increasingly used in the antibody reduction for high risk kidney transplantation. There were some reports of post-transplant bleeding in patients who had a large number of plasma exchange. In addition, wide variation in technique is reported, thereby adding to the confusion that exists about both efficacy and safety. Since changes in coagulation factors are known to occur to following plasmapheresis, we studied serial changes of serum fibrinogen in patients undergoing plasma exchange for antibody reduction before high risk kidney transplantation. Methods: Eighty eight times of plasma exchange were carried out at every other day in 18 patients before kidney transplantation, using the COBE® Spectra™ apheresis system. Sixteen patients were received ABO incompatible living donor kidney transplantation and 2 patients were received cross matching positive living donor kidney transplantation in our hospital from 2009 to 2011. The levels of serum fibrinogen were measured at pre-exchange, post-exchange one day and two days. In procedure, 1.0 time the calculated plasma volume was replaced with an electrolyte solution containing 5% salt-free human albumin or fresh frozen plasma (FFP). Anticoagulation was achieved using a whole venous blood to acid-citrate dextrose ratio of 15 to 1. Median flow rates, plasma collection, and procedure times were respectively 80 ml/minute, 20 ml/ minute, 80 minutes in cases of 5% albumin solution replacement and 40 ml/minute, 20 ml/minute, 150 minutes in cases of FFP replacement. Results: The cases with 5% albumin solution replacement were 55, and with FFP were 28. In cases of 5% albumin solution replacement, the mean serum fibrinogen level was 230.35 mg/dL, 138.93 mg/dL and 167.07 mg/dL at pre-exchage, post-exchage 1 day and post exchage 2 days. And in case of FFP replacement, the mean serum fibrinogen level was 168.68 mg/dL, 178.25 mg/dL and 181.18 mg/dL at the same time as before. The serum fibrinogen levels were markedly reduced immediately following the procedure and did not have returned to prior levels within 48 hours in cases of 5% albumin solution replacement. But the serum fibrinogen levels were increased in cases of FFP replacement.Table: [The serum fibrinogen levels in subjects(mg/dL).]Conclusion: In spite of every other day schedule, consecutive plasma exchange with 5% albumin solution replacement has a decrease of serum fibrinogen in patients with end stage renal disease before high risk kidney transplantation. And it may be associated with decrease coagulation and post-transplant bleeding. It is useful to prevent post-transplant bleeding that the use of FFP as replacement fluid or the use of cryoprecipitate containing fibrinogen and other coagulation factors.